Vitamin D Basics
The most common forms of vitamin D are vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Vitamin D3 is produced in human skin following exposure to sunlight, whereas vitamin D2 originates in certain plants and fungi. Both forms of vitamin D are widely available as dietary supplements.
The level of vitamin D is normally stable in human blood. Slight, if any, increase occurs after meals since human diets typically have low vitamin D content, even those containing foods fortified with vitamin D. Exposure of human skin to sunlight usually causes blood vitamin D levels to rise only gradually and modestly.
Both vitamin D2 and vitamin D3 are metabolized into pro-hormones by CYP27A, CYP2R1 and certain other cytochrome P450 enzymes located in the liver. These enzymes metabolize vitamin D2 into the pro-hormone known as 25-hydroxyvitamin D2 and correspondingly, vitamin D3 into the pro-hormone known as 25-hydroxyvitamin D3. The two pro-hormones are collectively referred to as “25-hydroxyvitamin D”. In general, unless an individual is taking vitamin D2 supplements, most or all of the “25-hydroxyvitamin D” in the human body consists of 25-hydroxyvitamin D3.
It is widely accepted that the determination of serum 25-hydroxyvitamin D level is the best indicator of an individual’s vitamin D status. The level of vitamin D pro-hormone which is currently considered sufficient is 30 ng/mL, although there is growing evidence suggesting that this level should be increased to at least 40 ng/mL.
The two vitamin D pro-hormones are further metabolized by the kidneys into hormones by a 1α-hydroxylase enzyme known as CYP27B1, located in the proximal kidney tubule. Vitamin D hormone production in the kidney is tightly regulated by parathyroid hormone (PTH), a hormone secreted by the parathyroid glands. The pro-hormone 25-hydroxyvitamin D2 is metabolized by CYP27B1 into the hormone known as 1α,25-dihydroxyvitamin D2 (ercalcitriol). Likewise, 25-hydroxyvitamin D3 is metabolized by the same enzyme into 1α,25-dihydroxyvitamin D3 (calcitriol). These hormones, collectively referred to as “1,25-dihydroxyvitamin D”, are secreted by the kidneys into the bloodstream for systemic delivery.
Vitamin D pro-hormones are also metabolized into hormones by organs outside of the kidneys, including skin, lung, intestine, those of the immune system (e.g., macrophages) and certain other cells containing CYP27B1 or similar enzymes. Extrarenal production of vitamin D hormones, in contrast to the renal production described above, is not precisely regulated. Such extrarenal hormone production contributes little to the circulating blood levels of 1,25-dihydroxyvitamin D, but provides a “local” supply of hormones that may prove critical to cell growth regulation and the prevention of cancer, autoimmune disorders such as psoriasis and certain types of infection. An adequate “local” production of hormone often depends on sufficient levels of circulating 25-hydroxyvitamin D. Epidemiological studies clearly indicate that vitamin D insufficiency, characterized by low serum 25-hydroxyvitamin D levels, associates very strongly with these diseases.