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Vitamin D Deficiency

GMJ News knowledge hub · last reviewed August 2026 · Georgian Medical Journal

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Vitamin D deficiency and insufficiency — arising from inadequate sun exposure, dietary intake or metabolic impairment of the skin→liver→kidney synthesis pathway to active calcitriol — affects an estimated 1 billion people globally across all ages, income levels and latitudes, with established consequences ranging from rickets and osteomalacia (the classic skeletal manifestations) to impaired immune function, muscle weakness and increased fracture risk, while active research continues into contested but potentially significant associations with cancer, cardiovascular disease, type 2 diabetes, multiple sclerosis and respiratory infection susceptibility (WHO). The COVID-19 pandemic amplified attention to vitamin D given observational evidence linking low levels to more severe disease — though large RCTs (VITAL, VITDALIZE) delivered mixed results on hard clinical outcomes, tempering early enthusiasm while reinforcing the established bone and muscle benefits of adequate levels.

Key messages

1 billion people globally deficient or insufficient
Vitamin D deficiency (<30 nmol/L) or insufficiency (30-50 nmol/L) affects approximately 1 billion people across all ages, income levels and latitudes — from populations near the equator (clothing-covered skin) to high-latitude communities with limited sunlight exposure (WHO/Lancet 2022).
Rickets and osteomalacia — the classic deficiency diseases
Severe vitamin D deficiency causes rickets in children (softening of bones, bowed legs, skull bossing, delayed teeth) and osteomalacia in adults (bone pain, proximal muscle weakness, pseudo-fractures on X-ray). Both are now seeing resurgence globally — including in HICs — among at-risk groups.
Sun exposure + diet + supplementation — the triad
Adequate vitamin D requires all three: sun exposure (UV-B converts 7-dehydrocholesterol in skin to vitamin D3); dietary intake (oily fish, fortified dairy, eggs — provide limited vitamin D in most diets); supplementation (400-2000 IU/day depending on risk). 15-30 minutes of midday sun on arms and legs produces approximately 1000 IU.
Established benefits — bone, muscle, immune
Strong evidence: calcium absorption and bone mineralisation; muscle function (reduces falls risk in elderly); prevention of rickets/osteomalacia. Vitamin D is essential for innate and adaptive immunity — deficiency impairs macrophage and T-cell function, increasing susceptibility to respiratory infections (meta-analysis: supplementation reduces ARI risk by approximately 12%).
Non-skeletal claims — more cautious
Large RCTs (VITAL — 25,871 participants; VITDALIZE — critically ill) found no significant reduction in cancer incidence, cardiovascular disease, or COVID-19 mortality from supplementation, despite strong observational associations. The paradox likely reflects reverse causation (illness causes low vitamin D) and unmeasured confounders.
Safety and toxicity
Vitamin D toxicity (hypervitaminosis D) requires very high doses sustained over time (typically >10,000 IU/day for weeks-months). Toxicity causes hypercalcaemia: nausea, constipation, weakness, confusion, polyuria, nephrocalcinosis, cardiac arrhythmias. Standard supplementation doses (1,000-4,000 IU/day) are safe for virtually all adults.

Key statistics

~1B
people globally vitamin D deficient or insufficient (WHO/Lancet)
WHO/Lancet 2022
<30 nmol/L
25(OH)D serum threshold for vitamin D deficiency (WHO)
WHO
~12%
reduction in acute respiratory infection risk from vitamin D supplementation
BMJ meta-analysis 2017/2021
400-2000 IU
recommended daily vitamin D3 supplement range for adults at risk
WHO/SACN
No benefit
VITAL trial: supplementation did not reduce cancer incidence or CVD in healthy adults
NEJM 2022
>10,000 IU/day
sustained doses needed to cause vitamin D toxicity (hypervitaminosis D)
WHO

Vitamin D synthesis and metabolism — the skin-liver-kidney pathway

Source: WHO. Each step in the vitamin D pathway can be disrupted by disease, drugs, ageing or inadequate sun/dietary intake.

Glossary of key terms

25-hydroxyvitamin D (25(OH)D)
WHOThe main circulating vitamin D metabolite — the standard laboratory marker of vitamin D status. Produced in the liver by 25-hydroxylation of vitamin D3 (from skin or dietary sources). Serum 25(OH)D reference ranges: <30 nmol/L (<12 ng/mL) = deficiency; 30-50 nmol/L = insufficiency; >50 nmol/L = sufficiency; optimal for musculoskeletal health approximately ≥75 nmol/L by some authorities. Half-life approximately 2-3 weeks.
1,25(OH)2D (calcitriol)
WHO/EndocrinologyThe active hormone form of vitamin D — produced in the kidneys by 1-alpha-hydroxylation of 25(OH)D, regulated by PTH and serum calcium/phosphate. Calcitriol binds the vitamin D receptor (VDR) — expressed in virtually all tissues including immune cells, muscle, heart, brain, cancer cells — mediating the classical (calcium absorption) and non-classical (immune, muscle, other) effects of vitamin D.
Vitamin D receptor (VDR)
ResearchThe nuclear receptor through which calcitriol acts — present in most human cells. VDR activation regulates gene transcription (approximately 3% of the human genome). VDR polymorphisms (Fok1, Bsm1, Apa1, Taq1) affect transcriptional activity and may partly explain individual variation in vitamin D response. The VDR presence in immune cells, neurons, cardiomyocytes and cancer cells explains the biological plausibility of non-skeletal vitamin D effects — but clinical trial evidence has not consistently confirmed benefit.
VITAL trial
NEJM 2019/2022The Vitamin D and Omega-3 Trial (VITAL) — 25,871 US adults randomised to vitamin D3 2000 IU/day vs placebo (+ omega-3 ± placebo), median follow-up 5.3 years. Results: no significant reduction in primary endpoints (cancer incidence, major CV events). Post-hoc: possible reduction in cancer mortality; possible benefit for those with low baseline vitamin D. The largest and most rigorous vitamin D supplementation trial — its largely negative results tempered widespread enthusiasm.
Rickets resurgence
WHO/RCPCHNutritional rickets is re-emerging in HICs — particularly in: infants exclusively breastfed without vitamin D supplementation (breast milk contains negligible vitamin D); infants and children with dark skin (reduced UV-B skin synthesis at northern latitudes); infants whose mothers were severely vitamin D deficient in pregnancy; communities with limited sun exposure due to religious clothing practices. WHO/RCPCH recommend all breastfed infants receive vitamin D 400 IU/day from birth.
Groups at highest risk of deficiency
WHO/SACNHighest risk: infants (especially exclusively breastfed); children and adults with dark skin living at northern latitudes (reduced UV-B skin synthesis); housebound elderly; people covering skin for religious/cultural reasons; people with fat malabsorption (coeliac, IBD, bariatric surgery); end-stage renal disease (reduced 1-alpha-hydroxylase); severe hepatic disease (reduced 25-hydroxylation); obesity (vitamin D sequestered in adipose tissue); prolonged anticonvulsant use (accelerated catabolism).

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Related health topics

OsteoporosisNutritionSupplementsRickets in childrenAgeing (falls prevention)Immune function

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