Vitamin D deficiency

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 7 Apr 2025

Last updated: 25 Feb 2025

Vitamin D deficiency is the most common nutritional deficiency worldwide, characterized by serum 25-hydroxyvitamin D <20 nanograms/mL. Vitamin D insufficiency is regarded as a serum 25-hydroxyvitamin D concentration between 21-29 nanograms/mL.

Main causes include sun avoidance, using sun protection, increased skin pigmentation, inadequate dietary and supplemental vitamin D intake, malabsorption syndromes, obesity, and medication use. Acquired and inherited disorders that either reduce or prevent the metabolism of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D also present with biochemical and skeletal abnormalities seen with vitamin D deficiency, but in a more severe form.

Most patients are asymptomatic. Severe prolonged vitamin D deficiency causes growth retardation and rickets in children and osteomalacia, osteopenia, and osteoporosis in adults.

In addition to the skeletal effects, it is now recognized that vitamin D deficiency increases the risk of many chronic diseases, including cancer, autoimmune diseases, type 2 diabetes, heart disease and hypertension, neurocognitive dysfunction, infectious diseases (including respiratory tract infections, tuberculosis, and COVID-19), and schizophrenia. Vitamin D deficiency/insufficiency has been associated with increased risk for morbidity and mortality associated with COVID-19.

Both vitamin D deficiency and vitamin D insufficiency are corrected by giving vitamin D2 or vitamin D3 in treatment doses followed by lifelong maintenance doses; adequate, sensible sunlight exposure should be encouraged. Additional replacement with 1,25-dihydroxyvitamin D or one of its active analogs is necessary for those with disorders of vitamin D metabolism, including patients with chronic kidney disease.

Definition

To maximize vitamin D effects on the skeleton and on calcium metabolism, serum 25-hydroxyvitamin D concentration should be >30 nanograms/mL. Therefore, vitamin D deficiency is defined as a serum 25-hydroxyvitamin D level of <20 nanograms/mL, whereas vitamin D insufficiency is regarded as a 25-hydroxyvitamin D level of between 21-29 nanograms/mL.[1][2] Vitamin D sufficiency is defined by a 25-hydroxyvitamin D of 30-100 nanograms/mL. Vitamin D toxicity is usually seen when serum 25-hydroxyvitamin D concentrations >150 nanograms/mL.[2]

History and exam

Key diagnostic factors

inadequate sunlight exposure
increased skin pigmentation
age >50 years
history of inadequate dietary and supplemental vitamin D intake
history of malabsorption
obesity
medication use (e.g., dexamethasone, phenytoin, carbamazepine, ritonavir)
history of chronic kidney disease
history of benign or malignant tumor
bowing of the legs
widening of the ends of the long bones
delayed tooth eruption and early dental caries
chest deformity
throbbing, aching bone discomfort and/or irritability
head sweating
localized or generalized bone tenderness
proximal muscle weakness
rachitic rosary
frontal bossing
waddling gait

Full details

Other diagnostic factors

faltering growth
delayed achievement of motor milestones
fatigue and malaise
symptoms of hypocalcemia

Full details

Risk factors

inadequate sunlight exposure
increased skin pigmentation
age >50 years
inadequate dietary and supplemental vitamin D intake
malabsorption
obesity
medication use
genetic mutations
tumor
chronic kidney disease
granulomatous disorders
primary hyperparathyroidism
hyperthyroidism

Full details

Diagnostic tests

1st tests to order

serum 25-hydroxyvitamin D
serum calcium
fasting serum phosphate
serum alkaline phosphatase
plain film radiographs of knees and wrists

Full details

Tests to consider

intact PTH
serum 1,25-dihydroxyvitamin D
bone density (DEXA) scan

Full details

Treatment algorithm

ACUTE

insufficiency

deficiency

Contributors

Authors

Michael F. Holick, PhD, MD

Director Vitamin D, Skin, and Bone Research Laboratory

Director Ehlers-Danlos Clinical Research Program

Professor of Medicine, Physiology, and Biophysics and Molecular Medicine

Departments of Medicine, Physiology, and Biophysics

Section of Endocrinology, Diabetes, Nutrition and Weight Management

Boston University School of Medicine

Boston

Disclosures

MFH has a clinical research contract and consultant for Solius Inc., clinical and basic research contract and grant from Carbogen-Amcis, and is a consultant for Faes Farma. He is a speaker for Pulse Ltd, Abbott Inc., Sanofi Inc., Menarini Inc., and a board member Bridge to Life. He also chaired the Endocrine Society’s practice guidelines on vitamin D. MFH is an author of references cited in this topic.

Peer reviewers

Vin Tangpricha, PhD, MD

Professor of Medicine

Division of Endocrinology

Metabolism and Lipids

Emory University School of Medicine

Atlanta

Disclosures

VT is an author of references cited in this topic.

Stefan Pilz, MD

General Practitioner

Resident at the Department of Internal Medicine

Division of Endocrinology and Nuclear Medicine

Medical University of Graz

Graz

Austria

Disclosures

SP is an author of references cited in this topic.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Hossein-Nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc. 2013 Jul;88(7):720-55.Full text Abstract

Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30.Full text Abstract

Chanchlani R, Nemer P, Sinha R, et al. An overview of rickets in children. Kidney Int Rep. 2020 Jul;5(7):980-90.Full text Abstract

Cashman KD. Global differences in vitamin D status and dietary intake: a review of the data. Endocr Connect. 2022 Jan 11;11(1):e210282.Full text Abstract

Charoenngam N, Holick MF. Immunologic effects of vitamin D on human health and disease. Nutrients. 2020 Jul 15;12(7):2097.Full text Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials
- Primary hyperparathyroidism
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Guidelines
- Nutritional interventions update: vitamin D supplements during pregnancy
- KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder
More Guidelines
Patient information
Vitamin D deficiency
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More Patient information
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Vitamin D deficiency

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Treatment algorithm

insufficiency

deficiency

Contributors

Authors

Michael F. Holick, PhD, MD

Disclosures

Peer reviewers

Vin Tangpricha, PhD, MD

Disclosures

Stefan Pilz, MD

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Patient information

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice