By Aly Becraft, MS and Kevin C Maki, PhD

 

Despite scientific uncertainty surrounding the benefits of dietary supplements, many U.S. adults use them, along with various dietary interventions, with the belief that they will improve their overall health (1).  Khan et al. (2) recently published a systematic review to assess the effect of various nutritional supplements and dietary interventions on cardiovascular outcomes.  The criteria for inclusion were randomized controlled trials (RCTs) and meta-analyses of RCTs that assessed the effect of nutritional supplements (vitamins, minerals, dietary supplements) or dietary interventions on all-cause mortality and cardiovascular outcomes in adults and written in English.  The main outcome of interest was all-cause mortality and secondary outcomes included cardiovascular mortality, myocardial infarction (MI), stroke, and coronary heart disease (CHD).  From these criteria, 942 articles were identified, and after initial title and abstract screening, 140 full-text articles remained to be reviewed for eligibility.  Ultimately, 9 systematic reviews and 4 new RCTs were included, comprising a total of 105 meta-analyses, 24 interventions (16 types of nutritional supplements and 8 dietary interventions), 277 RCTs and 922,129 participants.  A list of these interventions is shown in Table 1 and the significant findings from the present analysis are summarized in Table 2.

 

Table 1. List of interventions analyzed in Khan et al. (2)

Nutritional Supplements	Dietary Interventions
Antioxidants	Mediterranean diet
Vitamin B6	Reduced dietary fat
Vitamin B3 or niacin	Modified dietary fat
Vitamin B complex	Reduced saturated fat
Carotene	Reduced salt (hypertensive)
Selenium	Reduced salt (normotensive)
Vitamin E	Increased omega-3 α-linolenic acid
Vitamin A	Increased omega-6 PUFA
Vitamin C
Vitamin D
Calcium and calcium plus vitamin D
Folic acid
Iron
Omega-3 long-chain PUFA
Multivitamins

Abbreviation: PUFA, polyunsaturated fatty acids

 

 

 

Table 2. Summary of statistically significant findings from Khan et al. (2)

	Intervention	RR (95% CI)	P-value	Certainty
All-cause mortality	Reduced salt intake in normotensive patients	0.90 (0.85 to 0.95)	0.01	Moderate
Cardiovascular mortality	Reduced salt intake in hypertensive patients	0.67 (0.46 to 0.99)	0.04	Moderate
MI	Omega-3 LC-PUFA	0.92 (0.85 to 0.99)	0.03	Low
CHD	Omega-3 LC-PUFA	0.93 (0.89 to 0.98)	0.01	Low
Stroke	Folic acid	0.80 (0.67 to 0.96)	0.02	Low
Stroke	Calcium plus vitamin D	1.17 (1.05 to 1.30)	0.01	Moderate

Abbreviations: CHD, coronary heart disease; CI, confidence interval; LC-PUFA, long-chain polyunsaturated fatty acids; MI, myocardial infarction; RR, risk ratio

 

Comment.  Overall, the researchers found little evidence for nutritional supplements or dietary interventions to significantly reduce risk for all-cause mortality or cardiovascular outcomes, with some exceptions as outlined in Table 2.  Interventions associated with lower risks included reduced salt intake and lower total (normotensives) or cardiovascular mortality (hypertensives), omega-3 fatty acid supplementation and reduced risks for CHD and MI, and folic acid supplementation associated with lower risk for stroke. 

 

Of note, calcium plus vitamin D intake was associated with increased risk for stroke.  This finding could be related to hypercalcemia-mediated vascular calcification and/or effects on coagulation, although additional research is needed to more firmly establish causality and mechanistic explanations (3-5).

 

Certainty of evidence from this systematic review was low for most interventions due to low precision of estimates, qualitative and quantitative heterogeneity, and publication bias.  Regardless, these findings can be a useful resource for healthcare professionals who would like to recommend evidence-based nutritional interventions and provide a basis for future studies to explore the gaps in the currently available evidence base. 

 

References:

1. Gahche JJ, Bailey RL, Potischman N, et al. Dietary supplement use was very high among older adults in the United States in 2011-2014. J Nutr. 2017;147:1968-76.
2. 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. 2019;E-pub ahead of print
3. Chin K, Appel LJ, Michos ED. Vitamin D, calcium, and cardiovascular disease: A”D”vantageous or “D”etrimental? An era of uncertainty. Curr Atheroscler Rep. 2017;19(1):5.
4. Anderson JJ, Kruszka B, Delaney JA, et al. Calcium intake from diet and supplements and the risk of coronary artery calcification and its progression among older adults: 10-year follow-up of the Multi-Ethnic Study of Atherosclerosis (MESA). J Am Heart Assoc. 2016;5(10).
5. Heaney RP, Kopecky S, Maki KC, Hathcock J, MacKay D, Wallace TC. A review of calcium supplements and cardiovascular disease risk. Adv Nutr. 2012;3:763-771.