Dietary Supplements for Heart Health: What the Science Actually Shows
- Dr. Mike
- Jan 23
- 9 min read
Updated: Jan 26
Summary
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Outline
This document is provided for educational and informational purposes only and is not intended as, nor should it be construed as, medical advice. The information contained herein is not a substitute for professional medical advice, diagnosis, or treatment. Always consult your physician or other qualified healthcare provider before starting, stopping, or changing any medication, supplement, or treatment plan. |
The $30 Billion Question: Do Supplements Really Work?
Can dietary supplements available at the grocery store or boutique supplement shop help or harm? Are they better or safer than the chemicals from pharmaceutical companies? These are certainly important questions, as Americans spend at least $30 billion annually (Ronis, 2018).
Understanding the Evidence: 27 Supplements, 884 Clinical Trials
An (2022) took an exhaustive look at 27 different dietary supplements and their potential influences on traditional cardiovascular risk factors and outcomes in a meta-analysis that started by considering 7,302 articles, ultimately including 751 articles that covered 884 randomized, controlled trials which involved a total of 883,627 participants. Given an evaluation of this complexity, they found interesting signals of potential benefit and harm, but importantly were also careful to look for evidence of publication bias and variation between studies. If there is concern for publication bias, even if there is a suggestion of a clinically relevant finding, the presence of bias raises concern of the validity and applicability of the study. Similarly, if there is evidence of too much variation or heterogeneity between the studies, that raises concern about how broadly the findings can be applied and uncertainty about how the findings apply to the person buying the supplement. Lastly, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was performed to indicate a level of confidence in each study, with scoring being very low, low, moderate, and high. Performing GRADE is nuanced and is at risk of overly simplifying a complex evaluation, such as downgrading a quality observational trail and upgrading a poorly designed randomized, controlled trial. Nonetheless, GRADE remains an important tool in performing meta-analyses.
The supplements evaluated by An (2022) are shown in Table 1 and include common supplements such as omega-3 fatty acid, folic acid, and coenzyme Q10. The cardiovascular disease risk factors and outcomes evaluated include blood pressure, cholesterol, and cardiovascular mortality (Table 2). Due to the nature of the meta-analysis and the incorporated studies, not every supplement was evaluated against every cardiovascular risk factor or outcome. Importantly, the supplemental materials provided by An (2022) provided a thorough listing of supplements and dosages used in each trial.
α-lipoic acid | Genistein | omega-6 fatty acid |
Anthocyanin | Hesperidin | omega-9 fatty acid |
β-carotene | Isoflavone | Quercetin |
Catechin | L-arginine | Resveratrol |
Coenzyme Q10 | L-citrulline | Selenium |
Curcumin | Lycopene | Vitamin C |
Flavanol | Magnesium | Vitamin D |
Flavonoid | Melatonin | Vitamin E |
Folic acid | omega-3 fatty acid | Zinc |
Table 1. 27 Dietary Supplements
Systolic/Diastolic Blood Pressure | Cholesterol (Total, LDL-C, TG, HDL-C) |
|
Hemoglobin A1c | Fasting Blood Glucose | Fasting Blood Insulin |
All-Cause Mortality | Cardiovascular Disease Mortality | Stroke |
Arrhythmia | Coronary Artery Disease | Type 2 Diabetes |
Table 2. Cardiovascular Risk Factors and Outcomes
In going from clinical research to the actual clinic, it is essential to determine not only if something is rigorously significant, but also clinically relevant. The work by An (2022) appropriately focused on identifying statistical significance. To ensure findings were clinically relevant, I chose to focus on the dominant cardiovascular risk factors of systolic blood pressure, LDL-C, fasting blood glucose, hemoglobin A1c, while including all cardiovascular outcomes. This blog post would have been far longer if I listed all of the associations which were insignificant and all of the associations which were not tested. For those details, I direct the reader to the source article listed in the references. Again, I focused on those findings which were felt to be significant statistically. My process in evaluating the data was as follows:
Include only those evaluations with significant confidence intervals, monitoring for potentially clinically irrelevant findings.
Screening for heterogeneity, downgrading those studies with heterogeneity well above 0.50.
Screening for publication bias, downgrading those studies with Egger’s Test values < 0.10.
Focus on findings with moderate or high GRADE scores, while those of low or very low are seen as hypothesis-generating and less suitable for clinical application.
Certainly, going through an evaluation such as this may exclude useful data, such as genistein possibly having a role with improving systolic blood pressure and LDL-C. However, genistein data related to blood pressure are so limited a thorough evaluation of heterogeneity and bias could not be performed. Consequently, I would not recommend widespread use of the supplement and would recommend waiting for more data. As for genistein’s effect on LDL-C, the study was downgraded in GRADE due to marked heterogeneity among trials and marked imprecision.
Which Supplements for Heart Health Show Potential Promise?
The supplements α-lipoic acid (-6.02 mmHg [-9.73 to -2.31]) and L-citrulline (-3.10 mmHg [-5.25 to -0.95]) scored well in terms of their effects on lowering systolic blood pressure, followed by L-arginine (-4.51 mmHg [-6.64 to -2.37]). Importantly, the heterogeneity evaluation of the three supplements was reasonable, though worse for L-arginine, raising concern about how broadly the findings can be applied to those interested in taking L-arginine. Importantly, a typical guideline to determine if a medicine is effective in treating high blood pressure is to see a systolic blood pressure reduction of at least 5-10 mmHg. Consequently, even though L-citrulline and L-arginine do appear to have significant impacts on blood pressure, the decrease is not clinically relevant and impact of α-lipoic acid may be barely useful.
Folic acid was the only supplement evaluated which showed a signal for lowering LDL-C (-5.94 mg/dL [-7.74 to -4.14]), though only 297 patients were treated with folic acid when evaluating for influences on LDL-C, which raises doubt in how broadly the data can be applied. An important caveat about data related to folic acid is that some studies were conducted in countries without folic acid fortification and which may be why those countries see greater benefit from folic acid treatment than those countries with traditional folic acid fortification (Jenkins, 2021).
The work by An (2022) suggests the cardiovascular mortality absolute risk reduction (ARR) for omega-3 fatty acids is 0.4%. Put another way, 250 people would need to take omega-3 fatty acids to prevent one death from a cardiovascular cause. This is a very large number and suggests a very limited role for omega-3 fatty acids. Similarly, omega-3 has a coronary heart disease absolute risk reduction of 0.6%, indicating 167 people would need to be treated with omega-3 fatty acids to prevent one coronary heart disease event. Consequently, while there does appear to be a small, significant effect of omega-3 fatty acids, there may be little clinical relevance with such high numbers needing to be treated. Of note, most of the work on omega-3 fatty acids referenced utilized a combination of DHA and EPA, which is important, because DHA may actually be harmful due to it potentially raising LDL-C. It appears the isolated EPA-only agent may provide the greatest cardiovascular benefit. EPA acts as a free-radical scavenger and an antioxidant, as well as improving mitochondrial function. Once EPA-only agents are readily available, such as the ethyl ester of eicosapentaenoic acid (EPA), referred to as icosapent ethyl (US) or ethyl icosapentate (Japan), that is starting to appear on the market, we may get a better understanding of the role of EPA-only agents on cardiovascular health and mortality.
In An (2022), coenzyme Q10 appeared to improve all-cause mortality, though the association was downgraded due to imprecision. The ARR was 2.8%, indicating 36 people would need to take coenzyme Q10 to prevent one death from any cause. By comparison, a study of statins for secondary prevention showed the number needed to treat (NNT) was 125 for death from any cause (Byrne, 2022) and statins are considered standard of care. A study of coenzyme Q10 in heart failure showed interesting signs of improved all-cause mortality with RR 0.64, ARR 4.0%, and NNT 25 (Xu, 2024). Coenzyme Q10 acts as a free-radical scavenger, an antioxidant, and participates in mitochondrial energy transfer. Importantly, there was a fairly wide range of dosing from 10mg to 100mg three times per day, with the dominant trial for mortality utilizing 100mg three times per day.
Magnesium may have beneficial effects in lowering blood pressure (Argeros, 2025; An, 2022). Importantly, the effects on systolic blood pressure were modest, with Argeros et. al (2025) showing a mean 2.8 mmHg reduction (95% CI -4.32 to -1.29) and An (2022) showing a 4.9 mmHg reduction (95% CI -8.04 to -1.78). Consequently, neither study is able to demonstrate a clinically relevant reduction in blood pressure. Furthermore, both meta-analyses suggested the findings may be weakened by significant heterogeneity, raising a question as to how broadly the findings can be applied. Perhaps the findings would be more significant if the baseline magnesium levels were normalized prior to enrollment?
Supplements to Avoid or Question
The work by An (2022) did not find an association between vitamin D and cardiovascular outcomes, supported by a meta-analysis of Mirza (2024). Lastly, β-carotene was suggested as causing harm in terms of mortality and stroke, though GRADE was low for these outcomes so likely should be seen as hypothesis-generating.
Important Safety Considerations
Importantly, taking dietary supplements is not without risks. Risks are most often associated with fat-soluble vitamins (A, D, E, and K), though polyneuropathy can be associated with excessive vitamin B6 (Ronis, 2018). There are potential interactions to be aware of between dietary supplements and prescription medicines, as well as between different dietary supplements (Ronis, 2018). Interestingly, while genistein has potential for improving blood pressure and LDL-C, as mentioned earlier, the purified isoflavones including genistein have been associated with androgen inhibition, reduced testis size, endometriosis, and uterine hypertrophy (Ronis, 2018). Furthermore, the US Preventive Services Task Force (USPTF) recommends avoiding β-carotene due to potential for harm and avoiding vitamin E due to lack of benefit for the prevention of cardiovascular disease or cancer (Mangione, 2022). The USPTF also indicated there is inadequate data to suggest there is benefit from taking either a multivitamin or individual nutrients to prevent cardiovascular disease or cancer (Mangione, 2022). For instance, the COSMOS (Cocoa Supplement and Multivitamin Outcomes Study) with 21,442 participants found no effect on all-cause mortality from multivitamins after a median of 3.6 years follow-up (Mangione, 2022). Work by Jenkins (2021) corroborates that multivitamins, calcium, and vitamins C and D lack cardiovascular benefit and lack all-cause mortality benefit.
Quality Control: The USP Verified Mark
It is vital to be aware that dietary supplements are not regulated by the US Food and Drug Administration (US FDA; Ronis, 2018). As a result, there is no guarantee that the dietary supplement people purchase contains the ingredient on the front label and no guarantee that it is available in a form that is able to be used by the body. If the only form of validation available is data provided by the manufacturer, it would be wise to have a healthy skepticism and seek truly independent verification. Such an option exists for many dietary supplements and is provided by the US Pharmacopeia (USP), as the USP applies a “USP Verified Mark”, shown below (Figure 1). Here is a link for USP Verified dietary supplements. The USP Verified Mark indicates the product contains the ingredient on the label, does not contain specified contaminants, complies with US FDA good manufacturing practices, and will be available to the body when ingested.
Figure 1. USP Verified Mark
The Bottom Line: Food Over Supplements
In summary, after reviewing 27 dietary supplements for heart health, An (2022) found a number of interesting trends worth monitoring, such as potential benefits from α-lipoic acid, folic acid, EPA omega-3 fatty acids, and coenzyme Q10. Nonetheless, professional organizations such as the American Heart Association continue to recommend healthy food choices over dietary supplements, encouraging eating whole food, such as following a Mediterranean Diet or pescatarian diet. Nutrients obtained from whole food continue to be superior to manufactured or processed supplements (Lichtenstein, 2021; Rock, 2020). Eat a colorful variety of vegetables, fruits, whole grains, fish, nuts, and olive oil daily while minimizing processed foods.
References
An P, et al. Micronutrient Supplementation to Reduce Cardiovascular Risk. J Am Coll Cardiol. 2022;80(24):2269-2285.
Argeros Z, et al. Magnesium Supplementation and Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Hypertension. 2025;82(11):1844-1856.
Byrne P, et al. Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment: A Systematic Review and Meta-analysis. JAMA Intern Med. 2022;182(5):474-481.
Jenkins DJA, et al. Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment: JACC Focus Seminar. J Am Coll Cardiol. 2021;77(4):423-436.
Lichtenstein AH, et al. 2021 Dietary Guidance to Improve Cardiovascular Health: A Scientific Statement From the American Heart Association. Circulation. 2021;144:e472–e487.
Mangione CM, et al. Vitamin, Mineral, and Multivitamin Supplementation to Prevent Cardiovascular Disease and Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;327(23):2326-2333.
Mirza AM, et al. Effect of vitamin D supplementation on cardiovascular outcomes: an updated meta-analysis of RCTs. Ann Med Surg. 2024;86(11):6665-6672.
Rock CL, et al. American Cancer Society Guideline for Diet and Physical Activity for Cancer Prevention. CA Cancer J Clin. 2020;70:245-271.
Ronis MJJ, et al. Adverse Effects of Nutraceuticals and Dietary Supplements. Annu Rev Pharmacol Toxicol. 2018;58:583-601.
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