Lipid Luminations: Dietary Supplements or Statins for LDL-C Lowering

Introduction

More than half of adults in the United States report taking dietary supplements.¹ For example, some choose supplements in place of statins in hopes of lowering low density lipoprotein cholesterol (LDL-C) and consequently the risk of atherosclerotic cardiovascular disease (ASCVD).¹ Indeed Americans currently spend almost 50 billion US dollars annually on supplements for a spectrum of clinical disease states, and this amount is increasing.² High-quality data supporting the use of dietary supplements to decrease LDL-C levels and ASCVD risk is limited at best. Given the above factors, investigators at the Cleveland Clinic performed the Supplements, Placebo or Rosuvastatin Study (SPORT) to compare supplements commonly marketed for “heart health” to a low dose of rosuvastatin and placebo.³

Methods

SPORT was a single-center, prospective, randomized, single-blind clinical trial, evaluating the efficacy of a moderate-intensity statin, compared with placebo and with common dietary supplements.⁴ The study population consisted of 199 primary prevention patients, 40 – 75 years of age, with LDL-C between 70 and 189 mg/dL and a 10-year ASCVD risk between 5 and 20%. The primary endpoint was the percent change in LDL-C at 28 days for rosuvastatin 5 mg daily compared to the following in a hierarchical fashion: placebo, fish oil, cinnamon, garlic, turmeric, plant sterols, and red yeast rice extract. Secondary endpoints were the observed changes in other lipid biomarkers and hsCRP.

Results

Rosuvastatin 5 mg daily achieved a greater LDL-C percent reduction (-37.9%; 95% confidence interval (CI): -42.1 to -33.6%) compared with placebo and each supplement (p< 0.001 for all comparisons) at 28 days (Table 1). Among secondary outcomes, rosuvastatin demonstrated a significant percent reduction in total cholesterol (-24.4%; 95% CI: -27.6% to -21.3%) compared with placebo and each supplement (p < 0.001 for all comparisons), and in serum triglycerides (-19.3%; CI -27.6% to -9.9%, p < 0.05 for all comparisons). The change in hsCRP and HDL-C with rosuvastatin compared with placebo was not statistically significant. None of the supplements demonstrated a statistically significant decline in LDL-C levels compared with participants randomized to placebo. Interestingly, garlic increased the levels of LDL-C (+7.8% 95% CI: 1.7-13.8, p=0.01) and plant sterols decreased HDL cholesterol (-7.1%, 95% CI: -13.1 to -1.1, p=0.02), compared with placebo. Adverse event rates were similar among treatment groups, although numerically higher in the plant sterol and red yeast rice treatment groups.

Discussion

SPORT demonstrated the ability of a moderate-intensity statin to reduce LDL-C as well as other lipid biomarkers, compared to several popular dietary supplements. SPORT also offers evidence that supplements may not be effective in decreasing cholesterol, and some may have negative impacts on lipid biomarkers. Prior clinical trials in primary prevention populations demonstrate that statins not only reduce clinically relevant biomarkers, but also reduce the incidence of ASCVD - there are no such data for dietary supplements.^5,6 

Clinicians can use data from SPORT to better educate patients who may think that they can achieve significant LDL-C reductions with dietary supplements, rather than a statin. Using the below waterfall plot (Figure 1) of the individual participant response may help with patient education. All participants randomized to statin had at least an 18% decrease in LDL-C and over half had a 50% reduction, whereas supplements and placebo showed inconsistent percentage changes.

SPORT has limitations including a short time period of treatment and that it reflects only the specific brand of supplements studied. For example, there are other data demonstrating certain formulations of red yeast rice can significantly decrease LDL-C levels, which was not observed in SPORT.⁴ However this reflects the reality of supplements, as formulations are variable without any guarantee of consistency for the consumer.

Conclusion

Rosuvastatin 5 mg daily is more effective than placebo and each studied supplement in decreasing LDL-C. There was no difference in LDL-C reduction with fish oil, cinnamon, garlic, turmeric, plant sterols and red yeast rice when compared to placebo.

Dr. Mejia Morales has no financial relationships to disclose. Dr. Laffin has received consulting fees from Medtronic, Eli Lilly, and Crispr Therapeutics. He has received research funding from Astrazeneca, royalties from Belvoir Media Group and Elsevier. He has ownership interest in LucidAct Health and Gordy Health and is a member of Meneralys Therapeutics’ advisory committee. 

References

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3. Grand View Research. North America Dietary Supplements Market Size, Share & Trends Analysis Report By Ingredient, By Form, By Application, By End-User, By Distribution Channel, By Region, And Segment Forecast, 2021-2028. Accessed on Feb 20, 2023. 2023. https://www.grandviewresearch.com/industry-analysis/north-america-dietary-supplements-market
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