Vitamin D (25-OH)

Physiological Role

25-OH vitamin D (calcidiol) is the circulating form of vitamin D, produced by the liver from vitamin D3. The latter comes from two sources: cutaneous synthesis under UVB sunlight and dietary intake (fatty fish, egg yolk, UV-exposed mushrooms). Calcidiol is then converted to calcitriol (1,25-dihydroxyvitamin D), the active hormonal form, primarily by the kidneys.

Calcitriol regulates intestinal absorption of calcium and phosphorus, two minerals essential for bone mineralisation. It acts through a nuclear receptor (VDR) present in nearly all human tissues: bone, intestine, muscle, immune cells, pancreas. This ubiquity explains why vitamin D is involved in functions well beyond bone metabolism.

On the immune side, vitamin D modulates innate response by stimulating the production of antimicrobial peptides (cathelicidins, defensins). It contributes to the normal functioning of the immune system. On the muscular side, calcitriol is involved in the contraction of type II muscle fibres, those responsible for strength and postural balance.

Reference Ranges

These reference ranges are derived from scientific literature and may differ from your laboratory's reference values.

Source : NIH ODS / Endocrine Society, Vitamin D sufficiency discussion (2024)

Biological Significance

The 25-OH vitamin D assay reflects the body's reserves over the two to three weeks preceding the blood draw. It is the reference marker used by medical societies to evaluate vitamin D status.

A level within the optimal range reflects a balance between intake (sunlight, diet, supplementation) and the body's needs. The optimal range defined by Singular sits between 30 and 60 ng/mL, in line with the Endocrine Society recommendations.

Low values are common at temperate latitudes, particularly between October and April, when the angle of UVB incidence no longer allows sufficient cutaneous synthesis. Age, skin pigmentation, sunscreen use and time spent indoors are well-known factors of variation.

Regular monitoring allows observation of the seasonal trend and adjustment of supplementation accordingly. The plasma half-life of calcidiol (two to three weeks) makes a check every three to six months relevant to evaluate the trend.

Influencing Factors

Sun exposure. Cutaneous vitamin D3 synthesis depends on UVB intensity, which varies with latitude, season, time of day and area of skin exposed. At European latitudes, endogenous production is virtually nil from November to March.

Diet. Natural dietary sources remain limited: fatty fish (salmon, mackerel, sardine), egg yolk, cod liver, sun-dried shiitake mushrooms. Fortified foods (milk, cereals) contribute modestly to intake.

Skin pigmentation. Melanin absorbs UVB and slows vitamin D3 synthesis. People with darker skin require longer exposure to produce the same amount of vitamin D.

Age. The skin's ability to synthesise vitamin D decreases with age. A 70-year-old produces roughly four times less cutaneous vitamin D than a 20-year-old at identical exposure.

Body composition. Vitamin D is fat-soluble and distributes into adipose tissue. A high body mass index is associated with lower circulating levels, as vitamin D is sequestered in lipid stores.

Magnesium. Magnesium is an essential cofactor for the conversion of calcidiol to calcitriol. Insufficient magnesium intake can limit vitamin D activation even when circulating reserves are adequate.

Vitamin D3 supplementation. Vitamin D3 (cholecalciferol) is the most documented supplementation form for raising and maintaining serum 25-OH vitamin D levels. Vitamin K2-MK7, often paired with it, helps direct calcium toward bone matrix.

In the Singular Formula

Vitamin D is one of the markers most directly connected to the Singular formulation engine. Its level determines the calibration of vitamin D3 included in the formula.

When 25-OH vitamin D falls in the low or very low range (below 30 ng/mL), the formulation engine activates a reinforced vitamin D3 dosage. The goal is to support a gradual rise in vitamin D status toward the optimal range. The engine also generates a personalised lifestyle recommendation (sun exposure, diet).

When the level sits in the optimal range (30 to 60 ng/mL), the vitamin D3 dosage is adjusted to a maintenance level. This calibration aims to sustain status without excessive accumulation, accounting for the fat-soluble nature of vitamin D.

When the level exceeds 60 ng/mL (high or very high range), vitamin D3 is removed from the formula. The body's reserves are deemed sufficient and supplementation would not provide additional benefit.

The Singular formula also includes vitamin K2-MK7, whose synergy with vitamin D in calcium metabolism is documented in the literature. Magnesium, a cofactor in the conversion of calcidiol to calcitriol, is also present in the formula and contributes to optimal vitamin D utilisation.

Scientific Studies

Frequently Asked Questions