Vitamin D; sources, significance, toxicity

THE SIGNIFICANCE OF VITAMIN D

Vitamin D,1 the “sunshine vitamin,” is actually a hormone produced from sterols in the body by the photolytic action of ultraviolet light on the skin; individuals who receive modest exposures to sunlight are able to produce their own vitamin D. However, this is not the case for many people, such as those who live in northern latitudes, spend most of their days indoors, and/or have darker skin, and for animals reared in controlled environments. Such individuals must obtain the nutrient from their diets; for them, vitamin D is a vitamin in the traditional sense.

vitamin D


Vitamin D plays an important role, along with the essential minerals calcium, phosphorus, and magnesium, in the maintenance of healthy bones and teeth – where problems appear to have existed in a variety of past populations from various parts of the world.2 They remain contemporary issues of major public health impact; an estimated 40–90% of adults worldwide are of insufficient vitamin D status. The prevalence of low vitamin D status has been estimated at 11–84% of adults in the United States, 5–40% of adults in the United Kingdom, and 93% of youth in Canada.

Rickets, the deforming and debilitating disease involving delayed or failed endochondral ossification (mineralization at the growth plates) of the long bones, remains a problem in many countries, having been reported at prevalences as great as 10% among infants exclusively fed breast milk and children with little sun exposure.

SOURCES OF VITAMIN D Distribution in Foods

Vitamin D, as either ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3), is rather sparsely represented in nature; however, its provitamins are common in both plants and animals. Ergocalciferol and its precursor ergosterol are found in plants, fungi,9 molds, lichens, and some invertebrates (e.g., snails and worms). In fact, some microorganisms are quite rich in ergosterol, in which it may comprise as much as 10% of the total dry matter.

Ergosterol does not occur naturally in higher vertebrates, but it can be present in low amounts in tissues of those species as the result of their consuming it. The actual distribution of ergocalciferol in nature is much more limited and variable than that of ergosterol (e.g., grass hays and alfalfa contain vitamin D only after they have been cut and left to dry in the sun). Whereas vitamin D2 is probably present only in small amounts from natural sources, it has been a major synthetic form used in animal and human nutrition for several decades.

Skin

Vitamin D has a paracrine function in the skin. Keratinocytes express 25-(OH)2-D3 1-hydroxylase; therefore, they can not only produce vitamin D3 with solar exposure, but also metabolize it to 1,25-(OH)2-D3. VDRs are also expressed throughout the epidermis as well as in hair follicles. Among the gene products induced by VDR activation in the skin is cathelicidin antimicrobial peptide (CAMP), which functions both in the direct killing of pathogens as well as a host response involving cytokine release, inflammation, and cellular immune response.

Mutations of VDR occur in patients with hereditary vitamin D-resistant rickets. They show alopecia, the basis of which is unclear as the condition is not caused by vitamin D deficiency per se or by loss of 25-OH-D3 1-hydroxylase activity.

Muscular Function

That vitamin D plays an important role in muscle is evidenced by the muscle weakness that is typical of vitamin D-deficient subjects, the presence of VDR in myocytes, and the lack of muscle development observed in VDRknockout mice. Vitamin D, 1,25-(OH)2-D3, has been shown to be essential for the homeostatic control of intracellular Ca2, thus affecting both contractility and myogenesis.

Brain Development

A role of vitamin D in brain development and function was first indicated by the finding of 25-OH-D3 in cerebrospinal fluid, and of nVDR and 25-OH-D3 1-hydroxylase activity in brain tissue. Maternal deprivation of vitamin D affects rat pups, which show alterations in brain morphology, stem cell proliferation, gene expression, and expression of neurotrophic factors.

Rheumatoid Arthritis (RA)

VDR is expressed by articular chondrocytes in osteoarthritic cartilage, which also express matrix metalloproteinases (MMPs) not found in normal cartilage. Such observations, and the finding that vitamin D treatment prevented experimentally induced RA and prostaglandin E2 production in animal models, suggest a role of the vitamin in this immune-mediated disease characterized by articular inflammation leading to disability. One study noted an inverse relationship of vitamin D intake, particularly from supplements, and risk of developing RA.

Multiple Sclerosis

It has been long recognized that multiple sclerosis (MS), an autoimmune disease characterized by immune attacks on the myelin sheaths of nerves, is more prevalent in northern, temperate parts of the world than in the tropics. In fact, the prevalence has been found to be strongly inversely related to the numbers of hours of annual or winter sunlight. Two studies have found the use of vitamin D supplements to reduce the risk of developing MS by as much as 40%.100 The only study to date with MS subjects found vitamin D supplementation to increase circulating levels of the anti-inflammatory cytokine transforming growth factor β1 (TGF-β1), suggesting potential for alleviating symptoms.

Insulin-Dependent Diabetes (Type 1 Diabetes, T1D)

It has been suggested that vitamin D may play a role in reducing the risk of T1D, which results from the T-cell dependent destruction of insulin-producing pancreatic β cells by cytokines and free radicals from inflammatory infiltrates. It has been suggested that vitamin D may be beneficial in the treatment of T1D by inhibiting the production of IL-12 and suppressing the activity of IL-12-dependent Th1 cells in activating cytotoxic CD8 lymphocytes and macrophages. diet, as most foods contain only minuscule amounts. Vitamin D deficiency can have privational and nonprivational causes.

Privational causes involve inadequate vitamin D supply.

They include:

inadequate exposure to sunlight, and

insufficient consumption of food sources of vitamin D.

Non-privational causes relate to impairments in the absorption, metabolism or nuclear binding of the vitamin.

They include:

diseases of the gastrointestinal tract (e.g., small bowel disease, gastrectomy, pancreatitis), involving malabsorption of the vitamin from the diet

diseases of the liver (biliary cirrhosis, hepatitis), involving reduced activities of the 25-hydroxylase

diseases of the kidney (e.g., nephritis, renal failure),

involving reduced activities of the 1-hydroxylase, the major source of 1,25-(OH)2-D3, or of 25-OHDas in individuals with nephrotic syndrome, who lose 25-OH-D3 along with its globulin-binding protein into the urine exposure to certain drugs (e.g., the anticonvulsives phenobarbital and diphenylhydantoin) which induce the catabolism of 25-OH-D3 and ,25-(OH)2-D3reduce circulating levels of the former, and reduce elevated PTH levels impaired parathyroid function resulting in

hypoparathyroidism (reduced production of PTH), which impairs the ability to respond to hypocalcemia by increasing the conversion of 25-OH-D3 to 1,25-(OH)2-D3

 

REFERENCE

The Vitamins

Fourth Edition

Gerald F. Combs, Jr

Professor Emeritus

Cornell University

Ithaca, NY

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