What is vitamin D?

What is Vitamin D?

Vitamin D is a fat-soluble prohormone that is primarily synthesized in the skin through UVB radiation exposure and can also be obtained from limited dietary sources, functioning as a critical regulator of calcium-phosphorus homeostasis, bone health, and numerous extra-skeletal processes including immune function, cardiovascular health, and cellular differentiation. 1

Forms and Sources

Vitamin D exists in two main forms:

• Vitamin D3 (cholecalciferol): Synthesized in human skin from 7-dehydrocholesterol upon UVB exposure, or obtained from animal sources including fatty fish (salmon, mackerel, herring), fish liver oils, and eggs 1
• Vitamin D2 (ergocalciferol): Derived from UV irradiation of yeast sterol ergosterol, found naturally in sun-exposed mushrooms 1

The primary source of vitamin D for most humans is cutaneous synthesis from sunlight exposure, not dietary intake, as very few foods naturally contain significant amounts of vitamin D 1. This explains why vitamin D deficiency remains pandemic despite adequate caloric nutrition—a form of "hidden hunger" 2.

Metabolism and Physiology

The metabolic pathway follows this sequence:

1. Vitamin D (from skin or diet) is converted to 25-hydroxyvitamin D [25(OH)D] in the liver—this is the primary circulating form and the best biomarker for vitamin D status 1, 3
2. 25(OH)D undergoes further hydroxylation to 1,25-dihydroxyvitamin D, the active hormone form, primarily in the kidneys but also in many other tissues 4
3. The active form binds to vitamin D receptors (VDR) expressed in most body tissues, regulating gene expression and cellular differentiation 5, 4

Clinical Functions

Skeletal Effects

Vitamin D maintains calcium and phosphorus homeostasis by:

• Increasing intestinal calcium and phosphorus absorption
• Preventing secondary hyperparathyroidism
• Ensuring adequate mineralization of bone matrix 1

Deficiency causes rickets in children (skeletal deformities) and osteomalacia in adults (bone pain, muscle weakness, increased fracture risk) 1.

Extra-Skeletal Effects

Beyond bone health, vitamin D influences:

• Immune system modulation: Inhibits Th1 cell proliferation, relevant in autoimmune diseases 3, 5
• Cardiovascular health: Associated with reduced cardiovascular disease risk 3
• Cancer prevention: Linked to lower cancer incidence and mortality 3
• Muscle function: Deficiency causes muscle weakness and increased fall risk in elderly 1

Deficiency: A Global Pandemic

Vitamin D insufficiency affects a substantial portion of the global population, with 41.6% of US adults having serum 25(OH)D levels below 20 ng/mL 5. In Europe, approximately 40% have deficiency (<50 nmol/L) and 13% have severe deficiency (<30 nmol/L) 6.

High-Risk Populations

• Dark-skinned individuals (require 3-5 times more sun exposure) 1
• Elderly and institutionalized individuals 3
• Veiled individuals with minimal sun exposure 3
• Obese individuals (BMI >30 kg/m²) 1
• Those with malabsorption syndromes or post-bariatric surgery 1
• Patients on anticonvulsants or HIV medications 1

Contributing Factors to Deficiency

• Limited sun exposure: Modern lifestyle exposes <5% of skin to sun; sunscreen with SPF 30 reduces vitamin D synthesis by >95% 3, 1
• Geographic latitude: Above/below 33° latitude, vitamin D3 synthesis is minimal during winter months 1
• Dietary insufficiency: Few foods naturally contain vitamin D; fortification practices vary by country 1

Measurement and Target Levels

The serum 25(OH)D level is the appropriate biomarker for assessing vitamin D status 1. The 1,25-dihydroxyvitamin D assay should not be used for routine assessment 1.

Recommended Target Levels

• Deficiency: <20 ng/mL (50 nmol/L) 1
• Insufficiency: 21-29 ng/mL (52.5-72.5 nmol/L) 1
• Optimal for at-risk populations: ≥30-40 ng/mL for musculoskeletal health, cardiovascular disease, autoimmune disease, and cancer prevention 3
• Upper safety limit: 100 ng/mL 3

Supplementation Recommendations

For high-risk populations (elderly, institutionalized, dark-skinned, veiled individuals), empiric supplementation with 800 IU/day is recommended without baseline testing 3.

For patients with documented deficiency or at-risk conditions:

• Initial correcting dose followed by maintenance of 800 IU/day 3
• Recheck 25(OH)D levels at least 3 months after initiating supplementation 3
• Use assays measuring both 25(OH)D2 and 25(OH)D3 3

Clinical Pitfalls

• Do not confuse vitamin D with a true vitamin: It functions as a hormone precursor and can be endogenously synthesized, unlike true vitamins 4
• Do not measure 1,25-dihydroxyvitamin D for routine screening: This is not the appropriate biomarker for vitamin D status 1
• Do not assume dietary intake alone is sufficient: Most populations cannot achieve adequate vitamin D status through diet without supplementation or sun exposure 1, 2
• Recognize that vitamin D deficiency is often "hidden hunger": Patients may have adequate caloric intake but still be vitamin D deficient 2