Table 2

Wide-ranging systematic reviews, Cochrane reviews and health technology assessments of RCTs of vitamin D supplementation since the SACN report search completed

ReviewEndpointDescriptionFindings
Comprehensive, large, wide-ranging systematic reviews
 Autier, 201423 Cardiovascular disease, mortality, cancer incidence172 RCTs*
  • No effect on disease occurrence

  • Small reduction in all-cause mortality (RR range 0.93–0.96)

 Bolland, 201424 Stroke, myocardial infarction, cancer, fractures, mortalityTrial sequential analysis of RCTs*
  • Does not reduce skeletal or non-skeletal outcomes by >15% in unselected community dwelling individuals

 Bolland, 201417 Falls20 RCTs*
  • Supplementation with vitamin D, with or without calcium, does not reduce falls by 15% or more

 Theodoratou, 201425 Clinical and surrogate endpoints87 meta-analyses of RCTs†
  • No consistent difference in health outcomes

 Rejnmark, 201726 Cardiovascular disease, type 2 diabetes, cancer, respiratory tract infections, mortality, depression, blood pressure54 meta-analyses of RCTs*†
  • Most meta-analyses reported null findings on cardiovascular disease, type 2 diabetes, cancer

  • 1 of 4 meta-analyses on depression, 2 of 9 on blood pressure, 3 of 7 on respiratory tract infection, 8 of 12 on mortality reported beneficial effects

 Autier, 201727 Non-skeletal disorders35 recent good quality meta-analyses*
  • Most meta-analyses and trials have found no evidence of an effect on preventing or treating acute and chronic conditions. No evidence for effect on cardiovascular disease or colorectal adenomas

  • Can reduce all-cause mortality, mainly in hospital or an institution, and cancer mortality

  • Might help to prevent upper respiratory tract infections and asthma exacerbations

 Bolland, 201828 Fractures, falls, bone mineral density81 RCTs
  • Does not prevent fractures or falls or having clinically meaningful effects on bone mineral density

 Kahwati, 201829 Fractures, mortality, cardiovascular events, cancer8 RCTs*
  • No effect on fractures, all-cause mortality, cardiovascular disease, cancer incidence in community dwelling adults

 Zhang, 201930 All-cause mortality52 RCTs
  • No effect on all-cause mortality (RR 0.98, 95% CI 0.95 to 1.02)

 Barbarawi,201931 Cardiovascular disease21 RCTs*†
  • No reduction in major cardiovascular events, myocardial infarction, stroke, cardiovascular mortality, all-cause mortality

Recent Cochrane reviews or health technology assessments
 Bjelakovic 201432 Cancer18 RCTs*†
  • No effect on cancer incidence

  • Reduced cancer mortality in 4 trials of vitamin D alone (RR 0.88, 95% CI 0.78 to 0.98), rated low quality evidence

 Bjelakovic, 201433 All-cause mortality56 RCTs*†
  • Reduced mortality by small amount (RR 0.97, 95% CI 0.94 to 0.99)

  • Authors state that risks of attrition bias, outcome reporting bias and other weaknesses warrant further placebo-controlled RCTs

 Ferguson, 201434 Cystic fibrosis3 RCTs*†
  • Insufficient evidence to draw reliable conclusions

 LeBlanc, 201535 Benefits of screening, mortality, fractures, falls17 RCTs or case-control studies*
  • No RCTs of screening vs. not screened

  • Vitamin D with or without calcium reduced mortality in institutionalised older people in 3 RCTs

  • No effect on risk of fall, but decreased falls per person

  • No effect on fractures

 Straube, 201536
 (CD007771)
Chronic pain10 RCTs†
  • Insufficient evidence to draw reliable conclusions but large effect unlikely

 Martineau, 201637 Asthma7 RCTs (2 in adults)
  • In each trial, vitamin D had no effect on the primary or secondary clinical endpoints

  • Reduced rate of exacerbations requiring corticosteroids or hospital visit. These were not the primary or secondary endpoints of the RCTs

  • Authors state caution warranted applying evidence to practice because results come from relatively few trials

 Soe, 201738
 (CD010858)
Sickle cell disease1 RCT
  • One low-quality study which had high risk of bias, evidence insufficient quality to guide clinical practice

 Bjelakovic, 201739 Liver disease15 RCTs*†
  • Uncertain whether vitamin D supplements have important effect on all-cause mortality, liver-related mortality, or adverse events because results were imprecise

  • No evidence on effect of vitamin D supplementation on liver-related morbidity or health-related quality of life

  • Overall quality of evidence is very low

 Guirguis-Blake, 201740 Falls by community-dwelling older adults7 RCTs*†
  • 1 trial of annual high-dose cholecalciferol showed an increase in people experiencing a fall

  • 1 trial of calcitriol showed a reduction in people experiencing a fall

  • 5 trials showed no significant difference in people experiencing a fall

 Zhao, 201741 Fractures33 RCTs*
  • Not associated with lower risk of fractures in community dwelling older adults

 Jagannath, 201842 Multiple sclerosis12 RCTs*
  • Very low-quality evidence suggests no benefit of vitamin D for patient-important outcomes

 Martineau, 201943 Acute respiratory infections25 RCTs
  • Adjusted OR 0.88 (95% CI 0.81 to 0.96) representing 2% reduction in participants experiencing at least one infection with vitamin D. Most benefits if 25OH <25 nmol/L

  • *Results include some RCTs examining calcium in addition to vitamin D.

  • †Results include some RCTs examining activated forms of vitamin D.

  • CI, confidence interval; 25OHD, 25-hydroxyvitamin D; OR, odds ratio; RCT, randomised controlled trial; RR, risk ratio.