Are vitamin D supplements effective?

Several newly-released meta-analyses suggest that there is not enough clear evidence of health effects of vitamin D preparations – such as maintaining bone health and reducing the risk of developing chronic diseases. Experts describe these conclusions as inadmissible and refer to the sufficiently documented need for a reasonable supply of vitamin D, which is essential for many bodily functions.

One of the current meta-analyses, which included data from 20 randomized controlled trials, came to the conclusion that a dietary supplement with vitamin D, with or without calcium, in older subjects would not reduce the number of falls by even 15% (1). As a result, there would be no reason to prescribe vitamin D supplements for the prevention of falls. Experts noted that this finding contrasts with the results of other meta-analyses, such as the data analyses of the US Preventive Services Task Force (2) and the Cochrane Collaboration (3), according to which a targeted intake of vitamin D for the prevention of bone fractures in adults dwelling in retirement homes is recommended. While very specific recommendations for the use of vitamin D supplements for the prevention of fractures were derived from the USPSTF and Cochrane ana- lyses, the new data analysis focused on the number of falls, based on a relatively unusual sequential meta- analysis. Although fractures usually result from falls, not all falls result in fractures. The influence of the number of falls as the parameter for the effectiveness of supplemental vitamin D intake (1) is much less significant than analysis of risk of fall-related fractures (2, 3). Therefore, according to the experts, the results of the new meta-analysis on the existing recommendations for the use of vitamin D supplements to prevent (fall-related) fractures in adults with insufficient vitamin D intakes change nothing.

It is believed that adequate vitamin D blood levels can positively affect the preservation of bone density and muscle mass. While the effect on the muscles could prevent falls, an increase of bone mineral density (which can also be increased through improving muscle tone) would reduce the risk of bone fractures after a fall. The European Food Safety Authority (EFSA) has confirmed that sufficient intakes and vitamin D production can contribute to the maintenance of normal muscle function and reduce the risk of falls (4). The danger of falling, which leads to fractures, is particularly high for people age 60 and above. To achieve the desired preventive effect, daily doses of 800 IU (20 µg) of vitamin D from all possible sources are recommended by EFSA.

In three other meta-analyses the results of previously performed meta-analyses (5) and randomized con- trolled studies (6) were partly pooled together in combination with the results of observational studies (5, 7). One of the data analyses concluded that of the numerous potential health benefits from targeted vitamin D intakes only one (positive influence of birth weight of the child from increased vitamin D levels of the mother in late-stage pregnancy) was sufficiently conclusive, while potentially positive impact was shown, however, such as on birth weight in general as well as dental cavity prevention in children (5). The second study as- sessed the results of several studies on vitamin D in the prevention of cardiovascular diseases, cancer and associated deaths in adults (6) resulting in a sequential meta-analysis. The results were assessed by the responsible researchers with reference to their conclusiveness and found to be insufficient: Vitamin D intakes by means of food supplements (with and without calcium) were shown to reduce disease risk by not more than 15% by all indications. Finally, the third overview summed up the results of numerous studies on the possible link between vitamin D blood concentrations of subjects and their risk of cardiovascular-disease- or cancer-related death (7). The meta-analysis showed that low vitamin D levels were connected to an increa- sed risk of mortality. The use of nutritional supplements with vitamin D3 (but not with vitamin D2) led to a reduction in the risk of death in general.

In comments (8, 9) referring to the studies, experts stressed that the conclusions were at odds with the comprehensive analyses and evaluations of the Institute of Medicine, which noted in its report the proven sufficiency requirements of 25-hydroxy-vitamin-D levels between 30 and 50 nmol/L for maintaining bone health (10), a value that many people would not achieve without supplemental vitamin D intakes. As a target to maintain bone health, vitamin D values above 50 nmol/L are recommended (11). An increase of vitamin D intake ultimately only makes sense if deficits exist. Unfortunately, the majority of studies failed to investigate the subjects at the beginning of each study with regard to their nutritional status, according to the experts. This was the case for almost all the studies that were included in the above-mentioned meta-analyses. In general, conclusions based on meta-analyses are problematic, because the analyses summarize and distort results of various studies (different study designs, study periods, groups of participants and doses of vitamin D used). Furthermore, they pointed out that the randomized placebo-controlled study design – taken as gold standard for drug testing from evidence-based medicine – is only very limited for research on nutrients.

In addition to the positive impact of sufficiently high vitamin D levels on bones, teeth and muscles, vitamin D also contributes to the normally functioning immune system, healthy inflammatory response, as well as well-functioning cell division according to the EFSA (12). The latter functions suggest a possible preventive effect of sufficient vitamin D supply against the development of chronic inflammatory diseases (such as atherosclerosis and cancer). Studies proving these possible relationships however still have yet to be carried out.

1. Bolland M. J. et al. Vitamin D supplementation and falls: a trial sequential meta-analysis. The Lancet Diabetes & Endocrinology. Published online April 2014.
   
2. Chung M. et al. Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med. 2011; 155(12):827–838.
   
3. Avenell A. et al. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev. 2009; (2):CD000227.
   
4. EFSA Panel on Dietetic Products, Nutrition and Allergies. Scientific Opinion on the substantiation of a health claim related to vitamin D and risk of falling. EFSA Journal. 2011; 9(9):2382.
   
5. Theodoratou E. et al. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. Published online April 2014.
   
6. Bolland M. J. et al. The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis. Lancet Diabetes Endocrinol. 2014; 2(4):307-320.
   
7. Chowdhury R. et al. Vitamin D and risk of specific death: systematic review and meta-analyses of observational cohort and randomised intervention studies. BMJ. Published online April 2014.
   
8. Hill T. R. Vitamin D status is poor in the UK. BMJ. 2014; 348:g2818.
   
9. Rhein H. M. Vitamin D deficiency in Scotland. BMJ. 2014; 348:g2821.
   
10. Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Institute of Medicine. Dietary reference intakes for calcium and vitamin D. 2010.
    
11. Institute of Medicine. Dietary reference intakes for calcium and vitamin D. National Academies Press. 2011.
    
12. EFSA Panel on Dietetic Products, Nutrition and Allergies. Scientific Opinion on the substantiation of health claims related to vitamin D and normal function of the immune system and inflammatory response, maintenance of normal muscle function and maintenance of normal cardiovascular function. EFSA Journal. 2010; 8(2):1468.