Khan SU, Khan MU, Riaz H, et al. Effects of Nutritional Supplements and Dietary Interventions on Cardiovascular Outcomes: An Umbrella Review and Evidence Map. Ann Intern Med. 2019 Jul 9. pii: 2737825. doi: 10.7326/M19-0341. (Systematic review)

Background: The role of nutritional supplements and dietary interventions in preventing mortality and cardiovascular disease (CVD) outcomes is unclear.

Purpose: To examine evidence about the effects of nutritional supplements and dietary interventions on mortality and cardiovascular outcomes in adults.

Data Sources: PubMed, CINAHL, and the Cochrane Library from inception until March 2019; ClinicalTrials.gov (10 March 2019); journal Web sites; and reference lists.

Study Selection: English-language, randomized controlled trials (RCTs) and meta-analyses of RCTs that assessed the effects of nutritional supplements or dietary interventions on all-cause mortality or cardiovascular outcomes, such as death, myocardial infarction, stroke, and coronary heart disease.

Data Extraction: Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence.

Data Synthesis: Nine systematic reviews and 4 new RCTs were selected that encompassed a total of 277 trials, 24 interventions, and 992 129 participants. A total of 105 meta-analyses were generated. There was moderate-certainty evidence that reduced salt intake decreased the risk for all-cause mortality in normotensive participants (risk ratio [RR], 0.90 [95% CI, 0.85 to 0.95]) and cardiovascular mortality in hypertensive participants (RR, 0.67 [CI, 0.46 to 0.99]). Low-certainty evidence showed that omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) was associated with reduced risk for myocardial infarction (RR, 0.92 [CI, 0.85 to 0.99]) and coronary heart disease (RR, 0.93 [CI, 0.89 to 0.98]). Folic acid was associated with lower risk for stroke (RR, 0.80 [CI, 0.67 to 0.96]; low certainty), whereas calcium plus vitamin D increased the risk for stroke (RR, 1.17 [CI, 1.05 to 1.30]; moderate certainty). Other nutritional supplements, such as vitamin B6, vitamin A, multivitamins, antioxidants, and iron and dietary interventions, such as reduced fat intake, had no significant effect on mortality or cardiovascular disease outcomes (very low- to moderate-certainty evidence).

Limitations: Suboptimal quality and certainty of evidence.

Conclusion: Reduced salt intake, omega-3 LC-PUFA use, and folate supplementation could reduce risk for some cardiovascular outcomes in adults. Combined calcium plus vitamin D might increase risk for stroke.

Primary Funding Source: None.

Discipline Area Score
Family Medicine (FM)/General Practice (GP) 7 / 7
General Internal Medicine-Primary Care(US) 7 / 7
Cardiology 6 / 7
Public Health 6 / 7
Internal Medicine 5 / 7
Comments from MORE raters

Cardiology rater

Useful summary of the evidence, or lack thereof, which should be helpful in our discussions with our patients regarding these agents.

General Internal Medicine-Primary Care(US) rater

Very interesting, however, as the authors state, most of the evidence is low quality. Take home points for me: don`t prescribe calcium and Vit D, which increase risk for stroke; forget about most supplements except folic acid and possibly fish oil; and, a low-salt diet is good even for normotensive individuals.

Internal Medicine rater

I worry about the enormous number of comparisons being made and using 95% CI for all of them. No large-size effects seen for anything.

Internal Medicine rater

Well done meta-analysis. The effect sizes are small and the data do not seem to be of high validity. This is probably useful for clinicians who want to counsel their patients about diet and supplement interventions.

Public Health rater

Ultimately, this analysis depends on the previously done studies, which in the nutritional field are often of uncertain validity.

Public Health rater

Reinforces the lack of clarity around benefits/harms of dietary supplements. At the very least, it provides support for NOT endorsing or promoting the use of supplements in the general population.
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