Vitamin D

Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique because it can be ingested as cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2) and because the body can also synthesize it (from cholesterol) when sun exposure is adequate (hence its nickname, the "sunshine vitamin").

Although vitamin D is commonly called a vitamin, it is not actually an essential dietary vitamin in the strict sense, as it can be synthesized in adequate amounts by all mammals from sunlight. An organic chemical compound (or related set of compounds) is only scientifically called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from their diet. However, as with other compounds commonly called vitamins, vitamin D was discovered in an effort to find the dietary substance that was lacking in a disease, namely, rickets, the childhood form of osteomalacia. Additionally, like other compounds called vitamins, in the developed world vitamin D is added to staple foods, such as milk, to avoid disease due to deficiency.

Measures of serum levels (from a vitamin D3 blood test) reflect endogenous synthesis from exposure to sunlight as well as intake from the diet, and it is believed that synthesis may contribute generally to the maintenance of adequate serum concentrations. The evidence indicates that the synthesis of vitamin D from sun exposure works in a feedback loop that prevents toxicity but, because of uncertainty about the cancer risk from sunlight, no recommendations are issued by the Institute of Medicine, USA, for the amount of sun exposure required to meet vitamin D requirements. Accordingly, the Dietary Reference Intakes for vitamin D assume that no synthesis occurs and that all of a person's vitamin D is from their diet, although that will rarely occur in practice.

In the liver vitamin D is converted to calcidiol, which is the specific vitamin D metabolite that is measured to determine a person's vitamin D status.Part of the calcidiol is converted by the kidneys to calcitriol, the biologically active form of vitamin D. Both calcidiol and calcitriol were identified by Michael F. Holick. Calcitriol circulates as a hormone in the blood, regulating the concentration of calcium and phosphate in the bloodstream and promoting the healthy growth and remodeling of bone. Calcidiol is also converted to calcitriol outside of the kidneys for other purposes, such as the proliferation, differentiation and apoptosis of cells; calcitriol also affects neuromuscular function and inflammation.

Beyond its use to prevent osteomalacia or rickets, the evidence for other health effects of vitamin D supplementation in the general population is inconsistent. The best evidence of benefit is for bone health and a decrease in mortality in elderly women.

Health effects of supplements

The effects of vitamin D supplementation on health are uncertain. A United States Institute of Medicine, (IOM) report states: "Outcomes related to cancer, cardiovascular disease and hypertension, diabetes and metabolic syndrome, falls and physical performance, immune functioning and autoimmune disorders, infections, neuropsychological functioning, and preeclampsia could not be linked reliably with calcium or vitamin D intake and were often conflicting. Some researchers claim the IOM was too definitive in its recommendations and made a mathematical mistake when calculating the blood level of vitamin D associated with bone health. Members of the IOM panel maintain that they used a "standard procedure for dietary recommendations" and that the report is solidly based on the data. Research on vitamin D supplements, including large scale clinical trials, is continuing.

Mortality

Low blood levels of vitamin D are associated with increased mortality, and giving supplementary vitamin D3 to elderly women in institutional care seems to decrease the risk of death. Vitamin D2, alfacalcidol, and calcitriol do not appear to be effective. However, both an excess and a deficiency in vitamin D appear to cause abnormal functioning and premature aging. The relationship between serum 25OHD level and all-cause mortality is U-shaped,  Harm from vitamin D appears to occur at a lower vitamin D level in the black population than in the white population,

Bone health

Vitamin D deficiency causes osteomalacia (called rickets when it occurs in children). Beyond that, low serum vitamin D levels have been associated with falls, and low bone mineral density.

The United States Preventive Services Task Force issued a draft statement on 12 June 2012 recommending that healthy postmenopausal women should not take low doses of calcium or vitamin D supplements to prevent fractures.

Some studies have shown that supplementation with vitamin D and calcium may improve bone mineral density slightly, as well as decreasing the risk of falls and fractures in certain groups of people, specifically those older than 65 years. This appears to apply more to people in institutions than those living independently. The quality of the evidence is, however, poor. And there does not appear to be a benefit to bone health from vitamin D without sufficient calcium.

Cardiovascular disease

Evidence for health effects from vitamin D supplementation for cardiovascular health is poor. Moderate to highdoses may reduce cardiovascular disease risk but are of questionable clinical significance.

Multiple sclerosis

Low levels of vitamin D are associated with multiple sclerosis. Supplementation with vitamin D may have a protective effect but there are uncertainties and unanswered questions. The reasons why vitamin D deficiency is thought to be a risk factor for MS are as follows: (1) MS frequency increases with increasing latitude, which is strongly inversely correlated with duration and intensity of UVB from sunlight and vitamin D concentrations; (2) prevalence of MS is lower than expected at high latitudes in populations with high consumption of vitamin-D-rich fatty fish; and (3) MS risk seems to decrease with migration from high to low latitudes. A clinical trial sponsored by Charite University in Berlin, Germany was begun in 2011, with the goal of examining the efficacy, safety and tolerability of vitamin D3 in the treatment of Multiple Sclerosis.

Cancer

Low vitamin D levels are associated with some cancers and with worse outcomes in other cancers, but taking supplements does not appear to help people with prostate cancer. Currently evidence is insufficient to support supplementation in those with cancer. Results for a protective or harmful effect of vitamin D supplementation in other types of cancer are inconclusive.

Other

Vitamin D appears to have effects on immune function, It has been postulated to play a role in influenza with lack of vitamin D synthesis during the winter as one explanation for high rates of influenza infection during the winter. For viral infections, other implicated factors include low relative humidities produced by indoor heating and cold temperatures that favor virus spread. Low levels of vitamin D appear to be a risk factor for tuberculosis, and historically it was used as a treatment. As of 2011, it is being investigated in controlled clinical trials. Vitamin D may also play a role in HIV. Although there are tentative data linking low levels of vitamin D to asthma, there is inconclusive evidence to support a beneficial effect from supplementation. Accordingly, supplementation is not currently recommended for treatment or prevention of asthma. Also, preliminary data do not support a role for supplemental vitamin D in promotion of human hair growth