In brief

Dietary supplements are commonly used by individuals with indications for lipid-lowering therapy.¹ However, their effectiveness in reducing low-density lipoprotein cholesterol (LDL-C) has not been sufficiently studied, especially when compared with statins.¹ A single-center, prospective, randomized, single-blind trial was conducted to compare the efficacy of a low-dose statin, rosuvastatin, with placebo and 6 common supplements in impacting lipid and inflammatory biomarkers.¹ The study provides evidence for the superior efficacy and similar safety profile of rosuvastatin compared with placebo and dietary supplements in LDL-C reduction.¹

Background

The use of dietary supplements has drastically increased over the years with an estimated 150 million users in the United States (US).² Dietary supplements are marketed and promoted for their ability to improve health, prevent diseases, and treat a variety of illnesses ranging from hypertension to cancer.² However, the marketing and advertisement of these supplements are regulated by the Federal Trade Commission, rather than the Food and Drug Administration (FDA), under the provisions of the Dietary Supplement Health and Education Act (DSHEA).² Hence, governmental oversight remains limited with insufficient evidence of the efficacy and safety of these dietary supplements.²

The use of dietary supplements is very common among patients with proven or suspected cardiovascular (CV) risk.³ Many patients with hypercholesterolemia have reported using cholesterol health supplements instead of prescription medications like statins, believing that they are safe and equally or more effective than statin medications.^3,4 These concerns along with misinformation about prescription drugs may drive people away from using statins which are relatively well-regulated, inexpensive, safe, potentially life-saving, and have decades of supporting evidence.¹ Since the prevalence of CV diseases and risk factors is projected to increase over the following years, studies that examine the effect of dietary supplements on lipid and inflammatory biomarkers are needed.^1,5 The Supplements, Placebo, or Rosuvastatin Study (SPORT) was conducted to assess the efficacy of commonly used dietary supplements compared with low-dose statin and placebo on reducing lipid and inflammatory biomarkers in patients with an increased 10-year atherosclerotic cardiovascular disease (ASCVD) risk.¹

Methodology

The SPORT study was a single-center, prospective, randomized, single-blind clinical trial, comparing the 6 common dietary supplements with rosuvastatin and placebo among patients with an increased 10-year risk for ASCVD.¹

Patients aged 40-75 years with no history of ASCVD, an LDL-C of 1.8mmol/L-4.9mmol/L, and a 10-year ASCVD risk between 5% and 20%, not receiving statins, other prescription lipid-lowering therapy, or dietary supplements were included.¹ Patients were randomized in a 1:1:1:1:1:1:1:1 ratio to receive one of the supplements (fish oil 2,400mg, cinnamon 2,400mg, garlic with allicin 5,000μg, turmeric curcumin with bioperine 4,500mg, plant sterols 1,600mg, or red yeast rice 2,400mg), rosuvastatin 5mg, or placebo.¹

The primary endpoint assessed was the percent change in LDL-C from baseline to day 28 for rosuvastatin 5mg daily compared hierarchically with placebo, followed by fish oil, cinnamon, garlic, turmeric, plant sterols, and red yeast rice.¹ Secondary endpoints included total cholesterol, serum triglycerides, and high-density lipoprotein cholesterol (HDL-C) for each study group compared with rosuvastatin as well as the percent change in lipid and inflammatory biomarkers of each supplement compared with placebo.¹ A total of 1,003 patients were screened, of whom 199 patients were randomized.¹

Results

Of the 190 patients who completed the study, 24 were allocated to receive rosuvastatin, 23 to placebo, 22 to fish oil, 24 to cinnamon, 25 to garlic, 25 to turmeric, 24 to plant sterols, and 23 to red yeast rice.¹ In those who were randomized, the mean age was 64.4 ± 6.4 years, and most patients (59%) were women.¹

Rosuvastatin demonstrated a significantly greater LDL-C percent reduction from baseline compared with placebo, fish oil, cinnamon, garlic, turmeric, plant sterols, and red yeast rice (p<0.001).¹ The mean LDL-C percent reduction from baseline to day 28 in patients receiving rosuvastatin was -37.9% (95% CI: -42.1 to -33.6) (figure 1).¹ Participants receiving rosuvastatin had a 19.3% reduction in serum triglycerides (95% CI: -27.6 to -9.9), which was the greatest reduction among all other groups (p<0.05) (figure 2).¹ Similarly, the percent reduction in total cholesterol was significantly lower in the rosuvastatin group compared with the placebo and supplements groups.¹ At day 28, the mean percent reduction in total cholesterol was 24.4% (95% CI: -27.6 to -21.3).¹ Compared with placebo, none of the dietary supplements demonstrated a meaningful reduction in LDL-C, while garlic was associated with a 7.8% increase in LDL-C (95% CI: 1.7-13.8; p=0.01).¹

Rosuvastatin had a similar safety profile as placebo and the supplements tested.¹ Adverse events occurred in 16% of patients receiving rosuvastatin compared with those receiving placebo (16%), fish oil (13%), cinnamon (12%), garlic (20%), turmeric (16%), plant sterols (28%), and red yeast rice groups (28%).¹ The rates of adverse events were comparable in all groups, although numerically higher in patients receiving plant sterols or red yeast rice.¹ There were no serious adverse events in the rosuvastatin group compared with one deep venous thrombosis event that occurred in the placebo group and one liver adenocarcinoma event that occurred in the fish oil group.¹ There were no significant changes in the results of liver function tests, estimated glomerular filtration rate (eGFR), or blood glucose with rosuvastatin (table 1).¹

Discussion 

The SPORT demonstrated a greater LDL-C reduction and an improvement in total cholesterol and serum triglycerides over the 28-day study period with rosuvastatin than with placebo, fish oil, cinnamon, garlic, turmeric, plant sterols, and red yeast rice in patients with an LDL-C >70mg/dL and an increased 10-year ASCVD risk.¹ The LDL-C improvements observed with rosuvastatin are in accordance with prior findings.⁶ None of the dietary supplements marketed or promoted for “cholesterol health” assessed in this study led to a significant reduction in LDL-C or an improvement in lipid biomarkers compared with rosuvastatin or placebo.¹ These results support data from other studies on supplements and cholesterol health. In a meta-analysis including over 2 million individuals, dietary supplements did not improve CV outcomes or mortality.⁷ A review published by the US Preventive Services Task Force also suggested that vitamin and mineral supplementation were associated with little to no benefit in preventing CV diseases.⁸ Furthermore, other meta-analyses have demonstrated that cinnamon and turmeric do not have any significant effect on LDL-C.^9,10 Although plant sterol is included in the 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) Guidelines as an LDL-C-lowering option, its efficacy has been considered controversial with a possibility of being atherogenic.^11,12 This is in stark contrast to the large amount of data produced in various meta-analyses on the benefits of statins on CV morbidity and mortality.¹¹ Studies have shown that over the span of only 5 years, each additional mmol/L reduction in LDL-C from statin medications led to a 22% reduction in major vascular events.¹¹ Major coronary events also reduced by 23%, coronary artery disease deaths by 20%, total stroke by 17%, and total mortality by 10%.¹¹ Furthermore, the 2019 ESC/EAS Guidelines also stated that poor responses to statin are attributed to poor compliance and patients’ genetic backgrounds.¹¹

Since the DSHEA do not classify dietary supplements as drugs, the FDA’s jurisdiction in overseeing the compliance of good manufacturing practices (GMP) has been severely limited.^1,2 Consumers may be unaware of the potential harm of dietary supplements.² There have been many cases of supplements with microbial contamination, heavy metal contamination, and the addition of unapproved prescription ingredients.^1,13,14 Dietary supplements have also been shown to interact with the cytochrome system and impact the metabolism of prescription drugs which may be harmful.^1,15 It has been suggested that adverse events related to dietary supplements contribute to approximately 23,000 emergency department visits in the US every year.¹⁶

Patient preferences for non-statin alternatives are often multifactorial, but it is often due to statin-associated toxicities like hepatotoxicity, muscle symptoms, and neurological side effects.¹ However, the current study has shown rosuvastatin to be safe, whilst significantly reducing LDL-C, which supplements that are often marketed for cholesterol control were unable to induce.⁴

Conclusion

In conclusion, rosuvastatin is effective in reducing LDL-C and has a safety profile comparable to placebo and the supplements assessed.¹ None of the supplements demonstrated a significant reduction in LDL-C, lipids, nor other inflammatory biomarkers suggestive of CV benefit when compared with rosuvastatin or placebo, contrary to the cholesterol health claims marketed by supplement manufacturers.¹ It is important for patients to be educated on the lack of benefit of these supplements on key CVD risk factors.¹