Calcifediol (25OH Vitamin D3) Deficiency: A Risk Factor from Early to Old Age

Nutrients. 2022 Mar 10;14(6):1168. doi: 10.3390/nu14061168.


Vitamin D deficiency is the main cause of nutritional rickets in children and osteomalacia in adults. There is consensus that nutritional access to vitamin D can be estimated by measuring serum concentrations of 25OHD and vitamin D deficiency can thus be considered as calcifediol deficiency. However, the threshold for vitamin D/calcifediol sufficiency remains a matter of debate. Vitamin D/calcifediol deficiency has been associated with musculoskeletal effects but also multiple adverse extra-skeletal consequences. If these consequences improve or if they can be treated with vitamin D supplementation is still unclear. Observational studies suggest a higher infection risk in people with low calcifediol levels. There is also a consistent association between serum calcifediol and cardiovascular events and deaths, but large-scale, long-term intervention studies did not show any benefit on cardiovascular outcomes from supplementation, at least not in subjects without clear vitamin D deficiency. Cancer risk also did not change with vitamin D treatment, although there are some data that higher serum calcifediol is associated with longer survival in cancer patients. In pregnant women, vitamin D supplementation decreases the risk of pre-eclampsia, gestational diabetes mellitus, and low birth weight. Although preclinical studies showed that the vitamin D endocrine system plays a role in certain neural cells as well as brain structure and function, there is no evidence to support a beneficial effect of vitamin D in neurodegenerative diseases. Vitamin D supplementation may marginally affect overall mortality risk especially in elderly subjects with low serum calcifediol concentrations.

Keywords: COVID-19; calcifediol; immunology; osteomalacia; osteoporosis; rickets; vitamin D.

Publication types

  • Review

MeSH terms

  • Aged
  • Calcifediol* / therapeutic use
  • Child
  • Cholecalciferol / therapeutic use
  • Female
  • Humans
  • Pregnancy
  • Risk Factors
  • Vitamin D
  • Vitamin D Deficiency* / complications
  • Vitamin D Deficiency* / drug therapy


  • Vitamin D
  • Cholecalciferol
  • Calcifediol