Vitamin D and immune seasonality

Many diseases show an increased incidence with less sun exposure (i.e. living in the north) which may be correlated insufficient levels vitamin D. Does vitamin D affect immune regulation? Yes, an increasing amount of evidence shows that vitamin D and individual vitamin D receptor polymorphism (“gene variants”) are very important for immune regulation. The VDR is present in almost every cell in the body. Much of the basic research has been done with so called VDR null (3) mice and it indicates that VDR differences in vitamin D deficiency cause different risk for respiratory diseases, stomach ulcers, auto-immunity, cancers (breast, skin, colon, prostate, pancreas etc), hypertension, IBS, diabetes, increased thrombogenicity (“clot forming”), thyroid disturbances, rheumatic disease, MS (4) (which “is essentially unknown at the equator”), osteoporosis, diffuse muscular pain, ostearthrosis, connective tissue disorders, caries, skin disorders (including acne), rickets, SLE, myopathy (“weak muscles”), schizophrenia and on and on and on.

Main ways of action of vitamin D (or rather its metabolites) are immuno-regulatory. It regulates immunity by suppressing the proliferation of immunoglobulin, inhibit differentiation of dendritic cells (“the most potent of antigen presenting cells”), slowing B cell differentiation and inhibit Th1 cell proliferation (innate, cellular response) thus decreasing e.g. IFN-gamma and IL-2 productiion. It may also increase Treg and IL-4, 5 and 10 production thus in sum inducing a more Th2 (adaptive, humoral) biased response and attenuating any excessive Th1 inflammatory response.. It does also regulate and inhibit Th17 response. Innate immunity is also enhanced by expression of antimicrobial peptides (AMPs, e.g. cathelicidin and defensins). Innate (cellular) immunity is important for epithelial integrity of e.g. lungs, gengiva, bladder, skin (epidermis) and intestine. VDR-driven immune response is strongly impaired in vitamin D deficiency. Other effects are anti-neoplastic (regulation of cell growth and differentiation) and inhibition of angiogenesis (growth of new blood vessels, especially into tumors). Influenza and auto-immune disease are typically worsening (exacerbating / flaring) in winter (3) and spring, and improving in summer and fall.(4-12)

125 micrograms vitamin D per day reach steady state at about 150 nmol/l 25(OH)D after 3 months and 250 micrograms at about 200 nmol/l after 3 months (starting point was 70 nmol).(13) Intoxication has been observed at levels above 375 nmol/l (50000 IU/day). Skin production of vitamin D is self-limiting so intoxication is not possible by tanning. Hyperthyroidism increases 25(OH)D metabolism rates. (Holick)
Useful amounts of vitamin D are only present in certain wild fat fish. E.g. fresh *wild* salmon that contains 600-1000 IU per 100 grams. Darkskinned African skin equals approximately a sun protection factor 15 sun screen (Holick).

CPPS, prostatit, kroniskt bäckenbottensmärtsyndrom, nokturi, trängningar, immunity, seasonality, D-vitamin, auto-immune disease.
_________________
(1) Caveat: murine immune system differs from human in certain important aspects.
(2) In a trial reported by J Burton, at the 2009 meeting of American Academy of Neurology, vitamin D supplementation for, on average, 14000 IU/day induced remission and about a halved relapse rate.
(3) Immune response is upregulated during winter to counter environmental adversities. In the wild the net effect is a relative immune suppression (due to limited energy availability / high energy expense), but in laboratory conditions this may not be the case.
(4) Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, Lieben L, Mathieu C, Demay M. Vitamon D and human health: lesosn from vitamin D receptor null mice. Endocr Rev 29(6):726-776, 2008.
(5) Cantorna MT. Vitamin D and its role in immunology: multiple sclerosis and inflammatory bowel disease. Prog Biophys Mol Biol. 92(1):60-64, 2006.
(6) Lips P. Vitamin D physiology. Prog Biophys Mol Biol. 92(1):4-8, 2006.
(7) Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 81:353-373, 2006.
(8) Holick MF. Vitamin D deficiency. NEJM 357(3):266-281, 2007.
(9) Mouyis M, Ostor AJK, Crisp AJ, Ginawi A, Halsall DJ, Shenker N, Poole KES. Hypovitaminosis D among rheumatology outpatients in clinical practice. Rheumatology 47:1348-1351, 2008.
(10) Nelson RJ. Seasonal immune function and sickness response. Trends Immunol 25(4):187-192, 2004.
(11) Bikle D. Nonclassic actions of vitamin D. J Clin Endocrinol Metab 94(1):26-34, 2009.
(12) White JH. Vitamin D signaling, infectious diseases and regulation of innate immunity. Inf Immun 76(9):3837-3843, 2008.
(13) 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 77:204-210, 2003.