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The Vitamin D Newsletter February 2006

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Professor Barbara Gilchrest

I'm calmer these days. A few years ago, I was angry about the epidemic of vitamin D deficiency and the millions of needless deaths, somehow thinking I wasn't getting the word out. Now I plug along, knowing the truth will prevail, regardless of what I do, knowing we need decades, not months, for the work ahead. As the poet, Patmore, said:

"For want of me the world's course will not fail: When all its work is done, the lie shall rot; The truth is great, and shall prevail, When none cares whether it prevail or not."

Attack On Vitamin D

I knew a backlash against vitamin D was coming. This month, Professor Barbara Gilchrest of Boston University fired the first broadside. I'm happy the paper didn't upset me that much, although, like anything that you don't agree with, it was difficult to read carefully. Scientists, experts, physicians, and advocates should always read opposing views carefully, lest they get drunk on their own whiskey.

Professor Barbara Gilchrest is the same Boston University academic who turned me livid eighteen months ago when she fired Professor Michael Holick for writing a book. Holick's book simply questioned current dermatology dogma that sunlight is evil and she fired him: Boston University's version of academic freedom.

Dr. Gilchrest and Dr. Deon Wolpowitz wrote an attack on vitamin D and sunlight. The two authors have something in common: neither had ever published a peer-reviewed paper about vitamin D (just search PubMed).

The article received little press. Reuters picked it up, but few other news outlets chose to. Supplements, not sun, best for boosting vitamin D Reuters.

Vitamin D Workshop

As an aside, Dr. Gilchrest is one of the invited speakers at the upcoming 13th Annual Workshop on Vitamin D in Victoria, British Columbia, from April 8–12, 2006. Professor Tony Norman and Professor Roger Bouillon, both giants in the vitamin D field, organized this meeting. Tickets are going fast. The conference is at the gorgeous Fairmont Empress , a historic hotel one should experience at least once in your life. Be warned, this is a conference for scientists. Most of the presentations are technical, just the work that needs to be done to better understand vitamin D.

However, mixed in with the highly technical papers are some very useful clinical papers. Heike Bischoff-Ferrari, Hector Deluca, Edward Giovannucci, Robert Heaney, Bruce Hollis, Jo Ellen Welsh, Susan Whiting, and others usually present their data in ways educated lay people can understand. I was sorry to see that Michael Holick, Cedric Garland, and Reinhold Vieth were not invited to speak—sorry because Holick is the giant of the field, Garland because of his recent incredible paper on vitamin D and cancer, and Vieth because he started the current vitamin D revolution.

At first, I was upset (not livid) to see Dr. Gilchrest invited to speak at a vitamin D conference. However, the more I thought about it, the more I realized this is academic freedom at its best. One of the harshest critics of sun exposure, Dr. Gilchrest, invited to a conference where many of the attendees are staunch advocates of sensible sun exposure. I respect her for coming. I only hope that Professor Norman will invite Professor Michael Holick to debate her. Now that would be a free exchange of ideas!

Getting back to her paper, the most depressing thing about it was the emails I got from vitamin D experts, who complained it is useless to write a rebuttal to the Journal of the American Academy of Dermatology. That journal will not print any view that opposes their dogma that God was confused when she created sunlight, another blow against academic freedom.

Gilchrest's Scientific Inaccuracies

After reading Professor Gilchrest's paper twice, I found so many inaccuracies that I can't list them all. Some of the errors are basic. Professor Gilchrest, cholecalciferol is not previtamin D; it is vitamin D. Professor Gilchrest, vitamin D is not in the "superfamily of steroid hormones that includes vitamin A and thyroid hormone," its receptor is in that family. Professor Gilchrest, vitamin D is not a steroid hormone; it is a prehormone. Professor Gilchrest, vitamin A is not a steroid hormone; it has a retinol base, not a sterol one. Professor Gilchrest, thyroid hormone is not a steroid hormone; it has a tyrosine base, not a sterol one. When she makes basic mistakes on freshman biochemistry, how can readers trust her interpretation of scientific studies with immense medical and social consequence?

No Link Between Melanoma, UV Exposure

Her first argument is sunlight and sunbeds kill people, mainly due to malignant melanoma. However, she failed to cite the two biggest and best studies! A large, multi-center European study, perhaps the best one ever done, "found no association between melanoma and risk factors related to UV exposure such as sunbed use, sunbathing, or number of weeks of holidays in sunny areas." The authors actually found sunbeds were associated with a small decreased risk for melanoma! They also found that sun bathing and sunburns were not associated with melanoma. Fair skin and the number of moles were the major risk factor for melanoma, not sunbeds or sunshine. They even found some evidence of decreasing risk with increasing sunbed use, concluding "The observed decrease in risk (of melanoma) with increasing use (of sunbeds) suggest either a protective effect or could be explained by recall bias with cases under reporting their true exposure." Bataille V, Boniol M, De Vries E, Severi G, Brandberg Y, Sasieni P, Cuzick J, Eggermont A, Ringborg U, Grivegnee AR, Coebergh JW, Chignol MC, Dore JF, Autier P. A multicentre epidemiological study on sunbed use and cutaneous melanoma in Europe. Eur J Cancer. 2005 Sep;41(14):2141–9.

Actually, recall bias (errors due to what patients tell researchers they remember), as the authors admit, will likely skew the results the other way. Patients with melanoma are more likely to report sun exposure or sun bed use in an "effort after meaning." That is, humans tend to explain their problems by falsely remembering factors—in this case factors they believe might explain their melanoma.

Gilchrest Ignores Another Study

Gilchrest also ignored another recent large European study looking at melanoma and sun/sunbed exposure. The British authors concluded, "This case-control study of melanoma did not find that exposure to natural or artificial radiation was significantly associated with an increased melanoma risk in the population overall." Although they found ten or more sunburns and exposure to sunbeds for individuals with fair skin yielded significant but small melanoma risks, they found no overall risks. "The fact that no dose response was found for hours and years of exposure to sunbeds, even in young subjects, suggests that the use of sunbeds...is unlikely to be a major environmental risk factor for melanoma." Bataille V, Winnett A, Sasieni P, Newton Bishop JA, Cuzick J. Exposure to the sun and sunbeds and the risk of cutaneous melanoma in the UK: a case-control study. Eur J Cancer. 2004 Feb;40(3):429–35.

Melanoma and Vitamin D Deficiency

After she ignores the two best, biggest, and most recent studies of melanoma and UV light, she argues sunlight is largely responsible for the 8,000 melanoma deaths per year. It is more likely that the current epidemic of melanoma, like many other cancers, is partially due to vitamin D deficiency. Vitamin D is such a stellar anti-carcinogen, doing everything an ideal, anti-neoplastic drug should do, it is likely that dermatologists' advice to melanoma patients—avoid the sun at all costs—is actually killing patients. A recent large multi-center trial (another one Professor Gilchrest ignored) looked at the effects of ongoing sun-exposure in melanoma patients. "Sun exposure is associated with increased survival from melanoma." Berwick M, Armstrong BK, Ben-Porat L, Fine J, Kricker A, Eberle C, Barnhill R. Sun exposure and mortality from melanoma. J Natl Cancer Inst. 2005 Feb 2;97(3):195–9.

Professor Gilchrest then argues that the health benefits of vitamin D beyond bone disease are unproven. She explains that controlled interventional trials using vitamin D are rare, which is true. However, it is also true that science never proved that low fat diets prevent heart disease or stroke with good controlled interventional trials. The lack of good interventional trials did not prevent modern medicine from advising low fat diets—uselessly it seems. Howard BV, et al. Low-fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006 Feb 8;295(6):655–66. Low-Fat Diet Does Not Cut Health Risks, Study FindsNew York Times. 2006.02.08.

Physicians' Risk-Benefit Analysis

In implying physicians should not act until scientists conclusively prove a point, Professor Gilchrest misses the point. Sometimes physicians must act before scientists conclusively prove a point. Physicians can't wait. Scientists can wait. Physicians are obligated to perform what is called a risk-benefit analysis based on available data and treat their patients accordingly. If a new therapy is risky (like a new cancer chemotherapy with numerous side effects), then physicians should only use the drug on patients facing death. If the therapy or advice is safe (drink eight glasses of water a day), it can be recommended. (Although I dare the reader to find a single controlled interventional trial showing eight glasses of water a day does anything other than increase bottled water sales.)

Humans Evolved In The Sun

Unlike advising a low fat diet (assuming one warns against trans-fats and excess omega 6 consumption), advising people to avoid the sun is risky advice. Why is it risky? First, it is unnatural advice for a species that evolved in the sun. Second, it goes against mammalian instincts, as any pet owner will verify. Third, it goes against human instincts—the sun draws humans to it—and such instincts evolved for a reason. Finally, it goes against a large body of data that associates both sun exposure and low latitude with reduced incidence of many diseases. Thus, sun avoidance is risky advice and physicians should dispense it only after science has conclusively proven the benefits outweigh the risks.

Consider the advice of the Lancet Editorial Board, commenting on a petition to set aside public land for nude sunbathing! "On first consideration, the idea of a community of people deliberately practicing nudity, especially with public encouragement, strikes the average person as ridiculous…But the discovery that the rays of the sun on the skin exert a beneficent effect on health has done something to undermine these prejudices." Naked and unashamed [editorial]. Lancet 1932;1:688.

Physicians Recommend Sun Exposure

Granted, the Lancet proffered this advice in 1932, when organized medicine knew the health benefits of sun exposure and before dermatologists scared us out of the sun. Whatever you think of the government sponsoring nudist colonies, you should know that the best physicians in the '20s and '30s routinely recommended sun exposure for a wide variety of diseases—the same diseases now being associated with vitamin D deficiency. Albert MR, Ostheimer KG. The evolution of current medical and popular attitudes toward ultraviolet light exposure: part 2. J Am Acad Dermatol. 2003 Jun;48(6):909–18.

Gilchrest's "Evidence"

Professor Gilchrest goes on to say, "No trial data support the conclusion that vitamin D supplementation, in the absence of concomitant calcium supplementation, is effective in preventing falls." I guess she did not have time to read Sato's recent study that showed a 59% reduction in falls with ergocalciferol (vitamin D2) supplementation alone. Sato Y, Iwamoto J, Kanoko T, Satoh K. Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures in women after stroke: a randomized controlled trial. Cerebrovasc Dis. 2005;20(3):187–92.

She then cites five "high-quality epidemiological and observational studies," which she claims "do not support a role for vitamin D in preventing cancers." The problem is that two of her studies are reviews, both of which call for better studies. Two others found the opposite of what she claimed. For example, the first study she cited concluded, "Calcium supplementation and vitamin D status appear to act largely together, not separately, to reduce risk of colorectal adenoma recurrence." Grau MV, Baron JA, Sandler RS, Haile RW, Beach ML, Church TR, Heber D. Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trial. J Natl Cancer Inst. 2003 Dec 3;95(23):1765–71.

The other "negative" study she cited actually concluded, "This trial cohort provides some evidence that calcium and vitamin D may be inversely associated with adenoma recurrence." Hartman TJ, et al.; Polyp Prevention Study Group. The association of calcium and vitamin D with risk of colorectal adenomas. J Nutr. 2005 Feb;135(2):252–9.

Professor Edward Giovannucci recently reviewed the evidence and concluded, "Recent studies add more support to a potential role of vitamin D on risk of colorectal cancer, but suggest that intakes higher than customary are required if solar ultraviolet-B exposure is low." Giovannucci E. The epidemiology of vitamin D and colorectal cancer: recent findings. Curr Opin Gastroenterol. 2006 Jan;22(1):24–9.

Professor Gilchrest also cited a prostate cancer study as negative, which actually showed protective effects for those with mid range vitamin D blood levels, while showing increased risk for those with high and low levels. She failed to point out the author of this study accepted Vieth's explanation that high levels put one at risk because such patients do not maintain them throughout the year. Vitamin D levels fall precipitously in the autumn and winter, triggering even lower intracellular levels. It appears that falling levels may be as dangerous as low levels. Tuohimaa P, et al. Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries. Int J Cancer. 2004 Jan 1;108(1):104–8. Vieth R. Enzyme kinetics hypothesis to explain the U-shaped risk curve for prostate cancer vs. 25-hydroxy vitamin D in nordic countries. Int J Cancer. 2004 Sep 1;111(3):468; author reply 469.

Then she makes another mistake, but I have made it myself. She says humans make all the vitamin D we can make in the first few minutes of sun exposure then we can't make anymore. Although we make a lot very quickly, production continues to rise with sun exposure—up to about 50,000 units after four minimal erythemal doses (if you stay in the sun four times longer than it takes your skin to begin to turn pink). In 1982, Adams proved that by measuring levels after steadily increasing artificial UVB exposure into the sunburn range. Increased melanin in the skin (suntan) and other factors will eventually block such robust production. Adams JS, Clemens TL, Parrish JA, Holick MF. Vitamin-D synthesis and metabolism after ultraviolet irradiation of normal and vitamin-D-deficient subjects. N Engl J Med. 1982 Mar 25;306(12):722–5.

She also fails to mention the role vitamin D may play in preventing cardiovascular disease (potentially a greater lifesaver than preventing cancer), a topic recently reviewed by Zittermann. Zittermann A, Schleithoff SS, Koerfer R. Putting cardiovascular disease and vitamin D insufficiency into perspective. Br J Nutr. 2005 Oct;94(4):483–92.

Gilchrest's Risky Advice

She goes on to say that if science eventually proves that vitamin D is important, then supplementation, not sunshine, is the answer. That is risky advice. How does she know all the sun does? She correctly thinks that sun exposure increases the risk of non-melanoma skin cancers and ages the skin. She incorrectly thinks sun exposure is the major risk factor for melanoma.

She overlooks the benefit side of the safe sun exposure equation. The sun provides vitamin D, which looks as if it may help protect humans from most of the diseases of civilization. What else does the sun do? Before I told someone to avoid the sun, I would wait until science completely understood the relationship between the sun and humans. Until then, supplementation in the colder months, moderate safe sun exposure in the warmer ones, and visits to the dermatologists should you develop signs of skin cancer, is the safest advice.

Reduced Risk Of Internal Cancers

Remember, non-melanoma skin cancers are mostly a nuisance, unless you ignore them. I have a few frozen every year. I thank my dermatologist and then go out to celebrate, knowing that long ago science associated non-melanoma skin cancers, a marker for sun exposure, with a reduced risk of dying from internal cancers. Apperly FL. The relation of solar radiation to cancer mortality in North America. Cancer Res 1941; 1:191–5. Cannell, J. Vitamin D Quiz Vitamin D Newsletter. 2003.01.18.

Casual Exposure Not Sufficient

She then points out that misapplied sunscreen lotion, and thank God most people misapply it, will not block vitamin D production in the skin. However, she misinterprets Matsuoka's classic paper which not only showed properly applied sunblock prevents vitamin D production, but showed casual exposure of the arms and face will only produce minimal amounts of vitamin D. That is an important point, because some say casual exposure of the arms and face is sufficient. It is not for many people. Furthermore, does it make sense to expose those parts of your body with the highest cumulative lifetime radiation burden to additional radiation? When I go in the sun, I cover my face and hands but expose as much of the rest of my body as prudence dictates. Matsuoka LY, Wortsman J, Hollis BW. Use of topical sunscreen for the evaluation of regional synthesis of vitamin D3. J Am Acad Dermatol. 1990 May;22(5 Pt 1):772–5.

Towards the end of the paper, she makes some excellent points. "Recent reviews have summarized an impressive amount of data showing that hypervitaminosis D from diet (and I infer supplements from her context) is more a theoretic concern than a reality." Good for her! I guess she read your paper Reinhold? As Reinhold Vieth once said, "Worrying about vitamin D toxicity is like worrying about drowning when you are dying of thirst." Everyone should read Reinhold's paper, the paper that started the vitamin D revolution. By the way, Reinhold Vieth's seminal paper is now free to download thanks to the American Journal of Clinical Nutrition. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999 May;69(5):842–56.

Winter Sun Not Effective

She also competently discusses a pet peeve of mine. Casual sun exposure won't work in the winter at many latitudes; it won't work for African Americans, the aged, and certain cultural groups who veil their skin. Supplementation is critical for many people. Although she sees no reason to strive for natural blood levels, 50 ng/mL year-round, she correctly points out that casual sun exposure will not protect our most vulnerable populations from vitamin D deficiency. Professor Heaney and Professor Hollis have both recently warned us that vulnerable patients may have to take more than 2,000 units a day—especially in the winter—to prevent deficiency. Heaney RP. The Vitamin D requirement in health and disease. J Steroid Biochem Mol Biol. 2005 Oct;97(1–2):13–9. Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr. 2005 Feb;135(2):317–22.

At the end of her paper, a paper filled with inaccuracies, selective references, and apparent ignorance of the melanoma literature, she surrenders. She grudgingly admits vitamin D is probably important and the issue needs more attention, even obliquely taking the Food and Nutrition Board to task for not raising guidelines.

Dermatologists' Potential Liability

However, she doesn't discuss potential liability for dermatologists—an important omission for her dermatology readers. What will happen to dermatologists who promulgate sunphobia without taking steps to ensure that their advice doesn't induce vitamin D deficiency? Dermatologists in England have already provided the expert opinion needed in a court of law. After reviewing the role vitamin D plays in cancer prevention, including prevention of malignant melanoma, they concluded: "It would seem mandatory to ensure an adequate vitamin D3 status if sun exposure were seriously curtailed, certainly in relation to carcinoma of the breast, prostate, and colon and probably also malignant melanoma." Osborne JE, Hutchinson PE. Vitamin D and systemic cancer: is this relevant to malignant melanoma? Br J Dermatol. 2002 Aug;147(2):197–213.

Eighteen months ago, after she fired Professor Michael Holick, I was livid. I sent her a registered letter (PDF format), threatening to file complaints with the AMA's Council on Ethical and Judicial Affairs for violating the Principles of Medical Ethics, and with Board of Registration in Medicine of the Commonwealth of Massachusetts for dispensing harmful medical advice. I also threatened to run ads in Boston newspapers to find patients who had developed life-threatening cancers due to her sunphobe advice, patients who could sue her should she not educate herself about vitamin D. After I calmed down, and after Michael Holick calmed me down, I didn't do any of these things.

Now I'm looking forward to hearing her speak at this year's Vitamin D Workshop. Even with all the mistakes in her paper, I think Professor Gilchrest has come a long way in the last eighteen months.

Then again, perhaps so have I.

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