Vitamin D deficiency

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 <50 nanomoles/L (<20 nanograms/mL) are suboptimal for human health. Furthermore, many guidelines and experts recommend maintaining a serum 25-hydroxyvitamin D concentration >75 nanomoles/L (>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 recognised 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 analogues is necessary for those with disorders of vitamin D metabolism, including patients with chronic kidney disease.

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]Giustina A, Adler RA, Binkley N, et al. Controversies in vitamin D: summary statement from an international conference. J Clin Endocrinol Metab. 2019 Feb 1;104(2):234-40. https://academic.oup.com/jcem/article/104/2/234/5148139 http://www.ncbi.nlm.nih.gov/pubmed/30383226?tool=bestpractice.com [2]Fuleihan Gel-H, Bouillon R, Clarke B, et al. Serum 25-hydroxyvitamin D levels: variability, knowledge gaps, and the concept of a desirable range. J Bone Miner Res. 2015 Jul;30(7):1119-33. https://onlinelibrary.wiley.com/doi/10.1002/jbmr.2536 http://www.ncbi.nlm.nih.gov/pubmed/25952470?tool=bestpractice.com ​​​​​​​

Vitamin D deficiency may be defined as a serum 25-hydroxyvitamin D concentration <50 nanomoles/L (<20 nanograms/mL), whereas vitamin D insufficiency may be regarded as a 25-hydroxyvitamin D level between 52 and 72 nanomoles/L (21 and 29 nanograms/mL).[3]Hossein-Nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc. 2013 Jul;88(7):720-55. http://www.mayoclinicproceedings.org/article/S0025-6196(13)00404-7/fulltext http://www.ncbi.nlm.nih.gov/pubmed/23790560?tool=bestpractice.com ​​​​ The Endocrine Society in 2024 no longer endorses specific 25-hydroxyvitamin D concentrations to define vitamin D sufficiency, insufficiency, and deficiency.[4]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. https://academic.oup.com/jcem/article/109/8/1907/7685305?login=false http://www.ncbi.nlm.nih.gov/pubmed/38828931?tool=bestpractice.com

Vitamin D toxicity is usually seen when serum 25-hydroxyvitamin D concentrations >375 nanomoles/L (>150 nanograms/mL).[5]Marcinowska-Suchowierska E, Kupisz-Urbańska M, Łukaszkiewicz J, et al. Vitamin D toxicity - a clinical perspective. Front Endocrinol (Lausanne). 2018;9:550. https://pmc.ncbi.nlm.nih.gov/articles/PMC6158375 http://www.ncbi.nlm.nih.gov/pubmed/30294301?tool=bestpractice.com

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]Sempos CT, Vesper HW, Phinney KW, et al. Vitamin D status as an international issue: national surveys and the problem of standardization. Scand J Clin Lab Invest Suppl. 2012;243:32-40. http://www.ncbi.nlm.nih.gov/pubmed/22536760?tool=bestpractice.com ​