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Cited by 110Lipoproteins and Cardiovascular HealthNatural Products and Biological ResearchComplementary and Alternative Medicine Studies

Nutraceuticals in the Management of Dyslipidemia: Which, When, and for Whom? Could Nutraceuticals Help Low-Risk Individuals with Non-optimal Lipid Levels?

Open access
Cicero, Arrigo F. G., Fogacci, Federica, Stoian, Anca Pantea, Vrablik, Michal, Al Rasadi, Khalid, Banach, Maciej, Toth, Peter P., Rizzo, Manfredi·2021·Current Atherosclerosis Reports
DOI 10.1007/s11883-021-00955-yPMC PMC8332568
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Abstract

Purpose of Review: The aim of this review is to summarize the available clinical efficacy and safety data related to the most studied and used lipid-lowering nutraceuticals. Recent Findings: A growing number of meta-analyses of randomized clinical trials supports the effectiveness and tolerability of some lipid-lowering nutraceuticals such as red yeast rice, plant sterols and stanols, soluble fibers, berberine, artichoke extracts, bergamot polyphenol fraction, garlic, green tea, and spiruline. No significant safety concern has been raised for the use of such products. Association of more lipid-lowering nutraceuticals and of some nutraceuticals with lipid-lowering drugs has been tested as well. Summary: Current evidence suggests that some clinically tested lipid-lowering nutraceuticals could be safely used to improve plasma lipid levels in subjects affected by mild-to-moderate dyslipidaemia with low cardiovascular risk.

AI snapshot

Written from the paper’s full text.

TL;DR

This review summarizes clinical efficacy and safety data for the most studied lipid-lowering nutraceuticals, concluding that some can safely improve plasma lipids in low-CV-risk subjects with mild-to-moderate dyslipidemia. It stresses that nutraceuticals should not replace guideline-indicated drugs and that primary-prevention outcome evidence is still lacking.

Key findings

  • Plant sterols/stanols: a meta-analysis of 124 studies (201 strata) found an average LDL-C reduction of 12%, increasing up to intakes of approximately 3 g/day; combined with statins, they produced an additional LDL-C reduction of 0.30 mmol/L (95% CI −0.35 to −0.25) versus statins alone.
  • Red yeast rice (RYR): a meta-analysis of 20 RCTs found LDL-C reduction of 1.02 mmol/L (39.4 mg/dL) versus placebo, not different from moderate-intensity statins; in a Chinese trial of 1445 patients aged 65–75 with prior myocardial infarction followed for a mean of 4 years, RYR reduced CHD risk by 31.0% (p = 0.04), all-cause mortality by 31.9% (p = 0.01), and stroke by 44.1% (p = 0.04). A safety meta-analysis of 53 RCTs (8535 subjects) found monacolin K was not associated with increased muscle-related side effects (OR = 0.94, 95% CI 0.53–1.65) and was associated with reduced non-muscle-related side effects (OR = 0.59, 95% CI 0.50–0.69) and serious adverse events (OR = 0.54, 95% CI 0.46–0.64).
  • Berberine: a meta-analysis of 27 clinical studies with 2569 participants found LDL-C −0.65 mmol/L (25.14 mg/dL), TG −0.39 mmol/L (34.5 mg/dL), and HDL-C +0.07 mmol/L (2.71 mg/dL); effects appeared additive to statins.
  • Other agents: artichoke extract in a meta-analysis of 9 RCTs (702 subjects) reduced TC by 17.6 mg/dL, LDL-C by 14.9 mg/dL, and TG by 9.2 mg/dL; omega-3 EPA/DHA in a meta-analysis of 47 RCTs (16,511 participants) at an average 3.25 g/day reduced TG by 14% (−0.34 mmol/L); spirulina in a meta-analysis of 7 trials reduced LDL-C by 1.1 mmol/L, TC by 1.2 mmol/L, TG by 0.5 mmol/L, and increased HDL-C by 0.16 mmol/L.

Methods

  • Narrative review of available clinical efficacy and safety data for the most studied lipid-lowering nutraceuticals, classified by mechanism: inhibitors of intestinal cholesterol absorption, inhibitors of hepatic cholesterol synthesis, enhancers of LDL-C excretion, and mixed-mechanism agents.
  • Evidence base consists of meta-analyses of randomized clinical trials and individual randomized trials, including studies of nutraceutical combinations and combinations with lipid-lowering drugs; no primary patient data were collected.
  • No systematic search strategy, inclusion criteria, or formal risk-of-bias assessment is described in the text.

Limitations

  • The paper states there are still no outcome studies proving that nutraceuticals can prevent CVD morbidity or mortality in a primary prevention setting; clinical relevance, long-term maintenance of effects, and impact on CVD risk remain concerns.
  • The paper states most nutraceutical combinations have been tested only in a single study/RCT, some tested combinations contained underdosed components, and results have not been confirmed, so recommendations cannot be made.
  • Evident from the text: this is a narrative review without a described systematic search or quality appraisal, and many conclusions rely on heterogeneous meta-analyses and trials, with efficacy and safety often specific to particular products, doses, or populations.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1007/s11883-021-00955-y

Cites

110 of 110 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 60 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Plant sterols and stanols are safe.

    “A large meta-analysis of 124 studies (201 strata) concluded that the PS are safe and that their LDL cholesterol-lowering effect continues to increase up to intakes of approximately 3 g/day with an average LDL-C reduction of 12% [12].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] Ras RT, Geleijnse JM, Trautwein EA. LDL-cholesterol-lowering effect of plant sterols and stanols across different dose ranges: a meta-analysis of randomised controlled studies. Br J Nutr. 2014;112(2):214–9. source

      Not checked in the free run.

  • Premisecitation

    Elevated plasma low-density lipoprotein cholesterol (LDL-C) level is the most important modifiable risk factor for atherosclerotic cardiovascular disease.

    “Among the modifiable ones, elevated plasma low-density lipoprotein cholesterol (LDL-C) level is the most important [3].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Colantonio LD, Bittner V, Reynolds K, Levitan EB, Rosenson RS, Banach M, Kent ST, Derose SF, Zhou H, Safford MM, Muntner P. Association of Serum Lipids and Coronary Heart Disease in Contemporary Observational Studies. Circulation. 2016;133(3):256–64. source

      Not checked in the free run.

  • Premisecitation

    Reducing LDL-C reduces risk for developing atherosclerotic cardiovascular disease and its clinical sequelae.

    “Many clinical trials have demonstrated that reducing LDL-C reduces risk for developing ASCVD and its clinical sequelae [4].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Hobbs FD, Banach M, Mikhailidis DP, Malhotra A, Capewell S. Is statin-modified reduction in lipids the most important preventive therapy for cardiovascular disease? A pro/con debate. BMC Med. 2016;14:4. source

      Not checked in the free run.

  • Interpretationreasoning

    Every 1% reduction of LDL-C levels corresponds to a 1% reduction in cardiovascular events.

    “Hence, it has been estimated that every 1% reduction of LDL-C levels corresponds to a 1% reduction in CV events.”
    Quote in the paperNot a substantial claim
  • Premisecitation

    Red yeast rice supplementation has shown efficacy in reducing cardiovascular disease risk in adult and elderly patients in secondary prevention.

    “RYR supplementation has shown efficacy in reducing CVD risk in adult and elderly patients in secondary prevention [38].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [38] Luo Z, Kou W, Du B, Wu Y, Zhao S, Brusco OA, Morgan JM, Capuzzi DM, Chinese Coronary Secondary Prevention Study Group, Li S. Effect of Xuezhikang, an extract from red yeast Chinese rice, on coronary events in a Chinese population with previous myocardial infarction. Am J Cardiol. 2008;101(12):1689–93. source

      Not checked in the free run.

  • May combine two claims. 23
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 2

  • May combine two claims.

    Premisecitation

    Garlic extracts for at least 2 months reduce LDL-C by 0.23 mmol/L in mild-to-moderate hypercholesterolemic subjects, more evident in individuals with TC < 5.17 mmol/L at baseline.

    “the consumption of garlic extracts for at least 2 months showed a reduction of LDL-C (− 0.23 mmol/L [9 mg/dL], more evident in individuals with TC < 5.17 mmol/L [200 mg/dL] at baseline) [47].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [47] Ried K, Toben C, Fakler P. Effect on garlic on serum lipids: an updated meta-analysis. Nutr Rev. 2013;71(5):282–99. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Rational combinations of nutraceuticals with different lipid-lowering activities, particularly when associated with an appropriate lifestyle, can provide an alternative to drug treatment in patients in primary CVD prevention with mildly elevated LDL-C and in some statin-intolerant patients.

    “Rational combinations of nutraceuticals with different lipid-lowering activities (Fig. 1), particularly when associated with an appropriate lifestyle, can provide an alternative to drug treatment in patients in primary CVD prevention with mildly elevated LDL-C (especially for those not being at their target LDL-C)) and in some statin-intolerant patients [90].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [90] Cicero AF, Colletti A. Combinations of phytomedicines with different lipid lowering activity for dyslipidemia management: The available clinical data. Phytomedicine. 2016;23(11):1113–8. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Red yeast rice supplementation reduces LDL-C on average by 1.02 mmol/L compared to placebo, not different from moderate-intensity statins.

    “A meta-analysis of 20 RCTs evaluated the efficacy of RYR supplementation after 2–24 months that reduced LDL-C on average of 1.02 mmol/L (− 1.20; − 0.83) (39.4 mg/dL) compared to placebo which was not different from moderate-intensity statins (pravastatin 40 mg, simvastatin 10 mg, lovastatin 20 mg) (0.003 mmol/L; − 0.36; 0.41) (0.12 mg/dL).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36] Gerards MC, Terlou RJ, Yu H, Koks CH, Gerdes VE. Traditional Chinese lipid-lowering agent red yeast rice results in significant LDL reduction but safety is uncertain - a systematic review and meta-analysis. Atherosclerosis. 2015;240(2):415–23. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Bergamot-derived polyphenols (500 to 1500 mg/day) reduce LDL-C, triglycerides, non-HDL-C, malonyl dialdehyde, fasting plasma insulin, leptin, leptin/adiponectin ratio, hs-CRP, and TNF-α in a dose-dependent manner.

    “bergamot-derived polyphenols (500 to 1500 mg/day) are able to reduce LDL-C, triglycerides, non-HDL-C, malonyl dialdehyde [52], fasting plasma insulin, leptin, leptin/adiponectin ratio, hs-CRP, and tumor necrosis factor alpha (TNF-α) [53], in a dose-dependent manner”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [52] Gliozzi M, Walker R, Muscoli S, Vitale C, Gratteri S, Carresi C, Musolino V, Russo V, Janda E, Ragusa S, Aloe A, Palma E, Muscoli C, Romeo F, Mollace V. Bergamot polyphenolic fraction enhances rosuvastatin-induced effect on LDL-cholesterol, LOX-1 expression and protein kinase B phosphorylation in patients with hyperlipidemia. Int J Cardiol. 2013;170(2):140–5. source

      Not checked in the free run.

    • cites [53] Cicero AFG, Fogacci F, Bove M, Giovannini M, Borghi C. Three-arm, placebo-controlled, randomized clinical trial evaluating the metabolic effect of a combined nutraceutical containing a bergamot standardized flavonoid extract in dyslipidemic overweight subjects. Phytother Res. 2019;33(8):2094–101. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    MonK administration is associated with reduced risk of non-muscle-related side effects (OR = 0.59) and serious adverse events (OR = 0.54) versus control.

    “reduced risk of non-muscle-related side effects (OR = 0.59, 95% CI 0.50, 0.69) and serious adverse events (OR = 0.54, 95% CI 0.46, 0.64) versus control was shown [44••].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [44••]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Berberine side effects are mild to moderate, mostly gastrointestinal, and comparable in frequency to control groups.

    “Side effects from BBR are mild to moderate, mostly gastrointestinal (diarrhea, constipation, abdominal distension) and comparable in frequency to the control groups.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [64] Derosa G, Maffioli P, Cicero AF. Berberine on metabolic and cardiovascular risk factors: an analysis from preclinical evidences to clinical trials. Expert Opin Biol Ther. 2012;12(8):1113–24. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Spirulina supplementation reduces LDL-C by 1.1 mmol/L, total cholesterol by 1.2 mmol/L, TG by 0.5 mmol/L, and increases HDL-C by 0.16 mmol/L.

    “with a reduction of LDL-C by − 1.1 mmol/L (95% CI: − 1.6; − 0.6, p < 0.001), TC by 1.2 mmol/L (95% CI: − 1.7; − 0.7, p < 0.001), and TG by − 0.5 mmol/L (95% CI: − 0.6; − 0.4, p < 0.001) and an increase of HDL-C of + 0.16 mmol/L (95% CI: 0.06; 0.25, p = 0.001) [89].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [89] Serban MC, Sahebkar A, Dragan S, Stoichescu-Hogea G, Ursoniu S, Andrica F, Banach M. A systematic review and meta-analysis of the impact of Spirulina supplementation on plasma lipid concentrations. ClinNutr. 2016;35(4):842–51.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Krill oil supplementation significantly reduces LDL-C (−0.4 mmol/L) and TG (−0.16 mmol/L) and increases HDL-C (0.17 mmol/L).

    “Ursoniu et al. showed a significant reduction in plasma concentrations of LDL-C [− 0.4 mmol/L (− 15.52 mg/dL); 95% CI: − 0.73; − 0.07 mmol/L (− 28.43; − 2.61 mg/dL); p = 0.018], TG [− 0.16 mmol/L (− 14.03 mg/dL); 95% CI: − 0.24; − 0.08 mmol/L (− 21.38; − 6.67 mg/dL)], and significant elevation in plasma concentrations of HDL-C [0.17 mmol/L (6.65 mg/dL); 95% CI: 0.06; 0.28 mmol/L (2.30; 10.99 mg/dL”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [86] Ursoniu S, Sahebkar A, Serban MC, Antal D, Mikhailidis DP, Cicero AF, Athyros V, Rizzo M, Rysz J, Banach M, Lipid and Blood Pressure Meta-analysis Collaboration Group. Lipid-modifying effects of krill oil in humans: systematicreview and meta-analysis of randomized controlled trials. Nutr Rev. 2017;75(5):361–73. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In patients undergoing percutaneous coronary intervention, berberine 600 mg/day versus placebo shows a marked reduction in TG (26% vs 13%, not significant) and LDL-C (24% vs 17%, p < 0.001).

    “The BBR group showed a marked reduction in TG (26% BBR vs. 13% control: the difference did not reach statistical significance due to large inter-individual variations) and LDL-C (24% vs. 17% BBR control: p < 0.001) compared to the control group.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [63] Meng S, Wang LS, Huang ZQ, Zhou Q, Sun YG, Cao JT, Li YG, Wang CQ. Berberine ameliorates inflammation in patients with acute coronary syndrome following percutaneous coronary intervention. Clin Exp Pharmacol Physiol. 2012;39(5):406–11. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Glucomannan significantly reduces LDL-C and TG by −0.41 mmol/L and −0.13 mmol/L, respectively, compared to placebo.

    “the use of glucomannan (at doses ranging between 1.2 and 15.1 g/day) significantly reduces LDL-C and TG respectively by − 0.41 mmol/L (15.9 mg/dL) and − 0.13 mmol/L (11.5 mg/dL) (p < 0.05 for both), compared to placebo.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26] Sood N, Baker WL, Coleman CI. Effect of glucomannan on plasma lipid and glucose concentrations, body weight, and blood pressure: systematic review and meta-analysis. Am J ClinNutr. 2008;88(4):1167–75.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Plant sterols and stanols' LDL cholesterol-lowering effect continues to increase up to intakes of approximately 3 g/day, with an average LDL-C reduction of 12%.

    “their LDL cholesterol-lowering effect continues to increase up to intakes of approximately 3 g/day with an average LDL-C reduction of 12% [12].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Ras RT, Geleijnse JM, Trautwein EA. LDL-cholesterol-lowering effect of plant sterols and stanols across different dose ranges: a meta-analysis of randomised controlled studies. Br J Nutr. 2014;112(2):214–9. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Berberine reduces LDL-C by 0.65 mmol/L, TG by 0.39 mmol/L, and increases HDL-C by 0.07 mmol/L.

    “LDL-C: − 0.65 mmol/L (95% CI − 0.75; − 0.56, p = 0.00001) (25.14 mg/dL); TG: − 0.39 mmol/L (95% CI − 0.59; − 0.19, p = 0.0001) (34.5 mg/dL); HDL-C: 0.07 mmol/L (95% CI 0.04; 0.10, p = 0.00001) (2.71 mg/dL).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [62] Lan J, Zhao Y, Dong F, Yan Z, Zheng W, Fan J, Sun G. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol. 2015;161:69–81. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Berberine's lipid-lowering effects seem to be additive to those of statins and associated with a positive impact on glucose metabolism and blood pressure.

    “These effects seem to be additive to those of statins and associated with a positive impact also on glucose metabolism and blood pressure [62].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [62] Lan J, Zhao Y, Dong F, Yan Z, Zheng W, Fan J, Sun G. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol. 2015;161:69–81. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    An average daily dose of 3.25 g of EPA/DHA for 24 weeks significantly reduces TG by 14% (−0.34 mmol/L), with a small insignificant reduction of LDL-C and no differences in HDL-C.

    “The results showed a significant reduction in TG of 14% [− 0.34 mmol/L (30.12 mg/dL), 95% CI: − 0.41; − 0.27 mmol/L (− 36; − 24 mg/dL)]. In addition, there was a small insignificant reduction of LDL-C of 0.06 mmol/L (2.3 mg/dL), but no differences in HDL-C [82].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [82] Eslick GD, Howe PR, Smith C, Priest R, Bensoussan A. Benefits of fish oil supplementation in hyperlipidemia: a systematic review and meta-analysis. Int J Cardiol. 2009;136(1):4–16. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Soy proteins have a cholesterol-lowering effect with a mean reduction in LDL-C of 3%, TG of 4%, and increase HDL-C by 3%, the effect being proportional to baseline LDL-C level.

    “soy proteins have a cholesterol-lowering effect with a mean reduction in LDL-C of 3% (− 0.12 mmol/L/4.6 mg/dL) and TG of 4% (− 0.06 mmol/L/5.3 mg/dL) and are able to increase HDL-C by 3% (+ 0.04 mmol/L/1.6 mg/dL), the effect being proportional to the baseline LDL-C level [74].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [74] Tokede OA, Onabanjo TA, Yansane A, Gaziano JM, Djoussé L. Soya products and serum lipids: a meta-analysis of randomised controlled trials. Br J Nutr. 2015;114(6):831–43. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a large trial in China, red yeast rice supplementation reduced the risk of CHD (31.0%), all-cause mortality (31.9%), stroke (44.1%), need for coronary artery bypass graft or percutaneous coronary intervention (48.6%), and malignancies (51.4%).

    “RYR supplementation showed a reduction in the risk of CHD (31.0%, p = 0.04), all-cause mortality (31.9%, p = 0.01), stroke (44.1%, p = 0.04), the need for coronary artery bypass graft or a percutaneous coronary intervention (48.6%, p = 0.07), and malignancies (51.4%, p = 0.03).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [46] Ackermann RT, Mulrow CD, Ramirez G, Gardner CD, Morbidoni L, Lawrence VA. Garlic shows promise for improving some cardiovascular risk factors. Arch Intern Med. 2001;161(6):813–24. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The red yeast rice, policosanols, and berberine combination has been tested in adult and elderly patients previously intolerant to statins, being well tolerated in 80% of cases.

    “This combination has also been tested in adult and elderly patients previously intolerant to statins [94, 95], being well tolerated in the 80% of cases.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [94] Marazzi G, Cacciotti L, Pelliccia F, Iaia L, Volterrani M, Caminiti G, Sposato B, Massaro R, Grieco F, Rosano G. Long-term effects of nutraceuticals (berberine, red yeast rice, policosanol) in elderly hypercholesterolemic patients. Adv Ther. 2011;28(12):1105–13. source

      Not checked in the free run.

    • cites [95] Cicero AF, Derosa G, Borghi C. Red yeast rice and statin-intolerant patients. Am J Cardiol. 2010;105(10):1504. source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Both single components and some combinations (in particular red yeast rice, berberine, policosanol combination) maintain their efficacy in the long term (years).

    “both single components and some combinations (in particular red yeast rice, berberine, policosanol combination) have been demonstrated to maintain their efficacy in the long term (years)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    Both single components and some combinations have a positive impact on CVD risk factors other than LDL-C.

    “to have a positive impact on CVD risk factors other than LDL-C”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Many nutraceuticals have an additive effect on lipid-lowering drugs, allowing reduction of statin doses without diminishing TC and LDL-C reduction and significantly limiting adverse effects.

    “many nutraceuticals have an additive effect on lipid-lowering drugs, allowing reduction of the statins’ doses without diminishing the results in terms of TC and LDL-C reduction and significantly limiting adverse effects [106••]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites 106••

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Most of the presented combinations have been tested only in a single study and the obtained results have not been confirmed yet.

    “most of the presented combinations have been tested only in a single study and the obtained results have not been confirmed yet”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning

    Both single components and some combinations improve some markers of vascular aging (endothelial function, pulse wave velocity).

    “to improve some markers of vascular aging (endothelial function, pulse wave velocity)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The association of plant sterols/stanols with certain lipid-lowering ingredients strengthens cholesterol-lowering efficacy and adds TG-lowering effects.

    “The association of plant sterols/stanols with certain lipid-lowering ingredients also demonstrated to strengthen cholesterol-lowering efficacy and add TG-lowering effects [96].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [96] Cicero AF, Fogacci F, Rosticci M, Parini A, Giovannini M, Veronesi M, D’Addato S, Borghi C. Effect of a short-term dietary supplementation with phytosterols, red yeast rice or both on lipid pattern in moderately hypercholesterolemic subjects: a three-arm, double-blind, randomized clinical trial. Nutr Metab. 2017;14:61. source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    A meta-analysis of 12 randomized double-blind placebo-controlled clinical trials suggests that dietary supplementation with red yeast rice (3 mg MonK), policosanols (10 mg), and berberine (500 mg) exerts significant effects on BMI, LDL-C, TG, HDL-C, hs-CRP, and fasting glucose.

    “A recent meta-analysis of 12 randomized double-blind placebo-controlled clinical trials including 1050 subjects suggested that dietary supplementation with this nutraceutical combination exerts a significant effect on body mass index (mean difference (MD) = − 0.25 kg/m2, p = 0.008) and serum levels of LDL-C (MD = − 26.67 mg/dL, p < 0.001), TG (MD = − 11.47 mg/dL, p < 0.001), HDL-C (MD = 1.84 mg/dL”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [93] Cicero AFG, Kennedy C, Knežević T, Bove M, Georges CMG, Šatrauskienė A, Toth PP, Fogacci F. Efficacy and Safety of Armolipid Plus®: An Updated PRISMA Compliant Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials. Nutrients. 2021;13(2):638. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Combinations of lipid-lowering nutraceuticals could improve their safety by reducing the dosages of the single components.

    “Combinations of lipid-lowering nutraceuticals could improve their safety (reducing the dosages of the single components)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Some of the tested nutraceutical combinations contained underdosed components.

    “some of the tested nutraceutical combinations contained underdosed components”
    Quote in the paperNot a substantial claim
26 of 26

  • The paper relies on this without support.

    The available data are sufficient to detect serious safety concerns of the evaluated nutraceutical combinations.

    “Based on the available data, no serious safety concerns have been observed.”
1 of 1

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Red yeast rice HDL-C estimate falls outside its stated interval

    Minor

    The reported HDL-C increase of 0.007 mmol/L is below both stated interval endpoints, 0.03 and 0.11.

  • β-glucan confidence interval conflicts with its significance claim

    Minor

    The stated 95% confidence interval includes zero, despite the reported p-value below 0.00001; its endpoints are also printed in reverse order.

  • Two different EFSA citrinin limits are stated

    Minor

    The text gives the EFSA limit as both 0.2 and 20 μg/kg body weight per day, a hundredfold difference.

3 of 3

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. EFSA. Scientific Opinion on the risks for public and animal health related to the presence of citrinin in food and feed. EFSA Panel on Contaminants in the Food Chain (CONTAM). European Food Safety Authority (EFSA), Parma, Italy. EFSA J. 2012;10(3):2605.
  2. EFSA Panel on Dietetic Products NaAN Scientific Opinion on the substantiation of health claims related to EPA, DHA, DPA and maintenance of normal blood pressure (ID 502), maintenance of normal HDL-cholesterol concentrations (ID 515), maintenance of normal (fasting) blood concentrations of triglycerides (ID 517), maintenance of normal LDL-cholesterol concentrations (ID 528, 698) and maintenance of joints (ID 503, 505, 507, 511, 518, 524, 526, 535, 537) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J. 2009;7:1263–1289.

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Authors
Cicero, A. F. G., Fogacci, F., Stoian, A. P., Vrablik, M., Al Rasadi, K., Banach, M., Toth, P. P., & Rizzo, M.
Affiliations
  • IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
  • University of Bologna (IT)
  • Carol Davila University of Medicine and Pharmacy (RO)
  • Medical University of Lodz (PL)
  • Johns Hopkins University (US)
Corresponding author
Cicero, Arrigo F. G.
ORCID
Venue
Current Atherosclerosis Reports
Publisher
Springer Science and Business Media LLC
Published
2021-08-04
Volume
23
Issue
10
Pages
57-57
ISSN
  • 1523-3804 (ISSN-L)
  • 1534-6242
DOI
10.1007/s11883-021-00955-y
PMC
PMC8332568
OpenAlex
W3190295594
Semantic Scholar
af855c4967242aae75893d734155b63f9adeed60
Cited by
110
References
110
Citations by year
2026: 11 · 2025: 21 · 2024: 24 · 2023: 23 · 2022: 28 · 2021: 3
FWCI
4.70
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Atherosclerosis Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by)
  • Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion, other-oa)
Funders
Alma Mater Studiorum - Università di Bologna
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Surgery › Natural Products and Biological Research
  • Health Sciences › Medicine › Complementary and alternative medicine › Complementary and Alternative Medicine Studies
Keywords
nutraceuticals, dyslipidemia, lipid-lowering drugs, red yeast rice, soluble dietary fiber, berberine, artichoke extract, garlic, green tea, low cardiovascular risk, plasma lipids, safety and tolerability
MeSH terms
Hypolipidemic Agents, Humans, Lipids, Phytosterols, Dietary Supplements, Dyslipidemias

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