Forms of Vitamin D and their sources
Vitamin D encompasses a group of fat-soluble compounds. Two forms are clinically significant — vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Ergocalciferol is derived mainly from plant sources, while cholecalciferol comes from animal foods (fatty fish, liver, egg yolk, dairy products).
The bioavailability of D3 is higher than that of D2; therefore, cholecalciferol is preferred when choosing a supplement. Ergocalciferol is appropriate for patients following a vegan diet, keeping its lower absorption rate in mind.
Cutaneous synthesis under UV radiation
The stratum spinosum and stratum basale of the epidermis contain 7-dehydrocholesterol, a cholesterol precursor. Upon exposure to ultraviolet radiation, the double bond in the molecule is cleaved, forming cholecalciferol.
Solar radiation is divided into three types: UV-A, UV-B, and UV-C. UV-C is blocked by the ozone layer, UV-A is constantly present but does not participate in vitamin synthesis. Vitamin D production is triggered solely by UV-B, which reaches the Earth's surface approximately from 10:00 AM to 3:00 PM.
Cutaneous vitamin D synthesis does not occur under the following conditions:
- use of high-SPF sunscreen;
- staying behind window glass (UV-B does not penetrate it);
- sun exposure outside the period of active UV-B;
- fully covered clothing.
Therefore, even in sunny regions, marked vitamin D deficiency is possible.
Absorption and metabolic activation
Dietary vitamin D is absorbed in the small intestine. Because it is fat-soluble, its absorption requires emulsification by fats with bile acids and the action of pancreatic lipases. Functional disorders of the liver, biliary tract, and pancreas impair vitamin D absorption.
From enterocytes, vitamin D is transported within chylomicrons into the blood and subsequently to the liver, where it is converted by 25-hydroxylase into 25(OH)D — calcidiol. This is the storage form that reflects the body's vitamin D reserves.
Calcidiol is transported to the kidneys, where 1α-hydroxylase converts it into 1,25(OH)₂D — calcitriol, the active hormonal form. Both hydroxylases are magnesium-dependent, so magnesium deficiency impairs vitamin D activation. In chronic kidney disease (especially stages 3–4), calcitriol synthesis is reduced, leading to functional vitamin D deficiency.
Biological effects of calcitriol
Calcitriol binds to the nuclear VDR (vitamin D receptor), inducing the synthesis of transport proteins:
- TRPV6 — enhances active calcium absorption in the intestine;
- sodium-phosphate cotransporter — enhances phosphate absorption.
Through the VDR, calcitriol suppresses the synthesis of parathyroid hormone (PTH) in the parathyroid glands. PTH activates osteoclasts, increasing bone resorption and renal calcium reabsorption. By suppressing PTH secretion, calcitriol reduces bone tissue resorption.
In bone tissue, calcitriol acts via VDRs on osteoblasts to stimulate the synthesis of osteocalcin. Osteocalcin activation requires hydroxylation involving vitamin K2. Activated osteocalcin directs calcium into the bone matrix. With K2 deficiency against the background of high D3 doses, the risk of ectopic calcification increases, including vascular wall calciphylaxis.
Clinical manifestations of deficiency
Vitamin D deficiency leads to decreased intestinal absorption of calcium and phosphates. Hypocalcemia activates PTH, resulting in secondary hyperparathyroidism with enhanced bone resorption. Simultaneously, osteocalcin synthesis decreases, leading to reduced bone formation.
Clinically, deficiency manifests as rickets in children, osteomalacia and osteoporosis in adults, muscle weakness, and is associated with a number of autoimmune diseases.
Indications for laboratory assessment
To assess vitamin D status, 25(OH)D (calcidiol) is measured rather than active calcitriol, whose levels fluctuate sharply. Analogous to ferritin in anemia, calcidiol reflects body stores.
Routine screening is not indicated for asymptomatic patients. Testing is justified in the following groups:
- patients with suspected osteopenia, osteoporosis, and other bone disorders;
- women planning pregnancy and pregnant women;
- children with suspected rickets and developmental delay;
- patients with autoimmune diseases (multiple sclerosis, Crohn's disease);
- patients with secondary hyperparathyroidism and hypocalcemia;
- individuals over 60 years of age and those taking medications affecting vitamin D metabolism.
Uncontrolled long-term intake of high doses of vitamin D is potentially dangerous and has been described as a risk factor for secondary arterial hypertension, especially in the presence of reduced glomerular filtration rate.
Key points
- Forms D2 (ergocalciferol) and D3 (cholecalciferol) are clinically significant; D3 has superior bioavailability.
- Cutaneous synthesis from 7-dehydrocholesterol occurs exclusively under UV-B exposure (approximately 10:00 AM–3:00 PM).
- Vitamin D activation involves two stages: 25-hydroxylation in the liver and 1α-hydroxylation in the kidneys; both hydroxylases are magnesium-dependent.
- Calcitriol via VDR enhances calcium and phosphate absorption, suppresses PTH secretion, and stimulates osteocalcin synthesis.
- Vitamin K2 is essential for activating osteocalcin and directing calcium into bone tissue.
- The standard laboratory marker of status is 25(OH)D (calcidiol).
- Screening in asymptomatic patients is not indicated; testing is justified for bone pathology, pregnancy, in children, autoimmune diseases, and hyperparathyroidism.
- Prolonged high-dose vitamin D supplementation without monitoring carries a risk of hypercalcemia and vascular calcification.