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Cited by 281Lipoproteins and Cardiovascular HealthNatural Products and Biological ResearchFatty Acid Research and Health

Lipid lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel

Open access
Cicero, Arrigo F.G., Colletti, Alessandro, Bajraktari, Gani, Descamps, Olivier, Djuric, Dragan M., Ezhov, Marat, Fras, Zlatko, Katsiki, Niki +20 more·2017·Archives of Medical Science
DOI 10.5114/aoms.2017.69326PMC PMC5575230
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Abstract

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, reaching 31% of deaths in 2012 [1]. In particular, atherosclerosis and ischemic heart disease (IHD) are the main causes of premature death in Europe and are responsible for 42% of deaths in women and 38% in men under 75 years old [2]. The global economic impact of CVD is estimated to have been US $906 billion in 2015 and is expected to rise by 22% by 2030 [3]. Cardiovascular diseases also represent the major cause of disability in developed countries. It has been estimated that their growing burden could lead to a global increase in loss of disability-adjusted life years (DALYs), from a loss of 85 million DALYs in 1990 to a loss of ~150 million DALYs in 2020, becoming a major non-psychological cause of lost productivity [4]. Several risk factors contribute to the etiology and development of CVD; they are divided into those modifiable through lifestyle changes or by taking a pharmacologic treatment (e.g. for hypertension, smoking, diabetes mellitus, hypercholesterolemia) and those that are not modifiable (age, male gender, and family history) [5]. Elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) blood concentrations are the major modifiable risk factors for coronary heart disease (CHD), whereas high concentrations of plasma high-density lipoprotein cholesterol (HDL-C) in certain conditions are considered protective [6]. Moreover, LDL-C remains a fundamental CV risk factor (and a main target of therapy) even when statins are largely used in the general population [7]. An examination of the data of 18 053 participants aged ≥ 20 years who participated in the National Health and Nutrition Examination Surveys (NHANES) from 1999 to 2006 showed that the unadjusted prevalence of hypercholesterolemia ranged from 53.2% to 56.1% in United States adults [8]. Differences related to gender and race or ethnicity were observed; in particular, a lower rate of control was found among women than men and lower rates of having a cholesterol check and being told about hypercholesterolemia were reported by African Americans and Mexican Americans than whites [8]. A recent report from the American Heart Association confirmed that in the US only 75.7% of children and 46.6% of adults present targeted TC levels (TC < 170 mg/dl for children and < 200 mg/dl for adults, in untreated individuals) [9]. The pattern is similar in other Western countries [10, 11].

AI snapshot

Written from the paper’s full text.

TL;DR

This International Lipid Expert Panel position paper reviews lipid-lowering nutraceuticals and their combinations, grading evidence and recommending selected agents as adjuncts for mild dyslipidemia or statin intolerance. It emphasizes that nutraceuticals cannot replace indicated lipid-lowering therapy and that outcome data proving CVD event reduction are still lacking.

Key findings

  • Red yeast rice (RYR) reduced LDL-C by 1.02 mmol/l (39.4 mg/dl) versus placebo in a meta-analysis of 20 trials, comparable to moderate-intensity statins; it was graded Class I, Level A, with expected LDL-C reduction of –15% to –25%.
  • Berberine, in a meta-analysis of 27 clinical studies with 2569 participants, reduced LDL-C by –0.65 mmol/l (25.14 mg/dl), TG by –0.39 mmol/l (34.5 mg/dl), and increased HDL-C by 0.07 mmol/l (2.71 mg/dl); it was graded Class I, Level A.
  • The RYR–policosanol–berberine combination, in a meta-analysis of 14 RCTs with 3159 subjects, improved LDL-C by –0.61 mmol/l (23.6 mg/dl), HDL-C by 0.07 mmol/l (2.71 mg/dl), TG by –0.16 mmol/l (14.2 mg/dl), and glucose by –0.14 mmol/l (2.52 mg/dl); it was graded Class I, Level A.
  • Omega-3 EPA/DHA, in a meta-analysis of 47 RCTs with 16,511 hypercholesterolemic participants using a mean 3.25 g/day for 24 weeks, reduced TG by 14% (–0.34 mmol/l/30.12 mg/dl), with no significant HDL-C difference; it was graded Class I, Level A for TG lowering.

Methods

  • Position paper/consensus from an International Lipid Expert Panel, endorsed by multiple national societies, providing a narrative review of clinical evidence on individual lipid-lowering nutraceuticals and nutraceutical combinations.
  • Evidence was drawn from randomized controlled trials and meta-analyses; treatment options were graded by Class of recommendation (I–III) and Level of evidence (A–C) as defined in Tables I and II.
  • For each nutraceutical, the paper describes mechanism of action, active principles, effective dosages, effects on lipid profile, extra-lipid-lowering properties, and safety profile where available.

Limitations

  • The paper states that there are still no outcome studies proving that nutraceuticals can prevent CVD morbidity or mortality; many combinations have been tested only in a single study and results have not been confirmed, and some tested combinations contained underdosed components.
  • The paper notes long-term safety data are lacking for some agents, such as plant sterols beyond 2 years, beta-glucan long-term efficacy/safety, and silymarin safety data.
  • Evident from the text: the evidence base is heterogeneous, with small or short trials, inconsistent RCT results for some agents (e.g., curcumin, policosanols), and bergamot efficacy data largely from a single research unit and not confirmed elsewhere.

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

Integrity signals

Registry

Crossref · 10.5114/aoms.2017.69326

Cites

294 of 294 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 352 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    The same meta-analysis showed that the red yeast rice-policosanol-berberine association improved glucose by -0.14 mmol/l (2.52 mg/dl) (p = 0.010).

    “glucose by –0.14 mmol/l (2.52 mg/dl) (p = 0.010)”
    Quote in the paperSubstantial claim
  • Findingcitation

    The same meta-analysis showed that the red yeast rice-policosanol-berberine association improved HDL-C by 0.07 mmol/l (2.71 mg/dl) (p < 0.001).

    “HDL-C by 0.07 mmol/l (2.71 mg/dl) (p < 0.001)”
    Quote in the paperSubstantial claim
  • Findingcitation

    The same meta-analysis showed that the red yeast rice-policosanol-berberine association improved TG by -0.16 mmol/l (14.2 mg/dl) (p < 0.001).

    “TG by –0.16 mmol/l (14.2 mg/dl) (p < 0.001)”
    Quote in the paperSubstantial claim
  • Findingcitation

    A meta-analysis of 14 RCTs including 3159 subjects showed that the red yeast rice-policosanol-berberine association improved plasma LDL-C by -0.61 mmol/l (23.6 mg/dl) (p < 0.001).

    “A recent meta-analysis of 14 RCTs including data from 3159 subjects showed than the red yeast rice-policosanol-berberine association improved the plasma level of LDL-C by –0.61 mmol/l (23.6 mg/dl) (p < 0.001)”
    Quote in the paperSubstantial claim
  • Findingcitation

    Three polymorphisms in the 3′ UTR region of LDLR and two in the 5′ UTR region of PCSK9 were associated with response to treatment with the red yeast rice-policosanol-berberine supplement.

    “Three polymorphisms in the 3′ UTR region of LDLR and two in the 5′ UTR region of PCSK9 were associated with response to the treatment.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [247] De Castro-Orós I Solà R Valls RM Genetic variants of LDLR and PCSK9 associated with variations in response to antihypercholesterolemic effects of armolipid plus with berberine PLoS One 2016 11 e0150785 27015087 PMC4807809

      Not checked in the free run.

  • May combine two claims. 181
  • The quote only partly states this claim. 17
  • Classified as probably not a substantial claim. 20

  • May combine two claims.

    Findingcitation

    The improvement of lipid profile was not dependent on duration of supplementation or baseline lipid levels.

    “Then, the improvement of lipid profile was not dependent on duration of supplementation or baseline lipid levels”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [244] Pirro M Mannarino MR Ministrini S Effects of a nutraceutical combination on lipids, inflammation and endothelial integrity in patients with subclinical inflammation: a randomized clinical trial Sci Rep 2016 6 23587 27004462 PMC4804276

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The red yeast rice-policosanol-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 [245, 246], being well tolerated in 80% of cases.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [245] Marazzi G Cacciotti L Pelliccia F Long-term effects of nutraceuticals (berberine, red yeast rice, policosanol) in elderly hypercholesterolemic patients Adv Ther 2011 28 1105 13 22113535

      Not checked in the free run.

    • cites [246] Cicero AF Derosa G Borghi C Red yeast rice and statin-intolerant patients Am J Cardiol 2010 105 1504 20451704

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    The association of red yeast rice (3 mg MonK), policosanols (10 mg) and berberine (500 mg) is the most studied in RCTs and the only one for which meta-analyses of RCTs are available.

    “The association of the lipid-lowering properties of red yeast rice (3 mg MonK), policosanols (10 mg) and berberine (500 mg) is the most studied in RCTs and the only one for which meta-analyses of RCTs are available.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    In that trial, LDL-C change was positively associated with hs-CRP (p = 0.04) and endothelial microparticle changes (p < 0.001).

    “It was highlighted that LDL-C change was positively associated with hs-CRP (p = 0.04) and endothelial microparticle changes (p < 0.001)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [244] Pirro M Mannarino MR Ministrini S Effects of a nutraceutical combination on lipids, inflammation and endothelial integrity in patients with subclinical inflammation: a randomized clinical trial Sci Rep 2016 6 23587 27004462 PMC4804276

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In that trial, hs-CRP and endothelial microparticle levels were significantly decreased (-41% and -16%, respectively).

    “hs-CRP and endothelial microparticle levels were also significantly decreased (–41% and –16%, respectively)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [244] Pirro M Mannarino MR Ministrini S Effects of a nutraceutical combination on lipids, inflammation and endothelial integrity in patients with subclinical inflammation: a randomized clinical trial Sci Rep 2016 6 23587 27004462 PMC4804276

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    A greater glucose-lowering effect was found with higher baseline glucose levels and longer durations of supplementation.

    “while a greater glucose-lowering effect was found with higher baseline glucose levels and longer durations of supplementation [244]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [244] Pirro M Mannarino MR Ministrini S Effects of a nutraceutical combination on lipids, inflammation and endothelial integrity in patients with subclinical inflammation: a randomized clinical trial Sci Rep 2016 6 23587 27004462 PMC4804276

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    In the available studies of red yeast rice and plant sterols, none of the participants reported any muscle pains and no abnormal liver function tests were observed while taking this supplement.

    “In the available studies none of the participants reported any muscle pains and no abnormal liver function tests were observed while taking this supplement.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    In a 16-week, randomized, double-blind, placebo-controlled trial on 100 subjects, the same combination reduced LDL-C by 14.3% (-0.57 mmol/l, 95% CI: -0.8; -0.31), as well as TC, apoB100 and apoB100/apoA-I ratio, without modifying safety parameters.

    “the authors observed a reduction of LDL-C by 14.3% (–0.57 mmol/l (22 mg/dl), 95% CI: –0.8; –0.31), as well as TC, apoB100 and apoB100/apoA-I ratio, without modifying safety parameters [254].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [254] Barrat E Zaïr Y Ogier N A combined natural supplement lowers LDL cholesterol in subjects with moderate untreated hypercholesterolemia: a randomized placebo-controlled trial Int J Food Sci Nutr 2013 64 882 9 23815518

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In a clinical trial on 107 pharmacologically untreated subjects with primary polygenic hypercholesterolemia and MetS in primary prevention, after 8 weeks of treatment with red yeast rice (5 mg monacolin K) and PUFAs (610 mg: 183 mg EPA, 122 mg DHA), there was significant decrease in LDL-C (-0.97 ±0.35 mmol/l; -22 ±3%), TG (-0.22 ±0.28 mmol/l; -9 ±5%) and non-HDL-C (-21 ±3%) and significant

    “After 8 weeks of treatment, the results showed a significant decrease in LDL-C (–0.97 ±0.35 mmol/l (37.5 mg/dl); –22 ±3%), TG (–0.22 ±0.28 mmol/l (19.5 mg/dl); –9 ±5%) and non-HDL-C (–21 ±3%) and a significant increase in HDL-C (+1.5 ±0.5%) (p < 0.001 for all), without the modification of safety parameters.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [267] Cicero AF Derosa G Pisciotta L Barbagallo C SISA-PUFACOL Study Group Testing the short-term efficacy of a lipid-lowering nutraceutical in the setting of clinical practice: a multicenter study J Med Food 2015 18 1270 3 26274827 PMC4638196

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    Based on the available data, no serious safety concerns have been raised for red yeast rice and artichoke, but further studies with longer follow-up are necessary to conclusively confirm this.

    “Based on the available data, no serious safety concerns have been raised, but further studies with longer follow-up are necessary to conclusively confirm this.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    In a double-blind, placebo-controlled trial of 134 low-risk dyslipidemic patients, after 3 months of treatment with red yeast rice (334 mg containing monacolin 10 mg), policosanol (30 mg), and silymarin (150 mg), the supplement decreased LDL-C compared to baseline (p = 0.041) and to placebo (p = 0.037).

    “After 3 months of treatment, the nutraceutical supplement decreased LDL-C compared to baseline (p = 0.041) and to placebo (p = 0.037, respectively).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [257] Derosa G Bonaventura A Bianchi L A randomized, placebo-controlled study on the effects of a nutraceutical combination of red yeast rice, silybum marianum and octasonol on lipid profile, endothelial and inflammatory parameters J Biol Regul Homeost Agents 2014 28 317 24 25001663

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In that trial, triglycerides were reduced by the active product (p = 0.039), but not by placebo, although group-to-group comparison showed no significant difference (p = 0.061).

    “Triglycerides were reduced by the active product (p = 0.039), but not by the placebo, even though, in the group-to-group comparison, no significant difference was recorded (p = 0.061).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [257] Derosa G Bonaventura A Bianchi L A randomized, placebo-controlled study on the effects of a nutraceutical combination of red yeast rice, silybum marianum and octasonol on lipid profile, endothelial and inflammatory parameters J Biol Regul Homeost Agents 2014 28 317 24 25001663

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In a double-blind, randomized, parallel controlled study on 39 subjects with moderate hypercholesterolemia, after 16 weeks of treatment with red yeast rice, policosanols, and artichoke leaf extracts, LDL-C was reduced by 21.4% (95% CI: -13.3; -24.9%, p < 0.001) and TG decreased by 12.2% (95% CI: -24.4; -0.1%, p < 0.05).

    “after 16 weeks of treatment, LDL-C was reduced by 21.4% (95% CI: –13.3; –24.9%, p < 0.001), while TG decreased by 12.2% (95% CI: –24.4; –0.1%, p < 0.05) [253].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [253] Ogier N Amiot MJ Georgé S LDL-cholesterol-lowering effect of a dietary supplement with plant extracts in subjects with moderate hypercholesterolemia Eur J Nutr 2013 52 547 57 22527287

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Findingnone given

    No safety concerns have been reported for psyllium and n-3 PUFAs; very limited data and further studies are necessary.

    “No safety concerns. Very limited data; further studies are necessary.”
    Quote in the paperNot a substantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingnone given

    Based on the available data, no serious safety concerns have been raised for red yeast rice and antioxidants.

    “Based on the available data, no serious safety concerns have been raised.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    In a randomized, crossover trial on 34 mild hypercholesterolemic subjects, treatment with glucomannan (10 g/day) and plant sterols (1.8 g/day) improved lipid parameters (LDL-C 2.9 ±0.2 mmol/l vs. control 3.6 ±0.2 mmol/l, p < 0.05) and lowered plasma lathosterol concentrations (p < 0.05).

    “An improvement of lipid parameters was assessed after the treatment (LDL-C 2.9 ±0.2 mmol/l (112 mg/dl) vs. control group 3.6 ±0.2 mmol/l (140 mg/dl), p < 0.05). Plasma lathosterol concentrations, an index of cholesterol biosynthesis, were lowered after the combination treatment (p < 0.05), as well [274].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [274] Yoshida M Vanstone CA Parsons WD Zawistowski J Jones PJ Effect of plant sterols and glucomannan on lipids in individuals with and without type II diabetes Eur J Clin Nutr 2006 60 529 37 16391591

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In a small cohort of hypercholesterolemic subjects, intake of soy proteins (16.2 g/1000 kcal) and plant sterols (1.2 g/1000 kcal) combined with viscous fibers (8.3 g/1000 kcal) and almonds (16.6 g/1000 kcal) for 4 weeks reduced LDL-C by 35.0 ±3.1% (p < 0.001) and the ratio of LDL-C to HDL-C by 30.0 ±3.5% (p < 0.001).

    “after their intake for 4 weeks, there was reported a reduction of LDL-C of 35.0 ±3.1% (p < 0.001), and the ratio of LDL-C to HDL-C (30.0 ±3.5%, p < 0.001) [266].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [266] Jenkins DJ Kendall CW Marchie A The effect of combining plant sterols, soy protein, viscous fibers, and almonds in treating hypercholesterolemia Metabolism 2003 52 1478 83 14624410

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    No safety concerns have been reported for red yeast rice and omega-3 PUFAs; very limited data and further studies are necessary.

    “No safety concerns. Very limited data; further studies are necessary.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In an 8-week randomized clinical trial of 80 hypercholesterolemic subjects, compared to placebo, the same nutraceutical combination treated patients experienced a more favorable percentage change in LDL-C (-23.3%), hs-CRP (-2.4%), and endothelial function (pulse volume displacement vs. baseline: +17%).

    “When compared to placebo, nutraceutical combination treated patients experienced a more favorable percentage change in LDL-C (–23.3%), hs-CRP (–2.4%), and endothelial function (pulse volume displacement vs. baseline: +17%).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [258] Cicero AF Colletti A Rosticci M Grandi E Borghi C Efficacy and tolerability of a combined lipid-lowering nutraceutical on cholesterolemia, hs-CRP level and endothelial function in moderately hypercholesterolemic subjects J Biol Regul Homeost Agents 2016 30 593 8 27358154

      Not checked in the free run.

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

    Findingnone given

    No safety concerns have been reported for psyllium and plant sterols; very limited data and further studies are necessary.

    “No safety concerns. Very limited data; further studies are necessary.”
    Quote in the paperNot a substantial claim

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

    Findingnone given

    No safety concerns have been reported for glucomannan and plant sterols; very limited data and further studies are necessary.

    “No safety concerns. Very limited data; further studies are necessary.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In a clinical trial on 30 hyperlipidemic untreated patients, a nutraceutical product with pantethine (900 mg), soybean plant sterols (800 mg), green tea extract (600 mg containing 50% epigallocatechin gallate), γ/δ tocotrienols from annatto seed (75 mg) and Phytolens from lentil husks (5 mg) significantly reduced LDL-C by 14% (p < 0.003), VLDL by 20% (p < 0.01) and sdLDL particles by 25% (type III

    “After 2 months of treatment, there was a significant reduction of LDL-C by 14% (p < 0.003), VLDL dropped by 20% (p < 0.01) and sdLDL particles fell by 25% (type III and IV) [275].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [275] Houston M Sparks W Effect of combination pantethine, plant sterols, green tea extract, delta-tocotrienol and phytolens on lipid profiles in patients with hyperlipidemia JANA 2010 13 15 20

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    Based on the available data, no safety concerns have been raised for soy proteins and plant sterols, but further studies with a long follow-up are still necessary to confirm this.

    “Based on the available data, no safety concerns have been raised, but further studies with a long follow-up are still necessary to confirm this.”
    Quote in the paperSubstantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingnone given

    No safety concerns have been reported for red yeast rice, bitter gourd chlorella, soy protein, and licorice; very limited data and further studies are necessary.

    “No safety concerns. Very limited data; further studies are necessary.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In a double-blind, placebo-controlled, crossover, randomized clinical trial on 25 healthy, mildly hypercholesterolemic subjects, after 4 weeks, compared to placebo, monacolins/CoQ10-treated patients experienced a more favorable percent change in LDL-C (-21.99%, 95% CI: -26.63; -17.36), non-HDL-C (-14.67%, 95% CI: -19.22; -10.11), MMP-2 (-28.05%, 95% CI: -35.18; -20.93), MMP-9 (-27.19%, 95% CI: -36

    “When compared to the placebo group, monacolins/CoQ10-treated patients experienced a more favorable percent change in LDL-C (–21.99%, 95% CI: –26.63; –17.36), non-HDL-C (–14.67%, 95% CI: –19.22; –10.11), MMP-2 (–28.05%, 95% CI: –35.18; –20.93), MMP-9 (–27.19%, 95% CI: –36.21; –18.15), and hs-CRP (–23.77%, 95% CI: –30.54; –17.01).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [259] Cicero AF Derosa G Parini A Red yeast rice improves lipid pattern, high-sensitivity C-reactive protein, and vascular remodeling parameters in moderately hypercholesterolemic Italian subjects Nutr Res 2013 33 622 8 23890351

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In a 12-week, randomized, placebo-controlled clinical trial (106 participants) in subjects with MetS, treatment with extracts from red yeast rice, bitter gourd, chlorella, soy protein and licorice (three tablets/day) significantly decreased LDL-C (3.4 ±0.7 to 2.7 ±0.5 mmol/l, p < 0.001) and reduced TGs (-0.2 ±0.3 mmol/l, p = 0.039).

    “LDL-C decreased significantly after the treatment (3.4 ±0.7 (131 mg/dl) to 2.7 ±0.5 mmol/l (104 mg/dl), p < 0.001). In addition, TGs were reduced (–0.2 ±0.3 mmol/l (18 mg/dl), p = 0.039).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [268] Lee IT Lee WJ Tsai CM Su IJ Yen HT Sheu WH Combined extractives of red yeast rice, bitter gourd, chlorella, soy protein, and licorice improve total cholesterol, low-density lipoprotein cholesterol, and triglyceride in subjects with metabolic syndrome Nutr Res 2012 32 85 92 22348456

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In another double-blind, placebo-controlled, crossover RCT in 102 dyslipidemic patients, administration of Berberis aristata (588 mg extract containing 500 mg berberine) with Silybum marianum (105 mg extract) twice a day resulted in reduction of LDL-C and TG, and an increase of HDL-C after the first 3 months; the lipid profile worsened after a 2-month washout period and improved again when the nut

    “The results showed a reduction of LDL-C and TG, and an increase of HDL-C after the first 3 months of treatment; the lipid profile worsened after a 2-month washout period and improved again when the nutraceutical combination was reintroduced for a further 3 months [263].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [263] Derosa G Bonaventura A Bianchi L Berberis aristata/Silybum marianum fixed combination on lipid profile and insulin secretion in dyslipidemic patients Expert Opin Biol Ther 2013 13 1495 506 23971720

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In that trial, 75% of subjects reached an LDL-C target of less than 160 mg/dl and 25% of less than 130 mg/dl.

    “In particular, 75% of subjects reached an LDL-C target of less than 160 mg/dl and 25% of less than 130 mg/dl.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [267] Cicero AF Derosa G Pisciotta L Barbagallo C SISA-PUFACOL Study Group Testing the short-term efficacy of a lipid-lowering nutraceutical in the setting of clinical practice: a multicenter study J Med Food 2015 18 1270 3 26274827 PMC4638196

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The combination of γ-oryzanol (40 mg) with ω-3 PUFAs (1100 mg) improved lipid profile (LDL-C -0.93 ±0.97 mmol/l, p < 0.0001, TG -0.60 ±0.63 mmol/l, all p < 0.001), as well as inflammatory and oxidative status in dyslipidemic volunteers.

    “The combination of γ-oryzanol (40 mg) with ω-3 polyunsaturated fatty acids (1100 mg) was demonstrated to improve lipid profile (LDL-C –0.93 ±0.97 mmol/l (36 mg/dl), p < 0.0001, TG –0.60 ±0.63 mmol/l (23.2 mg/dl), all p < 0.001), as well as inflammatory and oxidative status in dyslipidemic volunteers [272].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [272] Accinni R Rosina M Bamonti F Effects of combined dietary supplementation on oxidative and inflammatory status in dyslipidemic subjects Nutr Metab Cardiovasc Dis 2006 16 121 7 16487912

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In a placebo-controlled clinical trial on 33 patients with LDL-C levels between 2.58 and 4.13 mmol/l, treatment with psyllium (7.68 g) and plant sterols (2.6 g) reduced LDL-C from 3.5 ±0.7 mmol/l to 3.1 ±0.8 mmol/l (p < 0.01) and reduced plasma apoB concentrations (p < 0.01).

    “The improvement in lipid profile included a reduction of LDL-C from 3.5 ±0.7 mmol/l (135 mg/dl) to 3.1 ±0.8 mmol/l (120 mg/dl) after the intake of the nutraceutical product (p < 0.01). Moreover, this combination led to a reduction of plasma apoB concentrations (p < 0.01) [269].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [269] Shrestha S Volek JS Udani J A combination therapy including psyllium and plant sterols lowers LDL cholesterol by modifying lipoprotein metabolism in hypercholesterolemic individuals J Nutr 2006 136 2492 7 16988115

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    Based on the available data, no serious safety concerns have been raised for berberine combinations, but further studies with a long follow-up are still necessary to confirm this.

    “Based on the available data, no serious safety concerns have been raised, but further studies with a long follow-up are still necessary to confirm this.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    In a double-blind, cross-over trial versus placebo in 40 overweight subjects with mixed hyperlipidemia, after 8 weeks of treatment with Berberis aristata extract (588 mg, containing 500 mg berberine) combined with chlorogenic acid (67 mg) and tocotrienols (143 mg), there was significant improvement in LDL-C (-24%), TG (-19%), non-HDL-C (-22%), fasting insulin (-5%) and HOMA index (-10%).

    “After 8 weeks of treatment, there was observed a significant improvement in LDL-C (–24%), TG (–19%), non-HDL-C (–22%), fasting insulin (–5%) and HOMA index (–10%) [262].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [262] Cicero AF Rosticci M Parini A Short-term effects of a combined nutraceutical of insulin-sensitivity, lipid level and indexes of liver steatosis: a double-blind, randomized, cross-over clinical trial Nutr J 2015 14 30 25886384 PMC4410738

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Findingnone given

    No safety concerns have been reported for γ-oryzanol and ω-3 PUFAs; very limited data and further studies are necessary.

    “No safety concerns. Very limited data; further studies are necessary.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In that study, the association of pea protein + oat fiber also showed 4% glucose reduction, 57% insulin reduction and 25% decrease of the HOMA index.

    “The association of pea protein + oat fiber also showed 4% glucose reduction, 57% insulin reduction and 25% decrease of the HOMA index [273].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [273] Sirtori CR Triolo M Bosisio R Hypocholesterolaemic effects of lupin protein and pea protein/fibre combinations in moderately hypercholesterolaemic individuals Br J Nutr 2012 107 1176 83 22032303

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Doubling the daily dose of red yeast rice and artichoke seemed not to add additional benefits, while there were no safety concerns also with the higher dosage.

    “Doubling the daily dose seemed not to add additional benefits, while there were no safety concerns also with the higher dosage [255].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [255] Barrat E Zaïr Y Sirvent P Effect on LDL-cholesterol of a large dose of a dietary supplement with plant extracts in subjects with untreated moderate hypercholesterolaemia: a randomised, double-blind, placebo-controlled study Eur J Nutr 2013 52 1843 52 23266743

      Not checked in the free run.

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

    Findingnone given

    No safety concerns have been reported for plant proteins and soluble fibers; very limited data and further studies are necessary.

    “No safety concerns. Very limited data; further studies are necessary.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    The association of plant sterols/stanols with certain lipid-lowering ingredients was demonstrated to strengthen cholesterol-lowering efficacy and add TG-lowering effects.

    “The association of plant sterols/stanols with certain lipid-lowering ingredients was demonstrated to strengthen cholesterol-lowering efficacy and add TG-lowering effects [250].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [250] Kamal-Eldin A Moazzami A Plant sterols and stanols as cholesterol-lowering ingredients in functional foods Recent Pat Food Nutr Agric 2009 1 1 14 20653521

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Findingcitation

    In a double-blind, placebo-controlled, cross-over trial in 30 adults with suboptimal LDL-C levels in primary prevention, after active treatment with red yeast rice (200 mg, monacolin K 10 mg), artichoke extract (500 mg), and banaba extract (50 mg), there was significant improvement in LDL-C (-18.2%), non-HDL-C (-15%), glutamic oxaloacetic transaminase (-10%), glutamate-pyruvate transaminase (-30.9

    “After the active treatment, there was observed a significant improvement in LDL-C (–18.2%), non-HDL-C (–15%), glutamic oxaloacetic transaminase (–10%), glutamate-pyruvate transaminase (–30.9%), and hs-CRP (–18.2%) vs. placebo.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [256] Cicero AF Colletti A Fogacci F Bove M Rosticci M Borghi C Effects of a combined nutraceutical on lipid pattern, glucose metabolism and inflammatory parameters in moderately hypercholesterolemic subjects: a double-blind, cross-over, randomized clinical trial High Blood Press Cardiovasc Prev 2016 24 13 8 27339779 PMC5315731

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In a double-blind, placebo-controlled, randomized clinical trial on 40 moderately hypercholesterolemic subjects, after 6 months of active treatment with red yeast rice (10 mg MonK) and CoQ10 (30 mg), there was a more favourable percentage change in LDL-C (-26.3%; p < 0.05), endothelial reactivity (PV displacement: +6.0%; p < 0.05) and arterial stiffness (PWV: -4.7%; p < 0.05).

    “After 6 months of active treatment, the results showed a more favourable percentage change in LDL-C (–26.3%; p < 0.05), endothelial reactivity (PV displacement: +6.0%; p < 0.05) and arterial stiffness (PWV: –4.7%; p < 0.05) [260].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [260] Cicero AF Morbini M Rosticci M D’Addato S Grandi E Borghi C Middle-term dietary supplementation with red yeast rice plus coenzyme Q10 improves lipid pattern, endothelial reactivity and arterial stiffness in moderately hypercholesterolemic subjects Ann Nutr Metab 2016 68 213 9 27055107

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims. The quote only partly states this claim.

    Findingnone given

    No safety concerns have been reported for pantethine, soybean plant sterols, green tea extract, delta-tocotrienol and phytolens; very limited data and further studies are necessary.

    “No safety concerns. Very limited data; further studies are necessary.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In a crossover, double-blind, placebo-controlled randomized clinical trial on 25 moderately hypercholesterolemic, pharmacologically untreated subjects in primary prevention, after 4 weeks of active treatment with red yeast rice (10 mg monacolins) plus antioxidants (green tea dry extract 100 mg; CoQ10 20 mg; astaxanthin 2 mg; resveratrol 20 mg; quercetin 50 mg), patients experienced improvement of

    “After 4 weeks of the active treatment patients experienced an improvement of cholesterol levels (LDL-C –22.36%; non-HDL-C –22.83%), hs-CRP –2.33% and endothelial function (PV displacement after monacolin treatment, 18.59%) [261].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [261] Cicero AF Morbini M Parini A Effect of red yeast rice combined with antioxidants on lipid pattern, hs-CRP level, and endothelial function in moderately hypercholesterolemic subjects Ther Clin Risk Manag 2016 12 281 6 26966368 PMC4770063

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In a 3-week randomized, placebo controlled clinical trial on 60 hyperlipidemic individuals, the combination of phytosterols (2 g) and ω-3 PUFAs (1.4 g/day) reduced LDL-C by 12.5% (p = 0.002) and TG by 25.9% (p = 0.005), and increased HDL-C by 8.6% (p = 0.04).

    “The combination of phytosterols and ω-3 PUFAs reduced LDL-C by 12.5% (p = 0.002) and TG by 25.9% (p = 0.005); moreover, it increased HDL-C (8.6%, p = 0.04) [270].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [270] Micallef MA Garg ML The lipid-lowering effects of phytosterols and (n-3) polyunsaturated fatty acids are synergistic and complementary in hyperlipidemic men and women J Nutr 2008 138 1085 90 18492838

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Clinical trials have reported that many nutraceuticals have an additive effect to lipid-lowering drugs, allowing the statin doses to be reduced without diminishing the results in terms of TC and LDL-C reduction and significantly limiting adverse effects.

    “Clinical trials have reported that many nutraceuticals have an additive effect to lipid-lowering drugs, allowing the statin doses to be reduced without diminishing the results in terms of TC and LDL-C reduction and significantly limiting adverse effects [281].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [281] Cicero AF Colletti A Banach M Statins and nutraceuticals/functional food: could they be combined? Combination Therapy In Dyslipidemia 2016 127 42

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based). May combine two claims. The quote only partly states this claim.

    Findingnone given

    No safety concerns have been reported for garlic and omega-3 PUFAs; very limited data and further studies are necessary.

    “No safety concerns. Very limited data; further studies are necessary.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based). May combine two claims.

    Findingnone given

    No safety concerns have been reported for ezetimibe, red yeast rice, policosanol and berberine; limited data and further studies are necessary.

    “No safety concerns; limited data – further studies are necessary.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In that study, all reported side effects lasted a few days and did not lead to interruption of treatment.

    “All reported side effects lasted a few days and did not lead to interruption of treatment [291].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [291] Di Pierro F Bellone I Rapacioli G Putignano P Clinical role of a fixed combination of standardized Berberis aristata and Silybum marianum extracts in diabetic and hypercholesterolemic patients intolerant to statins Diabetes Metab Syndr Obes 2015 8 89 96 25678808 PMC4322873

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In that study, TGs were reduced by 36% and HDL-C increased by 37%, significantly higher than with rosuvastatin alone.

    “In addition, TGs were reduced by 36% and HDL-C increased by 37%, an effect that was significantly higher when compared to the use of rosuvastatin alone.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [120] Gliozzi M Walker R Muscoli S 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 170 140 5 24239156

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims. The quote only partly states this claim.

    Findingnone given

    No safety concerns have been reported for statins and garlic; limited data and further studies are necessary.

    “No safety concerns; limited data – further studies are necessary.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In that study, the triple treatment increased the serum lathosterol/cholesterol ratio (p < 0.01), showing upregulation of cholesterol synthesis, and increased the serum sitosterol ratio (p < 0.01).

    “It also increased the serum lathosterol/cholesterol ratio (p < 0.01), thus showing upregulation of cholesterol synthesis, and increased the serum sitosterol ratio (p < 0.01).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [293] Gylling H Miettinen TA LDL cholesterol lowering by bile acid malabsorption during inhibited synthesis and absorption of cholesterol in hypercholesterolemic coronary subjects Nutr Metab Cardiovasc Dis 2002 12 19 23 12125225

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In eleven hypercholesterolemic coronary patients on a low-fat, low-cholesterol baseline diet, simvastatin (20 mg/day) for 3 months reduced LDL-C by 39% (p < 0.001) and additional dietary plant stanol ester margarine (2.25 g stanols/day) for 8 weeks reduced it by a further 13% (p < 0.05).

    “The results highlighted that simvastatin reduced LDL-C by 39% (p < 0.001) and additional stanol ester margarine reduced it by a further 13% (p < 0.05).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [293] Gylling H Miettinen TA LDL cholesterol lowering by bile acid malabsorption during inhibited synthesis and absorption of cholesterol in hypercholesterolemic coronary subjects Nutr Metab Cardiovasc Dis 2002 12 19 23 12125225

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims. The quote only partly states this claim.

    Findingnone given

    No safety concerns have been reported for statins and bergamot; limited data and further studies are necessary.

    “No safety concerns; limited data – further studies are necessary.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    No safety concerns have been reported for statins and PUFAs; limited data and further studies are necessary.

    “No safety concerns; limited data – further studies are necessary.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Ezetimibe and nutraceuticals have been introduced, alone or in association, as alternative therapies for statin-intolerant patients and proved to be effective and well tolerated.

    “Ezetimibe and nutraceuticals have been both introduced, alone or in association, as alternative therapies for statin-intolerant patients and proved to be effective and well tolerated.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based). May combine two claims. The quote only partly states this claim.

    Findingnone given

    No safety concerns have been reported for ezetimibe or statins and berberine with silymarin; limited data and further studies are necessary.

    “No safety concerns; limited data – further studies are necessary.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In a randomized clinical trial with parallel arms of 86 subjects, compared with baseline, atorvastatin 40 mg reduced LDL-C (22%, p < 0.05) and increased β-sitosterol, campesterol/cholesterol, and β-sitosterol/cholesterol ratios (39%, 47%, and 32%, respectively, p < 0.05); ezetimibe 10 mg reduced campesterol and campesterol/cholesterol ratio (67% and 70%, respectively, p < 0.05); combined therapy

    “Compared with baseline, atorvastatin 40 mg showed a reduction of LDL-C (22%, p < 0.05), and increased β-sitosterol, campesterol/cholesterol, and β-sitosterol/cholesterol ratios (39%, 47%, and 32%, respectively, p < 0.05); ezetimibe 10 mg reduced campesterol and campesterol/cholesterol ratio (67% and 70%, respectively, p < 0.05), while the combined therapy decreased LDL-C (38%, p < 0.05), campester”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [292] Malina DM Fonseca FA Barbosa SA Additive effects of plant sterols supplementation in addition to different lipid-lowering regimens J Clin Lipidol 2015 9 542 52 26228672

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In that trial, among patients treated with highly effective lipid-lowering therapy, intake of 25 g of fibers added favorable effects: a reduction of phytosterolemia, improvement in blood glucose (p = 0.047), weight loss (p = 0.04) and reduced body mass index (p = 0.002).

    “Among patients treated with highly effective lipid-lowering therapy, the intake of 25 g of fibers added favorable effects: a reduction of phytosterolemia, improvement in blood glucose (p = 0.047), weight loss (p = 0.04) and reduced body mass index (p = 0.002) [288].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [288] Ramos SC Fonseca FA Kasmas SH The role of soluble fiber intake in patients under highly effective lipid-lowering therapy Nutr J 2011 10 80 21810257 PMC3159132

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In a study of 77 patients with mixed hyperlipidemia, combined therapy with bergamot-derived polyphenolic fraction (1000 mg/daily for 30 days) and rosuvastatin (10 mg/day for 30 days) significantly reduced LDL-C (-53%) compared to rosuvastatin alone, an effect nearly the same as that produced by 20 mg of rosuvastatin.

    “It was observed that the combined therapy significantly reduced LDL-C (–53%) compared to rosuvastatin alone, an effect which was nearly the same as the one produced by 20 mg of rosuvastatin.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [120] Gliozzi M Walker R Muscoli S 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 170 140 5 24239156

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In 45 patients with type 2 diabetes with hypercholesterolemia and statin intolerance, intake of Berberis aristata (588 mg, containing berberine 500 mg) and Silybum marianum (105 mg) extracts twice a day with statins led to improvement of lipid parameters (LDL-C -15% and -28% after 6 and 12 months) and also when added to ezetimibe (LDL-C -20% and -33% after 6 and 12 months).

    “The intake of berberine/silymarin with statins led to an improvement of lipid parameters (LDL-C –15% and –28%, respectively after 6 and 12 months) and also when added to ezetimibe (LDL-C –20% and –33% respectively after 6 and 12 months).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [291] Di Pierro F Bellone I Rapacioli G Putignano P Clinical role of a fixed combination of standardized Berberis aristata and Silybum marianum extracts in diabetic and hypercholesterolemic patients intolerant to statins Diabetes Metab Syndr Obes 2015 8 89 96 25678808 PMC4322873

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In that study, triple treatment with simvastatin, stanol ester margarine, and cholestyramine led to 67% reduction from baseline (p < 0.001), with all LDL-C values < 2.6 mmol/l, and increased HDL-C by 15% (p < 0.01).

    “The triple treatment led to 67% reduction from baseline (p < 0.001), with all LDL-C values being < 2.6 mmol/l, and increased HDL-C by 15% (p < 0.01).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [293] Gylling H Miettinen TA LDL cholesterol lowering by bile acid malabsorption during inhibited synthesis and absorption of cholesterol in hypercholesterolemic coronary subjects Nutr Metab Cardiovasc Dis 2002 12 19 23 12125225

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Data from a long-term randomized clinical trial support that combining statins with ω-3 fatty acids seems to further decrease CHD risk by 19% in primary prevention and CHD mortality by 17% in secondary prevention.

    “Data from a long-term randomized clinical trial support the concept that combining statins with ω-3 fatty acids seems to further decrease CHD risk by 19% in primary prevention [284] and CHD mortality by 17% in secondary prevention [285].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [284] Yokoyama M Origasa H Matsuzaki M Japan EPA lipid intervention study (JELIS) investigators Lancet 2007 369 1090 8

      Not checked in the free run.

    • cites [285] Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico Lancet 1999 354 447 55 10465168

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims. The quote only partly states this claim.

    Findingnone given

    No safety concerns have been reported for statins and tocotrienols; limited data and further studies are necessary.

    “No safety concerns; limited data – further studies are necessary.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In a 12-week blinded placebo-controlled study of 68 patients, after 8 weeks, the mean lowering of LDL-C (-63 mg/dl/-1.63 mmol/l; p = 0.03) in the group receiving 20 mg simvastatin plus placebo was the same as that in the group receiving 10 mg simvastatin plus psyllium and was greater than that obtained with 10 mg simvastatin plus placebo (55 mg/dl/1.42 mmol/l; p = 0.03).

    “After 8 weeks, the mean lowering of LDL-C (–63 mg/dl/–1.63 mmol/l; p = 0.03) in the group receiving 20 mg of simvastatin plus placebo was the same as that in the group receiving 10 mg of simvastatin plus psyllium and was greater than that obtained with 10 mg of simvastatin plus placebo (55 mg/dl/1.42 mmol/l; p = 0.03).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [287] Moreyra AE Wilson AC Koraym A Effect of combining psyllium fiber with simvastatin in lowering cholesterol Arch Intern Med 2005 165 1161 6 15911730

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims. The quote only partly states this claim.

    Findingnone given

    No safety concerns have been reported for statins and soluble fibers; limited data and further studies are necessary.

    “No safety concerns; limited data – further studies are necessary.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In that study, addition of plant sterols further reduced LDL-C by ~6.5% in the atorvastatin therapy group and 5.0% and 4.0% in the combined therapy group (p < 0.05 for all).

    “This study demonstrated that the addition of plant sterols further reduced LDL-C by ~6.5% in the atorvastatin therapy group and 5.0% and 4.0% in the combined therapy group (p < 0.05 for all) [292].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [292] Malina DM Fonseca FA Barbosa SA Additive effects of plant sterols supplementation in addition to different lipid-lowering regimens J Clin Lipidol 2015 9 542 52 26228672

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In that study, similar results were reported for apoB and TC, while no significant changes of TG or HDL-C levels were observed.

    “Similar results were reported for apoB and TC, while there were not observed significant changes of TG or HDL-C levels [287].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [287] Moreyra AE Wilson AC Koraym A Effect of combining psyllium fiber with simvastatin in lowering cholesterol Arch Intern Med 2005 165 1161 6 15911730

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In a randomized, parallel-design clinical trial of 116 patients with primary hypercholesterolemia, therapies with rosuvastatin 40 mg plus fiber, rosuvastatin 40 mg alone, simvastatin 40 mg plus ezetimibe 10 mg plus fiber, or simvastatin 40 mg plus ezetimibe 10 mg alone during 12 weeks led to similar reductions in LDL-C and TC (p < 0.001 vs. baseline), while no change was observed in HDL-C.

    “These therapies led to similar reductions in LDL-C and TC (p < 0.001 vs. baseline), while no change was observed in HDL-C.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [288] Ramos SC Fonseca FA Kasmas SH The role of soluble fiber intake in patients under highly effective lipid-lowering therapy Nutr J 2011 10 80 21810257 PMC3159132

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In a randomized, double-blind, placebo-controlled, two arms parallel study on 258 subjects who met ATP-III criteria for drug treatment of hyperlipidemia and dietary intervention, patients who followed 8-week treatment with simvastatin (10 mg) plus placebo obtained a significant reduction in non-HDL-C (-10.8%), TG (-6.9%), and LDL-C (-11.6%) (p ≤ 0.01), and an increase in HDL-C (+10.4%) (p = 0.02).

    “Patients who followed 8-week treatment with simvastatin (10 mg) plus placebo obtained a significant reduction in non-HDL-C (–10.8%), TG (–6.9%), and LDL-C (–11.6%) (p ≤ 0.01), and an increase in HDL-C (+10.4%) (p = 0.02).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [295] Ahmad Alobaidi AH Effect of Nigella sativa and Allium sativum coadminstered with simvastatin in dyslipidemia patients: a prospective, randomized, double-blind trial Antiinflamm Antiallergy Agents Med Chem 2014 13 68 74 23848231

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In 36 volunteers, after 4 weeks, mean LDL-C and TG levels in the group receiving lovastatin 20 mg plus psyllium 10 g fell by 30.9% and 26.2% from baseline compared with 24.8% and 32.9% in the lovastatin group and 3.6% and 10.9% in the psyllium group.

    “After 4 weeks of treatment, the mean LDL-C and TG levels in the group receiving 20 mg of lovastatin plus 10 g of psyllium fell by 30.9% and 26.2% from baseline compared with 24.8% and 32.9% in the group receiving 20 mg of lovastatin and 3.6% and 10.9% in the group receiving 10 g of psyllium, respectively [286].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [286] Agrawal AR Tandon M Sharma PL Effect of combining viscous fibre with lovastatin on serum lipids in normal human subjects Int J Clin Pract 2007 61 1812 8 17935545

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims. The quote only partly states this claim.

    Findingnone given

    No safety concerns have been reported for statins/ezetimibe and plant sterols; limited data and further studies are necessary.

    “No safety concerns; limited data – further studies are necessary.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In that study, a significant reduction of biomarkers used for detecting oxidative vascular damage was reported, suggesting antioxidant activity of bergamot in patients on statin therapy.

    “Moreover, a significant reduction of biomarkers used for detecting oxidative vascular damage was reported, suggesting antioxidant activity of bergamot in patients on statin therapy [120].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [120] Gliozzi M Walker R Muscoli S 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 170 140 5 24239156

      Not checked in the free run.

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

    Premisecitation

    The range of people intolerant to conventional statin treatment is estimated between 45,000 and 290,000 individuals/year.

    “This is particularly relevant since it is estimated that the range of people intolerant to conventional statin treatment is between 45 000 and 290 000 individuals/year [36]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Bangalore S Fayyad R Hovingh GK Treating to New Targets Steering Committee and Investigators Statin and the risk of renal-related serious adverse events: analysis from the IDEAL, TNT, CARDS, ASPEN, SPARCL, and other placebo-controlled trials Am J Cardiol 2014 113 2018 20 24793673

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Very old patients (especially those aged over 75) or patients with sarcopenia might benefit from lipid-lowering nutraceuticals.

    “Another group of patients who might benefit from such nutraceuticals consists of very old patients (especially those aged over 75) or patients with sarcopenia [40].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] Banach M Serban MC Discussion around statin discontinuation in older adults and patients with wasting diseases J Cachexia Sarcopenia Muscle 2016 7 396 99 27030814 PMC4782254

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    New powerful lipid-lowering drugs will be able to fill the gap and reduce residual CV risk.

    “The development of new powerful (and very expensive) lipid-lowering drugs will be able to fill the gap (and in consequence reduce the residual CV risk)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [41] Banach M Aronow WS Serban MC Rysz J Voroneanu L Covic A Lipids, blood pressure and kidney update 2015 Lipids Health Dis 2015 14 167 26718096 PMC4696333

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Cholesterol-lowering drug therapy is not associated with an increased risk of cancer or non-CV-related death.

    “in the absence of an increased risk of cancer or non-CV-related death [13].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Baigent C Blackwell L Emberson J Cholesterol Treatment Trialists’ (CTT) Collaboration Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials Lancet 2010 376 1670 81 21067804 PMC2988224

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Levels of LDL-C < 100 mg/dl (~2.5 mmol/l) are associated with a low risk for CHD and are considered optimal in the absence of CVD or other risk factors.

    “Levels of LDL-C < 100 mg/dl (~2.5 mmol/l) are associated with a low risk for CHD and are considered optimal in the absence of CVD or other risk factors [17].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Law MR Wald NJ Thompson SG By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? BMJ 1994 308 367 72 8043072 PMC2539460

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Nutraceuticals can have positive pleiotropic effects, including improvement of endothelial dysfunction and arterial stiffness, as well as anti-inflammatory and anti-oxidative properties.

    “Moreover, they can have a large number of positive pleiotropic effects, including improvement of endothelial dysfunction and arterial stiffness, as well as anti-inflammatory and anti-oxidative properties [33].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [33] Houston M The role of nutraceutical supplements in the treatment of dyslipidemia J Clin Hypertens 2012 14 121 32 PMC9645405 22277145

      Not checked in the free run.

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

    Premisecitation

    Complete statin intolerance is estimated at less than 5%.

    “(complete statin intolerance is estimated at less than 5%)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Bangalore S Fayyad R Hovingh GK Treating to New Targets Steering Committee and Investigators Statin and the risk of renal-related serious adverse events: analysis from the IDEAL, TNT, CARDS, ASPEN, SPARCL, and other placebo-controlled trials Am J Cardiol 2014 113 2018 20 24793673

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  • May combine two claims.

    Premisecitation

    Elevated total cholesterol and LDL-C blood concentrations are major modifiable risk factors for coronary heart disease, whereas high plasma HDL-C is protective in certain conditions.

    “Elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) blood concentrations are the major modifiable risk factors for coronary heart disease (CHD), whereas high concentrations of plasma high-density lipoprotein cholesterol (HDL-C) in certain conditions are considered protective [6].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6] Australian Institute of Health and Welfare High Blood Cholesterol. Cat. No. AUS 156 2012-2013 Canberra Australian Institute of Health and Welfare

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  • May combine two claims.

    Premisecitation

    Plant sterols and stanols intensify the expression of ABCA1 transporter and inhibit ACAT enzyme, reducing the amount of cholesterol absorbed from 30% to 50%.

    “PS also intensify the expression of ABCA1 transporter and inhibit the acyl-CoA:cholesterol O-acyltransferase (ACAT) enzyme, reducing the amount of cholesterol absorbed from 30% to 50%.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [44] Ras RT Hiemstra H Lin Y Vermeer MA Duchateau GS Trautwein EA Consumption of plant sterol-enriched foods and effects on plasma plant sterol concentrations: a meta-analysis of randomized controlled studies Atherosclerosis 2013 230 336 46 24075766

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    • cites [45] Ferguson JJ Stojanovski E MacDonald-Wicks L Garg ML Fat type in phytosterol products influence their cholesterol-lowering potential: a systematic review and meta-analysis of RCTs Prog Lipid Res 2016 64 16 29 27497855

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  • May combine two claims.

    Premisecitation

    EFSA confirmed that oat β-glucan is able to reduce plasmatic cholesterol levels; at least 3 g/day of β-glucan is necessary.

    “In 2010 the European Food Safety Authority (EFSA) confirmed that oat β-glucan is able to reduce plasmatic cholesterol levels; however, at least 3 g/day of β-glucan is necessary [54].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [54] EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) Scientific opinion on the substantiation of a health claim related to oat beta-glucan and lowering blood cholesterol and reduced risk of (coronary) heart disease pursuant to Article 14 of Regulation (EC) No 1924/2006 EFSA J 2010 8 188

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  • May combine two claims.

    Premisecitation

    β-glucan is a soluble fiber with high viscosity, which confers lipid-lowering action.

    “β-glucan has high viscosity, which confers lipid-lowering action [32].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Sahebkar A Serban MC Gluba-Brzózka A Lipid-modifying effects of nutraceuticals: an evidence-based approach Nutrition 2016 32 1179 92 27324061

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  • May combine two claims.

    Premisecitation

    The reduction of cholesterol obtained by soluble fibers is variable and dependent on the type of fiber, doses, subjects treated, study size and different diets: the effective range of reduction of TC varies from 0 to 18% for oat-based fibers, 3-17% for psyllium, 5-16% for pectin, and 4-17% for guar gum.

    “The reduction of cholesterol obtained by soluble fibers described in the literature is variable and dependent on the type of fiber, doses, subjects treated, study size and different diets: the effective range of the reduction of TC varies from 0 to 18% for oat-based fibers, 3–17% for psyllium, 5–16% for pectin, and 4–17% for guar gum [51].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [51] Brown L Rosner B Willett WW Sacks FM Cholesterol-lowering effects of dietary fiber: a meta-analysis Am J Clin Nutr 1999 69 30 42 9925120

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  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The level of evidence and the strength of recommendation of particular lipid-lowering treatment options have been weighed and graded according to predefined scales.

    “The level of evidence and the strength of recommendation of particular lipid-lowering treatment options have been weighed and graded according to predefined scales, as outlined in Tables I and II.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In some cases minor gastrointestinal side effects were reported with psyllium (especially with micronized fibers) that might slightly reduce adherence.

    “However, in some cases minor gastrointestinal side effects were reported (especially with micronized fibers) that might slightly reduce the adherence to this nutraceutical [64].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [64] Anderson JW Allgood LD Lawrence A Cholesterol-lowering effects of psyllium intake adjunctive to diet therapy in men and women with hypercholesterolemia: meta-analysis of 8 controlled trials Am J Clin Nutr 2000 71 472 9 10648260

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

    Study design and conductnone given

    The experts of the writing and reviewing panels completed Declaration of interest forms where real or potential sources of conflicts of interest might be perceived.

    “The experts of the writing and reviewing panels completed Declaration of interest forms where real or potential sources of conflicts of interest might be perceived (at the end of the paper).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The mechanisms of action of psyllium include increased excretion of bile acids, reduced absorption of intestinal cholesterol and reduction of hepatic cholesterol synthesis.

    “The mechanisms of action of psyllium are similar to those of other fibers discussed, including increased excretion of bile acids (stimulating 7α-hydroxylase), reduced absorption of intestinal cholesterol and a reduction of hepatic cholesterol synthesis (via the short-chain fatty acid byproducts of fiber fermentation) [58].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [58] Anderson JW Dietary fibre, complex carbohydrate and coronary artery disease Can J Cardiol 1995 11 Suppl G 55G 62G 7585294

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  • May combine two claims.

    Premisecitation

    Unlike other fibers, glucomannan does not act by binding bile acids, but it seems to reduce the absorption of cholesterol in the jejunum and the absorption of bile acids in the ileum, yielding improvements in apolipoprotein B (ApoB) and plasma LDL-C levels.

    “Unlike other fibers, glucomannan does not act by binding bile acids, but it seems to reduce the absorption of cholesterol in the jejunum and the absorption of bile acids in the ileum, yielding improvements in apolipoprotein B (ApoB) and plasma LDL-C levels.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [65] Behera SS Ray RC Konjac glucomannan, a promising polysaccharide of Amorphophallus konjac K. Koch in health care Int J Biol Macromol 2016 92 942 56 27481345

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  • May combine two claims.

    Premisecitation

    Plant sterols/stanols have shown a high safety profile in the middle-term; data for treatment longer than 2 years are still not available.

    “PS have also shown a high safety profile in the middle-term; however, data for treatment longer than 2 years are still not available [44, 50].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [44] Ras RT Hiemstra H Lin Y Vermeer MA Duchateau GS Trautwein EA Consumption of plant sterol-enriched foods and effects on plasma plant sterol concentrations: a meta-analysis of randomized controlled studies Atherosclerosis 2013 230 336 46 24075766

      Not checked in the free run.

    • cites [50] Gylling H Halonen J Lindholm H The effects of plant stanol ester consumption on arterial stiffness and endothelial function in adults: a randomised controlled clinical trial BMC Cardiovasc Disord 2013 13 50 23841572 PMC3717082

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  • May combine two claims.

    Premisecitation

    The lipid-lowering effect of plant sterols/stanols is dose dependent and proportional up to a plateau reached at approximately 3 g/day, achieving an average effect on LDL-C of -12%.

    “The lipid-lowering effect of PS is dose dependent and proportional up to the attainment of a plateau (reached at approximately 3 g/day of PS achieving an average effect on LDL-C of –12%)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [48] Talati R Sobieraj DM Makanji SS Phung OJ Coleman CI The comparative efficacy of plant sterols and stanols on serum lipids: a systematic review and meta-analysis J Am Diet Assoc 2010 110 719 26 20430133

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  • The quote only partly states this claim.

    Premisecitation

    In a meta-analysis of 41 clinical trials with 2084 individuals, plant sterols/stanols significantly reduced LDL-C by 0.33 mmol/l (12.8 mg/dl) (-8.5%) compared to controls.

    “The meta-analysis showed not only the significant reduction of LDL-C of 0.33 mmol/l (12.8 mg/dl) (–8.5%)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [44] Ras RT Hiemstra H Lin Y Vermeer MA Duchateau GS Trautwein EA Consumption of plant sterol-enriched foods and effects on plasma plant sterol concentrations: a meta-analysis of randomized controlled studies Atherosclerosis 2013 230 336 46 24075766

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  • May combine two claims.

    Premisecitation

    The lipid-lowering mechanisms of soluble fibers include prolonged gastric emptying time, an increase of satiety, inhibition of hepatic cholesterol synthesis and an increase of fecal excretion of cholesterol and bile salts.

    “The lipid-lowering mechanisms of action of soluble fibers are different, including prolonged gastric emptying time, an increase of satiety, the inhibition of hepatic cholesterol synthesis and an increase of fecal excretion of cholesterol and bile salts [52].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Doi K Effect of konjac fibre (glucomannan) on glucose and lipids Eur J Clin Nutr 1995 49 Suppl 3 S190 7 8549522

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  • May combine two claims.

    Premisecitation

    A meta-analysis of 6 RCTs including 416 patients with hypercholesterolemia concluded that chitosan has a significant effect on TC (-0.3 mmol/l (11.6 mg/dl), p = 0.002), but not on LDL-C, HDL-C or TG.

    “A meta-analysis of 6 RCTs including 416 patients with hypercholesterolemia concluded that it has a significant effect on TC (–0.3 mmol/l (11.6 mg/dl), p = 0.002), but not on LDL-C, HDL-C or TG [71].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [71] Baker WL Tercius A Anglade M White CM Coleman CI A meta-analysis evaluating the impact of chitosan on serum lipids in hypercholesterolemic patients Ann Nutr Metab 2008 55 368 74 19923803

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  • May combine two claims.

    Premisecitation

    In the same trial, NNT to prevent one coronary event, one coronary death, and one all-cause mortality in elderly patients were 18, 33, and 23; in adults, 23, 82, and 51.

    “It was also estimated that following RYR treatment for 4 years, the number needed to treat (NNT) to prevent one coronary event, one coronary death and one mortality due to all causes in elderly patients were respectively 18, 33 and 23. In adults, however, these numbers were 23, 82 and 51.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [93] DFG Permanent Senate Commission on Food Safety Toxicological evaluation of red mould rice: an update 2012

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  • May combine two claims.

    Premisecitation

    Probiotics are generally very safe, and side effects are rare.

    “Probiotics are considered to be generally very safe, and side effects are rare.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [84] Doron S Snydman DR Risk and safety of probiotics Clin Infect Dis (Review) 2015 60 Suppl 2 S129 34 PMC4490230 25922398

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  • May combine two claims.

    Premisecitation

    In a meta-analysis of RCTs, Lactobacillus had a stronger cholesterol-lowering effect, with most promising results after >4 weeks.

    “A stronger cholesterol-lowering effect of Lactobacillus was confirmed in the meta-analysis of RCTs by Shimizu et al., where the most promising results were obtained after a treatment period of more than 4 weeks”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [83] Shimizu M Hashiguchi M Shiga T Tamura HO Mochizuki M Meta-analysis: effects of probiotic supplementation on lipid profiles in normal to mildly hypercholesterolemic individuals PLoS One 2015 10 e0139795 26473340 PMC4608827

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  • May combine two claims.

    Premisecitation

    In a meta-analysis of 39 RCTs (2298 mild-to-moderate hypercholesterolemic subjects), garlic extracts for at least 2 months reduced LDL-C by 0.23 mmol/l (9 mg/dl), more evident in individuals with TC <5.17 mmol/l at baseline.

    “In a meta-analysis of 39 RCTs enrolling 2298 mild-to-moderate hypercholesterolemic subjects 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) [103].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [103] Ried K Toben C Fakler P Effect on garlic on serum lipids: an updated meta-analysis Nutr Rev 2013 71 282 99 23590705

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  • May combine two claims.

    Premisecitation

    This gender-dependent effect was also observed with other soluble fibers, and it would seem to be caused by the interaction between sex hormones and lipid metabolism; nevertheless, further corroboration is necessary.

    “This gender-dependent effect was also observed with other soluble fibers, and it would seem to be caused by the interaction between sex hormones and lipid metabolism; nevertheless, further corroboration is necessary [69].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [69] Martino F Martino E Morrone F Carnevali E Forcone R Niglio T Effect of dietary supplementation with glucomannan on plasma total cholesterol and low density lipoprotein cholesterol in hypercholesterolemic children Nutr Metab Cardiovasc Dis 2005 15 174 80 15955465

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  • May combine two claims.

    Premisecitation

    In a large trial of 1445 patients with prior MI followed for 4 years, RYR reduced risk of CHD by 31.0% (p=0.04), all-cause mortality by 31.9% (p=0.01), stroke by 44.1% (p=0.04), need for CABG/PCI by 48.6% (p=0.07), and malignancies by 51.4% (p=0.03).

    “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 (CABG) or a percutaneous coronary intervention (PCI) (48.6%, p = 0.07) and malignancies (51.4%, p = 0.03).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [93] DFG Permanent Senate Commission on Food Safety Toxicological evaluation of red mould rice: an update 2012

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a 6-week trial of 50 CHD patients, RYR 1200 mg/day reduced hs-CRP and TG-AUC and improved postprandial and pre-prandial FMD, with no significant changes in placebo.

    “The results showed that the group treated with RYR at the end of the 6-week follow-up obtained a reduction of hs-CRP and the area under the curve (AUC) of triglyceride (TG-AUC) (p < 0.001 for each), in addition to an improvement of postprandial and pre-prandial FMD (p < 0.001). There were no significant changes in serum lipids and FMD in the placebo group [92].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [92] Zhao SP Liu L Cheng YC Xuezhikang, an extract of cholestin, protects endothelial function through antiinflammatory and lipid-lowering mechanisms in patients with coronary heart disease Circulation 2004 110 915 20 15313947

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  • May combine two claims.

    Premisecitation

    The intake of glucomannan may interfere with the absorption of certain drugs, in particular lipophilic drugs/nutraceuticals: for example, glucomannan could reduce the absorption of vitamin E, calcium and other minerals, whereas it does not hinder the absorption of water-soluble vitamins.

    “The intake of glucomannan may interfere with the absorption of certain drugs, in particular lipophilic drugs/nutraceuticals: for example, glucomannan could reduce the absorption of vitamin E, calcium and other minerals, whereas it does not hinder the absorption of water-soluble vitamins.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Sahebkar A Serban MC Gluba-Brzózka A Lipid-modifying effects of nutraceuticals: an evidence-based approach Nutrition 2016 32 1179 92 27324061

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  • May combine two claims.

    Premisecitation

    Garlic reduces apoB and increases the LDL/Apo B ratio.

    “Jung et al. [106] underlined that it is able to reduce apoB and increase the LDL/Apo B ratio.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [106] Jung ES Park SH Choi EK Reduction of blood lipid parameters by a 12-wk supplementation of aged black garlic: a randomized controlled trila Nutrition 2014 30 1034 9 24976429

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  • May combine two claims.

    Premisecitation

    TG and HDL-C did not change significantly compared to control groups with probiotics.

    “TG and HDL-C did not change significantly compared to the control groups.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [81] Cho YA Kim J Effect of probiotics on blood lipid concentrations: a meta-analysis of randomized controlled trials Medicine 2015 94 e1714 26512560 PMC4985374

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  • May combine two claims.

    Premisecitation

    The AHRQ 2011 report concluded that existing probiotic clinical trials reveal no evidence of increased risk, but there are not enough data to answer safety questions in intervention studies with confidence.

    “The report released by the Agency for Healthcare Research and Quality (2011) concluded that, although the existing probiotic clinical trials reveal no evidence of increased risk, there are not enough data to answer questions on the safety of probiotics in intervention studies with confidence [84].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [84] Doron S Snydman DR Risk and safety of probiotics Clin Infect Dis (Review) 2015 60 Suppl 2 S129 34 PMC4490230 25922398

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The consumption of probiotics is considered safe and free of serious side effects.

    “The consumption of probiotics is considered safe and free of serious side effects [76].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [76] Guarner F Schaafsma GJ Probiotics Int J Food Microbiol 1998 39 237 8 9553803

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  • May combine two claims.

    Premisecitation

    The reduction of serum triglycerides is a peculiarity of glucomannan, probably due to its high viscosity and its ability to interact with the hepatic cholesterol and lipoprotein metabolism, but not of other soluble fibers, which have only a very modest action on triglyceride levels.

    “The reduction of serum triglycerides is a peculiarity of glucomannan, probably due to its high viscosity and its ability to interact with the hepatic cholesterol and lipoprotein metabolism, but not of other soluble fibers, which have only a very modest action on triglyceride levels [66].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [66] 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 Clin Nutr 2008 88 1167 75 18842808

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  • May combine two claims.

    Premisecitation

    Side effects of garlic are usually minimal (mostly gastrointestinal) and extracts are well tolerated.

    “Side effects are usually minimal (mostly gastrointestinal) and the extracts are well tolerated [104].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [104] 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 161 813 24 11268223

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  • May combine two claims.

    Premisecitation

    Data on weight reduction with glucomannan are controversial; in general glucomannan is able to promote maintenance of weight and in some cases (with at least 5.2 weeks of treatment) it can cause a small reduction of weight, although only less than 1 kg.

    “Data on weight reduction are controversial; in general it can be said that glucomannan is able to promote the maintenance of weight and in some cases (with at least 5.2 weeks of treatment) it can cause a small reduction of weight (according to some meta-analyses significant, according to others not), although only less than 1 kg [67].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] Onakpoya I Posadzki P Ernst E The efficacy of glucomannan supplementation in overweight and obesity: a systematic review and meta-analysis of randomized clinical trials J Am Coll Nutr 2014 33 70 8 24533610

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  • May combine two claims.

    Premisecitation

    In a meta-analysis of 27 clinical studies (2569 participants), berberine reduced LDL-C by 0.65 mmol/l (25.14 mg/dl), TG by 0.39 mmol/l (34.5 mg/dl), and increased HDL-C by 0.07 mmol/l (2.71 mg/dl).

    “The effects of berberine on lipids were: 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 [138] Lan J Zhao Y Dong F 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 25498346

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

    Premisenone given

    The tolerability of policosanols is usually very good.

    “The tolerability of policosanols is usually very good.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In a 16-week triple-blinded RCT of 120 subjects with low to moderate CVD risk, pantethine 600-900 mg/day significantly reduced TC by 3%, LDL-C by 4%, and apoB by 5% from baseline to week 16.

    “The authors showed that following an adequate diet in comparison with placebo, pantethine 600–900 mg/day demonstrated significant (p < 0.005) and sustained reductions (from baseline to week 16) in TC (3% – 0.16 mmol/l (6 mg/dl)), LDL-C (4% – 0.10 mmol/l (4 mg/dl)) and apoB (5% – 0.0001 mmol/l (4 mg/dl)).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [113] Rumberger JA Napolitano J Azumano I Kamiya T Evans M Pantethine, a derivative of vitamin B(5) used as a nutritional supplement, favorably alters low-density lipoprotein cholesterol metabolism in low- to moderate-cardiovascular risk North American subjects: a triple-blinded placebo and diet-controlled investigation Nutr Res 2011 31 608 15 21925346

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  • May combine two claims.

    Premisecitation

    A third RCT showed that lupin reduced LDL-C by 12%, comparable to previous studies.

    “The cholesterol-lowering properties of lupin were also highlighted in a third RCT proving a reduction of LDL-C (–12%) comparable to the studies described previously [160].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [160] Fechner A Kiehntopf M Jahreis G The formation of short-chain fatty acids is positively associated with the blood lipid-lowering effect of lupin kernel fiber in moderately hypercholesterolemic adults J Nutr 2014 144 599 607 24572041

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  • May combine two claims.

    Premisecitation

    In a meta-analysis of 35 RCTs (2670 subjects), soy proteins reduced LDL-C by 3% (-0.12 mmol/l/4.6 mg/dl), TC by 2% (-0.14 mmol/l/5.4 mg/dl), TG by 4% (-0.06 mmol/l/5.3 mg/dl), and increased HDL-C by 3% (+0.04 mmol/l/1.6 mg/dl), with effect proportional to baseline LDL-C.

    “a recent one including 35 RCTs and 2670 subjects concluded that soy proteins (in particular B-conglycinin globulin) have a cholesterol-lowering effect with a mean reduction in LDL-C of 3% (–0.12 mmol/l/4.6 mg/dl), TC of 2% (–0.14 mmol/l/5.4 mg/dl) and TG of 4% (–0.06 mmol/l/5.3 mg/dl) and is able to increase HDL-C by 3% (+0.04 mmol/l/1.6 mg/dl), the effect being proportional to the baseline LDL-C”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [154] 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 114 831 43 26268987

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  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    In 107 patients with MetS and NAFLD, bergamot 1300 mg/day for 120 days reduced sdLDL and TG and increased HDL-C compared to placebo.

    “They found that the treated group experienced a marked reduction of small dense LDL (sdLDL) and TG, and increased HDL-C levels compared to placebo.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [121] Gliozzi M Carresi C Musolino V The effect of Bergamot-derived polyphenolic fraction on LDL small dense particles and non alcoholic fatty liver disease in patients with metabolic syndrome Adv Biol Chem 2014 4 129 37

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  • May combine two claims.

    Premisecitation

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

    “These effects seem to be additive to those of statins and associated with a positive impact on glucose metabolism and blood pressure as well [138].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [138] Lan J Zhao Y Dong F 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 25498346

      Not checked in the free run.

  • May combine two claims.

    Study design and conductnone given

    The main limitation of bergamot efficacy evidence is that most clinical literature comes from a single research unit and has not been confirmed elsewhere.

    “The main limitation of the evidence on bergamot efficacy is related to the fact that the greater part of the clinical literature has been provided by a single research unit and not confirmed elsewhere.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Clinical studies of bergamot at 500-1500 mg/day showed a good safety profile with no side effects detected.

    “Clinical studies conducted to date with dosages between 500 and 1500 mg/day showed a good safety profile, with no side effects detected.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    The evidence indicates that bergamot has lipid-lowering effects, especially by reducing sdLDL and TG and significantly increasing HDL-C.

    “In summary, the evidence indicates that bergamot has lipid-lowering effects, both quantitative and qualitative, especially by reducing the levels of sdLDL and TG and significantly increasing HDL-C levels.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The cited meta-analyses and RCTs are of sufficient methodological quality and their results are valid for the populations studied.
    • Rests on an assumption: The effects of nutraceuticals observed in trials generalize to clinical practice in the broader patient populations for whom they are recommended.

  • May combine two claims.

    Premisecitation

    In the same randomized cross-over study, the LPI group showed a significant increase in HDL-C (p < 0.036) and a decrease in LDL/HDL ratio (p = 0.003) compared to the MPI group.

    “In the LPI group, the levels of HDL-C increased significantly (p < 0.036) and the LDL/HDL ratio decreased (p = 0.003), compared to the MPI group [158].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [158] Bähr M Fechner A Krämer J Kiehntopf M Jahreis G Lupin protein positively affects plasma LDL cholesterol and LDL:HDL cholesterol ratio in hypercholesterolemic adults after four weeks of supplementation: a randomized, controlled crossover study Nutr J 2013 12 107 23902673 PMC3735452

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  • May combine two claims.

    Premisecitation

    Isoflavones have direct positive effects on endothelial function and arterial stiffness.

    “they seem to have direct positive effects on endothelial function [155] and arterial stiffness [156].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [155] Beavers DP Beavers KM Miller M Stamey J Messina MJ Exposure to isoflavone-containing soy products and endothelial function: a Bayesian meta-analysis of randomized controlled trials Nutr Metab Cardiovasc Dis 2012 22 182 91 20709515

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    • cites [156] Hazim S Curtis PJ Schär MY Acute benefits of the microbial-derived isoflavone metabolite equol on arterial stiffness in men prospectively recruited according to equol producer phenotype: a double-blind randomized controlled trial Am J Clin Nutr 2016 103 694 702 26843154 PMC4763500

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    Premisecitation

    In a study of 130 patients undergoing PCI, berberine 600 mg/day reduced LDL-C by 24% vs 17% in control (p<0.001) and reduced TG by 26% vs 13% (not statistically significant).

    “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.”
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    • cites [137] Meng S Wang LS Huang ZQ Berberine ameliorates inflammation in patients with acute coronary syndrome following percutaneous coronary intervention Clin Exp Pharmacol Physiol 2012 39 406 11 22220931

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    Premisecitation

    In vitro, pantethine inhibits fatty acid synthesis and HMG-CoA reductase.

    “In vitro it inhibits fatty acid synthesis and HMG-CoA reductase [109, 110].”
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    • cites [109] Cighetti G Del Puppo M Paroni R Galli Kienle M Modulation of HMG-CoA reductase activity by pantetheine/pantethine Biochim Biophys Acta 1988 963 389 93 3196742

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    • cites [110] Cighetti G Del Puppo M Paroni R Fiorica E Galli Kienle M Pantethine inhibits cholesterol and fatty acid syntheses and stimulates carbon dioxide formation in isolated rat hepatocytes J Lipid Res 1987 28 152 61 3106549

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    Premisecitation

    Bergamot's HMGF fraction acts as statins by inhibiting HMG-CoA reductase and ACAT, reducing cholesterol ester formation and limiting cholesterol transport in blood.

    “In particular, the 3-hydroxy-3-methyl-glutaryl flavanone enriched fraction (HMGF: brutieridin, melitidin and HMG-neoeriocitrin) has been extracted from the bergamot peel; they act as statins by inhibiting HMG-CoA reductase and ACAT, reducing the formation of cholesterol esters and limiting the transport of cholesterol in the blood.”
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    • cites [118] Di Donna L De Luca G Mazzotti F Napoli A Salerno R Taverna D Sindona G Statin-like principles of bergamot fruit (Citrus bergamia): isolation of 3-hydroxymethylglutaryl flavonoid glycosides J Nat Prod 2009 72 1352 4 19572741

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    • cites [119] Miceli N Mondello MR Monforte MT Hypolipidemic effects of Citrus bergamia Risso et Poiteau juice in rats fed a hypercholesterolemic diet J Agric Food Chem 2007 55 10671 7 18038978

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    Premisecitation

    Pantethine supplementation for 16 weeks (600 mg/day weeks 1-8 then 900 mg/day weeks 9-16) is safe and significantly lowers TC and LDL-C over and above TLC or diet alone.

    “The data suggest that pantethine supplementation for 16 weeks (600 mg/day for weeks 1–8 then 900 mg/day for weeks 9–16) is safe and significantly lowers TC and LDL-C (although with relatively limited clinical relevance) over and above the effect of therapeutic lifestyle changes (TLC) or diet alone [114].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [114] Bertolini S Donati C Elicio N Lipoprotein changes induced by pantethine in hyperlipoproteinemic patients: adults and children Int J Clin Pharmacol Ther Toxicol 1986 24 630 7 3098691

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    Premisecitation

    In a randomized, controlled, double-blind three-phase crossover trial of 72 patients with hypercholesterolemia treated for 28 days with LPI, MP, or MPA, LPI and MPA reduced LDL-C, and LPI improved homocysteine (compared to MPI and MPA), uric acid, and TG.

    “These results were confirmed by the same author in the next randomized, controlled, double-blind three-phase crossover trial, including 72 patients with hypercholesterolemia treated for 28 days with LPI, MP (milk protein) or MPA (milk protein 1.6 g/day of arginine). In addition to reducing LDL-C levels (in MPA and LPI groups), the LPI group showed an improvement in the levels of homocysteine (comp”
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    • cites [159] Bähr M Fechner A Kiehntopf M Jahreis G Consuming a mixed diet enriched with lupin protein beneficially affects plasma lipids in hypercholesterolemic subjects: a randomized controlled trial Clin Nutr 2015 34 7 14 24746974

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    Interpretationcitation

    Berberine at doses 500-1500 mg is effective in lipid lowering and relatively safe in primary and secondary prevention.

    “In summary, the use of BBR at doses ranging between 500 and 1500 mg has proved to be effective in lipid lowering and relatively safe both in primary and secondary prevention.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The cited meta-analyses and RCTs are of sufficient methodological quality and their results are valid for the populations studied.
    • Rests on an assumption: The effects of nutraceuticals observed in trials generalize to clinical practice in the broader patient populations for whom they are recommended.
    • Rests on an assumption: The safety data from clinical trials adequately reflect real-world safety of these nutraceuticals.

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

    “Based on the abovementioned data, side effects are mild to moderate, mostly gastrointestinal (diarrhea, constipation, abdominal distension) and comparable to the control groups [139].”
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    • cites [139] 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 1113 24 22780092

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    Premisecitation

    In the same study, atherogenic sdLDL decreased by 35% and large buoyant LDLs increased by 38% compared to baseline.

    “Moreover, the amount of atherogenic sdLDL significantly decreased (–35%), while large buoyant LDLs increased (+38%; both p < 0.05) compared to baseline levels.”
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    • cites [121] Gliozzi M Carresi C Musolino V The effect of Bergamot-derived polyphenolic fraction on LDL small dense particles and non alcoholic fatty liver disease in patients with metabolic syndrome Adv Biol Chem 2014 4 129 37

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    Premisecitation

    Green tea is usually well tolerated, but rash, transient elevation of blood pressure, and mild gastrointestinal disorders may occur; high doses can cause iron and folate deficiency.

    “Usually the consumption of green tea is well tolerated; however, in some cases rash, transient elevation of blood pressure and mild gastrointestinal disorders may occur. Moreover, high doses of green tea can cause a deficiency of iron and folate due to its capacity to bind and reduce their intestinal absorption.”
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    • cites [143] Onakpoya I Spencer E Heneghan C Thompson M The effect of green tea on blood pressure and lipid profile: a systematic review and meta-analysis of randomized clinical trials Nutr Metab Cardiovasc Dis 2014 24 823 36 24675010

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    Premisecitation

    Compared to nutraceuticals with a statin-similar mechanism, berberine has a greater effect in reducing triglyceridemia, partly related to its positive effect on insulin resistance.

    “Compared to nutraceuticals with a statin-similar mechanism of action, BBR has a greater effect in the reduction of triglyceridemia, partly related to its positive effect on insulin-resistance [139].”
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    • cites [139] 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 1113 24 22780092

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    Premisecitation

    Green tea is associated with improvement in FMD and PWV, despite no apparent effect on hs-CRP levels.

    “Moreover, green tea is associated with an improvement in FMD [144] and pulse wave velocity (PWV) [145], despite no apparent effect on hs-CRP levels [146].”
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    • cites [144] Park CS Kim W Woo JS Green tea consumption improves endothelial function but not circulating endothelial progenitor cells in patients with chronic renal failure Int J Cardiol 2010 145 261 2 19962201

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    • cites [145] Lin QF Qiu CS Wang SL A cross-sectional study of the relationship between habitual tea consumption and arterial stiffness J Am Coll Nutr 2016 35 354 61 26709673

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    • cites [146] Serban C Sahebkar A Antal D Ursoniu S Banach M Effects of supplementation with green tea catechins on plasma C-reactive protein concentrations: a systematic review and meta-analysis of randomized controlled trials Nutrition 2015 31 1061 71 26233863

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    Premisecitation

    In a trial of 143 hypercholesterolemic subjects, policosanols at 10, 20, 40, 80 mg or placebo did not statistically improve TC, TG, HDL-C, or LDL-C, and no group showed >10% LDL-C reduction after 12 weeks.

    “The study by Berthold et al. showed that the administration of policosanols in hypercholesterolemic patients does not statistically improve the levels of TC, TG, HDL-C and LDL-C. This trial included 143 subjects divided into five groups each treated with 10, 20, 40, 80 mg of policosanols or placebo. Nobody in any group at the end of the study (12 weeks) showed a reduction of more than 10% in LDL-C”
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    • cites [126] Berthold HK Unverdorben S Degenhardt R Bulitta M Gouni-Berthold I Effect of policosanol on lipid levels among patients with hypercholesterolemia or combined hyperlipidemia: a randomized controlled trial JAMA 2006 295 2262 9 16705107

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    Premisecitation

    In the same study, group D (statin-intolerant hyperlipidemic patients) had LDL-C and TG reductions of 25.0% and 27.6% (p<0.001) without side effects.

    “Group D showed a reduction of LDL-C and TG (–25.0% and –27.6%, respectively; p < 0.001 for all), without any side effects [123].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [123] Mollace V Sacco I Janda E Hypolipemic and hypoglycaemic activity of bergamot polyphenols: from animal models to human studies Fitoterapia 2011 82 309 16 21056640

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    Premisecitation

    In the same study, bergamot reduced serum glucose, transaminases, γ-glutamyl-transferase, hs-CRP, and TNF-α.

    “Moreover, this was accompanied by a significant reduction of serum glucose, transaminases, γ-glutamyl-transferase, and inflammatory biomarkers such as hs-CRP and tumor necrosis factor-α (TNF-α) [121].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [121] Gliozzi M Carresi C Musolino V The effect of Bergamot-derived polyphenolic fraction on LDL small dense particles and non alcoholic fatty liver disease in patients with metabolic syndrome Adv Biol Chem 2014 4 129 37

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  • May combine two claims.

    Premisecitation

    The tolerability of pantethine is overall high, with acceptable safety confirmed in children and hemodialysis patients.

    “The tolerability of pantethine is overall high, with acceptable safety confirmed also in children [114] and patients in hemodialysis [116].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [114] Bertolini S Donati C Elicio N Lipoprotein changes induced by pantethine in hyperlipoproteinemic patients: adults and children Int J Clin Pharmacol Ther Toxicol 1986 24 630 7 3098691

      Not checked in the free run.

    • cites [116] Donati C Barbi G Cairo G Prati GF Degli Esposti E Pantethine improves the lipid abnormalities of chronic hemodialysis patients: results of a multicenter clinical trial Clin Nephrol 1986 25 70 4 3516477

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  • The quote only partly states this claim.

    Premisecitation

    In a study of 237 patients, bergamot showed dose-dependent lipid-lowering action: groups A and B had LDL-C reductions of 24.1% and 30.6%, TG reductions of 28.2% and 37.9%, and HDL-C increases of 22.3% and 40.1% (p<0.001).

    “The results showed dose-dependent lipid-lowering action of bergamot (groups A and B respectively LDL-C: –24.1% and –30.6%, TG: –28.2% and –37.9%, HDL-C: +22.3% and +40.1%, p < 0.001 for all) compared to baseline.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [123] Mollace V Sacco I Janda E Hypolipemic and hypoglycaemic activity of bergamot polyphenols: from animal models to human studies Fitoterapia 2011 82 309 16 21056640

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    Premisecitation

    γ-oryzanol has lipid-lowering actions by inhibiting HMG-CoA reductase and reducing intestinal cholesterol absorption.

    “γ-oryzanol is a mix of triterpene alcohol and sterol ferulates with lipid-lowering actions by the inhibition of HMG-CoA reductase and the reduction of intestinal cholesterol absorption [183].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [183] Mäkynen K Chitchumroonchokchai C Adisakwattana S Failla M Ariyapitipun T Effect of gamma-oryzanol on the bioaccessibility and synthesis of cholesterol Eur Rev Med Pharmacol Sci 2012 16 49 56 22338548

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    Premisecitation

    Curcumin has low solubility in water and is a substrate of rapid metabolism, and in vivo data of new formulations are lacking.

    “Nevertheless, a major problem is its oral bioavailability: curcumin has low solubility in water and it is a substrate of rapid metabolism. New strategies of release have been studied and tested such as phytosomal complexation with phosphatidylcholine, coadministration of piperine, using turmeric oleoresin, reducing particle size, and changing the formulation (nanoemulsion, solid lipid nanoparticle”
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    • cites [203] Rahimi HR Nedaeinia R Sepehri Shamloo A Nikdoust S Kazemi Oskuee R Novel delivery system for natural products: nano-curcumin formulations Avicenna J Phytomed 2016 6 383 98 27516979 PMC4967834

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    Premisecitation

    The ω-3 present in krill oil (EPA + DHA) appears to be better absorbed in the gastrointestinal tract than that found in fish oil because phosphatidylcholine binds EPA and DHA and confers greater stability.

    “The ω-3 present in krill oil (EPA + DHA) appears to be better absorbed in the gastrointestinal tract than that found in fish oil: this is possible because of phosphatidylcholine (the main phospholipid present in krill (40%), which binds EPA and DHA), which confers greater stability to fatty acids.”
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    • cites [173] Cicero AF Colletti A Krill oil: evidence of a new source of polyunsaturated fatty acids with high bioavailability Clin Lipidol 2015 10 1 4

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    Premisecitation

    PUFAs might be associated with an improvement of FMD and PWV, and with larger dosages, with positive effects on inflammatory diseases and mood.

    “PUFAs might also be associated with an improvement of FMD and PWV, and, with larger dosages, with positive effects on inflammatory diseases and mood [171].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [171] Cicero AF Reggi A Parini A Borghi C Application of polyunsaturated fatty acids in internal medicine: beyond the established cardiovascular effects Arch Med Sci 2012 8 784 93 23185186 PMC3506235

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  • May combine two claims.

    Premisecitation

    In a study including MetS patients, treatment with 1 g/day of curcuminoids as an add-on to standard therapy resulted in a significant reduction of LDL-C (-0.78 mmol/l, p < 0.001), TG (-0.2 mmol/l, p = 0.006), and Lp(a) (-0.286 μmol/l, p < 0.001) and an elevation of HDL-C (+0.18 mmol/l, p = 0.003).

    “In a study including MetS patients, treatment with 1 g/day of curcuminoids as an add-on to the standard therapy resulted in a significant reduction of LDL-C (–0.78 mmol/l (30 mg/dl), p < 0.001), TG (–0.2 mmol/l (17.7 mg/dl), p = 0.006), and Lp(a) (–0.286 μmol/l (8 mg/dl), p < 0.001) and an elevation of HDL-C (+0.18 mmol/l (7 mg/dl), p = 0.003) [196].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [196] Yang YS Su YF Yang HW Lee YH Chou JI Ueng KC Lipid-lowering effects of curcumin in patients with metabolic syndrome: a randomized, double-blind, placebo-controlled trial Phytother Res 2014 28 1770 7 25131839

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    Interpretationcitation

    Omega-3 EPA and DHA represent a valid nutraceutical to reduce TG in the blood (by 18-25%) while their effects on LDL-C and HDL-C are clinically insignificant.

    “In conclusion, omega-3 EPA and DHA represent a valid nutraceutical to reduce TG in the blood (by 18–25%) while their effects on LDL-C and HDL-C are clinically insignificant.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The lipid-lowering effects of nutraceuticals observed in short-term trials translate into reduced cardiovascular risk.

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    Premisecitation

    A meta-analysis of 7 RCTs with 662 participants found that krill oil supplementation significantly reduced LDL-C (-15.52 mg/dl, 95% CI -28.43 to -2.61, p = 0.018) and TG (-14.03 mg/dl, 95% CI -21.38 to -6.67, p < 0.001), and significantly elevated HDL-C (6.65 mg/dl, 95% CI 2.30 to 10.99, p = 0.003).

    “In the most recent meta-analysis of 7 RCTs with 662 participants Ursoniu et al. found a significant reduction in plasma concentrations of LDL-C (–15.52 mg/dl (0.4 mmol/l); 95% CI: –28.43 to –2.61; p = 0.018), and TG (–14.03 mg/dl (0.16 mmol/l); 95% CI: –21.38 to –6.67; p < 0.001), and significant elevation in plasma concentrations of HDL-C (6.65 mg/dl (0.17 mmol/l); 95% CI: 2.30 to 10.99; p = 0.00”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [176] Ursoniu S Sahebkar A Serban MC Lipid and Blood Pressure Meta-analysis Collaboration Group Lipid-modifying effects of krill oil in humans: systematic review and meta-analysis of randomized controlled trials Nutr Rev 2017 75 361 73 28371906

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    Premisecitation

    A meta-analysis including 63,030 patients from 20 clinical trials showed that treatment with ω-3 did not have an impact on a composite CVD endpoint or total mortality but was associated with a significantly decreased rate of vascular death.

    “A relatively recent meta-analysis including data from 63 030 patients from 20 clinical trials showed that treatment with ω-3 did not have an impact on a composite CVD endpoint or total mortality but was associated with a significantly decreased rate of vascular death [181].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [181] Kotwal S Jun M Sullivan D Perkovic V Neal B Omega 3 fatty acids and cardiovascular outcomes: systematic review and meta-analysis Circ Cardiovasc Qual Outcomes 2012 5 808 18 23110790

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  • May combine two claims.

    Premisecitation

    Smaller doses than 2-4 g/day, such as 400 mg/day EPA + DHA or 2 g/day α-linolenic acid, do not significantly reduce TG levels, as confirmed in an RCT involving 4837 post-MI patients; such supplementation also did not reduce the rate of major CVD events.

    “Especially, it needs be noted that smaller doses than 2–4 g/day such as a low dose supplementation of a margarine with n-3 PUFAs (400 mg/day EPA + DHA) or α-linolenic acid (2 g/day) do not significantly reduce TG levels, as was confirmed in an RCT involving 4837 post-MI patients. Such supplementation also did not reduce the rate of major CVD events [180].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [180] Kromhout D Giltay EJ Geleijnse JM Alpha Omega Trial Group n-3 fatty acids and cardiovascular events after myocardial infarction N Engl J Med 2010 363 2015 26 20929341

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    Interpretationcitation

    CVD outcome studies with ω-3 have produced inconsistent results and their clinical efficacy appears to be related to non-lipid effects.

    “However, it has to be stressed that CVD outcome studies with ω-3 have produced inconsistent results and their clinical efficacy appears to be related to non-lipid effects.”
    Quote in the paperSubstantial claim

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    Premisecitation

    A meta-analysis of 7 clinical trials showed that spirulina supplementation reduced LDL-C by -1.07 mmol/l (95% CI -1.57; -0.57, p < 0.001), TC by 1.21 mmol/l (95% CI -1.74; -0.68, p < 0.001), TG by -0.5 mmol/l (95% CI -0.57; -0.43, p < 0.001), and increased HDL-C by +0.16 mmol/l (95% CI 0.06; 0.25, p = 0.001).

    “A recent meta-analysis that included 7 clinical trials to assess the effect of spirulina supplementation on plasma lipid concentrations showed the lipid-lowering efficacy of spirulina, with a reduction of LDL-C by –1.07 mmol/l (41.32 mg/dl) (95% CI: –1.57; –0.57, p < 0.001), TC by 1.21 mmol/l (46.76 mg/dl) (95% CI: –1.74; –0.68, p < 0.001) and TG by –0.5 mmol/l (44.23 mg/dl) (95% CI: –0.57; –0.43,”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [188] Pulido-Moran M Moreno-Fernandez J Ramirez-Tortosa C Ramirez-Tortosa M Curcumin and health Molecules 2016 21 264 26927041 PMC6273481

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    Premisecitation

    C-phycocyanin contains phycocyanobilin, which can activate atheroprotective heme oxygenase-1 (HMOX-1) in endothelial cells, and phycocyanin has antioxidant, anti-inflammatory and radical scavenging properties.

    “C-phycocyanin, a particular essential pigment of Spirulina, contains a phycocyanobilin, which can activate atheroprotective heme oxygenase-1 (HMOX-1), a key enzyme in the heme catabolic pathway in endothelial cells. Moreover, phycocyanin has proven antioxidant, anti-inflammatory and radical scavenging properties [187].”
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    • cites [187] Serban MC Sahebkar A Dragan S A systematic review and meta-analysis of the impact of Spirulina supplementation on plasma lipid concentrations Clin Nutr 2016 35 842 51 26433766

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    Premisecitation

    Administration of EPA or DHA individually gave comparable effects in reduction of TG, but not other lipid parameters; DHA showed a very modest reduction of LDL-C by 5% and slightly increased HDL-C, while EPA produced no significant changes.

    “It was also observed that the administration of EPA or DHA individually gave comparable effects in the reduction of TG, but not other lipid parameters; in fact, DHA showed a very modest reduction of LDL-C by 5% and slightly increased HDL-C, while EPA produced no significant changes [169, 170].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [169] Trumbo P Schlicker S Yates AA Poos M Food and Nutrition Board of the Institute of Medicine, The National Academies Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids J Am Diet Assoc 2002 102 1621 30 12449285

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    • cites [170] Wei MY Jacobson TA Effects of eicosapentaenoic acid versus docosahexaenoic acid on serum lipids: a systematic review and meta-analysis Curr Atheroscler Rep 2011 13 474 83 21975919

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    Premisecitation

    In the same meta-analysis, EPA/DHA produced a small insignificant reduction of LDL-C of 0.06 mmol/l and no differences in HDL-C.

    “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 [166].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [166] 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 4 16 18774613

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    Premisecitation

    Spirulina is a filamentous microalga with known lipid-lowering effects, but with an unclear mechanism of action.

    “Spirulina (Arthrospira platensis) is a filamentous microalga with known lipid-lowering effects, but with an unclear mechanism of action [186].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [186] Nagaoka S Shimizu K Kaneko H A novel protein C-phycocyanin plays a crucial role in the hypocholesterolemic action of Spirulina platensis concentrate in rats J Nutr 2005 135 2425 30 16177207

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  • May combine two claims.

    Premisecitation

    In a meta-analysis of 2270 individuals with optimal lipid or suboptimal TG profiles (TG < 2 mmol/l), studies using more than 4 g/day of ω-3 reduced TG by 9-26%, while doses from 1 to 5 g/day reduced TG by 4-51%.

    “These results were confirmed in normolipidemic and borderline subjects in the meta-analysis by Leslie et al. that included 2270 individuals with optimal lipid or suboptimal TG profiles (TG < 2 mmol/l (177 mg/dl)). In studies that used more than 4 g/day of ω-3 TG were reduced by 9–26%, while a reduction of 4–51% was found with doses from 1 to 5 g/day of ω-3 [167].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [167] Leslie MA Cohen DJ Liddle DM Robinson LE Ma DW A review of the effect of omega-3 polyunsaturated fatty acids on blood triacylglycerol levels in normolipidemic and borderline hyperlipidemic individuals Lipids Health Dis 2015 14 53 26048287 PMC4488064

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    Premisecitation

    No serious side effects have been reported for ω-3; most have been defined as mild gastrointestinal.

    “Safety: No serious side effects have been reported; most of them have been defined as mild gastrointestinal [169].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [169] Trumbo P Schlicker S Yates AA Poos M Food and Nutrition Board of the Institute of Medicine, The National Academies Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids J Am Diet Assoc 2002 102 1621 30 12449285

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  • May combine two claims.

    Premisecitation

    In recent RCTs, supplementation with curcumin (1 g/day) was associated with a reduction of serum uric acid (p < 0.001), increase of adiponectin (+76.78%, p = 0.033) and reduction of leptin (-26.49%, p = 0.238).

    “In recent RCTs, supplementation with curcumin (1 g/day) was associated with a reduction of serum uric acid (p < 0.001) [199], increase of adiponectin (+76.78%, p = 0.033) levels and reduction of leptin (–26.49%, p = 0.238) [189].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [199] Panahi Y Kianpour P Mohtashami R Jafari R Simental-Mendía LE Sahebkar A Curcumin lowers serum lipids and uric acid in subjects with non-alcoholic fatty liver disease: a randomized controlled trial J Cardiovasc Pharmacol 2016 68 223 9 27124606

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    • cites [189] Panahi Y Hosseini MS Khalili N Effects of supplementation with curcumin on serum adipokine concentrations: A randomized controlled trial Nutrition 2016 32 1116 22 27297718

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    Premisecitation

    Curcuminoids showed an increase in serum activities of superoxide dismutase (p = 0.0007) and catalase (p = 0.005) and glutathione concentrations (p = 0.01) and a reduction in serum lipid peroxides (p = 0.008) and of TNF-α.

    “As reported in recent meta-analyses of RCTs, curcuminoids showed an increase in serum activities of superoxide dismutase (p = 0.0007) and catalase (p = 0.005) and glutathione concentrations (p = 0.01) and a reduction in serum lipid peroxides (p = 0.008) [189] and of TNF-α [190].”
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    • cites [189] Panahi Y Hosseini MS Khalili N Effects of supplementation with curcumin on serum adipokine concentrations: A randomized controlled trial Nutrition 2016 32 1116 22 27297718

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    • cites [190] Sahebkar A Cicero AF Simental-Mendía LE Aggarwal BB Gupta SC Curcumin downregulates human tumor necrosis factor-alpha levels: a systematic review and meta-analysis of randomized controlled trials Pharmacol Res 2016 107 234 42 27025786

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  • May combine two claims.

    Premisecitation

    These data have been confirmed in a further trial on 100 MetS patients and in another one with 80 NAFLD patients.

    “These data have since been confirmed in a further trial carried out on 100 MetS patients [197] and in another one with 80 NAFLD patients [198].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [197] Panahi Y Khalili N Hosseini MS Abbasinazari M Sahebkar A Lipid-modifying effects of adjunctive therapy with curcuminoids-piperine combination in patients with metabolic syndrome: results of a randomized controlled trial Complement Ther Med 2014 22 851 7 25440375

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    • cites [198] Rahmani S Asgary S Askari G Treatment of non-alcoholic fatty liver disease with curcumin: a randomized placebo-controlled trial Phytother Res 2016 6 8 [Epub ahead of print] 10.1002/ptr.5659 27270872

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A recent meta-analysis of RCTs showed that sesame fractions intake is associated with a significant TG reduction (-0.24 mmol/l, 95% CI -0.32; -0.15, p < 0.001), while no changes occurred with LDL-C or HDL-C levels.

    “A recent meta-analysis of RCTs showed that sesame fractions intake is associated with a significant TG reduction (–0.24 mmol/l (21.3 mg/dl); 95% CI: –0.32; –0.15, p < 0.001), while no changes occurred with LDL-C or HDL-C levels [179].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [179] Khalesi S Paukste E Nikbakht E Khosravi-Boroujeni H Sesame fractions and lipid profiles: a systematic review and meta-analysis of controlled trials Br J Nutr 2016 115 764 73 26758593

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ω-3 reduce TG by reducing hepatic VLDL synthesis, reducing available substrate for TG synthesis, reducing TG-synthesizing enzyme activity, increasing β-oxidation of fatty acids, reducing endogenous fatty acid synthesis, and increasing phospholipid synthesis.

    “The mechanisms through which ω-3 reduce TG are: the reduction of synthesis of hepatic VLDL, the reduction of available substrate for the synthesis of new TG (ω-3 are false substrates), the reduction of the activity of TG-synthesizing enzymes (diacylglycerol acyltransferase or phosphatidic acid phosphohydrolase), the increase of β-oxidation of fatty acids, the reduction of the endogenous synthesis”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [165] Harris WS Bulchandani D Why do omega-3 fatty acids lower serum triglycerides? Curr Opin Lipidol 2006 17 387 93 16832161

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The cholesterol-lowering effects of flaxseed were more significant in females (in particular postmenopausal women) and in individuals with high cholesterol levels at baseline.

    “The cholesterol-lowering effects were more significant in females (in particular in postmenopausal women) and in individuals with high cholesterol levels at baseline [177].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [177] Pan A Yu D Demark-Wahnefried W Franco OH Lin X Meta-analysis of the effects of flexseed interventions on blood lipids Am J Clin Nutr 2009 90 288 97 19515737 PMC3361740

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Curcumin inhibits the expression of the NPC1L1 transporter via the SREBP2 transcription factor, increases cholesterol efflux via expression of ABCA1 and activating AMPK-SIRT1-LXRα signaling, enhances the number of LDL-R and promotes LDL particle uptake through downregulation of PCSK9.

    “The lipid-lowering mechanisms of action of curcuminoids are unclear; nevertheless, it seems that curcumin inhibits the expression of the NPC1L1 transporter via the SREBP2 transcription factor [191], and that it increases the efflux of cholesterol via expression of ABCA1 and activating AMPK-SIRT1-LXRα signaling in THP-macrophage-derived foam cells [192]. Furthermore, curcumin enhances the number of”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [191] Kumar P Malhotra P Ma K SREBP2 mediates the modulation of intestinal NPC1L1 expression by curcumin Am J Physiol Gastrointest Liver Physiol 2011 301 G148 55 21527728 PMC3129937

      Not checked in the free run.

    • cites [192] Liu XL Liu MH Hu HJ Curcumin enhanced choelsterol efflux by upregulating ABCA1 expression through AMPK-SIRT1-LXRalpha signaling in THP-1 macrophage-derived foam cells DNA Cell Biol 2015 34 561 72 26102194

      Not checked in the free run.

    • cites [193] Tai MH Chen PK Chen PY Wu MJ Ho CT Yen JH Curcumin enhances cell-surface LDLR level and promotes LDL uptake through downregulation of PCSK9 gene expression in HepG2 cells Mol Nutr Food Res 2014 58 2133 45 25164566

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    The combination of red yeast rice extract (200 mg, corresponding to 3 mg Monacolin K) with policosanol (10 mg) in a large single-blind, randomized, multicenter study in 411 centers, comparing nutraceutical association plus diet versus diet alone with 16 weeks follow-up, in 2408 eligible subjects (1665 adults and 743 elderly), reduced LDL-C by 21%, improved HDL-C by 13%, without significant changes

    “The combination of red yeast rice extract (200 mg, corresponding to 3 mg of Monacolin K) with policosanol (10 mg) was also tested in a large single-blind, randomized, multicenter study in 411 centers, comparing the effect of the nutraceutical association plus diet versus diet alone with a follow-up of 16 weeks. In 2408 eligible subjects (1665 adults and 743 elderly), LDL-C was reduced by 21%, wh”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [241] Cicero AF Benvenuti C ARMoweb study Group Efficacy of a red yeast rice based nutraceutical in large subgroups of hypercholesterolemic subjects in every day clinical practice Med J Nutr Metab 2010 3 239 46

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In diabetic patients, silymarin improves fasting plasma glucose and HbA1c, but not lipid parameters.

    “In diabetic patients, silymarin improves fasting plasma glucose (FPG) and HbA1c, but not lipid parameters [227].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [227] Voroneanu L Nistor I Dumea R Apetrii M Covic A Silymarin in type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials J Diabetes Res 2016 2016 5147468 27340676 PMC4908257

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Most nutraceuticals with significant lipid-lowering properties are used in combination with a low dosage of other nutraceuticals, statins and other lipid-lowering drugs, because that allows the risk of side effects to be reduced and the efficacy to be improved.

    “Most of them are used in combination with a low dosage of other nutraceuticals, statins and other lipid-lowering drugs, because that allows the risk of side effects to be reduced and the efficacy to be improved (reducing the residual CV risk) [237].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [237] Cicero AF Ferroni A Ertek S Tolerability and safety of commonly used dietary supplements and nutraceuticals with lipid-lowering effects Expert Opin Drug Saf 2012 11 753 66 22788832

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  • May combine two claims.

    Premisecitation

    Studies in vitro have shown an inhibitory effect of silybin on HMG-CoA reductase and in vivo an improved uptake of LDL by the liver and a reduction of hepatic cholesterol synthesis.

    “There are preliminary studies suggesting a potential role of silymarin as lipid-lowering agent; studies in vitro have shown an inhibitory effect of silybin on HMG-CoA reductase and in vivo an improved uptake of LDL by the liver and a reduction of hepatic cholesterol synthesis [227].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [227] Voroneanu L Nistor I Dumea R Apetrii M Covic A Silymarin in type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials J Diabetes Res 2016 2016 5147468 27340676 PMC4908257

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Artichoke leaf extract (ALE) has potential hypolipidemic and hepatoprotective effects, attributed to its antioxidant action.

    “According to some pre-clinical and clinical investigations, artichoke leaf extract (ALE) has potential hypolipidemic and hepatoprotective effects. The beneficial effects of artichoke can be attributed to its antioxidant action.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [208] Capasso F Gaginella TS Grandolini G Izzo AA Phytotherapy: a Quick Reference to Herbal Medicine 2003 Berlin Springer

      Not checked in the free run.

    • cites [209] Safaa M Hanaa A Abdel F Nahila A Abdelaaty S Cynara scolymus for relieving on nonalcoholic steatohepatitis induced in rat Int J Pharm Pharmac Sci 2013 5 57 66

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Even if vitamin E seems not to be an effective lipid-lowering treatment, its supplementation seems to be associated with reduced risk of fatal myocardial infarction.

    “Even if vitamin E seems not to be an effective lipid-lowering treatment, its supplementation seems to be associated with reduced risk of fatal myocardial infarction [219].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [219] Loffredo L Perri L Di Castelnuovo A Iacoviello L De Gaetano G Violi F Supplementation with vitamin E alone is associated with reduced myocardial infarction: a meta-analysis Nutr Metab Cardiovasc Dis 2015 25 354 63 25779938

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In 58 diabetic patients, 320 mg/day of anthocyanins for 24 weeks significantly decreased LDL-C (-7.9%, p < 0.05), TG (-23%, p < 0.01), apoB48 (-16.5%, p < 0.05), and apoCIII (-11%, p < 0.01) and increased HDL-C (+19.4%, p < 0.05) compared to placebo.

    “In 58 diabetic patients, 320 mg/day of anthocyanins for 24 weeks significantly decreased LDL-C (–7.9%, p < 0.05), TG (–23%, p < 0.01), apoB48 (–16.5%, p < 0.05), and apoCIII (–11%, p < 0.01) and increased HDL-C (+19.4%, p < 0.05) compared to placebo.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [222] Li D Zhang Y Liu Y Sun R Xia M Purified anthocyanin supplementation reduces dyslipidemia, enhances antioxidant capacity, and prevents insulin resistance in diabetic patients J Nutr 2015 145 742 8 25833778

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The bioavailability of anthocyanins is low and they are rapidly biotransformed into derivates of phenolic acid.

    “In fact it is well known that the bioavailability of anthocyanins is low and they are rapidly biotransformed into derivates of phenolic acid [225].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [225] Marques C Fernandes I Norberto S Pharmacokinetics of blackberry anthocyanins consumed with or without ethanol: a randomized and crossover trial Nutr Food Res 2016 60 2319 30 27306520

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A meta-analysis of 9 RCTs with 702 subjects suggested a significant decrease in plasma concentrations of TC (WMD -17.6 mg/dl, 95% CI -22.0, -13.3, p < 0.001), LDL-C (-14.9 mg/dl, 95% CI -20.4, -9.5, p = 0.011) and triglycerides (WMD -9.2 mg/dl, 95% CI -16.2, -2.1, p = 0.011).

    “The most recent meta-analysis of 9 RCTs with 702 subjects suggested a significant decrease in plasma concentrations of TC (weighted mean difference (WMD): –17.6 mg/dl (0.46 mmol/l), 95% CI: –22.0, –13.3, p < 0.001), LDL-C (–14.9 mg/dl (0.39 mmol/l), 95% CI: –20.4, –9.5, p = 0.011) and triglycerides (WMD: –9.2 mg/dl (0.1 mmol/l), 95% CI: –16.2, –2.1, p = 0.011) [214].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [214] Sahebkar A Pirro M Banach M Mikhailidis DP Atkin SL Cicero AFG Lipid-lowering activity of artichoke extracts: a systematic review and meta-analysis Crit Rev Food Sci Nutr 2017 6 13 10.1080/10408398.2017.1332572 28609140

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  • May combine two claims.

    Premisecitation

    In the same study, the anthocyanin group showed an improvement of fasting plasma glucose (-8.5%, p < 0.05), HOMA for insulin resistance index (p < 0.05) and adiponectin concentrations (+23.4%, p < 0.01).

    “Moreover, the anthocyanin group showed an improvement of fasting plasma glucose (–8.5%, p < 0.05), of homeostasis model assessment (HOMA) for insulin resistance index (p < 0.05) and of adiponectin concentrations (+23.4%, p < 0.01) [222].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [222] Li D Zhang Y Liu Y Sun R Xia M Purified anthocyanin supplementation reduces dyslipidemia, enhances antioxidant capacity, and prevents insulin resistance in diabetic patients J Nutr 2015 145 742 8 25833778

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Artichoke extract showed pleiotropic activities in the improvement of AST and ALT (p < 0.001), blood sugar (p = 0.029) and systolic blood pressure (p = 0.004).

    “In addition, artichoke extract showed pleiotropic activities in the improvement of certain liver enzymes such as AST and ALT (p < 0.001), blood sugar (p = 0.029) and systolic blood pressure (p = 0.004) [210].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [210] Rangboo V Noroozi M Zavoshy R Rezadoost SA Mohammadpoorasl A The effect of artichoke leaf extract on alanine aminotransferase and aspartate aminotransferase in the patients with nonalcoholic steatohepatitis Int J Hepatol 2016 2016 4030476 27293900 PMC4879230

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    An RCT of 75 patients treated for 12 weeks with 1280 mg/day ALE or placebo showed a mean reduction of TC by 4.2% compared to baseline and an increasing trend of TC in placebo; the total difference between groups was statistically significant (p = 0.0025), with no significant difference for LDL-C, HDL-C or TG.

    “An RCT (75 patients treated for 12 weeks with 1280 mg/day of artichoke leaf extract or placebo) showed a mean reduction of TC by 4.2% compared to baseline and an increasing trend of TC levels in the placebo group. The total difference between the two groups was statistically significant (p = 0.0025). No significant difference between groups was observed for LDL-C, HDL-C or TG levels [211].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [211] Bundy R Walker AF Middleton RW Wallis C Simpson HC Artichoke leaf extract (Cynara scolymus) reduces plasma cholesterol in otherwise healthy hypercholesterolemic adults: a randomized, double blind placebo controlled trial Phytomedicine 2008 15 668 75 18424099

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  • May combine two claims.

    Premisecitation

    At doses between 50 and 200 mg, vitamin E improved endothelial function (reducing serum levels of hs-CRP, advanced glycation end products, metalloproteinases and cell adhesion molecules) and arterial stiffness (improving PWV, pulse volume and augmentation index).

    “At doses between 50 and 200 mg it showed an improvement of endothelial function (reducing the serum levels of hs-CRP, advanced glycation end products, metalloproteinases and cell adhesion molecules) and arterial stiffness (improving PWV, pulse volume (PV) and the augmentation index (AI)) [217, 218].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [217] Rasool AH Rahman AR Yuen KH Wong AR Arterial compliance and vitamin E blood levels with a self emulsifying preparation of tocotrienol rich vitamin E Arch Pharm Res 2008 31 1212 7 18806966

      Not checked in the free run.

    • cites [218] Prasad K Tocotrienols and cardiovascular health Curr Pharm Des 2011 17 2147 54 21774782

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  • May combine two claims.

    Interpretationreasoning

    ALE could represent an adjuvant in the regulation of lipid profile and liver levels of AST and ALT; however, the available clinical data are still preliminary.

    “In conclusion, ALE could represent an adjuvant in the regulation of lipid profile and liver levels of AST and ALT; however, the available clinical data are still preliminary.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The lipid-lowering effects of nutraceuticals observed in short-term trials translate into reduced cardiovascular risk.

  • May combine two claims.

    Premisecitation

    A second RCT of 143 patients treated with 1800 mg/day ALE for 6 weeks showed a mean reduction of TC of 18.5% compared to 8.6% in placebo (p < 0.00001), and LDL-C significantly decreased in ALE group (mean -1.26 mmol/l) compared to placebo (mean -0.33 mmol/l, p < 0.00001), with no differences for other lipid parameters.

    “A second RCT (143 patients treated with 1800 mg/day of ALE for 6 weeks) showed a mean reduction of TC of 18.5% compared to 8.6% in the placebo group – the difference between the two groups was statistically significant (p < 0.00001). Moreover, the levels of LDL-C were also significantly decreased in the artichoke leaf extract group (mean: –1.26 mmol/l (48.7 mg/dl)) compared to the placebo group (”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [212] Englisch W Beckers C Unkauf M Ruepp M Zinserling V Efficacy of Artichoke dry extract in patients with hyperlipoproteinemia Arzneimittelforschung 2000 50 260 5 10758778

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  • May combine two claims.

    Interpretationcitation

    These genetic results could explain the variability observed in response among patients with moderate hypercholesterolemia, and they may be useful in identifying subjects who could potentially benefit the most from this supplementation.

    “These results could explain the variability observed in the response among patients with moderate hypercholesterolemia, and they may be useful in identifying subjects who could potentially benefit the most from this supplementation [247].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [247] De Castro-Orós I Solà R Valls RM Genetic variants of LDLR and PCSK9 associated with variations in response to antihypercholesterolemic effects of armolipid plus with berberine PLoS One 2016 11 e0150785 27015087 PMC4807809

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Astaxanthin is often cited as having a lipid-lowering effect, but this effect is not supported by clinical evidence, while its supplementation is associated with a mild but significant improvement in fasting plasma glucose.

    “Astaxanthin, a powerful antioxidant carotenoid, is often cited as having a lipid-lowering effect, but this effect is not supported by clinical evidence, while its supplementation is associated with a mild but significant improvement in fasting plasma glucose [235].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [235] Ursoniu S Sahebkar A Serban MC Banach M Lipid profile and glucose changes after supplementation with astaxanthin: a systematic review and meta-analysis of randomized controlled trials Arch Med Sci 2015 11 253 66 25995739 PMC4424245

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Vitamin E has several suggested mechanisms of lipid-lowering action: PPAR activation, HMG-CoA reductase inhibition and radical scavenger.

    “There are several suggested mechanisms of lipid-lowering action of vitamin E: peroxisome proliferator-activated receptor (PPAR-α, PPAR-β, and PPAR-γ) activation, HMG-CoA reductase inhibition and radical scavenger [215].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [215] Li F Tan W Kang Z Wong CW Tocotrienol enriched palm oil prevents atherosclerosis through modulating the activities of peroxisome proliferators-activated receptors Atherosclerosis 2010 211 278 82 20138624

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A third study of 44 patients treated with 1920 mg/day ALE for 12 weeks showed no significant differences in lipid profile, but subgroup analysis showed patients with baseline TC > 230 mg/dl had significant reduction of TC vs placebo (p = 0.0015).

    “The third study (44 patients treated with 1920 mg/day of ALE for 12 weeks) showed no significant differences in the lipid profile at the end of the treatment. However, according to a subgroup analysis, patients treated with artichoke leaf extract who had at baseline TC levels greater than 230 mg/dl showed a significant reduction of TC when compared with those treated with placebo (p = 0.0015) [213”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [213] Petrowicz O Gebhardt R Donner M Schwandt M Kraft K Effects of artichoke leaf extract (ALE) on lipoprotein metabolism in vitro and in vivo Atherosclerosis 1997 129 147

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The association of red yeast rice extract (340 mg containing 5 mg MonK) and octacosanols (10 mg) tested in 111 patients with moderate hypercholesterolemia, normal/border-line triglyceridemia and low CVD risk reduced LDL-C by 20%, similar to pravastatin 20 mg/day, without serious safety concerns.

    “The association of red yeast rice extract (340 mg containing 5 mg of MonK) and octacosanols (10 mg) was tested in 111 patients with moderate hypercholesterolemia, normal/border-line triglyceridemia and low CVD risk (< 20% according to the Framingham Risk Score (FRS)). The reduction of LDL-C was 20% and it was similar to that obtained with pravastatin at the dose 20 mg/day, without any serious”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [239] Cicero AF Brancaleoni M Laghi L Donati F Mino M Antihyperlipidaemic effect of a Monascus purpureus brand dietary supplement on a large sample of subjects at low risk for cardiovascular disease: a pilot study Complement Ther Med 2005 13 273 8 16338198

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  • May combine two claims.

    Premisecitation

    Natural products with different mechanisms of action can be associated to achieve a potential synergetic effect, acting on absorption of lipids from the bowel and/or increasing their excretion, enhancing hepatic uptake of cholesterol, inducing LDL-C excretion, inhibiting HMG-CoA reductase and limiting hepatic synthesis of cholesterol, reducing oxidation of LDL and increasing thermogenesis andlipid

    “Moreover, natural products with different mechanisms of action can be associated to achieve a potential synergetic effect, acting on the absorption of lipids from the bowel and/or increasing their excretion (soluble fibers, glucomannan, plant sterols, probiotics), enhancing the hepatic uptake of cholesterol (berberine, soybean proteins), inducing LDL-C excretion (berberine, soy proteins, chlor”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [238] Cicero AF Parini A Rosticci M Nutraceuticals and cholesterol-lowering action Int J Cardiol Med Endocr 2015 6 1 4

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Clinical trials have demonstrated that anthocyanins have antioxidant, anti-inflammatory and lipid-lowering effects.

    “Among the biological activities exerted by anthocyanins, clinical trials have demonstrated particular antioxidant, anti-inflammatory and lipid-lowering effects [221].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [221] Wallace TC Slavin M Frankenfeld CL Systematic review of anthocyanins and markers of cardiovascular disease Nutrients 2016 8 pii: E32 10.3390/nu8010032 PMC4728646 26761031

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A recent systematic review and meta-analysis found that CLA supplementation was associated with a significant decrease in LDL-C (MD -0.22 mmol/l, 95% CI -0.36; -0.08, p = 0.002), while non-significant results were obtained for HDL-C and TG.

    “In a recent systematic review and meta-analysis, CLA supplementation was associated with a significant decrease in LDL-C (MD: –0.22 mmol/l (8.5 mg/dl); 95% CI: –0.36; –0.08, p = 0.002), while non-significant results were obtained for HDL-C and TG [230].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [230] Derakhshande-Rishehri SM Mansourian M Kelishadi R Heidari-Beni M Association of foods enriched in conjugated linoleic acid (CLA) and CLA supplements with lipid profile in human studies: a systematic review and meta-analysis Public Health Nutr 2015 18 2041 54 25379623 PMC10271550

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The use of high-intensity statins increases the side effects and therefore reduces therapy adherence and compliance.

    “Even knowing that statins are the drugs of choice in patients with high LDL-C levels and moderate-to-high CV risk, the use of high-intensity statins increases the side effects and therefore reduces the therapy adherence and compliance [277, 278].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [277] Šimić I Reiner Ž Adverse effects of statins – myths and reality Curr Pharm Des 2015 21 1220 6 25312733

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    • cites [278] Banach M Stulc T Dent R Toth PP Statin non-adherence and residual cardiovascular risk: there is need for substantial improvement Int J Cardiol 2016 225 184 96 27728862

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  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    For the combined products in section 6.9, due to lack of enough data, it is not possible at this moment to suggest a final classification; the level of evidence might have been limited to "B" or "C" - expert opinion with the class of suggestion "IIb" waiting for confirmative trials.

    “For these combined products, due to lack of enough data, is not possible, at this moment, to suggest a final classification. The level of evidence might have been limited to “B” or “C” – expert opinion with the class of suggestion “IIb” waiting for confirmative trials.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    Most of the combinations presented in section 7 have been tested only in a single study, and the obtained results have not been confirmed yet, so no recommendations can be made.

    “However, most of the combinations presented below have been tested only in a single study, and the obtained results have not been confirmed yet, so no recommendations can be made.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductcitation

    The cited trial was double-blind, placebo-controlled, and randomized, with 56 hypercholesterolemic patients assigned to vitamin D 200 IU/day (n=28) or placebo (n=28) as an add-on to statin for 6 months.

    “A double-blind, placebo-controlled trial was assessed on 56 hypercholesterolemic patients, who were randomly assigned to receive vitamin D 200 IU/day (n = 28) or a placebo (n = 28) as an add-on to statin for 6 months.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [296] Qin XF Zhao LS Chen WR Yin da W Wang H Effects of vitamin D on plasma lipid profiles in statin-treated patients with hypercholesterolemia: a randomized placebo-controlled trial Clin Nutr 2015 34 201 6 24844869

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Low serum vitamin D level seems to be associated with CVD risk and development of statin-related myopathy.

    “Taking into consideration that low serum vitamin D level seems to be associated with CVD risk and development of statin-related myopathy, the supplementation of vitamin D should always be considered in subjects with low vitamin D levels [297].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [297] Michalska-Kasiczak M Sahebkar A Mikhailidis DP Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group. Analysis of vitamin D levels in patients with and without statin-associated myalgia – a systematic review and meta-analysis of 7 studies with 2420 patients Int J Cardiol 2015 178 111 6 25464233

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Vitamin D supplementation with statin has no safety concerns, though data are limited.

    “Safety: No safety concerns; limited data – further studies are necessary.”
    Quote in the paperSubstantial claim
188 of 188

  • The paper relies on this without support.

    The cited meta-analyses and RCTs are of sufficient methodological quality and their results are valid for the populations studied.

    “Based on available data it seems that the best results were obtained with Lactobacillus strains.”

  • The paper relies on this without support.

    The effects of nutraceuticals observed in trials generalize to clinical practice in the broader patient populations for whom they are recommended.

    “In summary, the administration of RYR can be recommended because of its effects on LDL-C in patients with moderately elevated cholesterol, especially in primary prevention.”

  • The paper relies on this without support.

    The safety data from clinical trials adequately reflect real-world safety of these nutraceuticals.

    “Clinical studies conducted to date with dosages between 500 and 1500 mg/day showed a good safety profile, with no side effects detected.”

  • The paper relies on this without support.

    The chronic use of a high quantity of soy products containing isoflavones could interfere with thyroid function and fertility.

    “Safety: The chronic use of a high quantity of soy products containing isoflavones could interfere with thyroid function and fertility.”

  • The paper relies on this without support.

    Soybean and its derivatives contain high amounts of phytic acid that reduces the absorption of minerals such as calcium, magnesium, copper, iron and zinc.

    “Furthermore, soybean and its derivatives contain high amounts of phytic acid that reduces the absorption of minerals such as calcium, magnesium, copper, iron and zinc.”

  • The paper relies on this without support.

    Lupine has a good safety profile, causing no severe side effects, and those which occurred were mostly gastrointestinal.

    “Lupine has shown a good safety profile, causing no severe side effects, and those which occurred were mostly gastrointestinal.”

  • The paper relies on this without support.

    In alloxan-injured mice, phycocyanin decreases TC and TG levels in serum, increases hepatic glycogen level and maintains glucokinase expression in the liver.

    “According to experimental studies in alloxan-injured mice, phycocyanin decreases TC and TG levels in serum, increases the hepatic glycogen level and maintains glucokinase (GK) expression in the liver.”

  • The paper relies on this without support.

    The lipid-lowering effects of nutraceuticals observed in short-term trials translate into reduced cardiovascular risk.

    “In conclusion, the intake of soy and lupine represents a potential, relatively weak adjuvant therapy in the treatment of hypercholesterolemia, especially in individuals with moderate cholesterol levels.”

  • The paper relies on this without support.

    The safety data from short-term studies are sufficient to establish long-term safety.

    “Long-term safety studies are not available yet.”

  • The paper relies on this without support.

    The cited studies' results are reliable and applicable to the populations described in the paper.

    “Based on the available data, no serious safety concerns have been raised.”

  • The paper relies on this without support.

    The absence of reported serious safety concerns in the available studies indicates that the nutraceutical combinations have no serious safety concerns.

    “Based on the available data, no serious safety concerns have been raised.”

  • The paper relies on this without support.

    Improvements in surrogate endpoints such as LDL-C, hs-CRP, and endothelial function translate into clinical cardiovascular benefit.

    “Many available data, including the most recent studies with PCSK9 inhibitors, support the LDL-C concept that “lower is better” [276].”

  • The paper relies on this without support.

    Low vitamin D status is associated with hyperlipidemia.

    “Low vitamin D status has been associated with hyperlipidemia.”
13 of 13

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?

  • Some evidence of additive efficacy is available for the association of statins with PUFAs, soluble fibers, plant sterols, bergamot, tocotrienols, garlic, and vitamin D.

    “Some evidence of additive efficacy is available for the association of statins with PUFAs, soluble fibers, plant sterols, bergamot, tocotrienols, garlic, and vitamin D [107]”

    From Nutraceuticals in the Management of Dyslipidemia: Which, When, and for Whom? Could Nutraceuticals Help Low-Risk Individuals with Non-optimal Lipid Levels? (2021) · cites this paper as [107]

  • Omega-3 acids may be an important natural option for statin-intolerant patients with persistent severe triglyceride elevations.

    “In certain clinical situations, such as in patients who are unable to tolerate statin therapy and who also have persistent severe elevations in triglycerides (TGs), omega-3 acids might represent an important natural alternative choice (19).”

    From The Role of Nutraceuticals in Statin Intolerant Patients (2018) · cites this paper as [19]

  • Nutraceuticals can help achieve lipid therapeutic goals and reduce cardiovascular residual risk, but data on cardiovascular residual risk are still limited.

    “Nutraceuticals can help achieve lipid therapeutic goals and reduce CV residual risk; however, data on the latter are still limited (19)”

    From The Role of Nutraceuticals in Statin Intolerant Patients (2018) · cites this paper as [19]

  • Soy has demonstrated direct vascular effects, chiefly on flow-mediated dilation.

    “Direct vascular effects, mainly on FMD, have been demonstrated (19).”

    From The Role of Nutraceuticals in Statin Intolerant Patients (2018) · cites this paper as [19]

  • Soybeans and their derivatives have high phytic acid, which lowers absorption of calcium, magnesium, copper, iron, and zinc.

    “Soybeans and their derivatives contain high amounts of phytic acid that reduces the absorption of some minerals (calcium, magnesium, copper, iron, and zinc) (19).”

    From The Role of Nutraceuticals in Statin Intolerant Patients (2018) · cites this paper as [19]

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.

  • Conclusion denies outcome evidence described earlier

    Major

    The conclusion says no outcome studies show prevention of CVD morbidity or mortality, but the paper describes a red yeast rice trial with significant reductions in CHD, all-cause mortality, and stroke.

  • LDL-C target attainment percentage uses the wrong denominator

    Major

    The reported 58 patients are 67.4% of the stated combined-therapy group of 86, not 72.5%. This changes the reported rate of achieving the therapeutic goal.

    Reported 72.5 · recomputed 67.44186

  • Two different EFSA citrinin limits are stated

    Major

    The paper gives the EFSA limit as both 0.2 and 20 μg/kg body weight per day-a hundredfold difference that affects its safety assessment.

  • β-glucan estimate falls outside its stated confidence interval

    Minor

    The LDL-C estimate is -0.21 mmol/l, whereas the printed confidence-interval endpoints are 0.27 and -0.14 mmol/l. The estimate is outside the interval formed by those endpoints.

  • Psyllium combination heading names an ingredient absent from the described trial

    Minor

    The subsection is headed as a psyllium-omega-3 combination, but its trial description identifies the combination as plant sterols and omega-3 fatty acids, without psyllium.

  • Pantethine table omits an LDL-C effect reported in the text

    Minor

    The pantethine table calls its expected LDL-C effect "Not applicable," while the accompanying text reports LDL-C reductions of 4% and 11% in trials.

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

    Minor

    The stated HDL-C estimate of 0.007 mmol/l is below both printed interval endpoints, 0.03 and 0.11 mmol/l.

  • Triglyceride unit conversions disagree

    Minor

    The paper pairs a 0.60 mmol/l triglyceride change with 23.2 mg/dl, but elsewhere pairs a smaller 0.34 mmol/l change with a larger 30.12 mg/dl change. Both pairs cannot use the same conversion between triglyceride units.

8 of 8

Cites

Flagged first, then by citations

Research works printed but not linked: 3

  1. [11]NCD Risk Factor Collaboration (NCD-RisC) Trends in total cholesterol and lipid fractions in 22 Western and Asian countries Lancet 2017 in press
  2. [207]Mazidi M Rezaie P Banach M Impact of L-carnitine on C-reactive proteIn: a systematic review and meta-analysis of 10 randomized control trials with 925 patients 2017 7 Presentation at 2nd CPPEI Congress in Vienna (data unpublished)
  3. [285]Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico Lancet 1999 354 447 55 10465168

Cited by

Sorted by citations

Related

Authors
Cicero, A. F. G., Colletti, A., Bajraktari, G., Descamps, O., Djuric, D. M., Ezhov, M., Fras, Z., Katsiki, N., Langlois, M., Latkovskis, G., Panagiotakos, D. B., Paragh, G., Mikhailidis, D. P., Mitchenko, O., Paulweber, B., Pella, D., Pitsavos, C., Reiner, Ž., Ray, K. K., Rizzo, M., Sahebkar, A., Serban, M.-C., Sperling, L. S., Toth, P. P., Vinereanu, D., Vrablík, M., Wong, N. D., & Banach, M.
Affiliations
  • University of Bologna (IT)
  • University Clinical Center of Kosovo (XK)
  • University of Belgrade (RS)
  • University of Ljubljana (SI)
  • Aristotle University of Thessaloniki (GR)
  • University of Pavol Jozef Šafárik (SK)
  • Harokopio University of Athens (GR)
  • The Royal Free Hospital (GB)
  • Paracelsus Medical University (AT)
  • National and Kapodistrian University of Athens (GR)
  • University Hospital Centre Zagreb (HR)
  • Imperial College London (GB)
  • Istituto Euro Mediterraneo di Scienza e Tecnologia (IT)
  • Mashhad University of Medical Sciences (IR)
  • Emory University (US)
  • Johns Hopkins University (US)
  • University of California, Irvine (US)
  • Medical University of Lodz (PL)
Corresponding author
  • Cicero, Arrigo F.G.
  • Banach, Maciej
ORCID
Venue
Archives of Medical Science
Publisher
Termedia Sp. z.o.o.
Published
2017
Volume
5
Issue
5
Pages
965-1005
ISSN
1734-1922 (ISSN-L)
DOI
10.5114/aoms.2017.69326
PMC
PMC5575230
OpenAlex
W2743820880
Semantic Scholar
ff099cb4733a1f447f72569bbb7dd31b1d41801e
Cited by
281
References
294
Citations by year
2026: 7 · 2025: 15 · 2024: 11 · 2023: 20 · 2022: 26 · 2021: 50 · 2020: 33 · 2019: 44 · 2018: 62 · 2017: 12
FWCI
42.32
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • Archives of Medical Science (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Repository of the Medical Faculty of the University of Zagreb (University of Zagreb) (acceptedVersion)
  • University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion, other-oa)
  • Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
  • University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion)
  • Spiral (Imperial College London) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Surgery › Natural Products and Biological Research
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Keywords
nutraceuticals, lipid-lowering drugs, cardiovascular disease, hypercholesterolemia, LDL cholesterol, HDL cholesterol, total cholesterol, atherosclerosis, ischemic heart disease, coronary artery disease, cardiovascular risk factors, statins, dietary cholesterol, dietary fiber, phytosterols, omega-3 fatty acids, clinical guidelines

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-08.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-08.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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