A network meta-analysis on the comparative effect of nutraceuticals on lipid profile in adults

It is estimated that 2.6 million deaths worldwide can be attributed to hypercholesterolemia. The main reason for non-adherence to statin therapy are the statin-associated muscle symptoms (including nocebo/drucebo effect). In this case, apart from ezetimibe, nutraceuticals are prescribed. We aimed to assess the comparative efficacy of different nutraceuticals in terms of lowering low density lipoprotein cholesterol (LDL-C) and improving lipid profile. Electronic and hand searches were performed until February 2021. The inclusion criteria were the following: (1) randomized trial with any of the reportedly LDL-C lowering nutraceutical: artichoke, berberine, bergamot, garlic, green tea extract, plant sterols/stanols, policosanols, red yeast rice (RYR), silymarin or spir-ulina. (2) outcome either LDL-C (primary outcome), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) or serum triglycerides (TG). Random effects network meta-analysis (NMA) was performed to rank the effect of each intervention using frequentist approach. Finally, a total of 131 trials enrolling 13,062 participants were included. All analysed nutraceuticals except for policosanols were more effective in lowering LDL-C (-1.21 [-46.8 mg/dL] to-0.17 [-6.6 mg/dL] mmol/l reduction) and TC (-1.75 [-67.7 mg/dL] to-0.18 [7 mg/dL] mmol/l reduction) than placebo/no intervention. The most effective approaches in terms of LDL-C-and TC-lowering were bergamot and RYR (-1.21 [-46.8 mg/dl] and-0.94 [-36.4 mg/dl] mmol/l) reduction respectively. In conclusion, bergamot and RYR appear to be the most effective nutraceuticals in terms of LDL-C and TC reduction. Evidence for bergamot effect was based on relatively small study group and may require further investigations. Policosanols have no effect on the lipid profile.

Automated summary

Hypercholesterolemia is responsible for an estimated 2.6 million deaths worldwide. Non-adherence to statin therapy is mainly due to statin-associated muscle symptoms. Nutraceuticals are prescribed as an alternative, and this study aimed to assess their efficacy in lowering LDL-C and improving lipid profile.