Vitamin D acts more like a hormone than a vitamin | Empirical Health

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Vitamin D acts more like a hormone than a vitamin<br>Brandon Ballinger<br>May 18, 2026

Vitamin D is a steroid hormone with a misleading name.

First, let me quickly define terms:

Vitamins, by definition, are compounds your body cannot make on its own (which is why you have to eat them). But your skin synthesizes vitamin D whenever UVB sunlight hits it.

Hormones are your body’s chemical messengers.

Steroid hormones in particular are hormones derived from cholesterol.

When researchers worked out Vitamin D’s full pathway in the 1970s, they found it binds a nuclear receptor that regulates roughly 1,000 to 2,000 genes (about 5 to 10% of the human genome). That receptor sits in the same family as the receptors for estrogen, testosterone, cortisol, and thyroid hormone.

This reframing explains why a “vitamin” reaches into immunity, blood pressure, glucose control, and (as the TARGET-D trial suggested) heart attack risk. In the rest of this post, we’ll trace how vitamin D became a hormone in everything but name, what the vitamin D receptor actually does, and what the hormone framing means for testing and supplementation.

Why vitamin D was originally misclassified as a vitamin

Vitamin D got its name in 1922. Elmer McCollum had spent the previous decade naming fat-soluble compounds in cod liver oil by letter (vitamin A, then B, then C), and the factor that cured rickets in rats became the fourth letter. The label stuck before anyone understood what the molecule did or where it came from. (Elmer McCollum became known as “Dr Vitamin” and famloulsly said, “Eat what you want after you have eaten what you should.”)

How vitamin D becomes an active hormone

What your skin produces (or what arrives in food) is not the active form. Vitamin D₃ is a precursor that has to be activated in two steps:

The liver adds a hydroxyl group, producing 25-hydroxyvitamin D (25(OH)D, calcidiol). This is the form measured by a standard vitamin D blood test, because it has a half-life of weeks and reflects overall stores.

The kidney adds a second hydroxyl, producing 1,25-dihydroxyvitamin D (calcitriol). Calcitriol is the biologically active hormone. Calcitriol’s half-life is hours, and its blood levels are tightly regulated by parathyroid hormone and serum calcium.

Vitamin D₃ from skin or diet is activated through hydroxylation in the liver and kidney before binding to the vitamin D receptor.

That two-step activation in distant endocrine organs is characteristic of a hormone. The kidney functions as an endocrine gland, and calcitriol is its product. The 25(OH)D level on a blood test is closer to a steroid pre-hormone reading (like checking pregnenolone) than to a nutrient status marker.

The vitamin D receptor (VDR)

Once activated, calcitriol travels through the blood and binds to the vitamin D receptor (VDR) , a protein that lives in the nucleus of nearly every cell type studied: intestine, kidney, bone, parathyroid, pancreatic beta cells, T and B lymphocytes, vascular smooth muscle, endothelium, heart muscle, and many neurons.

The VDR belongs to the nuclear receptor superfamily, the same family that contains the receptors for:

Estrogen

Testosterone

Cortisol

Thyroid hormone

Retinoic acid (the active form of vitamin A)

Each of these receptors works the same way. A hormone binds, the receptor changes shape, pairs up with a partner protein, slides into DNA at specific response elements, and turns genes on or off. VDR partners with the retinoid X receptor (RXR), then regulates transcription of an estimated 1,000 to 2,000 genes.

The vitamin D receptor (VDR) sits in the same superfamily as the receptors for estrogen, testosterone, cortisol, thyroid hormone, and retinoic acid. All bind a ligand, dock to specific DNA sequences, and switch genes on or off.

This is why vitamin D effects span so many systems: it’s a transcription factor running in parallel across most tissues at once.

How vitamin D drives different organ systems

The hormone framing predicts that vitamin D should reach well beyond bone. Vitmain D has affects across cardiovascular, autoimmune, respiratory, cancer, falls (obviously has some relation to bone health), and diabetes:

Body systemEffectStudyCardiovascular52% lower risk of repeat heart attackTARGET-D, post-MI patients held at 40 to 80 ng/mLAutoimmune22% lower rate of new autoimmune disease (RA, psoriasis, autoimmune thyroid, and others)VITAL, 25,871 adults, 2,000 IU/day, 5 yearsRespiratory infections12%...