Analysis of Monacolins and Berberine in Food Supplements for Lipid Control: An Overview of Products Sold on the Italian Market

Abstract

The use of dietary supplements for the prevention and management of diseases associated with excess of lipids is spreading in Western countries. Supplements containing red yeast rice (RYR) and extracts from Berberis species, characterized, respectively, by the active compounds monacolin K (MK) and berberine (BBR), are sold in pharmacies as over the counter medicines (OTC) and in regular markets without the need of medical prescription and medical surveillance. However, MK is chemically identical to lovastatin, a drug commonly used to treat hypercholesterolemia, and is characterized by the same mechanism of action, pharmacokinetic profile and toxicity. On the other hand, although BBR-containing supplements are considered to be well-tolerated and safe, they frequently show poor standardization of active ingredients, and this could lead to lack of effects. In this work, with the aim to give an overview on the potency of RYR- and BBR-containing supplements available on the Italian market, we analyzed a pool of supplements bought from both local pharmacies and markets. Results confirm the data already published by other authors, showing scarce standardization of bioactives and discrepancy between the doses of bioactives reported by the manufacturers and the amounts resulting from analysis of the same products. Overall, our data represent a further proof that a strict legislation regulating the production and marketing of dietary supplements and a close monitoring of these products by food and drug regulatory organs is mandatory.

Red Yeast Rice for the Improvement of Lipid Profiles in Mild-to-Moderate Hypercholesterolemia: A Narrative Review

“…RYR supplements differ widely in their monacolin K content, resulting in a daily dose range of approximately 0.1–14.5 mg [ 38 , 39 , 40 ]. This is partly because the relative abundances of monacolin K and other monacolin subtypes in RYR, including monacolins J, L, and X, are affected by the fermentation conditions and yeast strain used during their production [ 30 , 39 , 40 ].…”

“…RYR supplements differ widely in their monacolin K content, resulting in a daily dose range of approximately 0.1–14.5 mg [ 38 , 39 , 40 ]. This is partly because the relative abundances of monacolin K and other monacolin subtypes in RYR, including monacolins J, L, and X, are affected by the fermentation conditions and yeast strain used during their production [ 30 , 39 , 40 ]. In addition, RYR contains non-monacolin components, including sugars (25–73% mainly starch), proteins (14–31%), water (2–7%), fatty acids (1–5%), and other bioactive components such as pigments, sterols, isoflavones, and citrinin (discussed below) [ 5 , 17 ].…”

Dietary Habits and Musculoskeletal Pain in Statin and Red Yeast Rice Users: A Pilot Study

“…There were no statistically significant differences by gender and approximately two-thirds of the subjects were women in the group CYP3A4 and MON-K, while in the NO-CYP3A4 users were close to one-third. Menopausal state was present in 71.4% of CYP3A4 women, 85.7% of the NO-CYP3A4 and 45.4% of MON-K. Other drugs % Other lipid lowering 9.5 (1) 21.0 (1) 0 0.130 Hormones 4.8 (2) 10.5 (2) 18.7 (3) 0.351 BP lowering 57.1 (4) 36.8 (5) 18.7 (6) 0.076 Anti-platelets/anti-coagulant 23.8 (7) 26.3 (8) 0 0.099 Glucose lowering 23.8 (9) 15.9 (10) 0 0.134 Anti-inflammatory/analgesic % Oral drugs 42.8 (11) 42.1 (11) 18.8 (11) 0.245 Topical 33.3 (12) 36.8 (12) 31.2 (12) 0.939 Nutraceuticals % 0 5.2 (13) 87.5 (14) <0.001 CYP3A4: volunteers in treatment with lovastatin, atorvastatin or simvastatin; NO-CYP3A4: volunteers in treatment with rosuvastatin or pravastatin; MON-K: volunteers in treatment with monacolin K (red yeast rice, RYR); SBP: systolic blood pressure; DBP: diastolic blood pressure; HR: heart rate; Delta-CHOL: Cholesterol variation after treatment. (1) ezetemibe; (2) levothyroxine; (3) levothyroxine, norethisterone acetate; (4) amlodipine, atenolol, bisoprolol, candesartan, irbesartan, mesartan, metoprolol tartrate, nebivolol, rampiril, perindopril, valsartan, zofenopril calcium salt; (5) atenolol, bisoprolol, doxazosin, enalapril, rampiril, valsartan; (6) rampiril, olmesartan; (7) apixaban, clopidogrel, digitalis glycoside; (8) clopidogrel, acetylsalicylic acid; (9) dulaglutide, insulin, metformin; (10) metformin; (11) tapentadol, cortisone; (12) cortisone; (13) berberine, polyunsaturated ω-3 fatty acids; (14) policosanols, berberine...…”

“…Although citrinin (CIT), a nephrotoxic and hepatotoxic mycotoxin, is produced by Monascus spp., it has been reported that dietary supplements contained CIT below the established limit of detection [8]. On the other hand, monacolin K is often associated with berberine in commercial nutraceutical, but scarce standardization and discrepancy between the doses of bioactive molecules reported by the manufacturers and the amounts resulting from analysis of the same products were reported [9]. The European Food Safety Authority (EFSA) Panel on Food Additives and Nutrient Sources added to Food (ANS) in 2018 concluded that exposure to monacolin K from RYR could lead to severe adverse effects on musculoskeletal system [10].…”

Development of a novel human triculture model of non-alcoholic fatty liver disease and identification of berberine as ameliorating steatosis, oxidative stress and fibrosis

“…Berberis vulgaris grows in vast areas of Asia, America, and Europe and it is well known in Iran because its dried fruits are widely used as a food additive in culinary dishes ( Fouladi, 2012 ). Berberine is also sold in pharmacies and stores as over-the-counter supplements ( Marcheluzzo et al, 2021 ). Berberine has been shown to possess anti-inflammatory and anti-oxidative effects ( Zhou et al, 2008 ; Jeong et al, 2009 ; Rafiei et al, 2017 ; Rafie et al, 2018 ), with reported efficacy in preventing the progression of NAFLD in preclinical ( Sun et al, 2009 ; Zhang et al, 2016 ; Luo et al, 2019 ) and clinical studies ( Yan et al, 2015 ; Wei et al, 2016 ) by modulating multiple metabolic mechanisms and lowering inflammatory responses ( Zhu et al, 2016 ).…”