The Vitamin D Newsletter December 2006/January 2007
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It's Time to Get Serious...
An important new study was published several day ago. Dr. Consuelo Wilkins of the Washington University School of Medicine found that elderly patients with the lowest vitamin D levels were 11 (eleven!) times more likely to have symptoms of depression than were patients with the highest vitamin D levels. Her group also found that some measurements of dementia were higher in patients with the lowest 25(OH)D levels. Wilkins CH, Sheline YI, Roe CM, Birge SJ, Morris JC. Vitamin D Deficiency Is Associated With Low Mood and Worse Cognitive Performance in Older Adults. Am J Geriatr Psychiatry. 2006 Dec;14(12):1032–1040.
This study adds to the growing list of studies indicating that vitamin D deficiency is an important cause of depression—one that is easily treated. It also stresses the importance of Professor John McGrath's work (PDF format), showing that vitamin D is intimately involved in brain development. If you like your brain, the brain of your loved ones, the brain of the baby developing inside you, be sure to get adequate amounts of vitamin D.
Vitamin D and Hypothyroidism
Dr. Cannell: After reading as much as I could, my parents and I started taking 4000 IU of Vitamin D3 daily, starting in October. Since we live near a very cloudy, northern city (Cleveland), and since we were approaching the late fall and winter months, I felt this dosage was entirely appropriate. So far, my father and I have had absolutely no side effects. My mother, however, is a different story.
For 20 years, my mother has been taking Synthroid. For 15 years she took 75 mcg/day and over the last 5 years had been on 100 mcg/day. By sheer coincidence, less than a week after starting on the Vitamin D, it was time for her annual TSH test. When the results of the test came back, the doctor's office called and notified her that her TSH level was 13 and had "shot way up."
Accordingly, they upped her dose of Synthroid to 150 mcg/day as a result of this test. A few weeks later, she developed a rapid heartbeat (~140 bpm). Sensing that the increased dosage of Synthroid might be causing the rapid heartbeat, I checked Pub Med for any linkage between Vitamin D and TSH levels. I found the following two articles:
- TSH secretion stimulated by thyroliberin in patients with hypothyroidism receiving 1,25-hydroxyvitamin D3.
- Prophylaxis of vitamin D deficiency in hypothyroidism in the newborn infant.
We immediately contacted the doctor's office, who took her off the Vitamin D3 and told her to stop taking the Synthroid for 1 week. After 1 week, she resumed the Synthroid at 100 mcg/day, and her TSH levels are now back to normal. Thus, it does appear, in concert with the findings from the above articles, that those patients on synthetic thyroxine should not also be taking supplemental Vitamin D3. Roy Cleveland, Ohio
This is very interesting and, to my knowledge, the first such report. The first thing to keep in mind is that a TSH of 13, while elevated, is no emergency. Secondly, the studies you cite are in Polish and French and I cannot read them. From the abstract I see that the Polish patients were given calcitriol, not vitamin D. However, 4,000 IU per day (ideally 5,000 IU per day—a physiological dose of vitamin D) will increase tissue levels of calcitriol. People who work outdoors in the summer sun get about 10,000 IU a day.
If an elevated TSH is a side effect of vitamin D supplementation, one would think there would be some reports in the literature. A fairly large study of endocrinology outpatients given 4,000 IU/day, some of whom certainly had thyroid disease that was being monitored, reported no side effects other than an improved mood. Furthermore, if 4,000 IU per day can raise TSH, then summer sun should do the same; TSH levels peak in the spring not in the summer. Vieth R, Kimball S, Hu A, Walfish PG. Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients. Nutr J. 2004 Jul 19;3:8. Maes M, Mommen K, Hendrickx D, Peeters D, D'Hondt P, Ranjan R, De Meyer F, Scharpe S. Components of biological variation, including seasonality, in blood concentrations of TSH, TT3, FT4, PRL, cortisol and testosterone in healthy volunteers. Clin Endocrinol (Oxf). 1997 May;46(5):587–98.
Your mother's TSH apparently went up 5 years ago as well—without any vitamin D—as that would be the most common reason why her doctor would have increased her Synthroid back then. It's also possible that her TSH increased before she started the vitamin D, as she had not had a TSH for a year. I predict your mother's TSH will go up again in the future, without any vitamin D, as most thyroid failure is slowly progressive.
The increased dose of Synthroid, 150 mcg/day, is usually not supra-physiological (more than the thyroid normally makes), so she should not have become hyperthyroid from the Synthroid alone, unless she is a very thin person. Furthermore, without additional thyroid tests it's impossible to say for sure that her rapid heart rate was due to hyperthyroidism, although it sounds as if it was.
One possibility is that the vitamin D improved the function of her thyroid gland and the improved function of her thyroid gland, together with the additional Synthroid, made her hyperthyroid. This would imply that the pituitary did not have time to adjust to the thyroid's improved function or possibly that TSH production in the pituitary was independently up-regulated by the vitamin D. There is a seasonal variation in thyroid function, with increased production of thyroid hormone in the vitamin D rich months. Pasquali R, Baraldi G, Casimirri F, Mattioli L, Capelli M, Melchionda N, Capani F, Labo G. Seasonal variations of total and free thyroid hormones in healthy men: a chronobiological study. Acta Endocrinol (Copenh). 1984 Sep;107(1):42–8. Konno N, Morikawa K. Seasonal variation of serum thyrotropin concentration and thyrotropin response to thyrotropin-releasing hormone in patients with primary hypothyroidism on constant replacement dosage of thyroxine. J Clin Endocrinol Metab. 1982 Jun;54(6):1118–24.
It may be that vitamin D deficiency is one cause of thyroid failure, like it is with pancreatic failure in diabetes. Furthermore, I have had vitamin D deficient diabetic patients whose blood sugars go up for several weeks when their vitamin D deficiency is treated. Eventually, their blood sugars generally go down and their diabetes becomes easier to control. I have had several patients able to slowly reduce and even stop their oral diabetic medicines, once their vitamin D deficiency is fully treated. Perhaps you have discovered the same is true for hypothyroidism?
However, it is important to realize that as more people take more vitamin D, more people will report they developed heart attacks, headaches, cancer, ear infections, lupus, skin rashes, strokes, or constipation after they started taking vitamin D. Eventually, someone will contract a fatal case of influenza a day after starting vitamin D. Some people will start watching Desperate Housewives after they start taking vitamin D. Eventually, an angry wife will tell me that her hitherto faithful husband started having an affair after he started taking vitamin D. As lots of people start taking vitamin D, lots of things will happen afterwards. Associations are not causations; they often are, as you said, a "sheer coincidence."
The important question is, "What is your mother is going to do now?" I don't know what your mother's vitamin D level is now. If she is not going to take any vitamin D, go into sun tan booths, or vacation down south in the winter, then she will develop vitamin D deficiency, putting her at risk for its many associated diseases.
Summer Diagnosis Means Better Prognosis
Dr. Cannell: I have cancer of the colon and the doctors couldn't get it all. I've read about studies showing that cancer patients diagnosed in the summer have a better chance of living. Does this mean vitamin D might help my cancer? How much should I take? Katie Baltimore, MD
That is exactly what these studies mean—vitamin D might help treat cancer. They strongly imply a treatment effect. We won't know for sure until a direct study is done, that is, we need to give relatively high doses of vitamin D to cancer patients to see if they live longer compared to patients given sugar pills. Given what is known, I sure wouldn't want to be one of the cancer patients assigned to take the sugar pills.
Professor Johan Moan, from the Department of Physics at the University of Oslo, was the senior author that first reported an association between summer diagnosis and better prognosis. His group then verified it with colon cancer and breast cancer and extended it to Hodgkin lymphoma. They will soon publish a paper showing it is true for lung cancer as well. Robsahm TE, Tretli S, Dahlback A, Moan J. Vitamin D3 from sunlight may improve the prognosis of breast-, colon- and prostate cancer (Norway). Cancer Causes Control. 2004 Mar;15(2):149–58. Porojnicu AC, Lagunova Z, Robsahm TE, Berg JP, Dahlback A, Moan J. Changes in risk of death from breast cancer with season and latitude : Sun exposure and breast cancer survival in Norway. Breast Cancer Res Treat. 2007 May;102(3):323–8. Moan J, Porojnicu AC, Robsahm TE, Dahlback A, Juzeniene A, Tretli S, Grant W. Solar radiation, vitamin D and survival rate of colon cancer in Norway. J Photochem Photobiol B. 2005 Mar 1;78(3):189–93. Porojnicu AC, Robsahm TE, Ree AH, Moan J. Season of diagnosis is a prognostic factor in Hodgkin's lymphoma: a possible role of sun-induced vitamin D. Br J Cancer. 2005 Sep 5;93(5):571–4.
A group from Harvard led by Dr. Wei Zhou and Professor David Christiani took it one step further, combining season of diagnosis with vitamin D intake. They concluded that those lung cancer patients diagnosed during the sunny months who also had the highest vitamin D intake "had a 3-fold better recurrence free survival and a 4‑fold better overall survival than those with surgery in winter and low vitamin D intake." These results were truly amazing and suggest the long sought "cure" for cancer will not be coming out of the pharmaceutical industry but from health food stores and sun tan booths. Anything that prolongs survival is, by definition, effective treatment. Zhou W, Suk R, Liu G, Park S, Neuberg DS, Wain JC, Lynch TJ, Giovannucci E, Christiani DC. Vitamin D is associated with improved survival in early-stage non-small cell lung cancer patients. Cancer Epidemiol Biomarkers Prev. 2005 Oct;14(10):2303–9.
At this point, no one knows if oral vitamin D would slow down your cancer or how much you should take. I take 5,000 IU in the colder months and go into the sun in the warmer months, just to maintain my 25(OH)D around 50 ng/mL. Future research may show that 10,000 IU per day is indicated in cancer treatment, we just don't know. Anyone taking that amount should have be under the care of a knowledgeable physician and have their 25(OH)D and serum calcium checked on a regular basis. At this point, the question is not if cancer patients should take vitamin D. The question is: should cancer patients die vitamin D deficient? (PDF format.)
Cod Liver Oil Possible Reason for Conflicting Studies
Dr. Cannell: I'm a nutritionist and I'm confused. Two studies came out in the last several months about vitamin D and pancreatic cancer. One showed it helped and the other showed it made it worse. What's up? Kirstin Albuquerque, New Mexico
We are all confused. Now two studies, both from Scandinavia, have found higher risks of cancer with the highest vitamin D blood levels. One study was in prostate cancer and it conflicts with numerous other prostate cancer studies that show the opposite. Now we have a pancreatic cancer study that found Finnish male smokers with the highest vitamin D blood levels at baseline were at a three-fold risk for pancreatic cancer a decade later. Stolzenberg-Solomon RZ, Vieth R, Azad A, Pietinen P, Taylor PR, Virtamo J, Albanes D. A prospective nested case-control study of vitamin D status and pancreatic cancer risk in male smokers. Cancer Res. 2006 Oct 15;66(20):10213–9.
A month earlier, a group headed by Dr. Skinner at Northwestern, found higher vitamin D intakes reduced the risk of pancreatic cancer. Skinner HG, Michaud DS, Giovannucci E, Willett WC, Colditz GA, Fuchs CS. Vitamin D intake and the risk for pancreatic cancer in two cohort studies. Cancer Epidemiol Biomarkers Prev. 2006 Sep;15(9):1688–95.
Several months ago, a prospective study by Dr. Giovannucci at Harvard showed vitamin D exposure reduced the risk of pancreatic cancer. Giovannucci E, Liu Y, Rimm EB, Hollis BW, Fuchs CS, Stampfer MJ, Willett WC. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst. 2006 Apr 5;98(7):451–9.
An earlier Japanese study indicated sunlight reduced the incidence of pancreatic cancer. Mizoue T. Ecological study of solar radiation and cancer mortality in Japan. Health Phys. 2004 Nov;87(5):532–8.
A possible explanation for the inconsistent results from Scandinavian countries is the high consumption of cod liver oil in Scandinavia. I say possible because it is too early to indict cod liver oil. However, cod liver oil has noticeable concentrations of known carcinogens. Storelli MM, Storelli A, Marcotrigiano GO. Polychlorinated biphenyls, hexachlorobenzene, hexachlorocyclohexane isomers, and pesticide organochlorine residues in cod-liver oil dietary supplements. J Food Prot. 2004 Aug;67(8):1787–91.
Furthermore, the concentration of these carcinogens was much higher in the 1980s (when the Scandinavian pancreatic cancer study began) than it is now. Falandysz J, Tanabe S, Tatsukawa R. Most toxic and highly bioaccumulative PCB congeners in cod-liver oil of Baltic origin processed in Poland during the 1970s and 1980s, their TEQ-values and possible intake. Sci Total Environ. 1994 May 16;145(3):207–12.
The male Finnish smokers whose high vitamin D levels preceded their pancreatic cancer had those blood levels measured in the late 1980s, perhaps after a lifetime of ingesting cod liver oil with high concentrations of these known carcinogens. Also, cod liver oil has high amounts of vitamin A and, as I've written before, even the amount of vitamin A in most multivitamins—not to mention the huge amounts of vitamin A in cod liver oil—may be causing subclinical vitamin A toxicity.
Three studies suggest vitamin D reduces the risk of pancreatic cancer and one study suggests it increases the risk. Overall, there are several hundred studies indicating vitamin D, or sunlight, or both, dramatically reduces your risk from dying of cancer, while two studies in cod liver oil Scandinavian countries show high vitamin D levels increase risk. Take your pick.
Influenza in Hong Kong
Dr. Cannell: I live in Hong Kong. We are near the equator where sunshine is strong all year. If vitamin D prevents the flu, why do we get the flu? Deborah Hong Kong
Great question! If vitamin D is antivral and antibiotic, then influenza should be rare around the equator due to the high intensity of year-round ultraviolet B light. However, the incidence of influenza in Hong Kong is comparable to other countries. Understanding influenza in Hong Kong is particularly important because Hong Kong is close to what many consider to be the epicenter of new influenza strains in southern china and the next highly lethal influenza strain, destined to cause a devastating pandemic, may first be detected in Hong Kong. However, Hong Kong, in spite of being just south of the Tropic of Cancer at latitude 22 degrees, has a significant incidence of year-round vitamin D deficiency due to five factors: avoidance of sunlight, use of sunscreens, high rise buildings, terrible air pollution, and rainy seasons.
In 1990, a study reported that 55% of Hong Kong patients with fractured hips, 36% of healthy elderly, and 15% of healthy young people had 25(OH)D levels below 20 ng/mL. None of the subjects, even the healthy young adults, had levels above 40 ng/mL at any time of the year. In a 1988 study, 25% of subjects had levels less than 20 ng/mL in September and close to 50% had such levels in January. A 1989 study of Hong Kong infants showed almost half had levels less than 20 ng/mL in January through April. None of the infants had adequate levels (higher than 40 ng/mL), not even at the height of the Hong Kong summer. Pun KK, Wong FH, Wang C, Lau P, Ho PW, Pun WK, Chow SP, Cheng CL, Leong JC, Young RT. Vitamin D status among patients with fractured neck of femur in Hong Kong. Bone. 1990;11(5):365–8. MacDonald D, Swaminathan R. Seasonal variation in 25-OH vitamin D in plasma of Hong Kong Chinese. Clin Chem. 1988 Nov;34(11):2375. Leung SS, Lui S, Swaminathan R. Vitamin D status of Hong Kong Chinese infants. Acta Paediatr Scand. 1989 Mar;78(2):303–6.
Unfortunately, their are no recent studies of vitamin D levels in Hong Kong. However, a recent study in Miami, just a little further north of the equator at latitude 25 degrees North, found that 40% of adults had levels of less than 20 ng/mL at the end of winter—22% had these levels at the end of summer! Few had levels above 40 ng/mL, even at summer's end. Living in tropical climates simply does not prevent vitamin D deficiency. (This fact is important for all the sunlight and cancer studies because it suggests such studies significantly, perhaps dramatically, underestimate the effect of vitamin D on cancer.) Levis S, Gomez A, Jimenez C, Veras L, Ma F, Lai S, Hollis B, Roos BA. Vitamin d deficiency and seasonal variation in an adult South Florida population. J Clin Endocrinol Metab. 2005 Mar;90(3):1557–62.
In a recent study of attitudes about sunlight, 62% of Hong Kong women did not like going in the sun. Sunscreens and parasols are commonly used, even among those women who know sunlight to be important for adequate vitamin D. Kung AW, Lee KK. Knowledge of vitamin D and perceptions and attitudes toward sunlight among Chinese middle-aged and elderly women: a population survey in Hong Kong. BMC Public Health. 2006 Sep 7;6:226.
Surface UVB radiation in Hong Kong reaches its lowest level in January. This is interesting, because a 2002 article in the New England Journal of Medicine found that pediatric hospitalizations for influenza in Hong Kong peaked in January and February for two of the three years studied. A 2004 study found influenza deaths at all ages peaked in Hong Kong during January through March for three of the four years studied. Lam KS, Aijun Ding, Chan LY, Wang T, Wang TJ. Ground-based measurements of total ozone and UV radiation by the Brewer spectrophotometer 115 at Hong Kong Atmos. environ. 2002, vol. 36, no 12 (17 ref.), pp. 2003–2012. Chiu SS, Lau YL, Chan KH, Wong WH, Peiris JS. Influenza-related hospitalizations among children in Hong Kong. N Engl J Med. 2002 Dec 26;347(26):2097–103. Wong CM, Chan KP, Hedley AJ, Peiris JS. Influenza-associated mortality in Hong Kong. lin Infect Dis. 2004 Dec 1;39(11):1611–7.
What is urgently needed is a study assessing vitamin D levels in patients with influenza. Blood from patients infected during the 1997 Avian influenza outbreak is stored in Hong Kong. Six Hong Kong residents died terrible deaths from Avian flu in 1997 while others caught it but had few symptoms. Did 25(OH)D levels decide who lived and who died? Will 25(OH)D levels decide who lives and who dies from influenza this winter?
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John Jacob Cannell MD Executive Director