Jury Is Still Out on Cardiovascular Benefits of Nonprescription Supplements

The CDC indicates that cardiovascular disease (CVD) continues to be the leading cause of death among both men and women across most ethnic and racial groups in the United States.¹ Recent statistics show that in the United States, an individual dies every 34 seconds from CVD, accounting for 1 in every 5 deaths and representing an estimated 697,000 deaths in 2020.¹

Research results show that some supplements may decrease the risk of CVD, whereas others may cause harm to individuals with CVD risk factors and have the potential to cause drug-supplement interactions.² However, findings from clinical trials have also revealed mixed results and clinical evidence remains insufficient.²

In a recent publication, the American Heart Association (AHA) indicated that available trial data on the effect of nutrient supplements and CVD outcomes have generated mostly inconclusive and insignificant results and more research is warranted.² Moreover, there is still great debate and mixed views among consumers and health care providers about the clinical benefits associated with the use of nutritional supplements.

The AHA noted that it is preferable to obtain essential nutrients via dietary means instead of nutrient supplements.² The AHA recommends a nutritional plan that is high in antioxidants, minerals, and vitamins and is low in saturated fat and sodium to diminish the risk of CVD.² The AHA also notes that mineral and vitamin supplementations should not be used as a replacement for healthy eating. However, individual supplements may be required in cases of nutrient inadequacy or for those eating restricted diets, such as certain groups of older adults or vegans.²

The CDC has indicated that many individuals elect to use supplements to foster cardiovascular (CV) health and promote overall well-being.³ Examples of nutritional supplements marketed for CV health include coenzyme Q10, garlic, ginger, omega-3 fatty acids, plant sterols, and turmeric, as well as specialty mineral and multivitamin supplements formulated with a blend of essential nutrients specifically targeted for CV health.

Pharmacists can provide patients with pertinent efficacy and safety data from clinical trials and recommendations from various health organizations, such as the AHA and CDC, and guide their selection and proper usage of nutritional supplements often used for CV health.

Recent News and Clinical Studies

Findings presented at the AHA’s Scientific Sessions 2022 showed that 6 supplements extensively used for CV health, including cinnamon, fish oil, garlic, plant sterols, red yeast rice, and turmeric, were not more effective at lowering low-density lipoprotein cholesterol (LDL-C) more than a placebo after 28 days of use.^4,5 In the prospective, randomized, single-blind, single-center clinical trial, the SPORT study (NCT04846231), the results of which were published in the Journal of the American College of Cardiology (JACC), investigators sought to compare the efficacy of a low-dose statin with a placebo and 6 common supplements in affecting inflammatory and lipid biomarkers.^4,5 Health data for 190 adults between 40 and 75 years of age who had no personal history of CVD were examined.^4,5 Results indicated that none of the dietary supplements demonstrated a significant decrease in LDL-C compared with the placebo, and the adverse event rates were comparable across study groups. Investigators concluded that among individuals with an increased 10 year risk for atherosclerotic cardiovascular disease (ASCVD), rosuvastatin 5 mg daily lowered LDL-C considerably more than cinnamon, fish oil, garlic, a placebo, plant sterols, red yeast rice, and turmeric.^4,5

In an editorial comment on the aforementioned study, which was also published in JACC, the authors wrote, “We believe that the conclusions made by Laffin et al^4,5 should be qualified. We strongly agree that dietary adjuncts should not be viewed as a substitute for evidence-based LDL-C–lowering medication. However, we also think that selected dietary supplements or adjuncts, particularly plant sterols or stanols and viscous, soluble fibers [the latter were not studied by Laffin et al^4,5], can have a role in ASCVD risk reduction strategies, though clinicians should counsel patients regarding realistic expectations for the LDL-C response, as well as implications for ASCVD risk reduction.”⁶

Another study published in JACC explored the correlation between ardiometabolic risk and micronutrients.⁷ Findings showed that certain supplements, such as coenzyme Q10, folic acid, and omega-3 fatty acids, may be beneficial to CV health.⁷ The meta-analysis of more than 884 studies showed supplementation with α-lipoic acid, catechin, coenzyme Q10, curcumin, flavanol, genistein, melatonin, folic acid, L-arginine, L-citrulline, magnesium, n-3 fatty acid, omega-6 fatty acid, quercetin and vitamin D, and zinc demonstrated moderate- to high-quality evidence for diminishing CVD risk factors. In particular, n-3 fatty acid supplementation reduced coronary heart disease, CVD mortality, and myocardial infarction events. β-Carotene supplementation augmented all-cause mortality, mortality events, and stroke risk. Coenzyme Q10 supplementation diminished all-cause mortality events. Folic acid supplementation diminished stroke risk. Selenium and vitamins C, D, and E showed no effect on CVD or type 2 diabetes risk. The authors indicated that their findings emphasize the significance of the balance of health benefits and risks, individualized interventions, and micronutrient diversity and could be used for future clinical trials exploring the influence of specific combinations of micronutrients and their effect on CV health.⁷

In a recent publication in Circulation, authors indicated that coenzyme Q10 was correlated with a decrease in all-cause mortality. However, larger-scale randomized controlled trials are necessary before any definitive interpretations can be drawn.^8,9

Conclusion

Understanding and implementing preventive measures early on can be instrumental in lowering the risk of CVD, and it is important that patients discuss their individual modifiable and nonmodifiable risk factors with their primary health care providers, as well as measures that may decrease these risks.

Pharmacists can screen for potential contraindications and drug nutrient interactions and make clinical recom-mendations tailored to patient needs. To ascertain the appropriateness of use, pharmacists should also encourage patients with comorbidities and those taking medications to discuss the use of supplements with their primary health care providers prior to using supplements and to keep an updated list of them. In addition, pharmacists can remind patients about the importance of limiting alcohol intake and smoking cessation, as well as the value of nutritional plans, such as the Dietary Approaches to Stop Hypertension plan and the Mediterranean diet, which align with the most recent recommendations from the AHA that may aid in lowering and/or preventing the risk of CVD.² When feasible, the implementation of individualized routine exercise pro-grams can also be beneficial in fostering overall CV health.

References
1. Heart disease facts. CDC. Updated October 14, 2022. Accessed January 8,2023. https://www.cdc.gov/heartdisease/facts.htm

2. Lichtenstein AH, Appel LJ, Vadiveloo M, et al. 2021 dietary guidance to improve cardiovascular health: a scientific statement from the Ameri-can Heart Association. Circulation. 2021;144(23):e472-e487. doi:10.1161/CIR.0000000000001031

3. Mishra S, Stierman B, Gahche JJ, Potischman N. Dietary supplement use among adults: United States, 2017-2018. NCHS Data Brief. 2021;(399):1-8.

4. Laffin LJ. Late-breaking science: changing how we prevent cardiovascular and renal disease. Presented at: American Heart Association Scientific Sessions 2022; November 5-6, 2022; Chicago, IL.

5. Laffin LJ, Bruemmer D, Garcia M, et al. Comparative effects of low-dose rosuvastatin, placebo, and dietary supplements on lipids and inflam-matory biomarkers. J Am Coll Cardiol. 2023;81(1):1-12. doi:10.1016/j.jacc.2022.10.013

6. Maki KC, Dicklin MR. Caution against rejecting all dietary supplements for LDL cholesterol reduction. J Am Coll Cardiol. 2023;81(1):13-15. doi:10.1016/j.jacc.2022.11.004

7. An P, Wan S, Luo Y, et al. Micronutrient supplementation to reduce cardiovascular risk. J Am Coll Cardiol. 2022;80(24):2269-2285. doi:10.1016/j.jacc.2022.09.048

8. Chow SL, Bozkurt B, Baker WL, et al. Complementary and alternative med-icines in the management of heart failure: a scientific statement from the American Heart Association. Circulation. 2023;147(2):e4-e30. doi:10.1161/CIR.0000000000001110

9. Khan MS, Khan F, Fonarow GC, et al. Dietary interventions and nutritional supplements for heart failure: a systematic appraisal and evidence map. Eur J Heart Fail.2021;23(9):1468-1476. doi:10.1002/ejhf.2278

About the Author

Yvette C. Terrie, BSPharm, RPh, is a consulting pharmacist and medical writer in Haymarket, Virginia.