Fw: Vitamin D, the kidney steroid

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Cholecalciferol: the sunlight " vitamin "

Medical Sciences Bulletin, Aug. 1995

Cholecalciferol is commonly known as vitamin D, but it is not

really a vitamin at all. Technically, it is not even a

nutrient. It is a sterol formed naturally in the skin by the

photochemical conversion of a precursor -- 7-dehydrocholesterol

-- via sunlight, in particular the shortest wavelengths of

solar ultraviolet light. When it was first discovered, it was

mistakenly grouped with the fat-soluble vitamins (A, E, and K)

because it was found in small quantities in butter and because

deficiency leads to the bone diseases rickets and osteomalacia.

In a comprehensive report about vitamin D, Fraser described the

synthesis and activity of this interesting substance.

Cholecalciferol is referred to as vitamin D3, which

distinguishes it from vitamin D2, or ergocalciferol, a very

rare form of the vitamin that is produced by ultraviolet

irradiation of the fungal steroid ergosterol. (Vitamin D1 was

found to be a mixture of ergocalciferol and other sterols, and

so the term was abandoned.) Cholecalciferol itself is not

biologically active. It must be hydroxylated twice for

activation, the first time in the liver and the second in the

kidney (in the proximal convoluted tubule). The final product

-- 1,25-dihydroxycholecalciferol or 1,25(OH)2D -- is secreted

into the blood for delivery to target cells, where it acts the

same way as steroid hormones do: it binds to a receptor protein

in the cell's nucleus, which then binds to regulatory sequences

on DNA. This complex induces the transcription of RNA, which

codes for proteins involved in cell function.

The primary function of vitamin D is whole-body calcium

homeostasis. Along with parathyroid hormone and calcitonin,

vitamin D provides the control mechanism for preventing

hypocalcemia or hypercalcemia. One of the most important

proteins induced by vitamin D is a calcium-binding protein in

the duodenal mucosa. This protein increases calcium absorption

in response to low calcium supply or increased physiologic

requirements (such as growth or lactation). Vitamin D is also

involved in the handling of calcium by the kidney. Thus,

vitamin D is technically a steroid hormone synthesized in the

kidney in response to calcium needs. There is a specific

1,25(OH)2D receptor protein found in most nucleated cells in

the body. This implies that vitamin D has more functions than

just calcium homeostasis (which would only require receptors in

gut, bone, and kidney tissues). Vitamin D may be involved in

immune function and skeletal muscle activity and may suppress

cell proliferation.

Deficiency of vitamin D is usually the result of limited

exposure to ultraviolet sunlight and is more common in the

elderly than in younger persons (with the exception of heavily

veiled women). Deficiency is also caused by calcium

deficiency, which appears to increase the production of

1,25(OH)2D and deplete reserves. Rickets is generally related

to calcium deficiency, not vitamin D deficiency. Indeed,

according to Fraser, the decline in incidence of vitamin D

deficiency seen in developed countries is probably due to

improved dietary calcium intake and increased exposure to

sunlight, rather than to vitamin D supplementation. The

decline is often, and probably erroneously, attributed to the

vitamin D enrichment of milk.

Vitamin D deficiency is widely believed to cause osteoporosis,

but in general, osteoporosis in the elderly does not correlate

with vitamin D status. Vitamin D deficiency is associated with

a different bone disease: osteomalacia. This disease may

manifest as muscle weakness, which can lead to falls and

fractures, or it may manifest as secondary hyperparathyroidism.

Osteomalacia can be treated with a very small daily dose of

vitamin D (10 mcg orally).

In developed countries, vitamin D toxicity may be more of a

problem than vitamin D deficiency. Prolonged exposure of the

skin to sunlight can induce sunburn, said Fraser, but it cannot

produce an excess of vitamin D. What can produce an excess of

vitamin D is the self-medication of synthetic vitamin D in mg

doses for weeks or months for conditions such as arthritis,

psoriasis, and carpal tunnel syndrome. Overdosing leads to

hypercalcemia and deposition of calcium in arteries, joints,

and kidneys. Symptoms of hypercalcemia include anorexia,

nausea, vomiting, polyuria, polydipsia (suggestive of diabetes

mellitus), and ultimately coma. Rickets due to vitamin D

deficiency from low calcium intake and lack of sunlight was a

disease of the 19th century and earlier. Vitamin D toxicity is

a disease of the 20th century.

(Fraser DR. Lancet. 1995; 345: 104-107.)

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