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4 Most Liver Damaging Supplements (Avoid Over Usage)Resveratrol and metabolism -
A total of citations were initially identified by electronic database searches. Twenty-five articles were incorporated into the final meta-analysis after removal of duplicates by checking titles and abstracts and excluding non-relevant articles.
The process of study selection of relevant RCTs with more details is shown in the PRISMA flow chart Figure 1. All the 25 articles were placebo-controlled randomized controlled trials RCTs.
The number of participants in each group is ranged from 9 to The included articles were published from inception to October in our current meta-analysis. The clinical data extracted from the 25 articles were measured using specific enzymatic ELISA kits American Diabets Association, , including serum concentrations of TC, TG, HDL-C, LDL-C, adiponectin, leptin, insulin, and fasting glucose.
The characteristics of selected RCTs, with more details, are summarized in Table 1. The methodological quality and bias of all the eligible studies were assessed using the Cochrane Collaboration risk of bias tool and standard Excel forms.
Details on findings indicated that 8 studies had low bias risk, 19 studies had unclear bias risk, and 9 studies had high bias risk. Effects of RSV on metabolism indicators are presented in Figure 3. A random effects model was used to pool the results.
There was a significant decrease following RSV administration in WC with an SMD of —0. Meanwhile, we found that RSV had no significant effect on body weight with an SMD of. Figure 3. Standardized mean difference of metabolic markers meta-analysis for A body weight, B for body mass index, C for waist circumference, D fasting glucose, E insulin, F HOMA index, G HbA1c, H fat percentage, I total cholesterol, J low density lipoprotein cholesterol, K high density lipoprotein cholesterol, L triglyceride, M for adiponectin, N for leptin levels in resveratrol and control groups.
We found that heterogeneity was significantly high from prior comparisons. Subsequently, subgroup analyses were conducted to assess the possible source of heterogeneity, and the results are detailed in Table 2.
In our current meta-analysis, some subgroups did not complete the analysis because of under-representation in number of trials.
More detailed analyses were performed on subgroups with representation number of trials. WC was significantly decreased in obese patients SMD: —0. Regarding interval of intervention, our current meta-analysis indicated that RSV supplementation significantly reduced WC in trials with intervention interval of weeks —0.
There are approximately similar significant findings in fasting glucose, HbA1c, TC, HDL-C, and LDL-C based on potential moderator variables. Subgroup analysis of different grouping types produced significantly different results.
For HbA1c level, there was a significant reduction in type 2 diabetes mellitus T2DM group —1. For lipid metabolism, significant results were mainly focused on TC, HDL-C, and LDL-C.
Regarding different types of disease, we found that RSV supplementation significantly decreased TC and LDL-C in patients with T2DM vs. obese patients and other diseases.
However, for HDL-C, there was a significant reduction in obese patients vs. T2DM and other diseases. According to our current meta-analysis, the subgroup analyses indicated that no significant differences were observed based on moderator variables BW, BMI, insulin, HOMA index, TG, adiponectin, leptin, and fat percentage.
More details are presented in Table 2. In addition, the results for sensitivity-pooled SMD were not significant for BMI, insulin, HbA1c, LDL-C, TG, adiponectin, and leptin. The lower and higher pooled SMDs for these indicators in the sensitivity analysis with more details are presented in Table 3.
The Begg test to identify publication bias and funnel plots are shown in Supplementary Figure S1. However, the pooled SMDs were not significantly changed in terms of TC, HbA1c, and WC after the Duval and Tweedie test.
The conclusions of the current meta-analysis demonstrated that RSV intake had a significant effect on WC, HbA1c, TC, LDL-C, and HDL-C reduction, but that it had no effect on leptin and adiponectin levels.
The sensitivity analyses indicated that after exclusion of related RCTs, the pooled results of body weight, fasting glucose, and HOMA index had significant changes. In contrast, the finding has shown the opposite results for WC, TC, and HDL-C. The effects of modulating lipid by regulation of TC content, metabolic disturbances, and reduction in TC are thought to be exerted predominantly through LDL-C and HDL-C.
For people with diabetes, our findings indicated that RSV intake can reduce glycosylated HbA1c and blood glucose, and exhibits long-term glycemic regulation. However, the effect of reducing serum glucose is believed to be not associated with decreased insulin resistance or increased serum insulin.
To summarize, the findings indicated that RSV supplementation exerts anti-obesity effects by regulating glycolipid metabolism and improving metabolic disturbances.
Antioxidants are compounds that modulate the mechanisms of homeostasis of glucose and lipids by decreasing the levels of ROS Hussain et al. A tremendous amount of animal and clinical studies had proved that RSV could improve chronic diseases, especially metabolic syndrome.
Studies have suggested that RSV supplementation exerts effects on lipid by regulating genes involved in lipid metabolism Ahn et al. In rodents, RSV blunted high-fat diet HFD -induced hepatic lipid storage and metabolic disorders Alberdi et al. et al. In human trials, it was also observed that glucose and lipids were improved after RSV treatment Bhatt et al.
Discrepancies among existing bodies of evidence might be linked to insufficient sample size and characteristics existing in study design, such as study populations, statistical analyses, comorbid conditions, and dosages and formulations of RSV used.
Lipid metabolism played an important role in the physiological and pathological states, and disorder may lead to many pathophysiological consequences.
Hyperlipidemia is a sign of lipid metabolism disorder, one of the most common chronic diseases, and clinical diabetes; it associated with comorbidities such as hypertension and obesity, also known as a major driver of many metabolic diseases with no effective treatment.
Studies have found that body fat distribution is highly associated with altered lipid metabolism Zhang et al. Regulation of hepatic lipid metabolism is an integral component of overall regulatory program to maintain whole body metabolic homeostasis Warne et al.
It has been shown that lipid metabolism also influences modulation of inflammation and cytokine secretion Glass and Olefsky, ; Kumar et al. One of the most common tumors, ccRCC, is associated with dysfunctions in lipid metabolism, and the abnormal lipid accumulation phenomenon in ccRCC has been observed for a long time Wettersten et al.
A number of studies have reported the importance of lipid microdomains in protein sorting and transportation Gruenberg, Metabolic disorders, such as insulin resistance and obesity, have a basis in dysregulated lipid metabolism Sato et al. Host physiology and metabolic diseases are highly relevant to lipid homeostasis.
The observed changes in lipid compositions potentially indicate altered expression of diseased states. In metabolically compromised humans, RSV induced remodeling of myocellular lipid stores van Polanen et al.
In our current meta-analysis, we found that RSV supplementation exerts a beneficial effect on improving metabolic lipid and glucose disturbances. A previous study has suggested the role of RSV by regulating skeletal muscle, liver lipid, and energy metabolism Serrano et al. The liver plays a unique central role in modulating lipid absorption and energy homeostasis Mashek, In skeletal muscle, RSV ameliorates high-fat diet-induced insulin resistance and fatty acid oxidation via the ATM-AMPK axis Zhang Y.
Besides, other mechanisms have been proposed. For example, Zhang has suggested that the beneficial effect of RSV is related with change in the expression of several lipid metabolism-related miRNAs and genes Zhang H. Zhuang et al. Furthermore, in the future, large-scale and well-designed trials will be warranted to confirm the mechanism of the therapeutic effect of RSV.
Taken together, these results suggest that RSV has a dramatic impact on regulating lipid and glucose metabolism, and the major clinical value of resveratrol intake is for obese and diabetic patients.
The efficacy of resveratrol supplementation in lipid metabolism was clarified in the results of the systematic review. QZ and YW conceptualized and designed the study, and drafted and reviewed the initial manuscript. XH and CZ defined concepts and search items, data extraction process, and methodological appraisal.
QZ, YW, and SF planned the extraction of data and statistical analysis. QC and SF provided the critical insights. All authors approved and contributed to the final written manuscript.
This study was supported by Subsidy Funds for Improving Medical Services and Guarantee Capabilities Major Incurable Diseases CYW Funders and sponsors have no role in the design of this review. This study was partly supported by grants from the Chengdu Science and Technology Project No.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.
Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. BW, body weight; BMI, body index mass index; WC, waist circumference; TC, total cholesterol; TG; triglyceride; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; HbA1c, hemoglobin A1c; T2DM, type two diabetes mellitus.
Ahn, J. Dietary resveratrol alters lipid metabolism-related gene expression of mice on an atherogenic diet. doi: PubMed Abstract CrossRef Full Text Google Scholar. Alberdi, G. Hepatic lipid metabolic pathways modified by resveratrol in rats fed an obesogenic diet.
Nutrition 29, — Changes in white adipose tissue metabolism induced by resveratrol in rats. American Diabets Association Classification and diagnosis of diabetes.
Diabetes care 40 Suppl. Google Scholar. Apostolidou, C. Alterations of antioxidant status in asymptomatic hypercholesterolemic individuals after resveratrol intake. Food Sci. Arzola-Paniagua, M.
Efficacy of an orlistat-resveratrol combination for weight loss in subjects with obesity: a randomized controlled trial. Obesity 24, — Asghari, S.
Comparison of calorie-restricted diet and resveratrol supplementation on anthropometric indices, metabolic parameters, and serum sirtuin-1 levels in patients with nonalcoholic fatty liver disease: a randomized controlled clinical trial.
Azorín-Ortuño, M. Effects of long-term consumption of low doses of resveratrol on diet-induced mild hypercholesterolemia in pigs: a transcriptomic approach to disease prevention.
Batista-Jorge, G. Oral resveratrol supplementation improves metabolic syndrome features in obese patients submitted to a lifestyle-changing program. Life Sci. Bhatt, J. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus.
Cao, W. Chen, S. Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: a randomized controlled trial. Liver Dis. de Ligt, M.
Other microbial metabolites such as short-chain fatty acids SCFAs , branched chain amino acids, succinate, indole propionic acid, and endocannabinoids were implicated in mediating bacterial regulation of host metabolism 11 , Zhuang et al.
Likewise, metformin treatment in individuals with T2D significantly altered circulating SCFAs, including increasing acetate, which was correlated with lower fasting insulin Intestinal AMPKα1 deficiency altered energy expenditure and brown fat thermogenesis via changes in the gut microbiome and metabolites, particularly methylglyoxal Despite this, some important questions remain for future research.
For example, how is the gut microbiome involved in BA homeostasis in response to REV-I, including BA synthesis in the liver, gut modifications, and enterohepatic circulation? Further investigations are also needed to determine the relationships between CDCA-FXR and SR-B1 in complicated physiological and pathophysiological settings.
An intestinal FXR tissue-specific mouse line will assist in delineating the roles of intestinal FXR related to REV-1 effects.
Finally, human and rodent BAs have substantially different species and signaling properties, which calls for additional attention for proper interpretation and translational conclusions.
In summary, the study by Pang and colleagues 4 uncovers a new avenue for determining a prospective unified mechanism by which dietary polyphenols and other drugs exert their metabolic effects upon the gut microbiota and BA signaling cascades Fig. Resveratrol, metformin, berberine, and curcumin affect the gut microbiota, which results in host metabolic homeostasis via microbial metabolites production, including SCFAs, endotoxins, bile acids BAs , endocannabinoids, BCAA, and TMAO.
Within the intestinal lumen, conjugated primary bile acids are metabolized by bile salt hydrolase BSH from gut bacteria, which deconjugates and reconverts the conjugated primary BAs into free primary BAs CA and CDCA.
The multistep 7a-dehydroxylation pathway continues to perform dehydroxylation reactions on CA and CDCA to form secondary BAs. Namely, CA is converted into deoxycholic acid DCA and CDCA is converted into lithocholic acid LCA and ursodeoxycholic acid UDCA.
These BAs target BA receptors and related signaling pathways, which results in glucose homeostasis, chylomicron secretion, and energy homeostasis. Patel, K. et al. Sulfate metabolites provide an intracellular pool for resveratrol generation and induce autophagy with senescence.
Article PubMed Google Scholar. Cote, C. Resveratrol activates duodenal Sirt1 to reverse insulin resistance in rats through a neuronal network.
Article CAS PubMed Google Scholar. Sung, M. Improved glucose homeostasis in obese mice treated with resveratrol is associated with alterations in the gut microbiome. Diabetes 66 , — Juan, Pang et al.
Resveratrol intervention attenuates chylomicron secretion via 1 repressing fecal chenodeoxycholic acid and jejunal scavenger receptor SR-B1. Article ADS Google Scholar. Wahlström, A. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab. Sun, L.
Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. Article CAS PubMed PubMed Central Google Scholar. Shin, N. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Han, Z.
Gut microbiota mediates the effects of curcumin on enhancing Ucp1-dependent thermogenesis and improving high-fat diet-induced obesity. Food Funct. Zhang, Y. Gut microbiome-related effects of berberine and probiotics on type 2 diabetes the PREMOTE study.
Article ADS CAS PubMed PubMed Central Google Scholar. Li, M. Gut microbiota-bile acid crosstalk contributes to the rebound weight gain after calorie restriction in mice. de Vos, W. Gut microbiome and health: mechanistic insights. Cani, P. Microbial regulation of organismal energy homeostasis.
Zhuang, Y. Resveratrol improves growth performance, intestinal morphology, and microbiota composition and metabolism in mice. Article PubMed PubMed Central Google Scholar. Mueller, N. Metformin affects gut microbiome composition and function and circulating short-chain fatty acids: a randomized trial.
Diabetes Care 44 , — Zhang, E. Intestinal AMPK modulation of microbiota mediates crosstalk with brown fat to control thermogenesis. Download references. The figures were created using BioRender BioRender. Caloric restriction is known to extend the lifespan of a number of species, including yeast, worms, flies, fish, rats, and mice In yeast Saccharomyces cerevisiae , caloric restriction stimulates the activity of an enzyme known as Silent information regulator 2 protein Sir2 or sirtuin Yeast Sir2 is a nicotinamide adenine dinucleotide NAD -dependent deacetylase enzyme that removes the acetyl group from acetylated lysine residues in target proteins see the article on Niacin.
Resveratrol feeding also extended the lifespan of worms Caenorhabditis elegans and fruit flies Drosophila melanogaster by a similar mechanism Additionally, resveratrol dose-dependently increased the lifespan of a vertebrate fish Nothobranchius furzeri Resveratrol was also found to extend the lifespan of mice on a high-calorie diet such that their lifespan was similar to that of mice fed a standard diet Although resveratrol increased the activity of the Sir2 homologous human sirtuin 1 SIRT1 in the test tube , there are no epidemiological data to link resveratrol, SIRT1 activation, and extended human lifespan.
Moreover, the supraphysiological concentrations of resveratrol required to increase human SIRT1 activity were considerably higher than concentrations that have been measured in human plasma after oral consumption.
Based on a lack of correlation with baseline inflammatory markers, cardiovascular disease and cancer incidence, and all-cause mortality, the authors concluded that higher versus lower quartiles of urinary resveratrol metabolite concentrations did not predict risk of chronic disease or mortality.
However, key experts identified several limitations regarding the quality of the research , Specifically, the use of single measures of total urinary resveratrol metabolites at baseline has been highlighted as being unlikely to reflect lifetime consumption of wine or exposure to dietary resveratrol Similar to the effect of caloric restriction, resveratrol was found to improve obesity and diabetes -related metabolic deregulations via the activation of metabolic sensors, including SIRT and the AMP-activated protein kinase AMPK , as well as to promote the AMPK-dependent clearance of β-amyloid peptide in the brain of an AD mouse model Resveratrol has also exhibited additional neuroprotective properties in cultured cells and animal models see Biological Activities.
Although resveratrol bioavailability to the brain is uncertain 78 , a randomized , double-blind , placebo -controlled study has reported an increase in cerebral blood flow in the prefrontal cortex of healthy young subjects ages, years following a single oral dose of mg of resveratrol.
However, resveratrol intake did not improve performance in cognitively demanding tasks undertaken during the post-administration period Additional evidence of the potential of resveratrol to mimic the metabolic benefits of caloric restriction on cognitive health may come from ongoing clinical trials in both healthy older individuals and AD patients More than one out of three American adults has impaired glucose tolerance also known as prediabetes , which places them at increased risk of developing type 2 diabetes Impaired glucose tolerance is associated with insulin resistance in skeletal muscle — the major peripheral tissue for insulin -mediated glucose uptake — as well as defective insulin secretion by pancreatic β-cells.
Muscle insulin resistance, which is thought to be the earliest stage in the development of type 2 diabetes, is characterized by excess lipid exposure, impaired insulin receptor signaling , impaired glucose uptake, mitochondrial dysfunction, reduced fatty acid oxidation , and increased expression of pro-inflammatory cytokines.
In humans, short-term supplementation with resveratrol has been associated with beneficial effects on glucose and lipid metabolism in individuals with type 2 diabetes.
Comparison of changes between baseline and end-of-study measures between placebo and intervention groups showed that resveratrol significantly lowered both fasting glucose and fasting insulin concentrations and improved measures of glycemic control HbA1c level and insulin sensitivity HOMA-IR.
In addition, the level of HDL -cholesterol was increased while the level of LDL -cholesterol and systolic blood pressure were significantly reduced. No changes were found in measures of diastolic blood pressure , total cholesterol , triglycerides , and markers of liver function During the three-month study period, changes in biochemical and clinical parameters, including fasting glucose concentration, HbA1c level, systolic and diastolic blood pressure, total cholesterol, and LDL-cholesterol, were significantly improved with resveratrol compared to control i.
A few clinical studies have evaluated the effects of resveratrol on key metabolic variables in overweight or obese subjects with no overt metabolic dysfunction and found little or no metabolic benefits following resveratrol treatment Yet, at present, there is no available evidence to suggest whether overweight or obese individuals with impaired glucose tolerance could benefit from resveratrol supplements and reduce their risk of developing type 2 diabetes Current data suggest that resveratrol could improve specific metabolic variables in individuals with type 2 diabetes , , but more research is needed to assess its effect in individuals at risk for diabetes, including obese subjects with impaired glucose tolerance.
Resveratrol is found in grapes, wine, grape juice, peanuts, cocoa, and berries of Vaccinium species, including blueberries, bilberries, and cranberries In grapes, resveratrol is found only in the skins The amount of resveratrol in grape skins varies with the grape cultivar, its geographic origin, and exposure to fungal infection The amount of fermentation time a wine spends in contact with grape skins is also an important determinant of its resveratrol content.
Because grape skins are removed early during the production process of white and rosé wines, these wines generally contain less resveratrol than red wines 4. Therefore, because of variations between types of wine, vintages, and regions, it is very difficult to provide accurate estimates of resveratrol content in the thousands of wines from worldwide wineries.
Yet, it appears that resveratrol content in wine is usually low, highly variable and unpredictable, and resveratrol is only a minor compound in the complete set of grape and wine polyphenols The predominant form of resveratrol in grapes and grape juice is trans -resveratrolO-β-glucoside trans -piceid , and wines contain significant amounts of resveratrol aglycones, thought to be the result of sugar cleavage during fermentation 3 , Many wines also contain significant amounts of cis -resveratrol see Figure 1 above , which may be produced during fermentation or released from viniferins resveratrol polymers Red wine is a relatively rich source of resveratrol, but other polyphenols are present in red wine at considerably higher concentrations than resveratrol see the article on Flavonoids Estimates of resveratrol content of some beverages and foods are listed in Table 1 and Table 2.
These values should be considered approximate since the resveratrol content of foods and beverages can vary considerably. Most resveratrol supplements available in the US contain extracts of the root of Polygonum cuspidatum , also known as Fallopia japonica , Japanese knotweed, or Hu Zhang Red wine extracts and grape extracts from Vitis vinifera containing resveratrol and other polyphenols are also available as dietary supplements.
Resveratrol supplements may contain anywhere from less than 1 milligram mg to mg of resveratrol per tablet or capsule, but it is not known whether there is a safe and effective dosage for chronic disease prevention in humans also see the section on Safety.
Resveratrol is not known to be toxic or cause significant adverse effects in humans, but there have been only a few controlled clinical trials to date reviewed in A trial evaluating the safety of oral trans -resveratrol in 10 subjects found that a single dose of 5, mg resulted in no serious adverse effects Mild diarrhea was also reported in six out of eight individuals who consumed 2, mg of resveratrol twice daily for two periods of eight days in an open-label and within subject-control study The safety of resveratrol-containing supplements during pregnancy and lactation has not been established Because there is no known safe amount of alcohol consumption at any stage of pregnancy , pregnant women should avoid consuming wine as a source of resveratrol.
Until more is known about the estrogenic activity of resveratrol in humans, women with a history of estrogen-sensitive cancers , such as breast, ovarian, and uterine cancers, should avoid resveratrol supplements see Estrogenic and anti-estrogenic activities Resveratrol has been found to inhibit human platelet aggregation in vitro 53 , Theoretically, high intakes of resveratrol i.
Cytochrome P CYP enzymes are phase I biotransformation enzymes involved in the metabolism of a broad range of compounds, from endogenous molecules to therapeutic agents.
The most abundant CYP isoform in the human liver and intestines is cytochrome P 3A4 CYP3A4 , which catalyzes the metabolism of about half of all marketed drugs in the US Resveratrol has been reported to inhibit CYP3A4 activity in vitro , and in healthy volunteers Therefore, high intakes of resveratrol i.
Some of the many drugs metabolized by CYP3A4 include HMG-CoA reductase inhibitors statins , calcium channel antagonists felodipine, nicardipine, nifedipine, nisoldipine, nitrendipine, nimodipine, and verapamil , anti-arrhythmic agents amiodarone , HIV protease inhibitors saquinavir , immunosuppressants cyclosporine and tacrolimus , antihistamines terfenadine , benzodiazepines midazolam and triazolam , and drugs used to treat erectile dysfunction sildenafil.
Of note, a recently completed clinical trial NCT examined the potential for single and multiple doses of resveratrol 1, mg to interfere with the metabolism of midazolam in healthy volunteers, and results are soon to be published Other CYP enzymes e.
Finally, resveratrol was found to be a weak inducer of the expression and activity of CYP1A2, which catalyzes the metabolism of several drugs, including acetaminophen paracetamol and the antidepressant drugs, clomipramine and imipramine 28 , This suggests that resveratrol may interfere with CYP1A2-mediated drug metabolism by increasing drug clearance, possibly lowering circulating drug concentrations below therapeutic levels.
Originally written in by: Jane Higdon, Ph. Linus Pauling Institute Oregon State University. Updated in May by: Victoria J. Drake, Ph. Updated in May by: Barbara Delage, Ph. Reviewed in May by: Juan Carlos Espín, Ph. Soleas GJ, Diamandis EP, Goldberg DM.
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Corrigendum: Efficacy of resveratrol metabolisn on glucose and ans metabolism: Ressveratrol meta-analysis Resvrratrol Cooling and replenishing drinks review. Background: Lipids Resveratrol and metabolism ubiquitous Cooling and replenishing drinks with Pregnancy detox diets functions. Excessive lipid accumulation can trigger lipid redistribution among metabolic organs such as adipose, liver and muscle, thus altering the lipid metabolism. It has been revealed that disturbed lipid metabolism would cause multiple disease complications and is highly correlated with human morbidity. Resveratrol RSVa phytoestrogen with antioxidant, can modulate insulin resistance and lipid profile. Znd summarized 16 controlled Cooling and replenishing drinks and Resveragrol the correlation of metabo,ism supplementation with metabolic parameters such as the body weight, waist Reaveratrol WCsystolic Resveratrol and metabolism pressure sbp mehabolism, HDL, total cholesterol, triglyceride Resveratrol and metabolism glucose levels. This meta-analysis Resveeratrol carried Micronutrient deficiency to determine the association between the resveratrol intake with metabolic parameters in metabolic syndrome patients. PubMed, Scopus, Cochrane and Google Scholar were searched from inception to December using relevant keywords. All articles were independently reviewed by two authors using predetermined selection criteria. We have selected the studies that investigated the effects of resveratrol on metabolic parameters. Of 16 studies, 10 were performed on human subjects, and in 6 studies animal models were used. However, resveratrol was not significantly effective on total cholesterol in both samples.
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