Are Dietary Supplements Beneficial in Lowering Cholesterol?

SPORT Reflections and the Path Forward

Luke J. Laffin; Dennis Bruemmer; Steven E. Nissen


Eur Heart J. 2023;44(8):638-640. 

Americans spend almost 50 billion United States dollars (USD) annually on dietary supplements.[1] Estimates suggest the European dietary supplement market will reach 33.8 billion USD by 2027.[2] Although evidence of a beneficial impact on cardiovascular (CV) disease and its risk factors is limited at best, and non-existent for most supplements, consumers still choose to purchase these products. It is not surprising that patients gravitate towards supplements based on labelling that uses phrases such as 'Cholesterol's Natural Enemy', 'Supports Cardiovascular Health', 'Heart Health', 'Helps Support a Healthy Heart', and 'Healthy Cholesterol Formula' (Table 1).

The disconnect between ever-increasing supplement use and actual clinical evidence for benefit led us to perform the Supplements, Placebo, or Rosuvastatin Study (SPORT).[3] SPORT was a prospective randomized clinical trial conducted at the Cleveland Clinic Health system in the USA. One-hundred and ninety-nine primary prevention patients with elevated LDL-C and elevated 10-year risk of atherosclerotic CV disease were randomized to treatment with a low-dose statin (5 mg of rosuvastatin), placebo, or one of six dietary supplements for 28 days. The study's primary endpoint was the percent change in LDL-C with rosuvastatin compared first to placebo and then to each supplement in a hierarchical fashion (fish oil, cinnamon, garlic, turmeric, plant sterols, and red yeast rice). LDL-C was reduced by 37.9% (95% confidence intervals (CI): −42.1 to −33.6) in participants randomized to low-dose statin, which was superior to placebo and each of the studied supplements (P < 0.001 for all comparisons.) Secondary endpoints included changes in additional lipid parameters and hsCRP with the low-dose statin compared with placebo and each supplement, as well as similar comparisons between each supplement and placebo. Lipid biomarkers that were positively impacted by the low-dose statin were total cholesterol (−24.4%, 95% CI: −27.6 to −21.3, P < 0.001 for all comparisons) and serum triglycerides (−19.3%, 95% CI: −27.6 to −9.9, P < 0.05 for all comparisons.) No supplements demonstrated a beneficial impact on any lipid or inflammatory biomarkers compared with placebo. In fact, garlic raised LDL-C (+7.8%, 95% CI: 1.7–13.8, P = 0.01) and plant sterols lowered HDL-C (−7.1%, 95% CI: −13.1 to −1.1, P = 0.02).

The response to SPORT from the US supplement industry was predictable. The Council for Responsible Nutrition (CRN), a trade association paid to promote supplements, issued a press release criticizing the study.[4] Unfortunately, CRN appeared to have a lack of understanding of the basic study characteristics before commenting. When alerted to their misrepresentation of study characteristics, CRN withdrew certain criticisms.[5]

Much more importantly, countless positive responses to the publication of SPORT have come from clinicians in all corners of the world. We have received emails, text messages, and phone calls stating almost uniformly the same message, 'A large percentage of my patients take supplements with the notion that they will help with cholesterol lowering—often times in place of statins. I've tried to convince them otherwise but to no avail. Thank you for providing data I can share with them.'

As academic physicians, we strive to not only practice evidence-based medicine but produce evidence with rigorous, high-quality data. SPORT provides convincing data for clinicians, but a key question becomes how to implement these data into clinical practice in a way that is meaningful and compelling for individual patients. An easy start is making the waterfall plot of individual participant responses widely available to clinicians and patients (Figure 1). This clearly demonstrates that every participant randomized to rosuvastatin had significant LDL-C lowering and all other studied products were almost akin to the flip of a coin whether LDL-C would increase or decrease. Future trials assessing real-world implementation strategies are warranted.

Figure 1.

Individual participant percent change in LDL-C. All participants randomized to rosuvastatin demonstrated at least an 18.2% reduction in LDL-C and half of the participants saw a >40% decrease in LDL-C.

As one would expect, reactions to the SPORT results also included questions such as, 'What about lifestyle modifications?', 'Although not impacting biomarkers, would supplements impact cardiovascular outcomes?' and 'What about XYZ supplement?'

Answers to these questions are straightforward. First, it is never a question of medication or lifestyle, but rather the marriage of the two that produces the greatest impact in reducing future CV risk. Second, without a biomarker to suggest CV benefit, it would be ethically questionable to randomize participants at elevated CV risk (as were enrolled in SPORT) to supplements in place of well-studied and safe lipid lowering therapies. Third, we would be more than happy to discuss additional supplement trials, but we have no indication that a supplement manufacturer would put forward the effort and resources for such a study.

Notably, 11 days following the publication of SPORT, the United States Food and Drug Administration issued warning letters to seven companies for illegally selling dietary supplements that claim to cure, treat, mitigate or prevent CV disease or related conditions.[6] The warnings did not pertain to the specific supplement brands studied in the trial, but included supplements that contained red yeast rice and garlic.

SPORT studied supplements commonly perceived to have beneficial impacts on 'heart health' or 'cholesterol management'. However, we must not forget that supplement use is widespread for conditions beyond hyperlipidaemia. Drugstore aisles are littered with dietary supplements treating conditions as disparate as cognitive decline to hair loss. Generating evidence for their benefit, or lack thereof, is important given the limited oversight of supplement marketing by regulatory agencies. Particularly important to cardiologists, studies similar to SPORT should be pursued studying supplement effects in other highly prevalent CV risk factors such as obesity, diabetes, or hypertension.

Finally, mistrust of public health is increasing following the COVID-19 pandemic and health misinformation runs rampant. Operating within this ecosystem, it is our duty as clinicians to inform our patients, and the public, regarding health behaviours that demonstrate benefit or those that may be deleterious. SPORT serves this duty and reveals the beneficial impact of a low-dose statin, while refuting the notion that supplements provide benefits for 'cholesterol management 'or 'heart health.'