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Autoimmunity and vitamin D - several articles April 2010

UV radiation suppresses experimental autoimmune encephalomyelitis independent of vitamin D production.

Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6418-23. Epub 2010 Mar 22.
Becklund BR, Severson KS, Vang SV, DeLuca HF.
Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA.

Although the exact cause of multiple sclerosis (MS) is unknown, a number of genetic and environmental factors are thought to influence MS susceptibility. One potential environmental factor is sunlight and the subsequent production of vitamin D.

A number of studies have correlated decreased exposure to UV radiation (UVR) and low serum 25-hydroxyvitamin D(3) 25(OH)D(3) levels with an increased risk for developing MS. Furthermore, both UVR and the active form of vitamin D, 1alpha,25-dihydroxyvitamin D(3), suppress disease in the experimental autoimmune encephalomyelitis (EAE) animal model of MS.

These observations led to the hypothesis that UVR likely suppresses disease through the increased production of vitamin D.
However, UVR can suppress the immune system independent of vitamin D. Therefore, it is unclear whether UVR, vitamin D, or both are necessary for the putative decrease in MS susceptibility.

We have probed the ability of UVR to suppress disease in the EAE model of MS and assessed the effect of UVR on serum 25(OH)D(3) and calcium levels.
Our results indicate that continuous treatment with UVR dramatically suppresses clinical signs of EAE. Interestingly, disease suppression occurs with only a modest, transient increase in serum 25(OH)D(3) levels.

Further analysis demonstrated that the levels of 25(OH)D(3) obtained upon UVR treatment were insufficient to suppress EAE independent of UVR treatment.
These results suggest that UVR is likely suppressing disease independent of vitamin D production, and that vitamin D supplementation alone may not replace the ability of sunlight to reduce MS susceptibility. PMID: 20308557

EAE = Experimental Autoimmune Encephalomyelitis (animal disease ‘resembles’ human MS)

There are a great many articles on EAE on the web, such as

Clipped from http://www.mult-sclerosis.org/experimentalautoimmuneencephalomyelitis.html
Experimental Autoimmune Encephalomyelitis (EAE), also called Experimental Allergic Encephalomyelitis, is an animal model of Multiple Sclerosis. Animal models of human diseases are diseases of non-human species (often rodents) which closely resemble their human counterparts and are be studied with a view to better understanding and treating the human form. EAE is not multiple sclerosis, nor is it a single disease in a single species, but its different forms resemble the various forms and stages of MS very closely in a large number of ways.

Vitamin D's ability to boost health still uncertain

Publish date: Jun 1, 2010 By: John Jesitus Source: Dermatology Times
The vast majority of studies examining vitamin D's impact on illnesses such as cancer and multiple sclerosis (MS) find associations but not causality, adds James M. Spencer, M.D., clinical professor of dermatology, Mount Sinai School of Medicine, New York.
For instance, an analysis of data from the Nurses' Health Study (one of the largest and longest-running studies on women's health) compared the addresses, health outcomes and behavioral risk factors of 461 women with rheumatoid arthritis (RA) versus a control group. Investigators found that diagnoses of RA occurred more commonly in northern states than in southern ones (Vieira VM, Hart JE, Webster TF, et al. Environ Health Perspect. 2010 Mar 25. (Epub ahead of print)).
"That's another ecologic correlation — it correlates latitude with disease incidence, severity or mortality," Dr. Spencer says. The study does not prove that lower vitamin D levels cause these conditions, and "does not suggest that if people who lived in New Hampshire raised their vitamin D levels, they wouldn't get RA," he says.

Proving whether elevated vitamin D levels prevent certain illnesses would require large studies following patients for 15 to 20 years, Dr. Lim says.

"It's a very difficult and expensive study" that would fall to the government's responsibility, because no pharmaceutical manufacturers would support such an endeavor, he says.

Immune booster?

However, a recent randomized, controlled trial involving more than 300 Japanese schoolchildren represents a step in the right direction, Dr. Spencer says.

In this study, children who received 1,200 international units (IU) of vitamin D daily for four months had 42 percent fewer influenza B infections (p = 0.04 (Urashima M, Segawa T, Okazaki M, et al. Am J Clin Nutr. 2010 May;91(5):1255-1260).

Furthermore, children with a history of asthma who took vitamin D experienced a sixfold reduction in asthma attacks.

Outside of this study, says Michael F. Holick, M.D., professor of endocrinology, Boston University, Boston, and a vitamin D proponent, very few randomized, controlled trials have looked at 1,000 to 2,000 IU of vitamin D supplementation, which is what vitamin D experts believe everyone needs.

"Most of the trials have used around 400 IU," which has a negligible effect on serum vitamin D, he says. Other limitations: Along with using insufficient supplementation, "Most studies are retrospective, and don't have very good data for the true vitamin D intake," he says.

Dr. Rigel says another problem with some vitamin D studies is that they don't differentiate between vitamin D insufficiency and deficiency. Also, nearly all studies define the lower limit of normal vitamin D differently, he says.

Sunshine vs. supplements

If one accepts that higher vitamin D levels can be helpful in combating or preventing some diseases, Dr. Rigel says, "There are several ways to get vitamin D. Vitamin D itself does not come from sun — vitamin D in the body is converted to its usable form by UV radiation to the skin."

However, he says sun exposure is an inefficient mechanism of boosting vitamin D.

"Once you get about one-third of a minimal erythema dose (MED), the system is overloaded," he says. "You probably must wait a day to get more vitamin D" converted by sun exposure.

Moreover, Dr. Spencer says, "The primary wavelengths that convert vitamin D are UVB. But the primary wavelengths provided by tanning beds are UVA (Woo DK, Eide MJ. Dermatol Ther. 2010 Jan;23(1):61-71."

He says it's much safer to eat vitamin D-rich foods or take supplements.

"The vitamin D you get in both of these is preconverted. Dermatologists don't say vitamin D is bad. But why get elevated vitamin D in a way that puts you at risk of skin cancer?" he says.

Dr. Holick says he has "never had a problem" with oral vitamin D supplementation. Currently, there's no evidence showing any difference in health outcomes between the impact of oral supplements and sun exposure, he says.

"The only difference is that when you make vitamin D in your skin, it remains in your body two to three times longer," he says. "That's why I've been recommending that one should be exposed to sunlight may be two or three times a week (Holick MF. N Engl J Med. 2007 Jul 19;357(3):266-281. Review), whereas supplements are taken daily."

Other research appears to indicate a distinction between the benefits derived from supplementation and the effects of exposure to light.

John J. Cannell, M.D., executive director of the nonprofit Vitamin D Council, says a study has shown that UV radiation caused remissions in an animal model of MS, while oral vitamin D supplementation did not (Becklund BR, Severson KS, Vang SV, DeLuca HF. Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6418-6423).

"It's a shot over the bow of the vitamin D express," he says. Based on thousands of studies, "Everyone has always assumed that the benefits are entirely due to vitamin D," regardless of administration route. But that may not be so, he says.

Therefore, Dr. Cannell says the Vitamin D Council recommends "safe, sensible" sunbathing: five to 15 minutes, with the face and hands — which carry the highest radiation burden — covered.

"That's the conservative thing to do, until science knows more about the relationship between sunlight and humans," he says.

Dr. Rigel counters that this unnecessary, because "People rack up that time just on day-to-day activities."

Pediatric patients

Meanwhile, the American Academy of Pediatrics recommends that children start receiving 400 IU vitamin D soon after birth, a policy the AAD supports, Dr. Lim says.

A recent review recommends oral supplementation of 1,000 IU daily for adults, "which is what the American Academy of Dermatology recommends," Dr. Lim says.

Meanwhile, federal guidelines for vitamin D requirements are being studied.

A comprehensive Institute of Medicine (IOM) review of dietary reference intakes for vitamin D and calcium, originally slated for summer publication, likely will be issued this fall, according to Christine Stencel, IOM media officer.

Comments from our Readers

Wiliam B. Grant, Ph.D. / San Francisco, CA, UNITED STATES
Posted 2010-05-29 12:10:15.0
Drs. Rigel and Lim are dermatologists whose main mission in life is to protect people from skin cancer and melanoma. Thus, they mention the few papers in the literature that did not find a beneficial effect of vitamin D. Those papers are dwarfed by many that do show benefits. There are over 1000 journal papers on the benefits of vitamin D in reducing the risk of cancer, and my review indicates that the evidence is good for 20 types of cancer. Meta-analyses also show that vitamin D significantly reduces the risk of cardiovascular disease, diabetes type 2, all-cause mortality rate, falls and fractures, while randomized controlled trials show same for all-cancer incidence, type A influenza, etc. Please go to www.pubmed.gov and search for relevant papers using keywords.
Wiliam B. Grant, Ph.D. / San Francisco, CA, UNITED STATES
Posted 2010-05-29 12:13:20.0
As for Dr. Spencer's comment on causality, please see these open access papers: Grant WB. How strong is the evidence that solar ultraviolet B and vitamin D reduce the risk of cancer? An examination using HillÂ’s criteria for causality. Dermato-Endocrinology. 2009;1(1):17-24. Grant WB. A critical review of Vitamin D and Cancer: A report of the IARC Working Group on vitamin D. Dermato-Endocrinology. 2009;1(1):25-33.

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