Infertility is a reproductive disease which has an enormous impact on the quality of life for millions of patients. It affects 1 in 5 of all couples, and most patients undergo extensive diagnostic and treatment interventions on their journey to create a family. Infertility has a myriad of causes including endocrine disorders, gynecological disease, infectious disease, circulatory disease and aging and cellular health. Autoimmune disorders are also implicated in reproductive disorders and may especially play a role in unexplained cases of infertility.
It is known that autoimmune diseases such as diabetes, autoimmune thyroiditis and systemic lupus erythematosis are linked to decreased fertility. Other causes of infertility such as premature ovarian insufficiency, endometriosis and polycystic ovarian syndrome include autoimmune components. In many unexplained cases of infertility, inflammatory processes may be involved or antibodies may be directed against hormones, clotting factors, or reproductive tissues such as the ovaries or testes. The research into autoimmune infertility is just in its beginning, but as naturopathic physicians there are valuable tests and treatments we can provide to our patients who present either with known autoimmune disorders and difficulty conceiving, or with the ever enigmatic diagnosis of “unexplained infertility”.
The biological factors involved in autoimmune infertility are various. These include a multitude of cellular and inflammatory changes. Some of the most common factors are discussed below.
Endometriosis has many autoimmune components including elevated levels of cytokines, and T- and B-cell abnormalities. Peripheral monocytes are more active, and peritoneal macrophages are present in higher numbers with higher activity levels. This causes increased inflammatory cytokine release.
There are alterations in B-cell activity and an increased incidence of autoantibodies in women with endometriosis. Like classical autoimmune diseases, endometriosis has been associated with polyclonal B-cell activation, immunological abnormalities in T- and B-cell functions, increased apoptosis, tissue damage, multiorgan involvement, familial occurrence, possible genetic basis, involvement of environmental cofactors, and association with other autoimmune diseases. TNF-a, levels are elevated in the peritoneal fluid of patients with endometriosis. In women with endometriosis, TH2 mediated immunity humoral responses are commonly elevated.
A 2001 study found that 50% of endometriosis patients had autoantibodies to candida enolase. The same study found increased levels of these antibodies in patients with a list of other autoimmune conditions.
Autoimmune thyroid disease and infertility.
Thyroid diseases involving antithyroid antibodies have been correlated to infertility and increased pregnancy loss. Autoimmune thyroid disease, even in the absence of hypothyroidism has been associated with infertility and reduced response to fertility treatment. It has also been associated with gluten related autoimmunity. Autoimmune thyroid disease can lead to hypo or hyperthyroidism which can impact fertility and cause miscarriage.
Other Autoimmune Diseases and Fertility
Antinuclear antibodies (ANAs ) which have been associated with infertility can be present in conditions such as SLE, Sjogren’s syndrome, Raynaud’s syndrome, and can also be detected in women with a history of exposure to chemicals such as bisphenol-A.
Addison’s disease is associated with anti-ovarian antibodies which can reduce ovulatory function and cause premature ovarian failure in severe cases.
Patients with celiac disease may have multiple nutritional deficiencies that can lead to infertility. Celiac disease has been linked to recurrent miscarriage, pregnancy complication and infertility. A 2010 study found that between 5-10% of women with a history of stillbirth, recurrent miscarriage, intrauterine growth restriction, and infertility were seropositive for transglutaminase IgA compared to 1% of the control group. Latent celiac disease may be a major cause of unexplained infertility.
In approximately 20% of women with premature ovarian insufficiency(POI), autoimmune factors can be found. POI can be linked to autoimmune thyroid disease, Addison’s disease, or SLE or may have unknown etiology. Women may have antibodies against the ovarian tissues, or reproductive hormones such as FSH.
Antisperm antibodies are another cause of infertility. These can be present in either male or female patients. They are commonly found in males after vasectomy procedures, and their presence can make vasectomy difficult to reverse. Antisperm antibodies affect the ability of the sperm to penetrate the egg or reduce motility by attaching to the tail of the sperm . They have also been associated with antiphospholipid antibodies. Antisperm antibodies are generally produced by CD19+/5+ B cells and are associated with elevated natural killer cells and anti-dna antibodies.
Autoimmune blood clotting disorders
Disorders with increased antiphospholipid antibodies( APAs) including anti-cardiolipin antibodies cause a hypercoagulatory state in the blood and can be associated with reproductive failure and recurrent miscarriage. These antibodies can be found in systemic diseases such as SLE, or on their own.
Immunological Considerations for Patients with Reproductive Challenges
A condition of TH1 cytokine dominance can be associated with the inability to conceive or maintain a pregnancy. In women with high TH1/TH2 ratios there is an increased incidence of pregnancy loss and infertility however for different autoimmune conditions the predominant immune pathway may differ.
Natural killer(NK) cells
Elevated peripheral NK cells are associated with many systemic autoimmune diseases but can also be found in women with unexplained infertility conditions. NK cells produce TH1 cytokines including TNF-alpha and Interferon gamma. These cytokines are normally involved in cellular toxicity directed at cancerous cells and viruses . If increased in early pregnancy, the presence of NK cells and their cytokines can disrupt the growth and development of the embryo. TNF-alpha works as a signal to other immune cells which then migrate to the uterus to attack the non-self invader which has been immunologically detected. A 1999 study found that in women who had repeated miscarriage, there was markedly increased NK cell cytotoxicity associated with a rise in CD56+CD16+ and a drop in CD56+ cells. Another special type of NK cell called uterine NK (uNK) cells have a protective immunosuppressive effect locally in the endometrium. Dysfunction of these cells has been associated with pregnancy loss
Homocysteine and Folate Metabolism
ciency and hyperhomocysteinemia are known to be risk factors for infertility and pregnancy complications. Errors in these pathways caused by genetic mutations have been associated with autoimmune diseases Patients with a mutation of the MTHFR gene have difficulty reducing 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. 5- methyltetrahydrofolate is used to convert homocysteine to methionine by the enzyme methionine synthase. A 2010 study on a group of 71 Swedish and Finnish female patients with unexplained infertility found a higher incidence of folate metabolism polymorphisms compared to women in the general population. Folate receptor blocking autoantibodies have also been related to subfertility
Folate metabolism disorders can can lead to reduced cell division, inflammatory cytokine production, altered nitric oxide metabolism, increased oxidative stress, abnormal methylation reactions and thrombosis. This causes problems with folliculogenesis and implanting or maintaining a healthy pregnancy. In males, defects in this pathway can impair spermatogenesis.
Diagnostic testing in the naturopathic clinic
In addition to general and endocrine panels for infertility, consider testing for homocysteine, CRP, ESR, ANA panels, APA panels, PTT, Partial PTT, DHEA-S, TSH, Antithyroglobulin, Antithyroid peroxidase, HBA1C, CBC, diurnal cortisol, assessments for candida, and gluten sensitivity testing.
Clinically, I have found that optimal homocysteine levels should be 8mmol/L or below in patients with autoimmune infertility factors.
TH1 to TH2 ratios can be a very helpful tool for designing treatment plans. NK assays and testing for genetic variants of MTHFR are also available.
These vary depending on results found and can include low dose aspirin, anti-coagulants, corticosteroids, IVIG, Lymphocyte immunization therapy (LIT) and TNF-alpha blockers. These are often combined with IVF or other assisted reproductive technologies.
Treatments in the naturopathic clinic
Some of the following treatment options may be considered after a thorough assessment determines specific autoimmune factors.
To reduce TH1 dominant inflammatory responses in patients who require it, maritime pine extract (100mg bid), resveratrol ,(100mg bid) , and green tea EGCG (300mg catechins bid), . Maritime pine, and resveratrol also inhibit platelet aggregation and thrombosis,,. The antioxidant effects of these substances are also beneficial.
Proline rich polypeptides such as those found in bovine colostrum may favour a shift towards TH1 and downregulate overactive TH2 responses.
High quality omega 3 fish oil. 2 – 3g of EPA and DHA qd to aid with inflammatory and thrombotic disorders . A 2007 study on mice found that a ratio of 23:14 EPA HA decreased tnf alpha in 8 hours. EPA also regulates autoimmune markers in endometriosis
L-5-methyltetrahydrofolate 5mg daily, vitamin B12 1000mcg qd and vitamin B6 75mg qd to improve homocysteine and folate metabolism. Screen for history of cancer before using high dose folate. Trimethylglycine 1000mg qd may also be used to lower homocysteine levels in selected patients.
N-Acetyl Cysteine 600mg bid. Reduces inflammatory cytokines. Improves autoimmune thyroid disease NAC also enhances semen parameters and the oxidative status and quality of the endometrium . NAC also protects the integrity of ovaries subjected to physical and oxidative damage, and aids liver detoxifcation pathways.
For patients with thyroid antibodies, l-selenomethionine 200mcg daily,,,. If hypothyroid, use of bio-identical hormone therapy may be indicated to prevent miscarriage. Trace minerals for thyroid function are also be beneficial.
Thyroid protomorphogen may be useful for patients with antithyroid antibodies to act as a decoy. Increase dosage slowly to 1 tablet tid.
Elimination of gluten should be implemented as required for patients with positive serology.
Probiotics 20 billion CFUs daily. Rotate strains monthly to modulate immunity and repair gut lining. Treat candida if present.
Support liver detoxification pathways.
Bio-identical progesterone is a potent immunosuppressive agent capable of blocking both cytokine release and action . May be used in the luteal phase of the cycle to support early pregnancy.
DHEA – can be useful in premature ovarian insufficiency and to improve pregnancy rate and reduce miscarriage in advanced maternal age. It has also been found to be beneficial in the treatment of autoimmune disease,, and to reduce NK cell activity. DHEA should only be used after serum DHEA-S and androgen evaluation. Dose adjusted according to patient need but is often 25mg tid or less.
Addressing stress is very important in all patients suffering from the effects of reproductive challenges. Autoimmune diseases are aggravated by stress as it can increase humoral immunity and shift TH1:TH2 ratios. Adrenal therapies, sufficient sleep, yoga, meditation, movement therapy, and prayer can all positively effect patients in this journey
Beer, A, Kantecki J, Reed J. Is your Body Baby Friendly? 1st edition. AJR Publishing 2006.
Nothnick, WB. Treating endometriosis as an autoimmune disease. Fertility and sterility. 2001 Aug;76(2): 223-231.
Antsiferova YS, Sotnikova NY, Posiseeva LV, Shor AL. Changes in the T-helper cytokine profile and in lymphocyte activation at the systemic and local levels in women with endometriosis. Fertil Steril. 2005;84(6):1705-11.
Gitlits VM, Toh BH, Sentry JW. Disease association, origin, and clinical relevance of autoantibodies to the glycolytic enzyme enolase.J Investig Med. 2001. 49(2):138-45.
Kim NY, Cho HJ, Kim HY, et al. Thyroid Autoimmunity and its Association with Cellular and Humoral Immunity in Women with Reproductive Failures. Am J Reprod Immunol. 2011;65(1):78-87
Ott J, Aust S, Kurz C et al. Elevated antithyroid peroxidase antibodies indicating Hashimoto’s thyroiditis are associated with the treatment response in infertile women with polycystic ovary syndrome. Fertility and sterility. 2010;94(7): 2895-2897.
Guliter S, Yakaryilmaz F, Ozkurt Z, et al. Prevalence of coeliac disease in patients with autoimmune thyroiditis in a Turkish population. World J Gastroenterol 2007; 13(10): 1599-1601
Geva E, Lerner-Geva L, Burke M, Vardinon N, Lessing JB, Amit A. Undiagnosed systemic lupus erythematosus in a cohort of infertile women. Am J Reprod Immunol. 2004;51(5):336-40.
Kumar A, Meena M, Begum N, et al. Latent celiac disease in reproductive performance of women Fertility and sterility 24 November 2010. Epub ahead of print
Yamada H, Atsumi T, Kato EH, et al. Prevalence of diverse antiphospholipid antibodies in women with recurrent spontaneous abortion.Fertil Steril. 2003;80(5):1276-1278.
Kwak-Kim JY, Chung-Bang HS, Ng SC, et al. Increased T helper 1 cytokine responses by circulating T cells are present in women with recurrent pregnancy losses and in infertile women with multiple implantation failures after IVF. Human Reproduction. 2003;18(4):767-73.
Emmer P, Nelen W, Steegers, E et al. Peripheral natural killer cytotoxicity and CD56posCD16pos cells increase during early pregnancy in women with a history of recurrent spontaneous abortion Hum. Reprod. (2000) 15(5): 1163-1169
Dosiou C, and Giudice LC. Natural Killer Cells in Pregnancy and Recurrent Pregnancy Loss: Endocrine and Immunologic Perspectives. Endocr. Rev. 2005;26(1):44-62.
Tamura T, Picciano MF. Folate and human reproduction. Am J Clin Nutr. 2006;83:993–1016
Mao R, Fan Y, Zuo L, et al. Association study between methylenetetrahydrofolate reductase gene polymorphisms and Graves’ disease. Cell Biochem Funct. 2010; 28(7): 585-90.
Brustolin S, Giugliani R, Felix TM. Genetics of homocysteine metabolism and associated disorders. Braz J Medio Res, 2010; 43(1):1-7
Klotz L, Farkas M, Bain N, et al. The variant methylenetetrahydrofolate reductase c.1298A>C (p.E429A) is associated with multiple sclerosis in a German case-control study. Neurosci Lett. 2010; 468(3):183-5.
Altmäe S, Stavreus-Evers A, Ruiz JR, et al. Variations in folate pathway genes are associated with unexplained female infertility.Fertil Steril. 2010;94(1):130-7.
Klotz L, Farkas M, Bain N, et al. The variant methylenetetrahydrofolate reductase c.1298A>C (p.E429A) is associated with multiple sclerosis in a German case-control study. Neurosci Lett. 2010; 468(3):183-5.
Safarinejad MR, Shafiei N, Safarinejad S. Relationship Between Genetic Polymorphisms of Methylenetetrahydrofolate Reductase (C677T, A1298C, and G1793A) as Risk Factors for Idiopathic Male Infertility. Reprod Sci. 2010 Oct 26 [Epub ahead of print]
Cho KJ et al. Inhibition mechanisms of bioflavonoids extracted from the bark of Pinus maritime on the expression of pro inflammatory cytokines. Ann NY Acad Sci. 2001;(928)141-56.
Falchetti R, Fuggetta MP, Lanzilli G, Tricarico M, Ravagnan G. Effects of resveratrol on human immune cell function. Life Sci. 2001; 21;70(1):81-96.
Tian J, Gao J, Chen J, et al. Effects of resveratrol on proliferation and apoptosis of TNF-alpha induced rheumatoid arthritis fibroblast-like synoviocytes. Zhongguo Zhong Yao Za Zhi. 2010;35(14):1878-82.
Zvetkova E, Wirleitner B, Tram NT, Schennach H, Fuchs D. Aqueous extracts of Crinum latifolium (L.) and Camellia sinensis show immunomodulatory properties in human peripheral blood mononuclear cells. Int Immunopharmacol. 2001;1(12):2143-50.
Gillespie K, Kodani I, Dickinson DP, et al. Effects of oral consumption of the green tea polyphenol EGCG in a murine model for human Sjogren’s syndrome, an autoimmune disease. Life Sci. 2008 Oct 24;83(17-18):581-8.
Araghi-Niknam M, Hosseini S, Larson D, Rohdewald P, Watson RR. Pine bark extract reduces platelet aggregation. Integr Med. 2000 Mar 21;2(2):73-77
Belcaro G, Cesarone MR, Rohdewald P, et al. Prevention of venous thrombosis and thrombophlebitis in long-haul flights with pycnogenol. Clin Appl Thromb Hemost. 2004 Oct;10(4):373-7
Olas B, Wachowicz B, Saluk-Juszczak J, Zielinski T. Effect of resveratrol, a natural polyphenolic compound, on platelet activation induced by endotoxin or thrombin. Thromb Res. 2002 Aug 15;107(3-4):141-5.
Figueras M, Olivan M, Busquets S, López-Soriano FJ, Argilés JM. Effects of Eicosapentaenoic Acid (EPA). Treatment on Insulin Sensitivity in an Animal Model of Diabetes. Improvement of the Inflammatory Status. Obesity (Silver Spring). 2010 Sep 30. [Epub ahead of print]
Vanschoonbeek K, Feijge MA, Paquay M, et al. Variable hypocoagulant effect of fish oil intake in humans: modulation of fibrinogen level and thrombin generation. Arterioscler Thromb Vasc Biol. 2004 Sep;24(9):1734-40.
Dangardt F, Osika W, Chen Y, et al. Omega-3 fatty acid supplementation improves vascular function and reduces inflammation in obese adolescents. Atherosclerosis. 2010; 212(2):580-5.
Bhattacharya A, Sun D, Rahman M, Fernandes G. Different ratios of eicosapentaenoic and docosahexaenoic omega-3 fatty acids in commercial fish oils differentially alter pro-inflammatory cytokines in peritoneal macrophages from C57BL/6 female mice. J Nutr Biochem. 2007 Jan;18(1):23-30.
Netsu S, Konno R, Odagiri K, Soma M, Fujiwara H, Suzuki M. Oral eicosapentaenoic acid supplementation as possible therapy for endometriosis. Fertility and sterility. 2008; (90)4: 1496-1502.
Stanislaus R, Gilg AG, Singh AK, Singh I. N-acetyl-L-cysteine ameliorates the inflammatory disease process in experimental autoimmune encephalomyelitis in Lewis rats. J Autoimmune Dis. 2005 May 3;2(1):4.
Poncin S, Colin IM, Decallonne B, et al. N-Acetylcysteine and 15 Deoxy-?12,14-Prostaglandin J2 Exert a Protective Effect Against Autoimmune Thyroid Destruction in Vivo but Not Against Interleukin-1a/Interferon ?-Induced Inhibitory Effects in Thyrocytes in Vitro.The American journal of pathology. 2010;177(1)219-228
Ciftci H, Verit A, Savas M, Yeni E, Erel O. Effects of N-acetylcysteine on semen parameters and oxidative/antioxidant status.Urology. 2009;74(1):73-6.
Estany S, Palacio JR, Barnadas R, Sabes M, Iborra A, Martínez P. Antioxidant activity of N-acetylcysteine, flavonoids and alpha-tocopherol on endometrial cells in culture. J Reprod Immunol. 2007; 75(1):1-10.
Mishra DP, Dhali A. Endotoxin induces luteal cell apoptosis through the mitochondrial pathway. Prostaglandins Other Lipid Mediat. 2007;83(1-2):75-88.
Usta U, Inan M, Erbas H, Aydogdu N, Oz Puyan F, Altaner S. Tissue damage in rat ovaries subjected to torsion and detorsion: effects of L-carnitine and N-acetyl cysteine. Pediatr Surg Int. 2008; 24(5):567-73
Zagrodzki P, Ratajczak R. Selenium supplementation in autoimmune thyroiditis female patient–effects on thyroid and ovarian functions (case study). Biol Trace Elem Res. 2008; 126(1-3):76-82.
Turker O, Kumanlioglu K, Karapolat I, Dogan I. Selenium treatment in autoimmune thyroiditis: 9-month follow-up with variable doses. J Endocrinol. 2006;190(1):151-6.
Negro R, Greco G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol Metab. 2007;92(4):1263-8.
Gärtner R, Gasnier BC, Dietrich JW, Krebs B, Angstwurm MW. Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations. J Clin Endocrinol Metab. 2002; 87(4):1687-91.
Howard L. Weiner, MD. Oral tolerance for the treatement of autoimmune disease. Annual Review of Medicine. 1997; (48): 341-351.
Raghupathy R, Al-Mutawa E, Al-Azemi M, Makhseed M, Azizieh F, Szekeres-Bartho J. Progesterone-induced blocking factor (PIBF) modulates cytokine production by lymphocytes from women with recurrent miscarriage or preterm delivery. J Reprod Immunol. 2009 Jun;80(1-2):91-9
Mamas L, Mamas E. Premature ovarian failure and dehydroepiandrosterone Fertil Steril.2009;91(2):644-646.
Gleicher N, Ryan E, Weghofer A, Blanco-Mejia S, Barad DH. Miscarriage rates after dehydroepiandrosterone (DHEA) supplementation in women with diminished ovarian reserve: a case control study. Reprod Biol Endocrinol. 2009 Oct 7;7:108.
Solerte SB, Precerutti S, Gazzaruso C, et al. Defect of a subpopulation of natural killer immune cells in Graves’ disease and Hashimoto’s thyroiditis: normalizing effect of dehydroepiandrosterone sulfate. Eur J Endocrinol. 2005;152(5):703-12.
Crosbie D, Black C, McIntyre L, Royle PL, Thomas S. Dehydroepiandrosterone for systemic lupus erythematosus. Cochrane Database Syst Rev. 2007;(4):CD005114
Hazeldine J, Arlt W, Lord JM. Dehydroepiandrosterone as a regulator of immune cell function. J Steroid Biochem Mol Biol. 2010;120(2-3):127-36.
Calcagni E, Elenkov I. Stress system activity, innate and T helper cytokines, and susceptibility to immune-related diseases. Ann N Y Acad Sci.2006;1069:62-76
Who is calm and relaxed before surgery? I don’t know too many patients who are not anxious before surgery. Patients participating in a study in China who received acupuncture prior to surgery reported a greater than 50% decrease in their anxiety.
When patients have high levels of anxiety and stress hormones, lose sleep and cannot relax before an operation, the capacity to withstand the physiologic stress of surgery is decreased. This compromises the patient’s chances for a good outcome free of complications. Furthermore, having a good healing of surgical incisions, improved resistance to infection, normal digestion and elimination, restful sleep and decreased pain are all enhanced when a patient is less anxious and is experiencing less stress.
While there are many ways to help patients deal with the stressors associated with surgery, acupuncture is a cost effective method that can be offered to pre-surgical patients.
Although the study participants were all adults, children who are facing surgery would also benefit from the calming effects of acupuncture.
Additionally, other studies have shown that acupuncture modulates immune function further improving resistance to infection which is important after surgery and especially while in the hospital environment where risk of infection is much higher.
It is common to see patients in Chinese hospitals have the benefit of BOTH modern biomedicine as well as Traditional Chinese Medicine.
We live in a time with access to a wide array of healing and medical modalities. Whether that be the scalpel or the acupuncture needle, it is of great benefit to offer patients an Integrative and Collaborative approach to health care.
Posted By Administration,
Wednesday, April 13, 2011
Updated: Friday, April 18, 2014
Dr. Magaziner was interviewed live by Pat Ciarrochi on CBS' "Talk Philly" on April 12th. During the segment, he served up valuable information about the five foods he deems fabulous for health and wellness. These super foods include salmon, which is high in Omega-3 fatty acids and helps reduce inflammation, risk of heart disease and triglycerides, while helping combat depression, memory loss and arthritis; sweet potatoes, which are high in Vitamin A, antioxidants and calcium to help in maintaining bone density; celery, which can help lower blood pressure and stress; buckwheat, which stabilizes both blood sugar and blood pressure and cinnamon, which can help reduce blood sugar.
Your intestinal tract is home to approximately 100,000,000,000,000 (100 trillion) microorganism. Your gut actually has 10x more bacteria than all the cells that make you a human combined. Perhaps they have some therapeutic function!
This massive array of bacteria is responsible for synthesizing B vitamins, vitamin K , producing digestive enzymes, metabolizing proteins and carbohydrates, breaking down bile salts, enhancing short term and long term immunity, and inhibiting pro inflammatory mediators. They also breakdown nondigestable carbohydrates like fiber creating short-chain fatty acids, which lower the pH of the intestines creating an environment that is inhospitable to pathogenic bacteria such as E. coli and Salmonella. Sounds delicious…
Symptoms and diseases associated with mutant gut flora:
If you were going to add one foundational element to your dietary supplement regimen, I would add some living microbes. Many people think of yogurt as a great way to increase their good bacteria. It is true many yogurts have bacteria in them that are beneficial to your health. However, the levels in yogurt or kefir are not enough to overcome disease and dysfunction. You will need millions of little bacteria to enable the development of a healing environment.
Probiotics are best consumed with a moderate amount of food no warmer than room temperature.
If you are taking antibiotics, probiotics should be taken 1 hour before or 2 hours after the antibiotics. It is vital if you are taking or have taken antibiotics that you make a concerted effort to reestablished optimal gut flora.
Approximately 83 percent of people with cancer use at least one complementary and alternative medicine (CAM) modality (11).
Using my experience as a health and wellness expert, I have compiled a list of what cancer patients say about the choices they make regarding cancer treatment:
To be proactive, to take control, to take charge of decisions that affect my care, my health, my experience, my results and outcomes.
To participate in my own care and my own decisions rather than giving power to make all decisions away to my care providers.
To feel a sense of empowerment rather than be disenfranchised and disempowered.
To decrease and manage my fear, stress and anxiety and to support, increase and improve my peace of mind.
To ask my care providers to work with me as a team and to show respect for my values, my feelings and my choices in all decisions.
I choose to reject an approach based solely on a 'war on cancer' that only targets my cancer tumor cells and neglects the whole person and the environment.
I choose a comprehensive care approach using a wide range of therapies, tools and resources from many traditions and many points of view.
I choose individualized and targeted care which views me and my cancer as unique and in which decisions and choices are based on a careful analysis of the traits and characteristics of my cancer cells and my unique physiology, genetics and risk factors rather than a generic one size fits all approach.
To actively manage and reduce both short term and long term toxic side effects from conventional cancer treatments such as surgery, chemotherapy, radiation therapy, hormones and other drugs used by oncologists, radiologists and surgeons.
To protect my cells, tissues and organs from damage during my treatment.
To grow and develop effective coping strategies for myself.
To address the continuous small and large traumatic experiences that cancer patients undergo as part of every stage of my cancer journey.
To develop and cultivate positive, supportive healing relationships with my care providers, my team.
To utilize integrative cancer care and alternative treatments when the conventional oncology treatment offered to me is perceived as worse than the disease itself.
To utilize integrative cancer care when there are no conventional oncology treatments that offer me a therapeutic benefit.
To utilize integrative oncology care when the known risks of conventional oncology treatments are greater than the known benefits of those treatments.
To utilize integrative cancer and alternatives to conventional care and to use integrative cancer care without conventional oncology treatments when there are no effective conventional cancer treatments recommended or available to me.
I have fundamental confidence in the value and benefits of integrative cancer treatments that address the whole person and have my health, recovery, survival, quality of life and peace of mind (not just absence of disease) as both a short term and a long term goal.
Choosing an integrative cancer care approach makes a significant difference for each unique individual cancer patient. In this model, the patient is a fully empowered participant in making decisions and choices related to their cancer treatment, cancer recovery and cancer survivorship in concert with their team of care providers.
This is the goal of evidence based, compassionate person centered health care: combining the best of science and nature, modern knowledge and ancient healing wisdom, in order to transform disease, restore healthy function, wholeness and quality of life to each unique individual patient.
Rather than a model focused primarily on disease management, this is a model which also includes health, healing and the whole person as well as the internal and external environments of each unique individual to form a matrix in which the continuum of health and disease can be more fully met and understood.
When a health care model includes not only disease management, but also restored health and function, different choices are made by both patients and care providers.
Even if the disease is not eradicated and recovery is not possible, healing and wholeness may still unfold. Even in terminal illness, when compassionate care becomes the primary care, the patient can achieve integration of the experience and a capacity to face the end of life and make peace with what is so.
1. Block KI, Gyllenhaal C, Tripathy D, Freels S, Mead MN, Block PB, Steinmann WC, Newman RA, Shoham J. Survival Impact of Integrative Cancer Care in Advanced Metastatic Breast Cancer. Breast J. 2009 May 12. [Epub ahead of print] PubMed PMID: 19470134
2. Frattaroli J, Weidner G, Dnistrian AM, Kemp C, Daubenmier JJ, Marlin RO, Crutchfield L, Yglecias L, Carroll PR, Ornish D. Clinical events in prostate cancer lifestyle trial: results from two years of follow-up. Urology. 2008 Dec;72(6):1319-23. Epub 2008 Jul 7. PubMed PMID: 18602144.
3. Molassiotis A, Fernadez-Ortega P, Pud D, Ozden G, Scott JA, Panteli V, Margulies A, Browall M, Magri M, Selvekerova S, Madsen E, Milovics L, Bruyns I, Gudmundsdottir G, Hummerston S, Ahmad AM, Platin N, Kearney N, Patiraki E. Use of complementary and alternative medicine in cancer patients: a European survey. Ann Oncol. 2005 Apr;16(4):655-63. Epub 2005 Feb 2. PubMed PMID: 15699021.
4. Mulkins AL, Verhoef MJ. Supporting the transformative process: experiences of cancer patients receiving integrative care. Integr Cancer Ther. 2004 Sep;3(3):230-7. PubMed PMID: 15312264. 5. Nahleh Z, Tabbara IA. Complementary and alternative medicine in breast cancer patients. Palliat
7. Ornish, D., M. J. Magbanua, G. Weidner, V. Weinberg, C. Kemp, C. Green, M.D. Mattie, R. Marlin, J. Simko, K. Shinohara, C. M. Haqq, and P. R. Carroll. 2008a. Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention. Proc Natl Acad Sci U S A 105 (24):8369-74.
8. Pud D, Kaner E, Morag A, Ben-Ami S, Yaffe A. Use of complementary and alternative medicine among cancer patients in Israel. Eur J Oncol Nurs. 2005 Jun;9(2):124-30. PubMed PMID: 15944105.
9. Verhoef MJ, Balneaves LG, Boon HS, Vroegindewey A. Reasons for and characteristics associated with complementary and alternative medicine use among adult cancer patients: a systematic review. Integr Cancer Ther. 2005 Dec;4(4):274-86. Review. PubMed PMID: 16282504.
10. Verhoef MJ, Mulkins A, Boon H. Integrative health care: how can we determine whether patients benefit? J Altern Complement Med. 2005;11 Suppl 1:S57-65. PubMed PMID: 16332188.
11. Richardson MA, Mâsse LC, Nanny K, Sanders C. Discrepant views of oncologists and cancer patients on complementary/alternative medicine. Support Care Cancer. 2004 Nov;12(11):797-804. PMID: 15378417
12. Ruth E. Patterson, Marian L. Neuhouser, Monique M. Hedderson, Stephen M. Schwartz, Leanna J. Standish, Deborah J. Bowen, Lynn M. Marshall. The Journal of Alternative and Complementary Medicine. August 2002, 8(4): 477-485. doi:10.1089/107555302760253676.
Posted By Administration,
Wednesday, March 23, 2011
Updated: Friday, April 18, 2014
Dr. Robert Rowen will speak at the Oxidative Medicine workshop taking place at the iMosaic conference in Minneapolis, Minnesota, Thursday, April 7, 2011. He will speak about Ultraviolet Blood Irradiation Therapy as well as Ozone Therapy.
Here is a brief video of Dr. Rowen speaking about Oxidative Medicine:
Register for this course before next Monday, March 28, and qualify for the iMosaic Early Bird rate! Visit www.imosaic.org or call 1-800-532-3688 to register today!
A new research study published in Clinical Nutrition looked at magnesium intake and levels in patients diagnosed with Type II Diabetes. The researchers found that those with Diabetes had lower levels of magnesium in their body and there was a direct correlation between magnesium status and insulin control. Magnesium is used by the body in over 325 enzyme reactions and in the case of Diabetes, healthy insulin function is dependent upon magnesium! Try to keep your magnesium intake at a minimum of 500 mg per day and if you are not getting enough from food (a common occurrence), then consider supplementing with a high quality mineral supplement with magnesium. Some of the highest sources of magnesium in foods are dark green leafy vegetables, kelp, wheat bran, wheat germ and organic raw cashews.
We are all saddened as we watch the unfolding events in Japan. There is a growing sense of fear, as well.
The nuclear catastrophe raging through Japan's nuclear power complex is generating an intense fear of radioactive fallout potentially reaching North America. My patients and friends have been asking about how best to protect themselves and their families, as there is considerable confusion in the media about the issue.
Even as government officials and health experts downplay the health risk to U.S. citizens, pharmacies up and down the West Coast of the United States have been stripped bare of their stock of potassium iodide tablets -- a frontline treatment for radiation exposure. Anxious buyers turning to the internet are faced with a similar lack of available supplies. So, what do we do? It's a growing, ever-changing scenario, and here are my current thoughts, certainly open to modification.
Are we really at risk of exposure from radioactive fallout generated by a nuclear meltdown in Japan? I believe this is a question best left to qualified nuclear scientists and meteorologists. But after serving as a consultant to the Independent Safety Committee for the Diablo Canyon Nuclear Power Plant from 1990 to 2002, I know firsthand how important it is to be prepared for all possibilities when dealing with nuclear radiation.
One of the greatest dangers following a nuclear accident comes from exposure to gases containing radioactive isotopes of iodine. These highly carcinogenic isotopes are readily taken up by the thyroid gland, resulting in the development of thyroid cancer. Exposure to radioactive iodine calls for immediate treatment with another form of iodine, potassium iodide, to saturate the thyroid and block the absorption of radioactive iodine. This is especially critical for children, pregnant women, and nursing mothers, who are most at risk following a nuclear disaster. A lack of adequate supplies of potassium iodide tablets after theChernobyl nuclear disaster in 1986 resulted in thyroid cancer for thousands of untreated children.
Potassium Iodide (KI) Potassium iodide tablets are commonly stockpiled near nuclear power plants to allow for rapid distribution in case of a radioactive accident. In the absence of tablets, potassium iodide may also be administered as a "saturated solution of potassium iodide" (SSKI) which in the U.S.P. generic formulation contains 1000 mg of KI per ml of solution. Two drops of U.S.P. SSKI solution is equivalent to one 130 mg KI tablet (100 mg iodide).
Recommended Doses According to the World Health Organization (WHO), the following doses of potassium iodide should be taken as a single dose within three hours of exposure, or up to 10 hours after exposure, although this is less effective.
• Adults : 130 mg (see below as well for CDC addendum) • Adolescents: 12-18: WHO -- adult dose; CDC -- children's dose; if adult size (150 pounds or over) they should take the full adult dose, regardless of their age. • Children age 3-12 years: 65 mg • Infants : 1 mo. to 3 years, 32. 25 mg (ie half tablet) • Newborns to 1 mo., 1/4 capsule.
Note: Dosages may be crushed and taken mixed with milk or water. For kids, chocolate milk or raspberry syrup disguise the unpleasant taste.
Precautions While potassium iodide can be taken by a majority of people without any problems, it should only be used in case of a nuclear emergency. Doses in excess of the single (one time only) daily dose listed above should be taken only upon recommendation by a physician or public health authority. Patients should ask their doctor if taking quinidine, captopril, or enalopril, amiodarone, or if they are sensitive to iodine, or suffer from dermatitis herpetiformis, thyrotoxicosis or kidney problems before taking potassium iodate (or any thyroid blocker).
Prophylaxis It is best to take iodide prophylactically, prior to exposure. Every family should have a good supply in their homes. At this time we may recommend taking 10-40mg per day. A dose of 30-50mg is the range of dietary intake in Japan and relatively safe to take long term but under practitioner monitoring. Build up gradually: 10mg-20mg-30mg-40mg.
Then, in case there is an official announcement of significantly increased radiation, adults should go to the dose mentioned above: 130mg/day and children to lower doses per body weight, generally 65 mg, age 3-12 years. You can use a loading dose of two drops daily of Lugol's Iodine, a commonly available pharmaceutical form of potassium iodide, or SSKI, and increase to 130 mg if needed. See the U.S. Centers for Disease Control recommendations. Adults over 40 should not take KI unless public health officials say that contamination with a very large dose of radioactive iodine is expected, since have the lowest risk of developing thyroid cancer or thyroid injury after such contamination. They also have a greater chance of having allergic reactions to KI. Everyone should check with their doctor, in any case.
Avoid exposure to rain that may be laden with radiation if we are exposed. You'll be informed by authorities if that is the case.
Other Radiation Dangers Besides I-131, there are other toxic radio-isotopes, including cerium 137 and plutonium. Dr. Gabriel Cousens has provided some excellent advice in his book "Conscious Eating." To protect yourself from cesium poisoning, consume plenty of high potassium foods, as potassium competitively inhibits cesium uptake. Foods high in potassium include avocados, sea vegetables, and leafy green vegetables, and are more effective than taking a potassium supplement.
To protect yourself from plutonium poisoning, eat lots of dulse and consume iron from plant sources, namely sea algaes such as spirulina and chlorella, which provide more iron than red meat. Miso soup has also been shown to have a protective effect. See also Michio Kushi's well-referenced book, "The Cancer Prevention Diet." The mineral, zeolite, is being investigated for taking most radioactive materials out of the body.
Additionally, foods and supplements high in antioxidants, will also help the body cope with these higher toxic levels as radioactive materials cause antioxidant depletion and ill health.
Summary The Nuclear Regulatory Commission has admitted it is 'quite possible' that fallout from the Japanese reactors could reach America, though levels expected to be so low as to be almost undetectable. Given the unprecedented circumstances of the current crisis, though, it would be prudent to keep some potassium iodide on hand as a precautionary measure.
Stay tuned to news sources for ongoing information, as this story is clearly developing by the minute.
For both those directly affected and those of us who feel the stress of this tragedy, check out some simple trauma-releasing methods, such as EMDR, EFT: or download free EFT audio "Tapping for Japan."
If I am able to find sources of tablets, I'll put a note here in comments, and list them on my website, as well. Otherwise, I'd recommend using SSKI which I'll likely be getting for my patients in the absence of tablets or capsules.
Our prayers are with the people of Japan, those who have lost their lives and those who have survived, and are dealing with trauma, grief and unspeakable loss.
Posted By Administration,
Tuesday, March 15, 2011
Updated: Friday, April 18, 2014
Safety and Consistency is Our Priority
There is no compromise when it comes to health.
At McGuff compounding pharmacy, we have independent Quality Assurance and Quality Control programs to ensure that our products and patient care meet high quality standards and requirements. Our commitment is to provide a level of service that delivers safe compounded products consistently that patients and physicians can depend upon.
We use industry leading practices to meet your needs. We model our operations to meet manufacturing FDA Current Good Manufacturing Practice standards whenever possible.
When choosing a compounding pharmacy you want to feel confident that you will receive the highest quality compounded products and unparalleled patient care.
The following are some questions that you should ask when selecting a compounding pharmacy. Each affirmative answer should be followed by one additional question… "If so, how can you prove this to me?". The answer to this question, without independent audit reports of their pharmacy from national and international standards organizations, will more than likely be “because we said so”. If a pharmacy is not accredited by PCAB™ or ISO there must be a reason.:
Quality Assurance Checklist
McGuff Compounding Pharmacy
Does your pharmacy have specific assignment of quality functional responsibilities as defined in a Quality Assurance plan?
Does your pharmacy have an independent Quality Systems Department whose responsibility is to ensure that the facility, equipment and personnel meet the demanding standards set forth the United States Pharmacopeia?
Does your independent Quality Assurance department have the authority to over-ride the pharmacist-in-charge and stop the release of any compounded medication if the medication quality attributes are suspect?
Independent Standards Reviews
Is your pharmacy PCAB Accredited™ which assures that the pharmacy is dedicated to protecting patients by practicing safe, high-quality compounding ?
Is your pharmacy ISO 9001:2008 certified by an independent organization to assure compliance to international standards of customer care and product development?
In addition to your pharmacy license do you have a State Board of Pharmacy sterile compounding license?
Is your pharmacy committed to and in compliance with USP <1075>, Good Compounding Practices?
Is your pharmacy committed to and in compliance with USP <795>, Pharmaceutical Compounding – Non-sterile Preparations?
Is your pharmacy committed to and in compliance with USP <797> guidelines for sterile compounding?
Are all significant procedures performed in the pharmacy covered by Standard Operating Procedures (SOPs)? Is there documentation that the pharmacy staff has been trained and understands the SOPs?
Is the Pharmacy’s Quality Assurance plan reviewed annually and when changes are made to the plan?
Does the pharmacy maintain both a master formula and lot-specific compounding history records for all compounds?
Does the pharmacy's master formula document the name, strength, and dosage form of the compounded product, all ingredients and their quantities, assigned a beyond-use date, record the equipments to be used, mixing instructions, packaging instructions, and Quality Assurance checklist? (This documentation ensures that the compound is prepared consistently to reproduce the same each and every time.)
Does your pharmacy prepare a formulation checklist and perform a design review process to determine acceptable strength, quality, and purity of a new formulation request?
Does your pharmacy’s facility meet or exceed U.S.P. Guidelines for compounding pharmacies?
Does your pharmacy perform sterile filling in a class 100 (ISO Class 5) laminar flow hood located within class 10,000 (ISO Class 7) clean room?
Does your pharmacy have separate areas dedicated to perform sterile and non-sterile compounding, product inspections, labeling, raw material storage, and dispensing?
Is the air quality in your compounding pharmacy engineered for HEPA filtration to reduce particulates?
Does your pharmacy perform daily monitoring and documentation of raw material storage, sterile and non-sterile compounding areas, and final product storage for temperature and humidity?
Does your pharmacy conduct daily tests of air and surface samples of your clean-room and other controlled environments?
Does your pharmacy perform daily, weekly, and quarterly cleaning to assure a clean and safe facility?
Are your pharmacy’s pharmacists, technicians, and customer service staff dedicated exclusively to compounding?
Is your pharmacy’s staff properly trained to perform aseptic manipulation skills, gowning technique, clean-room use, and successfully perform media fills every six months?
Does your pharmacy’s staff take steps to minimize error and maximize the prescriber’s intent for the patient during the compounding process?
Does your pharmacy purchase pharmaceutical-grade chemicals (USP, NF equivalent) from FDA-registered suppliers?
Does your pharmacy obtain and keep Certificates of Analysis for all raw materials used in compounding?
Does your pharmacy perform sterility testing according to USP <71> - Sterility Tests and USP <85> - Bacterial Endotoxin Test on every lot prepared?
Does your pharmacy verify the potency of finished compounds through weight, volume and yield checks?
Does your pharmacy perform post-filtration filter-integrity testing?
Does your pharmacy have systems in place for handling complaints and investigating sterility failures and adverse events?
Is every step of the compounding process from prescribing to compounding and labeling through dispensing reviewed and verified by a licensed pharmacist
For more information, visit www.mcguffpharmacy.com.
Recent studies from the University of California, San Diego, published in the British Journal, NATURE, have discovered a molecule called RANKL, found in aggressive breast cancer cells that predicts more deadly, lethal and life threatening disease. The findings from these recent studies suggests that drugs that block RANKL may be effective in preventing both the early stages of breast cancer and the advanced progression of the disease. Research has also shown that curcumin, the active ingredient in the common spice, turmeric, has properties that also reduce the expression of these deadly molecules within cancer cells and can potentially slow the spread of breast cancer.
Breast Cancer is not one disease. There are actually many breast cancers. When a woman is diagnosed with breast cancer, the tumor cells in her body must be analyzed in order to understand the nature of her unique disease. Some cancer cells are more aggressive and fast growing. Some cancer cells are sleepy, slow growing and less dangerous.
It is the presence of these more aggressive cancer cells that predicts that the breast cancer will spread to other parts of the body through a process called metastasis. Metastasis kills. Cancer patients rarely die from the primary tumor, the site where the cancer originates in the body. Breast cancer patients typically die from cancer that has spread or metastasized to other parts of the body, debilitating the function of vital organs such as the liver, lungs or brain. When breast cancer cells are aggressive and able to spread throughout the body, long term survival is threatened. Identifying agents that stop or slow the spread of disease through these mechanisms can stop or slow the spread of cancer and save lives.This new research demonstrates that when a protein molecule called RANKL (Receptor Activated Nuclear Factor Kappa Ligand) is present in breast cancer cells in high amounts, these tumor cells are more activated, more aggressive and more likely to spread, more likely to kill. RANKL is produced by regulatory T-Cells that modulate our immune response. High levels of these T-cells means high levels of RANKL, high levels of inflammation and aggressive high risk disease.
Blocking tumor promoting RANKL can block the spread of breast cancer cells to other parts of the body. A new drug, denusomab, has recently been released by Amgen that performs this function. However, this new drug is not widely available to patients for all possible applications, requires insurance company approval and is very expensive. Therefore few patients will be able to have access to and benefit from this new therapy in the near future. The good news is that there is alternative cancer answer available now without a prescription, the natural substance curcumin, derived from turmeric that can lower inflammation, lower RANKL, lower risk.
Dr. Bharat Aggarwal, Ph.D. Professor, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX is one of many respected researchers and experts who has published many studies on the effects of curcumin on cancer cells. According to Dr. Aggarwal
Curcumin has a very special nature which will work both for cancer prevention as well as for cancer therapy.
Turmeric (Curcuma longa) is one of the most potent Cancer Fighting Foods. Curcumin, the active ingredient in this common medicinal and culinary herb has been widely studied. It is recognized as a potent cell protectant, anti-oxidant and anti-inflammatory agent. Turmeric has been used for centuries to support cancer patients in Traditional Chinese Herbal Medicine and Indian Ayurvedic Medicine. Now modern science demonstrates why it works. Curcumin has been shown to influence many cellular factors, including lowering RANKL.
Curcumin has been shown to decrease RANKL in tumor cells. Curcumin can block RANKL as well as other inflammatory and tumor promoting molecules in cells (COX-2, LOX-5, MMP2,TNFa, NFKbEGFR, HER2, bFGF, TGF-B1, and VEGF.) Turmeric is found in many herbal formulas for the prevention and treatment of cancer.
The active medicinal principle, curcumin, when taken orally, is best absorbed when taken with oil in traditional Indian curries. To use botanical medicine for the prevention and treatment of any serious health condition, the herb must be of pharmaceutical quality and taken in the proper doses. As with any potent botanical medicine, the use of curcumin as an anti-inflammatory and anti-tumor agent should be used under the supervision and guidance of a knowledgeable health care professional. Countries such as India in which tumeric is frequently consumed in the daily diet have lower rates of many cancers including prostate cancer, breast cancer and colon cancer. Tumeric can be safely added to your food as a cooking spice to add anti-inflammatory, anti-oxidant and anti-cancer properties to your daily diet.
The vegetables found under the ground and the heartier ones above ground are packed with vitamins and minerals and perfect for grating, roasting, steaming & mashing this time of year.
The below ground varieties include: Beets, Sweet Potatoes, & Carrots
The above ground varieties include Kale, Brussels sprouts, & Winter squash.
Lets tackle the above grounders first:
Kale and Brussels Sprouts are in the same famous family known as cruciferous. This famous family of vegetables has gained A LOT of press for its anti-cancer benefits. In fact half of the studies on brussels sprouts revolve around its cancer fighting properties. They are high in Vitamin A, C and folic Acid.
Kale is a coarser green and many people have no idea how to prepare it. Once you figure it out you can enjoy one of the healthiest, nutrient greens on the planet. Kale has Vitamins A, C, B6, and minerals of calcium and iron. Did you know that when prepared properly we would get more calcium out of kale than spinach? When preparing cut off the stem part about 1.5 inches and then chop. Try sautéing in a bit of olive oil and water.
Winter Squash comes in a number of varieties, such a butternut, kombucha, and acorn; there are multi-striped varieties as well. The toughest thing about squash is the preparation, the peeling, de-seeding, and chopping. If you have a man, put him to use in this department. Otherwise I suggest cutting in half and placing open side down on a baking sheet and roasting in the oven for 45 minutes. Remove from oven and let cool; the skin will be A LOT easier to remove. Once cooked squash can be mashed or added into soups. Any vegetables orange or yellow in color contain Beta-carotene, and vitamin C, these are antioxidant and anti-inflammatory. Winter squashes also contain B-vitamins, and folic acid.
Check out my latest You Tube cooking video on Sautéed Brussels and Kale, I also have one on making Kale chips. You can access my You Tube channel through the www.AskDrPurcell.com site.
Now for the below grounders:
Carrots and Sweet potatoes are little darlings of the culinary world because of their natural sweetness. In fact many people who don’t like vegetables will eat them. Due to their orange color and carotenoid content leading to anti-oxidant protection within the eye. They are high in Beta Carotene, which is converted inside our bodies to Vitamin A that helps boost the immune system, and protect our skin.
Beets are amazing grated fresh into salads, and roasted. Boiled beets are less appealing.
Beets are high in fiber and can assist with constipation. They are also high in iron and folic acid the two main causes of anemia. If you’re anemic eat your beets! They also contain choline, an important detoxifier for our livers. Beets can be roasted with sweet potatoes, or roasted and then added to chilled salads. Once cooked, beets can be marinated in any dressing and will absorb those flavors bringing a lot of sweet, tangy goodness to the table.
As a nutritionally-oriented internist, I have seen air travel take quite a toll on the health and well-being of many of my friends and patients. With the excitement of traveling to a new destination, the new food, the change in schedule, the stress, the hassle; it is easy to neglect one’s health. My patients are frequently asking me for health travel advice. While practicing in a city where both business and leisure travel are staples in the lives of many of my patients, I have developed a nutritional and lifestyle plan to help optimize health while traveling.
Drink 2 large glasses of water on an empty stomach in the morning of travel. This willhydrate you effectively. Have a high protein breakfast.
Stress plays a significant role in air travel. Aside from a healthy diet, restorative sleep, regular exercise, and the addition of key nutritional supplements to the regime are helpful. One mineral that helps to combat stress is magnesium. It is one of the first nutrients to be depleted in the setting of stress. Your adrenal glands depend on magnesium, as do over 300 different enzyme reactions in the body. I recommend my patients take 100mg of magnesium-taurate the morning of the flight, and then another 100mg just before the flight.
It is not uncommon for travelers to contract a respiratory infection, the flu, or other infection while flying. The poor air circulation in the cabin compounded by the proximity to other passengers who may potentially be sick poses a double threat. Those with weak sinuses are at a heightened risk, as well, due to the periodic changes in air pressure. Washing hands and using hand sanitizers in the plane may be of benefit. Hydration and optimal nutrition are integral components, as well. I recommend my patients take several key nutrients to help boost the immune system in the setting of travel. I recommend taking oleuropin before the flight, which is the active ingredient in the olive leaf that has potent antibacterial, antifungal, and antiviral properties. In addition, beta 1,3 glucans and the prickly pear are cutting edge nutrients that I recommend that have been studied for their anti-microbial effects. Vitamin C and a combination of immune boosting mushrooms, such as cordyceps, reishi, and maitake, may help to prevent colds and other respiratory ailments in flight.
Boosting the immune system by addressing the gut is essential. It is an established fact that over sixty percent of the immune system is in the gut, referred to as the gut associated lymphoid tissue (GALT). In addition to a healthy diet, intake of a probiotic (beneficial gastrointestinal flora) is imperative to optimizing function. I strongly recommend taking a probiotic a week before the date of travel and to continue for a week thereafter.
Constipation is common in the setting of travel. The change in food, regime, stress level, and diet are contributors to this phenomenon. Probiotics can help deal with this. Magnesium plays a crucial role as well, being that it is a muscle relaxor that can relax the muscles of the colon wall and therefore improve regularity. Hydration, exercise and healthy fiber intake are important as well.
It is not uncommon to get a muscle cramp during the flight. Magnesium, a natural muscle relaxer, can help to prevent this. Be careful, because what feels like a cramp may actually be a blood clot. I highly recommend taking natural supplements that improve circulation before the flight. Natural vitamin E and omega-3 fish oil have been shown to optimize the cardiovascular system. Their mild blood thinning effect may help to prevent a clot. I also recommend the use of nattokinase for clot prevention. There is a lot of research supporting nattokinase’s role as an anti-clotting agent. It is an enzyme extracted from natto, which is derived from fermented soybeans.
To make it more user-friendly, I have put together all the supplements described above into prearranged packets. I have blended the highest quality nutrients into the “Flight Pack,” the only physician-grade supplement pack on the market used to optimize health and well-being while flying. I hope you find them helpful. Take one packet with a meal before your flight. Each Flight Pack contains 8 supplements. If it is okay with your physician, you can take this packet daily while traveling. Do not take if you are pregnant, are taking a blood thinner, have kidney or liver disease, or a bleeding disorder. Living smarter, living longer… (The product can be ordered online at www.advanced-medicine.com.)
The relationship between cancer and inflammation is well established. There is a strong association between chronic, ongoing inflammation in the body and the occurrence of cancer. It is most obviously demonstrated with the increased chance (five to seven times higher than the general population) for people with chronic inflammatory diseases.
For example chronic acid reflux and heartburn which inflames the stomach and esophagus increases risk of stomach and esophageal cancer. Acid reflux may be caused by infection with H. Pyolori which can be treated with antibiotics as well as natural medicines.
Chronic infection of the liver with Hepatitis virus B and C increases risk of liver cancer.
Chronic autoimmune inflammation of the colon or lower intestine, Ulcerative Colitis and Crohn's Disease, increases risk for colon cancer.
Chronic inflammation of the lungs due to exposure to inhaled chemical irritants including chemicals found in cigarette smoke or volatile inhaled chemicals from resins and varnishes or inhaled particles such as asbestos increase risk of lung cancer.
Chronic inflammation of the skin due to repeated sunburns increases risk of skin cancer.
Inflammation fuels cancer in several ways:
Inflammatory chemicals release free radicals or free roving electrons that damage cells and may initiate damage to the genetic material in our cells, our DNA thus leading to cellular mutations, loss of normal cell functions and cancer.
Inflammatory chemicals stimulate the production of new capillaries, tiny blood vessels that feed cancerous growths.
Many cancer cells will spread and metastasize in clumps that contain both inflammatory white blood cells of the activated immune system, called lymphocytes and sticky blood cells called platelets, which allow the cells to attach to new organs and tissues.This allows cancer cells spread by travelling to and establishing growth in new locations.
Common Triggers of Inflammation:
chronic bacterial, viral or parasitic infections
chemical irritants such as formaldehyde or toluene found in many cosmetics or benzene found in oven cleaners, detergents, furniture polishes and nail polish removers
Inhaled particles from fiberglass, silica or asbestos found in building materials and insulation
Ionizing radiation from sun exposure or frequent medical scans and xrays
Once the immune system has become activated and inflammation unfolds, the inflamed cells are further damaged by oxidative stress... the presence of roving free electrons that can damage cellular genetic material, our DNA. Damaged DNA is a primary cause of cancer as the expression of genes becomes altered. Protecting cells from this damage is crucial in preventing and controlling cancer.
Recognizing that inflammation is occurring and is ongoing and poorly managed is the first step. The second step is to take action
Here are Five Ways to Reduce Inflammation Naturally
1/Eat an Anti-Inflammatory Diet An anti-inflammatory diet is organic and free of chemical additives and artificial colorings and flavorings and preservatives. Eat whole, fresh, unprocessed foods that are not charred or deep fried. Eat a wide variety of colorful fruits and vegetables. Eat healthy fats and oils, emphasizing Omega 3 fats found in cold water fish such as salmon and cod and sardines. Include other healthy oils such as walnuts, almonds, avocadoes, olives and flax seeds. Eat animal products from grass fed rather than grain fed (conventionally raised) animals. Emphasize a plant based diet over a diet derived primarily from animal products. Avoid refined sugars and flours and corn syrup. Eat plenty of fiber from whole grains, fruits and vegetables and beans. Drink plenty of fluids everyday.
2/Use Anti-Inflammatory Herbs to Manage Inflammation Common Herbs which reduce inflammation by lowering inflammatory and damaging molecules such COX2 and LOX5 in our cells include: Tumeric, Ginger root, Boswellia, Resveratrol, Milk Thistle and Cat’s Claw.
3/Avoid chemical exposures: Eat an organic, chemical free diet as noted above. Drink filtered water. Use only cosmetics that are free of irritating and carcinogenic additives. Identify chemical exposures in the home (cleaning supplies, garden supplies) and the workplace (chemical exposures, fumes, inhalants, radiation).
4/Identify and Treat Chronic Infections: Do you have persistent heartburn? Do you have chronic loose stool or diarrhea or gas and bloating? Have you been exposed to hepatitis or parasites while travelling internationally? Do you have a chronic post nasal drip or cough? See your health care provider to determine the cause and get proper treatment and follow up. Once the infection is resolved take measures to boost your immunity to prevent future infections. Eat fermented foods or use probiotic supplements which contain healthy organisms that are part of natural immunity in our digestive tract and intestines.
5/Keep your body lean. Keep your weight under control. Reduce your Body Fat. Build Muscle. Excess body fat is a factory for inflammatory molecules. All overweight and over fat people have much higher levels of inflammation than people who are lean. Eat a balanced diet, get regular cardiovascular and weight bearing exercise. Get enough sleep and manage your stress. All of these factors will contribute to normal body weight, reduced fat and increased lean muscle.
References: Ed Friedlander, “Inflammation and Repair,” www.pathguy.com/lectures/inflamma.htm (accessed fall 2006). Emily Shacter and Sigmund A. Weitzman, ”Chronic Inflammation and Cancer,” Oncology 16, no. 2 (February 2002). www.cancernetwork.com/journals/oncology/o0202d.htm (accessed fall 2006). National Cancer Institute Division of Cancer Biology, “Executive Summary of Inflammation and Cancer Think Tank.” http://dcb.nci.nih.gov/thinktank/Executive_Summary_of_Inflammation_and_ Cancer_Think_Tank.cfm (accessed fall 2006). Haiyan Xu et al., “Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance,” J. Clin. Invest. 112 (2003): 1821-30. Also available at www.ncbi.nlm.nih. gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=14679177 (accessed fall 2006). American Heart Association, Inc., “Inflammation, Heart Disease and Stroke: The Role of Schindler, Thomas, et al. 2006. Relationship Between Increasing Body Weight, Insulin Resistance, Inflammation, Adipocytokine Leptin, and Coronary Circulatory Function. JACC 47:1188-95.
Posted By Administration,
Monday, February 21, 2011
Updated: Friday, April 18, 2014
If you watched Dateline's interview with Suzanne Somers and are wondering about ACAM's position on alternative approaches to cancer treatment, this video outlines the basic differences between integrative and alternative medicine.
Posted By Administration,
Wednesday, February 16, 2011
Updated: Friday, April 18, 2014
An evaluation of 15 studies concludes that zinc lozenges, tablets or syrup can help cut the duration of cold symptoms by a day and reduce their severity. But the debate on the subject is far from over.
People who begin using zinc lozenges, tablets or syrup at the first signs of a cold are more likely to get well faster, researchers reported Tuesday. But the new findings probably won't be the last word on the issue, which has been the subject of debate since the idea was first proposed in 1984.
Since that time, 18 studies have examined zinc in preventing or treating colds. Some found zinc supplements were modestly helpful, others failed to turn up any benefits.
One analysis of 14 studies, published in 2007, concluded that many of the studies were too flawed to draw any conclusions.
In the latest report, published by the Cochrane Library, an international network of experts who conduct systematic reviews of research, scientists in India evaluated 15 studies, including four published since 2000.
Two of the studies evaluated focused on zinc's effectiveness in preventing colds and the rest on its ability to shorten the duration of colds. The 15 studies involved 1,360 participants ranging in age from 1 to 65 with good overall health.
Pooling the data, researchers found that people who took zinc within 24 hours of the start of symptoms were over their colds about one day sooner than people who took placebos. The analysis also found that the severity of cold symptoms was somewhat milder among people who took zinc.
Whether these results will be considered meaningful depends on whom you ask, said Dr. Kay Dickersin, a professor of epidemiology at Johns Hopkins University's Bloomberg School of Public Health and director of the U.S. Cochrane Center, one of the 12 centers around the world that facilitate the work of the Cochrane reviews. Dickersin was not involved in the research.
"I might say, 'A day less of symptoms is good; I'll do it.' But you might say, 'A day is nothing; it's not worth driving to the drugstore,' " she said.
Moreover, since the study designs varied widely, it's impossible to make recommendations on what doses are optimal, what formulations are best and how long to use the products, said the authors of the analysis, Meenu Singh and Rashmi R. Das of the Postgraduate Institute of Medical Education and Research in Chandigarh, India.
"I think there is a need for more research so we can get a sense of how well zinc works or if it even does work," Dickersin said.
Zinc lozenges and syrup, commonly available in drugstores, are typically taken every two to three hours during waking hours for at least five days. Most products recommend a standard daily dose for cold treatment is about 30 milligrams of syrup per day or about 60 milligrams in lozenges.
When a zinc acetate formulation is taken in a high enough dose and started early in the onset of a cold, it's likely to be effective, said Dr. Ananda Prasad, an expert on zinc at Wayne State University in Detroit who conducted two studies, both of which showed a positive effect.
"In our studies, we only included patients who had [begun treatment] within 24 hours" of the start of symptoms, he said. "If you don't take zinc within 24 hours, it does not have much effect."
But an examination of only the most scientifically rigorous of the zinc studies shows it probably doesn't shorten colds, said Dr. Terence M. Davidson, the director of the UC San Diego Nasal Dysfunction Clinic.
"The more rigorously scientific studies, where you took a group of people and gave half of them zinc and half a placebo and inoculated their nose with a cold virus, found there were no differences," Davidson said. "I think enough research has been done to show if there is some benefit, it's not going to be very significant."
There may also be risks from some of these products, said Davidson, who was the first to identify harmful side effects from zinc nasal spray.
In 2009, the Food and Drug Administration warned consumers to stop using three zinc-containing Zicam nasal products after receiving 130 reports about loss of smell associated with the products. The Cochrane Library analysis did not investigate zinc nasal sprays.
Researchers don't know why zinc may affect the common cold. It could be that zinc prevents rhinoviruses from attacking nasal cells, slows the replication of the virus or prevents histamine release (which causes sneezing, runny nose and rash).
In the United States, colds contribute to 75 to 100 million visits to doctors each year at a cost of about $7.7 billion. Colds are among the most common reasons for absenteeism from work and school.
"Any medication that is only partially effective in the treatment and prevention of the common cold could markedly reduce morbidity and economic losses due to this illness," Singh and Das wrote.
Source: Roan, Shari. February 16, 2011. The Los Angeles Times. Zinc found to be effective in treating colds. http://www.latimes.com/health/la-he-zinc-colds-20110216,0,1557679.story
It’s nothing to sneeze at: 54 million Americans suffer from seasonal allergies. Until now, many have either wearily resigned themselves to the watery eyes, runny nose, sneezing, wheezing and hives associated with the condition, or have opted to try to combat these symptoms with allergy shots that can be costly and inconvenient. That’s been the bad news. The good news is that a recent study of more than 60 patients allergic to pollen, dust mites and cat allergens has shown that an approach known as sublingual desensitization is indeed a safe and effective alternative to traditional immunotherapy injections. The study findings have prompted researchers to strongly recommend its use, especially in children. In the study, the practice was shown to significantly reduce the symptoms of hay fever and nasal allergies, as well as the need for medication, compared to placebo.
The study finally validates what we’ve been practicing at the Magaziner Center for Wellness with great success for more than 24 years. During this time, we’ve found sublingual desensitization (which is defined as immunotherapy using drops or pills) to be:
More convenient – as it can be self-administered by the patient
Without risk of anaphylactic shock, a potential side effect of immunotherapy injections.
Less taxing mentally and physically
This last bullet has been an important one for our patients who are children whose parents wisely sought a natural therapy. Sublingual desensitization is great for kids – it’s the difference between taking a drop or a pill orally versus being stuck with a needle. And, let’s face it, how many children do you know that aren’t a little upset at the sight of a needle?
Like all treatments at the Magaziner Center for Wellness, our patients first undergo a thorough evaluation. We test patients’ reactions to common, as well as unexpected, allergens, including:
Pollens (grass, trees and weeds)
Chemicals (perfumes, paint, carpets, etc.)
Why? Because, simply put, allergies are additive. If a person suffers from seasonal allergies, what he or she eats and breathes throughout the year affects his or her reaction during the documented allergy season. In fact, we have found that food allergies and food sensitivities have more to do with chronic complaints than almost any other factors.
After patients’ reactions are tested, we use injection therapy to place tiny amounts of the allergen into the bloodstream to assess clinical symptoms and behavioral reactions (i.e., change in frequency of headaches, even handwriting samples). When we get to the point that triggers a response, we give successive dosages until the symptoms that have been created disappear. Once the level is identified, we make up a vial of antigens that patients place as drops under their tongue on a daily basis.
In the simplest terms, we are naturally treating the immune system and getting it to respond appropriately to the allergens. This takes time, of course, so it is recommended that anyone who suffers from seasonal allergies receive treatment in mid-March so that the immune system’s response can be built well in advance of the blossoming of trees and flowers between April and October.
Posted By Administration,
Tuesday, February 15, 2011
Updated: Friday, April 18, 2014
LED lights have been marketed as environmentally preferable alternatives to traditional light bulbs, but many contain lead, arsenic and a dozen other potentially hazardous substances, according to new research out of UC Irvine.
"LEDs are touted as the next generation of lighting," says Oladele Ogunseitan, chairman of UCI's Department of Population Health & Disease Prevention, in a university statement about his published research. "But as we try to find better products that do not deplete energy resources or contribute to global warming, we have to be vigilant about the toxicity hazards of those marketed as replacements." A light-emitting diode (LED) is a semiconductor light source that for years has been used as indicator lamps for aviation, automobiles and traffic signals. Amid concerns about global warming and the need for devices that are safer and use less energy, LEDs have increasingly replaced traditional bulbs that contain mercury. An expansion into the household market is currently under way.
For the research, Ogunseitan and fellow scientists at UCI and UC Davis crunched multicolored lightbulbs sold in Christmas strands; red, yellow and green traffic lights; and automobile headlights and brake lights. They then measured the contents and found differing levels of toxic materials, including lead and arsenic.
Low-intensity red lights contained up to eight times the amount of lead allowed under California law. High-intensity, brighter bulbs had more contaminants than lower ones. White bulbs contained the least lead but had high levels of nickel.
Referring to the holiday lights in the January 2011 issue of Environmental Science & Technology, the team wrote, "We find the low-intensity red LEDs exhibit significant cancer and non-cancer potentials due to the high content of arsenic and lead."
Results from the larger lighting products will be published later, but as Ogunseitan indicates, "It's more of the same."
Toxins like those Ogunseitan and his team found in LEDs have been linked to different cancers, neurological damage, kidney disease, hypertension, skin rashes and other illnesses. The copper used in some LEDs also poses an ecological threat to fish, rivers and lakes.
As of now, LED products are not classified as hazardous waste. Ogunseitan believes his research exposes a need for mandatory product-replacement testing, something that was never done as manufacturers put LEDs in products that replaced incandescent bulbs.
As precautions, Ogunseitan advises refraining from throwing LEDs in landfills. He also recommends that crews dispatched to clean up vehicle collisions wear protective gear and that homeowners don gloves and masks when handling broken LED lights.
You won't be overcome by cancer if you breathe the contents of a broken or cracked LED light, he notes. It'll just be one more toxin your body is exposed to on the road to the Big C.
Source: February 15, 2011. OC Weekly Blog. Coker, Mike. LED Lights, Like Incandescent Bulbs They Replace, Contain Toxins: UC Irvine Research. http://blogs.ocweekly.com/navelgazing/2011/02/oladele_ogunseitan_uci_led_lig.php
Posted By Administration,
Monday, February 14, 2011
Updated: Friday, April 18, 2014
New research shows a link between use of two pesticides, rotenone and paraquat, and Parkinson's disease. People who used either pesticide developed Parkinson’s disease approximately 2.5 times more often than non-users.
The study was a collaborative effort conducted by researchers at the National Institute of Environmental Health Sciences (NIEHS), which is part of the National Institutes of Health, and the Parkinson's Institute and Clinical Center in Sunnyvale, Calif.
"Rotenone directly inhibits the function of the mitochondria, the structure responsible for making energy in the cell," said Freya Kamel, Ph.D., a researcher in the intramural program at NIEHS and co-author of the paper appearing online in the journal Environmental Health Perspectives. "Paraquat increases production of certain oxygen derivatives that may harm cellular structures. People who used these pesticides or others with a similar mechanism of action were more likely to develop Parkinson's disease.
The authors studied 110 people with Parkinson’s disease and 358 matched controls from the Farming and Movement Evaluation (FAME) Study (http://www.niehs.nih.gov/research/atniehs/labs/epi/studies/fame/index.cfm) to investigate the relationship between Parkinson’s disease and exposure to pesticides or other agents that are toxic to nervous tissue. FAME is a case-control study that is part of the larger Agricultural Health Study (http://www.niehs.nih.gov/research/atniehs/labs/epi/studies/ahs/index.cfm), a study of farming and health in approximately 90,000 licensed pesticide applicators and their spouses. The investigators diagnosed Parkinson's disease by agreement of movement disorder specialists and assessed the lifelong use of pesticides using detailed interviews.
There are no home garden or residential uses for either paraquat or rotenone currently registered. Paraquat use has long been restricted to certified applicators, largely due to concerns based on studies of animal models of Parkinson's disease. Use of rotenone as a pesticide to kill invasive fish species is currently the only allowable use of this pesticide.
"These findings help us to understand the biologic changes underlying Parkinson’s disease. This may have important implications for the treatment and ultimately the prevention of Parkinson's disease," said Caroline Tanner, M.D., Ph.D., clinical research director of the Parkinson’s Institute and Clinical Center, and lead author of the article.
The NIEHS supports research to understand the effects of the environment on human health and is part of NIH. For more information on environmental health topics, visit www.niehs.nih.gov. Subscribe to one or more of the NIEHS news lists (www.niehs.nih.gov/news/releases/newslist/index.cfm) to stay current on NIEHS news, press releases, grant opportunities, training, events, and publications.
The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visitwww.nih.gov.
Reference: Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, Korell M, Marras C, Bhudhikanok GS, Kasten M, Chade AR, Comyns K, Richards MB, Meng C, Priestly B, Fernandez HH, Cambi F, Umbach DM, Blair A, Sandler DP, Langston JW. 2011. Rotenone, paraquat and Parkinson’s disease. Environ Health Perspect; doi:10.1289/ehp.1002839 [Online 26 January 2011].
Source: National Institutes of Health (NIH). February 11, 2011. NIH study finds two pesticides associated with Parkinson's Disease. http://www.nih.gov/news/health/feb2011/niehs-11.htm?
Posted By Administration,
Tuesday, February 8, 2011
Updated: Friday, April 18, 2014
The US Department of Agriculture last Friday gave farmers the go-ahead to resume planting Roundup Ready sugarbeets—claiming it’s the only way to avoid a nationwide shortage of sugar!
Hot on the heels of the deregulation of genetically engineered (GE) alfalfa, the USDA said it would once again allow the GE sugarbeet to be planted, contrary to the order of district court judge Jeffrey S. White, who said a full environmental impact statement (EIS) needed to be done first. As the Wall Street Journal points out, an EIS of the type ordered by the judge is usually thousands of pages long and takes years to conduct. That would have kept the genetically modified sugarbeets out of the hands of farmers at least through 2012.
This would allow farmers to begin planting GE sugarbeets this spring. But the environmental and organic seed groups that originally sued the USDA said Friday they would ask Judge White to block this latest move by the USDA.
Processors say there aren’t enough non-GE sugarbeet seeds around for farmers to plant this spring. A study conducted for the sugar industry predicted that US sugar production would plunge 20% if the judge’s ban stays in place, and it appears this study alarmed food companies enough that they were able the pressure USDA into acting now. (For more on sugar and sweeteners, see our article elsewhere in this issue.)
In this case, the sugarbeets are being “partially deregulated”: USDA is permitting farmers to plant genetically modified sugarbeets this year only if they adhere to rules designed to prevent the plant’s wind-blown pollen from reaching organic fields, where its biotechnology traits could spread—though if the rules themselves prove ineffective, organic sugarbeets will be contaminated.
That contamination is what is most worrisome. The Organic Consumers Association had this to say about the deregulation of alfalfa: “[It is] guaranteed to spread its mutant genes and seeds across the nation; guaranteed to contaminate the alfalfa fed to organic animals; guaranteed to lead to massive poisoning of farm workers and destruction of the essential soil food web by the toxic herbicide, Roundup; and guaranteed to produce Roundup-resistant superweeds….” Health advocates have the same concerns about sugarbeets.
If you haven’t already done so, please visit the Aliance for Natural Health's Action Alert page where you can write to President Obama, Congress, and the USDA, and tell them to reverse this terrible decision. Please contact them today!
Posted By Administration,
Friday, February 4, 2011
Updated: Friday, April 18, 2014
Tom D. Thacher, MD and Bart L. Clarke, MD
The past decade has seen renewed interest in the sunshine vitamin, vitamin D, because new data suggest that its benefits extend beyond healthy bones. Accompanying this renewed interest has been a proliferation of published studies related to the effects of vitamin D in many varying clinical conditions. This article discusses the definition of vitamin D insufficiency, identifies the sources of variation in vitamin D status, reviews the evidence for the clinical benefits of vitamin D, and recognizes indications for vitamin D testing.
Representative studies were selected to highlight some of the limitations of current knowledge related to vitamin D insufficiency and the clinical benefits of vitamin D. We selected studies with the strongest level of evidence for clinical decision making related to vitamin D and health outcomes from our personal libraries of the vitamin D literature and from a search of the PubMed database using the term vitamin D in combination with the following terms related to the potential nonskeletal benefits of vitamin D: mortality, cardiovascular, diabetes mellitus, cancer, multiple sclerosis, allergy, asthma, infection, depression, psychiatric, and pain. The level of evidence was assessed with the following hierarchy: meta-analyses of randomized controlled trials (RCTs), RCTs, nonrandomized intervention studies, meta-analyses of observational studies (cohort and case-control studies), and observational studies.
The road to the discovery of vitamin D began with recognition of the childhood bone disease of rickets. The first formal medical treatise on rickets was published by Francis Glisson in 1650, when it was identified as a new disease that was more frequent in the rich than in the poor. During the industrial revolution of the 1800s, the prevalence of rickets increased dramatically, ranging from 40% to 60% among children in crowded and polluted urban areas. In 1822, Sniadecki was the first to recognize and report the association of rickets with a lack of sunlight exposure. By the mid-1800s, cod liver oil had been established as an effective treatment for rickets. The work of Mellanby and McCollum led to the discovery of vitamin D as the agent in cod liver oil that had antirachitic properties. This discovery eventually led to the fortification of milk and other foods with vitamin D in the 1930s, and as a result rickets all but disappeared in North America and Europe.
VITAMIN D METABOLISM
The terminology related to the biochemistry of vitamin D can be confusing. Vitamin D has 2 forms and several metabolites. The 2 forms are vitamin D2 and vitamin D3, also calledergocalciferol and cholecalciferol, respectively. Vitamin D3 is produced in the skin in response to ultraviolet B radiation from sunlight or can be obtained from the diet (ie, animal sources such as deep sea fatty fish, egg yolks, or liver) or from supplements. Few foods naturally have substantial vitamin D content, and dietary vitamin D is obtained primarily through fortified foods or supplements. Vitamin D2, which is found in some plants in the diet and is produced commercially by irradiation of yeast, is used for fortification and supplementation. Both vitamin D2 and vitamin D3 can be used for supplementation.
Vitamin D metabolism. Ca = calcium; 1,25(OH)2D = 1,25-dihydroxyvitamin D; 25(OH)D = 25-hydroxyvitamin D; PTH = parathyroid hormone.
Both forms of vitamin D undergo identical metabolism (Figure). Some evidence indicates that vitamin D2 may be metabolized more rapidly than vitamin D3,but with regular daily intake they can be considered bioequivalent. Both forms of vitamin D are converted to 25-hydroxyvitamin [25(OH)D] in the liver, and the serum level of 25(OH) D is measured to determine the adequacy of vitamin D status. In the kidney, 25(OH)D is hydroxylated to 1,25-dihydroxyvitamin D [1,25(OH)2D], which is the only biologically active form of vitamin D. Acting principally on the duodenum, 1,25(OH)2D increases calcium absorption. It also acts on bone cells, both osteoblasts and osteoclasts, to mobilize calcium.
The characteristics of 1,25(OH)2D are those of a hormone, and consequently vitamin D is a prohormone rather than a true vitamin. The structure of 1,25(OH)2D is similar to that of other steroid hormones. As long as sunlight exposure is adequate, 1,25(OH)2D can be produced by the body without the requirement for ingestion in the diet. Like other hormones, 1,25(OH)2D circulates at picogram concentrations that are 1000 times less than those of the precursor 25(OH)D. Based on the need for increased calcium absorption, the synthesis of 1,25(OH)2D is tightly regulated and stimulated primarily by serum parathyroid hormone (PTH), as well as low serum calcium or phosphorus levels, and inhibited by circulating FGF23 produced by osteocytes. Although produced in the kidney, 1,25(OH)2D acts at a distance in the intestinal cell to increase calcium absorption or in the bone to stimulate differentiation and activation of osteoblasts and osteoclasts.
ASSESSING VITAMIN D STATUS
Determination of vitamin D status is not based on measurement of serum 1,25(OH)2D concentrations. Vitamin D status is assessed by measuring the prohormone 25(OH) D, which is an indicator of supply rather than function. The most stable and plentiful metabolite of vitamin D in human serum, 25(OH)D has a half-life of about 3 weeks, making it the most suitable indicator of vitamin D status. In the past, vitamin D deficiency was identified by the presence of bone disease, either rickets or osteomalacia. Bone disease caused by vitamin D deficiency is associated with serum 25(OH)D values below 10 ng/mL (to convert to nmol/L, multiply by 2.496). More recently, the term vitamin D insufficiency has been used to describe suboptimal levels of serum 25(OH)D that may be associated with other disease outcomes. Precisely defining vitamin D deficiency or insufficiency on the basis of 25(OH)D values is still a matter of much debate. A useful but rather simplistic classification of vitamin D status is shown in the Table. A cutoff value of 30 ng/mL is sometimes used for optimal vitamin status. On the basis of measured concentrations of 25(OH)D, many patients are given a diagnosis of vitamin D deficiency or insufficiency when most have no evidence of disease.
Classification of Vitamin D Status by 25(OH)D Concentrationa,b
As discussed in detail in recent reviews, investigators have considered various functional measures to assess the adequacy of vitamin D status. One functional definition of optimal vitamin D status is the 25(OH)D level that maximally suppresses PTH secretion, because the major stimulus for PTH secretion is a low level of serum ionized calcium. In adults, multiple cross-sectional examinations of the relationship between serum PTH and 25(OH)D levels demonstrate a plateau in suppression of PTH when the 25(OH)D level reaches approximately 30 ng/mL. This is the rationale for selecting 30 ng/mL as the cutoff value for defining optimal vitamin D status. However, this definition represents an average value at a population level but does not account for the wide variation in the 25(OH) D level that represents adequacy at an individual level. Many patients have very low 25(OH)D values without evidence of increased production of PTH, and conversely, 25(OH)D levels greater than 30 ng/mL do not guarantee PTH suppression. Another limitation of this definition is that, in children, an elevated PTH level does not indicate inadequate vitamin D status and has been associated with increased calcium absorption. In puberty, the PTH concentration increases, which may stimulate increased periosteal bone formation and increased bone accrual. In fact, preliminary evidence suggests that, with adequate calcium intake, a high-normal PTH level and low-normal 25(OH)D level may result in greater bone size and mass during puberty.
Another method used in some research studies for defining optimal vitamin D status is the 25(OH)D level at which there is no incremental increase in 1,25(OH)2D levels after administration of vitamin D, because the level of 1,25(OH)2D is adequate to meet demand. Similar to the findings related to PTH in adults, an incremental increase in the level of 1,25(OH)2D was observed after administration of vitamin D in children when values of 25(OH)D were less than 25 to 30 ng/mL. In situations of very low calcium intakes, some evidence suggests that the demand for 1,25(OH)2D may be greater.Thus, vitamin D requirements may vary based on customary calcium intake.
Another functional measure of vitamin D status is the 25(OH)D level that results in maximal intestinal calcium absorption. By combining the results of 3 studies in adults, Heaney concluded that optimal calcium absorption occurred at 25(OH)D levels of 32 ng/mL or greater. In contrast, another study found no association between 25(OH)D levels and calcium absorption in healthy women. Fractional calcium absorption was high (>50%) in Nigerian children with presumed dietary calcium deficiency rickets and low dietary calcium intakes despite low normal serum 25(OH)D concentrations. After vitamin D administration and a marked increase in 25(OH) D and 1,25(OH)2D concentrations, fractional calcium absorption did not increase any further. In these studies in children, fractional calcium absorption was not related to serum 1,25(OH)2D levels either before or after vitamin D administration. In a study of adults attending an osteoporosis clinic, concentrations of 1,25(OH)2D and intestinal calcium absorption did not appear to decline until 25(OH) D concentrations fell to 4 ng/mL or less, a level that is generally considered to be indicative of severe vitamin D deficiency.
More recently, the criterion for optimal vitamin D status has moved away from being defined as the 25(OH) D concentration needed to achieve skeletal health to that which demonstrates optimal benefits on nonskeletal health outcomes. The evidence related to these outcomes will be considered later in this review.
SOURCES OF VARIATION IN VITAMIN D STATUS
Factors known to influence 25(OH)D levels include race, vitamin D intake, sun exposure, adiposity, age, and physical activity. Even when all the factors known to influence 25(OH)D concentrations are taken into account, most of the individual variation of 25(OH)D values is difficult to explain. Consequently, it is difficult to assess the risk of clinical or biochemical consequences of vitamin D insufficiency in a patient on the basis of concentrations of 25(OH) D alone. The duration of vitamin D insufficiency, the responsiveness of the vitamin D receptor, dietary calcium intake, and individual calcium requirements likely modify the clinical consequences of vitamin D deficiency or insufficiency based on levels of 25(OH)D.
A single exposure to summer sun in a bathing suit for 20 minutes produces the equivalent of 15,000 to 20,000 IU of vitamin D3. In a study of Hawaiian surfers with sun exposure of at least 15 hours per week for the preceding 3 months, 25(OH)D levels ranged from 11 up to 71 ng/mL, demonstrating wide individual variation. Outdoor sun exposure and time spent outdoors are better predictors of serum 25(OH)D values than dietary vitamin D intake.
The 25(OH)D level achieved with the same oral dose of vitamin D varies widely by individual. The level of 25(OH)D that results in clinical consequences probably varies with calcium intake, race, age, body fat, and individual genetic factors, all of which may influence calcium homeostasis. Genetic variation represented by polymorphisms of certain genes in the vitamin D metabolic pathway explains some of the interindividual variability of 25(OH)D concentrations, particularly polymorphisms of the enzyme 7-dehydrocholesterol reductase in the skin, cytochrome P450 25-hydroxylase in the liver, and vitamin D–binding protein in the circulation. The functional effect of a particular level of 25(OH)D depends on the uptake of 25(OH)D by target cells and the efficiency of 1α-hydroxylation to produce 1,25(OH)2D.
MEASUREMENT OF 25(OH)D LEVELS
Some controversy exists regarding the best method for measuring 25(OH)D levels. Radioimmunoassay has been the most common method reported in the literature and was the method used in some of the large-scale population studies of vitamin D, such as the National Health and Nutrition Examination Survey (NHANES) and the Women's Health Initiative (WHI).
The accuracy of measurement varies widely between individual laboratories and between different assay methods. In one study, identical serum samples were provided to 6 different laboratories, and the chemiluminescent assay tended to return higher values for 25(OH)D. Competitive protein-binding assays are also known to generally yield higher 25(OH)D values. When serum samples were spiked with an additional 20 ng/mL of 25(OH)D, the increment in 25(OH)D level was less than 20 ng/mL in all the laboratories, except the one using high-performance liquid chromatography. Antibodies used in some radioimmunoassays do not detect both 25(OH)D2 and 25(OH)D3. The use of a standard cutoff value for adequate vitamin D status is problematic if applied to all laboratories and all methods. A single serum sample could be assessed as showing adequate vitamin D status in one laboratory and an insufficient level in another, with differences of up to 17 ng/mL.
More recently, large medical laboratories have begun using liquid chromatography–tandem mass spectrometry, which identifies the 25-hydroxylated forms of both vitamin D2and D3. The total 25(OH)D, which is the sum of 25(OH)D2 and 25(OH)D3, is used to evaluate vitamin D status. Since 2003, there has been more than a 15-fold increase in the volume of 25(OH)D measurements at Mayo Clinic in Rochester, MN (Singh R., personal communication), reflecting the increasing attention clinicians are giving to vitamin D status.
CLINICAL MANIFESTATIONS OF VITAMIN D DEFICIENCY
The classical manifestation of vitamin D deficiency is nutritional rickets, which results from inadequate mineralization of growing bone. Consequently, rickets is a disease of children. Far from being eradicated, nutritional rickets continues to occur throughout the world, with reports from at least 60 countries in the past 20 years. In a review of published cases of rickets in the United States, most occurred in children younger than 30 months. The vast majority of cases in the United States occurred in African American infants who were fed with breast milk rather than formula. Florid rickets manifests with leg deformities; enlargement of the growth plates of the wrists, ankles, and costochondral junctions; and rib cage deformities. Subtle symptoms that should raise the clinical suspicion of rickets in children include bone pain in the legs, delayed age of standing or walking, frequent falling, and delayed growth. Hypocalcemic seizures in the first year of life may be the initial manifestation of rickets.
Radiography of the long bones at the knees and the wrists is necessary to confirm the diagnosis of rickets. Radiography demonstrates impaired mineralization of the growth plates, evident by widening of the growth plate and fraying of the margin of the metaphyses. Biochemical features most consistently include hypophosphatemia and an elevated alkaline phosphatase level. As a result of vitamin D deficiency, serum concentrations of 25(OH)D are very low in patients with rickets, usually less than 5 ng/mL. However, concentrations of 25(OH)D may not be markedly reduced if rickets results from calcium deficiency or if the child has recently received vitamin D or sun exposure. In some tropical countries, where sun exposure is plentiful, calcium deficiency is more important than vitamin D deficiency as a cause of rickets. However, even in the United States, only 22% of children with nutritional rickets had deficient levels of 25(OH)D, indicating that calcium deficiency as a cause of rickets needs to be considered domestically as well.
Osteomalacia refers to the failure of organic osteoid formed by osteoblasts to become mineralized with calcium and phosphorus. Although histological osteomalacia is characteristic of rickets, the term osteomalacia is generally used to describe the bone disease caused by vitamin D deficiency in adults, who no longer have growing bones. The clinical manifestations of these 2 conditions are different.
Bone pain is a characteristic feature of osteomalacia, and it can be confused with arthritis or fibromyalgia. Bone pain due to osteomalacia primarily affects the bones between the joints, whereas arthritis usually causes predominantly joint pain, and fibromyalgia causes more diffuse muscle and soft tissue pain; however, it can be difficult to distinguish between these disorders. Proximal muscle weakness and gait instability are often present. Because the growth plates have closed in adults, the radiographic features differ from those typical of rickets. Radiography may reveal pseudofractures of the pelvis, femurs, metatarsals, or lateral margins of the scapulae. The biochemical features of osteomalacia are similar to those of rickets, with increased serum alkaline phosphatase and PTH values, and low calcium, phosphorus, and 25(OH)D values in most cases. A review of all the archived cases of bone biopsy–proven osteomalacia seen by the Bone Histomorphometry Laboratory at Mayo Clinic concluded that radiographic examination as well as serum calcium, phosphorus, and alkaline phosphatase assays are adequate screening tests in patients who have a clinical presentation suggestive of osteomalacia, but that 25(OH)D values may be normal.
In a cross-sectional study of iliac bone biopsy specimens obtained at autopsy, an excess accumulation of osteoid, which corresponds with histological osteomalacia, was found only in patients with 25(OH)D values less than 25 ng/mL. However, even patients with very low values of 25(OH)D did not consistently have evidence of osteomalacia.
POTENTIAL BENEFITS OF VITAMIN D
Apart from the deficiency diseases of rickets and osteomalacia, recent evidence suggests other skeletal and nonskeletal benefits of vitamin D. In evaluating the evidence, it is important to recognize the limitations inherent in the study design and methodology. Important issues that apply to vitamin D research include the following:
Was the study design observational, which can only demonstrate associations and is subject to confounding, or was it an RCT that generally balances unmeasured confounding variables?
How was the intake of vitamin D measured? Was the serum 25(OH)D value considered a proxy measure of vitamin D intake?
What outcome was measured to assess the benefit of vitamin D? Was it the achieved 25(OH)D level or a specific clinical outcome that matters to the patient? Was assessment of the outcome the primary aim of the study?
Is 25(OH)D the most appropriate biomarker of vitamin D status in all situations?
In the following section, representative studies of the available evidence related to the skeletal and nonskeletal effects of vitamin D are reviewed.
Bone Density. In addition to the treatment and prevention of vitamin D–deficiency rickets in children, vitamin D has been associated with other beneficial skeletal effects. A retrospective cohort study of pubertal girls demonstrated increased bone mineral density (BMD) of the femoral neck, but not of the spine or radius, among those who received supplemental vitamin D in infancy. Evidence of a positive association between BMD and serum 25(OH)D concentrations in adolescents is fair, but the evidence for a positive association in infants is inconsistent. Serum 25(OH)D concentration was related to hip BMD in community-dwelling women and men aged at least 20 years who participated in the US NHANES III survey. Higher calcium intake was significantly associated with higher BMD only for women with 25(OH)D values less than 20 ng/mL. One of the limitations of a cross-sectional study like the NHANES survey is that it can demonstrate only associations, not cause-and-effect relationships. Another confounding factor may be associated with low vitamin D intake and low bone density. For example, healthier people who exercise more outside in the sun may have greater bone density because of their exercise and higher 25(OH)D levels because of sun exposure. The WHI calcium and vitamin D supplementation trial showed that hip bone density was 1.06% higher in women receiving calcium and vitamin D supplementation vs placebo at 9 years, but that their lumbar spine and total body bone density did not differ significantly from those receiving placebo during this interval.
Fractures and Falls. On the basis of RCTs, the strongest evidence for the benefit of vitamin D relates to the prevention of fractures and falls. In a meta-analysis of 12 RCTs, a reduced nonvertebral fracture risk was demonstrated only for doses of vitamin D greater than 400 IU/d (relative risk [RR], 0.80; 95% confidence level [CI], 0.72-0.89). Similarly, a meta-analysis of 8 RCTs demonstrated that vitamin D reduced the risk of falls (RR, 0.78; 95% CI, 0.64-0.94), but only if the dose was 700 IU/d or greater and the 25(OH)D concentration was at least 25 ng/mL. The benefit of vitamin D could have been limited to those with unrecognized osteomalacia, which is associated with proximal muscle weakness and gait instability. These high-quality studies provide clear evidence that a minimum dose of 800 IU/d of vitamin D will reduce the risk of falls and fractures in older adults. However, a recent RCT of a 500,000 IU annual dose of vitamin D in women of advanced age increased the median 25(OH)D concentration from 20 ng/mL to 48 ng/mL one month later but resulted in an increased risk of falls and fractures in the group receiving this regimen.
Interest in the nonskeletal effects of vitamin D has been increasing since the discovery of vitamin D receptors and the 1α-hydroxylase enzyme in multiple tissues, including cells of the pancreas, immune system, macrophages, vascular endothelium, stomach, epidermis, colon, and placenta. In these tissues, 25(OH)D can be converted to 1,25(OH)2D locally, without altering serum 1,25(OH)2D concentrations. Through these paracrine effects, 1,25(OH)2D influences the expression of genes in local tissues. However, the evidence for the nonskeletal benefits of vitamin D is not as strong as the evidence for the skeletal effects.
Lower Mortality Rate. In a prospective observational study of adults older than 65 years participating in NHANES III, the risk of death was 45% lower in those with 25(OH)D values greater than 40 ng/mL compared with those with values less than 10 ng/mL (hazard ratio [HR], 0.55; 95% CI, 0.34-0.88). However, this may simply reflect the fact that people with underlying illness or immobility (who are more likely to die) tend to have lower 25(OH)D levels, in part as a result of having spent less time outdoors or of having less adequate nutrition. Because vitamin D is sequestered in adipose tissue, obesity is also associated with lower 25(OH)D levels. However, observational studies cannot prove whether low 25(OH)D status is the cause of greater mortality or just a marker of other underlying risk factors.
In contrast, a meta-analysis of 18 RCTs of vitamin D supplementation in postmenopausal women of advanced age, with dosages ranging from 300 to 2000 IU/d, reported a 7% lower risk of death in those receiving a vitamin D supplement (RR, 0.93; 95% CI, 0.87-0.99). This highlights the difference often found between RCTs and observational studies. The effect sizes found in observational studies are often attenuated or absent in RCTs.The situation with vitamin D is analogous to that of hormone replacement therapy (HRT) in postmenopausal women. The beneficial effects of HRT were demonstrated for multiple health outcomes in observational studies, but the WHI RCT in older postmenopausal women failed to confirm the beneficial effects of HRT on dementia and cardiovascular disease. In the observational trials, healthier women were more likely to use estrogen replacement and had fewer adverse health outcomes, indicating a “healthy user” bias. Only an RCT definitively demonstrated that the risks of first-time use of HRT outweighed the benefits in women older than 60 years.
Despite the slight reduction in mortality associated with vitamin D supplementation, the primary aim of the RCTs included in the meta-analysis was not to assess mortality. Not all trials of vitamin D reported mortality outcomes, so those trials could not be included in the meta-analysis. Trials that showed a mortality effect would be more likely to report this outcome, leading to a high likelihood of reporting bias that could render the slight mortality reduction statistically insignificant.
Lower Cardiovascular Mortality. The reduced mortality in the aforementioned observational study mirrored in large part the reduced cardiovascular mortality in those with 25(OH)D values greater than 40 ng/mL compared with those with values less than 10 ng/mL (HR, 0.42; 95% CI, 0.21-0.85). In another observational cohort study, patients who had angiography and 25(OH)D measurements were followed up for 8 years. Those from the highest 25(OH)D quartile (median, 28 ng/mL) had a lower mortality (HR, 0.45; 95% CI, 0.32-0.64) than those from the lowest quartile (median, 8 ng/mL). Although these observational studies do not demonstrate that low 25(OH)D values accelerate cardiovascular mortality, low 25(OH)D concentrations were associated with serum markers of inflammation that are indicators of cardiac risk.
Recently, concern has been expressed that vitamin D could potentially accelerate vascular disease. In a study of African Americans with type 2 diabetes mellitus, 25(OH)D levels correlated with increased calcified plaque in the aorta and carotids, but not in the coronary arteries.Vascular disease associated with chronic kidney disease, especially that associated with very low bone turnover, may also be accelerated with supplementation with standard doses of vitamin D. Furthermore, concern has been raised recently that other disorders characterized by vascular inflammation, such as diabetes mellitus, rheumatoid arthritis, or systemic lupus erythematosus, may not benefit from standard recommended doses of vitamin D supplementation.
Vitamin D may affect other cardiovascular and metabolic disease risks. In an observational study of adolescents in NHANES III, those with the lowest 25(OH)D values (<15 ng/mL) had more than a 2-fold greater odds of having an elevated blood pressure compared with the group of adolescents with higher 25(OH)D levels (>26 ng/mL) (odds ratio [OR], 2.4; 95% CI, 1.3-4.2).
The NHANES III data in adults indicated that those with 25(OH)D levels of less than 21 ng/mL had an increased risk of hypertension, diabetes, obesity, and high triglyceride levels—all metabolic manifestations associated with increased cardiovascular mortality. Although obesity is associated with lower serum 25(OH)D levels because of the sequestration of vitamin D in adipose tissue, it is likely not the consequence of low 25(OH)D levels. Additionally, the 25(OH)D level may be a marker of other factors associated with obesity, such as physical inactivity and reduced outdoor sun exposure.
Reduced Risk of Diabetes Mellitus. A meta-analysis of 5 observational studies of vitamin D supplementation in childhood reported a nearly 30% reduction in the risk of type 1 diabetes in children who had ever received vitamin D supplements (OR, 0.71; 95% CI, 0.60-0.84). Unfortunately, most studies had no information about vitamin D dosage or adherence. Because these were observational studies, and vitamin D was not randomly assigned to children, it is possible that characteristics of families who provided supplemental vitamin D to their children contributed to the decreased risk of type 1 diabetes in children receiving supplements.
Vitamin D receptors are present in pancreatic β cells, and vitamin D may augment insulin secretion and insulin sensitivity. Adolescents in NHANES III with serum 25(OH)D levels of less than 15 ng/mL were more likely to have elevated blood glucose levels than those with the highest 25(OH)D values (>26 ng/mL) (OR, 2.5; 95% CI, 1.0-6.4). The observational Nurses Health Study found that vitamin D supplementation and calcium supplementation were both associated with a reduction in risk of type 2 diabetes.Current data related to vitamin D and the risk of type 2 diabetes are limited by inadequate adjustment for confounding variables, post hoc analyses, and inability to identify the separate effects of calcium and vitamin D. Because milk is the major source of both vitamin D and calcium in the diet, it is difficult to identify the independent effects of dietary calcium and vitamin D on the basis of intake or 25(OH)D levels. Skim milk intake is also inversely associated with obesity, which could account for an association between the intake of dietary calcium and vitamin D and a reduced risk of type 2 diabetes.
Reduced Risk of Cancer. Vitamin D is known to promote cellular differentiation, inhibit cellular proliferation, and reduce the growth of certain tumors in laboratory animals. A meta-analysis of case-control studies of those with and without colon cancer found that, for each 20 ng/mL increase in serum 25(OH)D levels, the odds of colon cancer were reduced by more than 40% (OR, 0.57; 95% CI, 0.43-0.76). Other studies have shown that dietary calcium intake is also associated with reduced colon cancer risk and adenoma formation. Because milk intake is a major determinant of serum 25(OH)D levels, it is difficult to separate the effect of vitamin D from that of calcium intake.
In the case of colon cancer, one large RCT was performed to evaluate the effect of combined supplementation with calcium and vitamin D on the risk of colon cancer. In the WHI trial, supplementation with calcium and vitamin D had no significant effect on the risk of colorectal cancer during 8 years of follow-up. Several limitations of this study may have contributed to this lack of effect. Colorectal cancer is a long latency disease, and 8 years may not have been sufficient time to observe the effect of calcium and vitamin D. Another criticism is that the relatively low dose of 400 IU of vitamin D may have not been protective or sufficient to increase serum 25(OH)D levels adequately. Concentrations of 25(OH)D were measured at baseline but not during follow-up. Declining adherence over time would have further reduced the effective doses of calcium and vitamin D.
Breast cancer has also been associated with vitamin D insufficiency. A meta-analysis combining 7 observational studies reported a lower risk of breast cancer among women in the highest compared with the lowest quartile of 25(OH) D values (OR, 0.55; 95% CI, 0.38-0.80). As with colon cancer, calcium intake was also associated with a reduced risk of breast cancer. Because obesity is associated with an increased risk of breast cancer and low 25(OH)D levels, it is a confounding factor in the association between breast cancer risk and vitamin D.
As with colon cancer, the WHI RCT of a combined regimen of calcium and vitamin D showed no benefit of supplementation on the risk of breast cancer, again highlighting the different conclusions of observational studies and RCTs. The limitations of the breast cancer study are similar to those of the study focused on colon cancer. This study demonstrated the potential confounding effects of physical activity and obesity. Baseline 25(OH)D levels were greater among women with lower body mass index and more recreational physical activity. When controlling for body mass index and physical activity, serum 25(OH)D concentration was not associated with breast cancer risk.
In a meta-analysis of 11 observational studies, prostate cancer was not associated with serum 25(OH)D levels. The evidence regarding an association between pancreatic cancer and 25(OH)D levels is conflicting. A multinational cohort study found no protective association between greater 25(OH)D values and gastric, esophageal, endometrial, ovarian, kidney, non-Hodgkin lymphoma, and pancreatic cancers. Drake et al recently showed that event-free survival and overall survival were reduced in vitamin D–insufficient patients newly diagnosed as having diffuse large B-cell lymphoma and T-cell lymphoma during 34.8 months of follow-up.
To date, studies have not shown impressive effects of vitamin D treatment on malignancies.
Reduced Risk of Multiple Sclerosis. The incidence of multiple sclerosis increases with increasing latitude, corresponding with reduced ultraviolet B sun exposure and lower serum levels of 25(OH)D. A case-control study demonstrated that the odds of having multiple sclerosis were lower in the group with the highest 25(OH)D levels. However, the association was found only in white patients [OR, 0.59; 95% CI, 0.36-0.97 for a 20 ng/mL increase in 25(OH)D], not in African American patients. It is difficult to exclude the possibility that other confounding exposures associated with increasing latitude and greater indoor activity during winter months contribute to the risk of multiple sclerosis. Little evidence supports a therapeutic role for vitamin D in the treatment of multiple sclerosis.
Reduced Risk of Allergy and Asthma. Several lines of evidence demonstrate the effects of vitamin D on proinflammatory cytokines, regulatory T cells, and immune responses, with conflicting interpretation of the effects of vitamin D on allergic diseases. In a cross-sectional study of Costa Rican children, low 25(OH)D levels were associated with elevated IgE and eosinophil counts, as well as with increased asthma-related hospitalizations and use of anti-inflammatory medication. However, an association does not prove causation, and alternative explanations can account for this association. For example, children with more severe asthma may spend more time indoors and have less sun exposure.
Low maternal vitamin D intake in pregnancy has been associated with an increased likelihood of childhood wheezing at ages 3 and 5 years. In contrast, maternal 25(OH)D levels of greater than 30 ng/mL in pregnancy have been associated with childhood eczema at age 9 months and asthma at age 9 years. Vitamin D supplementation in infancy has been associated with increased atopy and allergic rhinitis in adulthood. Increasing 25(OH)D levels were associated with increasing risk of allergic rhinitis among adults in NHANES III. The conflicting data indicate the need for RCTs to demonstrate the effect of vitamin D on the prevention and control of allergic diseases.
Reduced Risk of Infection. Vitamin D is required for the expression of cathelicidin by macrophages, which is involved in bacterial killing. A meta-analysis of 7 observational studies noted a reduced risk of active tuberculosis in those with the highest vs the lowest values of 25(OH)D (OR, 0.68; 95% CI, 0.43-0.93). However, an RCT in a West African population with baseline mean 25(OH)D values of 31 ng/mL showed no effect of 100,000 IU of supplemental vitamin D given at the beginning and at 3 and 8 months of tuberculosis treatment on the rate of sputum conversion or resolution of markers of clinical severity. However, this dose of vitamin D may have been insufficient because the increase in 25(OH)D concentration during treatment did not differ between the supplement and placebo groups.
In observational data from NHANES III, persons with 25(OH)D values lower than 10 ng/mL were more likely to have had a recent upper respiratory tract infection than those with higher 25(OH)D values in all 4 seasons of the year. This association was even stronger in those with asthma or chronic obstructive pulmonary disease. Whether this association is explained by the fact that people who remain indoors are more likely to catch colds remains unclear.
A case-control study reported that mean 25(OH)D values were lower in children with bronchiolitis or pneumonia admitted to the pediatric intensive care unit than in healthy control children or in children with pneumonia admitted to the general pediatric ward.
Reduced Risk of Mental Illness. A cohort of Finnish children who received supplemental vitamin D in their first year of life had a lower risk of developing schizophrenia.However, the significance of this association is unclear because it was unrelated to adherence to vitamin D supplementation, was only evident in males, and was not found with any other mental illness.
To examine the effect of vitamin D on depression, overweight and obese patients were randomized to receive 20,000 or 40,000 IU of vitamin D or placebo weekly for 1 year. At baseline, those with 25(OH)D concentrations lower than 16 ng/mL had greater Beck Depression Inventory scores, indicating that they were more depressed, than those with higher 25(OH)D levels. The 2 groups receiving vitamin D supplementation had significant improvement in their scores, whereas the placebo group did not.
Less Musculoskeletal Pain. A small descriptive study reported that most patients (93%) with persistent musculoskeletal pain had 25(OH)D values of 20 ng/mL or less. In one RCT, patients with diffuse musculoskeletal pain or osteoarthritis and 25(OH)D values lower than 20 ng/mL were randomized to receive vitamin D or placebo for 3 months.Those given vitamin D had no improvement in their pain compared with baseline or compared with placebo-treated patients. In another double-blind RCT, primary care patients with 25(OH)D levels of 10 to 25 ng/mL were randomized to receive 50,000 IU of vitamin D or placebo weekly for 8 weeks. The treated group showed significantly greater improvement in fibromyalgia assessment scores than the placebo group. Patients with 25(OH)D values lower than 10 ng/mL were treated in an unblinded fashion with 50,000 IU of vitamin D weekly for 8 weeks but had no symptom improvement.
Reduced Risk of Renal Disease. In a subgroup analysis of the NHANES III data set, low 25(OH)D values were associated with a greater risk of kidney failure in African American but not in white participants. However, the opposite trend was observed in whites.
INDICATIONS FOR VITAMIN D TESTING
Measurement of serum 25(OH)D levels is indicated in select circumstances. If clinical symptoms of rickets in children or osteomalacia in adults are present, measurement of 25(OH)D levels will confirm vitamin D deficiency. Such testing would be appropriate in adults or children with bone pain, elevated serum alkaline phosphatase or PTH levels, and low serum calcium or phosphorus levels. Persons of advanced age, those with osteoporosis, or those at increased risk of falls or fractures may also benefit from measurement of 25(OH)D levels. However, one could argue that providing at-risk groups with routine supplementation of adequate doses of vitamin D may make testing for vitamin D insufficiency unnecessary. When to test and how to treat adults with vitamin D deficiency have recently been reviewed in this journal. No evidence shows benefit for screening 25(OH)D levels in the asymptomatic population.
Critically evaluating the evidence regarding the purported benefit of vitamin D on a multitude of health outcomes is difficult. The bulk of current data is based on observational, epidemiological studies, which are useful for generating hypotheses but not for proving causality. It is particularly difficult to tease out the effects of confounding variables that relate both to health outcomes and to vitamin D status, such as physical activity, milk intake, and adiposity. Few of the observational associations have been confirmed by RCTs, and many of the interventional studies of vitamin D also included calcium supplementation. Future clinical trials, including a National Institutes of Health–funded 5-year 20,000-participant prospective RCT comparing the effect of supplementation with 2000 IU/d of vitamin D3 or placebo, will help clarify the benefits and risks of vitamin D supplementation in many of the disorders discussed in this review.
On the basis of the current data, it seems prudent for persons older than 60 years to take a vitamin D supplement of 800 to 2000 IU/d to reduce the risk of falls and fractures. These recommendations are consistent with the recently released report of the Institute of Medicine, which recommended that healthy adults take 600 IU/d to maintain skeletal health and also concluded that information about the health benefits beyond bone health could not be considered reliable. Dark-skinned infants who are exclusively breast-fed are at greater risk of rickets and should receive 400 IU/d of supplemental vitamin D. Vitamin D supplementation in these ranges is likely to prevent bone loss, may improve bone density, may reduce fractures, and appears to reduce falls. Although vitamin D intoxication has been associated only with intakes of 50,000 to 1 million IU/d over the course of months or years, the potential risks of kidney stones, vascular disease, and fractures with high-dose vitamin D regimens are unclear. Until more data from RCTs are available, a healthy dose of skepticism should be maintained regarding the other health claims for vitamin D.
Harbour R, Miller J. A new system for grading recommendations in evidence based guidelines. BMJ. 2001;323(7308):334-336.
Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004;89(11):5387-5391.
Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr. 1998;68(4):854-858.
Holick MF, Biancuzzo RM, Chen TC, et al. Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab. 2008;93(3):677-681.
Thacher TD, Obadofin MO, O'Brien KO, Abrams SA. The effect of vitamin D2 and vitamin D3 on intestinal calcium absorption in Nigerian children with rickets. J Clin Endocrinol Metab. 2009;94(9):3314-3321.
Plum LA, DeLuca HF. The functional metabolism and molecular biology of vitamin D action. In: Holick MF, ed. Vitamin D: Physiology, Molecular Biology, and Clinical Applications. 2nd ed. New York, NY: Humana Press; 2010:61-97.
Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-281.
Kennel KA, Drake MT, Hurley DL. Vitamin D deficiency in adults: when to test and how to treat. Mayo Clin Proc. 2010;85(8):752-757.
Prentice A, Goldberg GR, Schoenmakers I. Vitamin D across the lifecycle: physiology and biomarkers. Am J Clin Nutr. 2008;88(2):500S-506S.
Chapuy MC, Preziosi P, Maamer M, et al. Prevalence of vitamin D insufficiency in an adult normal population. Osteoporos Int. 1997;7(5):439-443.
Abrams SA, Griffin IJ, Hawthorne KM, Gunn SK, Gundberg CM, Carpenter TO. Relationships among vitamin D levels, parathyroid hormone, and calcium absorption in young adolescents. J Clin Endocrinol Metab. 2005;90(10):5576-5581.
Tylavsky FA, Ryder KM, Li R, et al. Preliminary findings: 25(OH)D levels and PTH are indicators of rapid bone accrual in pubertal children. J Am Coll Nutr.2007;26(5):462-470.
Peacock M, Selby PL, Francis RM, Brown WB, Hordon L. Vitamin D deficiency, insufficiency, sufficiency and intoxication: What do they mean? In: Norman AW,Schaefer K, Grigoleit H-G, Herrath DV, eds. Vitamin D: Chemical, Biochemical and Clinical Update. Berlin, Germany: Walter de Gruyter; 1985:569-570.
Thacher TD, Fischer PR, Isichei CO, Pettifor JM. Early response to vitamin D2 in children with calcium deficiency rickets. J Pediatr. 2006;149(6):840-844.
Docio S, Riancho JA, Perez A, Olmos JM, Amado JA, Gonzalez-Macias J.Seasonal deficiency of vitamin D in children: a potential target for osteoporosis-preventing strategies? J Bone Miner Res. 1998;13(4):544-548.
Steingrimsdottir L, Gunnarsson O, Indridason OS, Franzson L, Sigurdsson G. Relationship between serum parathyroid hormone levels, vitamin D sufficiency, and calcium intake. JAMA. 2005;294(18):2336-2341.
Thacher TD, Fischer PR, Obadofin MO, Levine MA, Singh RJ, Pettifor JM.Comparison of metabolism of vitamins D(2) and D(3) in children with nutritional rickets. J Bone Miner Res. 2010;25(9):1988-1995.
Heaney RP. Functional indices of vitamin D status and ramifications of vitamin D deficiency. Am J Clin Nutr. 2004;80(6 suppl):1706S-1709S.
Aloia JF, Chen DG, Yeh JK, Chen H. Serum vitamin D metabolites and intestinal calcium absorption efficiency in women. Am J Clin Nutr. 2010;92(4):835-840.
Graff M, Thacher TD, Fischer PR, et al. Calcium absorption in Nigerian children with rickets. Am J Clin Nutr. 2004;80(5):1415-1421.
Need AG, O'Loughlin PD, Morris HA, Coates PS, Horowitz M, Nordin BE.Vitamin D metabolites and calcium absorption in severe vitamin D deficiency. J Bone Miner Res. 2008;23(11):1859-1863.
Hollis BW, Wagner CL, Drezner MK, Binkley NC. Circulating vitamin D3 and 25-hydroxyvitamin D in humans: an important tool to define adequate nutritional vitamin D status. J Steroid Biochem Mol Biol. 2007;103(3-5):631-634.
Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003;77(1):204-210.
Aloia JF, Patel M, Dimaano R, et al. Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration. Am J Clin Nutr. 2008;87(6):1952-1958.
Ahn J, Yu K, Stolzenberg-Solomon R, et al. Genome-wide association study of circulating vitamin D levels. Hum Mol Genet. 2010;19(13):2739-2745.
Binkley N, Krueger D, Cowgill CS, et al. Assay variation confounds the diagnosis of hypovitaminosis D: a call for standardization. J Clin Endocrinol Metab.2004;89(7):3152-3157.
Granado-Lorencio F, Mosteiro JS, Herrero-Barbudo C, Navarro ED,Blanco-Navarro I, Perez-Sacristan B. 25-OH-vitamin D assay variation and subject management in clinical practice. Clin Biochem. 2010;43(4-5):531-533.
Singh RJ. Quantitation of 25-OH-vitamin D (25OHD) using liquid tandem mass spectrometry (LC-MS-MS). Methods Mol Biol. 2010;603:509-517.
Thacher TD, Fischer PR, Strand MA, Pettifor JM. Nutritional rickets around the world: causes and future directions. Ann Trop Paediatr. 2006;26(1):1-16.
Weisberg P, Scanlon KS, Li R, Cogswell ME. Nutritional rickets among children in the United States: review of cases reported between 1986 and 2003. Am J Clin Nutr. 2004;80(6 suppl):1697S-1705S.
↵ Thacher TD, Fischer PR, Pettifor JM, Lawson JO, Manaster BJ, Reading JC.Radiographic scoring method for the assessment of the severity of nutritional rickets. J Trop Pediatr. 2000;46(3):132-139.
Fischer PR, Rahman A, Cimma JP, et al. Nutritional rickets without vitamin D deficiency in Bangladesh. J Trop Pediatr. 1999;45(5):291-293.
Thacher TD, Fischer PR, Pettifor JM, et al. A comparison of calcium, vitamin D, or both for nutritional rickets in Nigerian children. N Engl J Med.1999;341(8):563-568.
DeLucia MC, Mitnick ME, Carpenter TO. Nutritional rickets with normal circulating 25-hydroxyvitamin D: a call for reexamining the role of dietary calcium intake in North American infants. J Clin Endocrinol Metab. 2003;88(8):3539-3545.
Bingham CT, Fitzpatrick LA. Noninvasive testing in the diagnosis of osteomalacia. Am J Med. 1993;95(5):519-523.
Priemel M, von Domarus C, Klatte TO, et al. Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients. J Bone Miner Res.2010;25(2):305-312.
Wagner CL, Greer FR. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics. 2008;122(5):1142-1152.
Zamora SA, Rizzoli R, Belli DC, Slosman DO, Bonjour JP. Vitamin D supplementation during infancy is associated with higher bone mineral mass in prepubertal girls. J Clin Endocrinol Metab. 1999;84(12):4541-4544.
Cranney A, Horsley T, O'Donnell S, et al. Effectiveness and safety of vitamin D in relation to bone health. Evidence Report/Technology Assessment No 158. Published August 2007. AHRQ Publication No 07-E013. Rockville, MD: Agency for Healthcare Research and Quality.
Bischoff-Ferrari HA, Kiel DP, Dawson-Hughes B, et al. Dietary calcium and serum 25-hydroxyvitamin D status in relation to BMD among U.S. adults. J Bone Miner Res. 2009;24(5):935-942.
Jackson RD, LaCroix AZ, Gass M, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006;354(7):669-683.
Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med. 2009;169(6):551-561.
Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ. 2009;339:b3692.
Sanders KM, Stuart AL, Williamson EJ, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA.2010;303(18):1815-1822.
Ginde AA, Scragg R, Schwartz RS, Camargo CA Jr.. Prospective study of serum 25-hydroxyvitamin D level, cardiovascular disease mortality, and all-cause mortality in older U.S. adults. J Am Geriatr Soc. 2009;57(9):1595-1603.
Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007;167(16):1730-1737.
Lawlor DA, Davey Smith G, Kundu D, Bruckdorfer KR, Ebrahim S. Those confounded vitamins: what can we learn from the differences between observational versus randomised trial evidence? Lancet. 2004;363(9422):1724-1727.
Grady D, Rubin SM, Petitti DB, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med. 1992;117(12):1016-1037.
Grodstein F, Manson JE, Stampfer MJ. Postmenopausal hormone use and secondary prevention of coronary events in the nurses' health study: a prospective, observational study. Ann Intern Med. 2001;135(1):1-8.
Kawas C, Resnick S, Morrison A, et al. A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease: the Baltimore Longitudinal Study of Aging. Neurology. 1997;48(6):1517-1521.
Shumaker SA, Legault C, Rapp SR, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA.2003;289(20):2651-2662.
Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002;288(3):321-333.
Dobnig H, Pilz S, Scharnagl H, et al. Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Arch Intern Med. 2008;168(12):1340-1349.
Freedman BI, Wagenknecht LE, Hairston KG, et al. Vitamin D, adiposity, and calcified atherosclerotic plaque in African-Americans. J Clin Endocrinol Metab.2010;95(3):1076-1083.
Reis JP, von Muhlen D, Miller ER III., Michos ED, Appel LJ. Vitamin D status and cardiometabolic risk factors in the United States adolescent population.Pediatrics. 2009;124(3):e371-e379.
Martins D, Wolf M, Pan D, et al. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med.2007;167(11):1159-1165.
Zipitis CS, Akobeng AK. Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis. Arch Dis Child.2008;93(6):512-517.
Pittas AG, Dawson-Hughes B, Li T, et al. Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes Care. 2006;29(3):650-656.
Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes: a systematic review and meta-analysis. J Clin Endocrinol Metab.2007;92(6):2017-2029.
Yin L, Grandi N, Raum E, Haug U, Arndt V, Brenner H. Meta-analysis: longitudinal studies of serum vitamin D and colorectal cancer risk. Aliment Pharmacol Ther. 2009;30(2):113-125.
Jenab M, Bueno-de-Mesquita HB, Ferrari P, et al. Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations: a nested case-control study. BMJ. 2010;340:b5500.
Pufulete M. Intake of dairy products and risk of colorectal neoplasia. Nutr Res Rev. 2008;21(1):56-67.
Wactawski-Wende J, Kotchen JM, Anderson GL, et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med.2006;354(7):684-696.
Chen P, Hu P, Xie D, Qin Y, Wang F, Wang H. Meta-analysis of vitamin D, calcium and the prevention of breast cancer. Breast Cancer Res Treat.2010;121(2):469-477.
Chlebowski RT, Johnson KC, Kooperberg C, et al. Calcium plus vitamin D supplementation and the risk of breast cancer. J Natl Cancer Inst.2008;100(22):1581-1591.
Gandini S, Boniol M, Haukka J, et al. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma [published online ahead of print July 21, 2010]. Int J Cancer.doi: 10.1002/ijc.25439.
Stolzenberg-Solomon RZ. Vitamin D and pancreatic cancer. Ann Epidemiol.2009;19(2):89-95.
Helzlsouer KJ, VDPP Steering Committee. Overview of the cohort consortium vitamin D pooling project of rarer cancers. Am J Epidemiol. 2010;172(1):4-9.
Drake MT, Maurer MJ, Link BK, et al. Vitamin D Insufficiency and Prognosis in Non-Hodgkin's Lymphoma. J Clin Oncol. 2010;28(27):4191-4198.
Krishnan AV, Trump DL, Johnson CS, Feldman D. The role of vitamin D in cancer prevention and treatment. Endocrinol Metab Clin North Am.2010;39(2):401-418.
Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA.2006;296(23):2832-2838.
Ascherio A, Munger KL, Simon KC. Vitamin D and multiple sclerosis. Lancet Neurol. 2010;9(6):599-612.
Litonjua AA. Childhood asthma may be a consequence of vitamin D deficiency.Curr Opin Allergy Clin Immunol. 2009;9(3):202-207.
Wjst M, Dold S. Genes, factor X, and allergens: what causes allergic diseases?Allergy. 1999;54(7):757-759.
Brehm JM, Celedon JC, Soto-Quiros ME, et al. Serum vitamin D levels and markers of severity of childhood asthma in Costa Rica. Am J Respir Crit Care Med.2009;179(9):765-771.
Camargo CA Jr., Rifas-Shiman SL, Litonjua AA, et al. Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Am J Clin Nutr. 2007;85(3):788-795.
Devereux G, Litonjua AA, Turner SW, et al. Maternal vitamin D intake during pregnancy and early childhood wheezing. Am J Clin Nutr. 2007;85(3):853-859.
Gale CR, Robinson SM, Harvey NC, et al. Maternal vitamin D status during pregnancy and child outcomes. Eur J Clin Nutr. 2008;62(1):68-77.
Hypponen E, Sovio U, Wjst M, et al. Infant vitamin D supplementation and allergic conditions in adulthood: northern Finland birth cohort 1966. Ann N Y Acad Sci. 2004;1037:84-95.
Wjst M, Hypponen E. Vitamin D serum levels and allergic rhinitis. Allergy.2007;62(9):1085-1086.
Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311(5768):1770-1773.
Nnoaham KE, Clarke A. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. Int J Epidemiol. 2008;37(1):113-119.
Wejse C, Gomes VF, Rabna P, et al. Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2009;179(9):843-850.
Ginde AA, Mansbach JM, Camargo CA Jr.. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009;169(4):384-390.
McNally JD, Leis K, Matheson LA, Karuananyake C, Sankaran K,Rosenberg AM. Vitamin D deficiency in young children with severe acute lower respiratory infection. Pediatr Pulmonol. 2009;44(10):981-988.
McGrath J, Saari K, Hakko H, et al. Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study. Schizophr Res.2004;67(2-3):237-245.
Jorde R, Sneve M, Figenschau Y, Svartberg J, Waterloo K. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. J Intern Med. 2008;264(6):599-609.
Plotnikoff GA, Quigley JM. Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc.2003;78(12):1463-1470.
Warner AE, Arnspiger SA. Diffuse musculoskeletal pain is not associated with low vitamin D levels or improved by treatment with vitamin D. J Clin Rheumatol.2008;14(1):12-16.
Arvold DS, Odean MJ, Dornfeld MP, et al. Correlation of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment: a randomized controlled trial. Endocr Pract. 2009;15(3):203-212.
Melamed ML, Astor B, Michos ED, Hostetter TH, Powe NR, Muntner P. 25-hydroxyvitamin D levels, race, and the progression of kidney disease. J Am Soc Nephrol. 2009;20(12):2631-2639.
Source: Mayo Clin Proc. 2011 Jan;86(1):50-60. Thacher TD, Clarke BL. Department of Family Medicine, Mayo Clinic, Rochester, MN 55905, USA. email@example.com. http://www.mayoclinicproceedings.com/content/86/1/50.long
More than 80,000 chemicals now in use have never been fully assessed for toxic impacts on human health and the environment. Many of these chemicals are linked to increased incidence of cancer. Watch this shocking and disturbing video by expert Linda Greer, the Director of the Health Program at NRDC, the Natural Resources Defense Council, one of the most effective environmental protection groups. She clearly states that there is a lack of government oversight by the, EPA, the U.S. Environmental Protection Agency, the very department that is supposed to be protecting us, but protects corporate interests instead, putting our lives and our children’s health and wellbeing at risk.
The chemical industry should have to demonstrate that a chemical isn’t dangerous before it’s used in everyday products. But the Toxic Substances Control Act (TSCA) has no such requirements. These regulations have not been updated since 1976. It’s time to require that all chemicals be tested for safety and grant the EPA the authority to protect the public from toxic chemicals. But chemicals are “innocent until proven guilty”. This means chemicals are in use that have no proven safety record. Watch the video
The Breast Cancer Fund has a comprehensive report on the link between environmental toxic chemicals and breast cancer. The President's Cancer Panel released a report in April 2010 detailing the link between cancer and toxic exposures including chemicals used in industry, in the military and in medicine. The report states that “the link between exposure and cancer is strong” and ”the risk of cancer increases with more exposure”. Children, the unborn fetus and pregnant women are at greatest risk.
If you wish to be informed about the chemicals in products that you use at home and work, visit the website of the Environmental Working Group. They also have another website devoted to the many unregulated toxic chemicals found in personal care products such as shampoos, lotions, toothpaste and cosmetics. Another educational site that shows you how to feed your family safe and healthy food and reduce your chemical exposures at home is Organic Authority.
Dr. Sanjay Gupta, MD, a medical doctor and medical journalist produced a television series "Toxic America" which reveals the most common chemicals that are linked to a multiplicity of health problems, including many cancers that are ubiquitous in our daily lives. This report brings to light the many chemicals that find their way into the womb and into newborns who are come into life on day one with high levels of toxic chemicals in their tiny and developing bodies and then nurse on toxin laden breast milk increasing their body burden of dangerous chemicals.
Probiotics, we hear all about them now, on TV, radio and print ads! It’s great, considering that just a few years ago, most people didn’t know what they were.
Probiotics, otherwise known as “good germs”, are part of the normal flora of our intestinal tract. They begin to inhabit our intestinal tract as soon as we’re born (by vaginal delivery, rather than caesarian delivery). They are nourished by eating healthy foods from infancy, starting by drinking mother’s milk (rather than cow’s milk or soy milk). As we age and are exposed to poor diet, antibiotics, chlorinated water, steroids and environmental pollutants (xenoestrogens), their numbers begin to decline. When their numbers decline, pathogenic yeast begin to overgrow (as well as bacteria), causing symptoms in both men and (more obviously in) women (such as vaginal discharge).
Known functions of probiotics include:
The manufacture of B vitamins (such as folic acid, biotin, B3 and B6).
The manufacture of the enzyme “lactase”.
Produce antibacterial substances.
Produce anti-carcinogenic compounds.
Help reduce high cholesterol levels.
Improve the efficiency of the digestive tract.
Help recycle hormones such as estrogen.
Protect against radiation.
Deactivate certain toxins, among many others.
The primary bacteria inhabiting the small intestine is Lactobacillus acidophilus while that of the colon is Bifidobacterium bifidum. It is essential that these organisms be replaced when taking antibiotics of any kind.
In today’s world, it’s a good idea to incorporate probiotics in a wellness program because of the antibiotics that we’re unknowingly exposed to (from food and perhaps, our water supply). There are different brands available. Some need to be refrigerated while others do not. They come in various forms such as powders, liquid, capsules or “pearls”. To find out which brands are better, check out a study done by Consumer Labs. In the study, they found out that claims made by some companies such as number of viable organisms in their product somehow vary from the actual live cells. Factors such as improper storage and handling as well as shelf life affect these numbers. Therefore, it’s always important to do your own research.
Complexity and the roots of depression have always been a major and complex health issue. Depression contains other health issues such as behavioral, psychological, social, cultural, religious and the spiritual aspects of ones life. Because of the complexity aspects of depression, it should always be treated with one and the “Whole Person” ideology in mind.
The depression epidemic has gotten worse since the September 11th tragedy and all that followed. The stress of the tragedy has put a lot of old wounds of mind back in the front seat, dominating the daily activity in every aspect of everyone’s life, not only in the United States, but also throughout the world.
Dr. Jane Mak, a Neuropsychologist and clinical psychologist has stated that many of her past patients including children, have been back for visits to seek resolution to their flared up old wounds.
Today, four out of every six Americans are having difficulty concentrating on their jobs. Three out of 4 patients take some form of supplements totally unsupervised. Many take the supplements with or without their physician’s knowledge and sometimes in combination with prescription drug/s, presenting safety issues.
Despite the various aches and pains, irritability, difficulty concentrating, fatigue, digestive problems, anxiety, guilt and much more, Depression is not a disease by medical evidence. Depression is not more than a “trapped inward feeling”, with no two people experiencing exactly the same symptoms.
Depression may have underlying factors such as Thyroid Disease, Cardiovascular or Endocrine System problems, deficiency and or imbalances of certain nutrients, digestion, food sensitivities, artificial lighting, inactivity, numerous toxic environment chemicals found in the household. Heavy metal poisoning, adrenal, ovarian or testical problems, immune deregulation, anemia, blood sugar fluctuations, prolonged physical illness and many more symptoms can cause Depression.
True “healing” cannot be achieved by simply “relieving” the pain and symptoms. Studies have shown that if the cause and effect relationship between depression and functional decline is not understood properly, depression can become a killer disease.
Contrary to today’s only approach of treatment, stopping the pain, we must hear the message (the symptom) and understand the message (the symptom) that the body is trying to tell us. The message is simple, something is wrong somewhere. I recommend we stop shooting the messenger (pain) and start being a good listener to our body’s warning signs. My simple message to you, do not self-treat!
I often see patients who have decided to self-prescribe medications or supplements for various problems, depression included. Not only do they mask the real problem, not listening to their body and its symptoms, they run the risk of having dangerous drug interactions. If you are currently on any medication or supplements, please take the time to read the following Drug/s Interaction Dangers. It could save your life.
“Add-on” interactions are the most common type and can be the most dangerous, even fatal. These occur between drugs that have similar effects, either depressant + depressant or stimulant + stimulant.
Depressants include: alcohol, antianxiety agents, tranquilizers, anticonvulsants, antihistamines, certain high blood pressure drugs, muscle relaxants, narcotics and the popular pain reliever propoxyphene (e.g., Darvon).
Stimulants include: antidepressants (MAO inhibitor type drugs and tricyclics family drugs), appetite suppressants, some asthma drugs, caffeine, nasal decongestants, methylphenidate (Ritalin) and pemoline (Cylert). You should always ask your doctor and/or pharmacist about these types of interactions before you take any medication.
Amine-containing foods + MAO inhibitors:
MAO inhibitors are used in some cases of clinical depression. This can be a life threatening combination that may result in a dangerous rise in blood pressure, with severe headache, fever, visual disturbances, and confusion, possibly followed by brain hemorrhage/stroke.
Caution: Avoid amine-containing foods, even for several weeks after stopping MAO-inhibitor type antidepressant drugs.
Both types of antidepressant drugs MAOIs and Tricyclics require close monitoring to determine proper dosage. The drugs must be taken for at least three weeks before mood improves. And the side effects associated with these two families (Gambini’s and Kapone’s) can be severe and debilitating.
Trycyclics can induce dry mouth, constipation, weight gain, blurred vision, heart attacks, stroke, high or low blood pressure, heart block, seizure, hallucinations, delusions, confusion, disorientation, in coordination, tingling, abnormal involuntary movements, anxiety, insomnia, nightmares, dizziness, ocular pressure, rashes, bone marrow depression, elevation or lowering of blood sugar, edema, hair loss and more.
MAOI’s can provoke the same side effects plus an increased risk of hypertension and hepatitis.
Medical aromatherapy or the use of essential oils for therapeutic purposes, is one of the oldest forms of medicine and cosmetics known to man. According to Egyptian hieroglyphics and Chinese medical manuscripts, physicians and priests were using essential oils thousands of years before Christ to heal the sick. What are essential oils anyway? Essential oils are the subtle, aromatic and volatile liquids extracted from the flowers, seeds, stems, leaves, bark and roots of herbs, shrubs and trees. The extraction process is done primarily through distillation. Some of the oils that have been used since Biblical times include frankincense, myrrh and cinnamon. Modern clinical research has been confirming the medicinal properties of these oils. For instance, frankincense has been found to have superior immune stimulating properties while cinnamon has blood sugar regulating properties.
Are all essential oils equal? Unfortunately, that’s not the case. For example, the majority of the rose oils come from Bulgaria. In order to keep up with demand from the perfume or cosmetic industry, they have to produce large volumes and in the process compromise quality by using solvent extraction instead of steam distillation.
Some of the modern applications of oils include eugenol (from clove), which is used in the dental industry and thymol (from thyme) which is used as an antiseptic. For one of the best sources of essential oils, check out www.cleanbodycare.com.
The American College for Advancement in Medicine (ACAM) is a not-for-profit organization dedicated to educating physicians and other health care professionals on the safe and effective application of integrative medicine.