
Vitamin D
25-Hydroxyvitamin D (25(OH)D)
What it is
The measured form is 25-hydroxyvitamin D (25(OH)D, also called calcidiol) — the major circulating form of vitamin D and the appropriate measure of vitamin D status. Vitamin D is produced in the skin when 7-dehydrocholesterol absorbs UV-B radiation (forming vitamin D3, or cholecalciferol) and is also obtained from dietary sources and supplements as either D2 (ergocalciferol) or D3. The liver converts both forms to 25(OH)D, which is then converted by the kidneys to the biologically active form, 1,25-dihydroxyvitamin D (calcitriol). Vitamin D is more accurately described as a steroid prohormone than a vitamin: its active metabolite acts through the vitamin D receptor (VDR), a nuclear receptor expressed in virtually every tissue — immune cells, cardiac muscle, vascular endothelium, brain, colon, breast, prostate, and bone — and its activation controls the expression of hundreds to thousands of target genes. The systemic reach of vitamin D signalling is why deficiency produces effects across multiple physiological systems simultaneously, often without producing any of the classic symptoms associated with the clinical extremes of deficiency.
Why we measure it
Vitamin D deficiency is endemic. Surveys across multiple countries consistently find that 40–60% of adults have 25(OH)D below 30 ng/mL (75 nmol/L), and a substantial proportion fall below 20 ng/mL (50 nmol/L) — the level associated with clear physiological impairment in calcium absorption, bone mineralisation, and immune regulation. The consequences of deficiency extend well beyond the classic rickets and osteomalacia of severe insufficiency: low vitamin D status is associated in prospective epidemiological studies with increased all-cause mortality, cardiovascular disease, type 2 diabetes, autoimmune conditions, respiratory infections, cognitive decline, and several cancers. The VITAL trial — the largest randomised controlled trial of vitamin D supplementation (25,871 participants, 2,000 IU vitamin D3 daily, five-year follow-up), published in the New England Journal of Medicine in 2019 — found no primary prevention effect for major cardiovascular events or cancer incidence in a population with baseline mean 25(OH)D of approximately 31 ng/mL. But it did find a significant reduction in cancer mortality and potential metabolic benefits in subgroup analyses. The VITAL result is important for calibrating expectations: it suggests that correcting frank deficiency has measurable benefit, but supplementation above sufficiency threshold in a population that is already broadly sufficient does not proportionally reduce disease risk. This makes knowing your actual baseline 25(OH)D level — and targeting sufficiency rather than arbitrary high doses — the rational approach.
Why every 6 months
Vitamin D status has a marked seasonal pattern in populations without year-round strong UV-B exposure: 25(OH)D peaks in late summer and early autumn, reaching its nadir in late winter and early spring. For someone supplementing year-round, the seasonal fluctuation is attenuated but not eliminated; the nadir and peak still provide useful information about whether the supplementation dose is achieving sufficiency across the full annual cycle. The six-month testing interval captures both the seasonal high and low points, and provides sufficient resolution to confirm that a supplementation adjustment has achieved its target — vitamin D levels respond measurably to supplementation changes within 8–12 weeks, reaching a new steady state by approximately 16–20 weeks.
What movement means
The Endocrine Society's 2011 clinical practice guideline defines deficiency as 25(OH)D below 20 ng/mL (50 nmol/L), insufficiency as 20–29 ng/mL (50–74 nmol/L), and sufficiency as ≥ 30 ng/mL (75 nmol/L). Some researchers and clinicians advocate for a higher optimal target — typically 40–60 ng/mL (100–150 nmol/L) — based on observational associations with reduced cancer and cardiovascular risk; but this range is not universally adopted in clinical guidelines and is not supported as a primary prevention target by the VITAL RCT. Toxicity (hypercalcaemia) is rare from supplementation alone but has been reported at sustained levels above 150 ng/mL (375 nmol/L), typically only achievable with excessive supplementation doses.
Deficient
< 20 ng/mL (< 50 nmol/L)
Below the Endocrine Society's threshold for vitamin D deficiency. Associated with impaired calcium absorption, bone mineralisation loss, increased fracture risk, and immune dysregulation. Supplementation to restore sufficiency is generally recommended across all adult age groups.
Endocrine Society Clinical Practice Guideline — Holick et al., J Clin Endocrinol Metab, 2011 — doi:10.1210/jc.2011-0385
Insufficient
20 – 29 ng/mL (50 – 74 nmol/L)
Below the Endocrine Society's sufficiency threshold. Physiological function is partially maintained, but reserve is limited and seasonal troughs risk crossing into deficiency. Supplementation to reach and sustain sufficiency (≥ 30 ng/mL) is generally recommended, particularly in adults over 50 or those with limited UV-B exposure.
Endocrine Society Clinical Practice Guideline — Holick et al., J Clin Endocrinol Metab, 2011 — doi:10.1210/jc.2011-0385
Sufficient
≥ 30 ng/mL (≥ 75 nmol/L)
At or above the Endocrine Society-defined sufficiency threshold. Adequate for bone health and normal vitamin D-dependent physiological functions. Some researchers recommend a higher target of 40–60 ng/mL for broader immune and cardiometabolic benefit, though this is not universally supported by major guideline bodies.
Endocrine Society Clinical Practice Guideline — Holick et al., J Clin Endocrinol Metab, 2011 — doi:10.1210/jc.2011-0385
In the protocol
References
- 1.
Holick MF, Binkley NC, Bischoff-Ferrari HA, et al.. “Evaluation, Treatment, and Prevention of Vitamin D Deficiency: An Endocrine Society Clinical Practice Guideline.” Journal of Clinical Endocrinology & Metabolism. 2011.
- 2.
Manson JE, Cook NR, Lee I-M, et al.. “Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease.” New England Journal of Medicine. 2019.
- 3.
Schöttker B, Jorde R, Peasey A, et al.. “Vitamin D and Mortality: Meta-analysis of Individual Participant Data from a Large Consortium of Cohort Studies from Europe and the United States.” BMJ. 2014.
- 4.
Pludowski P, Holick MF, Pilz S, et al.. “Vitamin D Effects on Musculoskeletal Health, Immunity, Autoimmunity, Cardiovascular Disease, Cancer, Fertility, Pregnancy, Dementia and Mortality — A Review of Recent Evidence.” Autoimmunity Reviews. 2013.