Vitamin D deficiency

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

Last reviewed: 30 Apr 2025

Last updated: 29 May 2025

Vitamin D deficiency is the most common nutritional deficiency worldwide. Definitions regarding optimal serum concentrations vary according to the source used. However, there is broad clinical consensus that serum 25-hydroxyvitamin D concentrations <20 nanograms/mL are suboptimal for human health. Furthermore, many guidelines and experts recommend maintaining a serum 25-hydroxyvitamin D concentration >30 nanograms/mL, particularly in older adults.

Main causes include sun avoidance, increased skin pigmentation, inadequate dietary and supplemental vitamin D intake, malabsorption syndromes, obesity, and use of certain drugs. 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 decreased growth and rickets in children, and osteomalacia, osteopenia, and osteoporosis in adults.

In addition to the skeletal effects, it is now increasingly recognized that vitamin D deficiency is associated with an increased 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. 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

Definitions of optimal serum concentrations of 25-hydroxyvitamin D vary depending on the source, and there is no consensus on the ideal serum concentration for skeletal or extraskeletal health.[1][2]

Vitamin D deficiency may be defined as a serum 25-hydroxyvitamin D concentration <20 nanograms/mL, whereas vitamin D insufficiency may be regarded as a 25-hydroxyvitamin D level between 21 and 29 nanograms/mL.[3] The Endocrine Society in 2024 no longer endorses specific 25-hydroxyvitamin D concentrations to define vitamin D sufficiency, insufficiency, and deficiency.[4]

Vitamin D toxicity is usually seen when serum 25-hydroxyvitamin D concentrations >150 nanograms/mL.[5]

Definitions are further complicated by variability in serum 25-hydroxyvitamin D concentrations across different assay methods. Assay variability remains a significant concern and requires resolution through the widespread adoption of an international standard.[6]

History and exam

Key diagnostic factors

inadequate sunlight exposure
increased skin pigmentation
age >50 years
history of inadequate dietary and supplemental vitamin D intake
malabsorption
obesity
use of certain drugs
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

delayed 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
use of certain drugs
genetic mutations
history of benign or malignant 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

Full details

Tests to consider

plain film radiographs of knees and wrists
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, Adela, Ontometrics Inc., Eureka program, KBD Sperti Inc., and Biogena Inc. He is a speaker for Pulse Ltd, Abbott Inc., Sanofi Inc., Menarini Inc., PharmaEVO Pvt. Ltd., and a former board member of Bridge to Life. He also chaired the Endocrine Society’s 2011 practice guidelines on vitamin D. MFH is an author of The Vitamin D Solution and The UV Advantage. MFH is an author of references cited in this topic.

Peer reviewers

Linda Lester, MD, MS

Associate Professor of Medicine

Division of Endocrinology, Diabetes and Clinical Nutrition

School of Medicine

Oregon Health & Science University

Portland

Disclosures

LL declares that she has no competing interests.

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

Demay MB, Pittas AG, Bikle DD, et al. Vitamin D for the prevention of disease: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2024 Jul 12;109(8):1907-47.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

US Preventive Services Task Force, Krist AH, Davidson KW, et al. Screening for vitamin D deficiency in adults: US Preventive Services Task Force recommendation statement. JAMA. 2021 Apr 13;325(14):1436-42.Full text Abstract

Munns CF, Shaw N, Kiely M, et al. Global consensus recommendations on prevention and management of nutritional rickets. J Clin Endocrinol Metab. 2016 Feb;101(2):394-415.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.

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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

Linda Lester, MD, MS

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