Low blood vitamin D concentrations may increase mortality risk

December 30, 2011

A new review suggests that mortality risk decreases as the vitamin D serum level increases, with optimal concentrations of 75–87.5 nmol/L.

To evaluate a potential association of 25-hydroxyvitamin D [25(OH)D] serum concentrations and mortality among general populations, 14 prospective cohort studies were reviewed in which 5,562 deaths occurred among 62,548 individuals (1). A meta-analysis of the studies showed that an increase in vitamin D serum concentrations of 12.5, 25, and 50 nmol/L from a median reference level of 27.5 nmol/L resulted in a reduction in mortality risk of up to 31%. However, there was no significant decrease in mortality associated with levels increased to 87.5 nmol/L above the reference level.

The researchers commented that while the Institute of Medicine already considers concentrations of 50 nmol 25(OH)D/L to be adequate (2), other scientists maintain that the most advantageous serum concentrations begin at 75 nmol 25(OH)D/L and that the optimal are between 90 and 100 nmol 25(OH)D/L (3). The new data on overall mortality would be further evidence for a desirable concentration of 75–87.5 nmol 25(OH)D/L.

A meta-analysis of randomized, controlled trials that were designed mainly to evaluate musculoskeletal conditions of frail, elderly people showed a significant reduction of total mortality in the vitamin D treatment groups (4). In the majority of studies included in that meta-analysis, baseline circulating concentrations were 50 nmol 25(OH)D/L. Even in apparently healthy subjects, circulating concentrations 50 nmol 25(OH)D/L are common around the world (5). There is some evidence for a nonlinear association of 25(OH)D with conditions, such as breast cancer (6), incidence of cardiovascular diseases (7), and all-cause mortality (8).


  1. Zittermann A. et al. Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies. Am J Clin Nutr. Published online December 2011.
  2. Ross A. C. et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011; 96:53–58.
  3. Souberbielle J. C. et al. Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: recommendations for clinical practice. Autoimmun Rev. 2010; 9:709–715.
  4. Autier P. and Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007; 167:1730–1737.
  5. Hintzpeter B. et al. Vitamin D status and health correlates among German adults. Eur J Clin Nutr. 2008; 62:1079–1089.
  6. Abbas S. et al. Plasma 25-hydroxyvitamin D and premenopausal breast cancer risk in a German case-control study. Int J Cancer. 2009; 124:250–255.
  7. Wang T. J. et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008; 117:503–511.
  8. Melamed M. L. et al. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med. 2008; 168:1629–1637.