Hayes CE, Cantorna MT, DeLuca HF.Cancer and Other Diseases and Vitamin D
Department of Biochemistry, University of Wisconsin-Madison 53706, USA.
Recently, it has been clearly demonstrated that exogenous 1,25-dihydroxyvitamin D3, the hormonal form of vitamin D3, can completely prevent experimental autoimmune encephalomyelitis (EAE), a widely accepted mouse model of human multiple sclerosis (MS). This finding has focused attention on the possible relationship of this disease to vitamin D. Although genetic traits certainly contribute to MS susceptibility, an environmental factor is also clearly involved. It is our hypothesis that one crucial environmental factor is the degree of sunlight exposure catalyzing the production of vitamin D3 in skin, and, further, that the hormonal form of vitamin D3 is a selective immune system regulator inhibiting this autoimmune disease. Thus, under low-sunlight conditions, insufficient vitamin D3 is produced, limiting production of 1,25-dihydroxyvitamin D3, providing a risk for MS. Although the evidence that vitamin D3 is a protective environmental factor against MS is circumstantial, it is compelling. This theory can explain the striking geographic distribution of MS, which is nearly zero in equatorial regions and increases dramatically with latitude in both hemispheres. It can also explain two peculiar geographic anomalies, one in Switzerland with high MS rates at low altitudes and low MS rates at high altitudes, and one in Norway with a high MS prevalence inland and a lower MS prevalence along the coast. Ultraviolet (UV) light intensity is higher at high altitudes, resulting in a greater vitamin D3 synthetic rate, thereby accounting for low MS rates at higher altitudes. On the Norwegian coast, fish is consumed at high rates and fish oils are rich in vitamin D3. Further, experimental work on EAE provides strong support for the importance of vitamin D3 in reducing the risk and susceptibility for MS. If this hypothesis is correct, then 1,25-dihydroxyvitamin D3 or its analogs may have great therapeutic potential in patients with MS. More importantly, current research together with data from migration studies opens the possibility that MS may be preventable in genetically susceptible individuals with early intervention strategies that provide adequate levels of hormonally active 1,25-dihydroxyvitamin D3 or its analogs.
Cells that are dividing rapidly are said to be proliferating. Differentiation results in the specialization of cells for specific functions. In general, differentiation of cells leads to a decrease in proliferation. While cellular proliferation is essential for growth and wound healing, uncontrolled proliferation of cells with certain mutations may lead to diseases like cancer. The active form of vitamin D, 1,25(OH)2D, inhibits proliferation and stimulates the differentiation of cells (1).The Canadian Cancer Society recommends taking at least 1,000 IU [international units] of vitamin D each day. Most people don't even think about such supplements; most people are somewhat deficient in vitamin D if they live north or south of 40° latitude or eat a diet low in fish.
Risk Factors for Vitamin D Deficiency
- Exclusively breast-fed infants: Infants who are exclusively breast-fed and do not receive vitamin D supplementation are at high risk of vitamin D deficiency, particularly if they have dark skin and/or receive little sun exposure (20). Human milk generally provides 25 IU of vitamin D per liter, which is not enough for an infant if it is the sole source of vitamin D. Older infants and toddlers exclusively fed milk substitutes and weaning foods that are not vitamin D fortified are also at risk of vitamin D deficiency (19). The American Academy of Pediatrics recommends that all infants that are not consuming at least 500 ml (16 ounces) of vitamin D fortified formula or milk be given a vitamin D supplement of 200 IU/day (20).
- Dark skin: People with dark-colored skin synthesize less vitamin D on exposure to sunlight than those with light-colored skin (1). The risk of vitamin D deficiency is particularly high in dark-skinned people who live far from the equator. One U.S. study reported that 42% of African American women between 15 and 49 years of age were vitamin D deficient compared to 4% of White women (25).
- Aging: The elderly have reduced capacity to synthesize vitamin D in skin when exposed to UVB radiation, and the elderly are more likely to stay indoors or use sunscreen, which blocks vitamin D synthesis. Institutionalized adults who are not supplemented with vitamin D are at extremely high risk of vitamin D deficiency (26, 27).
- Covering all exposed skin or using sunscreen whenever outside: Osteomalacia has been documented in women who cover all of their skin whenever they are outside for religious or cultural reasons (28, 29). The application of sunscreen with an SPF factor of 8 reduces production of vitamin D by 95% (1).
- Fat malabsorption syndromes: Cystic fibrosis and cholestatic liver disease impair the absorption of dietary vitamin D (30).
- Inflammatory bowel disease: People with inflammatory bowel disease like Crohn’s disease appear to be at increased risk of vitamin D deficiency, especially those who have had small bowel resections (31).
- Obesity: Obesity increases the risk of vitamin D deficiency (32). Once vitamin D is synthesized in the skin or ingested, it is deposited in body fat stores, making it less bioavailable to people with large stores of body fat.