Vitamin D: Illuminating the Sunshine Vitamin

By Tam Herd and Robert Greenfield, Ph.D., Contributing Editors

 Vitamin D is recognized by the nutritional and scientific communities as one of the most important nutritional components for optimal human health. Since the 1940s, vitamin D has been used to fortify milk, foods and beverages to prevent rickets. However, new research in the last five to 10 years has established that vitamin D is critically involved with cancer, multiple sclerosis, types 1 and 2 diabetes, inflammatory illnesses, autoimmune diseases, cardiovascular disease, infectious diseases, osteoporosis, obesity and neurological disorders. Research has also demonstrated that vitamin D is a hormone-like molecule that directly regulates and controls over 200 human genes. Importantly, nearly 1 billion people worldwide are clinically deficient in vitamin D and suffer from serious disease due to their insufficiency.

D-fined

Synthetic vitamin D3 (cholecalciferol), found in most supplements, is manufactured from lanolin obtained from sheep's wool. Vitamin D2 (ergocalciferol) is a less potent vitamin D form synthesized from yeast and is preferred by strict vegans. Vitamin D3 is produced in the body through a photosynthetic reaction involving the suns UV irradiation of the skin, wherein 7-dehydroxycholesterol is converted to vitamin D. Vitamin D3 from the skin or diet is metabolized in the liver to 25-hydroxyvitamin D. This intermediate found in the blood is commonly used to determine a patients vitamin D status. 25-hydroxyvitamin D is metabolized in the kidneys to its active form 1,25 dihydroxyvitamin D. This active form of vitamin D is a hormonechemically akin to familiar steroid hormones, such as testosterone, oestrogen and cortisolwhich directly regulates gene expression.

Daily dose

Currently, vitamin D daily requirements for adults is 400 to 600 IU per day. These values have been determined based upon the prevention of rickets and effects on calcium and bone metabolism. There now is a large and growing body of scientific opinion that the current Recommended Dietary Allowance (RDA) of vitamin D needs to be significantly elevated to 1,000 to 2,000 IU per day to gain maximal benefit from the myriad new biological activities recently attributed to vitamin D.

Many studies have established that almost 50% of Americans and Europeans are deficient in vitamin D. Recent reports suggest that 50,000 to 70,000 U.S. citizens and 30,000 to 35,000 U.K. residents die prematurely from cancer annually due to insufficient vitamin D.

Vitamin D sufficiency and insufficiency is mainly based upon serum levels of the metabolite 25-dihydroxy vitamin D. Healthy levels of 25-hydroxy vitamin D range between 30 to 70 ng per ml. Levels below 30 ng per ml are considered to be insufficient or deficient. Factors with the largest effect on vitamin D blood levels are lifestyle-related: sun exposure, vitamin D supplementation and use of certain pharmaceutical drugs. While solar UVB irradiation is the main source of vitamin D, the fear of skin cancer due to overexposure to solar radiation has reduced sun-exposure rates and contributes to the low vitamin D in the population.

Through the years

Low birth weight appears to be a consequence of a mother's vitamin D insufficiency during pregnancy. An additional benefit of sufficient vitamin D and calcium during pregnancy is good maternal bone health. Maternal and infant 25(OH)D sufficiency is also linked to significant reduction of risk for multiple sclerosis.

The primary role of sufficient vitamin D during youth, adolescence and adulthood is optimization of bone mineral density (BMD). The primary risk factors for low BMD, osteoporosis and osteopenia include vitamin D insufficiency, inadequate calcium intake, lack of exercise and other dietary factors. Another benefit of vitamin D is maintenance of optimal muscle strength. The elderly have a particularly strong need to maintain vitamin D sufficiency to prevent common age-related conditions, such as cancer and osteoporotic fractures. Vitamin D sufficiency, adequate dietary calcium and related minerals, and exercise help reduce the risk of falls, fractures and tooth loss.

Vitamin D and cancer

Sufficient vitamin D levels in adulthood may significantly reduce the risk for many types of cancer. The interest in vitamin D as a risk-reduction factor for cancer began in 1980 when cancer researchers from the University of California, San Diego, looked at maps of cancer mortality rates in the United States and noticed low colon-cancer rates in the Southwest could be correlated with exposure to sunlight. A few years later they demonstrated that colon-cancer risk was inversely associated with prediagnostic serum 25(OH)D levels.

It was soon discovered that breast, ovarian and prostate cancer also had inverse correlations with solar UVB radiation. By the late 1990s, the mechanisms whereby vitamin D reduces the risk of cancer were fairly well known: facilitation of calcium absorption (colon cancer), increased cell differentiation and apoptosis, and reduction of both metastasis and angiogenesis. Calcium has been shown to decrease proliferation and induce differentiation in epithelial cells. In addition, it was discovered that most organs have vitamin DrReceptors (VDRs). Various alleles of VDRs may affect the risk of many cancer types, including cervical, breast, colon, gall bladder, laryngeal, oral, pancreatic, and Hodgkinʼs lymphoma, among others.

A closer look

Recent genetic studies are revealing specific genes, polymorphisms and proteins that may explain at the molecular level the function of vitamin D. In a collaboration between the University of Oxford, the Wellcome Trust and the MS Society, scientists reported 229 genes were directly regulated by vitamin D, and there were 2,766 binding sites for the vitamin D receptor along the length of the genome (Genome Research, 2010; 20:1,352-1,360). Vitamin D deficiency was shown to increase susceptibility to a wide range of diseases. The gene designated CYP27B1, which codes for the kidney enzyme 1-hydroxylase, which converts 25(OH)D to 1,25(OH)2D, has been clearly linked to multiple sclerosis in many scientific publications over the last ten years. More recently, a collaboration of U.K. and Canadian scientists (Annals of Neurology, 2011; 70(6):881-886) revealed that 35 of 35 children of parents with one copy of a mutation in the CYP27B1 gene have low vitamin D levels and multiple sclerosis. Additionally, they found that children with two copies of mutations in CYP27B1 gene exhibit multiple sclerosis and rickets. These genetic studies support observational population-based studies and provide molecular evidence that strongly link vitamin D deficiency to multiple sclerosis. This same vitamin D metabolic enzyme has also been associated with types 1 and 2 diabetes. The likelihood is high that the causes of other diseases linked to vitamin D deficiency reside in molecular anomalies related to vitamin D metabolism.

One of the biggest questions being asked now is whether vitamin D supplementation can treat diseases associated with vitamin D deficiency. Many ongoing studies are testing this hypothesis in cancer, multiple sclerosis, cardiovascular disease and diabetes. Multiple well-controlled clinical studies will be needed to clearly demonstrate that vitamin D supplementation will improve disease conditions brought on by vitamin D deficiency.

Tam Herd is marketing director, and Robert Greenfield, Ph.D., is chief science officer of Vitacyclix (vitacyclix.com), a manufacturer of vitamin D liquid concentrates, powders and supplements, as well as vitamins for fortification, food ingredients and natural skincare products.