From the Guidelines
Vitamin D synthesis begins when 7-dehydrocholesterol in the skin is exposed to ultraviolet B radiation from sunlight, converting it to previtamin D3, which then spontaneously isomerizes to vitamin D3 (cholecalciferol) 1.
Overview of Vitamin D Synthesis
The synthesis of vitamin D is a complex process that involves several steps and organs.
- Vitamin D3 from the skin or from dietary sources (along with vitamin D2 or ergocalciferol from plant sources) enters the bloodstream and is transported to the liver bound to vitamin D binding protein.
- In the liver, vitamin D undergoes hydroxylation by the enzyme 25-hydroxylase to form 25-hydroxyvitamin D (calcidiol), the major circulating form used to assess vitamin D status 1.
- The final activation step occurs primarily in the kidneys, where 1α-hydroxylase converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (calcitriol), the biologically active form.
Regulation of Vitamin D Synthesis
This activation is tightly regulated by parathyroid hormone, calcium, and phosphate levels 1.
- Calcitriol then acts on vitamin D receptors throughout the body to regulate calcium and phosphate homeostasis, bone metabolism, immune function, and cell differentiation.
- The pathway is controlled through negative feedback, as calcitriol inhibits its own production by suppressing parathyroid hormone secretion and 1α-hydroxylase activity.
Clinical Implications
It is essential to note that vitamin D deficiency has been associated with various conditions, including cancer, autoimmune disease, and cardiovascular disease 1.
- Dark-skinned individuals require more sun exposure to have the same vitamin D production as people with less skin pigmentation, and the same is true for older versus younger individuals 1.
- Supplementation with vitamin D can be done either with vitamin D2 or vitamin D3, but the optimal serum level of 25-hydroxyvitamin D needed for optimal health is unknown 1.
From the Research
Vitamin D Synthesis Pathway
The vitamin D synthesis pathway involves several steps, starting with the conversion of 7-dehydrocholesterol to previtamin D3 in the skin upon exposure to ultraviolet B (UVB) radiation 2, 3, 4, 5. This process is influenced by various factors, including season, time of day, latitude, altitude, air pollution, skin pigmentation, sunscreen use, and aging 2.
Key Steps in Vitamin D Synthesis
- 7-dehydrocholesterol in the skin absorbs UVB radiation and is converted to previtamin D3, which then isomerizes into vitamin D3 2, 3, 4, 5
- Vitamin D3 is transported to the liver, where it is hydroxylated to form 25-hydroxyvitamin D (25(OH)D) 2, 3, 5
- 25(OH)D is then transported to the kidneys, where it is hydroxylated to form 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active form of vitamin D 2, 3, 5
Regulation of Vitamin D Synthesis
The regulation of vitamin D synthesis is complex and involves various factors, including parathyroid hormone, calcium and phosphate homeostasis, and other hormones 5. The renal 25-OH-D-1alpha-hydroxylase activity is limited when calcium and phosphate homeostasis prevails, and instead, a non-cytochrome P450 mixed function oxidase metabolizes 25-OH-D to 24R,25(OH)2D 5.
Dietary Factors Influencing Vitamin D Synthesis
Dietary factors, such as oral intake of 7-dehydrocholesterol, can increase vitamin D3 concentrations in the liver and kidney 6. However, the underlying mechanism remains elusive and needs further investigation 6.