New Roles of Vitamin D


Vitamin D is a fat-soluble vitamin commonly associated with maintaining blood levels of calcium and the prevention of rickets. The “sunshine vitamin” is generally acquired by the body in two ways: sun exposure and dietary intake. Foods of animal origin are primary food sources, including liver, beef, veal, eggs, vitamin D-fortified foods and saltwater fish.1 Food sources contain relatively low levels of vitamin D. Exposure to sunlight is our primary method of receiving vitamin D. People living in areas with less sunlight due to geographic location, cloud cover and other factors should consider vitamin D supplements. Those who receive enough sun exposure for adequate vitamin D production must not receive overexposure, which carries its own health risks.


New research suggests that vitamin D may play roles in the prevention of infections, cancer and multiple sclerosis (MS). Several epidemiological studies demonstrate a higher risk of several health ailments in populations with reduced exposure from the sun.

Vitamin D acts as an innate immune system modulator.5 The innate immune system is the first line of defense against infection. Humans encounter potential disease-causing agents called pathogens regularly, but seldom do they cause disease. Most pathogens are destroyed by the innate immune system within minutes or hours after contact as it provides broad-spectrum (non-specific), short-lasting protection.6

The most important known role of vitamin D in innate immunity involves its ability to stimulate the expression of cathelicidin, an antimicrobial peptide produced in immune cells and the epithelial cells lining the respiratory tract.7,8 Cathelicidin expression is generally associated with inflammation.9,10 A study published in August 2006 demonstrated for the first time that vitamin D-induced cathelicidin expression produced innate antimicrobial activity independent of the release of pro-inflammatory molecules and did not result in inflammation.11

Vitamin D supplementation is most needed in the fall and winter months when we get the least sun exposure and when infections are most prevalent. Unfortunately, sufficient human studies examining the correlation of vitamin D status and infections have not been done. However, two papers published between 1949 and 1956 suggest that vitamin D may lessen the frequency and duration of the flu in animal models.12,13 Recent attention to vitamin D should prompt further investigation.

Good epidemiological evidence supports the theory that living at latitudes closer to the equator decreases the risks of many cancers such as prostate, colon, breast, endometrial, skin and pancreatic.14 Observations over the last 65 years have shown an increased association between sufficient sun exposure and cancer risks.15 In 1941, researchers noticed that people living at latitudes farther from the equator had an overall greater risk of dying from cancer than men and women of similar ages living at lower latitudes. This observation began to gain more attention in the 1980s when it was reported that risks of colon and breast cancers increased in higher-latitude populations.16

One study examining the amounts of vitamin D-producing UV light in seven different areas of the U.S. showed a clear difference during the winter months (November through February) based on latitude. At higher latitude locations (>25 degrees N), vitamin D-producing UV decreased dramatically compared to the eight warmer months. The lower latitude locations (<25 degrees N) showed no difference between the winter and warm months.17 A prospective study revealed that in populations with less vitamin D being formed from UV exposure, low levels of vitamin D in the blood increase the risk of cancer two-fold. Men and women with higher blood levels of vitamin D are also less likely to die prematurely as a result of cancer.16

We do not completely understand how vitamin D works as an anti-carcinogenic. Several mechanisms are known, such as promoting programmed cell death in abnormal cells (apoptosis), promoting cell differentiation, inhibition of cell proliferation in malignant cell lines, inhibition of blood vessel growth, stimulating the mutual adherence of cells, and enhancing cellular communication through gap junctions.2,18 (Gap junctions are intercellular channels that allow for the transfer of ions and other small molecules from cell to cell.) In the initial stages of carcinogenesis, mutagenic changes may occur that result proliferation of cells unable to communicate through gap junctions. Lack of mutual cell adherence and communication through gap junctions inhibits apoptotic, growth-suppressing and cell-differentiating signals from neighboring cells.19 A recently published study of malignant breast epithelial cells in culture demonstrated vitamin D’s promotion of apoptosis and differentiation, as well as inhibition of proliferation.20 The effectiveness of vitamin D has been found to be dose-dependant.2

Multiple sclerosis (MS) is an autoimmune disease involving inflammation that leads to the destruction of the myelin sheaths that surround and protect nerve fibers of the central nervous system (CNS).19 This disease occurs most frequently in geographic areas farthest from the equator, which suggests that vitamin D may protect against it.20-22 Very few treatments or particular diets have been shown to effectively counter MS. However, certain deficiencies in nutrients like vitamin D may potentially worsen MS symptoms.23

Very little information is available regarding the role of vitamin D in brain development. The white matter and branching cells called oligodendrocytes in the brain have been shown to be responsive to vitamin D and contain vitamin D receptors. It has been suggested that low levels of vitamin D during the development of oligodendrocytes may cause unnecessary death of these cells.20 Death of oligodendrocytes is devastating to the CNS, since these cells are known to form myelin.

Although the relationship between the increased frequencies of MS in populations most susceptible to vitamin D deficiencies has been observed for more than 25 years, it has not yet been thoroughly examined. A number of epidemiological studies have confirmed that both exposure to sunlight during early life and vitamin D supplementation reduce the prevalence of MS in women.20 Another study involving rats with experimental autoimmune encephalomyelitis (EAE), which is the animal model of MS, used a vitamin D treatment that reduced and even prevented the disease.21,22 In a recent study, researchers looked at 12 years of blood samples from US Army and Navy personnel and examined vitamin D levels and reported cases of MS in the Army physical disability database. The results showed clearly a reduced risk of MS in Caucasians with increasing blood levels of vitamin D. 24

More well-designed clinical trials are needed in order to determine if vitamin D deficiency increases risks of infections and if vitamin D supplements can be cancer-and MS-preventive. Supplemental vitamin D may offer a cost-effective and practical way to reduce the occurrence and symptoms of several diseases in the future. Other new areas of vitamin D research include type I diabetes, inflammatory bowel disease, rheumatoid arthritis, lupus and cardiovascular disease.

References

1. Groff JL and Gropper SS. Advanced Nutrition and Human Metabolism: 3rd Edition. Wadsworth ©
2000.
2. PDR for Herbal Medicines 2nd Edition 2000 Medical Economics Co. Inc.
3. Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, Tavera-Mendoza L, Lin R, Hanrahan JW,
Mader S, and White JH. “Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial
peptide gene expression.” J Immunol. 2004 Nov 15;173(10)
4. Unknown Authors. http://bioweb.wku.edu/courses/Biol328/Innate.htm. Access date December 4, 2006.
5. Lee PH, Ohtake T, Zaiou M, Murakami M, Rudisill JA, Lin KH, and Gallo RL. “Expression of an
additional cathelicidin antimicrobial peptide protects against bacterial skin infection” Immunology.
2005 Mar; 102(10):3750-3755.
6. Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, Garland CF, and Giovannucci E.
“Epidemic influenza and vitamin D.” Epidemiol Infect. 2006 Dec;134(6):1129-40.
7. Beisswenger C andBals R. “Antimicrobial peptides in lung inflammation.” Antimicrobial peptides in
lung inflammation. Chem Immunol Allergy. 2005;86:55-71.
8. Wehkamp J, Schauber J, Stange EF. “Microbial-epithelial cell crosstalk during inflammation: the host
response.” Ann N Y Acad Sci. 2006 Aug;1072:313-20.
9. Schauber J, Dorschner RA, Yamasaki K, Brouha B, Gallo RL. “Control of the innate epithelial
antimicrobial response is cell-type specific and dependent on relevant microenvironmental stimuli.”
Immunology. 2006 Aug;118(4):509-19.
10. Young GA Jr, Underdahl NR, and Carpenter LE. “Vitamin D intake and susceptibility of mice to
experimental swine influenza virus infection.” Proc Soc Exp Biol Med. 1949 Dec;72(3):695-7.
11. Underdahl NR and Young GA. “Effect of dietary intake of fat-soluble vitamins on intensity of
experimental swine influenza virus infection in mice.” Virology. 1956 Jun;2(3):415-29.
12. Schwartz GG and Skinner HG. “Vitamin D status and cancer: new insights.” Curr Opin Clin Nutr
Metab Care. 2007 Jan; 10(1):6-11.
13. Heany RP. “Long-latency deficiency disease: insights from calcium and vitamin D.” Am J Clin Nutr.
2003; 78:912-9.
14. Holick MF. “Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers,
and cardiovascular disease.” Am J Clin Nutr. 2004 Dec; 80(6):1678-88.
15. Kimlin MG, Olds WJ, and Moore MR. “Location and vitamin D synthesis: Is the hypothesis validated
by geophysical data?” J Photochem Photobiol B. 2006 Dec 1 (Not printed yet)
16. Daniells S. “Low vitamin D status may raise cancer risk, say scientists.”
www.nutraingredients.com/news/ng.asp?n=72441&m=1NIEN30&c= wlpuaxndraentjv. Access date
November 30, 2006.
17. Unknown Author. http://www.bioportfolio.com/LeadDiscovery/PubMed-020301.html. Adapted from
Upham et al, 2003 Int J Cancer 2003 Mar 10;104(1):12-18 Access date December 19, 2006.
18. Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, and Holick MF. “The role of
vitamin D in cancer prevention.” Am J Public Health. 2006 Feb; 96(2):252-61
19. Unknown Author. http://ww2.wfaa.com/global/story.asp?s=1230548. Access date December 28, 2006.
20. Chaudhuri A. “Why we should offer vitamin D supplementation in pregnancy and childhood to
prevent multiple sclerosis.” Med Hypotheses. 2005; 64(3):608-18.
21. Van Amerongen BM, Dijkstra CD, Lips P, and Polman CH. “Multiple sclerosis and vitamin D: an
update.” Eur J Clin Nutr. 2004 Aug; 58(8):1095-109.
22. Hayes CE. “Vitamin D: a natural inhibitor of multiple sclerosis.” Proc Nutr Soc. 2000 Nov; 59(4):531-
5.
23. Schwartz S and Leweling H. “Multiple sclerosis and nutrition.” Mult Scler. 2005 Feb; 11(1):24-32.
24. Munger KL, Levin LI, Hollis BW, Howard NS, and Ascherio A. “Serum 25-hydroxyvitamin D levels
and risk of multiple sclerosis.” JAMA. 2006 Dec 20; 296(23):2832-8.

Posted: Monday - January 08, 2007 at 12:56 PM          

©