Vitamin D is really a hormone
المؤلف:
Peter J. Kennelly, Kathleen M. Botham, Owen P. McGuinness, Victor W. Rodwell, P. Anthony Weil
المصدر:
Harpers Illustrated Biochemistry
الجزء والصفحة:
32nd edition.p538-540
2025-12-15
43
Vitamin D is not strictly a vitamin since it can be synthesized in the skin, and under most conditions this is the major source of the vitamin. Only when sunlight exposure is inadequate is a dietary source required. Vitamin D’s main function is to regulate calcium absorption and homeostasis; most of its actions are mediated by way of nuclear receptors that regulate gene expression. It also has a role in regulating cell proliferation and differentiation. There is evidence that intakes considerably higher than are required to maintain calcium homeostasis reduce the risk of insulin resistance, obesity, and metabolic syndrome, as well as various cancers. Deficiency, leading to rickets in children and osteomalacia in adults, continues to be a problem in north ern latitudes, where sunlight exposure is inadequate.
Vitamin D Is Synthesized in the Skin
7-Dehydrocholesterol (an intermediate in the synthesis of cholesterol that accumulates in the skin) undergoes a nonenzymic reaction on exposure to ultraviolet light, yield ingprevitamin D (Figure 1). This undergoes a further reaction over a period of hours to form cholecalciferol, which is absorbed into the bloodstream. In temperate climates, the plasma concentration of vitamin D is highest at the end of summer and lowest at the end of winter. Beyond latitudes about 40° north or south, there is very little ultraviolet radiation of the appropriate wavelength in winter.
Fig1. The synthesis of vitamin D in the skin.
Vitamin D Is Metabolized to the Active Metabolite, Calcitriol, in Liver & Kidney
Cholecalciferol, either synthesized in the skin or from food, undergoes two hydroxylations to yield the active metabolite, 1,25-dihydroxyvitamin D or calcitriol (Figure 2). Ergocal ciferol from fortified foods undergoes similar hydroxylation to yield ercalcitriol. In the liver, cholecalciferol is hydroxylated to form the 25-hydroxy derivative, calcidiol. This is released into the circulation bound to a vitamin D–binding globulin, which is the main storage form of the vitamin. In the kidney, calcidiol undergoes either 1-hydroxylation to yield the active metabolite 1,25-dihydroxyvitamin D (calcitriol), or 24-hydroxylation to yield a probably inactive metabolite, 24,25-dihydroxyvitamin D (24-hydroxycalcidiol). Some tissues, other than those that are involved in calcium homeostasis, take up calcidiol from the circulation and synthesize calcitriol that acts within that cell.
Fig2. Metabolism of vitamin D.
Vitamin D Metabolism Is Both Regulated by and Regulates Calcium Homeostasis
The main function of vitamin D is in the control of calcium homeostasis, and in turn, vitamin D metabolism is regulated by factors that respond to plasma concentrations of calcium and phosphate. Calcitriol acts to reduce its own synthesis by inducing the 24-hydroxylase and repressing the 1-hydroxylase in the kidney. The principal function of vitamin D is to maintain the plasma calcium concentration. Calcitriol achieves this in three ways: it increases intestinal absorption of calcium; it reduces excretion of calcium (by stimulating reabsorption in the distal renal tubules); and it mobilizes bone mineral. In addition, calcitriol is involved in insulin secretion, synthesis and secretion of parathyroid and thyroid hormones, inhibition of production of interleukin by activated T-lymphocytes and of immunoglobulin by activated B-lymphocytes, differentiation of monocyte pre cursor cells, and modulation of cell proliferation. In most of these actions, it acts like a steroid hormone, binding to nuclear receptors and enhancing gene expression, although it also has a rapid effect to mobilize calcium transporters in the intestinal mucosa.
Higher Intakes of Vitamin D May Be Beneficial
There is growing evidence that higher vitamin D status is protective against various cancers, including prostate and colorectal cancer, and also against prediabetes and metabolic syndrome. Desirable levels of intake may be considerably higher than current reference intakes, and certainly could not be met from unfortified foods. While increased sunlight exposure would meet the need, it carries the risk of developing skin cancer.
Vitamin D Deficiency Affects Children & Adults
In the vitamin D deficiency disease rickets, the bones of children are undermineralized as a result of poor absorption of calcium. Similar problems occur as a result of deficiency during the adolescent growth spurt. Osteomalaciain adults results from the demineralization of bone, especially in women who have little exposure to sunlight, especially after several pregnancies. Although vitamin D is essential for prevention and treatment of osteomalacia in the elderly, there is less evidence that it is beneficial in treating osteoporosis.
Vitamin D Is Toxic in Excess
Some infants are sensitive to intakes of vitamin D as low as 50 μg/d, resulting in an elevated plasma concentration of calcium. This can lead to contraction of blood vessels, high blood pressure, and calcinosis—the calcification of soft tissues. In at least a few cases, hypercalcemia in response to low intakes of vitamin D is due to genetic defects of calcidiol 24-hydroxylase, the enzyme that leads to inactivation of the vitamin. Although excess dietary vitamin D is toxic, excessive exposure to sun light does not lead to vitamin D poisoning, because there is a limited capacity to form the precursor, 7-dehydrocholesterol, and prolonged exposure of previtamin D to sunlight leads to formation of inactive compounds.
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