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Vitamin D

Vitamin D is a family of related compounds with hormone-like activity. Ocean plankton, most plants and most animals exposed to sunlight make vitamin D. Vitamin D is critical for the development, growth, and maintenance of a healthy skeleton from birth until death. Vitamin D-activity promotes the absorption and deposition of calcium in bones. Rickets is the best-known Vitamin D deficiency disease, characterized by under-mineralized, soft bone, which bends and breaks easily.

Vitamin D is really a hormone we can get from food if internal production is insufficient. In the best case, Vitamin D is produced by the skin exposed to sunlight: it was suggested that 20 minutes of daily sun exposure to face and hands will supply the requirement for D. However, there are too many variables to rely on such a simple rule. Food sources are required by people with little or no sun exposure. The most common food source of Vitamin D is fish liver oils – cod and halibut liver oil has been the most available source of Vitamin D. Plant foods are deficient in Vitamin D.

In adults, under-mineralized bone is known as osteomalacia. The incidence of rickets has been reduced in the past 2 or 3 decades by the addition of Vitamin D to milk and infant formulas. Rickets continues to plague undernourished, sun-deprived children. Daily intake goals are in the range of 200-800 IU/day.

Since plant foods have negligible quantities of Vitamin D, either sun exposure or supplementation is required to achieve adequate levels of Vitamin D activity in the body. Hypoallergenic diets typically exclude milk and other foods supplemented with Vitamin D and require vitamin D supplements in tablet or oil form, especially in the winter. Recommended daily intake goals are in the range of 200-400 IU/day, although new indications for Vitamin D require higher doses. Vitamin D is added routinely to foods such as milk, bread, fruit juices, in their manufacture or processing. Milk contains added Vitamin D in the range of 30 IU per ml. Sun or ultraviolet light exposure (wavelengths 290-320 nm) of skin excites skin cells to produce Vitamin D. Dietary sources are required when sun and skin are dissociated by clouds, buildings, and clothes.

Research into the physiological roles of the Vitamin D complex has differentiated many different members of this group, differing chemically in the placement of side chains and hydroxyl (-OH) groups around the basic ring structure of the molecule. The two important groups of compounds are: Vitamin D2 or ergocalciferols, and Vitamin D3 or cholecalciferols. The most active metabolite is 1,25-OH-D3 (the 1,25 refers to the location of the hydroxyl group -OH on the ring). A kidney enzyme, 1alpha-hydroxylase, produces this hormone also known as calcitriol. 1,25-OH-D3 inhibits proliferation of both normal and hyperproliferative cells and induces them to mature. Its analogs have been developed for treating the hyperproliferative skin disease, psoriasis.

Measurement of Vitamin D activity can be confusing and irregular: 1 international unit (IU) = .025 micrograms of ergocalciferol (D2). By weight, the required amounts of Vitamin D are miniscule; 5-10 micrograms per day represent the recommended intake; therapeutic levels up to 7000 mcg/day have been used to treat osteomalacia; toxicity appears at 1200 mcg/day (above 50-60,000 IU/day). Blood levels of Vitamin D are usually assessed by measuring the main transport form, 25-OH-D3; serum values less than 10 nanogram/ml indicate deficiency. Serum levels higher than 400 nanograms/ml are toxic. Symptoms of Vitamin D overdose include weakness, fatigue, loss of appetite, nausea, vomiting, bone pain, and heart rhythm irregularities.

Zittermann suggests that there many opportunities for Vitamin D supplementation that are relatively ignored. Calcitriol receptors are present in more than thirty different tissues. There is agreement that a low vitamin D status is involved in the pathogenesis of osteoporosis. Vitamin D insufficiency can also lead to a disturbed muscle function. Zimmerman states that: “epidemiological data also indicate a low vitamin D status in tuberculosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseases, hypertension, and specific types of cancer. Some intervention trials have demonstrated that supplementation with vitamin D or its metabolites can (i) reduce blood pressure in hypertensive patients; (ii) improve blood glucose levels in diabetics; (iii) improve symptoms of rheumatoid arthritis and multiple sclerosis. The oral dose necessary to achieve adequate serum 25(OH)D levels is probably much higher than the current recommendations.”

Holick suggested that: “Vitamin D deficiency is a major unrecognized health problem. Not only does it cause rickets in children, osteomalacia and osteoporosis in adults, but may have long lasting effects. Chronic vitamin D deficiency may contribute to hypertension, multiple sclerosis, cancers of the colon, prostate, breast, and ovary, and type 1 diabetes. There needs to be a better appreciation of the importance of vitamin D for overall health and well being.”

A meta-analysis of randomized controlled trials of 42,279 subjects who took vitamin D supplements with cholecalciferol or ergocalciferol and concluded that a dose-response relationship between vitamin D and fracture reduction is supported by data showing a significant positive trend between serum 25-hydroxyvitamin D concentrations, hip bone density and lower extremity strength. They concluded that: "A higher received dose of supplemental vitamin D (482-770 IU/d) should reduce nonvertebral fractures by at least 20% and hip fractures by at least 18%.” The addition of calcium did not further improve the antifracture efficacy of vitamin D. Doses of vitamin D below 400 U daily did not reduce fracture risk. Higher daily intake of vitamin D3 (up to 4000 iu/day) may be required for full benefit. Bischoff-Ferrar followed 173 patients who had hip fractures and stated:" Our study demonstrated that an extended physiotherapy program, together with 2000 IU per day of vitamin D, has complementary benefits for post-hip-fracture care, including a significant 25% reduction in falls and a 39% reduction in hospital readmission."

Hayes et al reviewed evidence that the vitamin D endocrine system influences immune system functions and in particular, that the vitamin D endocrine system functions in the establishment and/or maintenance of immunological self tolerance. They stated: “. Studies done in animal models of multiple sclerosis (MS), insulin-dependent diabetes mellitus (IDDM), inflammatory bowel disease (IBD), and transplantation support a model wherein the 1alpha,25-(OH)2D3 may augment the function of suppressor T cells that maintain self tolerance to organ-specific self antigens” In other words, Vitamin D deficiency may predispose susceptible individuals to autoimmune diseases.

Munger et al suggested that there is a protective effect of dietary vitamin D supplementation on the risk of multiple sclerosis (MS). They examined vitamin D intake in two cohorts of women in the Nurses' Health Study (NHS; 92,253 women followed from 1980 to 2000) and Nurses' Health Study II (NHS II; 95,310 women followed from 1991 to 2001). 173 cases of MS were confirmed. Intake of vitamin D from supplements was inversely associated with risk of MS; the relative risk comparing women with intake of >=400 IU/day with women with no supplemental vitamin D intake was 0.59.

Garland et al conducted a meta-analysis of 5 studies examining serum 25-hydroxyvitamin and the incidence of colorectal cancer and decided that raising the serum level of 25-hydroxyvitamin D to 34 ng/mL would reduce the incidence rates of colorectal cancer by half. This would require an intake of 1000 to 2000 IU per day. In another review, Garland et al concluded that the risk for breast cancer may be reduced by 50% through consumption of 4000 IU/day of vitamin D or 2000 IU of vitamin D per day and 12 minutes of sun exposure per day.

Kumar et al reviewed data gathered in the 2001 to 2004 US National Health and Nutrition Examination Survey (NHANES), a sample of 6,275 children aged 1 to 21 and concluded 70% of U.S. children have low vitamin D levels, putting them at risk of heart disease, rickets, and weak bones. Reis et al analyzed data from 3,577 12- to 19-year-olds in the NHANES database and concluded that low vitamin D put kids at risk of heart disease as adults.

In the laboratory, 1,25-dihydroxyvitamin D(3) is a potent inhibitor of tumor cell growth, and many analogues have be created to treat cancer; however, clinical trails have been disappointing. Vitamin D analog tend to have side effects, mostly hypercalcemia. Laboratory work continues with the hope of developing more effective and safe analogues of vitamin D. Dietary calcium and vitamin D acting together impede the development of colon cancer. Supplements of both nutrients are a reasonable preventive strategy for colon cancer.

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