Vitamin D: How Your Body Makes and Uses It

Vitamin D doesn’t behave like most vitamins. Call it a vitamin and you’re technically wrong. It’s a hormone precursor. Your body synthesizes it from cholesterol, not just extracts it from food. And it goes through two separate organ systems before it becomes biologically active.

That’s unusual. It’s also why deficiency is so widespread and why the metabolism matters practically, not just theoretically.

The Synthesis Pathway: From Skin to Active Hormone

The process starts in your skin. Your epidermis contains a compound called 7-dehydrocholesterol, which is derived from cholesterol. When UVB radiation (wavelengths 290-315 nm) hits skin, it converts 7-dehydrocholesterol into previtamin D3. Body heat then converts that unstable intermediate into vitamin D3, also called cholecalciferol.

Vitamin D3 travels from skin into the bloodstream, bound to vitamin D-binding protein. From there, it goes to the liver.

In the liver, an enzyme called CYP2R1 adds a hydroxyl group to carbon 25 of the molecule. The product is 25-hydroxyvitamin D, abbreviated 25(OH)D and called calcidiol. This is the storage form of vitamin D. It’s what blood tests measure when your doctor checks your vitamin D levels. It has a half-life of roughly 2-3 weeks, making it a useful indicator of long-term vitamin D status.

25(OH)D is not biologically active in that form. It needs one more step.

In the kidneys, the enzyme CYP27B1 adds another hydroxyl group, this time to carbon 1. The result is 1,25-dihydroxyvitamin D, abbreviated 1,25(OH)2D and called calcitriol. Calcitriol is the active hormone. It’s roughly 1,000 times more potent than 25(OH)D and has a much shorter half-life (4-6 hours).

Think of it like a two-stage rocket. The liver stage boosts the precursor into a stable storage form. The kidney stage converts it into the active fuel.

What Calcitriol Actually Does

Calcitriol works by binding to vitamin D receptors (VDR), which are present in almost every cell in the body. When calcitriol binds, it acts as a transcription factor, entering the cell nucleus and switching genes on or off.

The most well-established effect is calcium regulation. In the small intestine, calcitriol increases expression of calcium transport proteins, dramatically increasing the fraction of dietary calcium that gets absorbed. Without adequate calcitriol, calcium absorption drops from roughly 30-40% to around 10-15%. This is why calcium supplements taken without vitamin D have limited effectiveness, and why vitamin D deficiency leads to bone demineralization even when dietary calcium looks adequate.

In bone, calcitriol works alongside parathyroid hormone to regulate calcium release and deposition. Getting this balance right is central to bone density over time.

The immune role is real but more complex. VDRs are present on immune cells including T cells, B cells, and macrophages. Calcitriol modulates inflammatory responses and has shown antimicrobial properties in cell studies. The [Holick, 2007] review in the New England Journal of Medicine laid out the immune evidence, though the clinical implications are still being studied.

How Common Is Deficiency?

Very. The Forrest and Stuhldreher 2011 study in Nutrition Research (PMID: 21310306) analyzed NHANES data and found 41.6% of US adults had insufficient vitamin D levels (below 20 ng/mL).

Several factors reduce vitamin D synthesis or absorption:

Skin pigmentation. Melanin absorbs UVB, reducing how much reaches 7-dehydrocholesterol in deeper skin layers. The same amount of sun exposure produces less vitamin D3 in darker skin. The Forrest and Stuhldreher study found deficiency rates of 69.2% in Hispanic adults and 82.1% in Black adults, compared to 30.9% in white adults.

Latitude. UVB at angles below about 45 degrees (which happens in winter at latitudes above ~35 degrees north) doesn’t penetrate the atmosphere effectively enough for skin synthesis. Boston, Chicago, and Seattle get essentially no meaningful UVB for vitamin D synthesis from November through March. Holick documented this geographic effect in detail.

Obesity. Vitamin D is fat-soluble and gets sequestered in adipose tissue. Higher body fat means more storage and less circulating 25(OH)D for a given synthesis or intake.

Age. As skin ages, it contains less 7-dehydrocholesterol, reducing synthesis capacity. Kidney function also declines with age, reducing the conversion of 25(OH)D to calcitriol.

Food Sources and Their Limits

Food is not a reliable primary source of vitamin D for most people.

Fatty fish are the most significant food sources. Wild salmon contains roughly 400-600 IU per 3.5 oz serving. Mackerel and tuna are comparable. Farmed salmon has lower levels due to differences in diet.

Egg yolks contain about 40-50 IU each. Not a significant amount.

Fortified foods add vitamin D2 or D3 to dairy milk (typically 100 IU per cup), plant milks, and some cereals. These amounts are meaningful but still unlikely to achieve adequate levels alone.

Mushrooms exposed to UV light produce vitamin D2 and can contain substantial amounts, but the D2 form raises blood levels less efficiently than D3.

The Institute of Medicine’s 2011 Dietary Reference Intakes report set the recommended daily allowance at 600 IU for adults up to 70 and 800 IU for adults over 70. Many researchers, including Holick, argue these recommendations are too low for people with limited sun exposure, but the IOM’s tolerable upper limit of 4,000 IU/day remains the standard threshold for safe supplementation.

Supplements: D2 vs. D3, and the Fat Rule

Supplement form matters. D3 (cholecalciferol) raises and sustains blood 25(OH)D levels more effectively than D2 (ergocalciferol). The Endocrine Society and most researchers recommend D3 for supplementation.

How you take the supplement matters too. The Mulligan and Bhatt 2010 study (PMID: 19914053) found that taking vitamin D supplements with a fat-containing meal increased absorption by roughly 50% compared to taking it on an empty stomach. This is consistent with vitamin D being fat-soluble and requiring bile for absorption. A capsule with breakfast is better absorbed than a capsule alone.

The Toxicity Question

Vitamin D toxicity is rare but real. It doesn’t come from sun exposure, because skin synthesis self-limits when 7-dehydrocholesterol is depleted. It comes from excessive supplementation, typically doses well above 10,000 IU/day sustained over time.

The mechanism is hypercalcemia: too much calcitriol drives too much calcium absorption. Symptoms include nausea, weakness, kidney stones, and in severe cases, calcification of soft tissue.

The IOM’s tolerable upper limit of 4,000 IU/day provides a substantial safety margin. Most physicians who prescribe higher doses for confirmed deficiency do so with monitoring. Your care team should measure your 25(OH)D level before you supplement at high doses and recheck it after 3 months.

This article is for educational purposes only and does not constitute medical advice. Consult a qualified health professional before making changes to your diet or health regimen.