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Details of Vitamin D

Vitamin D is a group of fat-soluble prohormones, the two major forms of which are vitamin D₂ (or ergocalciferol) and vitamin D₃ (or cholecalciferol). The term vitamin D also refers to metabolites and other analogues of these substances. Vitamin D₃ is produced in skin exposed to sunlight, specifically ultraviolet B radiation.

Vitamin D plays an important role in the maintenance of organ systems.

Vitamin D regulates the calcium and phosphorus levels in the blood by promoting their absorption from food in the intestines, and by promoting re-absorption of calcium in the kidneys.

• It promotes bone formation and mineralization and is essential in the development of an intact and strong skeleton.
• It inhibits parathyroid hormone secretion from the parathyroid gland.
• Vitamin D affects the immune system by promoting immunosuppression, phagocytosis, and anti-tumor activity.

Vitamin D deficiency can result from inadequate intake coupled with inadequate sunlight exposure, disorders that limit its absorption, conditions that impair conversion of vitamin D into active metabolites, such as liver or kidney disorders, or, rarely, by a number of hereditary disorders.^[2] Deficiency results in impaired bone mineralization, and leads to bone softening diseases, rickets in children and osteomalacia in adults, and possibly contributes to osteoporosis. Vitamin D deficiency may also be linked to many forms of cancer.

Forms

Several forms of vitamin D have been described. The two major forms are vitamin D₂ or ergocalciferol, and vitamin D₃ or cholecalciferol.

• Vitamin D₁: molecular compound of ergocalciferol with lumisterol, 1:1
• Vitamin D₂: ergocalciferol or calciferol (made from ergosterol)
• Vitamin D₃: cholecalciferol (made from 7-dehydrocholesterol in the skin).
• Vitamin D₄: 22-dihydroergocalciferol
• Vitamin D₅: sitocalciferol (made from 7-dehydrositosterol)

Chemically, the various forms of vitamin D are secosteroids; i.e. broken-open steroids. The structural difference between vitamin D₂ and vitamin D₃ is in their side chains. The side chain of D₂ contains a double bond between carbons 22 and 23, and a methyl group on carbon 24.

Vitamin D₂ is derived from fungal and plant sources, and is not produced by the human body. Vitamin D₃ is derived from animal sources and is made in the skin when 7-dehydrocholesterol reacts with UVB ultraviolet light at wavelengths between 270-290 nm.

These wavelengths are present in sunlight at sea level when the sun is more than 45° above the horizon, or when the UV index is greater than 3. At this solar elevation, which occurs daily within the tropics, daily during the spring and summer seasons in temperate regions, and almost never within the arctic circles, adequate amounts of vitamin D₃ can be made in the skin only after ten to fifteen minutes of sun exposure at least two times per week to the face, arms, hands, or back without sunscreen. With longer exposure to UVB rays, an equilibrium is achieved in the skin, and the vitamin simply degrades as fast as it is generated.

In most mammals, including humans, D₃ is more effective than D₂ at increasing the levels of vitamin D hormone in circulation; D₃ is at least 3-fold, and likely closer to 10-fold, more potent than D₂. However, in some species, such as rats, vitamin D₂ is more effective than D₃. Both vitamin D₂ and D₃ are used for human nutritional supplementation, and pharmaceutical forms include calcitriol (1alpha, 25-dihydroxycholecalciferol), doxercalciferol and calcipotriene.

Vitamin D is a prohormone, that is, it has no hormone activity itself, but is converted to a hormone 1,25-D which does, through a tightly regulated synthesis mechanism.

Production in the skin

The epidermal strata of the skin. Production is greatest in the stratum basale (colored red in the illustration) and stratum spinosum (colored orange).

The skin consists of two primary layers: the inner layer called the dermis, composed largely of connective tissue, and the outer thinner epidermis. The epidermis consists of five strata; from outer to inner they are: the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale.

Vitamin D₃ is produced photochemically in the skin from 7-dehydrocholesterol. The highest concentrations of 7-dehydrocholesterol are found in the epidermal layer of skin, specifically in the stratum basale and stratum spinosum. The production of pre-vitamin D₃ is therefore greatest in these two layers, whereas production in the other layers is reduced.

Synthesis in the skin involves UVB radiation which effectively penetrates only the epidermal layers of skin. 7-Dehydrocholesterol absorbs UV light most effectively at wavelengths between 270-290 nm and thus the production of vitamin D₃ will only occur at those wavelengths. The two most important factors that govern the generation of pre-vitamin D₃ are the quantity (intensity) and quality (appropriate wavelength) of the UVB irradiation reaching the 7-dehydrocholesterol deep in the stratum basale and stratum spinosum.

A critical determinant of vitamin D₃ production in the skin is the presence and concentration of melanin. Melanin functions as a light filter in the skin, and therefore the concentration of melanin in the skin is related to the ability of UVB light to penetrate the epidermal strata and reach the 7-dehydrocholesterol-containing stratum basale and stratum spinosum. Under normal circumstances, ample quantities of 7-dehydrocholesterol (about 25-50 mg/cm² of skin) are available in the stratum spinosum and stratum basale of human skin to meet the body's vitamin D requirements, and melanin content does not alter the amount of vitamin D that can be produced.

Thus, individuals with higher skin melanin content will simply require more time in sunlight to produce the same amount of vitamin D as individuals with lower melanin content.