Supplements no ‘magic bullet’ — analysis of 277 clinical trials

Organisation: Position: Deadline Date: Location:

SupplementsIn an analysis of findings from 277 clinical trials using 24 different interventions, Johns Hopkins Medicine researchers found that almost no vitamin, mineral and other nutrient supplements or diets can be linked to longer life. Possible benefits were found from a low-salt diet, omega-3 fatty acid supplements and possibly folic acid supplements for some.

Although they found that most of the supplements or diets were not associated with any harm, the analysis showed possible health benefits only from a low-salt diet, omega-3 fatty acid supplements and possibly folic acid supplements for some people. Researchers also found that supplements combining calcium and vitamin D may, in fact, be linked to a slightly increased stroke risk.

Surveys by the US Centres for Disease Control and Prevention show that 52% of Americans take a least one vitamin or other dietary/nutritional supplement daily. As a nation, Americans spend $31bn each year on such over-the-counter products. An increasing number of studies – including this new one from Johns Hopkins – have failed to prove health benefits from most of them.

“The panacea or magic bullet that people keep searching for in dietary supplements isn’t there,” says senior author of the study Dr Erin D Michos, associate director of preventive cardiology at the Ciccarone Centre for the Prevention of Cardiovascular Disease and associate professor of medicine at the Johns Hopkins University School of Medicine. “People should focus on getting their nutrients from a heart-healthy diet, because the data increasingly show that the majority of healthy adults don’t need to take supplements.”

For the current study, the researchers used data from 277 randomised clinical trials that evaluated 16 vitamins or other supplements and eight diets for their association with mortality or heart conditions including coronary heart disease, stroke, and heart attack. All together they included data gathered on 992,129 research participants worldwide.

The vitamin and other supplements reviewed included: antioxidants, Beta-carotene, vitamin B-complex, multivitamins, selenium, vitamin A, vitamin B3/niacin, vitamin B6, vitamin C, vitamin E, vitamin D alone, calcium alone, calcium and vitamin D together, folic acid, iron and omega-3 fatty acid (fish oil).

The diets reviewed were a Mediterranean diet, a reduced saturated fat (less fats from meat and dairy) diet, modified dietary fat intake (less saturated fat or replacing calories with more unsaturated fats or carbohydrates), a reduced fat diet, a reduced salt diet in healthy people and those with high blood pressure, increased alpha linolenic acid (ALA) diet (nuts, seeds and vegetable oils), and increased omega-6 fatty acid diet (nuts, seeds and vegetable oils). Each intervention was also ranked by the strength of the evidence as high, moderate, low or very low risk impact.

The majority of the supplements including multivitamins, selenium, vitamin A, vitamin B6, vitamin C, vitamin E, vitamin D alone, calcium alone and iron showed no link to increased or decreased risk of death or heart health.

In the three studies of 3,518 people that looked at a low-salt diet in people with healthy blood pressure, there were 79 deaths. The researchers say that they found a 10% decrease in the risk of death in these people, which they classified as a moderate associated impact.

Of the five studies in which 3,680 participants with high blood pressure were put on a low-salt diet, they found that the risk of death due to heart disease decreased by 33%, as there were 674 heart disease deaths during the study periods. They also classified this intervention as moderate evidence of an impact.

Forty-one studies with 134,034 participants evaluated the possible impact of omega-3 fatty acid supplements. In this group, 10,707 people had events such as a heart attack or stroke indicating heart disease. Overall, these studies suggested that supplement use was linked to an 8% reduction in heart attack risk and a 7% reduction in coronary heart disease compared to those not on the supplements. The researchers ranked evidence for a beneficial link to this intervention as low.

Based on 25 studies in 25,580 healthy people, data also showed that folic acid was linked to a 20% reduced risk of stroke. Some 877 participants had strokes during the trials. The authors graded evidence for a link to beneficial effects as low.

The authors point out that the studies suggesting the greatest impact of folic acid supplementation on reducing stroke risk took place in China, where cereals and grains aren’t fortified with folic acid like they are in the US. Thus, they say, this apparent protective effect may not be applicable in regions where most people get enough folic acid in their diet.

Twenty studies evaluated the combination of calcium with vitamin D in a supplement. Of the 42,072 research participants, 3,690 had strokes during the trials, and taken together the researchers say this suggests a 17% increased risk for stroke. The risk evidence was ranked as moderate. There was no evidence that calcium or vitamin D taken alone had any health risks or benefits.

“Our analysis carries a simple message that although there may be some evidence that a few interventions have an impact on death and cardiovascular health, the vast majority of multivitamins, minerals and different types of diets had no measurable effect on survival or cardiovascular disease risk reduction,” says lead author Dr Safi U Khan, an assistant professor of medicine at West Virginia University.

Other authors include Muhammad U Khan and Shahul Valavoor of West Virginia University; Haris Riaz of Cleveland Clinic; Di Zhao, Michael Blaha and Eliseo Guallar of Johns Hopkins; Lauren Vaughan and Victor Okunrintemi of East Carolina University; Irbaz Bin Riaz and M Hassan Murad of Mayo Clinic; Muhammad Shahzeb Khan of the John H Stroger Jr Hospital of Cook County; and Edo Kaluski of the Guthrie Health System.

The authors received no financial support for this research study and declare no conflicts of interest.

Abstract
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.

Authors
Safi U Khan, Muhammad U Khan, Haris Riaz, Shahul Valavoor, Di Zhao, Lauren Vaughan, Victor Okunrintemi, Irbaz Bin Riaz, Muhammad Shahzeb Khan, Edo Kaluski, M Hassan Murad, Michael J Blaha, Eliseo Guallar, Erin D Michos

Johns Hopkins Medicine material
Annals of Internal Medicine abstract


Receive Medical Brief's free weekly e-newsletter



Related Posts

Thank you for subscribing to MedicalBrief


MedicalBrief is Africa’s premier medical news and research weekly newsletter. MedicalBrief is published every Thursday and delivered free of charge by email to over 33 000 health professionals.

Please consider completing the form below. The information you supply is optional and will only be used to compile a demographic profile of our subscribers. Your personal details will never be shared with a third party.


Thank you for taking the time to complete the form.