Vitamin D3

What It Is

Vitamin D3 (cholecalciferol) is a fat-soluble vitamin that the human body can make on its own when UV-B sunlight hits the skin. It can also be consumed in food (e.g., egg yolks, oily fish, fortified milk) or taken as a supplement. After entering the body, D3 is converted in the liver to calcidiol (25-hydroxyvitamin D), and then in the kidneys to calcitriol — the hormonally active form of vitamin D. These conversions are tightly regulated because vitamin D behaves less like a “vitamin” and more like a hormone with genomic effects.

How It Works

The active form of vitamin D (calcitriol) binds to the vitamin D receptor (VDR), a nuclear receptor present in many cell types. Once bound, the vitamin D–VDR complex regulates the transcription of genes involved in calcium absorption, bone remodeling, immune signaling, and cellular differentiation. One of its clearest roles is to raise blood calcium by increasing absorption from the gut, reducing loss in the kidneys, and mobilizing calcium from bone when needed. Beyond mineral metabolism, vitamin D also modulates innate and adaptive immunity, reduces inflammatory signaling, and influences the differentiation of many tissues — which is why deficiency affects systems far beyond bones.

Why It’s Important

Vitamin D is essential for maintaining mineral balance and skeletal integrity; deficiency can lead to osteomalacia in adults and rickets in children, and even subclinical deficiency increases the rate of fractures and bone loss. Its immunomodulatory actions appear to reduce the incidence or severity of some infections, especially respiratory ones in deficient individuals. Observationally, low vitamin D status has been associated with higher rates of autoimmune disease, cardiovascular disease, metabolic syndrome, some cancers, depression, and all-cause mortality — though association does not prove that supplementation prevents those outcomes. Nevertheless, population-level insufficiency is common due to indoor lifestyles, sunscreen use, higher latitudes, winter seasons, darker skin pigmentation (which reduces cutaneous synthesis), aging skin, and obesity (which sequesters fat-soluble vitamins in adipose tissue).

Considerations

Vitamin D is fat-soluble, so excess can accumulate and cause toxicity (hypercalcemia, kidney stones, vascular calcification), though this is usually from chronic high-dose supplementation, not sunlight or diet. Personal need varies by latitude, season, skin tone, age, body fat, and kidney/liver function, so a single fixed dose is not universally appropriate. Measuring serum 25-hydroxyvitamin D is the standard way to assess status; targets differ by guideline, but values persistently below ~20 ng/mL are generally considered deficient, whereas most toxicity reports involve sustained levels above ~100 ng/mL. Because vitamin D raises calcium absorption, adequate vitamin K2 and magnesium status may help maintain safer calcium handling, while thiazide use, sarcoidosis, and certain granulomatous diseases can increase sensitivity to vitamin D. In pregnancy and lactation, requirements rise, but dosing should still be individualized rather than assumed.