Vitamin D

Vitamin D is a fat-soluble vitamin found in food. It can also be made in your body after exposure to ultraviolet rays from the sun. Sunshine is a significant source of vitamin D because UV rays from sunlight trigger vitamin D synthesis in the skin [1-2].

Vitamin D exists in several forms, each with a different level of activity. Cholecalciferol is the most active form of vitamin D. Other forms are relatively inactive in the body. The liver and kidney help convert vitamin D to its active hormone form [3]. Once vitamin D is produced in the skin or consumed in food, it requires chemical conversion in the liver and kidney to form 1,25 dihydroxyvitamin D, the physiologically active form of vitamin D. Active vitamin D functions as a hormone because it sends a message to the intestines to increase the absorption of calcium and phosphorus [3].

The major biologic function of vitamin D is to maintain normal blood levels of calcium and phosphorus [3-4]. By promoting calcium absorption, vitamin D helps to form and maintain strong bones. Vitamin D also works in concert with a number of other vitamins, minerals, and hormones to promote bone mineralization. Without vitamin D, bones can become thin, brittle, or misshapen. Vitamin D sufficiency prevents rickets in children and osteomalacia in adults, two forms of skeletal diseases that weaken bones [5-6].

Research also suggests that vitamin D may help maintain a healthy immune system and help regulate cell growth and differentiation, the process that determines what a cell is to become [3,7,8].

Vitamin D as Anti-Inflammatory:

According to a recent German clinical trial, a high dose Vitamin D supplement was able to inhibit pro inflammatory molecules and increase anti-inflammatory molecules, which scientists believe may help people with chronic heart failure.

The randomized placebo-controlled trial was published in the April issue of the American Journal of Clinical Nutrition (Vol. 83, pp. 754-759). In the study, a high-dose vitamin D₃ supplement (50 micrograms, equivalent to 2000 International Units) was given to 120 patients with CHF and their cytokine levels and heart pumping ability were measured. Both placebo and vitamin D supplement groups were also given a daily supplement of 500 milligrams of calcium.

After nine months, the researchers reported that serum levels of 25-hydroxyvitamin D (the non-active ‘storage' form of the vitamin in the body) increased by 26.8 nanograms per milliliter (ng/mL) from the start of the study for the supplemented group, while the placebo group's levels decreased by 3.6 ng/mL.

Levels of TNF-alpha did not differ significantly before or after supplementation with vitamin D, but it did increase by 12% in the placebo group. Interleukin 10 (IL-10) levels increased by an impressive 43% in the supplemented group, but did not change in the placebo group.

No significant difference was observed in heart function, as measured by left ventricular ejection fraction (LVEF), for either of the groups; a result that differs from a previous study with lower vitamin D doses (400 IU) that reported improvements in LVEF, but no improvement in cytokine levels.

An accompanying editorial by Reinhold Vieth and Samantha Kimball from the University of Toronto, said that the study offered two important insights: “First, the article confirms previous evidence that vitamin D supplementation affects immune-modulating cytokines in desirable ways. Second, it points to a higher dose requirement for achieving this.”

Vitamin D has been reported to improve muscular function, control blood pressure, and improve glucose tolerance, all of which underlying causes of CHF, said Vieth and Kimball.

“The more realistic question raised by Schleithoff et al is whether the use of an appropriate dose of vitamin D, as one part of a nutritional strategy, could help in the primary prevention of CHF,” concluded the editorial.

Vitamin D and Cancer:

US scientists investigating the link between Vitamin D levels and cancer risk believe that raising the RDA of vitamin D from 400 IU to 1500 IU could cut the number of deaths from cancer by 30 per cent.

Vitamin D refers to two biologically inactive precursors – D₃, also known as cholecalciferol, and D₂, also known as ergocalciferol. The former, produced in the skin on exposure to UVB radiation (290 to 320 nm), is said to be more bioactive. The latter is derived from plants and only enters the body via the diet.

Both D₃ and D₂ precursors are hydroxylated in the liver and kidneys to form 25- hydroxyvitamin D (25(OH)D), the non-active ‘storage' form, and 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active form that is tightly controlled by the body.

There is growing evidence that 1,25(OH)2D has anticancer effects, but the discovery that non-kidney cells can also hydroxylate 25(OH)D had profound implications, implying that higher 25(OH)D levels could protect against cancer in the local sites.

The Health Professionals Follow-Up study, a prospective study of over 50,000 US male health professionals, is the first study to examine total cancer incidence and factors that determine 25(OH)D levels.

“In this cohort analysis, a 25(OH)D increment of 25 nanomoles per litre (nm/L) was associated with a 17 per cent reduction in total cancer incidence, a 29 per cent reduction in total cancer mortality, and a 45 per cent reduction in mortality of digestive-system cancer,” wrote Giovannucci in the April issue of the Journal of the National Cancer Institute (vol. 98, pp. 451-459).

The RDA of 400 International Units (IU), equal to 10 micrograms per day, raises plasma levels of 25(OH)D by a modest 7 nm/L.

“Achieving a 25(OH)D increment of 25 nm/L may require a vitamin D supplementation of at least 1500 IU per day, a safe but not generally encouraged level,” said Giovannucci.

The best source of vitamin D is from sun exposure, with a fair-skinned person estimated to produce up to 20,000 IU after 20-30 minutes in the sun. However, sun exposure is not recommended due to the increased risk of skin cancer.

In an accompanying editorial, Gary Schwartz from Wake Forest University and William Blot from the Vanderbilt University Medical Center said clinical trials of high dose vitamin D supplementation and the risk of cancer should be “undertaken speedily”.

“The potential for cancer prevention by vitamin D (in pill form) must now proceed to the clinical trial testing arena,” said the editorial.

Unlike beta-carotene and vitamin E, both of which were heralded as cancer preventatives only to be questioned by further studies, the evidence for vitamin D is strong, said the editorial.

“The biological evidence for inhibition of carcinogenesis is strong and, often, was predicted by the prior epidemiological findings on sunlight exposure.”

 The vitamin's protection is proposed to be multifaceted, by reducing the formation of blood vessels in tumors (angiogenesis), stimulating the mutual adherence of cells, and enhancing intercellular communication through gap junctions. All this adds up to stop proliferation of cancerous cells by contact inhibition.