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Cited by 17Lipoproteins and Cardiovascular HealthNatural Products and Biological ResearchCholesterol and Lipid Metabolism

ESSENS dyslipidemia: A placebo-controlled, randomized study of a nutritional supplement containing red yeast rice in subjects with newly diagnosed dyslipidemia

Open access
Kasliwal, Ravi R., Bansal, Manish, Gupta, Rajeev, Shah, Siddharth, Dani, Sameer, Oomman, Abraham, Pai, Vikas, Prasad, Guru Mallapa +4 more·2016·Nutrition
DOI 10.1016/j.nut.2016.01.012
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Abstract

OBJECTIVE: Evidence suggests prolonged exposure to lower levels of low-density lipoprotein cholesterol (LDL-C), starting at a younger age, substantially lowers cardiovascular (CV) risk. Accordingly, the CV pandemic affecting younger population in low- to low-middle-income countries, where statin usage is poor even in secondary prevention, may benefit from lipid-lowering nutritional products, as nutritional intervention is generally preferred in these cultures. However, the safety and efficacy of such preparations have not been systematically tested. METHODS: In this multicenter, double-blind study, 191 statin-free subjects with newly-diagnosed hyperlipidemia (LDL-C >120 mg/dL, 3.11 mmol/L) and no evidence of CV disease were randomized to one capsule of a proprietary bioactive phytonutrient formulation containing red yeast rice, grape-seed, niacinamide, and folic acid (RYR-NS) or matched placebo twice daily, along with lifestyle modification, for 12 wk. RESULTS: Mean baseline LDL-C levels were 148.5 ± 24.0 mg/dL (3.85 ± 0.62 mmol/L) and 148.6 ± 21.9 mg/dL (3.85 ± 0.57 mmol/L) in the RYR-NS and placebo groups respectively. Compared with placebo, RYR-NS resulted in a significant reduction in LDL-C (-29.4% versus -3.5%, P < 0.0001) and non-high-density lipoprotein cholesterol (non-HDL-C; -29.8% versus -10.3%, P < 0.0001) at 12 wk. With RYR-NS, 43.4% individuals attained desirable LDL-C levels and 55.4% desirable non-HDL-C levels by week 12, compared to only 0% and 1.1%, respectively, at baseline. No safety issues were observed. CONCLUSION: This study demonstrates the efficacy and safety of RYR-NS in lowering LDL-C and non-HDL-C after 12 wk, with magnitude of LDL-C reduction being comparable to that seen with moderate-intensity statin therapy. Further long-term studies are required to determine the impact of RYR-NS on treatment adherence and clinical outcomes.

AI snapshot

Written from the paper’s full text.

TL;DR

In a 12-week, multicenter, double-blind, placebo-controlled trial in India, a red yeast rice–containing nutritional supplement (RYR-NS) significantly lowered LDL-C and non-HDL-C in statin-free adults with newly diagnosed dyslipidemia. The reported LDL-C reduction was comparable to moderate-intensity statin therapy, with no safety issues observed over the short term.

Key findings

  • RYR-NS reduced LDL-C by 29.4% versus 3.5% with placebo at 12 weeks (P < 0.0001), and non-HDL-C by 29.8% versus 10.3% (P < 0.0001).
  • RYR-NS also reduced total cholesterol by 22.7% (P < 0.0001), triglycerides by 4.5% (P = 0.01), and increased HDL-C by 9.5% (P = 0.01) from baseline to week 12.
  • By week 12, 43.4% of RYR-NS participants attained desirable LDL-C levels and 55.4% attained desirable non-HDL-C levels, compared with 0% and 1.1% at baseline, respectively.
  • Adverse events were infrequent and similar between groups (overall P = 0.91); no study drug discontinuations occurred, and no safety issues were observed.

Methods

  • Multicenter, randomized, double-blind, placebo-controlled trial at nine clinical sites in India; 191 statin-free adults aged 18–65 years with newly diagnosed hyperlipidemia (LDL-C >120 mg/dL or 3.11 mmol/L) and no known cardiovascular disease were randomized 1:1 to RYR-NS 600 mg twice daily or matching placebo for 12 weeks, along with lifestyle modification.
  • Of 191 randomized, 180 completed and were analyzed; primary efficacy outcomes were absolute and percent change in LDL-C at weeks 4 and 12, with additional lipid and safety measures at week 12.
  • Analyses used descriptive statistics, Student’s t test or chi-square test, paired t test or repeated measures ANOVA, McNemar test, and SAS version 9.1; P < 0.05 was considered significant.

Limitations

  • The paper states the main limitations were the relatively small sample size and short 12-week duration, so long-term safety of RYR-NS could not be determined.
  • The paper states that only statin-free patients were included, so it could not assess whether RYR-NS provides incremental LDL-C reduction in patients already on statin therapy.
  • Evident from the text: the study evaluated surrogate lipid endpoints rather than clinical cardiovascular outcomes, and the authors note that further large-scale, long-term studies are needed to determine effects on treatment adherence and clinical outcomes.

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

Integrity signals

Registry

Crossref · 10.1016/j.nut.2016.01.012

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 55 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    There were no clinically relevant changes in any safety parameters during the study.

    “There were no clinically relevant changes in any of the safety parameters during the course of the study (Table 3).”
    Quote in the paperSubstantial claim
  • Findingown data

    RYR-NS significantly increased HDL-C levels from baseline to week 12 by 9.5%.

    “whereas HDL-C levels increased from 42.1 Æ 9.1 mg/dL (1.09 Æ 0.24 mmol/L) to 46.1 Æ 14.7 mg/dL (1.19 Æ 0.38 mmol/L), (þ9.5%, P ¼ 0.01).”
    Quote in the paperNot a substantial claim
  • Findingown data

    By week 12, 87.0% of RYR-NS patients had desirable or above desirable non-HDL-C levels, compared with 44.3% in the placebo group.

    “Similarly, 39.1% patients in the RYR-NS group had desirable (<130 mg/dL or 3.37 mmol/L) or above desirable (130-159 mg/dL or 3.37-4.12mmol/L) non-HDL-C levels at baseline, which increased to 87.0% at wk 12 (P < 0.0001).In the placebo group, the percentage of such patients increased from 23.9% at baseline to only 44.3% at the end of wk 12.”
    Quote in the paperSubstantial claim
  • Findingown data

    RYR-NS significantly reduced total cholesterol from baseline to week 12 by 22.7%.

    “RYR-NS resulted in significant reductions from baseline to wk 12 in the levels of TC (220.3Æ 32.4 mg/dL [5.71 Æ 0.84 mmol/L] to 168.4 Æ 34.8 mg/dL [4.36 Æ 0.90 mmol/L], À22.7%, P < 0.0001)”
    Quote in the paperSubstantial claim
  • Findingown data

    Total bilirubin increased slightly in the placebo group from baseline to week 12.

    “whereas total bilirubin level increased slightly in the placebo group from 0.46 Æ 0.22 mg/dL to 0.51 Æ 0.21 mg/dL (P ¼ 0.028; P ¼ 0.08 for comparison with the RYR-NS group).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 33
  • Classified as probably not a substantial claim. 24

  • May combine two claims.

    Findingown data

    Despite a greater LDL-C-lowering effect, RYR-NS was not associated with any adverse events during the study period.

    “More importantly, despite a greater LDL-C-lowering effect, RYR-NS was not associated with any adverse events during the study period.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    By week 12, 84.8% of RYR-NS patients had desirable or above desirable LDL-C levels, compared with 27.3% in the placebo group.

    “However, by the end of wk 12, this percentage increased to 84.8% (P < 0.0001) with only 15.2% patients having borderline high (130-159 mg/dL or 3.37-4.12mmol/L), high (160-189 mg/dL or 4.14-4.90mmol/L), or very high (!190 mg/dL or 4.92 mmol/L) LDL-C levels (Fig. 4).In contrast, 14.8% patients had desirable or above desirable LDL-C levels at baseline in the placebo group, and this proportion”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Placebo also reduced total cholesterol and non-HDL-C levels, but these reductions were significantly lower than those observed with RYR-NS.

    “Participants randomized to receive placebo also experienced reductions in TC and non-HDL-C levels (6.7% and 10.3%, respectively) but these changes were significantly lower than those observed in the RYR-NS group (both P < 0.0001).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Treatment with RYR-NS significantly reduced LDL-C from baseline to week 12 by 29% and to week 4 by 22%.

    “Treatment with RYR-NS resulted in a significant reduction in LDL-C levels from 146.7 Æ 22.8 mg/dL (3.80 Æ 0.59 mmol/L) at baseline to 113.5 Æ 30.1 mg/dL (2.94 Æ 0.78 mmol/L) at wk 4 and 102.6 Æ 31.2 mg/dL (2.66 Æ 0.81 mmol/L) at wk 12 (P < 0.0001 for trend) (Table 2, Fig. 2).This translated into 22% reduction in LDL-C levels at wk 4 and 29% at wk 12 (Fig. 3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    RYR-NS was well tolerated during the 12-week treatment period, with no study drug discontinuations in either group.

    “RYR-NS was well tolerated during the 12 wk of treatment period and no study drug discontinuations occurred in any of the two groups.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    All adverse events were unrelated to study treatment except for one treatment-related event of gastric acidity in the placebo group.

    “All adverse events were unrelated to the study treatment with the exception of one treatment-related event of gastric acidity in the placebo group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Adverse events were very infrequent and similar in the two groups.

    “Adverse events were very infrequent (gastric acidity/ discomfort: RYR-NS 2, placebo 2; diarrhea/vomiting: RYR-NS 3, placebo 0; fatigability/body aches: RYR-NS 0, placebo 4) and were similar in the two groups (overall P ¼ 0.91).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    All adverse events were transient and none was severe.

    “All adverse events were transient and none was severe.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    This study demonstrates the efficacy and safety of RYR-NS in LDL-C and non-HDL-C lowering after 12 wk of treatment in Indians.

    “This study demonstrates the efficacy and safety of RYR-NS in LDL-C and non-HDL-C lowering after 12 wk of treatment in Indians.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    While none of the patients had LDL-C levels within desirable limits at baseline, the proportion increased to 43.4% with just 12 wk of treatment with RYR-NS.

    “Importantly, while none of the patients had LDL-C levels within desirable limits at baseline, the proportion increased to 43.4% with just 12 wk of treatment with RYR-NS.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Prolonged exposure to lower LDL-C levels, starting at a younger age, substantially lowers cardiovascular risk.

    “Evidence suggests prolonged exposure to lower levels of low-density lipoprotein cholesterol (LDL-C), starting at a younger age, substantially lowers cardiovascular (CV) risk.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    A slightly lower LDL-C cut-off than traditionally defined was used because Indians are known to have lower LDL-C levels than Western populations.

    “We used a slightly lower cut-off of LDL-C than traditionally defined (130 mg/dL or 3.37 mmol/L), as Indians are known to have lower LDL-C levels than Western populations [28,29].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [28] Hughes, 1990, Relationship between plasma cholesterol and coronary artery disease in Asians, Atherosclerosis source

      Not checked in the free run.

    • cites [29] Enas, 1996, Coronary heart disease and its risk factors in first-generation immigrant Asian Indians to the United States Of America, Indian Heart J

      Not checked in the free run.

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

    Premisecitation

    Statins have been shown to reduce CV events in a wide variety of patient populations.

    “Statins are currently the most effective agents available for managing dyslipidemia and have been shown to reduce CV events in a wide variety of patient populations [10,25,31].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [10] Grundy, 2004, Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines, Circulation source

      Not checked in the free run.

    • cites [25] 2002, Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report, Circulation source

      Not checked in the free run.

    • cites [31] Stone, 2014, 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, Circulation source

      Not checked in the free run.

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

    Premisecitation

    Grapeseed extract has antioxidant properties and may also lower LDL-C.

    “Grapeseed extract has antioxidant properties and may also lower LDL-C [27].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27] Preuss, 2000, Effects of niacin-bound chromium and grape seed proanthocyanidin extract on the lipid profile of hypercholesterolemic subjects: a pilot study, J Med

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Concern about adverse effects and an inherent psychological barrier against being on a drug for life are among the major reasons for low uptake of statins.

    “suggesting that the concern of adverse effects and an inherent psychological barrier against being on a “drug for life” are among the major reasons for such a low uptake of statins.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] Yusuf, 2011, Use of secondary prevention drugs for cardiovascular disease in the community in high-income, middle-income, and low-income countries (the PURE study): a prospective epidemiological survey, Lancet source

      Not checked in the free run.

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

    Premisecitation

    Niacin is known to increase HDL-C and lower LDL-C levels, and folic acid reduces elevated homocysteine levels.

    “While niacin is known to increase HDL-C and lower LDL-C levels, folic acid reduces elevated homocysteine levels [25,26].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [25] 2002, Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report, Circulation source

      Not checked in the free run.

    • cites [26] Chambers, 2001, Homocysteine: a novel risk factor for coronary heart disease in UK Indian Asians, Heart source

      Not checked in the free run.

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

    Study design and conductown data

    The study was approved by institutional review boards and local independent ethics committees at all nine sites, and written informed consent was obtained from each participant before enrolment.

    “At all nine sites, the study was approved by the respective institutional review boards and the local independent ethics committees.Written informed consent was obtained from each participant before enrolment in the study.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Premisereasoning

    For any combination of food-derived ingredients, the exact preparation needs to be tested independently for efficacy and safety because of unknown interactions among ingredients.

    “However, for any combination of food-derived ingredients, the exact preparation needs to be tested independently for its efficacy and safety because of unknown interactions among different ingredients.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Not only the magnitude of LDL-C lowering is important, but the duration of exposure to elevated LDL-C levels is equally important.

    “At the same time, it has become increasingly evident now that not only the magnitude of LDL-C lowering is important but that the duration of exposure to elevated LDL-C levels is equally important [11,16,38].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [11] Cohen, 2006, Sequence variations in PCSK9, low LDL, and protection against coronary heart disease, N Engl J Med source

      Not checked in the free run.

    • cites [16] Brown, 2006, Biomedicine. Lowering LDL–not only how low, but how long?, Science source

      Not checked in the free run.

    • cites [38] Mihaylova, 2012, Cholesteral Treatment Trialists' (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials, Lancet source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The reduction in LDL-C achieved with RYR-NS was greater than what has been demonstrated with red yeast rice alone, indicating a possible synergistic action between red yeast rice and other ingredients of RYR-NS.

    “In our study, the reduction in LDL-C levels achieved with RYR-NS was more than what has been demonstrated with RYR alone.This indicates a possible synergistic action between RYR and other ingredients of RYR-NS, especially niacin, folic acid, grape seed and black pepper seed powder.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    This study demonstrates the efficacy and safety of RYR-NS in lowering LDL-C and non-HDL-C after 12 weeks.

    “This study demonstrates the efficacy and safety of RYR-NS in lowering LDL-C and non-HDL-C after 12 wk, with magnitude of LDL-C reduction being comparable to that seen with moderate-intensity statin therapy.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Niacin and grapeseed powder improve lipid profile through different mechanisms.

    “whereas niacin and grapeseed powder are known to improve lipid profile through different mechanisms [25][26][27]”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [25] 2002, Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report, Circulation source

      Not checked in the free run.

    • cites [26] Chambers, 2001, Homocysteine: a novel risk factor for coronary heart disease in UK Indian Asians, Heart source

      Not checked in the free run.

    • cites [27] Preuss, 2000, Effects of niacin-bound chromium and grape seed proanthocyanidin extract on the lipid profile of hypercholesterolemic subjects: a pilot study, J Med

      Not checked in the free run.

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

    Study design and conductown data

    A total of 337 subjects were screened, 191 were randomized to RYR-NS or placebo, 11 withdrew, and 180 completed the study and were included in the analysis.

    “A total of 337 subjects were screened, out of which 191 subjects satisfying eligibility criteria were randomized to receive RYR-NS (96 subjects) or placebo (95 subjects).Of these, 11 patients (four in the RYR-NS group and seven in the placebo group) withdrew from the study, citing their unwillingness to continue their participation in a research project.The remaining 180 patients who completed the”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    Subjects were randomly assigned in a 1:1 ratio using sealed envelopes to receive RYR-NS 600-mg capsule twice daily or matching placebo for 12 weeks in a double-blinded manner.

    “The subjects were randomly assigned in a 1:1 ratio using these sealed envelopes to receive either RYR-NS, 600-mg capsule twice a day (n ¼ 96) or a matching placebo (n ¼ 95), which was administered for 12 wk in a double-blinded manner.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Recent studies using non-statin therapies such as ezetimibe or PCSK9 inhibitors have shown that residual CV risk can be reduced with further LDL-C lowering.

    “Recent studies using non-statin therapies such as ezetimibe or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have shown that the residual CV risk can be print & web 4C=FPO reduced with further LDL-C lowering with these agents [18,[34][35][36][37].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18,[34][35][36][37]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In patients with statin intolerance, red yeast rice significantly lowered LDL-C, total cholesterol, and triglyceride levels without increasing creatine phosphokinase levels, and only two patients complained of myalgias compared with one in the placebo group.

    “Becker et al. randomized 62 patients with dyslipidemia and a history of discontinuation of statin therapy because of myalgias to RYR or placebo for 24 wk [22].RYR not only resulted in significant lowering of LDL-C, TC, and triglyceride levels, there was no increase in creatine phosphokinase levels and only two patients complained of myalgias as compared to one patient in the placebo group.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [22] Becker, 2009, Red yeast rice for dyslipidemia in statin-intolerant patients: a randomized trial, Ann Intern Med source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Red yeast rice powder contains monacolins, some of which are natural inhibitors of HMG-CoA reductase, an enzyme also inhibited by statins.

    “RYR powder, which is the key ingredient, contains a milieu of monacolins, some of which are natural inhibitors of hydroxymethylglutarylcoenzyme A reductase, an enzyme also inhibited by statins.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    At baseline, serum bilirubin was slightly higher in the RYR-NS group than in the placebo group, with no other significant differences between groups.

    “Although the serum bilirubin level was slightly higher in the RYR-NS group (0.6 Æ 0.3 mg/dL versus 0.5 Æ 0.2 mg/dL for placebo, P ¼ 0.01), there were no other significant differences between the two groups at baseline (Table 1).”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning

    Assuming an average standard deviation of 30 mg/dL for LDL-C, 72 subjects per group were required to detect a postintervention difference of 15 mg/dL with 85% power; allowing for 20% drop-out, at least 90 subjects per group were included.

    “Assuming an average standard deviation of 30 mg/dL (0.78 mmol/L) for LDL-C in the two groups, 72 subjects were required in each group to detect a postintervention difference of 15 mg/dL (0.39 mmol/L) with 85% power.Allowing a 20% drop-out rate, we included at least 90 subjects in each group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Most other studies with red yeast rice have been small but have consistently demonstrated its LDL-C-lowering efficacy.

    “Most of the other studies with RYR have been small but have consistently demonstrated its LDL-C-lowering efficacy [21].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Li, 2014, A meta-analysis of red yeast rice: an effective and relatively safe alternative approach for dyslipidemia, PLoS One source

      Not checked in the free run.

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

    Study design and conductown data

    The study was a multicenter, randomized, double-blinded, placebo-controlled study conducted at nine clinical sites across India.

    “This was a multicenter, randomized, double-blinded, placebo controlled study (Fig. 1) conducted at nine clinical sites across India (Appendix B).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Black pepper seed powder, with active principle piperine, has antioxidant effects and increases the bioavailability of various nutrients.

    “Black pepper seed powder (active principle, piperine) also has antioxidant effects and increases the bioavailability of various nutrients through a number of mechanisms [33].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Gulcin, 2005, The antioxidant and radical scavenging activities of black pepper (Piper nigrum) seeds, Int J Food Sci Nutr source

      Not checked in the free run.

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

    Study design and conductown data

    The study was registered with ClinicalTrials.gov under identifier NCT02187757.

    “The study was registered with Clinical Trials.Gov (#NCT02187757).”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Dyslipidemia is the single-most important cardiovascular risk factor because of its high prevalence and direct pathogenic association with atherosclerosis.

    “Of the major CVD risk factors, dyslipidemia remains the single-most important factor because of its high prevalence and direct pathogenic association with atherosclerosis [4].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Yusuf, 2004, Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study, Lancet source

      Not checked in the free run.

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

    Premisecitation

    Based on published reports, the European Food Safety Authority has approved red yeast rice as a food for maintenance of normal cholesterol levels.

    “Based on these published reports, the European Food Safety Authority has approved RYR as a food for maintenance of normal cholesterol levels [32].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] 2011, EFSA Journal source

      Not checked in the free run.

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

    Premisecitation

    A meta-analysis of studies evaluating spirulina supplementation documented a significant LDL-C lowering effect.

    “For example, a metaanalysis of studies evaluating the role of spirulina supplementation documented significant LDL-C lowering effect [42]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Serban, 2015, A systematic review and meta-analysis of the impact of spirulina supplementation on plasma lipid concentrations, Clin Nutr

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Substantial public health gains can be made if these reductions could be sustained over the long term.

    “Substantial public health gains can be made if these reductions could be sustained over the long term.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    Initiating even moderate LDL-C lowering at an early stage of life can result in substantial reduction in the lifetime CVD risk.

    “Since atherosclerosis begins during childhood, initiating even moderate LDL-C lowering at an early stage of life can result in substantial reduction in the lifetime CVD risk.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Atherosclerosis begins during childhood.

  • May combine two claims.

    Interpretationcitation

    A functional food/bioactive phytonutrient formulation could be potentially helpful in cases of actual statin intolerance or when statins alone are not able to bring about desired LDL-C reduction.

    “in cases of actual statin intolerance [41] or when statins alone are not able to bring about desired LDL-C reduction, as there is currently lack of effective pharmacologic options that could be used either in place of or in combination with statin therapy.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [41] Banach, 2015, Statin intolerance - an attempt at a unified definition. Position paper from an international lipid expert panel, Expert Opin Drug Saf source

      Not checked in the free run.

    • Rests on an assumption: There is currently a lack of effective pharmacologic options that could be used either in place of or in combination with statin therapy.

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

    Study design and conductnone given

    The funding agencies had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the manuscript for publication.

    “The funding agencies had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the manuscript for publication.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    No such changes were observed with other agents such as garlic and astaxanthin.

    “whereas no such changes were observed with other agents such as garlic and astaxanthin [43,44].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [43] Ursoniu, 2015, Lipid profile and glucose changes after supplementation with astaxanthin: a systematic review and meta-analysis of randomized controlled trials, Arch Med Sci source

      Not checked in the free run.

    • cites [44] Sahebkar, 2016, Effect of garlic on plasma lipoprotein(a) concentrations: a systematic review and meta-analysis of randomized controlled clinical trials, Nutrition source

      Not checked in the free run.

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

    Study design and conductnone given

    This was an investigator-initiated study.

    “This was an investigator-initiated study.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The study was double-blinded.

    “As the study was double-blinded, the placebo capsule used was double zero HPMC opaque red capsules and filled with 600 mg of maize starch.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductnone given

    The main limitations of the present study included its relatively small sample size and short duration.

    “The main limitations of the present study included its relatively small sample size and short duration.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Statins are limited by variable and largely poor uptake, with less than 5% of patients with CVD on regular statin therapy in low- and lower-middle-income countries.

    “Although statins may be an effective option, they are limited by variable and largely poor uptake, with less than 5% of patients with CVD shown to be on regular statin therapy in low-and lower-middle-income countries [20].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] Yusuf, 2011, Use of secondary prevention drugs for cardiovascular disease in the community in high-income, middle-income, and low-income countries (the PURE study): a prospective epidemiological survey, Lancet source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Availability of a food-based therapeutic solution that appeals to social and cultural sensibilities of people from countries like India, China, and others where traditional medicine systems coexist could be very beneficial.

    “Under these circumstances, the availability of a food-based therapeutic solution that appeals to the social and cultural sensibilities of the people from countries like India, China, and others where traditional medicine systems coexist could be very beneficial.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    RYR has been evaluated and found to be safe in a small group of statin intolerant patients.

    “In fact, as outlined earlier, RYR has also been evaluated and found to be safe in a small group of statin intolerant patients.”
    Quote in the paperNot a substantial claim
47 of 47

  • The paper relies on this without support.

    The safety and efficacy of lipid-lowering nutritional preparations have not been systematically tested.

    “However, the safety and efficacy of such preparations have not been systematically tested.”

  • The paper relies on this without support.

    The best approach to achieve early and effective LDL-C lowering is not clearly known.

    “However, despite the growing evidence emphasizing the need for early and effective LDL-C lowering, the best approach to achieve this is not clearly known.”

  • The paper relies on this without support.

    Many dietary supplements claim lipid-lowering efficacy, but none are backed with the rigor of randomized, double-blind clinical trial evidence.

    “However, while there are many dietary supplements that claim to exhibit lipid-lowering efficacy, none are backed with the rigor of randomized, double-blind clinical trial evidence.”

  • The paper relies on this without support.

    Red yeast rice has never been tested in Indian subjects.

    “However, RYR has heretofore never been tested in Indian subjects.”

  • The paper relies on this without support.

    Nutritional intervention is generally preferred in low- to low-middle-income cultures, so lipid-lowering nutritional products may be more acceptable.

    “as nutritional intervention is generally preferred in these cultures.”

  • The paper relies on this without support.

    The cardiovascular pandemic affecting younger populations in low- to low-middle-income countries, where statin usage is poor even in secondary prevention, may benefit from lipid-lowering nutritional products.

    “Accordingly, the CV pandemic affecting younger population in low-to low-middle-income countries, where statin usage is poor even in secondary prevention, may benefit from lipid-lowering nutritional products, as nutritional intervention is generally preferred in these cultures.”

  • The paper relies on this without support.

    It is not known how best to achieve effective LDL-C lowering from an early age.

    “However, despite these encouraging evidences, it is not known how best to achieve effective LDL-C lowering from an early age.”

  • The paper relies on this without support.

    Concerns of adverse effects and inherent psychological barrier against lifetime use of a drug are amongst the major reasons responsible for low uptake of proven drugs like statins.

    “The concerns of adverse effects and inherent psychological barrier against the lifetime use of a drug are amongst the major reasons responsible for such a low uptake of proven drugs like statins.”

  • The paper relies on this without support.

    Most side effects of various lipid lowering therapies, with the notable exception of statin-induced diabetes, are observed mainly during the initial few weeks of treatment.

    “These results are reassuring since most of the side effects of various lipid lowering therapies, with the notable exception of statin-induced diabetes, are observed mainly during the initial few weeks of treatment.”

  • The paper relies on this without support.

    Atherosclerosis begins during childhood.

    “Since atherosclerosis begins during childhood, initiating even moderate LDL-C lowering at an early stage of life can result in substantial reduction in the lifetime CVD risk.”

  • The paper relies on this without support.

    There is currently a lack of effective pharmacologic options that could be used either in place of or in combination with statin therapy.

    “as there is currently lack of effective pharmacologic options that could be used either in place of or in combination with statin therapy.”
11 of 11

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?

  • Red yeast rice has been used as an alternative to statin therapy in treating patients with mild to moderate hypercholesterolemia, particularly in those considered statin intolerant, and clinical studies suggest red yeast rice is well tolerated, safe, and effective for cardiovascular disease primary prevention.

    “RYR has been used as an alternative to statin therapy in treating patients with mild to moderate hypercholesterolemia, particularly in those considered to be statin intolerant, and clinical studies suggest that RYR is well tolerated, safe, and effective for CVD primary prevention (126-128).”

    From The Role of Nutraceuticals in Statin Intolerant Patients (2018) · cites this paper as [128]

  • For all previously mentioned studies, there were no safety concerns.

    “For all previously mentioned studies, there were no safety concerns (80,126-130).”

    From The Role of Nutraceuticals in Statin Intolerant Patients (2018) · cites this paper as [128]

Self-check

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

  • Listed ingredients fall short of the stated 600-mg capsule dose

    Minor

    The ingredients listed in milligrams sum to 552 mg. Adding the separately listed 100 mcg of vitamin B9 brings the total to 552.1 mg, still 47.9 mg short of the stated 600 mg.

    Reported 600 · recomputed 552

1 of 1

The citation lists haven’t been fetched yet

References 51 · Cited by 17

Authors
Kasliwal, R. R., Bansal, M., Gupta, R., Shah, S., Dani, S., Oomman, A., Pai, V., Prasad, G. M., Singhvi, S., Patel, J., Sivam, S., & Trehan, N.
Affiliations
  • Medanta The Medicity (IN)
  • Fortis Escorts Hospital (IN)
  • Bhatia Hospital (IN)
  • Life Care Institute of Medical Sciences & Research (IN)
Corresponding author
Kasliwal, Ravi R.
ORCID
Venue
Nutrition
Publisher
Elsevier BV
Published
2016-07
Volume
32
Issue
7-8
Pages
767-776
ISSN
0899-9007 (ISSN-L)
DOI
10.1016/j.nut.2016.01.012
OpenAlex
W2291215398
Semantic Scholar
0d94626fc53bea5410adc64d151cffce1e25cb52
Cited by
17
References
51
Citations by year
2025: 1 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 1
FWCI
3.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrition (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Surgery › Natural Products and Biological Research
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords
red yeast rice, dyslipidemia, LDL cholesterol, non-HDL cholesterol, dietary supplements, grape seeds, nicotinamide, folic acid, lipid lowering, cardiovascular risk, lifestyle modification, treatment efficacy and safety
MeSH terms
Adolescent, Adult, Aged, Anticholesteremic Agents, Biological Products, Cardiovascular Diseases, Double-Blind Method, Female, Humans, Hyperlipidemias, Lipids, Male, Middle Aged, Treatment Outcome, Dietary Supplements, Young Adult

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.

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