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Rhythm is the Answer

Posted By Administration, Thursday, July 1, 2010
Updated: Friday, April 18, 2014

by Joel Lopez, MD, CNS

411913693_09923741a9_zThere is a rhythm in life. You see it everywhere in nature. Moon cycles, seasonal changes, circadian rhythms, migratory patterns, growth spurts, planting/harvesting times, etc. There is nothing static in nature. Everything is in a constant flux. The only thing that’s static is death. At least, that’s what we know for now. If there are rhythmic patterns in our bodies, doesn’t it make sense to give hormones (if a person’s symptomatic, deficient or has sub-optimal numbers) in a rhythmic pattern as well? This idea was actually brought forth by a person named TS Wiley. She’s trained as an anthropologist and unfortunately (or fortunately?) is not an MD. Otherwise, a lot of doctors, especially in the anti-aging community would have jumped onto the bandwagon of prescribing bioidentical hormones in a rhythmic manner. That is, changing the dose every so often, to mimic nature. Doctors, just like every one else, are creatures of habit. Nobody wants to mess with the status quo. A German philosopher named Arthur Schopenhauer put it succinctly, “All truth passes through three stages. First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as being self-evident.” Anyway, hormonal imbalance is just one of the causes of accelerated, symptomatic aging. Other factors such as nutritional deficiencies, chronic inflammatory processes, toxicities, oxidative stress and mitochondrial dysfunction need to be addressed as well if a person wants to age well.

Tags:  rhythm 

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Do You Have a Toxic Workplace?

Posted By Administration, Tuesday, June 29, 2010
Updated: Friday, April 18, 2014

by, Holly Lucille, ND, RN

74046939_7b6c18ce63_bI am not talking about the "toxic workplace" often reported when a work environment is full of backstabbing, gossiping co-workers, a controlling boss or demanding clients. I am talking about toxic substances in your workplace that might be making you physically sick.

It is bad enough that we live in a society that is extremely dependent on harmful chemicals. We are exposed to these ubiquitous and devious substances everyday, hiding in plastics, pesticides, car exhaust, soaps, emulsifiers, health and beauty aids, household cleaning products and a number of other places. They are in the food we eat, the water we drink and the air that we breathe. However, depending on where you work, your exposure to toxic substances could be intensified, contributing significantly to your health issues.

Occupational allergies are becoming an extremely common concern with cases increasing in numbers and severity in recent years. There have been countless articles written on both "Sick Building Syndrome" and "Occupational Asthma." Under these two modern diagnoses, people have complained of a variety of symptoms including watery eyes, runny nose, headaches, dizziness, nausea and tightening sensation in the chest. The curious thing about most of these symptoms is that they have a distinct pattern of getting worse while in the work environment and significantly better over vacations or weekends.

If you work in an enclosed office space, you might feel falsely safe and protected from environmental allergens at work. Modern office buildings are not only being built with toxic chemicals but, in order to conserve energy, they are also built tight as a drum with poor ventilation, leaving allergens and irritants with no place to go. Common sources, such as malfunctioning or inappropriate, inefficient use of heating devices, can produce irritating pollutants such as carbon monoxide, nitrogen dioxide and sulfur dioxide at harmful levels. Formaldehyde exposure is widespread and found in resins in finishes, plywood, paneling, fiberboard and particleboard, and in some backings and adhesives for carpets. Biological air pollutants like dander, molds, and dust mites are carried by animals and people into and throughout buildings.

Scents and hairsprays, construction products such as finishes, heavy duty cleaners, paints, thinners, dry cleaning fluids, some copiers and printers, some glues and adhesives, markers, and photo solutions are among some of the common office products that emit harmful volatile organic compounds (VOC). New installations, carpet, wall coverings, paint or construction can all heighten problems with VOCs. If that isn’t enough to worry about, almost everyone has heard of the dangers of toxic mold thriving in cool, damp, dark places behind walls and under carpeting.

Some occupations that are even higher risk for exposure include: industrial workers handling paints, chemicals, solvents, and plastics; beauticians who work daily with hair dyes, perms, and nail polish/removers; people who are in the farming industry dealing with fertilizers and pesticides; photocopier technicians and dry cleaning merchants working with machines emitting potentially harmful gases.

If you feel that your workplace is making you sick, there are things you can do, short of quitting your job. Reducing exposure is important but it is also important to remember that having an allergic response to something often has less to do with the trigger and more to do with our body’s inability to respond to it appropriately. Make sure you are protecting your immune system by choosing healthy, organic foods in your diet for adequate nutrients and fiber, drink plenty of filtered water, exercise regularly, choose non-toxic products for your home and consider partnering with a qualified healthcare practitioner to partake in a comprehensive body detoxification. Enzymatic Therapy’s ( Whole Body Cleanse is a very effective and easy cleanse that you can get at a health food store near you.

In your workplace, consider talking with both your supervisor and your OSHA or union representative regarding the air exchange system in your building. Interior landscaping can help absorb some of the off-gassing from VOC and formaldehyde. Buying plants like a Dwarf date palm, Bamboo palm or Janet Craig is an inexpensive, efficient method of cleansing the air. Keep your work area free of clutter, dust regularly and use a HEPA-type table top air purifier. Even though we cannot completely escape the toxins that surround us, we can make a difference for us as individuals and, little by little, the environment as a whole!

Tags:  toxins  work 

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Insights into Vegetarianism

Posted By Administration, Wednesday, June 23, 2010
Updated: Friday, April 18, 2014


2085739779_b0dc7d4d28_bby Andrea Purcell, ND

Patients come to vegetarianism for a variety of reasons.

The three most common reasons I hear are:

I heard it was better for my health.

It’s a religious or customary choice.

It’s less cruel to animals and our planet.

The food choices I most commonly see among the vegetarian patient base are nothing close to vegetarianism as defined by the term.

So to clarify, the word vegetable is contained within the word vegetarian. In order to be a vegetarian you must eat vegetables, which means that you must buy, prepare, occasionally cook and chew them on a regular basis.

The type of vegetarianism I commonly find in my patients who come to the office and say that they are vegetarian, are really carbo-vegetarians. This means that they consume easy to prepare, on the run processed food forms of carbohydrates that are animal free.

These include, rice, pasta, breads, cakes, cookies, frozen yogurt, bean burritos in white flour tortillas, pancakes, bagels, waffles, fruit, veggie sandwiches, pizza, vegetable dumplings, vegetable lasagna, chips and salsa, hummus with carrots. All of the vegetarian options in this example are simple carbohydrates. They have been processed and refined, meaning that they have been bleached of their nutrients, and stripped of their fiber. Simple carbohydrates are exactly what they say, simple. Not the nutrient and fiber dense food, of what they once were, or of how nature intended it be delivered to us.

Being a healthy vegetarian means being a responsible vegetarian. This means that vegetarians need to work very hard to get enough fat and protein in their diets in order to maintain the level of health that famous vegetarians brag about.

Responsible vegetarianism includes a balance of fat, protein, complex carbohydrates, and of course vegetables at every meal and snack.

Eating fruit in place of vegetables would technically make a person a fruitarian, which is not the topic of this blog.

Complex Carbohydrates include: Whole grains such as brown rice, quinoa, amaranth, and millet. Whole beans, black, lentil, red, white, mung, garbanzo and vegetables in every color.

Protein sources include: Nuts, beans, seeds, tofu, tempeh, possibly eggs or dairy depending on the type of vegetarian, certain vegetables (avocado, spinach, broccoli).

Fat sources include: Nuts, seeds, avocado, coconut milk & meat, oils in many forms.

To Drink: Juiced Vegetables! Try my favorite mixture: Celery, cucumber, spinach, Swiss chard, ½ apple.

Be a responsible vegetarian, your body will thank you for it!

Tags:  food and drink  vegetarianism 

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Heavy Metals Increase Risk of Depression and Panic Disorder

Posted By Administration, Tuesday, June 22, 2010
Updated: Friday, April 18, 2014


by Gina Nick, NMD, PhD

Even at low levels generally considered to pose little or no risk, exposure to environmental lead might increase – by as much as 2.3 times – the risk of depression and panic disorder but not of generalized anxiety disorder. That was the suggestion of a Canadian study appearing in the December, 2009 issue of the Archives of General Psychiatry. Gender and ethnicity were also factors and the researchers stressed that lead exposure cannot be determined to be a cause of these psychological problems.

One of the main, and often overlooked, sources of heavy metals, including lead, is our water supply-both drinking water and shower water.   I recommend investing in a quality water filtration and ionization system to all of our patients.  The link between heavy metal exposure and mental illness suggested in this study and proven in many others (including practical, real life studies completed with patients at LTP Medical) is one of the reasons why we always test patients with mental health challenges for exposure to environmental toxins including heavy metals and treat them using the LTP Medical Custom Purification Program to remove the toxins from their systems.  This is one of the simplest and most effective ways to see immediate benefit in patients suffering needlessly with these challenges. Other treatments include custom amino acid therapy, fatty acid therapy, orthomolecular therapy, hormone therapy and food allergy testing and treatment.

Tags:  anxiety  depression  heavy metal  panic disorder 

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Curbing Inflammation May Reduce Heart Disease Risk

Posted By Administration, Monday, June 21, 2010
Updated: Friday, April 18, 2014


by Zina Kroner, DO

It has been established in prior studies that if one has an inflammatory condition such as psoriasis, for example, the risk of heart disease increases substantially.  A pro-inflammatory agent called tumor necrosis factor (TNF) tends to be elevated in patients with many  inflammatory conditions such as psoriasis and rheumatoid arthritis.  Prior studies have shown us that when patients took medication that act again TNF, the risk of heart disease decreased (J Am Acad Dermatol 2005; 52:262).

A recent study in Norway looked at patients with 3 different inflammatory conditions: rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis.  Patients were treated with TNF antagonists and aortic stiffness was assessed as a marker of heart disease.  It was found that those receiving anti-TNF agents as compared to placebo had statistically significant decreases in aortic stiffness and C-reactive protein levels (a marker for heart diseaes).  Although the study was of small sample size and of short duration, it can be concluded that TNF-antagonists may potentially decrease heart disease risk. 

Medications that are TNF antagonists have a wide and potentially detrimental side effect profile and need to be prescribed judiciously. There are an array of natural treatments that can be catered to one's condition that can potentially lower TNF and cardio-CRP levels as well. 

This is an important study in that it substantiates the fact that decreasing inflammation in our bodies will help reduce cardiovascular risk.  This can be done via a number of fronts depending on one's unique inflammatory condition. 

Source: Angel K et al. Tumor necrosis factor-{alpha} antagonists improve aortic stiffness in patient with inflammatory arthropathies: A controlled study. Hypertension 2010 Feb; 55:333.

Tags:  heart disease  inflammation 

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Glutathione and Parkinson's Disease

Posted By Administration, Wednesday, June 16, 2010
Updated: Friday, April 18, 2014


by Zina Kroner, DO

Glutathione has been used to help alleviate some of the symptoms of Parkinson's disease.  Glutathione is a small peptide made up of three amino acids – glutamic acid, cysteine and glycine.  The active group of this peptide is the sulfhydryl or thiol (SH) group, a bond formed between the amine (NH2) group of cysteine and carboxyl group (COOH) of glutamic acid.  

In the human body, glutathione occurs in two forms:

1. the majority of glutathione is present in the reduced form (GSH) 

2. and a small percentage of it is present in the oxidized form (GSSG or glutathione disulphide).  

The reduced form of glutathione is the active form, and it donates its electrons to highly reactive molecules like free radicals, peroxides and superoxides to stabilize them.  The process is called neutralizing the free radicals.  During this process, glutathione is oxidized and the harmful free radicals are reduced and neutralized.  

The free radicals, peroxides and superoxides are unstable and highly reactive molecules formed as part of normal metabolic processes.  These can literally snatch electrons from the surrounding molecules (like DNA, cell membrane and other cell organelles) to stabilize themselves, making the other molecules unstable, that repeats the process, setting off a chain reaction producing more unstable molecules, which can easily result in the collapse of the cell membrane and the membranes of other cell organelles.  

Glutathione is synthesized internally in the liver and does not need to be supplied in the diet.  A balanced diet has all the necessary precursors for the internal synthesis of glutathione. The ability of glutathione to neutralize these harmful free radicals makes it a major powerful intracellular antioxidant.  For glutathione to be active, it needs to be kept in the reduced form in the blood.  The oxidized glutathione is immediately recycled back to its reduced form by an enzyme called glutathione reductase, and glutathione is again ready to donate electrons to free radicals.  The reduced and oxidized forms of glutathione together are called a redox couple.  

Glutathione preserves the integrity and fluidity of the cell membrane.  It is available in the cells in relatively high concentrations in the reduced form.  Depletion of glutathione levels in the cells leads to excessive formation of reactive oxygen species which puts more stress on the cells.  This is called oxidative stress.  This increased oxidative stress causes the cell organelles to burn out gradually and lead to eventual cell death.  Increased oxidative stress plays a major role in increasing the risk for a variety of cancers, inflammatory and degenerative diseases.  

Glutathione and Parkinson’s disease

Glutathione has been extensively studied for its role as an antioxidant in Parkinson’s disease, an adult-onset progressive neurodegenerative disorder.  In Parkinson’s disease, there is a selective degeneration of dopaminergic neurons in the substantia nigra of midbrain.  Substantia nigra is the part of the brain responsible for physical movement (like walking, moving hands and legs, etc).  Hence, degeneration of dopaminergic neurons in substantia nigra causes physical symptoms like tremors, bradykinesia (slow movements), muscle stiffness and loss of automatic movements in Parkinson’s disease. 

Progressive degeneration of dopaminergic neurons in substantia nigra is caused by:

1. Excessive formation of reactive oxygen species (ROS)

2. Increased oxidative stress accumulation of abnormal proteins in the cells

3. Drastic depletion of glutathione (GSH) levels 

Dopaminergic neurons are more prone to oxidation due to a combination of factors like the metabolism of dopamines, auto-oxidation, increase in iron levels, decrease in glutathione levels and excessive formation of ROS. Oxidative stress needs to be reduced to slow down the progression of symptoms of Parkinson’s disease. Research suggests that oxidative stress can be effectively reduced by increasing the glutathione levels or slowing its degradation in the substantia nigra.

In the body, glutathione is synthesized from 3 amino acids – glutamic acid, cysteine and glycine.  The availability of cysteine is the deciding factor (or rate limiting factor) in the synthesis of glutathione.   

Dr. Perlmutter’s Research

Dr. David Perlmutter, a board certified neurologist from Naples, Florida, started using intravenous glutathione in 1998 for his Parkinson's patients after he did extensive research on Parkinson’s disease and effects of supplemental glutathione on improving the symptoms of Parkinson’s disease.  He is the pioneer in using intravenous glutathione in the treatment of Parkinson’s disease.  His research opened new doors in the treatment of Parkinson’s disease and other neurodegenerative diseases.  Dr. Perlmutter has successfully used intravenous glutathione in patients with significant improvement in the symptoms.  Although glutathione treatment cannot prevent the occurrence of symptoms, it significantly slows down the occurrence of symptoms with improvement in the existing symptoms.

Glutathione supplements do not directly raise the dopamine levels in the brain, instead they improve the efficiency of dopamine in the brain and also increase the sensitivity to dopamine and serotonin.

Glutathione Treatment

Glutathione supplements are available in oral, intramuscular, and intravenous forms.

Oral – Glutathione is available in capsule form and also precursors of glutathione are available in powder form to be used as oral supplements.  However, recent research suggests that glutathione is digested in the gastrointestinal tract and broken down to its constituents even before it enters the blood.  So, oral glutathione supplements are not effective.  I prefer to give the natural precursors to glutathione to my patients.  

Intramuscular – Glutathione injections are also given intramuscularly.  These are mildly effective according to anectodal data.

Intravenous – Glutathione injections given intravenously are the best and most effective form of supplementation. Not only does it reach the brain and potentially improves Parkinson’s symptoms, it also reaches the liver and helps in a variety of functions like neutralization of free radicals via detox pathways.  Standard dosage for glutathione supplements is 1400 milligrams mixed with saline, given intravenously for ten minutes three times a week.  

Contraindications and Safety:

Glutathione is in the GRAS (generally regarded as safe) category, according to the FDA.  However, if you are taking other prescription medicines, glutathione supplements may reduce the efficacy of these medicines.  This is because glutathione plays a role in the detoxification function in the liver, removing foreign substances from the body.  Prescription medicines may therefore be removed from the system, thus reducing their efficacy



1.Hauser, RA, Lyons, KE, McClain, T, et al. Randomized, Double-Blind, Pilot Evaluation of Intravenous Glutathione in Parkinson’s Disease. Movement Disorders. 2009;24(7): 979–983.

2.Sechi, G, Deledda, MG, Bua, G, et al. Reduced intravenous glutathione in the treatment of early Parkinson's disease. Prog Neuropsychopharmacol Biol Psychiatry. 1996;20(7):1159-70. 

3.Perlmutter, D. “New Advances in Parkinson’s Disease.” From Last updated 2004, currently unavailable. Chapter found at

4. Bharath S, Hsu M, Kaur D, Rajagopalan S, Andersen JK, Glutathione, iron and Parkinson's disease. Biochem Pharmacol. 2002 Sep;64(5-6):1037-48.

5. Martin HL, Teismann P. Glutathione--a review on its role and significance in Parkinson's disease. FASEB J. 2009 Oct;23(10):3263-72. Epub 2009 Jun 19.

6. Chinta SJ, Andersen JK. Redox imbalance in Parkinson's disease. Biochim Biophys Acta. 2008 Nov;1780(11):1362-7. Epub 2008 Mar 4.

Tags:  glutathione  parkinson's disease 

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The Diagnosis and Treatment of Hypothyroidism

Posted By Administration, Monday, June 14, 2010
Updated: Friday, April 18, 2014


by Michael Schachter, MD, CNS

Hypothyroidism, or an underactive thyroid system, is one of the most underdiagnosed and important conditions in the United States. It has been called the "unsuspected illness" and accounts for a great number of complaints in children, adolescents and adults.

What kinds of complaints characterize an underactive thyroid system? Low energy and fatigue or tiredness, especially in the morning are frequent in these patients. Difficulty losing weight, a sensation of coldness--especially of the hands and feet, depression, slowness of thought processes, headaches, swelling of the face or fluid retention in general, dry coarse skin, brittle nails, chronic constipation, menstrual problems-such as PMS and menstrual irregularities including heavy periods, fertility problems, stiffness of joints, muscular cramps, shortness of breath on exertion and chest pain are some of the symptoms that can be seen in people with underactive thyroid systems. Be aware that a person with a low functioning thyroid doesn't have to have all of these symptoms, he may have only a few.

Function of the Thyroid Gland
Where is the thyroid located in the body and what does it do? The thyroid gland consists of two small lobes connected together. It is located in the front of the neck, just below the voice box. The thyroid gland is responsible for the speed of metabolic processes in the body and therefore affects every organ and organ system. It is the metabolic stimulator, analogous to the accelerator of a car. Normal growth requires normal thyroid functioning. When the thyroid is not functioning properly, organs become infiltrated with metabolic wastes and all functions become sluggish.

When the thyroid gland is working properly, it uses the amino acid tyrosine and iodine to make the thyroid hormone called thyroxine or T4. Thyroxine is called T4 because it contains four iodine atoms. If a person is deprived of iodine in his diet, he develops an enlarged thyroid gland, called a goiter and symptoms of an underactive thyroid or hypothyroidism.

The other important thyroid hormone is triiodothyronine or T3, which has three iodine atoms. T3 is actually the major active thyroid hormone, being much more active than T4. T4 is produced within the thyroid gland and is later converted to the active T3 outside the thyroid gland in peripheral tissues. Under certain conditions, such as stress, the thyroid gland may produce sufficient amounts of T4 to obtain normal thyroid blood tests, but its conversion to T3 may be inhibited, causing a relative insufficiency of active T3. Under this circumstance, the patient will have hypothyroid symptoms in spite of normal thyroid blood tests. As you will see, this fact results in many missed diagnoses of an underactive thyroid system.

The production and release of T4 from the thyroid gland is controlled by a hormone from the pituitary gland, which is located at the base of the brain. This hormone is called thyroid stimulating hormone or TSH. When the level of T4 in the bloodstream is low, the pituitary increases TSH production and release, which in turn stimulates the thyroid gland to produce and release more T4. The T4 then feeds back to the pituitary, reducing the secretion of TSH in a negative feedback loop. When a person has trouble making T4 due to iodine deficiency or for some other reason, one would expect to find an elevated TSH. The pituitary's TSH is trying to get the thyroid gland to produce more T4. If both T4 and TSH are low, this may indicate a pituitary problem with a low TSH secretion resulting in the low production and secretion of T4.

Diagnosis of Hypothyroidism
So, how is hypothyroidism diagnosed today by conventional medicine? Unfortunately, the diagnosis by conventional physicians, including thyroid specialists called endocrinologists, is made almost exclusively from blood tests. Generally, T4 and TSH are measured in the bloodstream. Additionally, a protein that binds T4 is also measured. From this protein and T4, the free T4 is calculated. If a patient has a normal TSH and a normal free T4, he is told by the conventional physician that he does not have hypothyroidism, no matter how many symptoms or signs of hypothyroidism he has. This is the fatal error because these tests only pick up the most severe cases of hypothyroidism and miss virtually all of the milder cases that would respond favorably to thyroid hormone treatment.

If most hypothyroid cases cannot be diagnosed by the usual blood tests, how can they be diagnosed? Prior to the extensive use of blood tests, hypothyroid states were diagnosed by astute clinicians, who obtained careful medical histories, including family histories from the patient, and who performed a complete physical examination. Later basal metabolic rates were measured using special equipment. Then came the blood tests--the protein bound iodine or PBI, T4, TSH and even T3 by special radioactive studies. Instead of using the blood tests as adjuncts to diagnosis, they were soon relied upon exclusively. To properly diagnose hypothyroidism, the clinician must go back to the careful medical history, physical examination and measurement of the basal temperature of the body. I'll discuss important aspects of the medical history and physical examination relevant to the diagnosis of hypothyroidism.


Medical History
What in the medical history suggests the likelihood of hypothyroidism? With regard to infancy and childhood, a high birth weight of over 8 lbs. suggests low thyroid. During childhood, early or late teething, late walking or late talking suggests a low functioning thyroid in the child. Also, frequent ear infections, colds, pneumonia, bronchitis or other infections; problems in school including difficulty concentrating, abnormal fatigue--especially having difficulty getting up in the morning and poor athletic ability all suggest a low thyroid. Keep in mind that a person with low thyroid functioning may have only a few of these characteristics. You don't have to find all of them to suspect a low thyroid.

During puberty, we see the same types of problems in school and with fatigue, which is worse in the morning and gets a little better later in the day. Often, adolescent girls suffer from menstrual irregularity, premenstrual syndrome and painful periods. Drug and alcohol abuse are common.

Throughout life, disorders associated with hypothyroidism include headaches, migraines, sinus infections, post-nasal drip, visual disturbances, frequent respiratory infections, difficulty swallowing, heart palpitations, indigestion, gas, flatulence, constipation, diarrhea, frequent bladder infections, infertility, reduced libido and sleep disturbances, with the person requiring 12 or more hours of sleep at times. Other conditions include intolerance to cold and/or heat, poor circulation, Raynaud's Syndrome, which involves the hands and feet turning white in response to cold, allergies, asthma, heart problems, benign and malignant tumors, cystic breasts and ovaries, fibroids, dry skin, acne, fluid retention, loss of memory, depression, mood swings, fears, and joint and muscle pain.

With regard to the family history, all of the above disorders can be checked in family members. Particular emphasis should be placed on hypothyroid conditions in parents or siblings. Also, a family history of Tuberculosis suggests the possibility of low thyroid.

Physical Examination
The physical examination often reveals the hair to be dry, brittle and thinning. The outer third of the eyebrows is often missing. One often finds swelling under the eyes. The tongue is often thick and swollen. The skin may be rough, dry and flaky and show evidence of acne. The skin may also have a yellowish tinge due to high carotene in it. Nails tend to be brittle and break easily. The thyroid gland may be enlarged. The patient is more often overweight, but may also be underweight. Hands and feet are frequently cold to the touch. Reflexes are either slow or absent. The pulse rate is often slow even though the patient is not a well trained athlete.

Measuring Basal Body Temperature
Instructions for taking basal body temperatures are relatively easy. Use an oral glass thermometer. Shake the thermometer down before going to bed, and leave it on the bedside table within easy reach. Immediately upon awakening, and with as little movement as possible, place the thermometer firmly in the armpit next to the skin, and leave it in place for 10 minutes. Record the readings for three consecutive days. Menstruating women must only take the basal temperature test for thyroid function on the 1st, 2nd, 3rd or 4th day of menses(preferably beginning on the 2nd day). Males, pre-pubertal girls, and post-menopausal or non-menstruating women may take basal temperatures any day of the month. Women taking progesterone should not take it the day before and the days that the basal temperatures are taken.

Most of the information on the manifestations of hypothyroidism, its diagnosis, including the technique for measuring and interpreting basal temperatures, and the treatment to be discussed was compiled and described by the late Dr. Broda O. Barnes. He is the author of the book Hypothyroidism: the Unsuspected Illness. His work is disseminated to physicians and the public by the foundation bearing his name, which is located in Trumbull, Connecticut.

How does one interpret the results of the basal body axillary temperature test? If the average temperature is below 97.8 Fahrenheit, then the diagnosis of a low functioning thyroid system is likely. An average temperature between 97.8 and 98.2 is considered normal. An average temperature above 98.2 is considered high and might reflect an infection or a hyperthyroid condition.

Treatment of Hypothyroidism
Once a pattern of hypothyroid symptoms is established and the basal body temperatures are found to be low, the next step is a therapeutic trial of thyroid hormone. Dr. Barnes, his physician followers and many patients have found that the most effective thyroid medication is Armour Desiccated Thyroid Hormone. This medication is derived from the thyroid gland of the pig. It most closely resembles the human thyroid gland. It is dried or desiccated and processed into small tablets. In contrast, most conventional physicians prefer to use the synthetically produced thyroxine or T4. In my experience and the experience of many other physicians using Dr. Barnes' protocol, the synthetic T4 is not as effective as the desiccated thyroid.

How can we monitor the results of treatment if the blood tests are inadequate to the job? We do this by how the person feels, whether or not the thyroid symptoms and signs have improved or disappeared, whether or not symptoms of an overactive thyroid gland have developed, and by monitoring the basal body temperature.

Generally, the dosage of Armour thyroid is best started at a low dose, with a gradual increase every week or two, until the optimal therapeutic dosage is reached. It may take four to six weeks at the optimal dosage to feel the full therapeutic benefits. In my practice, I generally start the patient on 1/4 grain or 15 milligrams daily. Every week or two, I increase the dosage by 1/4 grain per day until 1 to 2 grains daily are reached. Usually, the optimal dosage is in this range, provided that the patient is doing the other adjunctive necessary things, which I will discuss in a moment. Occasionally, the dosage may need to be 2 and a half grains daily or more. Full therapeutic benefits many not be fully realized for months and the basal temperatures may not come up to normal for a year or more. The dosage for infants is usually 1/8 to 1/4 grain daily and from one to six years old, the dosage is usually 1/4 grain. From 7 years to puberty, 1/2 grain is usually used, but it may need to be increased.

Special Cases: Recent Heart Attacks and Weak Adrenal Function
There are a few special cases that needs to be discussed in the context of this treatment. If a person has recently had a heart attack, treatment should not begin for at least two months following the heart attack. After that, the protocol discussed above can be used.

If a person has evidence of weak adrenal function, the adrenal gland problem must be treated first or simultaneous to the thyroid treatment. The reason for this is that hydrocortisone is necessary for the conversion of T4 to the active T3. If the weak adrenal is not addressed, the patient may actually feel worse and/or develop symptoms of an overactive thyroid gland, such as palpitations, a rapid heart beat and increased sweating. Clues to low adrenal functioning include a low blood pressure (less than 120/80), allergies, asthma, breathing difficulties, skin problems (such as acne, eczema, psoriasis, lupus, dry flaky skin), joint or muscle pains, as in arthritis, and emotional problems, such as mood swings, weeping, fears and phobias. Using low physiologic doses of hydrocortisone along with Armour Thyroid, when the patient shows evidence of both low adrenal and low thyroid function, will help to assure the desired results.

Problems in Converting T4 to the T3 Hormone
The conversion of the relatively inactive T4 to the active T3 thyroid hormone is an important process. As mentioned previously, frequently low thyroid function is not due to the low production of thyroxine, T4, by the thyroid, but due to the failure of conversion of T4 to T3 by peripheral tissues. What nutrients are necessary to help with this conversion? In addition to sufficient quantities of cortisol, iron, zinc, copper and selenium are necessary for this conversion. Deficiencies of any of these minerals can prevent the conversion T4 to T3 and should be corrected if present. Sufficient protein and especially the amino acid, tyrosine, and iodine are necessary to make T4 in the thyroid gland.

Another approach to the problem of conversion failure of T4 to T3 has been proposed by a young physician, Dennis Wilson. He has found that the body often adapts to various stressful situations by switching to a conservative mode in order to preserve energy. For example, when a famine occurs, an excellent adaptive change that the body can make in order to use less energy because food calories are unavailable, is to stop converting T4 to T3. However, this response appears to occur to a wide variety of stressors and sometimes this mode is not reversed, even after the stress is removed. This can lead to all of the symptoms and signs of a low thyroid that I have been discussing.

He has suggested the use of a special long acting T3 preparation to reset the conversion of T4 to T3 process. Dosages of T3 are given exactly every 12 hours in increasing amounts with close monitoring of oral temperatures during the day. High doses of T3 may be given and in order to normalize the oral temperature to 98.6 F. After the optimal temperature is reached and maintained for approximately three weeks or if the patient develops an intolerance to the particular dosage of long-acting T3, the dosage is tapered down to zero.

When the treatment is successful, the temperature will remain optimal with the loss of hypothyroid symptoms, even after the medication is tapered to zero. In other words, the thyroid system is reset at a higher temperature. This process may take several cycles of going up and down on the T3. This treatment requires a lot of discipline from the patient and often leads to symptoms during the treatment. However, it does seem to be useful in some patients. If the patient is stressed significantly and again enters the low thyroid system mode, the entire process can be repeated again. Usually, the treatment is easier at each subsequent episode.

Nevertheless, for most patients, especially if there are adrenal problems or other medical complications, the use of Armour desiccated thyroid on a continuous basis is probably easier and preferable.

Recent studies indicate that patients who have been treated with excessive doses of thyroid hormone over long periods of time may be at increased risk for developing osteoporosis. This may be due not only to too much thyroid, but also to an imbalance between the anabolic and catabolic endocrine hormones. The catabolic hormones are those that help to break down dead tissues and rid the body of metabolic waste. These would include thyroid hormone and hydrocortisone. The anabolic hormones are those that help to rebuild the body and would include DHEA, estrogens, progesterone and the male hormone, testosterone. A physician who is trying to balance a person's thyroid system must also look at all of the other hormones and also all aspects of the person's lifestyle, including diet, nutritional supplements, exercise patterns and stress coping mechanisms. The nutrients that are especially important to a proper functioning thyroid system are iodine and the amino acid tyrosine to make thyroid hormone in the thyroid gland and the minerals iron, selenium, zinc and copper to convert the inactive T4 to the active T3.

How Long Should Patients Take Thyroid Hormone?
When using the desiccated thyroid protocol, patients often remain on the thyroid for life. However, there may be times when the patient can be weaned off the thyroid as all other functions improve, as long as the patient is carefully monitored for the development of low thyroid symptoms and signs and low basal temperatures. When a person's basal temperatures are low, many of the enzymes of the body function in a suboptimal way, which leads to all of the problems we have discussed.

On the other hand, well treated hypothyroid patients should enjoy a vibrant life with lowered risks of all of the degenerative diseases including arthritis, cancer and heart disease. I personally have seen a number of patients whose arthritis pains have completely cleared when treated with proper doses of thyroid. With regard to cancer, the well known alternative cancer treatment developed by Max Gerson, involves the use of Armour Desiccated Thyroid in virtually all of his cancer patients. High serum cholesterol and the development of atherosclerosis are well known effects of hypothyroidism. Therefore, all patients with coronary artery disease and other atherosclerotic conditions should be checked carefully for evidence of a low functioning thyroid condition and treated cautiously and appropriately if a low thyroid condition is found. Psychiatrists have found that the addition of thyroid hormone to patients suffering from refractory depression often is helpful, even when the blood tests are normal.

The proper appreciation of low thyroid conditions and their subsequent treatment should aid greatly in reducing the morbidity and premature mortality of virtually all degenerative diseases.

Schachter Director of the Schachter Center for Complementary Medicine, Michael B. Schachter, M.D., is a 1965 graduate of Columbia College of Physicians & Surgeons. He is board certified in Psychiatry, a Certified Nutrition Specialist, and has obtained proficiency in Chelation Therapy from the American College for Advancement in Medicine (ACAM). Dr. Schachter has more than 30 years experience in complementary and alternative medicine. Our talented staff of trained professionals work together to evaluate and treat patients who have a wide variety of medical complaints as well as those who simply wish to optimize their health. Sophisticated biochemical testing is available.

Using the latest advances, our clinical staff strives to uncover the underlying causes of disease and to change the physical and emotional terrain to establish an environment that supports the body's natural ability to heal itself. You can also see their website at

Source: The Diagnosis And Treatment of Hypothyroidism. Schachter, Michael.

Tags:  hypothyroidism 

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What Lies Behind the Vitamin D Revolution?

Posted By Administration, Friday, June 11, 2010
Updated: Friday, April 18, 2014


by Ronald Hoffman, MD

Generations of medical professionals have been taught to approach vitamin D supplementation with great caution and trepidation. As a fat-soluble vitamin known to enhance calcium absorption, vitamin D taken in excessive amounts was thought to raise the specter of hypercalcemia with its attendant risks of nephrolithiasis and even metastatic calcification. Our understanding of vitamin D's health benefits was limited to its familiar role in maintaining bone strength by means of regulating calcium uptake. But thanks to an explosion in vitamin D research, a broader perspective is rapidly evolving.

Powered by its pervasive influence on myriad physiological processes, vitamin D is staking its claim as "Nutrient of the Decade." We now recognize that vitamin D transcends the definition of a mere vitamin: It is actually a prohormone, and vitamin D receptors are expressed by cells in most organs, including the brain, heart, skin, gonads, prostate gland, and mammary glands. In the digestive tract and parathyroid glands, active vitamin D metabolites are responsible for calcium uptake. Vitamin D receptors are also involved in immune regulation and mediate response to infection and inflammatory processes. Additionally, the nutrient is associated with cell proliferation and differentiation.

Fracture prevention

Vitamin D's traditionally acknowledged role is in bone metabolism. The pathognomonic vitamin D deficiency disease is rickets, but less overt prolonged insufficiency results in osteomalacia. This condition is characterized by softening of the bones and musculoskeletal pain, the result of periosteal traction. Not surprisingly, an association between vitamin D repletion and relief of unexplained body aches has been observed in some studies. 

Chronic vitamin D deficiency can result in secondary hyperparathyroidism with consequent osteoporosis. Vitamin D deficiency in childhood and adolescence impairs attainment of optimal bone mass. Frequently, clinicians neglect to assess vitamin D status and don't consider the treatment option of aggressive repletion when using drugs to manage osteopenia or osteoporosis. A new minimum threshold for vitamin D of 50-75 nmol/L (20-30 ng/mL) was recently proposed to prevent osteoporosis. However, vitamin D receptor polymorphisms modulate skeletal response to vitamin D supplementation even in healthy girls, and individual requirements for bone optimization may vary. A minimal threshold of 40 ng/mL for healthy bone metabolism has also been proposed.

The ultimate goal of osteoporosis treatment is fracture prevention. Considerable evidence suggests vitamin D can support muscle strength and thereby reduce the incidence of falls, particularly in elderly, at-risk patients. In addition, vitamin D arguably has an indirect role in staving off fractures: As a nondrug treatment for osteoporosis, the use of vitamin D reduces polypharmacy with various cardiovascular, anti-inflammatory, and psychiatric medications that can induce nutrient depletions and impair balance in frail seniors. 

Cardiovascular disease

Vitamin D deficiency is associated with increased risk for cardiovascular events and mortality. In the Multi-Ethnic Study of Atherosclerosis, 25-hydroxyvitamin D (25[OH]D)levels were inversely associated with the risk of coronary artery calcification, a measure of coronary atherosclerosis.

Cardiovascular disease (CVD) represents the culmination of an array of predisposing influences, and vitamin D may intervene beneficially in several ways. Studies confirm an association between obesity and vitamin D deficiency, and low vitamin D status is predictive of insulin resistance. Overweight women replete with vitamin D shed pounds more successfully. Moreover, studies have found correlation between suboptimal vitamin D status and both hypertension and diabetes.

In renal disease, characterized by problematic vitamin D metabolism, CVD is rampant—but cardiovascular risk is known to be attenuated by vitamin D administration.

Evidence also indicates that vitamin D deficiency—common in elderly, debilitated patients—plays a role in congestive heart failure, which is mediated by the nutrient's effect on myocyte contractility.


Sun exposure is clearly required for vitamin D sufficiency. However, latitude, season, time of day, weather conditions, shade, skin pigmentation, air pollution, clothing, use of sunscreen, and age impact cutaneous vitamin D activation. Below 32º latitude (corresponding to a line stretching from Los Angeles to Columbia, S.C.), sunlight exposure can activate vitamin D year-round. But above 44º north latitude (which extends from the northern tip of California to Boston), no cutaneous activation is possible from November through February.

It has long been noted that colon cancer rates increase with higher geographic latitude. This epidemiologic correlation was initially attributed to Western diet and lifestyle, but subsequent studies controlled for extraneous factors and confirmed the protective role of sunlight. Scientists were then able to establish the biological plausibility for the impact of vitamin D in cancer prevention, recognizing the vitamin's effects on cell proliferation, oncogenesis, and apoptosis. Since then, investigators have explored a putative involvement of vitamin D in both primary and secondary prevention of prostate cancer and breast cancer as well as non-Hodgkin's lymphoma, melanoma, and other malignancies.


Cells involved in innate and adaptive immune responses —including macrophages, dendritic cells, T cells, and B cells—express the vitamin D receptor. In the 19th century, before the advent of antibiotics, caregivers recognized that individuals with TB could benefit from sunlight and fresh air during their stays in mountain sanitoria. Research has confirmed that host response to TB is partially mediated by vitamin D, and that vitamin D deficiency is associated with dysregulation of macrophage response. 

The observed seasonal correlation between sunlight exposure and the incidence of viral upper respiratory infections has prompted speculation about the role played by vitamin D. Research confirms that vitamin D dramatically stimulates the expression of potent antimicrobial peptides. These compounds exist in neutrophils, monocytes, natural killer cells, and epithelial cells lining the respiratory tract, where they play a major role in protecting the lung from infection. The action of vitamin D serves as a key link between Toll-like receptor activation and antibacterial responses in innate immunity. An association between vitamin D insufficiency (25[OH]D <40 nmol/L) and acute respiratory tract infection was recently confirmed. As yet, prospective intervention studies are few and small in scale.


The incidence of certain autoimmune diseases correlates positively with latitude from the equator, as reflected by the epidemiology of rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, and multiple sclerosis (MS). Studies confirm that patients suffering from autoimmune disease have vitamin D levels below the international norm. There is substantial biological rationale for vitamin D as a cytokine modulator. 

Animal models of autoimmune disease suggest a response effect with vitamin D administration; large human therapeutic trials using vitamin D are still lacking, but the first results of phase I/II studies are promising. Meanwhile, it is now acknowledged that administering vitamin D in patients with autoimmune diseases is justifiable. 

Other conditions

Perhaps the most persuasive rationale for considering vitamin D optimization comes from a study of 3,400 French men, age 50 years and older, correlating vitamin D status with all-cause mortality. Men in the lowest quartile of 25(OH)D levels had a 44% higher death rate. The authors qualified their findings by stating that although the study controlled for lifestyle variables and comorbidities, a possibility exists that low levels of vitamin D are merely reflective, and not causative, of poor health status.

Because of the ubiquity of the nutrient's impact on physiologic processes, some researchers have proposed associations between vitamin D status and incidence of autism, allergic diseases, depression, schizophrenia, cognitive impairment, pre-eclampsia, fibromyalgia, Parkinson disease, polycystic ovary syndrome, and benign prostatic hyperplasia. Athletic trainers, cognizant of research suggesting that vitamin D may augment muscle strength, are increasingly embracing oral supplementation and UV-light exposure for purposes of performance enhancement. 

Of course, a long-observed relationship between sunlight exposure and severity of psoriasis suggests mediation by vitamin D; topical calcipotriene (Dovonex), a synthetic vitamin D analogue, is a standard dermatologic treatment for the condition.

Vitamin D has received renewed interest for its role in pregnancy. Studies suggest that higher levels of vitamin D supplementation than are currently recommended for pregnant women may safeguard offspring from the risks of low birth weight, autism, juvenile diabetes, asthma and allergic rhinitis, and infectious diseases. The Canadian Pediatric Society recently recommended that pregnant women increase their intake of vitamin D to 2,000 IU/day.


Pervasiveness of deficiency and risk factors

A number of health authorities now acknowledge that vitamin D deficiency is a pervasive problem in the United States and the developed world. Sun deprivation, already a problem for inhabitants of temperate latitudes, is exacerbated by indoor occupations and recreation and is further encouraged by warnings against sun exposure to prevent skin cancer.

Although overt vitamin D deficiency is no longer common in U.S. children, lesser degrees of vitamin D insufficiency are widespread. Groups at heightened risk for vitamin D deficiency include: the homebound elderly; older individuals overall (due to the declining potential for vitamin D production as the skin ages); darker-skinned individuals (melanin in skin protects the skin from UV radiation but increases the exposure time required for photoactivation of pre-vitamin D in the skin); and members of communities that require their constituents to cover up. Obesity also is associated with vitamin D deficiency, and some evidence indicates that adipose tissue is involved in sequestration of the nutrient.

Conditions that predispose a person to vitamin D deficiency include liver disease, which interferes with the 25 hydroxylation of vitamin D; chronic renal failure, which interferes with 1 hydroxylation; and malabsorption syndromes, which are either iatrogenic (e.g., status after bariatric surgery or in users of fat-sequestering medications such as cholestyramine) or the result of biliary tract disease, cystic fibrosis, celiac disease, inflammatory bowel disease, or similar conditions. Certain drugs, including anti-epileptic medications, deplete vitamin D. To complicate matters, research points to vitamin D receptor polymorphisms, which attenuate end-organ response to circulating levels of vitamin D. 

Routine, modest supplementation is not a reliable bulwark against vitamin D deficiency. Researchers were recently surprised to note the high prevalence of vitamin D deficiency in pregnant women—the very group most likely to be shielded from this problem because of high compliance with prenatal-vitamin regimens. Additionally, living in the sunny, warm regions of the country may raise a person's chances of achieving vitamin D sufficiency, but a recent study of Hispanics in Arizona uncovered a high rate of vitamin D inadequacy.

Dietary sources of vitamin D are limited (Table 1). Milk, which is the only dairy product routinely fortified with the nutrient, supplies a mere 100 IU/cup, which represents only a quarter of the minimal requirement for adults. Human breast milk delivers only 25 IU/L on average. Herring, tuna, eel, and mackerel are all good sources of vitamin D, but many people avoid these foods because they do not like the taste. 


The two forms of vitamin D most commonly measured by clinical laboratories are 25(OH)D (calcidiol) and 1,25 hydroxyvitamin D (1,25[OH]2D) (calcitriol). Until recently, health-care providers predominantly relied on the latter for vitamin D assessment, but new findings suggest that its utility is limited (except in renal disease, in which 1 hydroxylation is an issue). Not infrequently, 1,25(OH)2D levels are found to be sufficient or even supra-normal while 25(OH)D levels remain suboptimal. 

Because of its greater reliability, a 25(OH)D level is now favored as the accepted method for determining vitamin D nutritional status. The optimal level of serum 25(OH)D is 35-55 ng/mL (90-140 nmol/L), with some medical scientists advocating for the slightly higher value.

Many reference labs have adopted a classification system that stratifies vitamin D levels as follows (to convert conventional [ng/mL] units to SI [nmol/L] units, multiply by 2.5):

0-14.9 ng/mL = Severely deficient 

15.0-31.9 ng/mL = Mildly deficient 

32.0-100.0 ng/mL = Optimal 

>100.0 ng/mL = Toxicity possible 

Findings of elevated bone isoforms of alkaline phosphorous, elevated parathyroid hormone, or urinary N-telopeptide should prompt suspicion of vitamin D deficiency (to be confirmed by serum measurement of 25[OH]D).


The threshold for vitamin D toxicity is currently being re-evaluated, with most experts now agreeing that previous benchmarks have been unduly conservative (Table 2). This change in thinking stems partially from the realization that a single, minimal erythemal dose of sun exposure promotes synthesis of 10,000 IU of vitamin D. Early reports of vitamin D toxicity with doses as low as 3,600 IU/day have been challenged due to methodologic flaws. It has been reported that human toxicity likely begins to occur after chronic daily vitamin D consumption of approximately 40,000 IU/day. 

A theoretical risk of vitamin D toxicity exists when prolonged sunlight exposure is combined with aggressive supplementation, but feedback inhibition occurs with UV-light activation of vitamin D in the dermis, rendering this possibility less likely.

Clinicians must administer vitamin D cautiously in patients with certain medical conditions. For example, individuals with primary hyperparathyroidism are at risk for hypercalcemia, which might be exacerbated by additional vitamin D. (Conversely, in secondary hyperparathyroidism, correction of the underlying vitamin D deficiency helps normalize elevated calcium).

In sarcoidosis and such malignancies as oat-cell cancer and non-Hodgkin's lymphoma, aberrant conversion of 25(OH)D to calcitriol results in hypercalcemia, offering a relative contraindication to vitamin D administration.

The main symptoms associated with vitamin D toxicity result from hypercalcemia. Anorexia, nausea, and vomiting can develop, followed in some cases by renal failure. The diagnosis can be confirmed through measurement of serum 25(OH)D (typically >140 ng/mL) in the presence of elevated serum calcium.

Treatment involves stopping vitamin D intake. If necessary, the clinician can hydrate the patient with IV normal saline and administer corticosteroids or bisphosphonates (which inhibit bone resorption) to reduce blood calcium levels.

Recommendations for supplementation 

The longtime government recommendation for vitamin D intake in adults and older children was set rather arbitrarily at 400 IU/day. This is thought to derive from the historical precedent that a teaspoon of cod liver oil, a traditional source of supplementation, delivers approximately 400 IU of vitamin D.

For infants younger than age 4 years, the Daily Value (developed by the FDA to help consumers compare the nutrient contents of products within the context of a total diet) is just 200 IU, but in 2008 the American Academy of Pediatrics took the lead in advancing the threshold to 400 IU in light of evidence of the safety and benefits of vitamin D.

The Food and Nutrition Board of the Institute of Medicine is currently re-examining Daily Values for vitamin D and calcium and plans to issue revised guidelines this year. Most nutrition scientists are expecting upward revisions.

Controversy now rages over what constitutes "deficiency" versus "sufficiency." Alternatively, optimal therapeutic levels may be appropriate for various health conditions. Guidelines for prevention of rickets, for example, may be inadequate for prevention or reversal of osteoporosis. Some argue that nutritional support for such autoimmune diseases as MS might call for pharmacologic doses of vitamin D. In a recent study, 16% of 25 MS patients who were given an average of 14,000 IU/day of vitamin D for one year suffered relapses. In contrast, close to 40% of 24 MS patients who took an average of 1,000 IU/day—the stepped-up supplementation belatedly acknowledged to be necessary by many MS specialists—relapsed. 

A clue to the amount of vitamin D needed to optimize serum levels of 25(OH)D in seniors comes from a study of men and women older than age 64 years. The intakes required to maintain serum 25(OH)D concentrations of >15 ng/mL, >20 ng/mL, and >32 ng/mL in 97.5% of the sample were 688 IU/day, 988 IU/day, and 1,548 IU/day, respectively. Note that these levels of supplementation are well above the current Daily Values yet do not even attain what some consider being optimal thresholds for vitamin D.

Vitamin D supplements are available in two forms, D2 (ergocalciferol) and D3 (cholecalciferol). High-dose prescription vitamin D 50,000 IU (Drisdol, Calderol, Calciferol), commonly prescribed for rapid remediation of vitamin D deficiency, is vitamin D2. Vitamin D2 is manufactured by the UV irradiation of ergosterol in yeast, and vitamin D3 is manufactured by the irradiation of 7-dehydrocholesterol from lanolin and the chemical conversion of cholesterol.

Some argue that vitamin D3 could be more than three times as effective as vitamin D2 in raising serum 25(OH)D concentrations and maintaining those levels for a longer time, and that its metabolites have superior affinity for vitamin D-binding proteins in plasma. Further research is required to compare the clinical efficacy of the two forms.

Most supplements available from health-food stores are vitamin D3. Commonly available doses range from 400 to 5,000 IU, variously delivered in tablet, capsule, and liquid forms. Parenteral forms of vitamin D are also available but are seldom needed to reach target levels outside the settings of chronic renal failure and dialysis.

Suggested treatment of vitamin D deficiency 

Vitamin D deficiency (25[OH]D level <20 ng/mL): Vitamin D 50,000 IU once a week for three months; repeat 25(OH)D level.

If >20 ng/mL but <30ng/mL, change the vitamin D supplement to 5,000 IU/day until levels of 40-50 ng/mL are attained.

If still <20 ng/mL, advance vitamin D to 50,000 IU twice a week, or consider giving it more frequently. (In certain clinical situations, especially those involving malabsorption syndromes, up to 50,000 IU three times a week may be needed.) 

Vitamin D insufficiency (25[OH]D level 20-30 ng/mL): Administer vitamin D 5,000 IU daily for three months, repeat 25(OH)D level.

If <30 ng/mL, advance vitamin D to 50,000 IU once a week or more frequently if needed.

Once 25(OH)D levels are restored to >40 ng/mL, administer maintenance supplementation of 2,000-5,000 IU/day. 

For reasons that are not yet completely clear, considerable variability in response to vitamin D supplementation exists among patients. Clinicians should monitor a patient's 25(OH)D levels frequently to assess reaction to therapy until stable levels are achieved, subject to seasonal variations and changes in health status.

- Ronald Hoffman, MD

Dr. Hoffman is founder and Medical Director of the Hoffman Center in New York City. The author has no relationships to disclose relating to the content of this article.

Read on

  • Arabi A, Zahed L, Mahfoud Z, et al. Vitamin D receptor gene polymorphisms modulate the skeletal response to vitamin D supplementation in healthy girls. Bone. 2009;45:1091-1097.

  • Lips P, Bouillon R, van Schoor NM, et al. Reducing fracture risk with calcium and vitamin D. Clin Endocrinol (Oxf). 2009; September 10 (published online ahead of print).

  • Stechschulte SA, Kirsner RS, Federman DG. Vitamin D: bone and beyond, rationale and recommendations for supplementation. Am J Med. 2009;122:793-802. 

  • Janssens W, Lehouck A, Carremans C, et al. Vitamin D beyond bones in chronic obstructive pulmonary disease: time to act. Am J Respir Crit Care Med. 2009;179:630-636.

  • Holick MF. The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action. Mol Aspects Med. 2008;29:361-368.

  • Rovner AJ, O'Brien KO. Hypovitaminosis D among healthy children in the United States: a review of the current evidence. Arch Pediatr Adolesc Med. 2008;162:513-519. 
  • Cannell JJ, Hollis BW. Use of vitamin D in clinical practice. Altern Med Rev. 2008;1:6-20.

  • Autier P, Gandini S. Vitamin D supplementation and total mortality: 
a meta-analysis of randomized controlled trials. Arch Intern Med. 2007;10:167:1730-1737. 
  • Arnson Y, Amital H, Shoenfeld Y. Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann Rheum Dis. 2007;66:1137-1142.

  • Holick MF. Medical Progress: vitamin D deficiency. N Engl J Med. 2007;357:266-281. 
  • Niino M, Fukazawa T, Kikuchi S, Sasaki H. Therapeutic potential of vitamin D for multiple sclerosis. Curr Med Chem. 2008;15:499-505.

  • Garland CF, Gorham ED, Mohr SB, Garland FC. Vitamin D for cancer prevention: global perspective. Ann Epidemiol. 2009;19:468-483.

  • de Boer IH, Kestenbaum B, Shoben AB, et al. 25-hydroxyvitamin D levels inversely associate with risk for developing coronary artery calcification. J Am Soc Nephrol. 2009;20:1805-1812. 

  • Cannell JJ, Zasloff M, Garland CF, et al. On the epidemiology of influenza. Virol J. 2008;5:29.
  • Laaksi I, Ruohola J-P, Tuohimaa P, et al. An association of serum vitamin D concentrations <40 nmol/L with acute respiratory tract infection in young Finnish men. Am J Clin Nutr. 2007;86:714-717. 
  • Szulc P, Claustrat B, Delmas PD. Serum concentrations of 17beta-E2 and 25-hydroxycholecalciferol (25[OH]D) in relation to all-cause mortality in older men—the MINOS study. Clin Endocrinol (Oxf). 2009;71:594-602.

  • Cashman, KD, Wallace J MW, Horigan G, et al. Estimation of the dietary requirement for vitamin D in free-living adults >64 y of age. Am J Clin Nutr. 2009;89:1366-1374.

All electronic documents accessed February 10, 2010.

Published March 1, 2010. The Clinical Advisor. What Lies Behind the Vitamin D Revolution. By Ronald Hoffman, MD.

Tags:  vitamin D 

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Getting the Lead Out for Optimal Health

Posted By Administration, Tuesday, June 8, 2010
Updated: Friday, April 18, 2014

Sensible steps for purging lead and other toxic metals can have profound health implications for people of all ages.

by John Pittman, MD, and Mark N. Mead, MSc


Lead is a toxic metal with an ancient relationship to public health.  The Greek physician Hippocrates, considered the “father of Western Medicine”, is thought to have written the first case report of lead poisoning in 600 BC. In ancient Rome, lead’s extensive use in cooking utensils, cosmetics, wine vessels, aqueducts and water pipes may have contributed to widespread toxic effects—possibly even accounting for imperial madness, infertility, and miscarriage rates that kept the ruling class from replacing themselves.  The bones from Roman graves show high concentrations of lead.  It seems ironic that the powerful empire may have been defeated more primarily by its lack of environmental health awareness than by any opposing army per se.  

Our recent history has again boosted the lead count, but by very different means. Three industrial centuries have greatly increased the mining and smelting of lead, resulting in its widespread dispersal in air, water, and soil. In the 1970s, when leaded gasoline was in vogue, automobiles were the number one contributor to lead pollution here in the United States.  Thankfully, this form of gasoline was phased out, and blood lead levels dropped as a consequence.  Other preventive strategies such as eliminating lead as an additive from paint and as a component of lead solder in food cans have resulted in further lowering of blood lead levels among U.S. children.  (Note:  Lead from solder leaches more readily into acidic foods, like tomatoes and citrus, than into nonacid and dry foods.  Tests of canned tomato products in the late 1980s found that about one quarter of the cans tested contained lead-soldered seams.) 

Despite these important public health measures, lead continues to be a problem today. Modern body burdens of lead are still hundreds of times higher than those natural, prehistoric levels with which we evolved.  The metal is used in construction, for decorations, in pottery glazes, and even as a food additive. Lead soldering in old water supply pipes results in some lead leaching into drinking water supplies. Imported toys and other children’s products may be a major source of lead exposure for U.S. children.   In 2007, tests on more than 1,200 children’s products found that 35 percent contain lead—many with levels far above the federal recall standard used for lead paint, according to the Michigan-based Ecology Center along with the national Center for Health, Environment and Justice and groups in eight other states. 

Much of the concern about lead’s harmful effects has focused on younger people.  An estimated 310,000 U.S. children younger than five years have elevated blood lead levels, according to a 2009 estimate by the Centers for Disease Control and Prevention.  Unfortunately, younger brains are uniquely susceptible to the toxic effects of lead.   By the same token, however, many children with elevated blood lead levels show huge improvements in their health and behavior when we take the proper steps to “get the lead out.”   

 A Threat to Adults as Well 

It’s not just young people who are at risk of lead-related health effects.  We now know that lead promotes hypertension and boosts the risk of dying from cardiovascular disease.  For example, in the October 2006 issue of Environmental Health Perspectives, researchers reported on a 12-year study of nearly 9,800 adults, all over age 40, who were part of the Third National Health and Nutrition Examination Survey, or NHANES III.  Those people with blood lead levels higher than 10 µg/dL were 59% more likely to die from cardiovascular disorders compared with people who had blood lead below 5 µg/dL. 

Another NHANES III-based study looked into the connection between blood lead levels and overall mortality over a 12-year period. Reporting in the medical journal Circulation on September 26, 2006, the researchers concluded that blood lead levels as low as 2 µg/dL—a level deemed safe by the U.S. Centers for Disease Control—were linked with a significantly increased risk of overall mortality and an increased risk of dying from both coronary heart disease and stroke.  Given that nearly 40% of U.S. adults have a 2 µg/dL blood lead level, the public health implications of these findings are immense.  Yet another study from NHANES found that people with higher blood lead levels were nearly three times more likely to have chronic kidney disease, and twice as likely to have peripheral arterial disease, as reported in the 10 October 2005 Archives of Internal Medicine. 

These research findings prompt the question: How many people seeking mainstream medical treatment for these conditions never get their lead levels checked and therefore end up taking costly medications for the rest of their lives?  How many people are going in for costly cardiac drugs and surgery without realizing that metal toxicity may be a critical underlying cause or promoting factor?  Imagine how health care could be improved by addressing this common yet widely unrecognized biological insult. 

Long-term effects of lead on the brain have also been identified.  A recent look at data from the Nurses Health Study found a significant link between cognitive deficits in the elderly and higher lead levels in the tibia or “shinbone” (a leg bone that records long-term lead exposure). Several studies have now shown that memory loss and other kinds of psychological deterioration are associated with the tibia lead levels in older people.  In the January 2009 issue of Neuropsychology, experts reported that bone lead levels predicted cognitive decline in people over age 55. Also, hypertension could play a mediating role in the relationship between lead exposure and age-related cognitive decline, as reported online in the 27 May 2009 issue of Neurotoxicology. 

It’s important to remember that the development of senile dementia is most likely preceded by small and often subtle decreases in cognitive functioning over time.  In this regard, adults are at risk of “silent” toxicity from low-level lead exposures that gradually damage the brain over decades.  Thus, the brain-toxic effects of lead may be very hard to perceive or sort out in the context of the aging process. 

How Low Can You Go?

Overt symptoms of lead toxicity are rare at blood lead levels of less than 70 µg/dL.  But much lower levels are still toxic to the brain, and as we just noted above, lead can alter brain function in a gradual, silent manner, whereby the cognitive and behavioral changes are themselves so gradual as to be almost imperceptible.  For very young people, however, the effects of lead exposure are more readily seen in the form of reduced test scores, spelling ability, reading comprehension, and attention span—all outcomes that have been significantly correlated with blood lead levels. 

The U.S. Centers for Disease Control has set a safe blood lead level for children at 10 µg/dL.  Any lead level above 10 µg/dL may promote hyperactivity, distractibility, memory loss, hearing loss, and low IQ scores. But new research indicates that even lower lead levels—on the order of 3 to 5 µg/dL—may compromise one’s cognitive ability.  For infants and young children, there currently appears to be no safe threshold for lead exposure, especially if other brain-toxic pollutants (e.g., mercury and all pesticides on the market) and poor dietary habits are thrown into the mix. 

Just how bad is the problem of lead exposure in the general population? A study in the March 2, 2009 issue of Pediatrics concludes that, although blood lead levels have dropped since the 1970s, they continue to be higher for low-income children, non-Hispanic black children, and children living in older housing (built before 1950).  Some of the children with high blood lead levels have been exposed to lead from consumer products, imported toys, imported traditional medicines, and house wares.  And children whose parents work with lead are confronted with “take-home” lead exposure. 

The authors of the above-mentioned Pediatrics report recommended more aggressive efforts to identify sources of lead, and to measure blood lead levels in those children most at risk.  In this regard, North Carolina was among the first states to institute such proactive strategies.  In the 1980s, public health officials suspected a link between high lead levels and the state’s low national ranking in SAT scores.  All NC property owners were required by law to begin eliminating lead hazards such as peeling paint or contaminated soil in places where younger children (under age 6) spend time.  The state’s Childhood Lead Poisoning Prevention Act, which went into effect on July 1, 1990, was designed to detect and correct high-lead situations prior to exposing the children. 

Nutritional Keys and the Calcium Connection

Lead’s health effects also bear a close relationship to calcium.  Like various radioactive elements, most of the lead we absorb is eventually stored in our bones, where over 99% of the body’s calcium is also stored.  Scientists once thought the bone’s lead deposits were relatively harmless; however, when calcium leaves the bones, lead is released simultaneously, and this results in a rise in the blood lead level. 

Whenever the blood’s calcium level is low, calcium is drawn from the bones to function in more essential body processes like nerve transmission and heartbeat. Such losses are most dramatic when people consume diets high in meats and other protein-rich foods, and high-fat foods and caffeine can further exacerbate the losses. For woman, bone-calcium losses occur naturally during pregnancy, lactation, and menopause—a process further amplified by the dietary habits just mentioned. 

People who minimize these dietary habits and consume plenty of dark leafy greens—which are rich in calcium—will be less likely to experience the lead-calcium time bomb.  Taking a high-quality calcium supplement is also recommended, ideally one that contains either calcium citrate or hydroxyapatite. 

A substantial amount of today’s lead exposure happens through the food chain—from airborne lead that falls on agricultural areas. Such fallout has resulted in major increases in the lead content of rice, oats, lettuce, cabbage, and other vegetable foods. Once lead enters the food chain, it becomes increasingly concentrated in animal flesh, which is yet another reason to avoid a heavy meat diet.  EPA officials estimate that U.S. adults consume, on average, about 30 to 40 micrograms of lead each day through food, the major route for adult exposure. 

Successful Removal of Toxic Metals

Since lead has an obvious potential to promote hypertension, hamper learning ability, and disrupt other aspects of behavior and personality, it behooves us to find ways to pull the lead out of our bodies.  At this time, chelation therapy is the only established way to do eliminate toxic metals.  The word chelation derives from the Greek word “chele”, which refers to the claw of a crab or lobster.  The “claw” in chelation therapy is the chelator itself, a substance that binds to toxic metals, essentially pulling them out of the body through the urine and feces.   

Among the oldest of these “claws” is the synthetic amino acid disodium ethylenediamine tetra-acetic acid (EDTA).  When given intravenously, EDTA binds ionic calcium, trace elements and other divalent cations and transports these bound components out of the body in the urine.  The standard approach to EDTA chelation is to mix the compound with antioxidant nutrients in an intravenous solution that is administered repeatedly over weeks to months.  Between chelation sessions, high oral doses of antioxidant vitamins and mineral supplements are typically recommended. 

Chelation therapy with EDTA and/or DMSA has long been used for the treatment of lead poisoning.  The U.S. Food and Drug Administration has approved both drugs as a treatment for lead and heavy metal poisoning.  Some physicians only recommend chelation therapy when the blood lead level reaches 45 μg per dL (2.17 μmol per L) or greater, as reported in the 15 March 2010 American Family Physician.  However, this high blood level usually only reflects an acute lead exposure.  Repeated or chronic low-level exposures are more common and result in accumulations of lead in the bones.   Thus, it is possible to have a much lower blood level, on the order of 10 μg per dL or lower, yet still have a high body burden of lead. 

To assess your child’s overall body burden—and to get some sense of how much of the metal might be stored in the bones—the urinary chelation challenge test should be used in addition to the blood test.  The challenge test involves giving EDTA and then measuring how much lead comes out in the urine.  If findings from the challenge test indicate a high body burden, then the chelation approach can be very beneficial.  (Note:  Another method entails the use of Kappa x-ray fluorescence, which measures lead in bone, usually in the tibia and patella.) 

If your child’s lead count is unacceptably high, oral or intravenous EDTA, along with natural chelating agents, can be used to draw the lead out of the tissues and blood before sending it on to the kidneys and being excreted in the urine.  When properly administered, such chelation sessions may help safeguard your child’s intellectual potential. For example, kids with either ADHD or Autism Spectrum Disorders who have high lead levels often show substantial improvements in their overall behavior when the lead levels are brought down. 

Similarly, adults with high lead levels will generally experience a gradual improvement in symptoms after a series of chelation treatments and an extended period whereby their blood lead level remains low.  Those with very high lead levels will show greater improvements after chelation, including better cognitive function.  But in most cases, the improvements will lag behind the decline in blood lead levels, probably because of the relatively slower removal of lead from the brain and central nervous system. The pace of improvement can be highly variable from one individual to the next, ranging from weeks to a year or more depending on the magnitude of the lead burden as well as the individual’s overall nutritional status. 

Many people only show the neuro-cognitive benefits when chelation therapy is used in the context of comprehensive nutritional support and other forms of treatment, such as cognitive rehabilitation and occupational therapy.  It’s important to note that short-term improvements in cognitive functioning following a decline in the blood lead level may not be able to override or reverse the harmful effects of long-term cumulative lead exposures. 

This is why getting the lead out at an earlier stage of life is so critical, and why preventing or minimizing lead exposures is always the top priority.  There is a critical time period—less than 3 years of age—during which lead and other toxic metals can have a profound long-range impact on IQ, attention span, and antisocial behaviors.  Chelation therapy’s ability to impact neurobehavioral development is clearly greatest in these early years.  But older children, too, can benefit from appropriate removal of lead and other metals.  In many cases, we find that children with ADHD, learning disabilities, or Autism Spectrum Disorders will not respond well to other biological therapies or to behavioral approaches until their toxic metal burden has been substantially reduced. 

An Integrative Approach is Essential 

Chelation is clearly the best treatment against metal poisoning, but it must be performed correctly in order to be effective.   Research reviewed in the October 2008 issue of the Indian Journal of Medical Research indicates that chelation therapy is most effective when combined with specific antioxidants and nutritional factors that support the body as it attempts to eliminate the toxic metals. Along these same lines, research reported in the 15 April 2007 issue of Cellular & Molecular Biology confirms the value of chelation therapy for reversing a situation of toxic overload with lead and arsenic.  The authors of this paper, titled “Arsenic and lead-induced free radical generation and their reversibility following chelation”, emphasized the importance of judicious chelation therapy in combination with specific antioxidant nutrients and herbals to support optimal detoxification. 

Our own clinical experience at the Raleigh-based Carolina Center for Integrative Medicine suggests, similarly, that chelation is most effective when accompanied by supportive strategies such as selenium, zeolites, herbal chelators, and glutathione-boosting nutritional strategies.  The lack of inclusion of these supportive measures in randomized clinical trials may explain why the few trials completed to date have not demonstrated any major benefits.  You can have the most rigorous clinical study design on the planet, but if your intervention is bogus, so too will be the results of the study.  

If lead-laced wine did indeed cause the madness of Caesars and bring the Roman Empire to ruin, then the rising tide of toxic metal pollution means that our society’s sanity and intelligence may be at stake.  Unless we clean up our act and fast, we may be putting our brains at risk for the indefinite future.  Using chelation therapy within the framework of integrative medicine—that is, coupled with individually tailored nutritional and herbal support—is our best hope for turning the biological tide in a body already burdered with lead, mercury, cadmium, and other toxic metals.  


To reach the authors or schedule a consultation, or to obtain more information on how to optimize the removal of toxic metals, contact the Carolina Center for Integrative Medicine in Raleigh, NC at 919-571-4391, or visit the website at

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Clinical Aspects and Management of Fibromyalgia Syndrome

Posted By Administration, Friday, May 21, 2010
Updated: Friday, April 18, 2014



Fibromyalgia syndrome (FMS) is a chronic and debilitating musculoskeletal pain disorder of unknown aetiology with usual accompanying features of fatigue, sleep disturbances and stiffness. Its place in medical textbooks was controversial with rheumatologists holding the helm of its management for many years. Over the last decade, abnormalities have been identified at multiple levels in the peripheral, central, and sympathetic nervous systems as well as the hypothalomo-pitutary-adrenal axis stress response system. With the elucidation of these pathways of pain, FMS is known more as a central sensitivity syndrome. This led to tremendous increment in interest in both pharmacological and non-pharmacological treatment of FMS. The United States Food and Drug Administration (FDA) has also successively approved 3 drugs for the management of fibromyalgia – pregabalin, duloxetine and milnacipran. Non-pharmacological modalities showed aerobic exercise, patient education and cognitive behavioural therapy to be most effective. Overall, management of FMS requires a multi-disciplinary approach. 

                                                        Ann Acad Med Singapore 2009;38:967-73 

Key words: Aetiology, Fibromyalgia-Fibromyositis Syndromes, History, Pain syndrome


Fibromyalgia syndrome (FMS) has been referred to as a medically unexplained syndrome; a rheumatological entity described in rheumatology textbooks and taught to all training rheumatologists,and lately with newer development in research particularly in neurophysiology, as a central sensitivity syndrome. Due to its lack of objective findings on physical examination, laboratory and imaging modalities, FMS was once dismissed by physicians and the public as a psychological disorder. It was thought to be a society-driven disorder, whereby expressions of the distressed patient’s problems are made into a “disease”, hence becoming more legitimate for equal social support and sympathy from the medical community. Whether this is actual social or economic medicalisations, there are real patients suffering real symptoms. 


FMS is a chronic musculoskeletal pain disorder of unknown aetiology, characterised by chronic widespread pain and muscle tenderness and the presence of tender points on examination. Patients experience both allodynia (pain from a normally nonpainful stimulus) and hyperalgesia (inappropriately intense pain from a normally painful stimulus). Other common accompanying features are fatigue, sleep disturbances, stiffness, paraesthesias, headaches, Raynaud’s like symptoms, depression and anxiety. FMS is much more than widespread pain as it overlaps substantially with other central sensitivity syndromes such as chronic fatigue syndrome, irritable bowel syndrome, chronic pelvic pain syndrome/ primary dysmenorrhoea; temporomandibular joint pain, multiple chemical sensitivity, restless legs syndrome and interstitial cystitis. In 1990, the American College of Rheumatology (ACR) published the classification criteria of Fibromyalgia. Patients who fulfilled these criteria must have firstly, pain for at least 3 months involving the upper and lower body, right and left sides, as well as axial skeleton, and secondly, pain in at least 11 of 18 tender points on digital examination. The second criterion requires these tender points to be digitally palpated with about 4 kg per unit area of force. Although the criteria provided a sensitivity of nearly 88% and specificity of 81% in distinguishing FMS, it is important to exclude other causes of chronic musculoskeletal pain.

Systemic diseases, such as hypothyroidism, systemic lupus erythematosus (SLE) and malignancies, can mimic FMS and have to be excluded. The classifi cation criteria initially drew considerable criticisms of over-relying on tender points, referring fibromyalgia as a discrete entity rather than a cut-point along a pain-distress continuum and under- emphasising on central symptoms of the syndrome, has now gained wide recognition in the medical community. Presumably, one understands that like most ACR criteria for other rheumatic diseases, it is developed for research purpose and over the years, it has aided our understanding of FMS in both research and clinical settings. 

History in Brief 

Clinical description of fibromyalgia has been reported since mid-1800s. In 1904, Sir William Gowers created the term “fibrositis” when he was actually referring to regional pain syndrome. The term “fibrositis” hence was a misnomer and no longer used as studies have shown that there were no inflammation within the connective tissues. “Fibromyalgia” was first introduced in 1976 in an editorial to the section on non-articular rheumatism in the 22nd “Rheumatism Review” of the American Rheumatism Association (currently known as ACR). Derived from both Latin (fi bra – fi ber) and Greek words (myo-muscle and algos –pain), it literally means “pain in the muscle and fibrous tissues”. Since then, the studying of fibromyalgia has gathered momentum. A Medline literature review found that the total number of medical articles dealing with fibromyalgia/FMS has increased 5-fold during this past decade,with non rheumatology journals publishing substantially more articles compared to a decade ago. 

Fibromyalgia Syndrome and Rheumatology 

Rheumatologists tend to be ambivalent about FMS though the condition has been traditionally perceived to be an entity from the rheumatology specialty due to the presence of physical pain and body tenderness. With the development of the ACR criteria in 1990 and the World Health Organization (WHO) providing Fibromyalgia ICD code, it has been conferred a “diagnosis” status. The general perception amongst rheumatologists is that patients with FMS takes up too much time for a busy clinical practice and having little success in managing these patients, most find FMS difficult to treat. Literature also showed FMS symptom measurements, such as pain, global severity, fatigue, sleep disturbance, anxiety, depression and health status, can remain unsatisfactory despite years of therapy. In the last 2 years, some even questioned whether FMS should be cared for by the rheumatologists at all as latest evidence showed FMS to be a pain syndrome centred in the nervous system. Although there was a recent study which showed that family physicians could be trained to diagnose FMS correctly in 70% of patients, there were many factors such as physician training, ethnicity and cultural biases which can affect the outcome of that study. Historical clinical evidence showed FMS can mimic autoimmune diseases, which was why its diagnosis was a constant challenge even to the rheumatologists. FMS patients can display symptoms suggestive of SLE such as peripheral neuropathy or manifest with low titre ANA levels ranging from 8.8% to 30% in FMS patients. Furthermore, FMS patients often present with bodily ache and joint pain but physical examination shows no objective evidence of synovitis. In addition, immunoglobulin depositions without complement fixations in the skin were documented in the skin of FMS patients. Sicca symptoms such as dry eyes and mouth which are characteristic of Sjorgren’s syndrome has been demonstrated in FMS patients. Despite these mimics, a retrospective analysis with long-term follow-up of FMS patients however showed no increased probability of FMS patients developing into any connective tissue disease.24 Nonetheless, FMS is the second most common musculoskeletal disorder which takes up the second most amount of time in rheumatologists’ offi ces. FMS can co- exist and affect management of other rheumatic diseases. It was estimated that 20% of patients with rheumatoid arthritis and 50% of patients with SLE suffer from fibromyalgia. 


Local Perception of Fibromyalgia Syndrome 

Local studies are however lacking. In 1999, a study in Singapore showed that fibromyalgia patients exist amongst our patients. Looking into 101 patients randomly selected from medical clinics and using dolorimeter to confirm the tender points, 6 patients (5.99%) fulfilled the ACR criteria for fibromyalgia. These patients had mean tender point count of 14.17 as compared to 5.58 from a sample population. Eighteen patients (17.8%) had 11 or more tender points but did not satisfy the criteria of widespread pain of more than 3 months’ duration. A survey on the awareness and perceptions of FMS in Malaysia and Singapore showed more than 90% of rheumatologists surveyed believed that FMS is a distinct entity, an illness rather than a disease, involving medical and psychological realms, and is confirmed by excluding other well-defined clinical diseases through a combination of clinical evaluation and screening tests. A more recent survey (personal communication – Feng PH. Short survey on fibromyalgia. August 2009) of Singapore rheumatologists/rheumatology trainees was undertaken in 2009. Although less than half responded, those responded believe FMS exists, do see FMS patients, use the ACR criteria for diagnosis, and treat FMS patients via a multi-disciplinary methods by co-managing these patients with pain specialists, psychiatrists, rehabilitation physicians, physiotherapists, psychologist and medical social workers. Majority are also of the opinion that they can play a role in managing FMS patients although some think that other specialists are more suited to managing FMS patients. Indeed, there were a few responders who believed that the diagnosis of FMS need not be a diagnosis of exclusion but it is imperative to exclude certain systemic diseases such as autoimmune diseases, malignancies or metabolic diseases. Literature evidence shows FMS patients underwent unnecessary operations thus consumed unnecessary healthcare resources. Positive diagnosis of FMS, on the other hand, is associated with reduced healthcare utilisation and reduction in investigations. Unfortunately, there is still no gold standard for diagnosis of fibromyalgia. The presence of ACR criteria, however, has inadvertently made the diagnosis of fibromyalgia simply to be “the blessing” of the rheumatologists. 

Epidemiology of FMS 

FMS is a very common condition, estimated to affect 2% to 4% of the population although local epidemiologic study is lacking. It has a prevalence of 3.4% in women versus only 0.5% in men with a female-to-male ratio of approximately 9:1. Usually diagnosed between 20 to 50 years of age, it increased with age until aged 70 after which it decreased slightly. FMS can also occur in children at prevalence rate of 1.2% and 1.4%. The prevalence of FMS is considerably higher in rheumatology clinic at 12% to 20% of new patients seen whereas it occurs in 5% to 6% of adult patients presenting at general medical and family practice clinics. 

Aetiology and Pathogenesis 

It is beyond the scope of this article to discuss the various aetiologies and pathogenesis of FMS. The exact aetiology of FMS is unknown and no single factor can lead to all the symptoms of FMS. Stress and medical illness can trigger FMS. Early studies showed there was no peripheral damage or infl ammation within the muscles or tissues. Focus then shifted for alternative explanations. Investigations have focused upon central pain processing systems such as disturbances in neurotransmitter and neuroendocrine regulations, reduced levels of biogenic amines, increased concentrations of excitatory neurotransmitters, including substance P, and dysregulation of the hypothalamic- pituitary-adrenal axis. FMS patients experience pain differently; they have allodynia, hyperalgesia as well as lower pain threshold as compared to normal. Sleep disruption has been implicated in FMS39,40 and over 90% of FMS patients complain of sleep problem. Fibromyalgia-like symptoms were reproduced in normal volunteers by depriving them of deep sleep. Evidence using functional brain imaging allow visualisation of structures involved in pain processing further suggest central cause of pain. Patients with FMS are thought to develop functional changes in the central nervous system (CNS) that result in central pain sensitisation that is manifested as increased excitability of neurons, enlargement of their receptive fields, reduction in pain threshold and recruitment of novel afferent inputs. Abnormalities have been identified at various levels in the peripheral, central, and sympathetic nervous systems, as well as the hypothalamo-pitutary-adrenal axis stress- response system. Despite evidence that emphasises the role of sensory and CNS abnormalities for the chronic pain associated with FMS, psychosocial factors also play an important role in the development and course of FMS. These include exposure to negative life events and chronic stress, increased focus on bodily symptoms and passive pain-coping mechanisms. A recent family study also found that FMS coaggregates with mood disorders in families, suggesting the possibility of shared pathophysiologic factors in FMS and mood disorders. 

Management of Fibromyalgia 

Numerous literatures are available on the management of fibromyalgia. Most FMS patients have been evaluated by different specialists and undergone multiple tests. The approach is to establish a correct diagnosis, to exclude differentials and to explain the implications of the diagnosis to the patients. The goals of therapy are to improve symptoms, function and emotional well-beings. Empathetic listening and acknowledgment that the patient is indeed experiencing pain would go a long way to validate the patient’s illness and establish rapport for further treatment. Prior to prescribing any form of treatment, it is imperative to assess any possible causal or perpetuating factors, including attention to psychological and sociocultural factors. Concomitant treatment of any possible nociceptive pain from an apparent pathology is important, for example, treating the pain from an infl amed bursitis or degenerative spondylosis. Excessive investigations or testings if not indicated should be discouraged. Physicians are also reminded to avoid comments such as “It’s all in your mind” or “I cannot find anything wrong with you”. Besides management of clinically relevant symptoms such as fatigue, depression, rigidity and sleep disorders; physical and emotional stress may aggravate FMS and needs to identified and treated appropriately. Evidence has shown that multi-disciplinary rehabilitation helps at least in the short term but effort needed to maintain long-term benefits.

Pharmacological Treatment 

A range of medical therapeutics, such as anti-infl ammatory like symptoms were reproduced in normal volunteers by depriving them of deep sleep. Evidence using functional drugs, opioids, muscle relaxants, antidepressants, sedatives and antiepileptics, have been used to treat FMS. With newer understanding of the neurophysiology of the FMS pointing to a central pain processing, research into drugs has intensified. This led to drugs being approved by the United States Food and Drug Adminstration (FDA). In June 2007, pregabalin became the first treatment approved by the FDA for the treatment of FMS. Currently there are 3 FDA-approved drugs for FMS. They are Pregabalin (Lyrica; Pfi zer, Inc), Duloxetine (Cymbalta; Eli Lily and Company) and Milnacipran (Savella; Forest Laboratories and Cypress Bioscience). Market survey showed the most frequent drugs used for treatment of FMS is non-steroidal anti-inflammatory drugs (NSAIDS) and since FMS is largely devoid of infl ammation, it is of little wonder that these treatment failed. 

Alpha-2-delta ligands such as gabapentin and pregabalin were used in the treatment of many pain conditions such as painful diabetic neuropathy and postherpetic neuralgia. As a α 2δ calcium-channel antagonist that acts by limiting the neuronal release of excitatory neurotransmitters, it can decrease pain, decrease sleep latency and modify sleep architecture by improving slow-wave sleep. Pregabalin was approved by the FDA for fi bromyalgia after demonstrating effi cacy in 3 published trials. Generally starting at lower doses, it should reach doses such as 600 mg daily. Most patients who discontinue pregabalin do so because of somnolence and dizziness especially with higher doses. However, a meta-analysis58 showed pregabalin at 150 mg daily was generally ineffective hence higher doses (such as 300 mg, 450 mg or 600 mg) were required. Gabapentin with the same mechanism of action has also been effective in the treatment of FMS.

Anti-depressants such as tricyclic anti-depressants (TCA), selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, citalopram and paroxetine as well as dual receptor inhibitors serotonin-norepinephrine reuptake inhibitors (SNRIs) have been found to be helpful in relieving symptoms of fibromyalgia. However, it was the SNRIs which provide more benefit as compared to pure serotonergic drugs. Initial trials with the first available SNRI, venlafaxine, showed conflicting results in the management of FMS. In June 2008, another SNRI duloxetine was approved by the FDA for the management of FMS. Duloxetine was previously approved for the treatment of peripheral neuropathic pain, depression and generalised anxiety disorder. This new approval was based on data from 2 pivotal double-blind, fixed-dose, randomised, phase-3 clinical trials of 12 weeks’ duration. A subsequent 6-month multi-centre, randomised, double-blind placebo-controlled trial showed reduction in pain severity and global assessments at 3 and 6 months, irrespective of depression status. The recommended dose of duloxetine is 60 mg once daily and no additional benefit was observed in patients receiving 120 mg once daily. Treatment should be initiated at 30 mg once daily for 1 week to allow patients to adjust to the medication before increasing to 60 mg once daily dosing. Improvement in pain can be felt as early as the first week and this benefit persisted throughout the study period. The common side effects of duloxetine were nausea, dry mouth, constipation, decreased appetite, somnolence, hyperhidrosis and agitation. 

Another SNRI, milnacipran, was approved in January 2009 for the management of fibromyalgia after its efficacy was established in 2 pivotal US phase 3 trials. Milnacipran was found to have greater efficacy than placebo for pain relief, improvement in global well-being and physical function. The recommended dose of milnacipran is 100mg or 200 mg daily. Adverse effects of milnacipran such as nausea, headache and constipation are the main reasons for discontinuation of treatment. Milnacipran is not available in Singapore at this point of time. 

In practice, patients often respond to combination of pharmacological treatments, although studies of combination pharmacotherapy are still limited. A α 2δ calcium-channel antagonist gabapentin in combination with SNRI venlafaxine was found to be more effective in improving symptoms of pain, fatigue, mood disturbance and insomnia in patients with neuropathic pain who did not respond to gabapentin monotherapy. Combinations of TCA and SSRI have also been proven more effective than either medication used alone. 

Other SSRIs (fluoxetine, fluvoxamine, citalopram and paroxetine ) and TCA (amitriptyline, desipramine) have all been studied for treatment of FMS but most showed modest effi cacy at best. A 2009 meta-analysis of 18 randomised, placebo-controlled studies of a variety of anti-depressants showed strong evidence for efficacy of anti-depressants for pain relief, fatigue, depressed mood, sleep disturbance and in improving health-related quality of life. 

As there is no inflammation present in FMS patients, anti-inflammatory drugs such as NSAIDS and steroids, are not effective. However, they have a role if there is concomitant inflammation condition which serves as a nociceptive trigger. Paracetamol helps pain relief but often insuffi cient when taken alone. Paracetamol in combination with tramadol, a narcotic that combines μ-opioid agonist- antagonist and SNRI activities may be helpful. Common side effects of tramadol are nausea, constipation and pruritis. However, the risk of abused and dependence with tramadol is low as compared to other opioids. 

Other pharmacologic modalities included use of human growth hormone, dehydroepiandrosterone (DHEA), 5-hydroxytryptophan, topisetron and pramipexole remain under investigation. Most of these drugs attempt to combat fatigue, rigidity, insomnia or poor sleep.

Non-pharmacological Treatment 

Non-pharmacolgical treatment modalities, including aerobic exercises, physical therapy, cognitive behavioural therapy (CBT), massage and acupuncture can be helpful. Few of these approaches have been demonstrated to have clear-cut benefi ts in randomised controlled trials. 

The role of aerobic exercise has been supported by systematic review. It was postulated that aerobic exercises can stimulate endogenous analgesic systems, increase time spent in deep sleep and increase a sense of well-being and control. The challenge is to start and maintain FMS patients in a structured exercise programme and the key here is to encourage exercise according to fitness level. Low impact exercise may be tailored to individuals with musculoskeletal problems. 

Adjunctive CBT will be indicated for patients with prominent psychosocial stressors, and/or difficulty coping, and/or difficulty functioning. CBT has also been proven on metaanalysis to improve FMS. CBT addresses the various aspect of the biopsychosocial model of FMS and can decrease depression and pain.Patient education as a modality has been found to have therapeutic effect with patient undergoing education intervention having had signifi cantly more improvement than controls but improvements are short-term. Appropriate patient selection may improve efficacy. More research is needed to confirm the effectiveness and to determine the best match of treatment components to particular sets of FMS symptoms. 

Other modalities include acupuncture, trigger point or tender point injections, EMG-biofeedback, chiropractic or massage. There is increased interest to develop more effective non-pharmacological treatment modalities in FMS as our ability to accurately measure effect of treatment has improved. The multifaceted nature of FM suggests that multimodal individualised treatment programmes may be necessary to achieve optimal outcomes in patients with this syndrome. 


Management of fibromyalgia requires knowledge of its broad spectrum of symptomatology that goes beyond addressing simple complaint of pain. While diagnostic criteria do exist, they were originally developed for research purposes and need further refinement as understanding of fibromyalgia has evolved. Although diagnosis can be difficult, new treatments, better understanding of the pathophysiology and greater involvement of different specialities can pave the way for improvement in the diagnosis of FMS. Often, a multidisciplinary healthcare setting is required to address the multidimensional nature of FMS. Outcome measures borrowed from clinical research in pain, rheumatology, neurology and psychiatry enable treatment response in specifi c symptoms domains. Managing FMS patients encompass an art of practising medicine as much as knowing its scientific basis. 


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Mercury Induces Inflammatory Mediator Release from Human Mast Cells

Posted By Administration, Friday, May 7, 2010
Updated: Friday, April 18, 2014


Heavy metals such as mercury result in neurological injury that may lead to developmental defects, peripheral neuropathies, and enhanced neurodegenerative changes. Mercurials may be found in various drugs, in bleaching creams, antiseptics, disinfectants, as preservatives in cosmetics, tooth pastes, lens solutions, vaccines, contraceptives and immunotherapy solutions, fungicides, herbicides and in dental fillings, as well as in fish such as tuna due to water pollution. Mercury can cause immune, sensory, neurological, motor, and behavioral dysfunction similar to those associated with Autism Spectrum Disorders (ASD). The possible role of mercury used as preservative in vaccines has been debated extensively, but most epidemiological studies do not support a causal association between vaccines and autism. However, 87% of children included in the US Vaccine Adverse Event Reporting System (VAERS) had ASD. Moreover, a paper based on computerized medical records in the Vaccine Safety Data-link concluded there was "significantly increased rate ratios for ASD with mercury exposure from thiomerosal-containing vaccines." Mercury has been shown to induce proliferation and cytokine production from T lymphocytes. Mercuric chloride (HgCl2) in nontoxic doses induces the release of histamine and cytokines, such as IL-4 and tumor necrosis factor-alpha (TNF-α), from a murine mast cell line and from mouse bone marrow-derived cultured mast cells. HgCl2 (100 μM) also enhances immunoglobulin E-mediated mediator release from human basophils, and histamine release from a rat basophil cell line (RBL-2H3). 

We, therefore, investigated whether HgCl2 could stimulate human mast cells, an action that could be enhanced in subjects who already have an atopic background.  


HgCl2 was obtained from Fluka Chemical Corp. (Milwaukee, WI) and was diluted in Dulbecco's phosphate buffered saline (DPBS, GIBCO, Grand Island, NY) on the day of the experiments. 

Human mast cell culture 

LAD2 and human umbilical cord blood-derived cultured mast cells (hCBMCs) were cultured as previously described. Umbilical cord blood was collected as approved by the Tufts Medical Center's (Boston, MA) Investigation Review Board in tubes containing 10 U/ml heparin, blood was diluted 1:2 with DPBS, GIBCO) containing 2 mM ethylenediaminetetraacetic acid (Sigma, St. Louis, MO). Non-phagocytic mononuclear cells were separated by density-gradient centrifugation using Lymphocyte Separation Medium (LSM) from Organon Teknika Corp. (Durham, NC). The isolation of hematopoietic stem and progenitor cells (CD34+) was performed by positive selection of AC133-expressing cells by magnetic-associated cell sorting (MACS) using an AC133 cell isolation kit (Milltenyi Biotec, Auburn, CA) as reported previously [15,16]. CD34+ cells were suspended in AIM-V Medium (GIBCO BRL), supplemented with 100 to 200 ng/ml recombinant human stem cell factor (rhSCF, Amgen, Thousand Oaks, CA), 50 ng/ml IL-6 (Millipore, Temecula, CA) and cultured for 12 to 16 weeks. During this culture period, the cells were washed with DPBS every week and resuspended using fresh culture medium. The purity of hCBMCs was evaluated by immunocytochemical staining for tryptase as previously described. Mast cell viability was determined by Trypan blue (0.3%) exclusion method. LAD2 cells cultured over 10 days and hCBMCs cultured over 12 weeks were used for the experiments. 

Histamine assay 

LAD2 or hCBMCs cells were washed with DPBS and mast cell media, once in each. Cell suspensions (5 × 104 cells per tube, 500 μl/sample) were preincubated with either the neuropeptide substance P (SP, 0.1-2 μM) or anti-IgE (10 μg/ml) as positive controls, or HgCl2 (1-10 μM) for 30 min. After the reaction, the cells were centrifuged and the supernatant fluid was collected. 

Histamine levels were assayed using EIA histamine kit (# IM2015; Immunotech, Beckman Coulter Company, France) as per the directions. Histamine release was calculated as percent of total. 

β-Hexosaminidase assay 

β-Hexosaminidase release, as an index of mast cell degranulation, was assayed using a fluorometric assay as previously reported. Briefly, β-hexosaminidase activity in the supernatant fluid and cell lysates (LAD2 cells, 0.5 × 105/tube, were lysed with 1% Triton X-100 to measure residual cell-associated β-hexosaminidase) were incubated with substrate solution (p-nitrophenyl-N-acetyl-β-D-glucosaminide from Sigma, St Louis, MO) in 0.1 M citrate buffer (pH 4.5) for 60 min at 37°C. The reaction was terminated by the addition 0.2 M NaOH/0.2 M glycine. Absorbance was read at 405 nm in an enzyme-linked immunosorbent assay reader, and the results are expressed as the percentage of β-hexosaminidase activity released over the total. 

Cytokine assay 

LAD2 cells or hCBMCs were washed with DPBS, sterile Tyrode's buffer, and plain culture medium, once in each, and were suspended in complete culture medium without IL-6 (for hCBMCs). The LAD 2 cells or hCBMCs (2 × 105 cells/well/200 μl) were plated in 96-well, flat-bottom Falcon cell culture plates (Becton Dickinson) and were pre-incubated for 15 min at 37°C in a 5% CO2 incubator. The cells were then incubated with either neuropeptide SP (0.1-2 μM) or HgCl2 (1-10 μM) for 24 hours at 37°C. Control cells were treated with equal volumes of only the respective culture medium. After the reaction time, plates were centrifuged and the supernatant medium was gently collected from the wells and stored at -80°C until the cytokines were measured by enzyme-linked immunosorbent assay (ELISA) using a commercial kit (Quantikine, R&D Systems, Minneapolis, MN), as reported previously. The minimum detectable levels of VEGF and IL-6 were 5 pg/ml. Cell viability was assessed at 1 hour and at 24 hours using the Trypan blue exclusion method. 

Statistical analysis 

All conditions were performed in triplicate, and all experiments were repeated five times (n = 5). Results are presented as mean ± SD. Data from two conditions, such as stimulated and control samples, were compared using the Unpaired 2-tailed Student's t-test. Significance of comparisons is denoted by p < 0.05.   


Effects of HgCl2 on mast cell viability 

LAD2 mast cells and hCBMCs were incubated with HgCl2 for 1 hour or for 24 hours in their respective media, and cell viability was assessed by Trypan blue exclusion. HgCl2 reduced viability of LAD2 mast cells in culture medium only slightly (10%), only at concentration of 10 μM, and only after 24 hours of incubation. HgCl2 reduced viability of hCBMCs by 25% at concentration of 10 μM after 24 hours of incubation. 

Effects of HgCl2 on LAD2 mast cell histamine release 

We first tried to study the effect of HgCl2 on mast cell histamine release. We assayed histamine release from LAD2 mast cells and hCBMCs after incubation with HgCl2 (1-10 μM) for another 30 min at 37°C in Tyrode's buffer. Addition of HgCl2 for 30 min induced statistically significant histamine release from hCBMCs, compared to control cells, at HgCl2 concentrations of 0.1 and 1 μM. However, as the results were inconsistent due to interference of HgCl2 with the histamine assay, we do not present them. Instead, we investigated the effect of HgCl2 on the release of β-hexosaminidase, another secretory granule marker that is released in parallel with histamine. Only 10 μM HgCl2 was able to induce a 2-fold increase in β-hexosaminidase release. 

Effects of HgCl2 on LAD2 mast cell VEGF release 

We then investigated whether HgCl2 could stimulate release of proinflammatory mediators from mast cells. LAD2 mast cells released significantly more VEGF at HgCl2 concentrations of 0.1 and 1 μM (311 ± 32 pg/106 cells and 443 ± 143 pg/106 cells, respectively, compared to 227 ± 17 pg/106 cells for control cells, p < 0.05, Fig. ​Fig.2B).2B). HgCl2 (0.1 μM) had a statistically significant synergistic effect on LAD2 mast cell VEGF release (693 ± 102 pg/106 cells) when added with SP (0.1 μM). Combinations of higher concentrations of HgCl2 and SP did not induce any additional VEGF release. 

Effects of HgCl2 on hCBMC VEGF and IL-6 release 

HgCl2 (1 μM) also induced release of significantly more VEGF (182 ± 57 pg/106 cells) from hCBMCs (n = 5, p < 0.05) compared to control cells (360 ± 100 pg/106 cells).

LAD2 mast cells cannot synthesize IL-6. We, therefore, investigated the effect of HgCl2 on IL-6 release from hCBMCs. HgCl2 (0.1 and 1 μM) significantly induced IL-6 release (466 ± 57 pg/106 cells and 204 ± 47 pg/106 cells, respectively) compared to untreated control cells (13 ± 25 pg/106 cells, n = 5, Fig. ​Fig.3B).3B). SP (5 μM), used as a positive control, also significantly increased IL-6 release (609 ± 57 pg/106 cells) from hCBMCs. Addition of HgCl2 (0.1) with SP (5 μM) further increased IL-6 release to 745 ± 117 pg/106 cells.   



This is the first report to our knowledge showing that inorganic mercury in concentrations as low as 0.1 μM can induce VEGF and IL-6 release from human cultured mast cells. We also report for the first time that mercury has a significant synergistic effect with SP (0.1 μM) on VEGF release; this amount of VEGF release is higher than what has previously been reported for hCBMCs. One paper has reported that HgCl2 can induce release of histamine from primary lung and human leukemic mast cells (HMC-1 cells), but only at toxic levels of 0.33 mM. Here we show that HgCl2 induces β-hexosaminidase release, but only at a concentration of 10 μM. Mercury (10 μM) has previously been shown to induce release of β-hexosaminidase, IL-4 and TNF-α from a murine mast cell line and from mouse bone marrow-derived cultured mast cells; the secretion of cytokines mediated by HgCl2 is additive to that which follows FcepsilonRI-induced mast cell activation. In contrast, HgCl2 does not have an effect on its own on release of histamine and IL-4 from human basophil, but only enhances allergic release at concentrations of 1 and 10 μM. This is also true for IL-4 release from rat mast cells. Clinical symptoms of mercury poisoning may be expected at blood levels of 1 μM. However, brain mast cells may react to lower mercury concentrations, especially in vulnerable patient subpopulations. 

Mast cells, by virtue of their location in the skin, respiratory tract, and gastrointestinal system are potential targets for environmental agents with immunotoxic effects. Mast cells are critical not only for allergic reactions, but also important in both innate and acquired immunity, as well as in inflammation. In view of the fact that a subgroup of ASD patients have allergy symptoms that do not appear to be triggered by IgE, it is noteworthy that mast cells can be stimulated by non-allergic triggers originating in the gut or the brain, especially neuropeptides such as SP and neurotensin (NT). Once activated, mast cells secrete numerous vasoactive, neurosensitizing and proinflammatory molecules that are relevant to ASD; these include histamine, proteases, VEGF, prostaglandin D2, as well as cytokines such as IL-6. In particular, mast cells can secrete VEGF, an isoform of which is vasodilatory and is over expressed in delayed hypersensitivity reactions. In fact, mast cells can release VEGF, IL-6 and other mediators "selectively" without degranulation. Such mediators could disrupt the gut-blood and blood-brain barriers (BBB) permitting brain inflammation. It is important to note that mercury can cross the BBB through a transport mechanism that can lead to significant brain concentrations, and that can persist for prolonged periods of time. Activated brain mast cells can disrupt the BBB and further increase brain mercury levels. 

The mechanisms of heavy metal neurotoxicity are not fully understood. Mercury increases cytosolic calcium levels in PC12 cells, and thimerosal does so in thymus lymphocytes. Mercury may also increase cellular oxidative stress since neurons are highly susceptible to reactive oxygen species (ROS) and neuronal mitochondria are especially vulnerable to oxidative damage. In fact, the primary dietary source of neurotoxic mercury compounds is via the ingestion of methylmercury from fish, which has been previously linked to neurological damage. 

Mercury's activation of mast cell inflammatory mediator release may enhance allergic reactions in atopic individuals and exacerbate IgE-dependent diseases. Allergic symptomatology is often present in ASD patients, and a survey of children with ASD in Italy reported that the strongest association was with a history of allergies. Moreover, a recent study reported increased atopic diseases, as well as elevated serum IgE and eosinophils in Asperger patients. In a National Survey of Children's Health, parents of autistic children reported symptoms of allergies more often than other children, with food allergies showing the greatest difference. A case series study also reported higher rate of food allergies in ASD children. In one study, 30% of autistic children (n = 30) had a history of atopy as compared to 2.5% of age-matched "neurologic controls" (n = 30), but there was no difference in serum IgE or in skin prick tests to 12 common antigens, implicating triggers other than IgE. In another study, ASD patients did not have increased incidence of allergic asthma or allergic dermatitis, but this study included only ASD patients that were positive to RAST/skin testing. Finally, a preliminary report indicated that the prevalence of ASD may be 10-fold higher than the general population (1/100 children) in mastocytosis patients, characterized by increased number of hyperactive mast cells in many tissues, with symptoms that include allergies, food intolerances and "brain fog." 

Some epidemiological studies have failed to find a significant relationship between mercury exposure from vaccines and autism. Nevertheless, 87% of children included in the US Vaccine Adverse Event Reporting System (VAERS) have ASD. Moreover, a paper based on computerized medical records in the Vaccine Safety Datalink concluded there was "significantly increased rate ratios for ASD with mercury exposure from Thimerosal-containing vaccines." Also, there are a series of epidemiological studies conducted in the USA that have found significant associations between environmental sources of mercury exposure and ASDs. In addition, patients with severe ASD have evidence of significantly increased urinary porphyrins consistent with mercury intoxication. Mercury toxicity may also affect critical methylation pathways in vulnerable cells. 

ASD are a group of pervasive developmental disorders that include autistic disorder, Asperger's disorder, and atypical autism - also known as pervasive developmental disorder-not otherwise specified (PDD-NOS). These are neurodevelopmental disorders diagnosed in early childhood. They are characterized by various degrees of dysfunctional communication and social skills, repetitive and stereotypic behaviors, as well as attention, cognitive, learning and sensory defects. ASD cases have increased more than 10-fold during the last decade to a prevalence of 1/100 children. However, there is no known distinct pathogenesis, there are no biomarkers, and there is no effective treatment. 

ASD may result from a combination of genetic/biochemical susceptibility and epigenetic exposure to environmental factors, including reduced ability to excrete mercury and/or exposure to mercury at critical developmental periods. A number of papers have suggested that ASD may be associated with immune dysfunction, while a recent review made the case that ASD may be a neuroimmune disorder involving mast cell activation. 


The results of the present study support the biological plausibility of how mercury could contribute to ASD pathogenesis by inducing VEGF and IL-6 release from mast cells, and as a result disrupt the BBB and thus permit brain inflammation. Further studies should investigate the effect of mercury and thimerosal alone or together with allergic and non-immune triggers. 


ASD: Autism Spectrum Disorders; (DPBS): Dulbecco's phosphate buffered saline; hCBMCs: human umbilical cord blood-derived cultured mast cells; ELISA: enzyme-linked immunosorbent assay; HgCl2: mercury chloride; PDD-NOS: pervasive developmental disorder-not otherwise specified; (NT): neurotensin; (SP): Substance P; rhSCF: recombinant human stem cell factor; VAERS: Vaccine Adverse Event Reporting System; VEGF: vascular endothelial growth factor. 

Competing interests 

TCT is on the Scientifc Advisory Board of The Mastocytosis Society. TCT is the inventor of US patents No. 6,624,148; 6,689,748; 6,984,667 and EPO 1365777, which cover methods and compositions of mast cell blockers in neuroinflammatory conditions, as well as US patent application No.12/534,571 for diagnosis and treatment of ASD. 

Authors' contributions 

This study is based on an original idea of TCT. TCT and DK wrote the manuscript. DK and SA carried out the cytokine, β-hexosaminidase and histamine assays. JH, AM, BZ carried out the viability assays and some mediator assays. EP provided umbilical cord blood. All authors have read and approved the manuscript. 


This work was funded in part by the Safe Minds (Huntington Beach, CA) and the Defeat Autism Now Coalition (San Diego, CA), as well as Theta Biomedical Consulting and Development Co., Inc. (Brookline, MA). Christos Damianos Kalogeromitros participated in some aspects of this work as part of his IB project at Athens College, Greece.   


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Source: Duraisamy Kempuraj, Shahrzad Asadi, Bodi Zhang, Akrivi Manola, Jennifer Hogan, Erika Peterson, and Theoharis C Theoharides. J Neuroinflammation. 2010; 7: 20. Published online 2010 March 11. doi: 10.1186/1742-2094-7-20.

Tags:  human mast cells  inflammatory mediator  mercury 

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The Second Brain: The Gut and Serotonin

Posted By Administration, Thursday, May 6, 2010
Updated: Friday, April 18, 2014



by Zina Kroner, DO

This is not the “shock and awe” study of the year, but it elucidates an excellent medical phenomenon.  A recent study in the American Journal of Gastroenterology showed that St. John’s Wort, an herb used to treat mild depression, was less effective than placebo at treating irritable bowel syndrome (IBS).  Improvements in quality of life were similar in both placebo and the herb treated groups.  Gastroenterologists have been treating IBS with anti-depressants for quite some time.   I would like to bring to light the theory behind it, as this may have clinical implications beyond the use of medication.

The gut, often referred to as the second brain due to the powerful enteric nervous system that it houses, is tightly connected to serotonin, the feel good neurotransmitter.   Dr. Michael D. Gershon, the chairman of the department of anatomy and cell biology at Columbia has brought this to light in his book entitled “The Second Brain.” 

We have all felt a twinge in the stomach prior to a major exam or a public speaking event.  It is quite common for my patients with a psychiatric disorder to have a concomitant gastrointestinal issue. 

There are several reasons why stress or anxiety can cause irritable bowel syndrome.  First, with any fight or flight response, cortisol, a stress hormone, is released. Cortisol fires up the sympathetic nervous system and makes the parasympathetic nervous system less efficient.  It is the parasympathetic nervous system that we need in order to maintain bodily homeostasis, such as breathing, digestion,etc.  Therefore, with a cortisol surge, digestion becomes ineffective and irritable bowel syndrome can kick in.

Second, it is important to note that serotonin has a profound effect on gastrointestinal function, being that 95% of the body’s serotonin is cradled in the gut.  At the start of digestion, it is the enterochromaffin cells that release serotonin into the gastrointestinal tract, which houses many serotonin receptors.  The receptors then initiate a process via nerve cells that starts the flow of digestive enzymes. 

Serotonin then relays messages up to the brain, letting it know what is happening.  Therefore, certain foods may elicit a feeling of nausea, etc.  Once serotonin is released in the gastrointestinal tract and the process of digestion is stimulated, normally, it is cleared out of the way by SERT, a serotonin transporter. 

These transporters are found in the gut walls.   Often, those with IBS, may not have an appropriate level of functioning SERTs, and they are therefore unable to clear out the serotonin cells.  This can stimulate diarrhea. Once the serotonin receptors are supersaturated, the effect is constipation, thus the infamous Irritable Bowel Syndrome.  Therefore, medications as well as supplements such as St. Johns Wort which manipulate the serotonin may potentially help IBS symptoms. It is no wonder that in this recent study, placebo was quite beneficial in IBS.  This shows how much mind and body are connected.  Focusing on stress management is key as well. 

A third contributor to IBS as it related to the enteric nervous system is allergens.  Often, the barrier of the gut becomes damaged and certain allergens, etc, may enter the bloodstream, triggering the brain to send a message to the gut to increase the production of histamines and other inflammatory cells in order to try to get rid of the allergens.  This inflammatory process may trigger the neurons in the enteric nervous system (in the gut) to become hyperactive and therefore contribute to diarrhea. 

The challenge now is to optimize the efficiency of the gastrointestinal tract by preventing unnecessary cortisol surges so not to disrupt the sympathetic and parasympathetic nervous system harmony, to maintain a healthy serotonin and SERT level, and to prevent unnecessary allergens from entering the GI tract so not to trigger the inflammatory process involved in diarrhea.  The gut really is the Second Brain! 

Citation:  Saito YA et al. A randomized, double-blind, placebo-controlled trial of St John's wort for treating irritable bowel syndrome. Am J Gastroenterol 2010 Jan; 105:170.

Tags:  gut health  inflammatory bowel disease 

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Role of Diet in the Management of Inflammatory Bowel Disease

Posted By Administration, Friday, April 30, 2010
Updated: Friday, April 18, 2014


Many studies have looked at connections between diet, etiology, signs and symptoms associated with inflammatory bowel disease (IBD). Although these connections are apparent to clinicians, they are difficult to prove qualitatively or quantitatively. Enteral feeding and polymeric diets are equally effective at bringing about remission in Crohn’s disease (CD). Parenteral feeding is also effective, although none of these methods is as effective as corticosteroid therapy. However, enteral feeding is preferred in the pediatric population because linear growth is more adequately maintained via this route. Exclusion diets in patients brought into remission using an elemental diet have been shown to maintain remission for longer periods. Studies that aim to isolate culpable food groups have shown that individuals react differently on exposure to or exclusion of various foods. The commonly identified food sensitivities are cereals, milk, eggs, vegetables and citrus fruits. Studies that have looked at gut mucosal antigen behavior have shown higher rectal blood flow, in response to specific food antigens, in those with CD over healthy subjects. Exclusion of sugar shows little evidence of amelioration in CD. Omega 3 fatty acids show promise in the treatment of IBD but await larger randomized controlled trials. Patients frequently notice that specific foods cause aggravation of their symptoms. Whilst it has been difficult to pinpoint specific foods, with advances in the laboratory tests and food supplements available, the aim is to prolong remission in these patients using dietary measures, and reduce the need for pharmacotherapy and surgical intervention.


The etiology of inflammatory bowel disease (IBD) is considered multifactorial. Genetic, infective and environmental theories exist, as well as those centered around host immunity, intraluminal gut flora, food allergies and hypersensitivity.

Whilst pharmacological therapy plays a major role, many patients prefer to control their symptoms by the most conservative means possible. Our aims in IBD therapy are to downregulate inflammation, and reduce the incidence of relapse and the healing time.

Dietary therapy encompasses dietary modifications suggested by physicians and those that patients make autonomously. The putative mechanisms of action are due to bowel rest, provision of nutrients, alteration of bowel flora or alteration of antigenic stimuli. The gastrointestinal flora and its interaction with nutritional factors has a huge impact on the environment, especially in genetically predisposed individuals. Nutrients as components of cell structure or antigens can induce inflammatory mediator expression and suboptimal levels of nutrients, which may have an impact on tissue repair and other cellular processes. Other reviews have concluded that nutrients that tend to affect the immune responses of the host (n-3 fatty acids, antioxidants) are likely to play a role in the treatment of IBD.

In this review, we examine the literature for dietary interventions in IBD, such as exclusion/elimination diets, enteral nutrition and total parenteral nutrition (TPN), and review the evidence that they induce and/or maintain remission in patients with IBD.


Elemental/polymeric diets

Elemental diets were chanced upon as a therapeutic option for CD patients when they were used to bolster their nutritional status and reduce inflammation. Liquid feeds are thought to work by reducing mucosal antigen exposure, partly due to the nature of the feed and partly to faster transit times. They also alter the fecal flora, which causes local immunomodulation downscaling, which enhances nutritional status and allows relative bowel rest.

Compliance may be poor as elemental diets are not known for their palatability and are often delivered via a nasogastric tube, whereas the polymeric drinks are far more palatable. Several trials and meta-analyses have shown no significant difference in the efficacy of elemental diets over polymeric diets.

Elemental diets offer a cheaper way of bringing about remission and without the side effect profile of TPN. In both adult and pediatric populations, elemental and polymeric feeds have been shown to be as effective as corticosteroid therapy in treating active CD. However, a Cochrane review by Zachos et al has shown, in a meta-analysis, that enteral nutrition is not as effective as steroid therapy for inducing remission.

However, enteral therapy for CD has its role in selected cases, in particular, in children in whom steroids may cause growth retardation. Food exclusion with liquid diet is very difficult to maintain, therefore, these are rarely long-term solutions. Unfortunately, a staged return to normal feeding often leads to relapse.

Exclusion diets

The East Anglia Multicentre Controlled Trial showed that various food intolerances were perceived in individual patients, and among the more common were cereals, dairy produce and yeast. This work looked at the use of exclusion diets as an intervention in active CD. The exclusion diet was based around daily reintroduction of a single food type. If it caused diarrhea or pain, it was eliminated. All patients were treated initially with an elemental diet, and those who attained remission followed a reduced prednisolone course or the exclusion diet pathway. Jones et al have shown that maintenance of remission, by identification and avoidance of food intolerances, is possible, often without pharmaceutical adjuncts. Testing for these sensitivities has proven difficult, because testing shows a large number of sensitivities in unselected populations, which are of doubtful clinical significance. Jones et al have tested a diet rich in unrefined carbohydrate against an exclusion diet. Seven out of 10 patients on the exclusion diet stayed in remission for 6 mo, while none of those on the carbohydrate-rich diet remained in remission. Pearson et al have conducted a study of 42 CD patients after induction of remission by elemental diet. Single foods were investigated using open and double blind rechallenge over 5 d. Fourteen patients dropped out due to flare-ups that were thought to be unrelated to food, and caused by inability to comply with the regimen. Twenty of the remaining patients identified food intolerances and eight did not. This research group has concluded that food intolerance is not as frequent as claimed in other studies, and that it is variable in its intensity and occurrence.

Parenteral feeding in CD

TPN allows bowel rest while supplying adequate calorific intake and essential nutrients, and removes antigenic mucosal stimuli. However, TPN is expensive, invasive and has a number of side effects. TPN has been shown to bring about remission in CD. Müller et al have found that, in 30 consecutive complicated CD patients, 3 wk of TPN as an inpatient followed by an additional 9 wk at home, during which time, no medication or oral intake was allowed, 25 patients avoided surgery. These patients returned to work and needed no further medication and ate normal meals subsequently. In a prospective randomized controlled trial (RCT), 51 patients with active CD refractory to medical treatment were treated with TPN and nil by mouth, defined formula diet via a nasogastric tube, or partial parenteral nutrition. Clinical remission was obtained in 71% of the patients on TPN, 58% on enteral feeding, and 60% on partial parenteral feed.

Enteral vs parenteral feeding

There has been controversy regarding the enteral vs parenteral route for feeding in patients with IBD. Comparison of TPN against elemental diet in a group of 36 patients showed no significant difference in the number of days to remission, the drop in Crohn’s disease activity index (CDAI) score, the erythrocyte sedimentation rate (ESR), or albumin. However, in other studies that have agreed with this finding, neither was proven to be as beneficial as corticosteroids, except one study in a pediatric population. In that study, Sanderson et al entered 17 children into an RCT, in which eight were given an elemental diet for 6 wk via a nasogastric tube, and seven were given adrenocorticotrophic hormone injections and oral prednisolone and sulfasalazine. The elemental diet was equally effective at improving the Lloyd-Still disease activity index scores, C-reactive protein (CRP), ESR and albumin. The elemental diet was markedly better at maintaining linear growth. Whilst strong evidence exists supporting the primary use of enteral feeding in children with CD, it is not commonplace in the treatment of adults.

Omega-3 fatty acids

Shoda et al have noted that the gradual replacement of n-3 polyunsaturated fatty acids with n-6 polyunsaturated fatty acids results in an increased incidence of CD. This implies that there is the potential to modulate immune responses by altering the ratio of polyunsaturated fatty acids in favor of n-3 rather than n-6. Meister and Ghosh have shown that fish-oil-enriched enteral diet, when incubated with intestinal tissue from 11 subjects with IBD and four controls, reduced inflammation modestly in CD and significantly in UC. Inflammatory improvement was assessed by analyzing the interleukin (IL)-1 receptor antagonist/IL-1β ratio. The greater the ratio, the less inflamed the tissue. A systematic review of the effects of n-3 fatty acids in IBD by MacLean et al has identified 13 controlled trials that investigated the effects of n-3 fatty acids. The results were mixed but in the three studies that looked at steroid requirements, this was found to be reduced. However, this was statistically significant in just one of these studies.



Exclusion diets

Jones has looked at exclusion diets for the maintenance of remission of CD and has shown that, in personalized exclusion diets, 62% of the patients maintained remission at 2 years and 45% at 5 years, with no other medical intervention. This was compared to the European Cooperative Crohn’s Disease Study in 1984 in which the placebo arm of the study had no patient who maintained remission after 2 years of follow-up.

A Cochrane review of the maintenance of remission in CD has suggested that larger, high-powered controlled trials are required to confirm current hypotheses relating to diet and maintenance of remission. Trials of diet against azathioprine and infliximab also have been suggested to investigate quantitative effects of nutritional supplements and their impact on cost-effectiveness and quality of life.

Enteral feeding

Enteral feeding has been shown to have a role in preventing relapse in inactive CD patients (predominantly in children), but the effect has also been observed in a Japanese study of adult CD patients. Esaki et al have demonstrated in a trial of 145 patients with CD (mostly induced into remission with TPN) that, under maintenance with elemental/polymeric nutrition, the risk of recurrence was lower in those with small bowel rather than large bowel involvement.



Maintenance of remission in UC

UC does not seem to be ameliorated by bowel rest and elemental diets in the same way as CD is. However, patients still express concern about specific food types, and there does appear to be an association with a western diet. In a study that has investigated self-reported food intolerance in chronic IBD, patients with CD and UC have reported that they felt intolerant to specific dietary triggers and restricted their diet accordingly. The same study has shown that the pattern and frequency of food intolerance did not differ between CD and UC patients. This has been reinforced by work from our own group that has investigated food intolerances detected by measuring IgG4 antibodies to specific food antigens. There is no evidence to support the use of elemental/polymeric feeding in the treatment of UC.

Omega-3 fatty acids

Omega-3 fatty acids derived from fish oils have been shown to be of benefit in a double-blind RCT that looked at patients with distal UC. That study found that the group treated with 3.2 g eicosapentaenoic acid or 2.4 g docosahexaenoic acid daily had significantly better clinical and sigmoidoscopic scores compared with the control group who took sunflower oil, after 3 and 6 mo. This supports the idea that omega-3 oils suppress natural cytotoxicity.




Dietary fiber has been investigated as a means of increasing short-chain fatty acid (SCFA) production. IBD has been linked with impaired SCFA production. SCFAs are mainly produced by the anaerobic bacterial fermentation of undigested carbohydrates and fiber polysaccharides. In 1995, Galvez et al reviewed a number of studies that concluded that dietary fiber confers clinical benefits in patients with IBD because it maintains remission and reduces colonic damage. This is thought to occur by increasing SCFA production and by altering the gut flora towards predominantly non-pathogenic bacteria.


The properties of omega-3 fatty acids have been discussed elsewhere in this review. Other studies have revealed an inverse correlation between the percentage of energy derived from long-chain triglycerides and the efficacy of enteral feeds in achieving remission.


A high intake of sugar has been shown to be linked to CD in a number of trials, hence its possible etiological role has led to therapeutic trials of sugar avoidance. Most of these trials also have promoted a high fiber intake. The only trial to look solely at sugar avoidance has shown no statistically significant benefit.




Van den Bogaerde et al have published a trial in which the reactivity of peripheral lymphocytes to food, yeast and bacterial antigens was studied. They found that 23 out of 31 patients with CD responded to one or more antigens, compared to five out of 22 in the control group. They also correlated in vitro sensitization and in vivochanges with histological and blood flow changes. Skin testing and rectal exposure to six food antigens and saline were tested in 10 patients and 10 controls. The results showed that CD patients demonstrated in vitro and in vivo sensitization to food antigens and this was gut specific.

Levo et al have shown that patients with IBD have higher serum concentrations of IgE. They also have shown that the levels are higher still in those with active disease over those in remission. However, this difference is not statistically significant. In 1998, another study was performed to investigate food-specific IgE as well as IgG, and IgE anti-IgE autoantibodies using serum from normal subjects, patients with CD and those with food allergies. They found that food-specific IgE was not detected at all in the CD group but they did have higher levels of IgG and IgE anti-IgE autoantibodies. They concluded that, even if IgE is an autoantigen in CD, it is not thought to take part in the pathophysiology of the adverse food reactions commonly reported by the patients.

Western diets are more strongly associated with CD. There are several theories as to whether this may relate to the increased intake of sucrose, refined carbohydrate, and omega-6 fatty acids, and reduced intake of fruit and vegetables. Urban diets contain large quantities of microparticles such as natural contaminants like dust, and food additives which may be antigenic. CD patients allocated to a low microparticle diet experienced a reduction in disease activity and in steroid requirement compared to a control group on a normal diet.


Although many studies have looked at diet therapy and IBD, mixed opinions exists as to the importance that food intolerance plays in the pathophysiology of IBD. In those that have looked at food sensitivity, this was done using different methods. Riordan et al have observed sensitivity to corn in seven patients; wheat, milk and yeast in six; egg, potato, rye, tea and, coffee in four; and apples, mushrooms, oats and chocolate in three. Ballegaard et al have found sensitivity, using questionnaires, to vegetables (particularly onions and cabbage), fruits (apples, strawberries, and citrus fruits) and to meat (especially beef). Van den Bogaerde et al have shown in a case-control study using lymphocyte proliferation that, out of 31 CD patients, 16 reacted to cabbage and peanuts, 14 to cereals, 13 to milk, and nine to citrus fruits.

As observed by Hunter, epidemiologists tend to look at statistical relationships that lead to studies of sugar, sweet, coke and chocolate intake because patients with CD eat and drink more of these substances than control subjects. Clinicians focus on the foods that patients associate with their symptoms and therefore avoid. As a result, exclusion diets have tended to concentrate more on dairy products, cereals and yeast. Other work is being carried out on polyunsaturated fatty acids, especially omega-3 oils, and their anti-inflammatory effects.

Current elemental and polymeric diets have a role to play in the management of CD, particularly in children. Exclusion diets are of use particularly for maintenance of remission. TPN is of value and has been shown to be as effective as elemental diets, but none have proven as effective as corticosteroid therapy. However, TPN remains a crucial method for administering nutrition in patients with severe disease, who are not able to tolerate enteral feeding.

Despite early ideas about the involvement of sugars in the etiology of CD, the omission of sugar has not been found to be of benefit. Omega oil has shown promising results, particularly in reducing inflammation in UC, and to a lesser degree, in CD.


IBD has a multifactorial etiology but food sensitivity/intolerance appears to play a role, and the culpable foods vary on an individual basis. Techniques to identify food intolerance require refining. Progress has been made by looking at factors such as IgG4 responses to food antigens, but a large expanse of work exists in trying to determine people’s food sensitivities and the degree to which these affect disease activity. Without further research, it remains unclear whether dietary manipulation will continue to have a role solely in symptom control, or whether complete remission may be possible using these methods in combination with pharmacological agents.




Peer reviewer: Wallace F Berman, MD, Professor, Division of Pediatric GI/Nutrition, Department of Pediatrics, Duke University Medical Center, Duke University School of Medicine, Durham, Box 3009, NC 27710, United States

S- Editor Tian L L- Editor Kerr C E- Editor Ma WH



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Source: Nirooshun Rajendran and Devinder Kumar. 

World J Gastroenterol. 2010 March 28; 16(12): 1442–1448.

Published online 2010 March 28. doi: 10.3748/wjg.v16.i12.1442





Tags:  diet  inflammatory bowel disease 

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Black Cohosh May Reduce Side Effects of Clomid/Clomiphene

Posted By Administration, Thursday, April 15, 2010
Updated: Friday, April 18, 2014



by Fiona McCulloch, ND

Clomid is one of the most commonly used pharmaceuticals in the treatment of fertility concerns today.  It is often the first therapy used.  Clomid (also known as clomiphene) binds to estrogen receptors, inhibiting the action of estrogen (which is produced by developing follicles) on the hypothalamus in the brain.   As a result, the pituitary gland perceives estrogen levels to be low (when they actually are not), and it responds by producing increased levels of both LH and FSH.  This causes increased follicle production by the ovaries, and stimulation of ovulation.pregnancy with clomid therapy

As effective as this therapy can be at inducing ovulation, studies have indicated fertility specific side effects of clomiphene, many of which are caused by its antagonism to estrogen. The major fertility related side effects are: 1) thinning of the endometrial lining and 2) reduction of cervical mucous required for entry of sperm into the uterus.

One of the isomer forms of clomiphene has a slow excretion rate from the body (it can take more than 6 weeks to be excreted).  If clomiphene therapy is used for longer than two months, side effects can be more pronounced, resulting in greater thinning of the endometrial lining which is needed for healthy implantation. In women over 40, endometrial lining thins naturally, and perhaps this is why clomiphene is often not an effective treatment in this group of patients.

For many women, the ovulation induction produced by this medication can be the answer to ovulation difficulties however therapy often must be stopped after a short period due to side effects over time. Estrogen therapy has been studied in conjunction with Clomid presumably to offset the anti-estrogenic effects of the medication, with mixed results.  Some studies have found giving additional estrogen to women to be helpful, and others have found it to be of no benefit.

Recently, two studies have been completed on combining black cohosh (also known as Cimicifuga racemosa) with clomiphene in patients seeking treatment for infertility.  Cimicifuga is a botanical therapy, often used in womens health to treat menopausal conditions such as hot flashes.  Estrogenic effects of black cohosh remain highly debated, with early studies indicating that it  directly affects estrogen receptors, and more recent studies showing that the effect of the plant may occur from an entirely different mechanism.  Without yet knowing the exact mechanisms through which black cohosh works, several convincing studies have indicated it to be beneficial in the clinical treatment of hormonal disorders.  A recent study has indicated that black cohosh may reduce proliferative effects of estrogens on tissues, which is in line with the effect of many phytoestrogens, however the mechanism for this remains to be elucidated.

In the first study conducted in 2008, black cohosh was found to significantly increase estradiol and LH concentrations in patients taking clomiphene therapy.   Endometrial thickness, serum progesterone and clinical pregnancy rate in patients were significantly higher in the black cohosh group as compared to control.

The second study was completed in 2009. In this study of patients taking clomiphene, black cohosh given in the follicular phase was compared to estrogen therapy, presumably in order to determine which could reduce side effects more effectively. The black cohosh group needed significantly fewer days for healthy follicular development, had a thicker endometrial lining and had higher estradiol concentration at the time of HGG ovulation trigger when compared to the estrogen replacement therapy group.  Clinical pregnancy rate was 14.0% in the estrogen replacement group versus 21.1% in the black cohosh group. Although this did not reach clinical significance, it appears that the black cohosh group did display many benefits overall when compared to the estrogen replacement group. When results from the previous study are also considered, it appears that this therapy may warrant serious consideration and further study for those undergoing clomiphene treatment.

More studies will need to be conducted in order to determine the mechanisms of this herbal medicine’s benefits for patients undergoing modern assisted reproductive technology therapies.


Homburg, I.  Clomiphene citrate—end of an era? a mini-review.  Human Reproduction 2005 20(8):2043-2051

Insler, V MB, BCh; Zakut, H MD; Serr, D M MB, ChB. Cycle Pattern and Pregnancy Rate Following Combined Clomiphene-Estrogen Therapy. April 73 (4) 4

Massai et al.  Clomiphene citrate affects cervical mucus and endometrial morphology independently of the changes in plasma hormonal levels induced by multiple follicular recruitment.  Fertil Steril. 1993 Jun;59(6):1179-86

Osmers et al. Efficacy and Safety of Isopropanolic Black Cohosh Extract for Climacteric Symptoms. Obstetrics & Gynecology:  May 2005 – Volume 105 – Issue 5, Part 1 – pp 1074-1083

Sandro Gerli, Hossein Gholami, Antonio Manna, Antonio Scotto Di Frega, Costantino Vitiello, Vittorio Unfer, Use of ethinyl estradiol to reverse the antiestrogenic effects of clomiphene citrate in patients undergoing intrauterine insemination: a comparative, randomized study, Fertility and Sterility, Volume 73, Issue 1, January 2000, Pages 85-89

Shahin AY, Ismail AM, Shaaban OM. Supplementation of clomiphene citrate cycles with Cimicifuga racemosa or ethinyl oestradiol–a randomized trial. Reprod Biomed Online. 2009 Oct;19(4):501-7.

Shahin, Ahmed Y.1; Ismail, Alaa M.1; Zahran, Kamal M.1; Makhlouf, Ahmad M.1 Adding phytoestrogens to clomiphene induction in unexplained infertility patients – a randomized trial. Reproductive BioMedicine Online, Volume 16, Number 4, April 2008 , pp. 580-588(9)

Tags:  black cohosh  clomid  clomiphene  side effects 

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The Relationship Between Alzheimer's Disease and Diabetes: Type 3 Diabetes?

Posted By Administration, Friday, April 9, 2010
Updated: Friday, April 18, 2014


Published in Alternative Medicine Review, Volume 14, Number 4 2009

by Zina Kroner, DO





In recent years, Alzheimer’s disease (AD) has been considered to be, in part, a neuroendocrine disorder, even referred to by some as type 3 diabetes. Insulin functions by controlling neurotransmitter release processes at the synapses and activating signaling pathways associated with learning and long-term memory. Novel research demonstrates that impaired insulin signaling may be implicated in AD. Post-mortem brain studies show that insulin expression is inversely proportional to the Braak stage of AD progression. It was also demonstrated that neurotoxins, coined amyloid beta-derived diffusible ligands (ADDLs), disrupt signal transduction at synapses, making the cell insulin resistant. ADDLs reduce plasticity of the synapse, potentiate synapse loss, contribute to oxidative damage, and cause AD-type tau hyperphosphorylation. Diabetes and AD have signs of increased oxidative stress in common, including advanced glycation end products (AGEs), when compared to normal subjects. Diabetic patients appear to have an increased risk for AD because AGEs accumulate in neurofibrillary tangles and amyloid plaques in AD brains. This research should encourage a more proactive approach to early diagnosis of diabetes and nutritional counseling for AD patients. (Altern Med Rev 2009;14(4):373-379) 


The epidemic of insulin resistance/prediabetes and type 2 diabetes may be associated with the emergence of higher rates of Alzheimer’s disease (AD). New research delineates a direct correlation between sugar imbalance and AD. AD is associated with consistent pathological findings, including neurofibrillary tangles, amyloid-beta deposits, and signs of oxidative stress. No common link among the proposed pathological processes has been identified. Novel evidence demonstrates that impaired insulin signaling may significantly contribute to the pathogenesis of AD, contributing to the idea that it is actually a neuroendocrine disease. Neurotoxins called amyloid beta-derived diffusible ligands (ADDLs) have been implicated as a cause of impaired insulin signaling. Advanced glycation end products (AGEs) are found in higher concentration in both hyperglycemia and AD, contributing to oxidative stress and cell damage. These AGEs are known to be further modified to reactive advanced glycation end products, (RAGEs), which can generate oxidative injury. 

Understanding the mechanism of action of this neuroendocrine disorder, termed type 3 diabetes by some, may shed light on new tools for diagnosing and treating AD and for the need for early intervention in obese patients with insulin resistance. 

The Clinical Link: Diabetes and AD 

The research linking diabetes and AD has its roots in the groundbreaking Rotterdam study. Of 6,370 elderly subjects studied for 2.1 years, 126 developed dementia; 89 of these were specifically diagnosed with AD. Type 2 diabetes doubled the risk of a patient having dementia and patients on insulin had four times the risk.As rates of insulin resistance and diabetes in the senior population are both increasing, this landmark study, conducted almost a decade ago, has been getting more attention in recent years since further studies have solidified the connection between diabetes and AD.

Since type 2 diabetes is reaching epidemic proportions and is under-diagnosed, and AD may be associated with hyperglycemia, more attention should be drawn to early diagnosis of diabetes. The Gertner Institute for Epidemiology and Health Policy Research in Israel, in a recently published 25-year, cross-sectional study of 623 adults, demonstrated that approximately 13 percent of the studied population had undiagnosed type 2 diabetes. This study reinforces the importance of early diagnosis of type 2 diabetes by identifying patients with risk factors, including hypertension, hypertriglyceridemia, and a large waist circumference (males: ≥40 inches [102 cm], females: ≥35 inches [88 cm]) – factors seen in metabolic syndrome. These results encourage early detection via screening methods targeting those with traits of metabolic syndrome in otherwise healthy adults.

Another study demonstrating the high prevalence of diabetes showed almost one-third of elderly patients in a sample of 7,267 subjects had diabetes, and three-fourths had impaired fasting glucose (glucose lev- els >99 but <126) or diabetes.

Elevated body mass index (BMI), adiposity, impaired fasting glucose, and diabetes increase the risk of AD substantially. The latest study, utilizing data on 2,322 participants in the Baltimore Longitudinal Study of Aging, shows the incidence of AD increased in men who gained weight between the ages of 30 and 45 and in women with a BMI >30 at ages 30, 40, and 45.7 This suggests more emphasis should be placed on early weight-loss strategies for preventing AD. 

A 2008 Swedish study showed a statistically significant increase in the risk of developing AD in men who develop type 2 diabetes in midlife. The researchers followed 2,269 men for 32 years and found that those with low insulin production at age 50 were 150-percent more likely to develop AD than those with adequate insulin production. This association was greatest in patients who did not have the apolipoprotein E4 (ApoE4) genetic predisposition to AD (which renders individuals less efficient at breaking down beta-amyloid plaques), thereby making diabetes a possible independent risk factor for AD. This study illustrates the importance of maintaining healthy blood glucose control in middle-aged men as a possible means of preventing AD later in life. 

A recent investigation suggests that AD is associated with metabolic syndrome. After studying 50 patients diagnosed with AD and comparing them to 75 cognitively normal controls, the AD patients had a greater waist circumference, higher triglyceride and glucose levels, and lower high-density lipoprotein cholesterol. Patients with metabolic syndrome are diagnosed with AD at a younger age than AD patients without metabolic syndrome.

Type 3 Diabetes: Is It Actually a Unique Condition? 

The term type 3 diabetes was coined in 2005 by Suzanne de la Monte, MD, MPH, Associate Professor of Pathology and Medicine and neuropathologist at Brown Medical School. Her team, examining postmortem brain tissue of AD patients, found that AD may be a neuroendocrine disease associated with insulin signaling. The team termed it type 3 diabetes because it harbors elements of both types 1 and 2 diabetes, since there is both a decrease in the production of insulin and a resistance to insulin receptors.

The team analyzed 45 postmortem brains of patients of varying Braak stages of AD neurodegeneration and found that insulin expression was inversely proportional to the Braak stage, with an 80-percent decrease in the number of insulin receptors in AD patients compared to normal subjects. In addition, the ability of insulin to bind to the receptors was compromised. There was a reduced level of mRNA corresponding to insulin, insulin-like growth factor-1 (IGF-1) and -2 polypeptides, and their receptors. The research team also noted a reduction in the tau protein, which is regulated by insulin and IGF-1. This phenomenon ultimately could lead to neuronal cell death and AD exacerbation.  

The postmortem studies inspired a rat study in which intracerebral injection of streptozotocin resulted in a chemical depletion of insulin and an alteration of IGF-signaling mechanisms together with oxidative injury. The combination of alterations resulted in neurodegeneration, including reduction in brain size and other neurological changes seen in AD.

AD is characterized by a reduction in the utilization of glucose, and treatment with insulin has been associated with improved memory. Insulin, important in memory processing, crosses the blood-brain barrier and is even produced in brain tissue itself. AD patients have less insulin and fewer insulin receptors than non-AD patients, and correction of insulin levels improves cognition. Insulin binds to insulin receptors in the brain, most of which are located in the cerebral cortex, olfactory bulb, hippocampus, cerebellum, and hypothalamus. Since there are more insulin receptors in the cognitionpertinent areas of the brain, it is logical to consider the association between insulin and cognition.

Several studies utilizing intranasal, intravenous, and intracerebral administration of insulin demonstrate improved cognition. A study utilizing intranasal insulin showed that its administration enhanced verbal recall in normoglycemic adults with early AD or cognitive impairment. In the study, 25 participants were randomly assigned to receive either placebo (n=12) or 20 IU intranasal insulin (n=13) twice daily. After 21 days of treatment, changes in cognition were measured. The fasting plasma glucose and insulin levels were unchanged with treatment. However, when compared with the placebo treated subjects, the insulin-treated subjects retained more verbal information and displayed superior attention and functional status. 

A study utilizing intravenous (IV) insulin assessed cognitive performance in 22 adults with AD and 15 normal adults receiving five consecutively higher IV doses of insulin resulting in five plasma insulin levels (10, 25, 35, 85, and 135 microU/mL), while plasma glucose levels of ~100 mg/dL were maintained. Cognitive performance was measured after 120 minutes of infusion. AD patients who were ApoE4-positive were found to have improved memory at lower insulin levels of 25 microU/mL, compared to their ApoE4-negative counterparts, who required a higher blood insulin level of 35 and 85 microU/mL before an improvement in memory was noted. Interestingly, normal adults also showed improved memory at insulin levels of 25 and 85 microU/mL. This shows that AD patients who are ApoE4-negative may not be as sensitive to insulin.  

A study utilizing intracerebroventricular insulin showed that its administration enhanced memory formation in rodents undergoing a step-through passive avoidance task These studies suggest that insulin may have a role in enhancement of cognition and memory. The other implication is that patients with the ApoE4 genetic predisposition to AD may not reap the benefits of improvement in AD by glycemic control. 

Based on a recent epidemiological study, individuals who are ApoE4-positive are not more likely to be insulin resistant than those who are ApoE4-negative. Therefore, insulin resistance and being positive for the ApoE4 allele are independent risk factors for AD; having both may pose an additive risk. 

Pathophysiological Connections between Insulin and AD 

AD is characterized by both low insulin levels and insulin resistance within the central nervous system (CNS), as opposed to type 2 diabetes, which is characterized by high insulin levels and insulin resistance outside of the CNS. Insulin resistance and hyperinsulinemia cause a reduction in brain insulin. Several mechanisms might explain why insulin mediates memory facilitation. As noted, insulin receptors are found in areas of the brain responsible for cognition. Insulin activates signaling pathways associated with learning and long-term memory. According to de la Monte, insulin helps to regulate processes such as neuronal survival, energy metabolism, and plasticity. These processes are required for learning and memory.  Peripheral insulin resistance, therefore, affects cognition.

In addition to regulating blood sugar levels, insulin functions as a growth factor for all cells, including neurons in the brain. Thus, insulin resistance or lack of insulin, in addition to adversely affecting blood sugar levels, contributes to degenerative processes in the brain.

When insulin levels reach an exceedingly high level, the beta-amyloid peptide, the hallmark of AD that accumulates in senile plaques, is modulated. Exaggerated elevation of plasma insulin levels causes amyloid peptide levels in the cerebrospinal fluid to increase, resulting in memory insult.

Amyloid beta-Derived Diffusible Ligands 

A group of researchers at Northwestern University studied why brains of AD patients are both low in, and resistant to, insulin. According to William Klein, PhD, who led the research, amyloid beta-derived diffusible ligands may be responsible for the phenomenon. ADDLs are oligomers similar in morphology and size to prions that have been linked to neurodegenerative disease. ADDLs may contribute to lowered insulin levels and insulin resistance in AD brains. Because the ADDLs are so small, they are more diffusible and therefore more harmful than amyloid. 

In healthy brains, insulin binds to a receptor at a synapse, resulting ultimately in memory formation. Klein’s team found that ADDLs disrupt this mechanism of communication by binding to the synapse and changing its shape, thereby causing dysfunction. Because the shape of the synapse is altered, insulin cannot effectively bind, disrupting signal transduction and resulting in insulin resistance. ADDLs have been shown to reduce the plasticity of the synapse, potentiate synapse loss, cause oxidative damage, and result in AD-type tau hyperphosphorylation, mechanisms linked to AD. Since ADDLs have been shown to affect neuronal insulin receptor signaling, it has been suggested that insulin resistance in the AD brain is a response to  ADDLs, inducing a neurological form of diabetes.  Neurons with no ADDLs show an adequate number of insulin receptors. 

Measuring ADDL levels may potentially be a novel tool for diagnosing AD. In 2005, the ultrasensitive bio-barcode assay was used to measure ADDL concentration in cerebrospinal fluid. Of 30 subjects, ADDL concentrations were found to be higher in those diagnosed with AD compared to non-AD patients. This test is not readily available and less invasive testing is underway. An ADDL vaccine is being studied and ADDL-blocking drugs are being considered by Klein et al.

Insulin and the Cholinergic Hypothesis 

The cholinergic hypothesis that suggests AD is caused by an inadequate production of acetylcholine may also have links to blood sugar abnormalities and insulin resistance. The researchers at Brown point out that insulin also participates significantly in neurological function by stimulating the expression of choline acetyltransferase (ChAT), the enzyme responsible for acetylcholine synthesis. Therefore, suboptimal insulin levels as well as poor insulin receptor sensitivity can ultimately contribute to a decrease in acetylcholine, which further elucidates a possible bio-chemical link between diabetes and AD.

AGEs and Oxidation – Common Thread between Diabetes and AD 

Another mechanism linking diabetes with AD is that both diseases, as mentioned previously, are associated with increased oxidative stress and production of AGEs. Although the association between vascular dementia and AGEs is well established, new research points to a link between AGEs and AD. AGEs are formed by a sequence of events originally identified in 1912 as the end-products of the Maillard reaction, during which reducing sugars can react with the amino groups of proteins to produce cross-linked complexes and unstable compounds. 

AGEs have been found in retinal vessels, peripheral nerves, kidneys, and the CNS of diabetics. AGEs couple with free radicals and create oxidative damage, which in turn leads to cellular injury. Diabetic patients could have an increased risk of AD via AGE production. Oxidative stress on its own also causes AGEs, creating a vicious cycle.

AGEs are also known to modify plaques and neurofibrillary tangles, both implicated in AD. AGEs have been identified in neurofibrillary tangles (consisting of tau protein) and senile plaques (consisting of beta-amyloid protein). Since type 2 diabetes accelerates the production of AGEs, it may be another causative factor in the development of AD. It has been proposed that a potential biomarker for early detection of AD may be measurement of toxic AGEs in the serum or cerebrospinal fluid.


Understanding that AD has its foundation in neuroendocrinology is persuasive evidence that there should be greater emphasis on early diagnosis of metabolic syndrome, insulin resistance, and type 2 diabetes. Referring to AD as type 3 diabetes has its foundation in the fact that the CNS in AD is characterized by a paucity of insulin and resistance of the insulin receptors. This results in cognitive dysfunction, since insulin is crucial for neurological signaling processes to occur. Insulin also participates in neurological function by stimulating the expression of ChAT, the enzyme responsible for acetylcholine synthesis; acetylcholine is in turn a necessary neurotransmitter for cognition. AGEs, found in greater amounts in diabetic patients compared to controls with normal glucose regulation, have also been found in high concentration in AD brains. 

The links between hyperglycemic states and AD can allow for better future diagnostic strategies. Since ADDLs may contribute to lowered insulin levels and insulin resistance in AD brains, the future of diagnosis may entail the measurement of ADDLs. Measurement of AGEs has also been proposed. 

Treatment strategies utilizing this information require more research. The knowledge that there is a reduction of the sensitivity to insulin in AD patients who are not ApoE4-positive suggests that optimization of blood sugar levels may have therapeutic benefits. Insulin-sensitizing agents may potentially be used in the setting of early AD. 


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Are Rice and Spicy Diets Good for Functional Gastrointestinal Disorders?

Posted By Administration, Friday, April 9, 2010
Updated: Friday, April 18, 2014


Rice- and chili-containing foods are common in Asia. Studies suggest that rice is completely absorbed in the small bowel, produces little intestinal gas and has a low allergenicity. Several clinical studies have demonstrated that rice-based meals are well tolerated and may improve gastrointestinal symptoms in functional gastrointestinal disorders (FGID). Chili is a spicy ingredient commonly use throughout Asia. The active component of chili is capsaicin. Capsaicin can mediate a painful, burning sensation in the human gut via the transient receptor potential vanilloid-1 (TRPV1). Recently, the TRPV1 expressing sensory fibers have been reported to increase in the gastrointestinal tract of patients with FGID and visceral hypersensitivity. Acute exposure to capsaicin or chili can aggravate abdominal pain and burning in dyspepsia and IBS patients. Whereas, chronic ingestion of natural capsaicin agonist or chili has been shown to decrease dyspeptic and gastroesophageal reflux disease (GERD) symptoms. The high prevalence of spicy food in Asia may modify gastrointestinal burning symptoms in patients with FGID. Studies in Asia demonstrated a low prevalence of heartburn symptoms in GERD patients in several Asian countries. In conclusion rice is well tolerated and should be advocated as the carbohydrate source of choice for patients with FGID. Although, acute chili ingestion can aggravate abdominal pain and burning symptoms in FGID, chronic ingestion of chili was found to improve functional dyspepsia and GERD symptoms in small randomized, controlled studies. 

Keywords: Chili pepper, Rice, Functional gastrointestinal disorder, Capsaicin, TRPV1 receptor 


Complaints of gastrointestinal symptoms after food ingestion are common in patients with functional gastrointestinal disorders (FGID) and are reported in 25-64% of irritable bowel syndrome (IBS) patients.IBS patients often complain of food-related gastrointestinal symptoms secondary to more than one specific food. A recent population-based study in the USA demonstrated that 16.5% and 28.3% of IBS patients had intolerance to 1-2 food items and > 2 items, respectively. These statistics suggest that hyper-sensitivity to the ingestion of foods is common in IBS. Research studies also demonstrate that certain foods, such as chili, fructose or fructan containing foods and fatty foods, can affect gastrointestinal motility and sensation and induce gastrointestinal symptoms more than other foods.This suggests that certain foods, and not just the process of eating foods, can aggravate symptoms in patients with FGID. Therefore, modification of either eating habits (reducing meal size and/or the time of meals) or the composition of meals (avoiding specific food items) may benefit patients with FGID, and studies on the effects of food on gastrointestinal functions and symptoms are important. 

The effects of food ingestion on gastrointestinal symptoms in patients with FGID have been extensively studied, mainly in Western countries and with Western diets. Moreover, information regarding the effects of typical Asian foods on gastrointestinal symptoms of FGID is quite limited. This review will focus on the effects of specific but widely used Asian diets/ingredients, "rice and chili or spicy foods," on gastrointestinal functions and their roles on the symptoms of FGID. 

Characteristics of the Asian Diet 

The Asian diet is characterized by a high-carbohydrate, high-fiber, low-fat, and low-meat protein composition. Typical Asian food generally consists of rice and vegetables as the major source of carbohydrate and fiber. Vegetable oil is a common source of fat, whereas fish, eggs, poultry, and pork are the main sources of protein. This is in contrast to Western diets, which are rich in animal fat and beef protein but lower in carbohydrate and fiber contents. In addition, Asian foods often consist of several ingredients, such as chili, to make the foods tastier. 


1. Role of rice and high-carbohydrate diet in FGID 

In general, food can aggravate gastrointestinal symptoms by several mechanisms including: exaggerated physiologic responses of the gastrointestinal tract, food intolerance, allergy, increased intestinal gas,and modification of gut motility and sensation. 

Food with high-carbohydrate content may cause symptoms of functional bowel disorders by both allergic and non-allergic mechanisms. As for the latter, carbohydrate may cause gastrointestinal symptoms because of incomplete absorption in the small bowel, such as lactose mal-absorption. In the allergic mechanism, the protein contents in the carbohydrate sources may cause allergic reactions to the gastrointestinal tract, such as gluten in wheat. 

Major types of carbohydrate in the human diet are: starches, sucrose, and lactose. They have to be digested into monosaccharide before being absorbed through the gut mucosa. If the complex-carbohydrate and monosaccharide are not completely absorbed into the small bowel, then these substances will enter the colon and will be fermented by colonic bacteria to produce gas and short-chain fatty acids, which may contribute to the symptoms reported in patients with FGID such as diarrhea, gas, bloating, and abdominal discomfort and pain. The non-absorbable carbohydrates and their metabolites may induce gastrointestinal symptoms by their effects on gut sensation and gut motility, such as decreased gastric tone, decreased lower esophageal sphincter pressure and accelerated small bowel transit. A recent study in Asia (India) demonstrated that there is a similar prevalence of lactose intolerance in IBS patients and healthy controls. The authors performed lactose hydrogen breath tests in 124 IBS patients and 53 age- and gender-matched healthy controls. They found a similar prevalence of abnormal lactose hydrogen breath tests in IBS patients and healthy volunteers (72% vs. 60%). However, IBS patients developed gastrointestinal symptoms more often than healthy volunteers after ingestion of lactose (56% vs. 34%). This higher rate of gastrointestinal symptoms suggests that there is a role of visceral hypersensitivity in the expression of carbohydrate mal-absorption symptoms and that the completeness of small intestinal absorption of carbohydrate is important in patients with IBS and can associate with their IBS symptoms. 

2. Rice is completely absorbed in the small intestine, producing little gas 

Major sources of complex carbohydrate or starch in the human diet are wheat, rice, oat, potato, and corn. The effects of each complex carbohydrate or starch on gastrointestinal symptoms depend on its fiber content, its allergenicity, and the completeness of the small bowel digestion and absorption. In Western countries, wheat is the major source of carbohydrate. It may cause gastrointestinal symptoms by allergic reaction to gluten, the major protein component of wheat. In a recent meta-analysis of 14 studies, patients who fulfill the criteria of IBS (n = 2,278) have a higher prevalence of celiac disease than controls (n = 1,926). The pooled prevalence of positive IgA-class antigliadin antibody, either positive endomysial antibody or tissue transglutaminase, and biopsy-proved celiac disease in IBS were 4.0%, 1.63%, and 4.1%, respectively. Pooled odds ratios (95% confidence interval) for positive IgA-class antigliadin antibody, either positive endomysial antibody or tissue transglutaminase, and biopsy-proved celiac disease in IBS patients compared with controls were 3.40 (1.62-7.13), 2.94 (1.36-6.35), and 4.34 (1.78-10.6), respecttively. This implies that, in a subgroup of IBS patients, ingestion of a gluten-containing diet may aggravate and avoidance of the diet may improve gastrointestinal symptoms.Furthermore, wheat ingestion produces the highest peak of breath hydrogen compared to other sources of carbohydrate such as corn, oats, potatoes, beans, and rice in healthy humans. This suggests that wheat carbohydrate is not completely absorbed in the small bowel and that it may produce gastrointestinal symptoms, independent of gluten hypersensitivity.

Rice is the major source of carbohydrate in Asian populations. In contrast to wheat and other sources of carbohydrate, rice is completely absorbed in the small bowel and produces very little intestinal gas after ingestion. A previous study demonstrated that the amount of hydrogen, a maker of carbohydrate metabolism by intestinal bacteria, in breath samples after rice ingestion is minimally increased and not significantly different from the fasting period. Furthermore, rice has been shown to have a low allergenicity. Previous studies demonstrated that serum IgG levels produced in reaction to several kinds of food such as wheat, beef, pork, lamb, soybean, shrimp, egg, and crab were increased in IBS patients compared to healthy humans, but the serum IgG levels produced to rice in IBS patients is mild or not increased. A study from China in 37 IBS,  functional dyspepsia, and 20 healthy controls demonstrated that serum IgG antibody titers to rice was similar in IBS (28.7 ± 0.5 U/mL) and functional dyspepsia patients (29.5 ± 0.7 U/mL) compared to healthy controls (28.4 ± 0.5 U/mL). In contrast, the serum IgG antibody titer to wheat was increased in IBS patients (60.6 ± 3.4 U/mL) compared to functional dyspepsia patients (49.4 ± 2.0 U/mL) and healthy controls (48.1 ± 2.0 U/mL). This low production of IgG suggests that rice has a low allergenicity compared to other common foods. 

3. Rice has lowest fiber content compared to other common sources of carbohydrate 

It has been reported that fiber speeds up human gut transit and can improve constipation symptoms. However, its benefit in FGID is limited. Recent meta-analysis studies on the effect of fiber on global symptoms of IBS patients demonstrated conflicting results. In addition, it may worsen abdominal pain and bloating symptoms. In healthy humans, ingestion of fiber (psyllium) can delay intestinal gas transit and cause more gas retention after intestinal gas perfusion. Thus, a high-fiber diet may worsen abdominal bloating and pain by delaying intestinal gas transit and increasing gas production in the colon secondary to bacterial fermentation. In certain parts of Asia, such as in India, healthy controls and patients with IBS have more dietary fiber (51.7 and 52.3 g/day, respectively) than the recommended amount for the general population (20-40 g/day). Therefore, increasing the dietary fiber consumption of functional gastrointestinal disorder patients in certain parts of Asia may not provide any benefit but may worsen the bloating and abdominal pain symptoms. 

Although the Asian diet is rich in fiber, rice - the widely used complex carbohydrate - has the lowest fiber content compared to other kinds of cereal. A previous study demonstrated that the total fiber content (insoluble + soluble fiber) of different kinds of cereal is lowest in rice and highest in wheat (4.1% in rice vs. 12.5% in wheat). As high-fiber may worsen abdominal pain and bloating symptoms, rice may be the most preferable carbohydrate source for functional gastrointestinal disorder patients with predominant symptoms of bloating and abdominal pain. 

4. Clinical studies suggest benefits of rice-base meal in IBS 

Rice has been the major source of carbohydrate in exclusion diets in several clinical studies. These studies demonstrated that the exclusion diet is well tolerated and can improve IBS symptoms in both open and controlled studies. A recent study by King et al. suggests that the rice-based exclusion diet may improve symptoms in IBS by reducing intestinal gas production. The study was performed in 6 female IBS patients and 6 female controls by measuring 24-hour hydrogen and methane production after ingestion of rice-based exclusion diet or standard diet, in a crossover controlled trial, using a whole-body calorimeter. The authors found that after standard diet the gas excretion rate and hydrogen production was higher in IBS patients (2.4 mL/min and 332 mL/24 hr, respectively) than in controls (0.6 mL/min and 162 mL/24 hr). The rice-based exclusion diet reduced hydrogen production compared to standard diet in both IBS (79 vs. 332 mL/24 hr) and controls (95 vs. 162 mL/24 hr). In addition, in IBS patients, the exclusion diet reduced symptoms [symptom score = 8 (5.25-10) vs. 4 (3-7)] and reduced the maximum gas excretion rate compared to the standard diet (0.5 vs. 2.4 mL/min). 

Recently, the very-low-carbohydrate strategy has been shown to improve IBS-D symptoms in a small open study. The authors found that 13 of the 17 patients who were enrolled completed the study. Ten (77%) of the patients who completed the study reported adequate relief of IBS symptoms. Furthermore, the stool frequency, stool consistency, pain scores, and quality of life were significantly improved. 

Because there have been reports of inadequate dietary intake because of food avoidance in IBS patients, the avoidance of poorly-absorbed carbohydrates combined with the consumption of well-absorbed carbohydrates or rice may be more appropriate than the use of very-low-carbohydrate diets in the dietary treatment strategy for IBS patients. 

All together, rice may be the best source of carbohydrate for patients with functional bowel disorder because of its low allergenicity, its nearly complete absorption in the small bowel, and its low fiber content. In addition, a small crossover controlled study supports its benefit in IBS. 

5. Effect of chili on FGID 

Chili and spicy food are common in most Asian countries. The average daily chili consumption in Asian people is 2.5-8 g/person. It is much higher than that of 0.05-0.5 g/person in European and American peoples. Recent studies suggest that acute and chronic ingestion of chili can modify gastrointestinal symptoms in FGID. Whether or not a high prevalence of spicy food modifies gastrointestinal symptoms at the population level is not known. In addition, data on the effect of chili or spicy foods on FGID in Asian countries with a high prevalence of spicy food have been limited. 

6. Capsaicin mediated visceral nociception in FGID 

The active ingredient of chili is capsaicin. Capsaicin can modulate gastrointestinal sensation via capsaicin or TRPV1 receptors. These receptors have been found at different levels throughout the gastrointestinal tract. Capsaicin, acid, and heat can stimulate the TRPV1 receptors and mediate a sensation of burning and pain. Several studies suggested that TRPV1 receptors can mediate sensations of warmth, pressure, cramping, and pain in the human gut. Increases in the number of TRPV1 receptors have been found in the gut mucosa of patients with conditions associated with visceral hypersensitivity, including in the esophagus of patients with non-erosive reflux disease (NERD), in the colon of patients with irritable bowel syndrome and in the rectum of patients with rectal hypersensitivity. Recent studies demonstrated that patients with FGID, including functional dyspepsia and irritable bowel syndrome, exhibit gut hypersensitivity to capsaicin or capsaicin containing chili. Hammer et al. studied the effect of 0.75 mg capsaicin powder ingestion on gastrointestinal symptoms in 54 functional dyspepsia patients and 61 healthy controls. They found that after capsaicin ingestion, nausea, a flutter-like sensation, warmth and abdominal pain scores were higher in functional dyspepsia patients than in healthy volunteers. A recent study in 20 IBS-D patients demonstrated that ingestion of chili-containing meals produces higher abdominal pain and abdominal burning symptom scores than standard meals and when compared to the symptoms reported by healthy volunteers in response to ingestion of chili-containing meals. Studies suggest that abdominal pain and burning symptoms seem to be the typical gastrointestinal symptoms of capsaicin hypersensitivity, whereas abdominal bloating symptoms seems to be independent of the capsaicin pathways. 

Low-grade inflammation in the gastrointestinal tract has been proposed as a major pathogenesis of FGID, especially in irritable bowel syndrome. Up-regulation of TRPV1 pathways resulting in visceral hypersensitivity to mechanical and chemical stimulations has been reported following an induction of colonic inflammation in an animal model. In humans, gut inflammation has been reported to be associated with an increased number of TRPV1-expressing nerve fibers. Thus, hypersensitivity of the TRPV1 pathways in patients with FGID is likely a result of low-grade inflammation and may be an important pathogenesis of gut hypersensitivity, abdominal pain, and abdominal burning symptoms in FGID. 

7. Desensitization of capsaicin receptors, its role on patients' symptom profiles and treatment of FGID 

It has been reported that prior exposure of esophageal mucosa to capsaicin solution do not affect esophageal sensation in response to acid perfusion or to balloon distention. However, the study evaluated the effect of single stimulation of esophageal mucosa by perfusion of capsaicin solution into the esophagus and could not exclude the desensitization effects of capsaicin receptors in the gut mucosa after repeated exposure to capsaicin agonists. 

It has been demonstrated that TRPV1 receptors can be desensitized by repeated exposure to capsaicin. Recent small studies suggested that chronic ingestion of capsaicin containing chili can modify dyspepsia symptoms in functional dyspepsia patients and GERD symptoms in NERD by decreasing dyspeptic and GERD symptoms, respectively. Bortolotti et al.randomized 30 functional dyspepsia patients to receive 2.5 g/day of red pepper powder or placebo in a double-blind manner for 5 weeks. They found that red pepper significantly improved overall symptom scores, epigastric pain, fullness, and nausea scores relative to placebo. The overall symptom scores decreased from 3.3 ± 0.6 at baseline to 1.7 ± 0.2 at the end of week 5 for red chili treatment compared to from 3.4 ± 0.7 to 2.5 ± 0.3 for placebo treatment. In a preliminary study in 8 patients with NERD, red chili ingestion for 6 weeks significantly improved total GERD, heartburn, and regurgitation symptom scores compared to placebo. The authors found that, at baseline, total GERD scores, heartburn, and regurgitation scores were similar comparing between chili and placebo capsules (chili vs. placebo: 7.6 ± 3.7 vs. 4.7 ± 2.8, 4.6 ± 2.3 vs. 3.2 ± 2.1, and 2.9 ± 2.4 vs. 1.5 ± 1.6, respectively). At the end of week 6, red chili significantly decreased GERD symptom scores (chili vs. placebo: 0.9 ± 1.2 vs. 4.9 ± 2.4), heartburn symptom scores (0.4 ± 0.6 vs. 3.7 ± 1.6), and food regurgitation symptom scores (0.5 ± 0.8 vs. 1.3 ± 1.6) compared to placebo. The effects of chili ingestion on functional dyspepsia and GERD symptoms were observed after the 2nd week of treatment in both studies. The similar effects of chronic ingestion of red chili in functional dyspepsia and NERD patients suggests that capsaicin receptors play role on the development of both functional dyspepsia and NERD symptoms and is consistent with previous reports of visceral hypersensitivity to capsaicin in functional dyspepsia54 and increase TRPV1 receptors in NERD.42 In contrast, a previous study in 12 healthy volunteers reported that chronic chili ingestion induce more gastroesophageal refluxes. However, the duration of chili ingestions was too short (≤ 1 week) in relative to the other studies, which showed the desensitization effect of chili (5-6 weeks). These limited data suggest that the natural capsaicin agonist (chili) may have a therapeutic role for pain and burning symptoms in FGID and more research studies are needed to confirm this hypothesis. 

The effect of spicy food, which is frequently eaten in Asia, on the gastrointestinal symptom profiles in FGID at population level is not clearly known. Studies of GERD symptoms in Asian patients have reported a lower prevalence of heartburn compared to Western patients. A study of GERD symptoms in German patients who underwent 24-hour esophageal pH monitoring showed that both heartburn and acid regurgitation are the main typical GERD symptoms, whereas a similar study in an Asian country (Thailand) with a high prevalence of spicy food reported only acid regurgitation, but not heartburn, as the main GERD symptom (Fig. 1). Furthermore, epidemiologic studies in Asian countries, including China, Iran, and Thailand, demonstrated lower heartburn/regurgitation symptom prevalence ratios compared to Western or developed countries with a low prevalence of spicy food. However, the low heartburn/regurgitation symptom prevalence ratio was not observed in Korea. In Turkey, an European country with a high prevalence of spicy food, the prevalence of heartburn in the population is much lower than the prevalence of acid regurgitation (weekly heartburn vs. acid regurgitation: 10% vs. 15.6%, respectively).71 When the studies that reported the prevalence of annual regurgitation and heartburn symptoms were included, studies of the American population reported a heartburn/regurgitation prevalence ratio of 0.91-0.94, whereas studies in China reported a lower ratio of 0.34. There has been no study that directly compares GERD symptom profiles between Asian and Western peoples or patients in the area of high and low prevalence of chili in the diet. However, the collective results of the available studies imply that acid or gastric content regurgitation into the esophagus in people in certain regions of Asia is not perceived as heartburn symptoms by the esophagus in the same way that heartburn symptoms are perceived by Western people. The high prevalence of spicy food may play a role in this finding, but this hypothesis has not been proven. The low prevalence of heartburn symptoms is not likely to be a misinterpretation of acid reflux symptoms in Thai people because acid perfusion tests produce no symptoms in most Thai GERD patients (GI Motility Research Unit, Chulalongkorn University, Thailand, un-published data). However, the heartburn/regurgitation symptom prevalence ratio is not lower in Mexico, where the prevalence of spicy food is high. This inconsistency suggests that not only spicy food, but also other factors, may influence the sensitivity of esophagus to gastro-esophageal reflux contents at the population level.   

In summary, capsaicin or TRPV1 receptors are involved in the pathogenesis of burning and pain symptoms of the gastrointestinal tract. Recent small studies suggest that the chronic use of capsaicin-containing chili can decrease heartburn and abdominal pain in GERD and dyspepsia, respectively. In addition, the ratio of the prevalence of heartburn/regurgitation symptoms in the population is lower in several parts of Asia; this lower rate may be related to the high prevalence of chili or spicy food. 


Rice seems to be the most preferable source of carbohydrate in patients with FGID. It has a low allergenicity and fiber content; it is also completely absorbed in the small bowel and produces little gas after ingestion. Therefore, it should be advocated as a major source of carbohydrate for patients with IBS and those with other functional GI disorders. 

There has been increasing evidence to support the role of capsaicin receptors in the pathogenesis of symptoms of FGID. Preliminary studies support the role of desensitization of capsaicin receptors by chili, a natural capsaicin receptor agonist, for the treatment of functional dyspepsia and NERD. However, more research studies are needed to confirm this hypothesis. 


Financial support: This review was supported by the Ratchadapisek Sompotch Endowment Fund (GI Motility Research Unit grant). Conflicts of interest: None. 


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Source: J Neurogastroenterol Motil. 2010 April; 16(2): 131-138. Published online 2010 April 27. doi: 10.5056/jnm.2010.16.2.131. By, Sutep Gonlachanvit MD.

Tags:  food and drink  gastrointestinal disease 

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Low Testosterone Linked to Heart Disease

Posted By Administration, Thursday, March 25, 2010
Updated: Friday, April 18, 2014

3227286803_3cbf819f60_m Low levels of testosterone have been associated with increased body weight, insulin resistance (a precursor to diabetes and a risk factor for heart disease), and poor cholesterol levels.  These metabolic factors ultimately lead to cardiovascular disease.   

A noteworthy overview of androgen deprivation therapy and its tight link to cardiovascular disease has been published in the journal Circulation.  In it, a group that included members of prominent heart, cancer and urological societies, issued a well-researched position stating that prostate cancer patients who are on androgen deprivation therapy (ADT) are at an elevated risk for getting heart disease.  

Evidence shows that when one’s androgen levels are lowered, a metabolic syndrome ensues.  This does not necessarily mean that patients should not be on ADT, but does pave the way to new screening strategies for metabolic syndrome for those on ADT.   

Most importantly, this brings to light, again, the negative effect that low testosterone has on insulin sensitivity and the heart.  Metabolic syndrome and cardiovascular disease can potentially be prevented via the optimization of testosterone levels.  

For males, it is important to understand what your “total” and “free” testosterone levels are, and to perform a thorough workup that focuses of deciphering the cause of why the levels are low (or high) in the first place.  Then, a treatment strategy should ensue.  This should focus on addressing the cause, first and foremost.  Thereafter, treating the cause is key.  

There are many options for patients with low testosterone.  Lifestyle changes should ensue as they are often significant contributors to low testosterone levels.  Supplements and/or medication that can boost testosterone levels can also be judiciously utilized.  There are also supplements and medications that can work on preventing the aromatization of testosterone (conversion of testosterone into estrogen in fatty tissue).  Those patients on intentional ADT in the setting of prostate cancer cannot be on androgen replacement therapy.   

- Zina Kroner, DO

Tags:  heart disease  testosterone 

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Have We Abandoned Our Children to Toxins?

Posted By Administration, Friday, March 19, 2010
Updated: Friday, April 18, 2014

Many of us are aware of the recent Centers for Disease Control (CDC) report indicating that 1 in every 110 children has some form of autism. Fewer know the work of Dr. Philip Landrigan, of Mt. Sinai Medical School, who was quoted in a February 25, 2010, New York Times editorial by Nicholas Kristof: "Do Toxins Cause Autism?"  According to Landrigan, 1 in 6 American children is currently learning or behaviorally disabled. childwithmaskAnother excellent resource is the work of ACAM member, Dr. Kenneth Bock, chronicled in his recent book Healing the New Childhood Epidemics: Autism, ADHD, Asthma and Allergies The Groundbreaking Program for the 4-A Disorders.

As the following, recent news stories indicate, our nation’s children live in an environment that is increasingly toxic:

  • Studies show danger of even small amounts of lead in children's blood
  • Dust bunnies tainted with toxins? Household dust consists of a potpourri that can include lead, arsenic, and other potentially harmful substances
  • Phthalates (plastics softeners used in children's products) predispose mice to allergies

Add to these the fact that our children are exposed to more vaccinations than ever before. In 1985, children were vaccinated for seven diseases; that number has swelled to 16. And vaccinations are grouped together solely to make children more likely to get them, even though the risks increase to an unknown degree.

Parents deserve to know that vaccines are neither 100 percent effective nor 100 percent safe. A 16-year old girl lost her vision following vaccination against the HPV virus. Do we have to wait until most children are autistic or otherwise damaged before we try to do something about this situation?

Published March 16, 2010 at Have We Abandoned Our Children to Toxins?

Tags:  toxins 

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Aging Gracefully Now

Posted By Administration, Thursday, March 18, 2010
Updated: Friday, April 18, 2014

4016109413_10fc490c33_m Aging in the West conjures up images of people in nursing homes, unable to enjoy the few remaining years in their lives and totally dependent on other people for some of the basic things in life such as eating or bathing themselves. Who wants to have a long life if this would be the eventual outcome for anyone? How many people live independently and abundantly into their senior years? How can someone make sure that they could enjoy their lives free from chronic disease or infirmities?

That’s where the concept of holistic preventive care comes in. Preventive care unfortunately, usually just involves early detection and screening in allopathic medicine. It’s the advice given to women about annual Pap’s smears and mammograms or PSA testing for men at a certain age. There’s more to prevention however than getting yearly tests. Prevention should be done on a daily basis by taking care of the body’s needs, primarily through clean food, water and air. Then, there are also important things such as sleep, exercise, stress reduction, detoxification and intake of nutritional supplements.

Our health is very closely related to that of the health of our environment. Just as clean air and water are necessary for the survival of the earth, they are also needed for our survival as a species.

There’s a concept called “internal milieu.” Dr. Louis Pasteur, on his deathbed, admitted that “the microbe is nothing, the terrain is everything.” What this means is that for instance, if several people were exposed to the same germ/pathogen, not everybody gets sick. Some people may be more resistant to illness because of genetics as well as other factors that influence their immune system (diet, presence of toxins.) If I may borrow one of my colleague’s analogies, “Our genes are like a loaded gun, our environment pulls the trigger.”

The major medical systems in the world, such as Chinese medicine, Tibetan medicine and Ayurveda, all emphasize the important role that food plays in prevention of illness as well as influencing the course of illness. Unfortunately, this is not the case in other medical systems where people are told that they can eat anything after a certain diagnoses. Ever wonder why there are fast food joints that sell deep fried or highly refined foods at major medical centers?

Anyway, in more practical terms, what are the factors that could cause premature aging?

Among the different reasons behind aging there are hormonal imbalances, nutritional deficiencies, oxidative stress, chronic inflammation and toxicities. Just like doing maintenance work on our cars is imperative to make them work more efficiently, we need to do the same thing to our bodies. Let’s start with the basics. The food we give our bodies could be compared to the things we do to maintain our cars. Again, to borrow another analogy, carbohydrates could be compared to the fuel system, fats to the oil used to lubricate the car and protein to the actual skeleton/frame of the car. Neglect one of these and it could lead to eventual breakdown of our cars and in this case, our bodies.

Regarding food, I believe that everybody is different and therefore, have different food requirements. One of my mentors taught me that we in North America, actually don’t have a traditional diet unlike peoples from Asia, Africa or the Mediterranean. The Standard American Diet (SAD) of meat and potatoes in general doesn’t give us adequate nutrition to prevent illness. What I would recommend for one person may be different from what I recommend to another.

For instance, for Asians in general, a typical meal of fish with rice and vegetables should suffice. However, for a Caucasian, I may recommend food combining with protein and vegetables without any starches during a meal.

There are many diets available out there. These include the blood type diet, the South Beach diet, raw food diet, etc. In general, I would recommend eating organic foods. Having greater portions of vegetables and fruits in the diet and a limited amount of meat would work for most people. As far as meat is concerned, free-range chicken or grass-fed beef would be a better choice than regular chicken or beef.

Then, there’s concern about fish or seafood. The higher you go up on the food chain, the greater the chances of mercury toxicity. I would recommend smaller fish such as anchovies or sardines.

There’s the timing of meals that’s also equally important. I would recommend small, frequent meals rather than three “square meals a day.” Not eating after 6 pm ideally would be best, but if necessary, at least keeping it light at night would be advisable.

Nutrition is a very touchy subject because of the different recommendations you get from authorities. What I would recommend in general is to only eat when hungry and only eat as natural as possible. Any food adulterated by man (boxed cereal grains, “low-fat” TV dinners) could cause more problems long-term. Just a quick note, fat is what tells our satiety centers that we’re full. Thus, a low-fat meal won’t really curb someone’s appetite or help with weight loss.

- Joel Lopez, MD, CNS

Tags:  anti-aging 

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Integrated Medicine for Neurologic Disorders

Posted By Administration, Tuesday, March 9, 2010
Updated: Friday, April 18, 2014

Imgres Integrated Medicine for Neurologic Disorders is a book which addresses herbal and holistic medicine for brain health and neurological disorders such as Alzheimer’s Disease, Parkinson’s Disease, Multiple Sclerosis, Stroke, Migraine, and Seizures. This book can help patients and medical practitioners to integrate Western medicine with herbal and holistic medicine to reduce symptoms and slow disease progression.

Sheryl Shook, Ph.D., a physiology professor with a Ph.D. in neuroscience, co-authored the book with Dr. Sidney Kurn. They have combined their expertise to work in the community educating about improving health by integrating the benefits of mainstream medicine with the rich and valuable practices from many cultures that rely on plants, nutrition, and lifestyle for healing. 

“Keeping your body healthy is an expression of gratitude to the whole cosmos - the trees, the clouds, everything.” Thich Nhat Hanh 

As one of the oldest medical subspecialties, neurology has a long history of clinical observation and theoretical development. The extreme complexity and inaccessibility of the nervous system continues to challenge researchers, compared with the rapid, technological development of other specialties such as cardiology or nephrology. Until the last 20 years, even drug treatments were rather limited. Neurologists have witnessed a rapid growth in our pharmacopoeia, including drugs for disorders previously untreatable such as ALS and Alzheimer’s disease.

 Most exciting is the seminal breakthrough in seeing an underlying order involving a few abnormal processes that manifest variably as Parkinson’s disease in one patient, Alzheimer’s disease in another, and so on. Numerous articles report on studies revealing inflammation, excitotoxicity, oxidation, genetic predilection, nutrient deficiencies and environmental toxicity in the onset and development of neurologic disorders. Disorders as disparate as stroke and multiple sclerosis, share these underlying processes. The contribution of each process, the particular positive feedback loops, and particularly the genetic predilection appear to determine the particular disease in any one individual. Even the fields of neuroprotection and system theory, generally not part of mainstream neurology, are receiving attention with numerous articles in peer-reviewed journals (1). 

Unfortunately, despite these important developments in clinical neuroscience, patients continue to suffer the symptoms of neurologic illness. Our drugs are not as effective as we would like, illnesses continue to progress, and the chronicity of some diseases overwhelm our best efforts. As patients and clinicians, we are committed to being pragmatic, finding what works, even if usage is based on tradition without good double-blind, placebo-controlled trials. Large randomized trials are expensive, and for natural herbs and nutrients, do not necessarily lead to a patentable product. Numerous studies on supplements exist and appear regularly in peer-reviewed journals. Studies may not rise to the level of large randomized trials necessary for FDA approval. The absence of this type of evidence is not proof of lack of efficacy. In regards to toxicity, the long history of usage provides ample information, and new interactions are reported on a regular basis. The “gold standard” of clinical drug usage, the Physician’s Desk Reference (PDR), has its second addition on herbs and nutrients. The standard pharmacist’s reference on herbs, nutrients and their interactions has also been re-edited. These texts, plus innumerable Medline references help guide the judicious use of supplements in clinical practice, or, what I call, clinical supplementation.

 Integrated Neurology is the practice of neurology utilizing all appropriate measures to alleviate suffering in an individual patient with a neurologic disorder. This may involve drugs, herbs, nutrients, acupuncture and a large group of bodywork modalities. It is an “open system”, drawing information as needed from science, medicine and the more traditional healing arts. It is “evidence based”, from large randomized trials, millennial long traditional usage as well as anecdotal evidence. The principle of “do no harm”, applies to Integrated Neurology as it does to medicine in general. Even though herbs and nutrients are generally much less toxic than drugs, known side effects, toxicities and drug interactions exist and require careful consideration. offers the reader an introduction to Integrated Neurology including basic principles, treatment suggestions, references and appropriate linkages. Feedback is welcome on the E-mail site. 

“The wisest mind has something yet to learn.”  George Santayana 

          - Sidney Kurn, MD


1. Albergina L and Colangelo AM The modular systems biology approach to investigate the control of apoptosis in Alzheimer’s disease neurodegeneration. BMC Neurosci. 2006 Oct 30;7 Suppl 1:82 (Epub ahead of print)

Tags:  integrative medicine  neurology 

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Soy and Fertility in Men

Posted By Administration, Thursday, March 4, 2010
Updated: Friday, April 18, 2014

There is so much controversy about the effect of soy foods on men’s fertility.  With each study that is released, a news article follows declaring it to be either safe or harmful for men’s fertility.   I would like to go through some of the studies in this area and review the significance of them before drawing a conclusion based on the current evidence.  Soy is well-known for its health benefits for men, including the reduction of risk for both cardiovascular disease and prostate cancer.  Due to these benefits, it has become a larger part of the North American diet than it ever has been in the past so it is important to fully understand its impact on hormones and fertility.

Effects of Soy on Infants and During Pregnancy on Adult Male Fertility

The following studies investigate reproductive effects on men who were given soy products either through infant formula, or while their mothers were pregnant.  This is a very sensitive time of development for the reproductive organs, so much concern remains about the possibility of permanent negative effects.

Soy Formula in Infant Male Marmoset Monkeys causes no Adverse Effects
This study concluded that infant feeding with soy formula has no major adverse reproductive effects in male marmoset monkeys. Although it did not appear to affect fertility, soy infant formula did alter testis size and cell composition.

Again I would like to mention here that both rats and monkeys produce much higher levels of equol (an estrogen like substance which is much stronger than soy isoflavones) in their intestines than humans in general.  The equol is produced through fermentation of isoflavones by bacteria which reside in the intestine.  It’s hard to compare humans directly with rats or monkeys especially when it comes to estrogenic effects.  Studies investigating the effects of phytoestrogens on the fertility of different animal species have been very inconsistent. This indicates that soy has very species specific effects on fertility and highlights the need for more studies on humans before we can draw definitive conclusions.

Study on Vegetarian Mothers and Hypospadias in Infants
This famous study investigated the difference between vegetarian and omnivorous women and the likelihood of a condition known as hypospadias in their newborns.  Hypospadias is a condition (which is currently on the rise) where the urethral opening is in a lower position.  This study found that significantly more of the vegetarian mothers had babies with hypospadias.  As vegetarians have a greater exposure to phytoestrogens than do omnivores, the researchers concluded that phytoestrogens may have a negative effect on the developing male reproductive system. However, this study was not specific for soy, it only examined whether or not vegetarians tended to have more infants with hypospadias. Other factors cannot be excluded for example, vegetarians could be more likely to be deficient in other vitamins or nutrients such as B12, and could also be consuming a larger amount of estrogenic pesticide 
Soy Infant Formularesidue, and this study did not question participants about consumption of organic foods.   It was also found that the vegetarian mothers who did not take iron supplements had more infants with hypospadias.  In Japan, there are 1/10th the number of infants born with hypospadias as there are in North America and yet there is a much higher level of phytoestrogen consumption.  Therefore, this study is not fully conclusive that phytoestrogens are the cause of this developmental condition since there are too many unaccounted for variables.

Study on Soy Formula in Infants and Reproductive Outcome In Young Adulthood
This study on 811 men and women, who were fed either soy or cow milk formula as infants were assessed in young adulthood for their pubertal maturation, menstrual and reproductive history, height/weight, and current health.  It concluded that exposure to soy formula does not appear to lead to different general health or reproductive outcomes than exposure to cow milk formula in infancy. This study did not go into details asking about length of time to conceive. Also, no reproductive health markers were reported for male subjects with the exception of sexual maturation. Although men were questioned about pregnancy outcomes in partners the results were not reported.

In conclusion on the subject of male reproduction and feeding of infant soy formula, it appears that overall there may be a risk for some long-term reproductive developmental changes, however, the full effects of this are unknown and may not go so far as to cause fertility concerns.  However, as we know from so much current data, breast milk is a far superior nutrition method for infants, and avoids any of the risks that soy formula may hold.

Studies on Male Adult Animals

Phytoestrogenic Plant given to Adult Male Mice – Some Effects on Reproduction
A phytoestrogenic plant(pueraria mirifica) was given in two doses, one high and one low,  to a group of adult male mice. Neither treatment had effect on testicular weight, sperm count, LH, FSH or testosterone. However the high (100mg/kg) dose reduced the weight of epididymis, seminal vesicle and sperm motility.  There were no effects on fertility. This effect was seen to be reversible after the phytoestrogen was stopped. However, this plant, though it does contain some of the same components as soy, is not identical to soy.

Acute Exposure of Adult Male Rats to Dietary Phytoestrogens Causes Temporary Reduction in Fertility
This study found that lipid peroxidation damage of sperm was increased in rats fed a high phytoestrogen diet for 3 days.   No such changes were noted in low phytoestrogen group.  As in the previous study, this effect was temporary, with fertility returning to control levels by day 12. Rats who were fed the phytoestrogens for longer than 6 days did not show this reduction in fertility and in fact showed no change in any reproductive parameters.

Phytoestrogens cause no Negative Effects on Fertility of Rhesus Monkeys
In this study, phytoestrogens were given to rhesus monkeys at the age of puberty.  They had no adverse effects on the reproductive systems of male or females as evaluated by hormone concentrations.  Cardiovascular benefits were observed in the monkeys receiving the phytoestrogens.

Studies on Adult Men

Soy Products Related with Slightly Lower Testosterone and Lower Estradiol in Japanese MenMale Symbol

This study on Japanese men investigated the relationship between soy product intake and serum testosterone and estrogen concentrations.  The results found that blood levels of estradiol concentration were significantly lower with increased soy product intake, and blood estrone levels were not related to soy intake.  Testosterone levels were also lower with increased soy intake but this effect was so slight it did not reach significance in the study.  This study also concluded that this may be part of the reason soy reduces risk of prostate cancer in men.

Soymilk Given to Japanese Men Results in Lower Estrogen Concentrations

This  second study on Japanese men investigates the effects of drinking 400 mL daily soymilk on serum estrogen and testosterone concentrations.  In contrast to the previous study, the results of this study indicate that soymilk consumption is associated with lower levels of the estrone form of estrogen.  In this study there was no effect of soymilk on any of the other hormones measured including testosterone, estradiol, and sex hormone binding globulin.

These two studies indicate that soy can affect serum estrogen levels.  It is known from other research that estrogen is required for proper formation of sperm, but also, that elevated levels of estrogen can interfere with fertility (especially if testosterone to estrogen ratios are altered).  So, what we can say is that a good level of balance of estrogen is required for optimal male fertility, and the real question is, does soy interfere with the balance of estrogen enough to impact actual fertility parameters in males.  These two studies do not answer this question, so we need to look more to studies on soy consumption and the end result on adult male fertility.

Soy Food Intake Related to lower Sperm Concentration Among Men from an Infertility Clinic
This very well-known study took a group of men from a fertility clinic and evaluated the relationship between soy food intake and sperm quality and count.  It found that there was a relationship between the intake of soy foods and the reduction of sperm concentration.  72% of men in this study were either overweight, or obese according to their BMI levels.  The relationship was more pronounced in the men who had the highest sperm concentration and among overweight or obese men. Soy foods did not reduce sperm motility, sperm morphology, or ejaculate volume.  This suggests that because androgens are converted into estrogen in fatty tissue,  this may increase tissue sensitivity to phytoestrogens in those who have higher amounts of body fat.   This study did not consider that those who eat more soy could be exposed to more estrogenic pesticides (it did not ask about consumption of organic versus non organic soy).  It also did not account for the addition of soy in many foods that may not have been reported by the participants (such as soy based additives in baked goods, processed foods and so forth).  Therefore, although this study is quite interesting, it not conclusive.   
Couple preparing a healthy mealThis study does however,  make an important association between elevated body mass index, and effects of soy on fertility in men.

Healthy Adult Men of Normal BMI: Soy Isoflavones have No Negative Effect on Sperm Parameters

This new study from the University of Guelph which involved healthy adult men with a healthy body mass index investigated the effects of isoflavones on sperm parameters.  In this study, men were given a daily serving of soy isoflavones in low concentration, high concentration, and then isoflavone free milk protein isolate.  The different substrates were given for 57 days each separated by a 28 day ‘break period’.  The study showed no significant effect of soy isoflavones on sperm concentration, motility and morphology of the men.  This study adds to the evidence that soy has a much lesser effect on semen parameters in men of healthy body mass index.


In summary, more research needs to be done before we can have any conclusive answers about the impact of soy on male fertility.  There are many conflicting studies on this subject, which indicates we need to investigate further.  There are a few points though that we can learn from the current research which can probably be protective to male fertility, and also allow men to have some of the health benefits that soy foods can provide.

1)  Soy can have a temporary, acute effect on adult male reproductive parameters if taken in high quantities, especially if not normally included in the diet.  Therefore, it would not be a good idea to consume large amounts of soy directly around the time when your partner is ovulating.

2)  Soy appears to reduce sperm concentration in males who are overweight or obese, so if you are overweight, try to achieve a healthy BMI.  In cases where BMI is high, soy foods might not be the best staple for the diet while trying to conceive.

3)  It is probably likely that small amounts of organic soy have little negative effect on reproduction in males of healthy body mass index and can provide health benefits such as improvement of cardiovascular profiles, and reduction of risk for prostate cancer.  More research still needs to be done in order to truly understand the impact of soy fertility of healthy adult males.

- Fiona McCulloch, ND


Anthony et al. J Nutr. 1996 January; 126(1): 43–50. Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkeys.Beaton et al. Soy protein isolates of varying isoflavone content do not adversely affect semen quality in healthy young men. Fertility Sterility in press


Chavarro et al. Hum Reprod. 2008 November; 23(11): 2584–2590Soy food and isoflavone intake in relation to semen quality parameters among men from an infertility clinic

Eddy et al. Targeted disruption of the estrogen receptor gene in male mice causes alteration of spermatogenesis and infertility. Endocrinology 1996 137 4796 – 4805.

A Glover et al. Acute exposure of adult male rats to dietary phytoestrogens reduces fecundity and alters epididymal steroid hormone receptor expression. J Endocrinol. 2006

Hess RA. Estrogen in the adult male reproductive tract: a review. Reprod Biol Endocrinol 2003; 1: 52.

Jaroenporn S et al. Effects of pueraria mirifica, an herb containing phytoestrogens, on reproductive organs and fertility of adult male mice. Endocrine 30(1) August 2006.
Jay et al. Aromatase Inhibitors for Male Infertility. The Journal of Urology – February 2002 (Vol. 167, Issue 2, Part 1, Pages 624-629)

Karen et al. Infant feeding with soy formula milk: effects on puberty progression, reproductive function and testicular cell numbers in marmoset monkeys in adulthood. Hum. Reprod. 21: 896-904.

Nagata et al. Nutr Cancer. 2000; 36(1): 14–18. Inverse association of soy product intake with serum androgen and estrogen concentrations in Japanese men.

Nagata et al. Cancer Epidemiol Biomarkers Prev. 2001 March; 10(3): 179–184. Effect of soymilk consumption on serum estrogen and androgen concentrations in Japanese men.

North et al. A maternal vegetarian diet in pregnancy is associated with hypospadias. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. BJU Int. 2000 January; 85(1): 107–113.

Rozman et al. NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Soy Formula. Birth Defects Res B Dev Reprod Toxicol. 2006 August; 77(4): 280–397.

Strom et al. Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood. JAMA 2001 August 15; 286(7): 807–814.


Tags:  fertility  soy 

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My Path to Integrative Medicine

Posted By Administration, Monday, February 22, 2010
Updated: Friday, April 18, 2014


Get to know ACAM member Stuart H. Freedenfeld, MD, and his passion for Integrative Medicine in his essay, My Path to Integrative Medicine.


I was a rebellious youth, born in the forties and inspired by the awareness movements of the sixties. Having aspired to scientific research since my earliest memories, it was during my last year in college that I shifted focus and came to know that my passion was to devote my life to the healing profession. Having excelled in high school and college, I felt drawn to the more glorious pursuits of the surgical subspecialties especially neurosurgery. While working in the inner city free clinics, which are training centers where inexperienced doctors-in-training practice their new skills on the areas poor and uninsured, I realized that my inspiration came from the people that I served and not from the skills that I had to offer them. Family Practice seemed the only area where I could devote myself to the patient rather than the procedure.

After completing my residency in Family Practice, I entered private practice with Kirk Seaton, MD, who had been the director of the Phillips Barber Family Health Center where I had trained. Together we formed Stockton Family Practice. After only two years he decided to return to academic medicine. For the next four years I was the solo physician at SFP. I worked six days per week including two evenings and every Saturday. I was taking call and even delivering babies seven days per week, fifty-two weeks per year. I still get excited with the memories of delivering over 500 babies during my medical career and am thrilled to have been present at the beginnings of so many new families.

These were exhausting years. So when Sal D'Angio knocked on my office door saying he was just finishing his residency training and wondered if I would consider letting him join SFP, I was more than eager to learn about this new physician. He told me about his background and how he had also studied homeopathy, acupuncture and herbal medicine. It intrigued me as it was a far different medical experience than I had had.

Medical school is a place for learning, but it is also a place for conforming. My training had not expanded my horizons, rather it had narrowed my focus. Now this new doctor reinvigorated my passion for learning and my natural tendency to think outside the box. We established a collaborative relationship as we each learned what the other had to offer. But this was not easy for me. Sal understood and taught his skills in ethereal terms but I was a scientist at heart and needed to understand healing in biochemical terms. In a sense, my early studies in these "alternative" approaches were like studying poetry in a foreign language in which I had only limited knowledge. I could say the words but could not grasp the intricacies of meaning. I could see that alternative therapies worked but I could not relate to them in terms that made sense to me.

My great awakening occurred in 1989. Three of my patients in one year had very poor outcomes related to conventional treatments for their coronary artery disease. One 54 year old died during the angiogram study, another died immediately after his bypass surgery and the third, a 79 year old woman had successful bypass but suffered terribly for a year with various complications. None of these individuals had severe symptoms and none had immediately life threatening disease, but each one suffered from standard medical care. I felt obligated to learn more about alternatives. I had heard about chelation therapy for cardiovascular disease but had no personal experience so I went to a 5-day conference on chelation and other aspects of complimentary medicine sponsored by ACAM (The American College for Advancement in Medicine).

I was blown away. Not only was there science behind chelation, but I found myself at a conference taught by world leading scientists, discussing their own particular area of research. Until then, all medical conferences that I had attended were taught by doctors discussing pharmaceutical treatments and presenting the research that was bought and paid for by the pharmaceutical industry. This same industry was also paying their speaker fees. How refreshing to hear information from people who held my own passion for research and shared their knowledge for the sake of healing rather for the sake of selling. Suddenly hawthorn, coenzyme Q 10, L-carnitine and magnesium took on whole different perspectives.

I was so overwhelmed with this abundance of information that I literally could not sleep for the entire five days of this conference. The speakers spoke of alternative medicine and they spoke in my own language, the language of science.

That five-day conference was my epiphany, Since then I have never lost my enthusiasm for learning or my zeal for the healing arts. In the years since 1989 I have continued to pursue knowledge for the sake of my patients with a driving passion that still gives me exhausted evenings and sleepless weekends. I wonder at the universe of knowledge and am humbled by the vastness of the unknown. My enthusiasm comes from the needs of symbiotic fashion, I am nourished by those that I nurture. I learn from those that I teach. I am healed by those I attend.

For the past 15 years Stockton Family Practice has been devoted to integrating the finest aspects of healing arts from around the world and throughout time. Our goal is to be able to provide the safest and most effective approaches to health and healing for those that come to learn and be well. There is no retirement from this pursuit, only gratification. And so to all of you who give me strength, I say thank you.


Dr. Freedenfeld is the medical director of Stockton Family Practice. He received his Bachelor of Science Degree with Distinction from the University of Rochester in 1970 and received his Medical Degree, with honors, from the College of Medicine and Dentistry of New Jersey in 1975.

He has become recognized as one of the leading experts on the integration of multiple forms of healing. He offers consultation on the most complex and challenging problems of our day. His forte is in the areas of autism, chronic fatigue, chronic pain, allergy, autoimmune disease, colitis, cancer, heart and cardiovascular diseases, diabetes, detoxification, longevity and health maintenance. He believes there is a vast array of routes to health and healing, and teaches the integration of the routes most appropriate to the individual.

For more information on Dr. Freedenfeld or the Stockton Family Practice, please visit




Tags:  integrative medicine 

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Posted By Administration, Tuesday, February 9, 2010
Updated: Friday, April 18, 2014

As many parts of the United States endure a winter chill, researchers at the University of California, Davis, researchers have published noteworthy findings in the current Journal of Nutrition. Their study suggests increasing the current recommended vitamin D intake by at least a factor of five (5). The new study states that in order to achieve vitamin D sufficiency (i.e., at least 75 nm/liter), someone of European ancestry needs 1,300 IU of vitamin D a day. People of African descent require 2,100-3,100 IU daily. Many experts consider that 25(OH)D levels less than 50 nmol/liter indicate vitamin D deficiency.

2096907196_1e72a36290 A pooled analysis published in the British Medical Journal found that the combination of vitamin D and calcium reduced fractures by 8 percent and hip fractures by 16 percent.

The call by Bill Faloon of Life Extension Foundation to test hospital patients for vitamin D status grows in importance as vitamin D deficiency is linked to the following:

  • osteopenia and osteoporosis
  • muscle weakness and chronic pain
  • fractures
  • common cancers
  • autoimmune diseases including type I diabetes
  • infectious disease
  • cardiovascular or heart diseases

Of those aged 50-70 enrolled in a Chinese study, 94 percent tested vitamin D deficient. Vitamin D deficiency is also now linked to metabolic syndrome or insulin resistance. Given the approximately 2,900 studies published to date and the growing awareness of vitamin D deficiency among those who live in the United States, why no public-health action?

From ANH-USA. Published on January 26, 2010.

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What's New in Regenerative Orthopaedics?

Posted By Administration, Monday, February 8, 2010
Updated: Friday, April 18, 2014

Platelet Rich Plasma (PRP)

Many people in this country are suffering needlessly from chronic pain. Whether it be back pain, neck pain, rotator cuff injuries, headaches, sports injuries, pain from automobile accidents, often patients will suffer for years with their pain. They search for causes, see numerous specialists, and occasionally have surgery, but still go on with pain. What could be wrong? Is it really in their head?

More often than not, the pain is not in their head (unless they have head and neck issues) but is caused by damage to the soft tissue of the joints such as ligament or tendon tissue. The ligaments and tendons of our body support nearly every joint, and also send the brain information of proprioception (the position of our body in space), and nociception (pain). If a ligament or tendon is damaged, it can cause both local pain and referred pain such as sciatica, or numbness down an arm, or into the head. The ligament and tendon damage is often not seen on MRI, CT scan, nor X-ray and needs to be found on a careful physical examination by a physician who is skilled in musculoskeletal injuries. Occasionally, ultrasound may be used to diagnose the problem.

Fortunately, we have a new method to make damaged ligaments and tendons heal - Platelet Rich Plasma (PRP). Our body has the ability to heal, and contains growth factors to regenerate damaged tissue. We have learned in recent years on how to harness that ability and concentrate it into a damaged area. With PRP, after a proper diagnosis has been established, a small amount of blood is extracted from the patient. The blood is then processed and the platelets and growth factors are extracted from the blood. Under appropriate guidance, it is directly and precisely injected into the damaged area. The injection will cause a scaffold to form around the damaged area, impregnated with growth factors, and will incite the healing response. After a series of treatments, the areas will heal, and the pain will end. Since PRP is regenerating joint damage, not just treating pain, the response will often be permanent, and normal activities can be resumed - then the patient can live happily ever after!!!

- Scott Greenberg, MD

Greenberg-61 Dr. Greenberg is a practicing physician at the Magaziner Center for Wellness and a long time member of ACAM. He specializes in natural approaches to family practice problems with a distinctive emphasis on nutrition, cancer, preventive medicine, anti-aging strategies and the use of  PRP and prolotherapy for pain management. Dr. Greenberg personally performs about 100 PRP treatments per month and 4000 prolotherapy treatments per year. For more information on the Magaziner Center for Wellness and PRP please visit:

Tags:  orthopaedics 

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Psychotherapy: What's Metaphyscial Got to Do With It?

Posted By Administration, Friday, February 5, 2010
Updated: Friday, April 18, 2014


Clinicians have a number of treatment options for dealing with the emotional ills of patients, including psychoeducation, psychotherapy, and pharmacotherapy. However, after years of experience in the clinical field, we have recognized that these treatment options may not be sufficient to adequately address the problems of some patients. We have found that adding a metaphysical/spiritual component may be helpful, particularly for those patients with histories of childhood trauma. In this edition of The Interface, we discuss four metaphysical techniques for facilitating patient healing—1) refocusing on the present, 2) reframing adversity, 3) practicing surrender, and 4) meditation. These approaches can be mutually integrated and compliment a psychological treatment in either the psychiatric or primary care setting, regardless of whether or not the patient has formal religious beliefs.


In working with patients for more than 25 years, we have relied on the cornerstones of our psychiatric/family-medicine training for the treatment of psychiatric disorders—psychoeducation, psychotherapy, and psychopharmacology. We candidly acknowledge that these three therapeutic approaches have been invaluable in treating many patients with emotional difficulties. However, despite this cache of clinical interventions, a number of patients continue to emotionally struggle. Something in the overall treatment strategy appears to be missing. We have long noted that these struggling patients oftentimes have histories of childhood adversity. In our earnest endeavors to address this enigmatic deficit and to enhance patient care, we began to explore additional therapeutic options and found some possible answers in the metaphysical/spiritual literature. Collectively, these metaphysical techniques seem to offer a spiritual component to the treatment of emotionally complex patients.

While novel for some healthcare professionals, the addition of a spiritual component to the preceding three conventional therapeutic components was described long ago by Native Americans. These pioneers developed the medicine wheel and its four key areas-of-life emphasis: the intellectual (i.e., psychoeducation), the emotional (i.e., psychotherapy), the physical (i.e., pharmacotherapy), and the spiritual (i.e., the metaphysical). In this edition of The Interface, we discuss this fourth component—the metaphysical/spiritual—and describe four techniques from this literature that may offer additional therapeutic support to patients.


A number of contemporary metaphysical authors stress the importance of “living in the present.”17 They pragmatically emphasize that the present is the only experiential space in which we realistically can live. This perspective essentially requires one to relinquish, to some degree, compulsive preoccupations with the past and the future. Neither past nor future allows one to experience the only reality that an individual can ever actually experience, which is the present.

Without reasonable anchorage in the present, one is left with the vicissitudes of the past and future, which at times may be entrapping through compulsive preoccupation. Indeed, Eckhart Tolle describes these mental past/future machinations as being “trapped in time [with] the compulsion to live almost exclusively through memory and anticipation.”8 This metaphysical emphasis on the present does not exclude the necessity of healthy reflection and realistic future planning in one’s life, but rather confronts the ongoing churning of distressing past/future mental movies.

Living in the past. For many of our patients, it is reflexive to emotionally anchor in the past, especially for those with traumatic life histories. Childhood adversities, particularly sexual, emotional, and physical abuses as well as physical neglect and observing repetitive violence, tend to be powerful and influential psychological material upon which to obsess. At its extreme, in some tragic cases, repeated victimization in childhood (i.e., genuine victim status) morphs into an artificial “victim” identity in adulthood, replete with its chronic self-defeating behaviors and continual re-enactments of self-destructive relationships. Such extreme mind identification with the past effectively defeats the genuine unfolding of the individual’s true identity in the present, leaving him or her trapped in a monotonous and robotic life script. In the aftermath, ongoing preoccupation with the losses and abuses of the past, which distracts from the experience of the present, may unintentionally precipitate intensely negative feelings, which may lead to clinical depression in susceptible individuals.

Living in the future. Like the past, the future is also fertile ground for mind play in a variety of forms. One common example is excessive and/or neurotic planning to avert some imaginary disaster, which behaviorally reaches a crest in the phobic patient. Another common example is the excessive mental activity focused upon “getting somewhere”—i.e., achieving a highly desirable endpoint (e.g., completing an education, closing a business deal, achieving the prescribed retirement nest egg). Granted, it is necessary to do a reasonable degree of planning for the future, but compulsive rumination about the future may set the stage for impatiently waiting for an imaginary future life to unfold—all at the expense of being able to experience the reality of the present.

As a corollary, many people seem to over-value the outcome of an experience and the foreshadowed rewards or relief that it may bring, rather than “experiencing the experience.” In this regard, American culture including the media tends to play an active role in nurturing these mental preoccupations with the future. We are constantly bombarded with futuristic formulas for success. Children have to get into the right private schools. Particular clothes, make-ups, fragrances, bodies, neighborhoods, and cars will ultimately garner social success and happiness—once one has accumulated the extensive financial resources to afford them. Happiness awaits when one moves into the big house. The folly of these cultural myths may seem self-evident, but for young patients and those with poor or absent mentoring (i.e., patients with deficient parental mentoring, whom we so commonly encounter in those with histories of childhood adversity), this cultural dogma may function as the only life guidance for scripting “success.” On an emotional level, this excessive preoccupation with the future may unintentionally reinforce worry and tension, which may lead to clinical anxiety states in susceptible individuals.

Case example 1. Regina described the situation exactly as she had experienced it. “I just sat there…thinking to myself over and over that the flight was going to be cancelled. After sitting for an hour on the tarmac, they started pulling off the luggage because of weight requirements. Then, after another hour of sitting on the plane, they started pulling people off. I just knew that I would never make my connecting flight in Atlanta. I just knew it! I would have to stay in a hotel overnight in Atlanta and get into town the next day. I hate unnecessary overnights! Then, I would never make my business appointments. I wondered if I should call work and cancel my appointments.”

Therapist: “What happened?”

Regina replied, “The plane took off two and half hours late, but I made my connection.”

Case example 2. Ben was working very hard as a first-year resident in the internal medicine program. “I’m working 80 hours a week, studying all the time, and I don’t get to spend much time with my family, but it will all pay off when I finish. I’m going to have a great salary, nice house, club membership…you know…that’s all I think about…I’m really going to have made it!”

Living in the present. Granted, the metaphysical principle of staying present appears to be a very easy concept—stay in the present and avoid an excessive focus on the past (depressogenic) or the future (anxiogenic). However, putting this principle into actual spiritual practice can be a frank challenge.

At this juncture, we wish to emphasize that the importance of living in the present is hardly a new concept. Indeed, “being present” appears to have its early roots in Buddhism and is described in the Third Noble Truth. Likewise, living in the present is not a novel concept in psychiatry. Cognitive behavioral therapy attempts to curb futuristic thinking (e.g., the endless “what ifs”) as well as the self-imposed constraints that have consolidated through past experience (e.g., “yes, but…”) by confronting unhealthy cognitive patterns. However, the importance of routinely sensing and being aware of what time frame one mentally experiences appears to be relatively novel to the field of psychiatry.

How can the clinician approach the patient who demonstrates compulsive preoccupation with either the past or the future? The initial intervention would seem to be psychoeducation. We believe that patients need to understand and accept (intellectually and emotionally) that their automatic and unattended mental activities are contributing to their overall life dissatisfaction. After explaining the benefits of present-minded thinking to the patient, we suggest several techniques that seem to promote better anchoring in the present.

One initial technique is simply beginning to recognize and be aware of past/future compulsive thinking. “Watch your thinking, observe it, witness it.” This alone may begin to result in the disruption of compulsive patterns of thought. This exercise needs to be undertaken in a nonjudgmental manner (i.e., neutral self-observation) and continually practiced.

A second technique is the immediate cueing on the environment. This technique entails using the five senses to instantaneously experience the immediate environment. “I want you to see, touch, smell, and hear your world…in the moment.” This practice relates to the principle of “mindfulness” or simply being aware. This form of mindfulness practice may be particularly helpful in a number of clinical situations. For example, in an individual with binge eating disorder, the clinician may augment the patient’s experiential tasting through mindfulness practice. “I want you to really experience, savor, and fully taste your meal. Focus solely on the food…it’s texture, color, and taste. This means no distractions, eating slowly, and fully concentrating on your eating.”

Another time-honored technique is focused attention on one’s breathing. Breathing is obviously a physiological experience that is very much “in the moment.” “I want you to concentrate on your breathing, as you breathe in and out. Observe and experience each breath.” This can be undertaken in conjunction with meditation practice.

A final technique is having the patient examine the world through the eyes of a newborn baby. “I want you to see the world in its wholeness and not focus on its parts. See the forest, not the trees. See the world as if it were the very first time you had ever seen it. Like a baby might see it.”

Again, we wish to emphasize that the shift from past/future to present-minded thinking is far easier said than done. It seems to require a consistent and authentic desire to retool one’s thinking processes and ongoing frames of experience. Like any skill, present-mindedness requires continual practice, so we frame this technique to patients as a lifestyle change. At the same time, just as any skill, it becomes easier with practice and more automatic with time.


Adversity—it sounds onerous—hardship, misfortune, difficulties. No one is immune to life’s obstacles. Yet, a number of metaphysical authors emphasize that all things happen for a reason.2,6,9 For some individuals, this proposition may require the proverbial “leap of faith.” How could all things happen for a reason? Certainly, bad things don’t purposefully occur. Whether the position that all-things-happen-for-a-reason is causally valid or not, believing so may improve mental health functioning by facilitating the patient’s adaptation to adverse circumstances.

How does reframing adversity promote patient adaptation? First, we must illustrate the differences between perceiving adversity as a random event versus perceiving adversity as an event by design. If the patient perceives adversity as a random event, then a series of well-honed cognitions are likely to follow—such as “I got screwed,” “I’m a loser,” and “Why me?” These distressing cognitions naturally result in negative feelings, such as helplessness, demoralization, and a sense of victimization, and may culminate in the troubling behaviors of either acting out or internalizing. However, by accepting that all things happen for a reason, the patient is actively challenged around determining what is to be learned from this adverse experience. There is a shift from random victim to psychological explorer. As an example, perhaps an impulsive son (the adversity) is there to remind an impulsive father to keep on his spiritual path of growth and not get side-tracked in his own impulsive behaviors. Perhaps an emotionally vacant mother (the adversity) is there to reinforce to the daughter the importance of being a good mother to her children.

Usually it is possible to construct a positive interpretation of most adverse events. Of course, this approach does not exclude the validation of the patient’s pain and sense of loss with such events. However, helping the patient to refocus in this way seems to redirect them from “stuckness” toward more productive problem-solving and self-awareness. This approach consistently promotes the development of responding rather than reacting to adverse situations. But, again, this reframing requires a spiritual leap of faith—that all things are in ongoing order and that nothing is left to random design.


Surrender is an emotionally charged concept in our culture. Yet, surrender is a word that has very different meanings when viewed from Western versus Eastern perspectives. From a Western perspective, surrender is associated with giving in, admitting defeat, submitting, or capitulating. The connotation is blatantly negative and implies weakness. However, in Eastern thought, surrender entails the relinquishing of unrealistic fantasies of controlling others or events. It is the active acceptance of what is. In other words, it reflects a positive mindset.

To be clear, surrender is not the equivalent of resignation. It is not the commonplace attitude of “whatever” that we so often encounter in adolescents. Surrender is about acknowledging one’s own internal resistance to a situation and relinquishing the belief that in resistance resides one’s strength. Surrender is an action that relates to truly and genuinely accepting what is. It is about not opposing the course of life. Perhaps another way to think about surrender is that it is simply and genuinely accepting one’s path at any given time, yet understanding that choice is always a part of that path.

As an example, this metaphysical concept is particularly useful in helping patients to deal with their seemingly unending comparisons with others. We all tend to look at others and compare ourselves. People around us may seem far more gifted or more fortunate than ourselves. By assessing ourselves in this way, however, we fall into a hazardous comparison trap. Realistically, there is always someone who is more accomplished, talented, attractive, well liked—we can rarely triumph. As a result, comparison tends to generate bad feelings about one’s self. At this juncture, the metaphysical intervention would entail encouraging the patient to accept his or her unique and personal current path as highly relevant and necessary to his or her overall life course, whatever that may be (i.e., surrender), while empowering him or her around active choices. From a pragmatic perspective, comparing one’s path with the paths of others is unproductive and redirects the patient away from his or her own individualized life course.

Case example 3. Danne, a female patient with an eating disorder (ED), commented, “I can’t believe this! Here I am in this ED unit, and these girls are all thinner than me, have more money, and are prettier! Why can’t I be like them?”

Therapist: “Danne, focusing on the other patients only distracts you from the work that you have to do. Everybody has a unique path in life. You cannot have their path and they cannot have your path. Each path is uniquely valid. I encourage you to accept the idea that your path, while distasteful to you, is your path. Stay focused on the inner and be careful about being caught up in the outer.”

As so eloquently summed up by Eckhart Tolle, “Surrender is the simple but profound wisdom of yielding rather than opposing the flow of life.”10 Indeed, opposing the flow of life is likely to precipitate profound negative emotional states.


Meditation is a structured mind/body experience that seems to transcend the thinking mind by allowing one to enter into a heightened state of relaxation and awareness. The techniques for undertaking meditation are numerous, but most, if not all, entail a relaxed sitting position in a quiet place and begin with a focus on breathing. The focus on breathing promotes relaxation as well as a sense of presentness. Following focused breathing, meditation practices may diverge into a variety of different directions. For example, some practitioners meditate to heighten relaxation. Some initiate auto-suggestion, which may be particularly effective in this relaxed state. Others seek a different level of consciousness, sometimes referred to as a fourth dimension. Yet others use meditation to broach and focus upon major life questions, hoping that the heightened sense of clarity in this unique state will facilitate a response (i.e., an intuitive “knowingness”). Whatever the reason, meditation is a strongly espoused spiritual practice by the metaphysical community, and certainly our patients may potentially benefit from any of the preceding functions. We do not espouse a particular meditation technique, but underscore with the patient the following: 1) the potential value of meditation, 2) the importance of meditating in a calm environment in a relaxed position, 3) the initiation of this experience with paced and focused breathing, and 4) the use of simple words (a mantra) for promoting focus. After continued practice, the patient will find it easier to “calm the mind” and contain intrusive thoughts. Note that meditation may be undertaken as a practice for mindfulness and present-moment awareness.


An interconnecting theme in the preceding metaphysical approaches is the practice of mindfulness. Mindfulness is simply being aware. This means being both internally and externally attuned, without the filters of judgment, the emotions, or the culture. Note that in each of the preceding techniques, there is an element of being present—i.e., being in a mindful and aware state. For example, dealing with adversity entails being mindful of the obstacle from the perspective of “here by design.” The technique of surrender requires one to experience and accept the nowness of the path. Finally, meditation and its attendant focus on breathing is clearly an exercise in mindfulness. Mindfulness seems to be the fabric that supports the metaphysical design in the presented techniques.


Religious beliefs are not, per se, a limitation to using any of the preceding metaphysical approaches. Nor is a religious orientation necessary to use them. However, religious belief may temper some interventions such that “by design” is easily interpretable as God determined. In addition, meditation may be translated as “prayer” or “spending time with God.”


The modern era has certainly provided clinicians with an invaluable array of psychotherapeutic tools to address the emotional difficulties experienced by patients. These tools include psychoeducation, psychotherapy, and psychopharmacology. Yet, for a number of patients, these approaches fall short of providing a satisfying resolution to their inner turmoil, particularly among those individuals with histories of childhood trauma. In our search to compliment these contemporary approaches to treatment, we have integrated a number of metaphysical/spiritual techniques that have the potential to offer comfort and peace to many patients. While we have only presented four specific techniques, there are others that can be gleaned from the recommended reading list in the sidebars. We are all pilgrims on this planet. We are all seeking inner harmony. Why not benefit from the centuries of wisdom that have preceded us?

From: Psychiatry (Edgmont). 2009 December; 6(12): 26–31. Randy A. Sansone, MD and Lori A. Sansone, MD.


Randy A. Sansone, Dr. R. Sansone is a professor in the Departments of Psychiatry and Internal Medicine at Wright State University School of Medicine in Dayton, Ohio, and Director of Psychiatry Education at Kettering Medical Center in Kettering, Ohio;

Lori A. Sansone, Dr. L. Sansone is a family medicine physician (government service) and Medical Director of the Primary Care Clinic at Wright-Patterson Air Force Base. The views and opinions expressed in this column are those of the authors and do not reflect the official policy or the position of the United States Air Force, Department of Defense, or US government;


1.Davis J. The Diamond Approach. Boston, MA: Shambala; 1999. p. 24.

2.Tolle E. Tolle E. Oneness With All Life. New York, NY: Penguin Group; 2008. The power of the present moment; pp. 21–35.

3.Almaas AH. The Unfolding Now. Boston, MA: Shambala; 2008.

4.Bodian S. Bodian S. Wake Up Now. New York, NY: McGraw Hill; 2008. The practice of presence; pp. 79–98.

5.Batchelor S. Batchelor S. Buddism Without Beliefs. New York, NY: Riverhead Books; 1997. Awareness; pp. 57–66.

6.Jacobson L. Journey into Now. La Selva Beach, CA: Conscious Living Publications; 2007.

7.Brown M. The Presence Process. New York, NY: Namaste Publishing; 2005.

8.Tolle E. Practicing the Power of Now. Novato, CA: New World Library; 1999. p. 31.

9.Richo D. The Five Things We Cannot Change. Boston, MA: Shambala; 2006. p. 27.

10.Tolle E. Practicing the Power of Now. Novato, CA: New World Library; 1999. p. 115.


Tags:  metaphysical  psychotherapy 

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