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How is Your Glutatione?

Posted By Matt Angove, ND, NMD, Thursday, August 11, 2011
Updated: Tuesday, February 4, 2014

In 1994, theJournal of Nutritional Biochemistrystated, "Disease states due to glutathione deficiency are not common.”

Well, 25 years and 90 thousand journal articles later we have found this statement to be false on all levels. Glutathione is recognized as an extremely important intracellular antioxidant that also plays a central role in the detoxification and elimination of potential carcinogens and toxins. Studies have found that glutathione synthesis and tissue glutathione levels become significantly lower with age, leading to decreased ability to respond to oxidative stress or toxin exposure.

The higher the glutathione peroxidasein the plasma or red blood cells, the more your body is running through and out of glutathione. Now consider the follow…

Total glutathione peroxidase activity was elevated in females 65 years of age or older. Cigarette smoking significantly elevated glutathione peroxidase. Alcohol elevated glutathione peroxidase, with the highest levels seen in drinkers who also smoked. Increased glutathione peroxidase was also seen in vigorous exercise, especially triathletes and marathoners.

According to the National Cancer Institute, dairy products, cereals and breads are low in glutathione. Fruit and vegetables have moderate to high amounts of glutathione. Frozen versus fresh foods had similar amounts of glutathione. Processing and preservation resulted in considerable loss of glutathione.

A 27% reduction in glutathionehas been reported in the cerebrospinal fluid of schizophrenic patients.

Studies have shown that dietary glutathione enhances the metabolic clearance and reduces net absorption of dietary peroxidized lipids, which cause intense cellular damage.

High altitude exposurereduces glutathione levels.

Glutathione functions as an antioxidant and can maintain vitamin C in its reduced and functional form.

Chronically low glutathione levelsare seen in premature infants,alcoholic cirrhotics and individuals with HIV.

Glutathione increases sperm motility patterns and sperm morphology. In a double-blind, placebo-controlled crossover trial of infertile patients, patients were randomly and blindly assigned to treatment with one injection every other day of either glutathione at 600 mg or an equal volume of placebo. All the glutathione selected patients showed an increase in sperm concentration and a highly statistically significant improvement in sperm motility, sperm kinetic parameters and sperm morphology. Want to get pregnant? Make sure your husband has optimal levels of glutathione.

From the journal of Digestion: Glutathione is extremely important in normal functioning of the pancreas, being needed for normal folding of the proteins that will ultimately form key digestive enzymes when the pancreas is stimulated after a meal. In patients with chronic pancreatitis, it has been found that glutathione is often significantly depleted, suggesting that lack of glutathione has a role in the generation and/or maintenance of the disease. In addition, many patients suffering from chronic pancreatitis appear to be under xenobiotic or oxidant stress, creating an evengreater need for glutathione. Since the pancreas is under relative glutathione "stress” during the normal process of packing and secreting digestive enzymes, it is easy to see how the lack of glutathione could have a role in chronic pancreatitis.

From the Journal of Brain Research Reviews:Glutathione depletioncan enhance oxidative stress and may increase levels of excitotoxic (toxins that excite neurons to the point of death) molecules, which may initiate cell death in specific nerve cell populations. Evidence of oxidative stress andreduced glutathione statusis found in Lou Gehrig’s disease, Parkinson’s disease and Alzheimer’s disease.

From the Annals of Pharmacotherapy:Glutathione is importantin DNA synthesis and repair, protein and prostaglandin synthesis, amino acid transport, metabolism of toxins and carcinogens, enhancement of immune function, prevention of oxidative cell damage and enzyme activation.

From the Journal Acta Dermato-Venereologica:Low levels of blood glutathionewere found in patients with pemphigoid, acne conglobata, polymyositis, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, atopic dermatitis, eczema and psoriasis.

From the Journal of the Federation of American Societies for Experimental Biology:Intracellular glutathione enhances the immunologic function of lymphocytes (perhaps the most important immune cell line in preventing infection and cancer).Low levels of glutathionelimit the optimal functioning of T cells. Cytotoxic T cell (necessary to eliminate cancer) responses and interleukin-II-dependent functions are inhibited even by a partialdepletion of the intracellular glutathionepool.

From the journal of Ocular Pharmacological Therapy:Susceptibility of the lens nucleus to oxidative damage and loss of transparency has been shown in experimental animal models, including exposure to hyperbaric oxygen, x-ray and UVA light.Depletion of glutathioneallows the levels of oxidant to damage lens tissue and structure.

From the Journal of Laboratory and Clinical Science:An increased incidence oflow glutathione levelsin apparently healthy subjects suggests a decreased capacity to maintain metabolic and detoxification reactions that are stimulated by glutathione. The authors stated thatglutathione status, physical health, and longevity are closely related.

From the Lancet: The plasma glutathione in young, healthy adults was 0.54 umol/L; in healthy elderly it was 0.29 umol/L; in elderly outpatients it was 0.24 umol/L; and in elderly inpatients it was 0.17 umol/L. Aging results in a decrease in plasma glutathione and an increase in oxidative damage in apparently healthy individuals.

Simply put, if you want young cells and the ability to overcome disease you need to work on getting your glutathione levels up!

Tags:  food and drink  nutrition 

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Enhance Your Practice with E-billing

Posted By Michelle Schiavo, Tuesday, August 9, 2011
Updated: Tuesday, February 4, 2014
As technology continues to advance the healthcare industry, physicians are discovering the benefits of electronic billing. Reduce your staff's billing administration time and consider switching to electronic billing. Kareo, an Irvine CA based company can help.
What is Kareo?

Kareo is a web-based medical billing and practice management software program. CEO, Dan Rodrigues founded the company in 2004 and had two goals: to create a software that is affordable and easy to use.

In the past, software companies sold a ‘client-server model’ where a physician would have to buy hardware, plus the server, have a representative come to the office for a demo, and come back again to install and train. This process was very time and cost-intensive. At the time, this process was acceptable, because most people were not highly educated consumers in terms of purchasing technology, including physicians.

Then came the release of the iPhone and people started to really understand what a consumer-oriented engagement is with technology. Many doctors got the iPhone and started developing a taste for what technology should be like. This is when Kareo came into the picture and decided to mimic this new experience.

What makes Kareo different?

When you visit the Kareo website, 90 to 95 percent of what a consumer wants to understand and needs to know is right there and easily accessible. The buying experience is done online, sign-up takes about 30 to 45 seconds, you receive your log in information and you’re ready to go.

Additionally, Kareo’s software is delivered in the ‘cloud’ versus on a web server, which means physicians can use their existing software, get into a browser, download the app, and they’re in. No matter where physicians are, they can access data from Kareo.

Kareo’s website also offers thought leadership content. They’ve partnered with experts that write content specifically for Kareo regarding not only medical billing, but other issues physicians are concerned about such as HIIPA, meaningful use and other items of interest that have come out of health care reform and stimulus. This content goes on the Kareo blog and they also incorporate that information into their thinking about product perspective, delivery, and sales experience.

How can Kareo help integrative physicians?

Kareo makes it simple for doctors to get paid. Whether it’s billing patients and being able to accept payments via credit card online or filing insurance claims, Kareo’s goal is to get the doctor maximum reimbursement in the quickest possible amount of time.

Kareo’s software allows physicians to keep track of finances, look at and analyze their client base and schedule appointments. From Kareo’s Dashboard, which users see when they log in, there are short-cuts that link to key functions, a list of tasks that need to be completed and a snapshot of financial metrics. Part of the financial metrics is the Payment Velocity feature. This number is featured in a large orange display and tells the number of days on average it’s taking the practitioner to receive payment from the time of service to the time payment has been posted.

Many practitioners use programs where only 60 to 70 percent of the features apply to them and the remaining 30 to 40 percent is almost always work-arounds. Kareo specializes their software specifically for physical therapists, chiropractors, dermatologists, etc. They understand that there are nuances in certain practices regarding the way they have to bill and how they have to document and one standard program will not work for every practice.

What’s next for Kareo?

They’ve made it easy for doctors to get paid, now they’re finding ways for physicians to connect with their patients beyond the office. Since data is stored in the cloud and can be accessed from anywhere, there are an endless amount of possibilities for physician-patient interaction.

Patients could have an app that connects to their medical records (stored in Kareo’s platform in the cloud) and input what they ate that day, then the app will tell them according to their data that they should watch their sugar intake or eat more iron-rich foods, etc. etc.

If a physician finds a fantastic article on diabetes and has a percentage of patients that are diabetic, he or she can send that article to the diabetic patients through an app.

If a patient is running low on a supplement or medication and does not need to see the doctor, an app could alert that patient, ask if he or she would like to order more, provide the ability to pay right there on the app and then the supplement or medication gets delivered to the patient.

Kareo has the ecosystem to be able to do these things and more. Look to Kareo for more innovative ways for physicians to live with their patients outside the office.

Visit to watch a free demo and to view their various plans and pricing.

Tags:  practice marketing 

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Metabolic Syndrome, Heart Health, and Risk Factors

Posted By John Gannage, MD, MCFP, DH, Monday, August 8, 2011
Updated: Tuesday, February 4, 2014
The medical community has recently seen a raft of literature instructing "aggressive” management of hypertension, diabetes and high cholesterol (the Big Three). The basic premise is to diagnose early and treat early, while at the same time lowering the upper limits of acceptability for these conditions. The aggressive intervention leads to polypharmacy, where a single one of these conditions is best managed with more than one medication, as conventional medical literature now recommends. In other words, if you have high blood pressure, your doctor has been instructed that control best comes from prescribing two medications. The goal is to reduce risk of death and morbidity due to heart disease, stroke and other complications.

The same literature often addresses lifestyle change, including nutrition considerations, as a footnote usually towards the end of a long article (similar to the proportion allocated to this topic when I was a medical student 25 years ago). Make no mistake: these three conditions do require the respect they deserve as risk factors for heart disease, the number one killer in North American society. But what do they have in common beyond the espoused aggressive management, and cardiac risk?


First line therapy in the management of these conditions comes through alteration of lifestyle habits - related to diet, exercise, and stress management. The fact that these conditions can be managed with a similar unifying approach tells us something about their commonality related to cause and biochemistry. The average North American diet, self-indulgent and high glycemic, triggers an insulin response that is self-destructive in many aspects. Consistently high levels of insulin, in and of itself, are damaging to the walls of arteries, leading to hardening and degeneration. Insulin is a fat-making hormone, explaining the relationship of each of the Big Three to obesity in many cases. In fact, diabetes, hypertension, obesity and heart disease, along with gout and hormone disturbances, can all be categorized into one syndrome: The Metabolic Syndrome.

At the core of Metabolic Syndrome is the high glycemic (sugar)-insulin connection, which leads to a cascade of biochemical disturbances. White sugar (and brown), white potatoes, white rice and white flour are all high glycemic foods that require restriction. The Glycemic Index of foods, gaining popularity worldwide in Westernized nations, was conceived by Toronto's Dr. David Jenkins. Food lists can be consulted to ensure a low glycemic diet, aiming for carbohydrates that are below 55 on the glycemic index scale.


Of course, successful management of excess weight is imperative. The hallmark of a good weight loss program, in my opinion, is not to achieve loss of the greatest amount of weight in the shortest time possible as the goal, but rather, with an emphasis on patient education and involvement, establishing HEALTH as the focus.

Obesity is indeed related to the aforementioned high glycemic diet, but also linked are exposures to toxins, lack of healthy bowel flora and sleep disturbances. The approach to weight management requires a comprehensive approach - with a low glycemic diet, incorporated beyond a temporary period, the foundation. Of importance is getting an early start to healthy body composition - studies link later heart disease to obesity beginning in adolescence, as an independent risk factor Indeed, pediatric obesity is one of the significant public health issues of our time.

Also of importance is the lack of exercise that aggravates the picture of Metabolic Syndrome. Exercise allows for better response of healthy cells to insulin itself, thereby improving blood sugar, fat and cholesterol metabolism. Exercise leads to the development of lean muscle mass, which has a higher level of cellular activity. Increased lean muscle is associated with decreased risk of acute and chronic illness, and healthier body composition long term due to less likelihood of regaining any lost weight. Simply put, exercise expends calories, lowers weight, increases muscle, lowers blood pressure, regulates blood sugar and improves the cholesterol profile, in addition to improving mood and sleep.

Stress chronically alters biochemistry as well, with increased output of cortisol long-term causing blood sugar disturbances and fat storage. Stress can heighten cholesterol levels through similar pathways, and is likely the single most important risk factor for heart disease.


High cholesterol is also an aspect of Metabolic Syndrome, and as a marker of the syndrome has been targeted for aggressive management mostly from a pharmacologic perspective. Sadly, when it comes to nutrition and cholesterol, if mentioned at all, the existence of myths remains pervasive in the medical mainstream.

Firstly, I am familiar with the school of thought that suggests cholesterol is misplaced as a dangerous chemical; that excessive lowering of cholesterol, which comprises 2 % of brain mass, is detrimental to neurologic health; that as a natural antioxidant substance, raised cholesterol is a programmed protective response to toxin exposure (suggesting a role for detoxification and antioxidant supplementation). Nonetheless, high cholesterol remains an entity most patients are not comfortable with, insomuch that treatment is desirable and requested.

Returning to the discussion of nutrition misperceptions, dietary cholesterol has virtually no effect on circulating levels of cholesterol in the bloodstream. Eggs are an excellent source of protein and nutrients, and should not be avoided for their cholesterol content. The lecithin that naturally occurs in the whole egg (with emphasis on whole) exists coincidentally with the egg's cholesterol for good reason. Mother Nature once again gets it right.

The myth that cholesterol can only be lowered a small percentage solely through dietary management has also been dispelled. This was the mainstay of medical thinking for decades, seemingly necessitating drug research and application. Dr. Jenkins and his colleagues at St. Michael's hospital constructed the Portfolio Diet, and showed results equal to the financially successful statin drugs in a study published by the prestigious Journal of the American Medical Association (JAMA) lowered LDL by 30-33 percent and the Portfolio Diet lowered LDL by nearly 30 percent. The portfolio was rich in soymilk, soy burgers, almonds, oats, barley, psyllium seeds, okra and eggplant.

Interestingly, Reuters News agency reported: "… people who cannot tolerate the statin drugs because of side-effects can turn to the diet, which they [the researchers] said their volunteers could easily follow.” A worthwhile question might be why not use the diet as first line therapy, as has always been footnoted. We now have a study with clear results supporting dietary management of a common condition, and the advice is to consider it a secondary intervention.


Eat whole, choose low glycemic foods, exercise regularly, supplement thoughtfully and maintain healthy body composition. Your heart will be thankful.

Tags:  health 

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Case Study on Link Between Sleep & Diabetes

Posted By Carol Touma, MD and Silvana Pannain, MD, Friday, August 5, 2011
Updated: Tuesday, February 4, 2014
Published in the Cleveland Clinic Journal of Medicine.

by Carol Touma, MD and Silvana Pannain, MD


Several lines of evidence indicate that chronic lack of sleep may contribute to the risk of type 2 diabetes mellitus. Adequate sleep and good sleep hygiene should be included among the goals of a healthy lifestyle, especially for patients with diabetes. We urge clinicians to recommend at least 7 hours of uninterrupted sleep per night as part of a healthy lifestyle.

Key Points

  • Sleep loss and sleep disturbances have become very common in our society, and so have obesity and type 2 diabetes.
  • In epidemiologic studies, people who reported sleeping less were at higher risk of diabetes or disordered glucose metabolism.
  • In laboratory studies, short-term sleep deprivation caused measurable changes in glucose metabolism, hormone levels, autonomic nervous system activity, and other variables, which are plausible mechanisms by which loss of sleep could contribute to diabetes.
  • Obstructive sleep apnea is very common in people with diabetes and may be directly linked to diabetes risk and worse diabetes control. Diabetic patients should be systematically assessed for obstructive sleep apnea, and patients with known obstructive sleep apnea should be screened for diabetes.

ADULTS ARE SLEEPING LESS AND LESS in our society. Yet sleep is no longer thought of as strictly a restorative process for the body. The importance of sleep for metabolic function and specifically glucose homeostasis is now widely accepted, as many studies have shown a correlation between sleep deprivation or poor sleep quality and an increased risk of diabetes.

Obesity and aging are both associated with worse sleep. As the prevalence of obesity and diabetes increases, and as the number of elderly people increases, it is imperative to target sleep in the overall treatment of our patients.

In the pages that follow, we examine the evidence of a link between sleep loss (both short sleep duration and poor-quality sleep) and the risk of diabetes. (For evidence linking short sleep duration and the related problem of obesity, we invite the reader to refer to previous publications on the topic.)


The prevalence of obesity and, consequently, of type 2 diabetes mellitus has increased alarmingly worldwide and particularly in the United States in the past few decades. Such a rapid increase cannot be explained simply by an alteration in the genetic pool; it is more likely due to environmental, socioeconomic, behavioral, and demographic factors and the interaction between genetics and these factors. Besides traditional lifestyle factors such as high-calorie diets and sedentary habits, other, nontraditional behavioral and environmental factors could be contributing to the epidemic of obesity and diabetes.

At the same time, people are sleeping less, and sleep disorders are on the rise. According to recent polls from the US Centers for Disease Control and Prevention, approximately 29% of US adults report sleeping less than 7 hours per night, and 50 to 70 million have chronic sleep and wakefulness disorders.

The sleep curtailment of our times probably is partly self-imposed, as the pace and the opportunities of modern society place more demands on time for work and leisure activities and leave less time for sleep.

The quality of sleep has also declined as the population has aged and as the prevalence of obesity and its related sleep disorders has increased. Furthermore, patients with type 2 diabetes tend to sleep less, and to sleep poorly. Poor sleep quality generally results in overall sleep loss.




The human body regulates blood levels of glucose within a narrow range.

Glucose tolerance refers to the ability to maintain euglycemia by disposing of exogenous glucose via insulin-mediated and non–insulin-mediated mechanisms. Normal glucose tolerance depends on the ability of the pancreatic beta cells to produce insulin. As insulin sensitivity declines, insulin secretion increases to maintain normal glucose levels. Diabetes becomes manifest when the pancreatic beta cells fail to compensate for the decreased insulin sensitivity.

Glucose tolerance varies in a circadian rhythm, including during the different stages of sleep.


Sleep has often been thought of as a "restorative” process for the mind and the body; however, many studies have shown that it also directly affects many metabolic and hormonal processes.

Sleep has five stages: rapid eye movement (REM) sleep and stages 1, 2, 3, and 4 of non-REM sleep. The deeper stages of non-REM sleep, ie, stages 3 and 4, are also known as slow-wave sleep and are thought to be the most restorative.

Additionally, the onset of slow-wave sleep is temporally associated with transient metabolic, hormonal, and neurophysiologic changes, all of which can affect glucose homeostasis. The brain uses less glucose, the pituitary gland releases more growth hormone and less corticotropin, the sympathetic nervous system is less active, and conversely, vagal tone is increased.

As a result, in the first part of the night, when slow-wave sleep predominates, glucose metabolism is slower. These effects are reversed in the second part of the night, when REM sleep, stage 1, and awakening are more likely.

In view of these important changes in glucose metabolism during sleep, it is not surprising that getting less sleep or poorer sleep on a regular basis could affect overall glucose homeostasis.


Laboratory and epidemiologic evidence supports an association between short sleep duration (< 7 hours per night) and the risk of diabetes, and also between poor sleep quality and the risk of diabetes. We will explore putative mechanisms for these relationships.

Laboratory studies of short sleep duration and glucose metabolism

Studies in small numbers of healthy volunteers who underwent experimental sleep restriction or disruption have revealed mechanisms by which sleep loss might increase the risk of diabetes.

Kuhn et al performed the very first laboratory study of the effect of sleep deprivation on metabolism. Published in 1969, it showed that total sleep deprivation led to a marked increase in glucose levels.

A caution in extrapolating such results to real-life conditions is that total sleep deprivation is uncommon in humans and is inevitably followed by sleep recovery, with normalization of glucose metabolism. However, people in modern society are experiencing recurrent partial sleep deprivation, and its effect on glucose metabolism may be different.

Spiegel et al, in landmark laboratory studies of partial sleep deprivation in healthy, lean adults, found that restricting sleep to 4 hours per night for 6 nights resulted in a 40% decrease in glucose tolerance, to levels similar to those seen in older adults with impaired glucose tolerance. This metabolic change was paralleled by an increase in the activity of the sympathetic nervous system, and both of these effects reversed with sleep recovery.

A criticism of these initial studies is that they restricted sleep to 4 hours, a restriction more severe than that seen in real life.

Nedeltcheva et al more recently examined the effects of less-severe sleep curtailment (5.5 hours per night for 14 nights) in sedentary middle-aged men and women. This degree of bedtime restriction led to a decrease in glucose tolerance due to decreased insulin sensitivity in the absence of adequate beta cell compensation.

Such recurrent bedtime restriction is closer to the short sleep duration experienced by many people in everyday life, and in people at risk it may facilitate the development of insulin resistance, reduced glucose tolerance, and ultimately diabetes. Indeed, epidemiologic studies suggest that people who sleep less than 6 hours per night are at higher risk of type 2 diabetes.

Epidemiologic studies of short sleep duration and glucose metabolism

Multiple cross-sectional epidemiologic studies have suggested an association between short sleep duration and diabetes, and several prospective epidemiologic studies have suggested that short sleep actually plays a causative role in diabetes.

The landmark observations of Spiegel et al led to a number of epidemiologic studies examining the relationships between sleep duration and sleep disturbances and diabetes risk.

The Sleep Heart Study was a large, cross-sectional, community-based study of the cardiovascular consequences of sleep-disordered breathing. The authors assessed the relationship between reported sleep duration and impaired glucose tolerance or type 2 diabetes in more than 1,400 men and women who had no history of insomnia. After adjustment for age, sex, race, body habitus, and apnea-hypopnea index, the prevalence of impaired glucose tolerance and type 2 diabetes was higher in those who reported sleeping 6 hours or less per night—or 9 hours or more per night (more below about the possible effect of too much sleep on the risk of diabetes).

The major limitations of the study were that it was cross-sectional in design, sleep duration was self-reported, the reasons for sleep curtailment were unknown, and possible confounding variables as physical activity, diet, and socioeconomic status were not measured.

Knutson et al, in our medical center, examined the association between self-reported sleep duration and sleep quality on the one hand and hemoglobin A1c levels on the other in 161 black patients with type 2 diabetes. In patients without diabetic complications, glycemic control correlated with perceived sleep debt (calculated as the difference between self-reported actual and preferred weekday sleep duration); the authors calculated that a perceived sleep debt of 3 hours per night predicted a hemoglobin A1cvalue 1.1 absolute percentage points higher than the median value. The analyses controlled for age, sex, body mass index, insulin use, and the presence of major complications; it excluded patients whose sleep was frequently disrupted by pain. The effect size was comparable to (but opposite) that of oral antidiabetic drugs. However, the direction of causality cannot be confirmed from this association, as it is possible that poor glycemic control in diabetic patients could impair their ability to achieve sufficient sleep.

To date, several major prospective studies have looked at the association between short sleep duration and sleep problems and the risk of developing type 2 diabetes in adults.

The Nurses Health Study followed 70,000 nondiabetic women for 10 years. Compared with nurses who slept 7 to 8 hours per 24 hours, those who slept 5 hours or less had a relative risk of diabetes of 1.34 even after controlling for many covariables, such as body mass index, shift work, hypertension, exercise, and depression.

The first National Health and Nutrition Examination Survey (NHANES I) examined the effect of sleep duration on the risk of incident diabetes in roughly 9,000 men and women over a period of 8 to 10 years. The statistical model included body mass index and hypertension and adjusted for physical activity, depression, alcohol consumption, ethnicity, education, marital status, and age. Findings: those who slept 5 hours or less per night were significantly more likely to develop type 2 diabetes than were those who slept 7 hours per night (odds ratio 1.57, 95% confidence interval [CI] 1.11–2.22), and so were those who slept 9 or more hours per night (odds ratio 1.57, 95% CI 1.10–2.24).

Kawakami et al followed 2,649 Japanese men for 8 years. Those who had difficulty going to sleep and staying asleep, which are both likely to result in shorter sleep duration, had higher age-adjusted risks of developing type 2 diabetes, with hazard ratios of 2.98 and 2.23, respectively.

Björkelund et al followed 6,599 nondiabetic Swedish men for an average of 15 years. Self-reported difficulty sleeping predicted the development of diabetes with an odds ratio of 1.52 even after controlling for age, body mass index at screening, changes in body mass index at follow-up, baseline glucose level, follow-up time, physical activity, family history of type 2 diabetes, smoking, social class, and alcohol intake.

Interestingly, the authors found that the resting heart rate was higher at baseline in the men who later developed diabetes. This finding could be interpreted as reflecting greater sympathetic nervous system activity, a putative mediator of the metabolic dysfunction associated with both short sleep duration and obstructive sleep apnea.

Meisinger et al, in a study of more than 8,000 nondiabetic German men and women 25 to 74 years old, found a hazard ratio of developing diabetes of 1.60 (95% CI 1.05–2.45) in men and 1.98 (95% CI 1.20–3.29) in women who reported difficulty staying asleep, who thus would have shortened sleep duration. This effect was independent of other risk factors for diabetes.

Yaggi et al, in a prospective study of 1,139 US men, also found a U-shaped relationship between sleep duration and the incidence of diabetes, with higher rates in people who slept less than 5 or more than 8 hours per night.

Cappuccio et al performed a meta-analysis of all the prospective studies published to date. Their review included 10 prospective studies, with 107,756 participants followed for a median of 9.5 years. Sleep duration and sleep disturbances were self-reported in all the studies. They calculated that the risk of developing diabetes was 28% higher with short sleep duration (≤ 5 or < 6 hours in the different studies), 48% higher with long sleep duration (> 8 hours), 57% higher with difficulty going to sleep, and 84% higher with difficulty staying asleep.

Limitations of these studies. A consideration when trying to interpret the relationship between length of sleep and the incidence of diabetes is that sleep duration in these studies was self-reported, not measured. If a patient reports sleeping more than 8 hours per night, it could mean that he or she is not truly getting so much sleep, but rather is spending more time in bed trying to sleep.

Another possibility is that the higher incidence of type 2 diabetes in people who slept longer is due to undiagnosed obstructive sleep apnea, which is associated with daytime sleepiness and possibly longer sleep time to compensate for inefficient sleep.

Finally, depressive symptoms, unemployment, a low level of physical activity, and undiagnosed health conditions have all been associated with long sleep duration and could affect the relationship with diabetes risk.

In summary, epidemiologic studies from different geographic locations have consistently indicated that short sleep or poor sleep may increase the risk of developing type 2 diabetes mellitus and suggest that such an association spans different countries, cultures, and ethnic groups.

Therefore, there is a need for additional prospective epidemiologic studies that use objective measures of sleep. Furthermore, studies need to determine whether the cause of sleep restriction (eg, insomnia vs lifestyle choice) affects this relationship. Randomized, controlled, interventional studies would also be useful to determine whether lengthening sleep duration affects the development of impaired glucose tolerance or type 2 diabetes mellitus.

Putative mechanisms linking short sleep duration and the risk of diabetes

The effects of sleep loss on glucose metabolism are likely multifactorial, involving several interacting pathways.

Decreased brain glucose utilization has been shown on positron emission tomography in sleep-deprived subjects.

Hormonal dysregulation. Sleep deprivation is associated with disturbances in the secretion of the counterregulatory hormones growth hormone and cortisol.

Young, healthy volunteers who were allowed to sleep only 4 hours per night for 6 nights showed a change in their patterns of growth hormone release, from a normal single pulse to a biphasic pattern. They were exposed to a higher overall amount of growth hormone in the sleep-deprived condition, which could contribute to higher glucose levels.

Also, evening cortisol levels were significantly higher in young, healthy men who were allowed to sleep only 4 hours per night for 6 nights, as well as in young, healthy women who were allowed to sleep only 3 hours for 1 night. A cross-sectional analysis that included 2,751 men and women also demonstrated that short sleep duration and sleep disturbances are independently associated with more cortisol secretion in the evening.Elevated evening cortisol levels can lead to morning insulin resistance.

Inflammation. Levels of inflammatory cytokines, inflammation, or both increase as sleep duration decreases, which in turn can also increase insulin resistance.

Sympathetic nervous system activity. Patients who have been sleep-deprived have been shown to have higher sympathetic nervous system activity, lower parasympathetic activity, or both. The sympathetic nervous system inhibits insulin release while the parasympathetic system stimulates it, so these changes both increase glucose levels.Moreover, overactivity of the sympathetic nervous system results in insulin resistance.

Excess weight is a well-established risk factor for type 2 diabetes mellitus, and several epidemiologic studies have suggested that sleep loss may increase the risk of becoming overweight or obese, which would ultimately increase the risk of type 2 diabetes.

A primary mechanism linking sleep deprivation and weight gain is likely to be hyperactivity of the orexin system. Orexigenic neurons play a central role in wakefulness, but, as suggested by the name, they also promote feeding. Studies in animals have indicated that the orexin system is overactive during sleep deprivation, and this could be in part mediated by the increase in sympathetic activity.

Increased sympathetic activity also affects the levels of peripheral appetite hormones, inhibiting leptin release and stimulating ghrelin release. Lower leptin levels and higher ghrelin levels act in concert to further activate orexin neurons, resulting in increased food intake.

One could also argue that less time sleeping also allows more opportunity to eat.

Reduced energy expenditure. Sleep loss and its associated sleepiness and fatigue may result in reduced energy expenditure, partly due to less exercise but also due to less nonexercise activity thermogenesis. To date, reduced energy expenditure is an unexplored pathway that could link short sleep, the risk of obesity, and ultimately diabetes. In many overweight and obese people, this cascade of negative events is likely to be accelerated by sleep-disordered breathing, a reported independent risk factor for insulin resistance.


Slow-wave sleep and diabetes

Slow-wave sleep, the most restorative sleep, is associated with metabolic, hormonal, and neurophysiologic changes that affect glucose homeostasis. Its disturbance may have deleterious effects on glucose tolerance.

Shallow slow-wave sleep occurs in elderly people and in obese people, even in the absence of obstructive sleep apnea. Both groups are also at higher risk of diabetes. One wonders if the decreased slow-wave sleep could in part contribute to the risk of diabetes in these groups.

A few studies specifically tested the effect of experimental suppression of slow-wave sleep on glucose homeostasis.

Tasali et al evaluated nine young, lean, nondiabetic men and women after 2 consecutive nights of undisturbed sleep and after 3 consecutive nights of suppressed slow-wave sleep without a change in total sleep duration or in REM sleep duration. Slow-wave sleep was disturbed by "delivering acoustic stimuli of various frequencies and intensities” whenever the subjects started to go into stage 3 or stage 4 sleep. This decreased the amount of slow-wave sleep by nearly 90%, which is comparable to the degree of sleep fragmentation seen in moderate to severe obstructive sleep apnea. After 3 nights of slow-wave sleep suppression, insulin sensitivity decreased by 25%, without a compensatory increase in insulin release, which resulted in a reduction in glucose tolerance of 23%, a value seen in older adults with impaired glucose tolerance.

Stamatakis et al confirmed these findings in a similar study of 11 healthy, normal volunteers whose sleep was fragmented for 2 nights across all stages of sleep using auditory and mechanical stimuli. Insulin sensitivity significantly decreased, as did glucose effectiveness (ability of glucose to dispose itself independently of an insulin response) after the 2 nights of disturbed sleep quality.

These results support the hypothesis that poor sleep quality with short durations of slow-wave sleep, as seen with aging and obesity, could contribute to the higher risk of type 2 diabetes in these populations. These data also suggest that more studies are needed to look at the relationship between amount and quality of slow-wave sleep and diabetes risk.

Obstructive sleep apnea and diabetes

The most robust evidence that not only short sleep duration but also poor sleep quality affects diabetes risk comes from studies of metabolic function in patients with obstructive sleep apnea, an increasingly common condition.

Obstructive sleep apnea is characterized by recurrent episodes of partial or complete upper airway obstruction with intermittent hypoxia and microarousals, resulting in low amounts of slow-wave sleep and overall decreased sleep quality.

Obstructive sleep apnea is common in patients with type 2 diabetes, and several clinical and epidemiologic studies suggest that, untreated, it may worsen diabetes risk or control.

The Sleep AHEAD (Action for Health in Diabetes) study revealed, in cross-sectional data, that more than 84% of obese patients with type 2 diabetes had obstructive sleep apnea (with an apnea-hypopnea index ≥ 5).

Aronsohn et al, in a study conducted in our laboratory in 60 patients with type 2 diabetes, found that 46 (77%) of them had obstructive sleep apnea. Furthermore, the worse the obstructive sleep apnea, the worse the glucose control. After controlling for age, sex, race, body mass index, number of diabetes medications, level of exercise, years of diabetes, and total sleep time, compared with patients without obstructive sleep apnea, the adjusted mean hemoglobin A1c was increased in a linear trend by (in absolute percentage points):

  • 1.49% in patients with mild obstructive sleep apnea (P = .0028)

  • 1.93% in patients with moderate obstructive sleep apnea (P = .0033)

  • 3.69% in patients with severe obstructive sleep apnea (P < .0001).

Other epidemiologic studies. A growing number of epidemiologic studies, in various geographic regions, have suggested an independent link between obstructive sleep apnea and risk of type 2 diabetes. Most of the studies have been cross-sectional, and while most had positive findings, a criticism is that the methodology varied among the studies, both in how obstructive sleep apnea was assessed (snoring vs polysomnography) and in the metabolic assessment (oral glucose tolerance test, homeostatic model assessment, hemoglobin A1c, medical history, physician examination, or patient report).

So far, 14 population studies (TABLE 1) have assessed obstructive sleep apnea with polysomnography, but only two of them were prospective. Of the cross-sectional studies, all but the earliest study, which also was the smallest, found an association between the increased severity of obstructive sleep apnea and alterations in glucose metabolism consistent with an increased risk of diabetes. The one retrospective study and the first published prospective study did not find an independent relationship between the severity of obstructive sleep apnea at baseline and the incidence of diabetes. Of note, the duration of follow-up in the prospective study was only 4 years, which may not be sufficient.

Table 1

Studies linking obstructive sleep apnea to altered glucose metabolism and diabetes

Author & Year No. of Patients Findings

Cross-Sectional Studies

Stoohs et al,62 1996 50 Increase in insulin resistance in obstructive sleep apnea (OSA) was entirely dependent on body mass index.

Elmasry et al,66 2001 116 Prevalence of severe OSA in people with diabetes was 36% vs. 14% in those without diabetes (P < .05)

Punjabi et al,55, 2002 150 Quartiles of OSA severity (apnea-hypopnea index [AHI] 5-40) had dose effect on 2-hour glucose and insulin levels.

IP et al,452002 270 One unit increase in AHI increased fasting insulin or homeostasis model

Reichmuth et al,64 2005 1,382 Odds ratio of diabetes with AHI > 15 vs. < 5 was 2.30 (95% confidence interval [CI] 1.28-4.11

Lam et al,67 2006 255 AHI greater than or equal to 5 (vs < 5) increased the odds of fasting glucose greater than or equal to 110 mg/dL, with an odds ratio of 2.74 (95% CI 1.16-6.49)

Okada et al,68 2006 207 12% of subjects with sleep-disordered breathing had hemoglobin A1c > 5.8%, vs. only 4% of those without sleep-disordered breathing (P < .05)

Sulit et al,69 2006 394 Subjects with oxygen saturation < 90% greater than or equal to 2% of time had odds ratio of 2.33 (95% CI 1.38-3.94) of impaired glucose tolerance.

Seicean et al,70 2008 2,588 Respiratory disturbance index greater than or equal to 10 events/hour was associated with odds ratio of 1.3 (95% CI 1.1-1.6) for impaired fasting glucose, 1.2 (1.0-1.4) for impaired glucose tolerance, 1.4 (1.1-2.7) for both impaired fasting glucose and impaired glucose tolerance, and 1.7 (1.1-2.7) for occult type 2 diabetes mellitus.

Punjabi et al,71 2009 118 26.7% reduction in insulin sensitivity with mild sleep-disordered breathing, 36.5% with moderate, and 43.7% with severe.

Steiropoulos et al,72 2009 56 Fasting glucose and hemoglobin A1c were not correlated with AHI or average oxygen saturation (P = .008).

Aronsohn et al,5 2010 60 Mean hemoglobin A1c significantly increased by 1.49% with mild OSA, 1.93% with moderate OSA, and 3.69% with severe OSA.

Prospective Studies

Reichmuth et al,64 2005 987 No change in odds ratio of type 2 diabetes with higher AHI when adjusted for waist girth.

Botros et al,65 2009 544 For every quartile of severity of OSA, there was a significant 43% increased incidence of type 2 diabetes.

Retrospective Study

Mahmood et al,63 2009 1,088 OSA was not independently associated with type 2 diabetes.

A more recent prospective study of 544 nondiabetic patients showed that the risk of developing type 2 diabetes over an average of 2.7 years of follow-up was a function of the severity of obstructive sleep apnea expressed in quartiles: for each increased quartile of severity there was a 43% increase in the incidence of diabetes. Additionally, in patients with moderate to severe sleep apnea, regular use of continuous positive airway pressure (CPAP) was associated with an attenuated risk.

Two prospective studies (not included in TABLE 1) used snoring as a marker of obstructive sleep apnea; at 10 years of follow-up, snoring was associated with a higher risk of developing diabetes in both men and women.

Does CPAP improve glucose metabolism? Other studies have specifically examined the effects of CPAP treatment on glucose metabolism, in both diabetic and nondiabetic populations. Accumulating evidence suggests that metabolic abnormalities can be partially corrected by CPAP treatment, which supports the concept of a causal link between obstructive sleep apnea and altered glucose control. This topic is beyond the scope of this review; please see previously published literature for further information. Whether treating obstructive sleep apnea may delay the development or reduce the severity of type 2 diabetes is another important unanswered question.

Is obstructive sleep apnea a cause or consequence of diabetes? It may be a novel risk factor for type 2 diabetes, and its association with altered glucose metabolism is well supported by a large set of cross-sectional studies, but there are still insufficient longitudinal studies to indicate a direction of causality.

If obstructive sleep apnea is the cause, what is the mechanism? There are likely many. High levels of sympathetic nervous system activity, intermittent hypoxia, sleep fragmentation, and sleep loss in obstructive sleep apnea may all lead to dysregulation of the hypothalamic-pituitary axis, endothelial dysfunction, and alterations in cytokine and adipokine release and are all potential mechanisms of abnormal glucose metabolism in this population.


Taken together, the current evidence suggests that strategies to improve the duration and the quality of sleep should be considered as a potential intervention to prevent or delay the development of type 2 diabetes mellitus in at-risk populations. While further studies are needed to better elucidate the mechanisms of the relationship between sleep loss and diabetes risk and to determine if extending sleep and treating obstructive sleep apnea decreases the risk of diabetes, we urge clinicians to recommend at least 7 hours of uninterrupted sleep per night as a goal in maintaining a healthy lifestyle. Additionally, clinicians should systematically evaluate the risk of obstructive sleep apnea in their patients who have type 2 diabetes mellitus and the metabolic syndrome, and conversely, should assess for diabetes in patients with known obstructive sleep apnea.


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Cleve Clin J Med. 2011 Aug;78(8):549-58. Does lack of sleep cause diabetes? Touma, C. Pannain, S.

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New Thyroid Guideliens for Pregnancy (and Fertility!)

Posted By ona McCulloch, BSc, ND, Wednesday, August 3, 2011
Updated: Tuesday, February 4, 2014

The American Thyroid Association has updated their guidelines for the management of thyroid concerns in pregnancy, the details of which were published in the journal Thyroid this past month. Many of us who work in the field of fertility have long been aware of research suggesting that ranges for TSH should be lower in pregnancy. It is truly great to see that this has been formally recognized. Although these guidelines were written for pregnancy, I also apply these to women with fertility concerns who are preparing for pregnancy. Prevention is always best when it comes to avoiding miscarriage.

Thyroid disease is very common in pregnancy. One of the reasons is thatone of the main thyroid hormones (free T4) decreases in pregnancy.Another reason is that TBG (thyroxine binding globulin) increases during pregnancy – TBG is a hormone that binds to the circulating thyroid hormone, making it unavailable to act on receptors. This aggravates cases of hypothyroidism by binding up the thyroid hormone that would normally be available to work in the body.

hCG, the pregnancy hormone, has a profound effect on thyroid function too. Normally in pregnancy, hCG causes TSH (Thyroid stimulating hormone) to decrease. TSH is produced by the pituitary gland and causes the thyroid gland to make thyroid hormones. So in a healthy pregnancy, we expect a woman to have a lower TSH than she usually would . This makes high levels of TSH in pregnancy to be of even more concern and gives us a lower "normal” reference range for pregnancy. When TSH levels are high, this indicates that the thyroid function is low, as the pituitary is attempting to stimulate more thyroid hormone production from the thyroid gland.

Autoimmune thyroiditisis very common in pregnancy as well. 1 in 10 pregnant women will develop antibodies to the thyroid. Hypothyroidism develops in 16% of women with thyroid antibodies. Thyroid antibodies are also associated with lower success rates in IVF cycles, and increased miscarriage rates, even if there is no hypothyroidism in the patient. Postpartum thyroiditis can occur in around 50% of women who develop antibodies during pregnancy.

As you can see, thyroid conditions are a very common health problem, and have great impact on pregnancies and fertility. Not only is thyroid disease related to miscarriage, but subclinical hypothyroidism or positive thyroid antibodies can impact the brain development of the fetus and have been linked to poor intellectual development in the baby. Hyperthyroidism is related to miscarriage and a host of problems such as intrauterine growth restriction. So this is an issue we must take seriously!

The new guidelines suggest the following:

  1. Trimester specific tighter ranges for TSH:
    First trimester normal range 0.1 to 2.5 mIU/L
    Second trimester 0.2 to 3.0 mIU/L
    Third trimester 0.3 to 3.0 mIU/L
  2. Women who are already receiving thyroid replacement therapy should increase their dose by 25% to 30% when they become pregnant.
  3. The total amount of iodine should be 250 ug from all dietary and supplemental sources.
  4. Monitoring is important to ensure that women with hypothyroidism or subclinical hypothyroidism are not at risk. TSH should be measured once every 4 weeks until 16 to 20 weeks’ gestation and at least once between 26 and 32 weeks’ gestation.

Basic nutrition for thyroid in pregnancy

Of note,although our salt is iodized in developed countries, there is a growing deficiency of iodine.This is because the iodine in our salt supply is not well absorbed and utilized. In pregnancy, there is a 50% increase in iodine requirements. So, choose a prenatal with some iodine content, usually around 150-200ug per day. Do not exceed 500mcg total intake daily, as this can pose an increased risk for hypothyroidism.

Selenium should be part of a prenatal vitamin. Several studies have shown that selenium decreases the levels of thyroid antibodies (anti thyroglobulin (anti TG) and anti thyroidperosidase (anti TPO). A randomized controlled trial found that supplementing with 200mcg of selenium daily during pregnancy and the post partum period reduced the incidence of postpartum thyroiditis in women who were positive for thyroid antibodies. 55 mcg should suffice as prevention in healthy women.

Perinatal thyroid disease is very common and new research is rapidly emerging on this topic. Thyroid disease affects fertility, pregnancy, maternal and fetal health. Women should optimally try to establish healthy thyroid function before conceiving: this way many concerns can be prevented, and the health of both moms and babies will be protected.


  • Selenium Supplementation in Patients with Autoimmune Thyroiditis Decreases Thyroid Peroxidase Antibodies Concentrations JCEM 2002 87: 1687-1691
  • Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and Postpartum. The American Thyroid Association Taskforce on Thyroid Disease During Pregnancy and Postpartum. THYROID Volume 21, Number 10, 2011
  • Dietary Iodine: Why Are So Many Mothers Not Getting Enough? Renner R 2010. Environ Health Perspect 118:a438-a442.
    Increased prevalence of thyroid antibodies in euthyroid women with a history of recurrent in-vitro fertilization failure Hum. Reprod. (2000) 15(3): 545-548

Tags:  Infertility  prenatal 

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5 Questions to Ask a Potential Practice Website Vendor

Posted By Drew McGray, Monday, August 1, 2011
Updated: Tuesday, February 4, 2014

As healthcare continues to be transformed by technology; refreshing or completely re-architecting your practice's website might be on your radar. Unless you have an in-house marketing team, you will probably be outsourcing your website design and production to a third party. How do you know who is going to deliver the most return on your investment? Here are five question to ask any potential vendor.

1.) Have you done this before?A provider that has experience in producing web properties for small business is probably a good fit. However, you want to be sure you are not their "guinea pig" and that they have experience in crafting websites that mesh well with your practice.

2.) What tools will be included for my patients? You want your website to be able to meet several objectives in order to make it relevant to your patient base. These objectives are:

  • Communicate information about your services offered and who you are.
  • Secure your practice's contact information, generate driving directions and provide hours of operation.
  • Allow people to contact your front office easily via web form.

Optionally you can give patients the ability to:

  • Book appointments online
  • Confirm appointments online
  • Cancel appointments online
  • Order supplements from your website

There are numerous companies that provide these optional tools that will transform your website from an information-only page to an interactive website.

3.) I have a change. How do I go about making edits? You don't want to have to call your web designer to make edits to your site and you want the ability to update information instantly. For this reason, its important you select a provider who can implement a Content Management System as opposed to simply building you practice a website. A CMS allows you to edit various parts of your website without having to know any code or programming language. It's basically as simple as editing a Word document and pushing "publish." In the case of CMS, simple is best. Ask your perspective web designer to demo a few systems for you.

4.) Can you work with my budget? A lot pricing in the website production industry is arbitrary. I recommend you be upfront with your website budget and have the provider quote products and services in that budget. Reject any supplementary marketing services they may offer (SEO / SEM) and focus on building a great web property.

5.) What sort of user engagement can I expect from the site?If your potential provider even flinches at this question, drop them. A good website developer knows that the focus of any website is on the visitor. They should answer this question with lots of good information related to engagement, conversion and functionality. If they do, they are probably worthy of further consideration.

Providers to consider:

Questions? Want us to help you? Our member-services team will be glad to provide you with a referral or review a proposal. Send to

Tags:  member benefit  practice marketing 

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Healthy Diet, Healthy Skin

Posted By Therese Patterson, NC, Monday, August 1, 2011
Updated: Tuesday, February 4, 2014

Diets rich in fruits and vegetables are good for us, skin included. Healthful foods reduce inflammation and decrease the likelihood of skin breakouts. On the flip side, there are also a few studies that scientifically support the role of two food groups in acne promotion: dairy products and simple carbohydrates (think processed foods and sugary soft drinks).

To keep your skin in tip-top shape, make sure you incorporate these foods into your diet (along with a good skincare routine that features natural skincareproducts):

Vitamin A. Vitamin A helps regulate the skin cycle and is also the main ingredient in Accutane, an effective prescription medicine for acne. Good food sources of vitamin A include fish oil, salmon, carrots, spinach, and broccoli. Too much vitamin A can lead to toxic side effects, however. Limit your daily dose to 10,000 IU and never take it while pregnant or nursing.

Zinc. There is some evidence that people with acne have lower than normal levels of the mineral zinc. Zinc appears to help prevent acne by creating an environment inhospitable to the growth of P. acnes bacteria It also helps calm skin irritated by breakouts. Zinc is found in turkey, almonds, Brazil nuts, and wheat germ.

Vitamins E and C. The antioxidants vitamin E and vitamin C have a calming effect on the skin. Sources of vitamin C include oranges, lemons, grapefruit, papaya, and tomatoes. You can get vitamin E from sweet potatoes, nuts, olive oil, sunflower seeds, avocados, broccoli, and leafy green vegetables.

Selenium. The mineral selenium has antioxidant properties that help protect skin from free radical damage. Food sources of selenium include wheat germ, tuna, salmon, garlic, Brazil nuts, eggs, and brown rice.

Omega-3 fatty acids. Omega-3 fatty acids support the normal healthy skin cell turnover that helps keep acne at bay. You can get omega-3 fatty acids from cold water fish, such as salmon and sardines; flaxseed oil; walnuts; sunflower seeds; and almonds.

Water. Last but definitely not least, water. Many of us have our morning coffee and then drink only one drink during the day and one at night. Water helps hydrate your body and leads to plump, healthy skin. Adequate hydration helps flush out toxins that can cause skin problems. It is also essential for skin metabolism and regeneration.

Sources: Mt. Sinai Medical Center,WebMD

Tags:  food and drink  gut health  health 

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It's Time to Clean Our Plates

Posted By Administration, Tuesday, July 26, 2011
Updated: Friday, April 18, 2014

Allan Magaziner, DO

In America, where obesity rates continue to increase, it is hard for me to tell anyone to clear their plate – unless I am confident that it is full of fruits, vegetables and whole grains! But, I have no problem urging people to clean their plates, or more specifically, opt for cleaner foods to put on them!

It goes without saying that I’d push for everyone to opt for clean, minimally processed, low sugar, low sodium, unrefined foods that include whole grains, fruits, vegetables, healthy fats, etc. But, this is about more than that. It’s about pushing the government to clean up its act when it comes to the production of our food.

It’s about time that, we, as a society, greatly curtail, and, eventually, eliminate, the use of synthetic, man-made herbicides and pesticides – which continue to be utilized in obscene quantities in both the agricultural and non-agricultural markets. In fact, genetically modified organisms (GMOs) are found in virtually all corn and soy products unless they are organically grown, yet another reason to purchase organic food whenever possible.

That government agencies would think that the use of more than 5.2 billion pounds of pesticides and herbicides each year would have no impact on human health is greatly near-sighted and short minded. Levels of many of these synthetic chemicals are measurable in human tissue at birth as well as in breast milk of mothers who are trying to opt for a healthy, natural, clean way to feed their babies. These chemicals are linked to the rise in chronic fatigue, fibromyalgia, learning disabilities, thyroid and hormone dysregulation, autoimmune disease and many of the inflammatory illnesses that we are seeing more and more in society. They’ve also been found to uncouple mitochondrial phosphorylation causing mitochondrial dysfunction, to stimulate autoimmunity and to increase inflammatory pathways.

The toll on human health and disease of these chemicals is probably more far-reaching than industry has led us to believe. In fact, a comprehensive review of existing data released this month by Earth Open Source, an organization that uses open-source collaboration to advance sustainable food production, suggests that industry regulators in Europe have known for years that the herbicide, glyphosate, causes birth defects in the embryos of laboratory animals, and, that by 1993, the herbicide industry, including the original makers of Roundup, knew that visceral anomalies such as dilation of the heart could occur in rabbits at low and medium-sized doses. The report further suggests that since 2002, regulators with the European Commission have known that glyphosate causes developmental malformations in lab animals. Even so, the commission’s health and consumer division published a final review of glyphosate in 2002 that approved its use in Europe for the next 10 years.

It’s maddening – especially knowing that much of this ingestion of chemicals is coming from the consumption of otherwise healthy foods like apples, celery, strawberries, peaches, spinach, nectarines (imported), grapes (imported), bell peppers, potatoes, blueberries (domestic), lettuce and kale/collard greens. These fruits and vegetables are known as the “dirty dozen,” meaning they are the 12 most contaminated fruits and vegetables and the most important to buy organic.

It’s time we DEMAND that additional independent studies be conducted to demonstrate the real safety of any pesticides or herbicides which affect our air, our food, our water and our future.

It’s time to seek more natural and safe solutions and put an end to this colossal human experiment that has been going on for decades at the expense of our health and the health of our future generations.
Until then, I encourage everyone to keep it clean – try to buy organic versions of the items on the “dirty dozen” list, when possible. When it is not, opt for fruits and vegetables that are grown with the use of less pesticides – as listed on the Environmental Working Group’s (EWG) list of “Clean 15.” These include asparagus, avocado, watermelon, mangoes, onions, sweet corn and pineapple, to name a few. According to the EWG, consumers who choose five servings of fruits and vegetables a day from this list rather than from the “Dirty Dozen” can lower their concentration of pesticides they consume by 92 percent and will also eat fewer types of pesticides, including Bt-Toxin, which has been in the news lately because of a recent study that has “blown” holes in the Environmental Protection Agency’s safety claims around corn grown using this substance.

The study, conducted by doctors at Sherbrooke University Hospital in Quebec found that genetically-modified “Bt” corn (corn grown using the Bt-toxin, a pesticide boasting a gene from soil bacteria that breaks open the stomach of certain insects, killing them instantly, thus protecting the corn crop) is – contrary to safety claims made by the EPA and the pesticide’s developer, Monsanto – harmful, very harmful, to humans.

The study, which has been accepted for publication in Reproductive Toxicology, found the corn's Bt-toxin present in the blood of pregnant women and their babies, as well as in non-pregnant women. (Specifically, the toxin was identified in 93% of 30 pregnant women, 80% of umbilical blood in their babies, and 67% of 39 non-pregnant women.) Bt-Toxin has been linked to allergies, rheumatoid arthritis, inflammatory bowel disease, osteoporosis, MS, cancer, ALS (Lou Gehrig’s Disease) and colitis. And that is the short list.
It is sad that we have to rely on lists to tell us which healthy food choice is, well, healthy. And that we cannot always rely on government agencies to be honest and keep our best interests at heart. Hopefully, though, with our collective voices, we can put pressure on the powers that be to put their money where their mouths are when it comes to the health and wellbeing of their constituents – both of today and tomorrow.

Dr. Allan Magaziner is one of the nation’s leading authorities on nutrition, preventive medicine and environmental illness. He is the founder and director of the Magaziner Center for Wellness in Cherry Hill, New Jersey, where he has treated dozens of patients with ailments resulting from exposure to herbicides and pesticide using medical detoxification. To find out more, contact the Magaziner Center at 856-424-8222 or at

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Too Much of a Good Thing

Posted By Administration, Monday, July 25, 2011
Updated: Friday, April 18, 2014


by Lena Edwards, MD, FAARM

The stress response is in place to allow us to survive hostile environments and adapt accordingly. It is when the stress response system (HPA Axis) is chronically stimulated that maladaptation and disease arise. Every organ system and hormone produced by the body is ultimately affected. 

Prolonged stress inhibits the non-essential functions of growth and reproduction. Both Corticotropin releasing hormone (CRH) and cortisol inhibit the release of Growth Hormone, Thyrotropin releasing hormone (TRH), Thyroid stimulating hormone, and Gonadotropin releasing hormone (GnRH), all of which are required for the production of the anabolic steroid hormones. Since these hormones antagonize the effects of cortisol, their absence further potentiates the actions of the unopposed catabolic corticosteroids further impairing growth, repair, and reproductive functions. Furthermore, even if present in small amounts, the anabolic hormones Growth hormone, DHEA, and testosterone are unable to exert their physiologic effect because of target tissue insensitivity. 

Stress induced GnRH deficiencies have been shown to cause delayed puberty, anovulation, and spontaneous abortion in women and decreased testosterone levels, impaired spermatogenesis, and decreased libido in men. In fact, stress induced abnormalities in cortisol are believed to contribute to up to 40% of infertility cases. Growth and reproduction are also influenced by thyroid hormone function which is adversely affected not only through CRH induced inhibition of TRH release but also by impaired peripheral conversion of the relatively inactive tetraiodothyronine into active triiodothyronine. 

Thus, when cortisol levels are chronically and abnormally elevated, numerous other hormone systems are adversely affected which may result in symptomatology despite 'normal' lab results. Keep this is mind when initiating hormone replacement with hormones since the catabolic action of cortisol can overpower the anabolic effects of the other hormones, DHEA in particular. Checking anabolic/catabolic balance via urine is an available diagnostic tool.

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Prolotherapy in Primary Care Practice

Posted By Administration, Friday, July 22, 2011
Updated: Friday, April 18, 2014


This case study was published on the National Library of Medicine (NLM) website.

Authors: David Rabago, MD, Andrew Slattengren, DO, and Aleksandra Zgierska, MD, PhD


Prolotherapy is an injection-based complementary and alternative medical (CAM) therapy for chronic musculoskeletal pain. It has been used for for approximately 100 years, however, its modern applications can be traced to the 1950s when the prolotherapy injection protocols were formalized by George Hackett, a general surgeon in the U.S., based on his clinical experience of over 30 years. While prolotherapy techniques and injected solutions vary by condition, clinical severity, and practitioner preferences, a core principle is that a relatively small volume of an irritant or sclerosing solution is injected at sites on painful ligament and tendon insertions, and in adjacent joint space over the course of several treatment sessions. Interest in prolotherapy among physicians and patients is high. It is becoming increasingly popular in the U.S. and internationally, and is actively used in clinical practice. A 1993 survey sent to osteopathic physicians estimated that 95 practitioners in the US were estimated to have performed prolotherapy on approximately 450,000 patients. However, only 27% of surveys were returned, likely dramatically underestimated true number of practitioners.  No formal survey has been done since 1993. The current number of practitioners actively practicing prolotherapy is not known but is likely several thousand in the US based on attendance at CME conferences and physician listings on relevant websites. Prolotherapy has been assessed as a treatment for a wide variety of painful chronic musculoskelatal conditions which are refractory to “standard of care” therapies. While anecdotal clinical success guides the use of prolotherapy for many conditions, clinical trial literature supporting evidence-based decision-making for the use of prolotherapy exists for low back pain, several tendinopathies and osteoarthritis.

The name of prolotherapy has changed over time. Consistent with existing hypotheses and understanding of possible mechanisms of action, the name of this therapy has evolved. Nomenclature has reflected practitioners’ perceptions of prolotherapy’s therapeutic effects on tissue. Historically, this injection therapy was called “sclerotherapy” because early solutions were thought to be scar-forming. “Prolotherapy” is currently the most commonly used name, and is based on the presumed “proliferative” effects on chronically injured tissue. It has also been called “regenerative injection therapy” (“RIT”),  and some contemporary authors name the therapy according to the injected solution. The precise mechanism of action is not known.
The National Institute of Health identifies prolotherapy as a CAM therapy and has funded two ongoing clinical prolotherapy trials. The Centers for Medicare and Medicaid Services and the Veteran’s Administration have reviewed the prolotherapy literature for low back pain and all musculoskeletal indications, respectively, and determined existing evidence to be inconclusive. Neither recommends third party compensation for prolotherapy. However, neither included the most recent clinically positive studies or reviews in their review. Private insurers are beginning to cover prolotherapy for selected indications and clinical circumstances; however, most patients pay “out-of-pocket”.

Prolotherapy Technique

While no formal practice guidelines have been published, prolotherapy treatment commonly consists of several injection sessions delivered every 2 to 6 weeks over the course of several months. During an individual prolotherapy session, therapeutic solutions are injected at sites of painful and tender ligament and tendon insertions, and in adjacent joint spaces. Injected solutions (“proliferants”) have historically been hypothesized to cause local irritation, with subsequent inflammation and tissue healing, resulting in enlargement and strengthening of damaged ligamentous, tendon and intra-articular structures. These processes were thought to improve joint stability, biomechanics, function and ultimately, to decrease pain.

Mechanism of Action

The mechanism of action for prolotherapy has not been clearly established and, until recently, received little attention. Supported by pilot-level evidence, the three most commonly used prolotherapy solutions have been hypothesized to act via different pathways: hypertonic dextrose by osmotic rupture of local cells, phenol-glycerine-glucose (P2G) by local cellular irritation, and morrhuate sodium by chemotactic attraction of inflammatory mediators and sclerosing of pathologic neovascularity associated with tendinopathy.The potential of prolotherapy to stimulate release of growth factors favoring soft tissue healing has also been suggested as a possible mechanism.

In vitro and animal model data have not fully corroborated these hypotheses. An inflammatory response in a rat knee ligament model has been reported for each solution, though it was not significantly different from that caused by needle stick alone or saline injections. However, animal model data do suggest a significant biological effect of morrhuate sodium and dextrose solutions compared to controls. Rabbit medial collateral ligaments injected with morrhuate sodium were significantly stronger (31%), larger (47%), and thicker (28%), and had a larger collagen fiber diameter (56%) than saline-injected controls; increase in cell number, water content, ground substance amount and a variety of inflammatory cell types were hypothesized to account for these changes. Rat patellar tendons injected with morrhuate sodium were able to withstand a mean maximal load of 136% (± 28%) – significantly more than the uninjected control tendon. Interestingly, in the same study, tendons injected with saline control solution were significantly weaker than uninjected controls. Dextrose has been minimally assessed in animal models. Recent studies showed that injured medial collateral rat ligaments injected with 15% dextrose had a significantly larger cross-sectional area compared to both non-injured and injured saline-injected controls. P2G solution has received the least research attention; although it is in active clinical use, no animal or in vitro study has assessed P2G effect using an injury model. Clinically, most clinicians report using these solutions as single agents, though concentration varies. In clinical practice, physicians sometimes mix prolotherapy solutions, or use solutions serially in a single injection session depending on experience and local practice patterns. Neither effect of varied concentration nor mixtures have been assessed in basic science nor clinical studies and no clinical trial has compared different solutions against one another.
Clinical Evidence
Early Research
Since its inception, prolotherapy has been primarily utilized outside of academic centers. This has lead to a pragmatic orientation of existing prolotherapy studies, and a relative paucity of major rigorous clinical trials in spite of significant clinical activity. While the first randomized controlled trial (RCT) did not appear until 1987, clinicians have enthusiastically reported the results of more modest, pilot-level clinical trials.
A 2005 systematic review of prolotherapy for all indications found 42 published reports of clincal prolotherapy trials since 1937. Thirty-six of the studies were case reports and case series that included 3928 patients aged from 12 to 88 years. These uncontrolled studies provide the earliest and most clinically-oriented evidence for prolotherapy. Each study reported positive findings for patients with chronic, painful, refractory conditions. Report quality of the included studies varied widely; their internal methodological strength was generally consistent with publication date. The older case studies documented injectants and methods that are no longer in use. Contemporary solutions were noted to start with P2G in the 1960s, dextrose in the 1980s, and morrhuate sodium in the early 1990s. The case reports and case series highlighted the fact that, over time, prolotherapy has been used and studied for a continually growing set of clinical indications. These case studies have also been used as pilots to develop new assessment techniques that could help elucidate pathophysiology of the condition in question, and test methodology for future, more robust randomized trials. In general, while lacking control groups and randomization, these pragmatic studies had the advantage of assessing effectiveness of prolotherapy in “real life settings” that patients encounter, including the prolotherapist’s ability to select the patient and to individually tailor the injection protocol. Most of the subjects (72%, 2691/3741) assessed in the early literature were treated for low back pain. However, other indications assessed by these early studies included knee osteoarthritis, shoulder dislocation, neck strain, costochondritis, lateral epicondylosis and fibromyalgia.
Contemporary Research
Since the mid 1980s, research on prolotherapy effects has accelerated and the number and methodological quality of studies assessing prolotherapy have increased dramatically (Figure 1).
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To date, prolotherapy has been best assessed as a treatment for low back pain, osteoarthritis and tendinopathy, each of which is a significant cause of pain and disability, and is often refractory to best standard-of-care therapies. The severity and prevalence of each condition is age-related. Because the U.S. population is aging, finding new effective therapies for these conditions can have an impact on both individual patient care and overall public health. In addition, prolotherapy has been assessed as a treatment for non-specific, non-surgical low back pain, osteoarthritis of the knee and hand, and for several tendinopathies, including lateral epicondylosis, Achilles, adductor and plantar fasciitis. The following section gives a brief description of studies assessing prolotherapy for these clinical indications, and level of evidence associated with each condition; this information is additionally summarized in Table 1.
Table 1
Strength of evidence for prolotherapy as a treatment for chronic musculoskeletal conditions: Low Back Pain (LBP), Osteoarthritis (OA) and Tendinopathy.
Key Clinical Recommendation on ProlotherapyEvidence RatingReference/s
Non-specific LBP: may be effective; conflicting results in several RCTs B 2528
Sacroiliac Joint Dysfunction: may be effective in patients with documented failure of load transfer (disability) at the sacroiliac joint B 34
Coccygodynia: may be effective based on prospective case series B 35
Lateral epicondylosis: likely effective based on strong positive data in these small RCTs A 6, 7
Achilles tendinopathy: may be effective based on high quality prospective case series B 9
Plantar fasciitis: may be effective, based on high- quality prospective case series B 60
Osteoarthritis: may be effective for knee and ? finger OA, based RCTs of moderately strong methodological quality B 17, 61
Low Back Pain (LBP)
LBP is among the most common reason patients see a primary care provider. Approximately 80% of Americans experience LBP during their lifetime. An estimated 15–20% of patients develop protracted pain, and approximately 2–8% experience chronic pain. LBP is second only to the common cold as a cause of lost work time. Productivity losses from chronic LBP approach $28 billion annually in the U.S.
Non-specific LBP
Four RCTs evaluated prolotherapy for musculoskeletal LBP; three used P2G as the injectant and the fourth used Dextrose. Each study used a protocol involving injections to the ligamentous insertions of the L4-S1 spinous processes, sacrum and ilium. While outcome measures varied, a common measure was the percentage number of participants reporting greater than 50% improvement in pain/disability scores at six months.
Two of these four RCTs reported positive findings compared to control injections. Ongley et al. and Klein et al. compared the treatment effects of prolotherapy combined with an adjacent treatment with injected steroids, spinal manipulation and exercise. In the Ongley study, the intervention and control groups differed markedly on the make-up of initial injections and type of spinal manipulation associated with the injections. Significantly more subjects in the prolotherapy (88%) group reported at least 50% reduction in pain severity compared to controls (39%). Also, prolotherapy subjects, compared to controls, reported significantly decreased pain and disability levels. Klein et al. used more similar treatment protocols in the two assessed groups, with subjects in both groups receiving steroid injections and spinal manipulation prior to prolotherapy. Again, significantly more prolotherapy subjects improved by 50% or more on pain or disability scores (77%) than controls (53%). Pain grid scores were also significantly lower in the prolotherapy group, with individual pain (p=0.06) and disability (p=0.07) scores trending toward significance, compared to the control group.
Two of the four RCTs reported negative outcomes compared to control injections. Dechow et al. implemented a refined study protocol; subjects in both groups underwent three injection therapy sessions without adjacent spinal manipulation or physical therapy. While both groups showed a trend toward improved severity scores on pain questionnaire, pain grid, and somatic perception measures, these changes did not reach statistical significance over time, within or between groups. At 6 months, improvements in both groups were smaller than those of the other RCTs. The largest and most methodologically rigorous prolotherapy study published to date has been conducted by Yelland et al. Study subjects (N=110), with an average of 14 years of LBP, were randomized to one of four intervention groups: dextrose and physical therapy, dextrose and “normal activity”, saline injections (“control” injection) and physical therapy, or saline injections and “normal activity”. By 12 months, subjects in all groups reported improved pain (26%–44%) and disability (30%–44%) scores, without significant differences between groups. The majority of subjects (55%) stated that their improvement in regards to both pain and disability had been worth the effort of undergoing the intervention. The percentage of subjects who reached at least 50% pain reduction varied between 36% and 46% though these differences were not statistically significant.
Overall, interpretation of findings from these 4 RCTs is challenging. Both experimental and control groups received different treatment protocols, and none of the trials was designed to elicit a possible mechanism of prolotherapy action. Therefore, it is impossible to attribute effects to prolotherapy or any other specific intervention. A recent Cochrane Collaboration systematic review did not find sufficient evidence to recommend prolotherapy for non-specific LBP. However, these four RCTs present overall promising results, calling for well-designed, sufficiently-powered research. All RCTs report improvements for pain and disability in all treatment groups consisting of subjects with chronic, moderate-to-severe LBP. In particular, Yelland et al. reported clinical improvement in excess of minimal clinical important difference, and in excess of subjects’ own perception of the minimum improvement necessary for prolotherapy to be worthwhile (25% for pain and 35% for disability).
LBP due to Specific Causes
Prolotherapy research methods for LBP have been evolving amid much debate surrounding effectiveness, indications, treatment protocols and solution types. Given the promising aspects of the above RCTs for non-specific LBP, combined with anecdotal clinical success, recent clinical researchers have begun to assess prolotherapy in patients with more specific forms LBP and loss of function in an effort to determine specific causes of LBP for which prolotherapy may be most effective.
Cusi et al. assessed 25 subjects with sacroiliac joint dysfunction and pain, refractory to 6 months or more of physical therapy, and with documented failure of load transfer (disability) at the sacroiliac joint. They used a strong prolotherapy solution of 18% dextrose, delivered in 3 sets of injections over 12 weeks. Compared to baseline, pain and disability scores on 3 multidimensional outcome measures significantly improved at 26 month follow-up in excess of minimal clinically important difference.
Khan et al. assessed 37 subjects with refractory coccygodynia. Using 25% dextrose in up to 3 prolotherapy injection sessions over 2 months, average pain scores, evaluated using a 0–10 visual analog scale (VAS), significantly decreased from a baseline score of 8.5 to 2.5 points at 2 months, far in excess of reported minimal clinical important difference for chronic pain. The authors reported “good” pain relief for 30 of 37 subjects, and “no improvement” for the remaining 7.
In an especially novel study, Miller et al. assessed prolotherapy for leg pain due to moderate-to-severe degenerative disc disease as determined by CT spell out discography. Subjects (N=76) who failed physical therapy and had substantial but temporary pain relief with two fluoroscopically-guided epidural steroid injections were included. After an average of 3.5 sessions of biweekly, fluoroscopically-guided injections to the relevant disc space with 25% dextrose with bupivacaine, 43% of responders showed a significant, sustained treatment response of 71% improvement in pain score, with VAS score for responders at 8.9 (± 1.4), 2.5 (±2.0), and 2.6 (± 2.2) at baseline, 2 and 18 months, respectively. While these three recent studies of prolotherapy for “specific” LBP were uncontrolled, they suggest the need for future RCTs with more focused clinical indications of axial pain and disability.
The strongest data supporting the efficacy of prolotherapy for any musculoskeletal condition, compared to control injections, is for chronic, painful overuse tendon conditions that were formerly called “tendonitis” and are now more correctly termed “tendinosis” or “tendinopathy” to reflect existing, underlying pathophysiology. Tendinopathies are common reasons why patients present to primary care providers and various medical specialists. Tendinopathies are sometimes discussed as a group because the current understanding of over-use tendinopathies identifies them as sharing underlying non-inflammatory pathology, resulting from a repetitive motion or overuse injury, and associated with painful degenerative tissue. Histopathology of tendon biopsies in patients undergoing surgery for painful tendinopathy reveals collagen separation, thin, frayed, and fragiletendon fibrils, separated from each other lengthwise and disruptedin cross-section, increase in tenocytes with my of ibroblastic differentiation (tendon repair cells), proteoglycan ground substance and neovascularization. Classic inflammatory cells are usually absent. Although this aspect of tendinosis was first described 25 years ago and content experts have advocated a change in nomenclature (from “tendonitis” to tendinosis), the misnomer and use of the term “tendonitis” continues. Prolotherapy has been assessed as a treatment for four tendon disorders: lateral epicondylosis, hip adductor, Achilles tendinopathies and plantar fasciitis.
Lateral epicondylosis (LE, “tennis elbow”) is an important common condition of the upper extremity with an incidence of 4–7/1000 patients per year in primary care settings. Its greatest impact is on workers with repetitive and high-load upper extremity tasks and on athletes. Its most common cause may be low-load, high-repetition activities such as keyboarding, though formal data is lacking. Cost and time away from job or activity are significant. While many non-surgical therapies have been tested for LE refractory to conservative measures, none have shown to be uniformly effective in the long term. Scarpone et al. conducted an RCT to determine whether prolotherapy improves self-reported elbow pain, and objectively measured grip strength and extension strength in patients with chronic LE. Twenty adults with at least 6 months of moderately-to-severely painful LE refractory to rest, non-steroidal anti-inflammatory medications (NSAIDs) and corticosteroid injections, were randomized to prolotherapy with dextrose and morrhuate sodium (1 part 5% sodium morrhuate, 1.5 parts 50% dextrose, 0.5 parts 4% lidocaine, 0.5 parts 0.5% sensorcaine and 3.5 parts normal saline)or control injections with normal saline. Three prolotherapy sessions were administered, with injection at the supracondylar ridge, lateral epicondyle and annular ligament. Compared to controls, prolotherapy subjects reported significantly decreased pain scores at 8 and 16 weeks. These between-group differences in pain scores were associated with a significant improvement in prolotherapy subjects (from 5.1±0.8 at baseline, down to 0.5±0.4 at 16 weeks), while the controls did not report significant change (4.5±1.7 to 3.5±1.5). In addition to pain reduction, prolotherapy subjects also showed significantly improved isometric strength compared to controls, and grip strength compared to baseline. These clinical improvements seen in prolotherapy subjects were maintained at 52 weeks.
Achilles tendinopathy is a common overuse injury seen both in athletes and in the general population. This painful condition is a cause of considerable distress and disability. Maxwell et al. conducted a well-designed case series to assess whether prolotherapy, administered during a mean of 4 injection sessions, at 6 week intervals, would decrease pain in 36 adults with painful Achilles tendinopathy. In this study, 25% dextrose solution was injected into hypoechoic regions of the Achilles tendon under ultrasound guidance. In addition to self-reported measures, the authors also assessed ultrasound-based tendon thickness, and the degree of hypoechogenicity and neovascularity - ultrasound findings recently reported to correlate to tendinopathy severity. At 52 weeks, prolotherapy-treated subjects reported decrease in VAS-assessed pain severity by 88%, 84% and 78% during rest, “usual” activity or sport, respectively. In addition, tendon thickness decreased significantly. The overall grade of tendon pathology, hypoechoic and anechoic tendon regions, and neovascularity were all improved in some, but not all subjects who reported clinical improvement. Therefore, the relationship between ultrasound-assessed characteristics and the degree of clinical improvement remains unclear.
Hip adductor tendinopathy, associated with groin pain, is a common problem among those who engage in kicking sports. Topol et al. conducted a case series assessing prolotherapy for chronic groin pain, a condition involving pain and tenderness at tendon and ligament insertions at the groin area. Male athletes (N=24), with an average duration of 15.5 months of groin pain in spite of standard therapy, were injected with 12.5% dextrose at the thigh and suprapubic abdominal insertions of the adductor tendon, and at the symphysis pubis at four-week intervals until pain resolved or subjects had no improvement for two consecutive sessions. On average, subjects received 3 prolotherapy sessions. At a mean of 17 months, subjects reported dramatic significant improvements on two pain scales (VAS and the Nirschl Pain Phase Scale). Of 24 subjects, 20 had no pain and 22 returned to sports without restrictions after therapy.
Plantar fasciitis is a common injury among athletes engaged in sports requiring running and among general primary care patients. It is reported to account for 15% of all adult foot complaints requiring professional consultation, and, in a 2002 survey of running-related injuries, plantar fasciitis was the third most prevalent injury. Among “standard of care” approaches, there is limited evidence for the effectiveness of any one treatment for plantar fasciitis, including steroid injections. Ryan et al. assessed prolotherapy for chronic plantar fasciitis refractory to conservative care. Twenty adults with an average of 21 month duration of heal pain underwent ultrasound-guided 25% dextrose injections for an average of 3 treatment sessions delivered at 6 week intervals. Pain scores were assessed, using a 100-point VAS, at baseline and at 11.8 months. Pain severity significantly improved at rest, during activities of daily living and sport activities by 26.5, 49.7 and 56.5 points, respectively, compared to baseline, and 16 of 20 subjects reported good or excellent treatment effects.
Osteoarthritis (OA)
Prolotherapy has been assessed as a treatment for knee and finger osteoarthritis and is the subject of ongoing studies. Arthritis is a leading cause of disability in the world and in the US, where it affects 43 million persons. OA is the most common form of arthritis and the most common joint disorder. In the US, symptomatic knee OA is present in up to 6% of the population over 30 years old, and has an overall incidence of 360,000 cases per year. Incidence increases up to 10-fold from ages 30 to 65 and more thereafter. OA results in a high burden of disease and substantial economic impact through its high prevalence, time lost off work, and frequent utilization of health care resources.
Allopathic and CAM treatment recommendations for OA, aimed at correcting modifiable risk factors, symptom control and disease modification, have been published. While these modalities may help some patients, none has proven to provide definitive pain control or disease modification for patients with knee OA. The Agency for Research Health and Quality (AHRC) has recently evaluated the most common standard treatment options including glucosamine, chondroitin, visco supplementation and arthroscopic debridement. These have not shown to be effective compared to placebo. The high burden of knee OA and the absence of cure continue to stimulate intense search for new agents to modify disease and control symptoms.
Reeves et al. assessed prolotherapy as a treatment for knee and finger OA. Subjects with finger or knee pain and radiological evidence of OA were randomly assigned to receive 3 injection sessions of either prolotherapy with 10% dextrose and lidocaine, or lidocaine and bacteriostatic water (control group). In the finger OA trial, intervention subjects significantly improved in ‘pain with movement’ and ‘flexion range’ scores compared to controls; pain scores at rest and with grip showed a tendency to improvement without reaching statistical significance. In the knee OA trial, subjects in both groups reported significant improvements in pain and swelling scores, number of buckling episodes, and flexion range of motion compared to baseline, but without statistically significant differences between the groups. Surprising and potentially important 12-month follow-up in both studies included improved radiological features of OA on plain x-ray films: authors reported decreased joint space narrowing and osteophyte grade in the finger study, and increased patellofemoral cartilage thickness in the knee study. These radiological findings may suggest disease modification properties of prolotherapy. Whether or not subjects in the knee study had a baseline concomitant meniscal pathology was not reported or included in entry criteria. Furthermore, the ability of plain x-ray to quantify patellofemoral cartilage thickness is questionable, limiting impact of these findings.
Absolute contraindications to prolotherapy are few and include acute infections such as cellulitis, local abscess or septic arthritis. Relative contraindications include acute gouty arthritis and acute fracture.
Common side-effects
The main risk of prolotherapy is pain and mild bleeding as a result of needle trauma. Patients frequently report pain, a sense of fullness and occasional numbness at the injection site at the time of injections. These side effects are typically self-limited. A post-injection pain flare during the first 72 hours after the injections is common clinically but its incidence has not been well documented. An ongoing study of prolotherapy for knee OA pain has noted that 10–20% of subjects experience such flares. Pain flares are likewise typically self-limited, and usually respond well to acetaminophen (500–650 mg every four hours as needed). On rare occasions, the occurrence of strong, post-injection pain may require treatment with narcotic medication. Non-steroidal anti-inflammatory agents are not routinely used after the procedure, but may be indicated if the pain does not resolve with other measures. Most patients with pain flares experience diminution of pain in 5–7 days after injections; regular activities can be resumed at this time.
Adverse events
While prolotherapy performed by an experienced injector appears safe, the injection of ligaments, tendons and joints with irritant solutions raises safety concerns. Theoretical risks of prolotherapy injections include lightheadedness, allergic reaction, infection or neurological (nerve) damage. Injections should be performed using universal precautions and the patient should be prone if possible. Dextrose is extremely safe; it is FDA approved for intravenous treatment of hypogylcemia and for caloric supplementation. As of 1998, FDA records for intravenous 25% dextrose solution reported no adverse events to Abbott Labs in 60 years. Morrhuate sodium is a vascular sclerosant, used in gastrointestinal procedures and vein sclerosing. Allergic reactions to morrhuate sodium are rare. Although P2G is not FDA approved for any indication, it has not been reported in clinical trials to cause significant side effects or adverse events.
Historically, a small number of significant, prolotherapy-related complications have been reported. They were associated with perispinal injections for back or neck pain, using very concentrated solutions, and included 5 cases of neurological impairment from spinal cord irritation and 1 death in 1959 following prolotherapy with zinc sulfate for low back pain. Neither zinc sulfate nor concentrated prolotherapy solutions are currently in general use. In a survey of 95 clinicians using prolotherapy, there were 29 reports of pneumothoraces after prolotherapy for back and neck pain, two of which required hospitalization for a chest tube, and 14 cases of allergic reactions, although none classified as serious. A more recent survey of practicing prolotherapists yielded similar results for spinal prolotherapy: spinal headache, pneumothoraces, nerve damage and non-severe spinal cord insult and disc injury were reported. The authors concluded these events were no more common in prolotherapy than for other spinal injection procedures. No serious side effects or adverse events were reported for prolotherapy when used for peripheral joint indications.
Practical Prolotherapy Incorporating Prolotherapy Into Practice
Similar to corticosteroid injections, prolotherapy is an unregulated procedure without certification by any governing body. Formal training is not provided by most medical schools, residencies and fellowships. However, prolotherapy, to be performed appropriately and safely, requires specialized training. In the U.S., it is taught to physicians and other health care providers (authorized to deliver joint-type injections) in semi-formal workshops and formal continuing medical education (CME) by several organizations, including university settings (Table 2).
Table 2
Educational and Informational Prolotherapy Resources
“The Anatomy, Diagnosis, and Treatment of Chronic Myofascial Pain with Prolotherapy”
Continuing medical education (CME) on the basics of prolotherapy. This 3.5 day conference is offered through the University of Wisconsin School of Medicine and Public Health. All aspects of clinical and research aspects of prolotherapy are covered.
Hackett-Hemwall Foundation List of Prolotherapists
The Hackett-Hemwall Foundation is a non-profit medical foundation whose mission is to provide high-quality treatment of musculoskeletal problems to underserved people around the world. Physicians listed on the site have completed the Foundation’s high-volume continuing medical education experience in prolotherapy.
Commercial Prolotherapy Physician Listing
This site lists physicians by state who perform prolotherapy. It includes contact information and a short biography and prolotherapy credentials. Physicians pay to list themselves on this site.
American Association of Orthopaedic Medicine
The American Association of Orthopaedic Medicine is a non-profit organization which provides information and educational programs on comprehensive nonsurgical musculoskeletal treatment including prolotherapy. This searchable site lists AAOM members who perform prolotherapy.
Patients and physicians who desire consultation for prolotherapy may have difficulty finding an appropriate consulting prolotherapist. Online resources (Table 2) are available that can help locate a prolotherapist, though information is limited by lack of a credentialing structure and governing body for prolotherapy.
Despite limited institutional support, interest in prolotherapy is increasing, and it is performed in increasing numbers, primarily in two settings. For several decades, prolotherapy has been mostly performed outside of mainstream medicine by independent physicians. More recently, multi-specialty groups that include family or sports medicine physicians, physiatrists, orthopedic surgeons, neurologists or anesthesiologists have been incorporating prolotherapy as a result of positive clinical experience and research reports. Prolotherapy is one of several injection therapies that may promote healing of chronically injured soft tissue. Other therapies receiving active clinical and research attention for chronic musculoskeletal pain include whole blood, platelet rich plasma and polidocanol injections. In both settings, prolotherapy is viewed as a valued procedure, primarily reserved for patients who have failed other treatments or in patients who are not surgical candidates.
The authors’ clinic
The authors practice in a community in which several primary care physicians and specialists perform prolotherapy; receptivity to prolotherapy in our setting is growing. Some health insurance plans in our area cover prolotherapy for the indications discussed. Referrals can be made similar to those for more conventional procedures. An initial consultation, including a complete history and physical, is performed by the prolotherapist to determine if the patient is a candidate for prolotherapy. If so, side effects, adverse events and expected course of injections are explained, and the patient is asked to sign a procedure consent form. Information is also provided to patients in written form. (Table 3) The patient is then scheduled for up to three outpatient prolotherapy sessions, typically four- six weeks apart. At each subsequent visit, an interval history is obtained and physical exam is performed. If the patient does not report improvement after three prolotherapy sessions, alternative interventions are pursued.
Table 3
Prolotherapy at a glance
What is prolotherapy? Prolotherapy is an injection-based complementary and alternative medical (CAM) therapy for chronic musculoskeletal pain. This treatment aims to stimulate a natural healing response at the site of painful soft tissue and joints.
What is involved? Prolotherapy treatment typically involves getting a series of 2–5 monthly injections of a topical anesthetic and a solution of other medicines directly on sore tendon or ligaments, or into painful joints.
What conditions is it used for, and is it effective? Prolotherapy is generally used for musculoskeletal pain of greater than 3 months. Conditions that have responded well to prolotherapy in published studies include tennis elbow, Achilles tendinopathy, and other overuse injuries involving tendons. Prolotherapy is also likely effective for knee osteoarthritis and low back pain, though studies assessing these conditions are less conclusive.
Is it safe? Studies indicate that prolotherapy is safe when performed by an experienced practitioner. It does not appear to have a greater risk than other injection techniques, such as steroid injections.
Does it hurt? No one loves getting a shot, though prolotherapy injections typically hurt less than most immunizations. Most patients tolerate prolotherapy injections related pain quite well with only topical and conservative measures. Physicians can pre- treat with a pain reliever if necessary.
Clinical Recommendations
Present data suggest that prolotherapy is likely an effective therapy for painful overuse tendinopathy. Specifically, Scarpone et al. provides level A evidence for prolotherapy as an effective therapy for lateral epicondylosis. Subjects with refractory lateral epicondylosis and treated with prolotherapy reported significant reduction in pain and improved isometric strength compared to those who received control injections. These findings are supported by the Maxwell, Topol and Ryan studies that report strong case series results for Achilles, hip adductor and plantar fasciitis, respectively and provide level B evidence for these conditions. Given that the underlying mechanism of injury and pathophysiologic effects are similar for tendinopathies, prolotherapy is a reasonable option for these conditions as well. Randomized controlled trials for all three tendinopathies and for other tendinopathies are indicated.
Recommendations are more difficult to make for osteoarthritis and low back pain, both of which are associated with more complex anatomy and less clear pathophysiology than that seen in tendinopathies. Side effect and potential adverse events of prolotherapy are likely to be more serious when performed for spinal or intra-articular indications and must be weighed against the potential for improvement. Existing studies provide level B evidence that prolotherapy is effective for non-specific low back pain compared to a patient’s baseline condition. Given that subjects with refractory, disabling low back pain significantly improved compared to their own baseline status in the Yelland study, patients may reasonably try prolotherapy when performed by an experienced injector. Future studies with more focused inclusion criteria may help determine which specific low back pathologies respond to prolotherapy. Existing studies provide level B evidence that prolotherapy is effective for knee and finger osteoarthritis compared to control injections. Prolotherapy by an experienced physician is a treatment modality worth of consideration by primary care physicians for these conditions, especially when they are refractory to more conventional therapy.
Jeffrey Patterson, DO
Grant Support: None
Contributor Information
David Rabago, University of Wisconsin School of Medicine and Public Health, Department of Family Medicine, 777 S. Mills St., Madison WI, 53715, Ph 608-265-2487, Fax 608-263-5813.
Andrew Slattengren, University of Wisconsin School of Medicine and Public Health, Department of Family Medicine, 777 S. Mills St., Madison WI, 53715.
Aleksandra Zgierska, University of Wisconsin-Madison, Department of Family Medicine, 777 S. Mills St., Madison WI, 53715.
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78. Keplinger JE, Bucy PC. Paraplegia from treatment with sclerosing agents - report of a case. Journal of the American Medical Association. 1960;173(12):1333–1336. [PubMed]
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A Little Less Beef Please!

Posted By Administration, Wednesday, July 20, 2011
Updated: Friday, April 18, 2014

Copyright © Environmental Working Group, Reprinted with permission.


Report Finds Wide Variation in Environmental, Health Impacts of Foods

WASHINGTON, D.C.–The Environmental Working Group today released its groundbreaking Meat Eater’s Guide to Climate Change and Health, a powerful, multi-featured tool that allows both consumers and experts to understand easily how food choices affect both their environmental footprint and their health.

Taking into account every stage of food production, processing, consumption and waste disposal, the guide documents in unprecedented detail how consumers who eat less meat and cheese can significantly reduce the greenhouse gas emissions, pollution and health risks linked to their dietary choices. Previous studies have focused mostly on emissions from the food production phase only.

The calculations reveal that if everyone in the U.S. ate no meat or cheese just one day a week, over a year, the effect on emissions would be the equivalent of taking 7.6 million cars off the road.

The research also highlights the surprisingly large environmental impact of meat that goes into the trash, which accounts for more than 20 percent of all meat-associated emissions.

“By eating and wasting less meat, consumers can help limit the environmental damage caused by the huge amounts of fertilizer, fuel, water, and pesticides, not to mention the toxic manure and wastewater, that goes along with producing meat,” said Kari Hamerschlag, EWG senior analyst and author of the report. “Choosing healthier, pasture-raised meats can also help improve people’s health and reduce the environmental damage associated with meat consumption.”

Mario Batali, chef, restaurateur, award-winning author, and television personality, said, “The fact is, most people in the U.S. eat way more meat than is good for them or the planet, but even knowing this, the chances are little that we are all going to become vegetarians, much less vegan. Asking everyone to go vegetarian or vegan is not a realistic or attainable goal, but we can focus on a more plant-based diet and support the farmers who raise their animals humanely and sustainably. This is why I am such a big believer in the Meatless Monday Movement and the Environmental Working Group’s Meat Eaters Guide to Climate Change and Health.” 

The study points to abundant research showing how eating large quantities of beef and processed meats increases exposure to toxins and increases the risk of heart disease, cancer, and obesity.

EWG teamed up with CleanMetrics, an environmental analysis and consulting firm, to calculate complete lifecycle assessments of the “cradle-to-grave” carbon footprint of 20 types of conventionally raised (not organic or grass-fed) meat, fish, dairy and vegetable proteins, counting emissions generated both before and after the food leaves the farm. These assessments included every step of the food cycle, from the pesticides and fertilizers used to grow animal feed through to the grazing, processing, transportation, cooking and finally, disposal of unused food. 

Other key findings of the report:

  • Beef generates more than twice the emissions of pork, nearly four times that of chicken, and more than 13 times that of vegetable proteins such as beans, lentils, and tofu.
  • Cheese has the third-highest emissions. Less dense cheese (such as cottage) results in fewer greenhouse gases since it takes less milk to produce it.
  • 90 percent of beef’s emissions, 69 percent of pork’s, 72 percent of salmon’s and 68 percent of tuna’s are generated in the production phase. Just half of chicken’s emissions are generated during production.

“The report also points out that making significant cuts in emissions will not come solely from individual action, but also citizen action,” said Ken Cook, EWG’s President. “Consumers need to convince Washington to enact comprehensive policies that put the nation on a path to green energy. Reducing meat production’s negative impact on soil, air and water quality will also require better policies and regulatory enforcement as well as curbing meat consumption.”

EWG recommends that consumers buy right-size portions to reduce waste, avoid eating meat and cheese at least one day a week and choose “greener” options such as grass-fed, organic and pasture-raised animal and dairy products that are produced in a more ethical manner and without antibiotics or hormones.

To make the report and findings as widely useful as possible, EWG’s Meat Eater’s Guide website includes a variety of consumer-friendly features, including an interactive graphic, an available printed wallet card and brochure that summarize the results, consumer tips, a quiz and a guide to decoding the maze of labels on meat other food products.

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Eat Your Greens

Posted By Administration, Thursday, July 14, 2011
Updated: Friday, April 18, 2014


by Therese Patterson, NC

Most people don’t realize that not all types of salad greens are created equal. I personally like to include a variety of different types of lettuce in my salad. Not only will a variety of greens allow you to enjoy a variety of different flavors and textures, but you also get to enjoy the range of nutrients each green has to offer. And while lettuce or salad greens are not often recognized as a great source of nutritional value, some varieties pack a surprising vitamin and mineral punch as you can see from the chart below.

Nutritional Comparison of Salad Greens Based on a 1 Cup Serving

Salad Greens Calories Vit A (IU) Vit C(Mg) Calcium (Mg) Potassium (Mg)
Romaine 8 1456 13 20 65
Leaf Lettuce 10 1064 10 38 148
Butterhead (Bib and Boston) 7 534 4 18 141
Arugula 5 480 3 32 74
Mixed Greens 9 1495 9 30 174
Baby Spinach 7 1200 8 20
Iceberg 7 182 2 10 87

Iceberg lettuce is included in the chart, not because I recommend it, but because it is so commonly served when eating out. Romaine lettuce has eight times more vitamin A and six times more vitamin C than iceberg lettuce, so iceberg would not be my lettuce of choice. After selecting your salad greens, creating a wonderful salad is only limited by your imagination— nuts, seeds, fish, poultry, beans, cheese, grains (try a spinach salad with lentils, garbanzo beans, tomatoes, cucumbers, feta and a light vinaigrette of olive oil and lemon juice-yum-o!).

Calorie for calorie, leafy green vegetables like spinach, with its delicate texture and jade green color, provide more nutrients than any other food. Baby spinach is a good source of calcium, fiber, iron, magnesium, provitamin A and vitamin C.

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Building Better Bone Health

Posted By Administration, Monday, July 11, 2011
Updated: Friday, April 18, 2014


by Andrea Purcell, ND

I was sitting around with a group of my colleagues the other day and we were discussing Integrative medicine and how it always seemed to have the other side of the story.

Lets take bone health for example. When we think of bone health we instantly think of bone mineral density (BMD). This is what is measured in the gold standard test, the DEXA scan, to evaluate osteoporosis risk. All of the bisphosphinate drugs are focused on maintaining and improving BMD, and all fracture prevention efforts have been focused on it. However BMD is one component of bone health, it contributes to the density and the rigidness of the bone.

The other side of bone health is its flexibility, which is determined by its collagen content. It is both of these that determine how susceptible a bone is to fracture; we must have both for good bone health.

The collagen matrix provides the bones with its shock absorption nature and its spring and helps to complement bone mineral density. We can easily think of our bones like a tree. Without a certain level of flexibility a tree in a windstorm would snap in half if it did not have a collagen matrix.

Bone health declines with age so it is important to provide and supplement our bones with a combination of items that will support the bone at both levels.

Medications that lead to bone demineralization:

**Oral Glucocorticoids – increase fracture risk significantly
**Antibiotics – interfere with Vitamin K absorption
**Acid Blocking Medications – interfere with mineral absorption

Testing to determine bone health:

In addition to the DEXA scan, blood markers of homocysteine and osteocalcin are useful in determining vitamin deficiencies that can lead to weakened bones. Elevated homocysteine shows vitamin B6, B12, And folate deficiencies and Osteocalcin shows vitamin K deficiency.

Supplements for better bone health:

**Calcium citrate, Magnesium & Vitamin D
**Vitamin K can improve bone health and improve fracture risk. In the US it comes in K1 (MK7), found in leafy greens, and K2 (MK4), produced by digestive bacteria, both of these are non-toxic and important for bones. K2 has the most impact on bones and collagen formation and a dose of 45 mg has been approved for treatment of osteoporosis in Japan.
**Strontium ranelate (SR) at a dose of 2.0 g/day was been shown to reverse osteoporosis, without side effect. Due to its higher mass than calcium, strontium can alter DEXA scans and the radiologist doing the test must be informed of this. Strontium citrate is the most common form in the US but is it best to find SR when at all possible.

Note from Dr. P:
Bone Health is just another example that without holistic medicine we are missing key pieces to the story. When we only focus on one component of a disease or expect one action of a drug to completely fix a problem we are setting ourselves up for failure and more disease. By only treating bone Mineral Density we are completely ignoring 50% of the bone story and that’s why women are still falling and breaking bones! It is essential that we embark on comprehensive care so that all pieces to the story are addressed and the patient is restored to health!

-Be Happy, Healthy, & Holistic

Tags:  bone health 

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Curcumin for Inflammatory Bowel Disease: A Review of Human Studies

Posted By Administration, Friday, July 8, 2011
Updated: Friday, April 18, 2014


Case study from the Alternative Medicine Review (AMR) - the official journal of the American College for Advancement in Medicine (ACAM)

by Rebecca A. Taylor, PharmD, MBA, BCPS and Mandy C. Leonard, PharmD, BCPS


OBJECTIVE: To evaluate the use of curcumin in inflammatory bowel disease. DATA SOURCES: ALTMEDEX, Comprehensive Database of Natural Medicines, MEDLINE/PubMed were searched from January 1980 through May 2009 using the terms curcumin, turmeric, ulcerative colitis, Crohn’s disease,
Curcuma longa, Curcuma domestica, Indian saffron, inflammatory bowel disease. Data was limited to human trials. References of identified articles were reviewed. DATA SYNTHESIS: Data evaluating the use of curcumin in inflammatory bowel disease (including ulcerative colitis and Crohn’s disease) is limited to two studies comprising data for only 99 patients. Curcumin in conjunction with mainstream therapy, consisting of sulfasalazine (SZ) or mesalamine (5-aminosalicylic acid [5-ASA] derivatives) or corticosteroids was shown to improve patient symptoms and allow for a decrease in the dosage of corticosteroids or 5-ASA derivatives. In one small study of 10 patients, some patients even stopped taking corticosteroids or 5-ASA. CONCLUSIONS: Although two small studies have shown promising results, all authors conclude
that larger-scale, double-blind trials need to be conducted to establish a role for curcumin in the treatment of ulcerative colitis. In addition to improving results when used in conjunction with conventional medications for UC, curcumin may pose a less-expensive alternative. (Altern Med Rev 2011;16(2):152-156)


Turmeric, used as a spice in curry powders and mustard, is known scientifically as Curcuma longa or Curcuma domestica. The perennial herb has multiple ingredients, including curcuminoids, the most active ingredients for medicinal use. These curcuminoids, comprising the yellow-pigmented fractions of turmeric, include diferuloylmethane (curcumin I), demethoxycurcumin (curcumin II), bisdemethoxycurcumin (curcumin III), and the recently discovered cyclocurcumin. The major components of commercial curcumin are curcumin I (77%), curcumin II (~17%), and curcumin III (~3%). Curcumin is also known by many synonyms and translated into various languages around the world; in Tibetan language it is known
as Gaser, in Swahili it is known as Manjano.

Curcumin has well-documented historical use in Chinese, Hindu, and Ayurvedic medicine. Curcumin has been used for a variety of disorders, from respiratory conditions to dyspepsia to malignancy. To date, no studies in animals or humans have discovered significant toxicity related to curcumin, even at very high doses.

Mechanisms of Action

Much is known about the molecular targets and interactions of curcumin with receptors, growth and transcription factors, cytokines, enzymes, and genes. Curcumin is often cited as pleiotropic, meaning it has the ability to interact with many cell targets. For the purposes of this discussion, curcumin’s molecular targets will be confined to those involved in gastrointestinal inflammation. Curcumin has been shown to inhibit the activity of lipoxygenase4 or binding to phosphatidylcholine micelles, thereby inhibiting lipoxygenase I. Of note in gastrointestinal disorders, curcumin has been found to inhibit the activation of various transcription factors that play a key role in inflammation, cell survival and proliferation, and
angiogenesis. These include nuclear factor-kappaB (NF-kB), activated protein-1 (AP-1), signal transducer and activator of transcription (STAT) proteins, peroxisome proliferator-activated receptor-gamma (PPAR-γ), and β-catenin. Inflammatory stimuli activate one of three independent mitogen-activated protein kinase (MAPK) pathways leading to activation of the p44/42 MAPK, JNK, or p38 MAPK pathway.
Cyclooxygenase-2 (COX-2) proteins are crucial to the inflammation cascade and have been linked to
certain cancers. There are several ways in which curcumin inhibits COX-2, both directly and indirectly. Curcumin downregulates the expression of COX-2, most likely through the downregulation of NF-kB that is required for COX-2 activation. In cancer cells, curcumin exerts anti-inflammatory and growth-inhibition by inhibiting expression of interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α).


Curcumin studies in animals show it is rapidly metabolized, conjugated in the liver, and excreted in the feces with minimal amounts found in the urine. A 40 mg/kg intravenous dose of curcumin given to rats resulted in complete plasma clearance at one hour post-dose, showing its rapid metabolism; data in humans is inconclusive. A phase I clinical trial conducted on 25 patients with precancerous lesions showed oral doses of 4, 6, and 8 g curcumin daily for three months yielded serum curcumin concentrations of only 0.51 ± 0.11, 0.63 ± 0.06, and 1.77 ± 1.87 µM respectively, indicating poor absorption of straight curcumin. In this study serum levels peaked one and two hours post-dose and declined rapidly.

Inflammatory Bowel Disease (IBD)

Inflammatory bowel disease is a chronic immune disorder that involves an overactive immune component in the intestinal mucosa. IBD is divided into two major categories, ulcerative colitis (UC) and Crohn’s disease (CD). The two diseases have a fair amount of overlap, including presenting symptoms, quality of life issues, and treatments. Patients with IBD often have symptoms of abdominal pain, cramping, diarrhea, rectal bleeding, urgency, nausea, fever, and weight loss. Major differences of the two types of IBD are listed in Table 1.11 Proctitis is ulcerative colitis confined to the rectal area.

Certain cytokines have been associated with IBD, including TNF-α, IL-1, IL-6, IL-8, and others. Targeted drug therapies, specifically infliximab, have been successful in treating IBD. Infliximab is an anti-TNF-α monoclonal antibody that has been extensively studied in myriad inflammatory disorders, including CD and UC. Widespread use of infliximab is limited because of adverse effects, cost, and the emergence of antibodies that result after multiple administrations.

Most recently, the role of NF-kB in IBD has been elucidated. Colon biopsies in IBD patients with active disease show increased levels of NF-kB p65 protein (a member of the NF-kB family of proteins). The amount of NF-kB p65 in the tissue samples correlated with the severity of intestinal inflammation. This increased expression of NF-kB results in an increased ability to secrete inflammatory cytokines, such as
TNF-α, IL-1, IL-6, IL-12, and IL-23, the latter of which are directly responsible for mucosal damage in IBD. TNF-α is also able to up-regulate the production of NF-kB, resulting in a cyclical feedback loop of inflammation.

Table 1. Differential Diagnosis of Ulcerative Colitis and Crohn's Disease


 Diagnosis and Staging of IBD in Clinical Studies

Ulcerative colitis is diagnosed through a colonoscopy, while the severity of symptoms can be rated on a number of severity index scales. Although several endoscopic indices are available to characterize the severity of ulcerative colitis, those currently used in clinical trials are not uniform. Hanai and colleagues, in the double-blind study discussed below, did not disclose their specific methodology for endoscopic index. The Clinical Activity Index (CAI) was used to assess UC severity in this same study. A CAI of ≤4
indicated remission, whereas a CAI ≥5 indicated relapse. A Crohn’s disease activity index (CDAI) is
often used to evaluate disease severity in CD – as was the case in the small pilot study discussed below.

Clinical IBD Studies
Small Pilot Study

Holt and colleagues conducted a small, open-label, pilot study of curcumin in five patients with ulcerative colitis/proctitis and five patients with Crohn’s disease. Five patients with ulcerative proctitis, who were currently using 5-aminosalicylic acid (5-ASA) compounds and corticosteroids (four of five patients were on corticosteroids + 5-ASA compounds), were given 550 mg curcumin twice daily for one month, then 550 mg three times daily for the second month. The five patients with Crohn’s disease received curcumin at a dose of 360 mg orally three times daily for one month and then 360 mg four times daily for an additional two months. Patient characteristics and demographics are reported in Table 2.

Patients were assessed at baseline and after two months of curcumin via hematological, biochemical, and inflammatory analysis (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) as well as sigmoidoscopy and biopsy. Subjective analysis was via a self-reported symptom diary. In the ulcerative
proctitis group, all five patients had significant improvement. Two patients stopped taking 5-ASA compounds, two reduced 5-ASA dosages, and one stopped corticosteroids entirely. Although only four of five CD patients completed the study, they also experienced a reduction in CDAI scores, ESR, and CRP. The Crohn’s disease group also reported symptomatic improvements of fewer bowel movements, less diarrhea, and less abdominal pain and cramping. In the absence of a clearly stated primary endpoint, it was considered to be the symptom diary. Based on the symptom diary (p<0.02), all patients improved from baseline after two months and inflammatory markers decreased to normal limits. The authors recommended larger scale, double-blinded, placebo-controlled trials in the future.

Table 2. Patient Characteristics and Medications at Study Entry


Adapted from: Holt PR, Katz S, Kirschoff R Curcumin therapy in inflammatory bowel disease; a pilot study. Dig Dis Sci 2005;50:2191-2193.

5-ASA = 5-aminosalicyllic acid

SZ = sulfasalazine

6-MP = 6-mercaptopurine

Double-blind, Placebo-controlled Trial

Hanai and colleagues conducted a randomized, multicenter, double-blind, placebo-controlled trial of curcumin plus sulfasalazine (SZ) or mesalamine compared to placebo plus SZ or mesalamine in 89
patients with UC. After a four-week washout period, subjects were randomly assigned to a six-month regimen of either placebo (n=44) or curcumin 1,000 mg after breakfast and 1,000 mg after dinner (n=45) in combination with SZ (1-3 g/ day; median 2 g/day) or mesalamine (1.5-3 g/day; median 2.25 g/day). The inclusion and exclusion criteria were extensive (Table 3).

Patients were followed during treatment and for six months after the treatment ended; patients received only SZ or mesalamine during the six-month follow-up. Seven patients requested to be excluded, leaving 82 evaluable patients. The relapse rate was significantly higher in the placebo group (20.5% [8/39]) than in the curcumin-treated group (4.7% [2/43]). Curcumin also suppressed disease-associated CAI and endoscopic index (EI) scores. The mean CAI in the curcumin group was improved from 1.3 to 1.0 at six months (p=0.38), while CAI in the placebo group increased from 1.0 to 2.2 (p=0.0003). Patients in the curcumin group also had significantly improved EI (1.3 to 0.8 [p=0.0001]), while EI values in the placebo group showed no significant improvement. The authors provided only before- and after-treatment data,
despite assessments every two months. There was a statistically significant (p=0.049) difference between the percentage of patients with recurrence at six months in the curcumin (4.44 [95% confidence interval (CI) 0.54-15.15]) compared to the placebo (15.15 [CI 8.18-32.71]) group. This difference was not significant at 12 months.

Side effects reported by study subjects included abdominal bloating, nausea, hypertension (one patient), diarrhea, and elevated γ-guanosine triphosphate (GGTP) levels (one patient). This latter patient was a heavy drinker. With the exception of the patient that experienced hypertension, no patient discontinued curcumin therapy due to side effects.

Only two of 43 patients treated with curcumin in combination with SZ or mesalamine relapsed during six months of therapy; whereas, eight of 39 patients who received placebo with SZ or mesalamine relapsed during the same period. Although this difference was not statistically significant, the authors postulate curcumin may have an effect on suppressing relapse. The authors drew three major conclusions: (1) curcumin had better clinical efficacy over placebo in the prevention of relapse, (2) curcumin significantly improved the CAI and EI, and (3) curcumin was well-tolerated. The authors, stating their results might have
been better had they used a higher dose of curcumin, recommend that future studies use dosages greater than 2 g/day.

Table 3. Inclusion and Exclusion Criteria in Hanai Study


Precautions and Contraindications

Patients with gallstones or bile duct obstructions should use curcumin with caution, primarily due to curcumin’s ability to cause gallbladder contractions. In a randomized, double-blind, cross- over study involving 12 healthy volunteers, 20 mg curcumin produced as much as 29-percent reduction in gallbladder size, indicating gallbladder contraction (statistically different than placebo). A subsequent study indicated
that doses of 40 and 80 mg curcumin produced 50- and 72-percent decreases in gallbladder volume, respectively.

Because curcumin inhibits platelet aggregation in vitro and in animal studies, it is theorized it could be additive in effect to antiplatelet medications such as aspirin, clopidogrel, and non-steroidal anti-inflammatories (NSAIDS).18,19 In a mouse model, 100 mg/kg curcumin or 25 mg/kg aspirin resulted in 60- or 61.1-percent protection from thrombosis, respectively. The concomitant use of curcumin and
anticoagulant or antiplatelet medications should be approached with caution.


Although this review discusses just two clinical studies of inflammatory bowel disease, the uses of curcumin far exceed the scope of this article. Curcumin shows promise in treating myriad disorders. It has recently been studied, at wide-ranging daily dosages of as little as 20 mg and as much as 12 g, for ailments such as psoriasis, colorectal cancer, renal graft function, pancreatitis, dyspepsia, and chronic anterior uveitis, to name a few. Larger-scale, prospective studies are needed to confirm its effect for IBD. Curcumin has an advantageous safety profile as well as low relative cost, making it an attractive option for IBD patients.

1. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “curecumin”: from kitchen to clinic. Biochem Pharmacol 2008;75:787-809.
2. Jurenka JS. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review
of preclinical and clinical research. Altern Med Rev 2009;14:141-153.
3. Hanai H, Sugimoto K. Curcumin has bright prospects for the treatment of inflammatory bowel disease. Curr Pharm Des 2009;15:2087-2094.
4. Skrzypczak-Jankun E, Zhou K, McCabe NP, et al. Structure of curcumin in complex with lipoxygenase and its significance in cancer. Int J Mol Med 2003;12:17-24.
5. Began G, Sudharshan E, Appu Rao AG. Inhibition of lipoxygenase 1 by phosphatidylcholine micelles-bound curcumin. Lipids 1998;33:1223-1228.
6. Shishodia S, Singh T, Chaturvedi MM.  Modulation of transcription factors by curcumin. Adv Exp Med Biol 2007;595:127-148.
7. Cho JW, Lee KS, Kim CW. Curcumin attenuates the expression of IL-1beta, IL-6, and TNF-alpha as well as cyclin E in TNF-alpha-treated HaCaT cells; NF-kappaB and MAPKs as potential upstream targets. Int J Mol Med 2007;19:469-474.
8. Sharma RA, Steward WP, Gescher AJ. Pharmacokinetics and pharmacodynamics of curcumin. Adv Exp Med Biol 2007;595:453-470.
9. Ireson C, Orr S, Jones DJ, et al. Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol esterinduced prostaglandin E2 production. Cancer Res 2001;61:1058-1064.
10. Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 2001;21:2985-2900.
11. Friedman S, Blumberg RS. inflammatory bowel disease. In: Fauci AS, Braunwald E, Kasper DL, Hauser SL, eds. Harrison’s Principles of Internal Medicine. 17th ed. Columbus, OH: McGraw-Hill Professional; 2008:1886- 1898. content.aspx?aID=2883197
12. Papadakis KA, Targan SR. Role of cytokines in the pathogenesis of inflammatory bowel disease. Annu Rev Med 2000;51:289-298.
13. Atreya I, Atreya R, Neurath MF. NF-kappaB in inflammatory bowel disease. J Intern Med 2008;263:591-596.
14. Hanai H, Iida T, Takeuchi K, et al. Curcumin maintenance therapy for ulcerative colitis: randomized, multi- center, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol 2006;4:1502-1506.
15. Holt PR, Katz S, Kirschoff R. Curcumin therapy in inflammatory bowel disease: a pilot study. Dig Dis Sci
16. Rasyid A, Lelo A. The effect of curcumin and placebo on human gall-bladder function: an ultrasound study. Aliment Pharmacol Ther 1999;13:245-249.
17. Rasyid A, Rahman AR, Jaalam K, Lelo A. Effect of different curcumin dosages on human gall bladder. Asia Pac J Clin Nutr 2002;11:314-318.
18. Srivastava KC, Bordia A, Verma SK. Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits aggregation and alters eicosanoid metabolism in human blood platelets. Prostaglandins Leukot Essent Fatty Acids 1995;52:223-227.
19. Srivastava R, Dikshit M, Srimal RC, Dhawan BN. Anti-thrombotic effect of curcumin. Thromb Res 1985;40:413-417.
20. Srivastava R, Puri V, Srimal RC, Dhawan BN. Effect of curcumin on platelet aggregation and vascular prostacyclin synthesis. Arzneimittelforschung 1986;36:715-717.

Tags:  inflammatory bowel disease 

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Detox - What Does that Mean?

Posted By Administration, Tuesday, June 28, 2011
Updated: Friday, April 18, 2014

IStock_000004322112Small Crop Duster

by Marsha Nunley, MD

I have gone through many changes on my journey to health: gluten-free/dairy-free diet, limited alcohol, no processed foods, bio identical hormones, many, many supplements, meditation, yoga, etc. and for me, doing a detox is the last frontier. I think I have resisted because I did not really understand and honestly, it seemed a bit daunting. Juice, shakes, and limiting food intake? Really, I love my food and because I have adrenal issues, I am used to eating frequently. Yes, I pretty much eat whole organic foods and even try to get in as many raw foods as possible, but I do love a good steak every now and then. (Sushi does not count on a raw food diet.) So let’s explore the reasons we should consider doing a detox every six months (or at least annually).

In medical school, I learned about detoxification that occurs in the body to remove waste – a part of normal bodily processes. We also learned about how the body metabolizes drugs and other foreign invaders. The assumption seemed to be that the body had a system that would readily get rid of whatever it needed to, when it needed. Not much was taught about augmenting the process of detoxification. In medicine, it is referred to as a metabolic process. To your average physician, drugs and toxins are metabolized (not detoxified), so detoxification in the sense of patient treatment is not something that your average physician will be interested in or familiar with necessarily. Not to criticize, just to let you know that if you try and talk to your family doc about detox, you will probably be met with a questioning look and dismissed. I think it is really that most doctors are simply not aware of the burden we are putting on our bodies’ detoxification capabilities.

Toxins can be classified as inner toxins, which are generated within the body, or outer toxins, which are toxins that enter the body from the outside. Inner toxins come from the body’s normal metabolic processes and from invaders, such as an infection. So where do outer toxins come from? Read this article from the Environmental Working Group about a study where they tested volunteers for 210 chemicals (San Francisco Chronicle, 2004).

“There are more than 75,000 chemicals licensed for commercial use; more than 2,000 new synthetic chemicals are registered every year; the Environmental Protection Agency has tallied close to 10,000 chemical ingredients in cosmetics, food and consumer products. The 210 we were tested for are just a few of the industrial chemicals in our world. We can surmise that the actual number of manufactured chemicals in our bodies is far greater than our results show. Very few of these chemicals were in our environment, or our bodies, just 75 years ago.

In 1998, U.S. industries reported manufacturing 6.5 trillion pounds of 9,000 different chemicals, and in 2000, major American companies — not even counting the smaller ones — dumped 7.1 billion pounds of 650 different industrial chemicals into our air and water.”

We are living in a sea of toxins and there is good evidence that it is affecting our health in a major way. Many chronic conditions such as arthritis, chronic fatigue, fibromyalgia, elevated cholesterol and triglycerides, depression, and on and on are related to our toxic world. These chemical toxins are stored in fat in the body and are likely a major contributing factor to the obesity epidemic in the U.S. and the world.
We are living in a different world from our parents and grandparents. Clearly, regular augmentation of the body’s detoxification process is essential for us to remain healthy and vital. Even though it’s not easy, I am putting regular detoxification into my health regimen and encourage you to do the same. I am currently a week into a 21-day detox. I will keep you posted on how it goes.

Good resources on detox and toxicity in our world:

Cleanse Your Body, Clear Your Mind. by Jeffrey Morrison, MD
Essential Cleansing. by Brenda Watson
Healing Digestive Illness. by Russell Mariani
Detoxify or Die. by Sherry Rogers
Environmental Working Group

Dr. Marsha Nunley is a Texas native who moved to California in 2000. She earned her medical degree from the University of Texas at San Antonio and is Board Certified in Internal Medicine. She currently practices Internal as well as Functional Medicine in San Francisco and Oakland, California. Dr. Nunley is also an expert in menopause, andropause and bio-identical hormone therapies. She has completed specialty training in Geriatric Medicine, Palliative Care, and Pain Management, and is also certified in the new area of Aging Medicine through the American Academy of Anti-Aging and Regenerative Medicine. She has completed an Associate Fellowship in Integrative Medicine at the University of Arizona, where she explored the benefits of mind-body medicine, chiropractics, acupuncture, homeopathy, craniosacral therapy, hypnotherapy, and energy healing. Visit Dr. Nunley's website at:

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Anti-Aging Lifestyle Prolongs Life

Posted By Administration, Wednesday, June 22, 2011
Updated: Friday, April 18, 2014

by Andrea Purcell, ND

In a study published in the Journal of Internal Medicine, researchers in Sweden have studied 900 men over the last 50 years and have come up with predictors of longevity. Of all of the subjects, 111 lived to 90 and had the following predictors:

  • They did not smoke
  • Moderate coffee intake < 2 cups
  • Good socio-economic status by age 50
  • Engaged in good physical work capacity at age 54
  • Low Cholesterol at age 50

In another study by the National Institutes of Health on 400,000 people showed that those who ate high fiber diets were 22% less likely to die over a nine-year period. The average American consumes 15 grams of fiber daily. Recommendations are 25g/day for women and 38g/day for men. Fiber is beneficial for heart health, respiratory and infectious disease, and cancer. Fiber’s benefits come from vitamins, micro-nutrients, and antioxidants which assist the body in detoxification and are present in whole grains, especially rice bran.

Consider Brown or Black Rice:

Most of us have heard of brown rice but black? Black rice also called forbidden rice, is nutty and chewy and filled with anthocyanins (same antioxidant found in blueberries.) This antioxidant rich food comes with all of its bran layers intact, and the black rice bran has more antioxidants per spoonful compared to blueberries along with less sugar, more fiber and more vitamin E. So go on cook up a pot tonight!

Note from Dr. P:

Reducing toxicity and body cleansing from the inside out are essential for longevity. Fiber is an essential component of this especially rice bran found in brown or black rice. Chlorophyll found in dark leafy greens is also essential in cleansing the body while providing fiber. Drop the coffee and have 2 cups of green tea instead and we have a winning combination.

Move your body! As we age we lose muscle due to inactivity and loss of hormones, this results in loss of mobility, strength and balance. In the words of Jack LaLanne “Let exercise be your king and nutrition be your queen and then you have a kingdom” Stay Healthy, Keep Moving!

-Be Happy, Healthy, & Holistic

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Hydration Nation

Posted By Administration, Tuesday, June 21, 2011
Updated: Friday, April 18, 2014


by John Gannage, MD, MCFP, DH

This article, as the warm weather arrives, is intended to provide guidance to those committed to physical activity as part of a healthy lifestyle. In the shorter term, the information will assist the prevention of electrolyte disturbances from exercise and improper fluid replacement which are common, and which can be dangerous. Long term, owing to the relationship between chronic mineral depletion and chronic disease, the article is also pertinent.

As a personal anecdote, I continue to play hockey at least twice a week in the winter months, and have found that, as I have optimized my detoxification metabolism and overall fitness, I actually sweat to a much greater degree. In recent years, this had led to a different kind of challenge for me - post-exertion fatigue and severe headaches. In fact, I was often wiped out into the next day after a particularly vigorous session, and for a while floundered trying to find the correct formula to prevent such debilitating episodes.

The answer lies in proper hydration - before, during and after exercise - with the understanding that when it comes to hydration and exercise, the rules are different compared to a non-athletic general population. My mistakes were too much plain water intake, risking low blood sodium concentration (hyponatremia), and inadequate pre-loading (i.e. entering exercise well hydrated) with fluid AND electrolytes, particularly sodium. Also, the widely available sport drinks didn't work well with me - I have since read (at that MSG is used as a flavour enhancer (not good for headache sufferers or anyone else) in some sports drinks, but have yet to confirm this.

I have had better success with a sport drink product named “e-load”, developed by a Toronto Sports Medicine specialist, Dr. Doug Stoddard. I like the formula for its sodium content and its “anti-bonking” effects. Not to be understated, it has had a huge impact on my life and allowed me to perform better, more vigorously and with longer endurance, while negating all of the previous post-exertion adverse effects. Simply, it kept me in the game.

Let it be known that dehydration is the most common performance-sapping mistake that athletes make, but it's also the most preventable. Here are some guidelines to help athletes stay well hydrated. Remember that everyone sweats differently (in sweat volume and sodium content - in fact I am likely a “high-salt sweater”) and therefore needs vary as to fluid and salt requirements before and during exercise. A general recommendation is 1 gram of sodium per hour of intense exercise.


Hydrate before exercise begins.

Drink 2-3 cups (475-700 ml) of fluid 2-3 hours before exercise to allow excess fluid to be lost as urine. This may mean drinking the evening before for early AM exercisers. About one-half hour before exercise, drink 5-10 oz (150-300 ml). Use a sports drink with adequate sodium content, as indicated below.

Drink during exercise.

Most athletes find it helpful to drink every 10 to 20 minutes during a workout. Heavy sweaters can benefit from drinking more often (e.g., every 10 minutes) and light sweaters should drink less often (every 20+ minutes).

Ingest sodium before and during exercise.

Sodium lost in sweat must be replaced during exercise. That's one reason why a good sports drink is better than plain water. Before a long endurance activity, increasing dietary salt 10 -25 grams for the few days prior is helpful.

Use weight as your guide.

The best way to determine if you'd had enough to drink during a workout is to check to see how much weight you've lost. Minimal weight loss means that you've done a good job staying hydrated. Remember that weight loss during an exercise session is water loss, not fat loss, and must be replaced.


Don't rely solely on water.

For the athlete, drinking large amounts of water is not only unnecessary, but can be downright dangerous. Drinking water alone keeps you from replacing the electrolytes lost in sweat (and from ingesting performance-boosting carbohydrates that help you train longer and stronger). Bloated stomach, swollen fingers and ankles, a bad headache, and confusion are warning signs of hyponatremia, a harmful electrolyte disturbance that can occur due to excessive water intake.

Don't gain weight during exercise.

A sure sign of too much fluid intake is weight gain during exercise. If you weigh more after your activity than you did before, that means that you drank more than you needed. Be sure to cut back for the next time.

Don't restrict salt in your diet.

Ample salt (sodium chloride) in the diet is essential to replace the salt lost in sweat. Because athletes sweat a lot, their need for salt is much greater than for non-athletes. During non-activity (or for the sedentary), I recommend a teaspoon of sea salt for every 2 litres of purified water - consumed daily.

Don't use aspirin, ibuprofen and other non-steroid anti-inflammatories
These medications increase the risk of hyponatremia in athletes, and should be avoided.


Drink adequate amounts of fluid designed for exercise, and enter your activity well hydrated while finding a drinking routine that suits your individual needs. (On the day of a hockey game, I'll drink 3.5 litres of sport drink - totalling the before, during and after fluid consumption.)

Disclaimer: The information contained in this article is for educational purposes only. One should always seek the personalized advice from a qualified practitioner before making the dietary and behaviour changes listed, as the needs and medical status of individuals are highly variable.

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Lowering Cholesterol Without Statin Medications

Posted By Administration, Monday, June 20, 2011
Updated: Friday, April 18, 2014

by Allan Magaziner, DO

Just last week, the FDA issued yet another warning regarding the use of  a statin medication, this time Simvastatin, which is frequently prescribed to lower cholesterol levels.  They noted that there is a significant risk of muscle damage (myopathy) in those patients taking high dose Simvastatin (brand name: Zocor).  In addition, the FDA warned against taking this drug along with some commonly utilized anti-fungal, antibiotic and cardiac medications.

I have always been critical of the use of high dose and, often, low dose, statin use especially in light of the numerous alternative treatments that are extremely effective.  In fact, in my previously published book, The All-Natural Cardio Cure, I highlighted many of the problems with statin drugs such as Zocor (Simvastatin), Lipitor (Atorvastatin), and Crestor (Rosuvastatin) and presented many effective options.  

Do all people with high cholesterol levels require cholesterol-lowering medications?  Of course not.  Drew, a 48 year old male, consulted with me when  struggling with seasonal allergies and a long history of sinus problems.  After a thorough evaluation, his cholesterol level was found to be high at 255 (with a normal range of 120-199) and the “bad” LDL cholesterol was also elevated at 184 (normal <99).   

Rather than starting him on a statin to lower his cholesterol, he was placed on an anti-inflammatory diet and I recommended the use of natural supplements including red yeast rice, plant sterols and omega-3 fatty acids.  

Within three short months, Drew’s lipid profile was greatly improved.  His latest total cholesterol had declined to a normal level of 177, while the LDL also fell to 101. Best of all, perhaps, Drew’s energy was better than ever, he felt his immune system was far stronger, he had not been sick at all and his allergy symptoms were completely gone...and all of this without any statin medications or any other prescription medicines!   

Drew is one of hundreds of patients who have been successfully treated at the Magaziner Center for Wellness for high cholesterol without the use of statins or other medications. 

In my opinion, statins should not be taken as first line therapy and should be used only as a last resort.  We have plenty of effective options…let’s use them. 

For more information about lowering your cholesterol level or other cardiac risk factors, contact the Magaziner Center for Wellness at 856-424-8222.

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Sickness Syndrome Depression - The Link Between Seasonal Allergies, Inflammation, and Depression

Posted By Administration, Wednesday, June 8, 2011
Updated: Friday, April 18, 2014


by Gina Nick, NMD, PhD

A recent article in the New York Times discusses several large studies that link seasonal allergies to  depression and anxiety. The cause is an increase in inflammatory cytokines that lower serotonin levels.  This is a classic example of Sickness Syndrome Depression, a condition identified years ago and finally gaining media attention.  We often see cases of wrongly diagnosed anxiety and depression at our practice where patients are prescribed antidepressant medications instead of being treated for Sickness Syndrome Depression. To learn more about the syndrome click here. One treatment that is not yet mentioned on the site but that we have recently been using successfully in practice to treat Sickness Syndrome Depression and other psychiatric illnesses with an inflammatory component is BRM4 by Daiwa Health Development- an immunomodulator that alters levels of inflammatory cytokines throughout the body. The effective dosage is 4 capsules three times per day for 4 weeks, and then 4 capsules per day thereafter.

In health and healing,

-Dr. G

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Ease Anxiety Naturally

Posted By Administration, Monday, June 6, 2011
Updated: Friday, April 18, 2014


by Andrea Purcell, ND

In this fast paced life anxiety is presenting itself in many different forms. Patients will describe nervousness, irritability, edginess, heart palpitations, difficulty breathing, hurriedness, and inability to turn off the mental motor. These are just a few descriptions that I hear daily in private practice. Stress is present, people become overwhelmed by it and then get stuck in an anxiety cycle that leads to sleeplessness and becomes very difficult to get out of.

Here are a few tools that can be used on a daily basis to help re-boot our nervous system and break the fight or flight cycle.

The top three-lifestyle ways to soothe anxiety are physical exercise, breathing exercises, and meditation.

Physical exercise has physical in the name so we forget how much it helps our mental health. Daily exercise can lift our moods, influence our food choices, which influence our moods, and act as a mental stress reliever. It helps us get out of our heads, and allows us to take a mental health break.

Deep breathing increases the amount of oxygen in the blood which acts to boost our immune system and give us more energy. It also calms down the sympathetic nervous system and in turn decreases our adrenalin output. So we feel like there is less of an emergency all the time. Breathing abdominally is better than chest breathing. I recommend the “breathing in a box technique”. Inhale slowly for 4 counts, hold your breath for 4 counts, exhale for four counts, and hold for four counts. And repeat. The slower you do it, the more you can focus on the air entering, moving through, and exiting your body. Posture is important! Sit up straight with your shoulders down and pulled back, align your neck over your spine and breathe. Poor posture promotes shallow breathing and more anxiety.

Meditation is a daily practice just like exercising and breathing. Many patients say that they have difficulty completely emptying their mind and find this practice hard to do. My recommendation is to get yourself a tape that will take you through a very short say 1 minute meditation to begin and then expands as you practice your meditation muscle. The Chopra Center has free online meditations; they gradually introduce a new-comer to meditation.
You do have to subscribe to their free online library.

Supplements to use when you are overwhelmed:
Rescue remedy by Bach flower
Calms forte –homeopathic remedy for an over stimulated nervous system.
Double bag of chamomile tea
L-theanine – found in green tea it has calming properties. 200mg capsule, 1-2 capsules usually help take the edge off.

Note from Dr. P
Stress is here to stay, so we all need to get a game plan that works for us to manage stress on a regular basis. I recommend calendaring everything, yes, even exercise. Items on your calendar will not get pushed to the side they will get done with everything else. Every woman I know has a daily list of items to accomplish that is greater than what is humanly possible. Have the immediate list and then the list that can be done over more time. I call it my doing “now” list and my “not” doing now list.
Another stress reduction tip is to be present! The gift is in the present! The present is all we have, so enjoy it, soak it up like a good piece of Italian bread in garlic and oil, ummm, that will help diffuse the anticipation of what is next on the to do list.
Finally, if you find that you just can’t keep it together, and that your day is running you instead of you running your day, there could be other factors that need to be evaluated by a trained professional. You may have a hormonal imbalance and need good council by an integrative doctor. So get the help, get balanced, and get on with your life!

-Be Happy, Healthy & Holistic

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Case Study - Neuroendocrine and Immune Contributors to Fatigue

Posted By Administration, Friday, June 3, 2011
Updated: Friday, April 18, 2014

Marni N. Silverman, PhD, Christine M. Heim, PhD, Urs M. Nater, PhD, Andrea H. Marques, MD, PhD, and Esther M. Sternberg, MD
Central fatigue, a persistent and subjective sense of tiredness, generally correlates poorly with traditional markers of disease. It is frequently associated with psychosocial factors, such as depression, sleep disorder, anxiety, and coping style, which suggest that dysregulation of the body's stress systems may serve as an underlying mechanism in the maintenance of chronic fatigue (CF). This article addresses the endocrine, neural, and immune factors that contribute to fatigue and describes research regarding the role of these factors in chronic fatigue syndrome as a model for addressing the biology of CF. In general, hypoactivity of the hypothalamic-pituitary-adrenal axis, autonomic nervous system alterations characterized by sympathetic overactivity and low vagal tone, as well as immune abnormalities, may contribute to the expression of CF. Noninvasive methods for evaluating endocrine, neural, and immune function are also discussed. Simultaneous evaluation of neuroendocrine and immune systems with noninvasive techniques will help elucidate the underlying interactions of these systems, their role in disease susceptibility, and progression of stress-related disorders.
Fatigue comes in various forms. Acute fatigue is a normal, protective mechanism in healthy individuals, is usually linked to a single cause, and is often relieved by rest or life-style change (ie, diet, exercise, rest, stress management). Rarely is it associated with long-term cognitive dysfunction, a state that most often returns to baseline after rest and recovery. However, chronic fatigue (CF) is considered maladaptive or pathologic, lasts 6 months or more, adversely affects physical and mental function, and may have multiple and unknown causes. Generally, no relief is gained from usual restorative measures aimed at relieving fatigue [1]. CF is especially apparent in individuals with chronic disease, such as autoimmune diseases (rheumatoid arthritis [RA], multiple sclerosis, systemic lupus erythematosus [SLE]), psychiatric disorders (major depressive disorder [MDD]); neurologic disorders, eg, stroke; cancer (during and after treatment); and idiopathic chronic multisymptom illnesses, eg, chronic fatigue syndrome [CFS] and fibromyalgia (reviewed in [2]). Peripheral fatigue is observed in chronic diseases associated with muscle wasting and inflammation or joint abnormalities, as often occurs in RA and SLE, myasthenia gravis, and cardiorespiratory diseases. Peripheral fatigue can be attributed to organ-system dysfunction and usually is not associated with cognitive loss.
Central fatigue generally correlates poorly with traditional markers of disease [2] and is frequently associated with other psychosocial factors, such as depression, sleep disorder, anxiety, and coping styles [3,4], which suggests that dysregulation of the body's stress systems may serve as an underlying mechanism of CF. Indeed, there appears to be an intricate interplay between the neural, endocrine, and immune systems in regulating the body's response to stress and the maintenance of homeostasis.

That the nervous and immune systems communicate with each other in a bidirectional manner is well established (reviewed in [5-12]). There are 2 main pathways by which psychogenic stress is relayed from the brain to the body: (1) via the hypothalamic-pituitary-adrenal (HPA) axis with the resultant release of glucocorticoids (cortisol in humans and primates; corticosterone in rodents) and (2) via the sympathetic nervous system (SNS), with the resultant release of catecholamines (noradrenaline and adrenaline). These neuroendocrine stress systems coordinate the response of many other physiologic systems to a stressor, including the immune and cardiovascular systems, as well as energy production and/or utilization and behavior, therefore, bringing the physiologic systems back to homeostasis [13].
However, maintenance of homeostasis during an immune challenge involves activation of the immune system, resolution of the challenge, and protection of the host against potentially detrimental inflammatory processes. Relevant to the latter, interleukins (IL) and/or cytokines (tumor necrosis factor [TNF]-α, IL-1, and IL-6 in particular) activate the same stress pathways to coordinate an appropriate immune response [5,6,12]. Cytokine receptors have been detected at all levels of the HPA axis, and, therefore, each level can serve as an integration point for immune and neuroendocrine signals [5]. In turn, glucocorticoids negatively feedback onto immune cells to suppress the further synthesis and release of innate proinflammatory molecules. Glucocorticoids also shape immunity by influencing immune cell trafficking to sites of inflammation and alter downstream adaptive immune responses by causing a shift from cellular (Th1 inflammatory) to humoral (Th2 anti-inflammatory) type immune responses [14,15]. Therefore, in contrast to the traditional view of glucocorticoids as immunosuppressant hormones, a more accurate view is that they are immunomodulatory hormones that stimulate as well as suppress immune function, depending on glucocorticoid concentration, type of immune response, immune compartment, and cell type. Glucocorticoids also play an important role in the regulation of the SNS. In addition to subserving permissive effects on relevant synthetic enzymes and receptors for catecholamines, endogenous glucocorticoids restrain SNS responses under resting conditions and after stress [16].
In addition to HPA axis-immune interactions, there is strong evidence for interactions between the immune system and the autonomic nervous system (ANS) (SNS and parasympathetic nervous system [PNS] pathways) and peripheral nerves. Whereas, circulating hormones, such as glucocorticoids, regulate immunity at a systemic level, neural pathways regulate immunity at a local and regional level. The SNS and peripheral nervous system innervate immune organs, where sympathetic influences can be both pro- and anti-inflammatory, depending on the type of adrenergic receptor to which the catecholamine binds [8,9]. Neuropeptides released from peripheral nerves, such as substance P, tend to be proinflammatory [7]. Locally released norepinephrine or circulating epinephrine also affect lymphocyte trafficking, proliferation, function, and cytokine production. With regard to the peripheral nervous system, both afferent and efferent parasympathetic activities have been shown to be immunomodulatory. Whereas, afferent vagal fibers express IL-1 receptors on paraganglia cells situated in parasympathetic ganglia [12], efferent vagal fibers have been shown to exert anti-inflammatory action via the release of acetylcholine [10, 11]. Therefore, the vagus nerve also serves as a source of negative feedback on the immune system, with the brain being an integral relay station.
Dysregulation of any of these stress systems can lead to dysregulation of multiple physiological and behavioral systems, which leads to a maladaptive response to stress [13-17]. Indeed, dysregulation of neural-immune interactions is described in many stress-related disorders, including inflammatory, autoimmune, metabolic, and cardiovascular disease, as well as psychiatric and somatic disorders.
The capacity of proinflammatory cytokines to cause changes in behavior, including symptoms of fatigue, psychomotor retardation, anorexia, anhedonia, hyperalgesia, somnolence, lethargy, muscle aches, cognitive dysfunction, and depressed mood, has led to the suggestion that proinflammatory cytokines may contribute to the behavioral features of depression [18,19] as well as somatic disorders, such as CFS and fibromyalgia [20].
The first indication that inflammation may induce psychosomatic symptoms came from research about depression. There is a strong similarity between neurovegetative symptoms (anorexia, sleep disturbance, psychomotor retardation, fatigue, and pain) of depression and inflammation-induced sickness behavior [21]. Indeed, cytokine-based immunotherapy (interferon [IFN]-α) induces 2 distinct behavioral syndromes: a neurovegetative syndrome, which appears early, persists, and is minimally responsive to classical antidepressants; and a mood-cognitive syndrome, characterized by depressed mood, anxiety, and cognitive dysfunction, which appears later and is responsive to classic antidepressants (ie, selective serotonin reuptake inhibitors [SSRIs]) [22]. Moreover, differential clustering of mood-cognitive and neurovegetative syndromes is observed in patients with cancer. Indeed, cancer-related fatigue does not respond well to antidepressants, which suggests that it is not exclusively a mood or behavioral problem. [23]. Of note, cancer-related fatigue has also been associated with elevated inflammatory biomarkers and impaired HPA axis function [24,25].
It appears that these 2 categories of symptoms are mediated by different biological mechanisms. For example, dopaminergic pathways may play a more prominent role relative to other monoamine neurotransmitters (serotonin, norepinephrine) in the neurovegetative subset [3,22]. In support of this notion, Meeusen et al [26] proposed a central fatigue hypothesis and suggested that an increase in the brain ratio of serotonin to dopamine is associated with feelings of tiredness and lethargy, which accelerates the onset of fatigue, whereas, increased dopamine levels favor improved performance through the maintenance of motivation and arousal.
Given the role of corticotropin-releasing hormone (CRH) in behavioral and HPA-axis activation, it has been hypothesized that defective central CRH synthesis and/or release may also contribute to symptoms of fatigue [27]. Indeed, abnormal central CRH pathways have been detected in various chronic disease states with a fatigue component, including SLE, multiple sclerosis, RA, fibromyalgia, and CFS [2,27]. Moreover, both psychogenic and immune stressors can induce similar neuroendocrine and neurotransmitter changes in the brain, therefore, sensitizing the brain to subsequent stressors, and, hence, inducing a state of increased stress vulnerability as seen in various psychiatric and psychosomatic disorders [28].
In the next section, we discuss how hypoactivity of the HPA axis, ANS alterations characterized by sympathetic over-activity and low vagal tone, as well as immune abnormalities, may play a role in CFS.
A diagnosis of CFS requires that an individual displays severe CF for more than 6 months without a defined cause (with all other medical conditions being excluded), as well as the presence of 4 of the following 8 symptoms: myalgia, arthralgia, sore throat, tender nodes, cognitive difficulty, headache, postexertional malaise, or sleep disturbance [29]. (See Clauw later in this supplement.)
HPA Axis
A substantial body of research on the pathophysiology of CFS has focused on dysregulation of the neuroendocrine systems. The HPA axis is the key neuroendocrine system that adapts the organism to various challenges, including emotional, physical, chemical, and immune stressors. These stressors have been associated with risks for developing CF. The secretion of glucocorticoids from the adrenal cortex results in multiple metabolic, behavioral, and immune regulatory responses that help the organism adapt to such challenges. Dysregulation of these regulatory functions may be causally associated with symptoms of CFS. Thus, insufficient glucocorticoid signaling has been associated with increased immune activation and inflammatory responses, potentially promoting symptoms of fatigue, malaise, somnolence, myalgia, and arthralgia (reviewed in [13,17]).
Dysfunction of the HPA axis, characterized by lower than normal cortisol secretion, is one of the hallmark biological features of CFS, although the literature is somewhat inconsistent. Poteliakhoff [30] first described attenuated basal plasma cortisol levels in patients with CFS. After these initial observations, Demitrack et al [31] reported lower than normal cortisol excretion in patients with CFS. Results of several subsequent studies confirmed lower than normal cortisol levels in plasma or saliva [32-39], flattened cortisol diurnal secretion [38-40], and decreased urinary free cortisol secretion in patients with CFS [41-44].
However, results of a substantial number of studies failed to identify hypocortisolism in CFS (eg, reviewed in [45-46]). Similarly, results of an array of endocrine challenge studies revealed signs of hypocortisolism in CFS, including enhanced negative feedback inhibition of the pituitary [47-50] or mild adrenal insufficiency [31,51], although results are inconsistent [45,46]. Results of a recent study found decreased glucocorticoid sensitivity of immune cells in persistently fatigued adolescent females [52], which suggests decreased cortisol signaling, consistent with the idea of a lack of cortisol effects contributing to CFS. However, in vitro studies on glucocorticoid sensitivity are also inconsistent [53]. Of note, glucocorticoid sensitivity was shown to be regulated in a tissue- and cell-specific manner (reviewed in [6]).
There may be important subgroups of patients with CFS, depending on etiologic pathways or clinical features. Heim et al [54], for example, demonstrated, in a population-based sample, that only those patients with CFS who reported childhood traumatic experiences exhibited low cortisol levels compared with well controls, whereas patients with CFS and without a history of severely stressful circumstances had normal cortisol levels. Thus, it is plausible that several of the neuroendocrine features of CFS covary with risk factors other than illness state and reflect a vulnerability to develop CFS in response to challenge [54]. Of note, hypocortisolism, as reported in patients with CFS, has been observed in animal models of early life stress (reviewed in [55]). Thus, CFS could be conceptualized as a disorder of adaptation that is promoted by developmental risk factors.
Some researchers have suggested that hypocortisolism in CFS might be a consequence of having the disorder, because low cortisol secretion has been associated with illness features, for example, inactivity [56]. In addition, the stress of symptoms themselves, such as fatigue, sleep and mood disturbances, and pain, can contribute to the further dysregulation of biological stress pathways, which lead to a positive feed-forward cascade. Whether or not hypocortisolism is a cause or a consequence of CFS remains to be evaluated in longitudinal studies. Perhaps it is both.
A number of studies examined the involvement of the ANS in the pathophysiology of CFS. The rationale for these studies is based on the observation that several symptoms of CFS, namely fatigue, dizziness, diminished concentration, tremulousness, and nausea, could be explained by autonomic dysfunction. In addition to the neuroendocrine system, the ANS is another key regulation system that adapts the organism to challenge. Thus, autonomic dysregulation could further trigger symptoms of CFS in response to challenges that disturb homeostasis.
Initial studies found an increased prevalence of neurally mediated hypotension and orthostatic intolerance in patients with CFS, measured by using a prolonged standing or a head-up tilt table test [57-64]. However, results of several studies failed to find differences between CFS and control groups regarding dysautonomia [65-68].
Another line of research in the study of ANS alterations in CFS has focused on cardiovascular autonomic measures. Results of most studies found increased heart rate measures in CFS, both at rest and in response to challenge [65,69-74]. Increased heart rate and/or reduced heart rate variability (HRV) is in accordance with other studies that reported low vagal tone [69,75-77] or general sympathetic overactivity [62,78-80], although inconsistent results exist (reviewed in [46]). Whether or not there are subgroups with CFS and altered autonomic function based on etiologic factors or illness features is unknown. Sympathetic overactivation, in concert with low glucocorticoid signaling, may contribute to an overactive immune system, particularly in response to challenge, which may lead to symptoms of CFS.
Immune System
Many findings suggest that infectious agents (viral and bacterial infections) and immunologic dysfunction (eg, inappropriate production of pro- and anti-inflammatory cytokines) may play a role in the pathophysiology of at least some cases of patients with CFS (reviewed in [81-83]). Indeed, persistent postinfection fatigue has been well documented [84]. Results of early studies showed that many individuals with CFS had evidence of enhanced antibody responses to Epstein-Barr virus (EBV). However, subsequent reports showed that many patients with CFS lacked evidence of EBV reactivity, although they displayed elevated antibody titers to a number of other viral agents. Interestingly, acute viral infection studies found that initial infection severity was the single best predictor of persistent fatigue [85]. Taken together, results of these studies suggest that, although some cases of CFS may be triggered by an infectious agent, the chronic symptoms of this syndrome are unlikely to be caused by an active infection.
Results of other studies indicated signs of immune disturbance in patients with CFS, especially in the form of elevated proinflammatory cytokine levels [86,87], such as IL-6 and TNFα in serum and cerebrospinal fluid [88,89]. Consistent with these findings, increased in vitro inflammatory cytokine release has been reported in stimulated peripheral blood mononuclear cells of patients with CFS [90]. Other indices of cytokine-mediated immune alterations that have been reported in patients with CFS include increased levels of auto-antibodies, decreased natural killer cell activity, high levels of type 2 cytokine–producing cells, activated T lymphocytes, CD19+ B cells, neopterin (a marker of activated cell-mediated immunity), and activated complement [91-94]. In addition, alterations in the expression of genes involved in immunity have been detected [95]. However, despite multiple indications of immune system activation in CFS, the best-replicated immunologic findings in this disorder are suppression of several immune functions, especially natural killer cell activity and mitogen-induced lymphocyte proliferation [94-96]. Nonetheless, these multiple findings need to be interpreted in light of a meta-analysis [81] that found no evidence for clear immune abnormalities in CFS.
Interestingly, results of a recent and robustly designed study by Raison et al [97] showed that fatigue not only in its severe and chronic form, as in CFS, but also in its milder forms, is associated with increased inflammation, as indexed by elevated plasma C-reactive protein levels and white blood cell count, even after adjusting for depressive status. This study further supports the notion that the symptom of fatigue, rather than a diagnosis of CFS itself, may be what is clinically associated with inflammation. In addition, childhood traumatic experiences appear to be an important risk factor for a hypocortisolemic profile in CFS [54], and adults with a history of childhood trauma exhibit elevated markers of inflammation, even in the absence of depression [98]. Moreover, patients with depression and childhood trauma show even higher levels of inflammation than with either risk factor alone [98,99]. Whether immune status is different in patients with CFS, with or without a history of childhood trauma, remains to be determined.
In summary, chronic (pathologic) fatigue can be attributed to hypoactivity of the HPA axis; ANS alterations characterized by sympathetic overactivity and low vagal tone; and immune abnormalities, including reduced cellular responses and enhanced inflammation and humoral responses. CFS is an exemplar, but not the only example, of fatigue conditions, with these associations. Disparate findings among various studies may be because of (1) differences in methodology, recruitment, and analysis; (2) comorbidities, including depression and/or other chronic diseases; (3) lack of an epidemiologically comparable control group; and (4) biological changes not present in all cases of a heterogeneous disorder, such as CFS, but rather related to particular symptoms or risk factors of the disorder. The latter indicates the importance of grouping by symptom subtypes rather than an arbitrarily defined disorder. Indeed, different symptom categories of CFS may be mediated by different biological mechanisms, as seen in cytokine-induced depressive symptomatology [22]. To help elucidate a “molecular signature” for clinical sub-types within a heterogeneous disorder, noninvasive methods for evaluating neural, endocrine, and immune function are available without causing further pain or distress, which could confound outcome measures of interest.
Measurement of hormones, cytokines, and neuroactive substances has frequently posed a problem for clinicians and investigators because of the need to perform invasive tests, such as drawing blood. Noninvasive and ambulatory methodologies of neural, endocrine, and immune biomarker collection can overcome several limitations intrinsic to invasive methods, reducing the stress triggered by collection of samples and allowing a wider application to community-based settings. Collection of sweat and saliva and measurement of HRV are noninvasive methods that can be applied to evaluate neuroimmune interactions. Ultimately, simultaneous evaluation of neural and immune systems with noninvasive techniques will help elucidate the underlying interactions of these systems and their role in disease susceptibility and progression of stress-related disorders.
HPA Axis: Salivary Cortisol
Because (1) the HPA axis is a self-regulated dynamic feedback system and (2) cortisol is secreted in a pulsatile fashion, single time-point measures of cortisol cannot be used to accurately interpret HPA axis function. An adequate assessment of HPA axis function requires multiple serial sampling (to test basal activity and circadian profiles) or dynamic testing by using pharmacologic or psychologic challenges (to test reactivity and/or feedback sensitivity). More recently, the salivary cortisol response to awakening has received considerable scientific attention and has been shown to be sensitive to detect HPA axis dysregulation related to stress and disease, including CFS [39,100]. When collected in the context of such sampling protocols, cortisol can be reliably measured in saliva as an index of HPA axis function [101].
The majority of circulating cortisol is bound to corticosteroid-binding globulin, which inactivates the biological actions of cortisol. Only the free fraction of cortisol is biologically active and can bind to glucocorticoid receptors to influence gene expression and protein synthesis. In saliva, only the free fraction of cortisol can be measured. Free cortisol measures in saliva reliably reflect the amount of free cortisol circulating in the blood stream [101]. In studies that focus on the actions of cortisol in target systems, it is advantageous to measure the free and biologically active fraction of cortisol. However, for studies that focus on assessment of total cortisol output of the adrenal gland or ratios of bound versus unbound cortisol and corticosteroid-binding globulin activity, blood measures are necessary. These differences must be considered when interpreting data from salivary cortisol studies.
ANS: Salivary α-Amylase and Heart Rate Variability
Because the transfer of norepinephrine from blood to saliva takes approximately 1 hour [102], which is too long for accurate assessment of stress-induced changes, salivary α-amylase (sAA), a digestive enzyme, has become an emerging biomarker for stress as an indicator of SNS activity. Both the sympathetic and parasympathetic branches of the ANS innervate the salivary glands, where SNS stimulation increases protein secretion and PNS stimulation increases salivary flow rate [103]. sAA has repeatedly been found to increase in response to physical stress or exercise, as well as psychological stress, and also correlates with plasma norepinephrine responses to those same stressors, although to a lesser extent to psychosocial stress (reviewed in [104]). sAA concentration can also serve as an index for pathologic dys-regulation of the ANS in specific clinical and subclinical conditions, such as anxiety and somatic disorders [104]. One important caveat of measuring sAA is that, in the presence of stress and SNS activation, the PNS is inhibited, which leads to reduced salivary flow rate, and hence, decreased saliva production. Therefore, stress-induced increases in sAA could be confounded with parallel decreases in salivary volume, thereby increasing sAA concentration.
Evaluation of the ANS can also be performed noninvasively through measurement of HRV. The heart is under tonic control by parasympathetic influences. Heart rate is characterized by beat-to-beat variability, which also implicates vagal dominance, because the sympathetic influence on the heart is too slow to produce rapid beat-to-beat variability. HRV is a term that describes variations of both instantaneous heart rate and the interval between consecutives beats. A prominent circadian variation in HRV, with significant increases during the night and decreases during the day, is observed in healthy individuals. Results of previous studies showed that this increase in nighttime HRV is blunted by acute stress and that decreased HRV is associated with increased overnight urinary cortisol and increased proinflammatory cytokines and acute-phase proteins [105]. Decreased HRV, indicative of reduced parasympathetic-vagal tone, is an independent risk factor for morbidity and mortality.
Neural and Immune Biomarker Profiles: Cutaneous Sweat Patch
Another noninvasive and nonstressful approach to evaluating neural and immune systems is through collection of sweat via a 24-hour cutaneous sweat patch. In our initial validation studies, we showed that immune biomarkers, such as proinflammatory cytokines, in sweat were tightly correlated with plasma levels in healthy women [106]. In addition, we have shown that a population of women with MDD in remission exhibited elevated sweat levels of proinflammatory cytokines, sympathetic neuropeptides (neuropeptide-Y), and pain-related neuropeptides (substance P, calcitonin gene–related peptide) but decreased parasympathetic (vasoactive intestinal peptide) neuropeptide levels relative to controls, which strongly correlated with plasma levels [107]. This pattern is consistent with a shift in MDD from parasympathetic to sympathetic tone and an underlying proinflammatory state that could account for enhanced susceptibility to conditions known to be comorbidly expressed with MDD, including cardiovascular disease, osteoporosis and diabetes. Moreover, biomarker levels strongly correlated with symptoms of depression and anxiety, which indicate functional significance of these biomarker profiles. A similar biomarker profile was reported in pain- and fatigue-related syndromes [2].
Ultimately, these noninvasive methodologies could provide a “molecular signature” for clinical subtypes within a heterogeneous disorder to be used for (1) diagnostic and prognostic purposes; (2) earlier intervention in asymptomatic conditions; (3) optimization of individualized treatment regimens; (4) patient monitoring in remote areas and in large-scale epidemiologic settings; (5) monitoring patients in whom invasive methodologies are unfeasible, especially vulnerable populations, including pregnant women, infants, children, and the elderly; and (6) to shed light on mechanisms that underlie individual vulnerability or resiliency to develop stress-related diseases and/or disorders.
In summary, CF states have been shown to be attributable to a dysregulation of stress systems, including hypoactivity of the HPA axis, ANS alterations characterized by sympathetic overactivity and low vagal tone, and immune abnormalities, such as reduced cellular responses and enhanced inflammation and humoral responses. Hypocortisolemia may develop through reduced synthesis or depletion of HPA-axis hormones, receptor downregulation, and/or increased negative feedback sensitivity [108]. Fries et al [108] proposed that the phenomenon of hypocortisolism may occur after a prolonged period of hyperactivity of the HPA axis because of chronic or traumatic stress, in which this “switch“ may prevent possible deleterious effects of excessive glucocorticoid exposure. CFS and related pain and fatigue disorders may then be interpreted as a maladaptive overadjustment, in which the HPA axis is then functioning at an alternate, more stress-sensitive steady state [109]. Interestingly, the consequences of insufficient glucocorticoid signaling, including hyperactive SNS activation and enhanced inflammation, result in similar deleterious effects to that of hyperactive glucocorticoid signaling, such as altered metabolic, cardiovascular, immune, neurologic, and behavioral functions [17], including the potentiation of fatigue and related symptoms. Given the complex nature of fatigue, with its many physiologic and behavioral risk factors and correlates, the most effective therapeutic strategy may require multimodal action. The simultaneous evaluation of a large array of neural, endocrine, and immune biomarkers, when using noninvasive methodologies, may help inform the design of more effective pharmacologic therapeutic interventions to be used along with nonpharmacologic interventions, such as cognitive-behavioral therapy. It may also inform clinicians of mechanisms by which these interventions act and how successful they are in altering the neuroendocrinologic and immunoregulatory aspects of fatigue.
Contributor Information
Marni N. Silverman, Section on Neuroendocrine Immunology and Behavior, National Institute of Mental Health, National Institutes of Health, Rockville, MD.
Christine M. Heim, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA.
Urs M. Nater, Department of Clinical Psychology and Psychotherapy, University of Zurich, Switzerland, Centers for Disease Control and Prevention, Atlanta, GA.
Andrea H. Marques, Genetic Epidemiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD.
Esther M. Sternberg, Section on Neuroendocrine Immunology and Behavior, National Institute of Mental Health, National Institutes of Health, Integrative Neural Immune Program, 5625 Fishers Lane (MSC-9401), Rockville, MD 20852.
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Bran Cancer Risk from Cell Phone Use

Posted By Administration, Thursday, June 2, 2011
Updated: Friday, April 18, 2014


by Nalini Chilkov, LAC, OMD

A scientific report released Tuesday by the World Health Organization concludes radio frequencies and electromagnetic fields – including those routinely emitted by mobile phones – are “possibly” carcinogenic to humans.

The World Health Organization and its subsidiary investigative panel, the International Agency for Research on Cancer, or IARC, stated today what many scientific studies have been suggesting for decades: that there is a possible connection between mobile phone use and malignant brain tumors.  Dr. Jonathan Samet, who heads IARC’s Working Group of 31 international scientists from 14 countries, made the announcement at the conclusion of the group’s week-long meeting in Lyon, France.

“The working group classifies the radio and electromagnetic fields as possibly carcinogenic to humans; that is within the classification used by the International Agency for Research on Cancer,” he said.

The group advised that, because five billion people around the world currently use mobile phones, therefore, much further research in the subject is needed.  The report places at most risk those with the greatest use of cell phones and exposure to other sources of radiation. ”We also carefully consider the sources of exposure of populations to radio frequency electromagnetic fields, the nature of these fields as they come from various devises, including wireless phones, and we look carefully at the physical phenomenon by which exposure to such fields may perturb biological systems and lead to cancers,” he said.

The IARC working group had gathered in France for the past eight days, reviewing all previous studies done on electromagnetic radiation’s effects on humans and animals over the past decade.

Health advocacy groups that have been warning of possible cell phone-cancer links are praising the WHO pronouncement.

Camilla Rees, the founder of a U.S. based group called Electromagnetic Health, says she is pleased but said much more needs to be done. ”They focused on brain cancer, and brain cancer includes a relatively small number of people.  But we only have had this technology for about 15 years and most carcinogens will take several decades before they develop into a cancer.  Early indicators from scientists are projecting a tsunami of brain cancer unless we do something to educate people to lower their exposure,” she said.

Rees says there are many other health effects of radiation, including damage to human cell tissue, that the World Health Organization has yet to recognize. But for now, she believes the most urgent need is to begin a campaign to protect children from the effects of electromagnetic fields, and in  particular, from cell phones.

“What microwave radiation does in most simplistic terms is similar to what happens to food in microwaves, essentially cooking the brain,” said Dr. Keith Black, chairman of neurology  and world class brain surgeon at Cedars-Sinai Medical Center in Los Angeles. “So in addition to leading to a development of cancer and tumors, there could be a whole host of other effects like cognitive memory function, since the memory temporal lobes are where we hold our cell phones.” Dr Black recommends using ear buds or texting to keep the cell phone away from the head.

While wireless carriers instruct users to keep cell phones a certain distance from their heads, such as Apple’s iPhone 4 safety manual that says to keep the device at least 15 millimeters from the body, CTIA – The Wireless Association noted that WHO’s announcement does not mean that cell phones cause cancer. In addition, the association denounced WHO’s results since it “did not conduct any new research, but rather reviewed published studies.”

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My Kid has ADD/ADHD

Posted By Administration, Tuesday, May 31, 2011
Updated: Friday, April 18, 2014


by Matt Angove, ND, NMD

No doubt, genetic susceptibility plays into the whole ADHD paradigm but that goes for everything. Whatever your state of being, good or bad has to do with how you bathe your genes.

I find it to be a modern day miracle that more people aren’t suffering from ADHD, depression, anxiety disorders, bipolar, schizophrenia, and the like considering the laboratory derived concoctions we douse our bodies with daily.

Before you put your child on Ritalin, a compound that has marked similarities to amphetamines and actions consistent with cocaine, just dampened somewhat, let us consider our options.

Let us Consider

Consider the Red No. 40, Yellow No. 5, MSG, aspartame, Splenda, partially hydrogenated oils, high fructose corn syrup, soybean oil (Is there anything in a box it is not in?), caffeine (Monster drinks, Red Bull, Soda, coffee), phosphorus (soda pop) and refined sugars.

Consider the refined foods and naked grains they are consuming.

Consider the hormone buffed and corn stuffed meats they are putting on their sandwiches.

Consider the hours of reckless television and video games that are being sprayed across their eyes and mind.

If you or your child is consuming items such as JELL-O, Lucky Charms, Pop-Tarts, Butterfinger bars, Skittles, Hostess Twinkies or Frito-Lay Doritos, to name a few, you should fully expect marked neurological dysfunction.  It is only natural!!!

Nutritionally based therapies for ADHD can be EXTREMELY beneficial!!!  Understand that 8-10% of school age children are considered to be in this spectrum.  So, there are plenty of children who are suffering and in most cases, I would suggest needlessly.

Available therapies


Avoidance of possible food sensitivities (start with gluten, refined sugars, dairy, chocolate, citrus, peanuts, eggs, soy) –an elimination and reintroduction diet may be in order.

Elimination of synthetic sweeteners, colors and whatever isn’t FOOD from the diet.

Evening Primrose oil coupled with Fish Oil

Flaxseed oil with Vitamin C

Nutrient optimization ( Magnesium, Zinc, Calcium, Iron, Potassium, B vitamins)


Amino acid combination’s (as monitored by your health provider)

Lifestyle is High Style

You have to realize that getting ADHD under control isn’t an overnight affair.  Just like any other chronic condition, you must set forth and live out a lifestyle conducive to the sustaining of life.  I know it is not easy.  Our current available knowledge state has given everyone the opportunity for abundant health.  However, the societal pace rarely allows us to utilize and practice that knowledge.

You simply have to choose what lane you want to live in.

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Gluten Free - The Latest Fad Diet

Posted By Administration, Wednesday, May 25, 2011
Updated: Friday, April 18, 2014


by Andrea Purcell, ND

The shocking news in 2003 was that 1 in 133 people had celiac disease. Celiac disease is a genetic intolerance to gluten contained in wheat, rye, and barley. Eating and cooking gluten free means consuming a whole food diet devoid of gluten containing grains.

Celiac disease once considered rare, is now a common autoimmune disease afflicting 1 in 133 people. If you or a loved one has Celiac disease there is a good chance that first and second-degree relatives have the diagnosis as well. As a medical necessity, there are three groups of people who should avoid gluten.

*Any person with a diagnosis of Celiac disease.

*Any person with an allergic reaction to wheat as determined either by an IgG or an IgE blood test.

*Any person with gluten sensitivity.

Many people are sensitive to wheat and/or gluten but do not have the diagnosis of celiac disease. Sensitivities can cause symptoms such as skin reactions, congestion in the throat, ears, or sinuses, digestive upset, or other body inflammation such as fatigue and aching joints. A recent study in 2010 found that people could lose their tolerance to gluten as they age. These people are not born with the genetic intolerance commonly seen with celiac disease but are developing the intolerance later on in life. This suggests a weakening of digestive function due to repeated exposure to gluten, which can cause leaky gut, toxin exposure, antibiotics, medications, and even vaccines.

The information about gluten and the awareness around celiac disease seems to have thrown the nation into a gluten free frenzy. Many people are eating gluten free as a type of fad diet. These people have heard that gluten is bad and have chosen to avoid it as a way to be healthy. As the awareness builds so does the variety of gluten free products. It is easier than ever to find gluten free cake, cookie, brownie mixes, breads, need I say more? Even if you are going gluten free filling your day with these will not bring you closer to health. Moving towards a plant-based diet however, will.


Cooking Gluten Free…

For those first diagnosed with Celiac disease the act of cooking and eating initially becomes very stressful. Learning a few tried and true recipes that you know you can whip up in a flash will be extremely helpful.

The first thing you should do when you find out that you need to eat gluten free is to focus on a plant based diet. This includes vegetables, fruits, nuts, seeds, and lean proteins. These foods will become the foundation of your daily food plan.

Experiment with alternative grains such as brown rice, wild rice, quinoa, amaranth, buckwheat, sorghum, and teff.

There are many benefits to home cooking. You have complete control over what you eat and the quality of ingredients, plus there will always be leftovers for lunch the next day, hooray!

Baking Gluten Free…

Cooking is one thing and baking is another. The general rule of thumb for mastering any gluten free baked good recipe is to experiment with the recipe at least three times. The first will be a flop, the second will be better, and you will try a different flour, moisture ingredient or sweetener, and by the third try you will be satisfied. Then you can actually bring the finished product to a social gathering. Making a bread or cupcake with one type of flour is not recommended, the success in baking gluten free comes from mixing the flours. You can mix bean flour with a gluten free flour to help with the texture. In gluten free baking many things can come out dry and crumbly so items must be added that create more moisture. These items could be mashed banana, tofu, honey, eggs, pumpkin, or xantham gum. In order to succeed you must experiment with a variety of flours. Become familiar with the tastes and textures of the alternative flours, then you can combine them. Once you master the moisture content, then you can experiment with the level of sweetness. Many recipes just have you add plain old white sugar but I prefer stevia, agave, brown rice syrup, honey or a combination of two sweeteners to reduce the calorie and sugar content of the recipe.

Note from Dr. P

In order to determine if you are sensitive to gluten you can do this simple experiment at home. Avoid all gluten for 14 days. This means all gluten. Read labels carefully because many items contain hidden gluten such as cereals, deli meats, and canned soups. After 14 days reintroduce gluten containing foods 1-2x daily for three days in a row. Observe your body for any signs of gluten sensitivity that I listed above. Looking for healthy gluten recipes? Get my book!


-Be Healthy, Happy, & Holistic

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You Have a Right to Make Healthy Choices!

Posted By Administration, Wednesday, May 18, 2011
Updated: Friday, April 18, 2014

It's no secret that pesticides are harmful to humans and the environment. According to the National Institutes of Health, pesticides are linked to diabetes, Parkinson's Disease, cancer and more. Below is a letter from the Environmental Working Group that invites you to sign their petition to urge the FDA not to cave in to the chemical agribusiness's campaign to limit the public's information to pesticides.

Dear Friend,

Since 1991, the U.S. Department of Agriculture has been testing fresh produce for pesticide residues and releasing the findings. Environmental Working Group analyzes these detailed technical reports to produce our Shopper's Guide to Pesticides. But this year, the USDA may cave in to an industry campaign to alter the results and give consumers less information. That's bad news for us all.

Chemical agribusiness interests have launched an expensive all-out campaign to silence EWG and deny you information you need to make healthy choices. Just last year, nearly $200,000 of taxpayers' money was used to support a misinformation campaign run by the Alliance for Food and Farming, a pro-agricultural chemicals lobby dedicated to combating pesticide critics like EWG.

Chemical agribusiness interests want to suppress the truth about pesticides. We can't let them get away with it. USDA officials need to hear that you want the truth, all of it and nothing but. Please join the more than 36,000 people who have called on USDA to not cave in to industry.

Click here to sign our petition that tells USDA officials to not cave to industry pressure and to stop funding industry's disinformation campaigns!

The evidence linking pesticides to health problems -- such as increased risk of cancer -- is overwhelming. New studies show that pesticide exposure may lead to developmental delays and lower IQs in children. Last year, the President's Cancer Panel recommended that consumers avoid foods with pesticide residues.

Instead of kowtowing to industry groups like the Alliance for Food and Farming, the USDA and other federal agencies should compile and analyze more information about pesticides. Industry spin should not drive disclosure of critical information about pesticides in our food. If you want to know whether your kids' lunch boxes contain fruits and veggies high in pesticide residues, take action today!

Click here to sign our petition today. It's unpalatable that your tax dollars fund disinformation about pesticides in food.

Thank you for standing with EWG against the pesticide lobby.


Ken Cook
President, Environmental Working Group


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