Vitamin D: The Sunshine Vitamin's Chemistry

Most vitamins have to come from food. Vitamin D is different: your own skin can make it, using nothing but a cholesterol-like molecule and sunlight. Chemically, it’s a remarkable piece of photochemistry, a reaction driven directly by ultraviolet light, followed by two enzyme steps that turn the product into a powerful hormone. That’s why vitamin D is often described as a hormone rather than a true vitamin.

Identity

Property	Vitamin D3 (cholecalciferol)
Formula	C₂₇H₄₄O
Molar mass	about 384.6 g mol⁻¹
Type	Secosteroid (a steroid with one ring broken)
Solubility	Fat-soluble; practically insoluble in water
Main sources	Skin exposed to UVB light; oily fish, egg yolk, fortified foods

There are two main forms:

• Vitamin D3 (cholecalciferol), made in animal skin and found in animal foods.
• Vitamin D2 (ergocalciferol), made when fungi such as mushrooms and yeast are exposed to UV light, starting from the fungal sterol ergosterol.

Both are converted into active hormones in the body; D3 appears to raise blood levels somewhat more effectively.

Step 1: making vitamin D in the skin

The starting material is 7-dehydrocholesterol, a close relative of cholesterol found in the skin. It has the four fused rings typical of steroids, with two C=C double bonds in ring B.

When ultraviolet B (UVB) light, wavelengths roughly 290–315 nm, is absorbed by 7-dehydrocholesterol, it breaks a carbon–carbon bond in ring B, opening the ring. The product is previtamin D3. This is a genuine photochemical reaction: the energy of a single UV photon (about 4 eV) drives it directly (see photons and energy levels).

Previtamin D3 then slowly rearranges, over hours, through a heat-driven shift of hydrogen and double bonds, into vitamin D3, which enters the bloodstream bound to a transport protein.

Because ring B has been broken, vitamin D is called a secosteroid (“seco” means cut).

Built-in safety: further UV exposure converts previtamin D3 into inactive by-products, so prolonged sunbathing doesn’t produce toxic amounts of vitamin D. (It does, of course, increase the risk of sunburn and skin cancer.)

Steps 2 and 3: activation in the liver and kidneys

Vitamin D3 itself is inactive. It’s converted by two hydroxylation reactions, each adding an –OH group:

1. In the liver: an enzyme adds –OH at carbon 25, forming 25-hydroxyvitamin D (calcidiol). This is the main circulating form, and it’s what a blood test for “vitamin D levels” measures, because it reflects both skin production and diet over the previous weeks.
2. In the kidneys: another enzyme adds –OH at carbon 1, forming 1,25-dihydroxyvitamin D (calcitriol), the active hormone.

The kidney step is tightly controlled: it’s increased when blood calcium or phosphate is low (signalled by parathyroid hormone) and decreased when they’re high.

What calcitriol does

Calcitriol acts like other steroid hormones. Being fat-soluble, it enters cells and binds to the vitamin D receptor in the nucleus, which then switches specific genes on or off.

Its main job is to keep blood calcium and phosphate at the right levels:

• In the intestine, it increases the production of proteins that absorb calcium and phosphate from food. Without vitamin D, only about 10–15% of dietary calcium is absorbed; with enough, roughly 30–40%.
• In bone, together with parathyroid hormone, it helps release calcium when blood levels are low.
• In the kidneys, it helps reduce calcium loss in urine.

Calcium and phosphate are then used to build the mineral of bone, a form of calcium phosphate called hydroxyapatite (see calcium, phosphate and bone chemistry).

The vitamin D receptor is found in many other tissues, including immune cells and muscle, and research continues into vitamin D’s wider roles, although many claims made for supplements haven’t been confirmed by large trials.

Deficiency: rickets and osteomalacia

Without enough vitamin D, the body can’t absorb enough calcium, and bones don’t mineralise properly:

• In children, this causes rickets: soft, weak bones that bend, giving bowed legs, and delayed growth.
• In adults, it causes osteomalacia: soft bones, pain and muscle weakness, and it contributes to osteoporosis.

Rickets was widespread in the smoky industrial cities of nineteenth-century Europe, where coal smoke blocked sunlight and children worked indoors. In the early twentieth century, scientists showed that both cod liver oil and sunlight (or UV lamps) could cure it, and later that irradiating certain foods with UV light gave them anti-rickets activity: the ergosterol in them was being converted to vitamin D2.

Why sunlight isn’t always enough

Skin production of vitamin D depends on UVB reaching the skin, which varies with:

• Latitude and season: at high latitudes in winter, the Sun is so low that most UVB is absorbed by the atmosphere. In the UK, for example, little vitamin D is made in skin from roughly October to March.
• Time of day: UVB is strongest around midday.
• Skin pigmentation: melanin absorbs UV, so people with darker skin need longer sun exposure to make the same amount of vitamin D.
• Sunscreen and clothing, which block UVB.
• Age: older skin contains less 7-dehydrocholesterol.
• Glass: window glass blocks most UVB, so sitting in a sunny room doesn’t help.

This is why many health authorities recommend vitamin D supplements in winter for people living far from the equator, and why some foods, such as milk, cereals and margarine, are fortified.

Food sources

Few foods naturally contain much vitamin D:

• oily fish (salmon, mackerel, sardines, herring);
• cod liver oil;
• egg yolks;
• liver;
• mushrooms exposed to UV light (vitamin D2);
• fortified foods.

Measuring vitamin D status

When a doctor orders a vitamin D test, the laboratory measures 25-hydroxyvitamin D in blood serum, usually by immunoassay or by liquid chromatography with tandem mass spectrometry, which can separate the D2 and D3 forms. Results are reported in nanomoles per litre (nmol L⁻¹) or nanograms per millilitre (1 ng mL⁻¹ ≈ 2.5 nmol L⁻¹). Guidelines differ slightly between countries, but levels below about 25–30 nmol L⁻¹ are generally regarded as deficient, and around 50 nmol L⁻¹ is widely considered adequate for bone health. The active hormone, calcitriol, isn’t a good measure of status: its level is kept stable by the kidneys and may even rise when the body is short of vitamin D.

Toxicity

Because vitamin D is fat-soluble and stored in the body, very high doses from supplements (not from sunlight) can accumulate and cause hypercalcaemia: too much calcium in the blood, leading to nausea, kidney stones, and damage to the kidneys and heart. This is rare but has occurred with large, prolonged over-dosing or manufacturing errors in supplements.

Key takeaways

• Vitamin D3 is made in skin when UVB light breaks ring B of 7-dehydrocholesterol, forming a secosteroid; D2 is made from ergosterol in fungi.
• It’s activated in two steps: 25-hydroxylation in the liver (calcidiol, the form measured in blood) and 1-hydroxylation in the kidneys (calcitriol, the active hormone).
• Calcitriol acts through a nuclear receptor to increase calcium and phosphate absorption, supporting bone.
• Deficiency causes rickets in children and osteomalacia in adults; production depends on latitude, season and skin pigmentation.
• It’s fat-soluble and can be toxic in excess from supplements. For the other vitamins, see vitamins: fat-soluble vs water-soluble.