Review
The vitamin D questions: How much do you need and how should you get it?

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UV radiation is a well-documented human carcinogen, indisputably linked to the current continued increased rate of skin cancer. UV radiation is also responsible for cutaneous synthesis of vitamin (vit) D3, a substance that is then sequentially hydroxylated in the liver and kidney to yield 1,25(OH)2 vit D, a hormone critical for calcium homeostasis and skeletal maintenance. Because the UV action spectra for DNA damage leading to skin cancer and for vit D photosynthesis are virtually identical, the harmful and beneficial effects of UV irradiation are inseparable. This has given rise to the argument that sun avoidance, with a goal of skin cancer prevention, may compromise vit D sufficiency. Public interest in this matter has been heightened in recent years by multiple studies correlating the level of 25-OH vit D, the readily measurable “storage” precursor form of the vit, with a variety of benefits separate from skeletal health. Although the studies are of variable quality and all alleged treatment benefits are based on dietary supplementation with vit D, not on increased sun exposure, they have been interpreted by some as support for advocating increased sun exposure of the public at large. The goal of this review is to provide a detailed, balanced, and referenced discussion of the complex literature underlying the current popular interest in vit D and sun exposure for the purpose of increasing vit D photosynthesis. We review the nomenclature, metabolism, and established functions of vit D; the evidence supporting the less well-established but purported vit D effects; the concept of vit D insufficiency; populations at risk for vit D deficiency; and finally the risk/benefit of obtaining vit D from cutaneous photosynthesis versus diet or supplementation.

Section snippets

The controversy

The vitamin (vit) D controversy is nearly 100 years old. It pits established risks of sun exposure against established benefits of cutaneous production of vit D and, more recently, against a variety of potential unproven benefits.

Two discoveries in the 1920s reinforced Coco Chanel's trendy new “tanned is beautiful” message1 and led to the public opinion that unprotected sunshine exposure was beneficial to health: (1) vit D is the active compound in cod liver oil that prevents childhood rickets2

Nomenclature and sources

Vit D obtained its name in the early part of the 20th century after the discovery of the antirachitic effect of cod liver oil. The suspected vit in cod liver oil was designated “D,” as vits A, B, and C had already been identified.2 The nomenclature for vit D precursors and metabolites is provided in Table I. The sources and production of vit D are summarized briefly in Fig 1 and extensively reviewed elsewhere.9 The term “vitamin D” specifically refers to two biologically inert precursors: vit D3

Established vit D hormonal function and the consequences of deficiency or excess

The principal physiologic function of the active vit, 1,25-(OH)2 vit D, is to maintain calcium homeostasis. In this essential role, vit D functions as a hormone, synthesized far from the sites of its biologic action (GI tract and bone) and reaching these distant sites through the blood stream. Vit D is indeed a member of the superfamily of steroid hormones that also includes corticosteroids, all trans-retinoic acid (vit A), and thyroid hormone, and act in the nucleus by binding their cognate

Vit D deficiency versus insufficiency

Vit D differs from most other vits and essential nutrients in having a large precursor pool in the body that varies over a wide range in healthy individuals and a small tightly regulated range of the active compound. By consensus, the circulating level of the inactive precursor 25-OH vit D is the universally accepted indicator of vit D status because it is easily measured, has the longest half-life in circulation (approximately 2 or 3 weeks), and the levels of 25-OH vit D correlate with

Does vit D insufficiency affect skeletal homeostasis?

Although randomized clinical trials of vit D supplementation have failed to clearly support clinical benefits of treating insufficiency (see below), some authorities have chosen to blur the distinction between insufficiency and deficiency. They suggest that the normal range for 25-OH vit D should be redefined as that required to minimize PTH levels (Table II).34, 38, 39, 40, 41 This change in definition causes individuals with 25-OH vit D levels in the insufficient range to be counted as

Skeletal muscle strength

1,25-(OH)2 vit D, a secosteroid hormone, enters the target cell, then binds and activates a nuclear receptor, the vit D receptor (VDR). This complex, which may form heterodimers with non-VDRs, then binds to specific DNA sequences (vit D–responsive elements), altering transcription of effector genes.9, 65 Thus, VDR-expressing tissues comprise a population of cells theoretically able to respond to 1,25-(OH)2 vit D. As would be expected for the classic hormonal function of 1,25-(OH)2 vit D in

The case for diet/supplementation versus UV exposure

Overwhelming evidence asserts that vit D through dietary supplementation can correct both deficiency and insufficiency, except for those patients with GI malabsorption as the cause of vit D deficiency. The endocrine community, through its consensus groups, and journal editorials, reviews, and letters, recognizes the carcinogenic potential of UV radiation and calls for more dietary vit D supplementation, not more sun exposure or tanning bed usage.25, 30, 105, 106, 107, 108 Dietary

The case against promoting reliance on photosynthesis

The action spectra for previt D3 formation, erythema, and formation of cyclobutane pyrimidine dimers in DNA all peak in the UVB range (Fig 2). Hence, vit D photosynthesis cannot be dissociated from acute and chronic photodamage, including photocarcinogenesis.121, 122, 123, 124, 125 As few as 6 sunburns in a lifetime have been shown to increase an individual's risk for nonmelanoma and melanoma skin cancer.125, 126, 127, 128 Moreover, in fair-skinned individuals maximum possible vit D synthesis

Conclusion

Given the scarcity of naturally occurring vit D in many otherwise adequate diets, human beings may once have depended on unprotected exposure to natural sunlight as the primary environmental source of vit D, at least during those periods of the year when sunlight can produce previt D3 in the skin.30 However, chronic unprotected exposure to carcinogenic UV radiation in sunlight not only results in photoaging, but also greatly increases the risk of skin cancer. This risk is further exacerbated by

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    Funding sources: None.

    Conflicts of interest: None identified.

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