Effects of Mediterranean diet supplemented with silybin–vitamin E–phospholipid complex in overweight patients with non-alcoholic fatty liver disease

Abenavoli, Ludovico; Greco, Marta; Nazionale, Immacolata; Peta, Valentina; Milić, Nataša; Accattato, Francesca; Foti, Daniela; Gulletta, Elio; Luzza, Francesco

doi:10.1586/17474124.2015.1004312

Cited by 75 publications

(50 citation statements)

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“…Four studies[8,39,40,45] reported blinding, describing methodological design as double-blind. Twelve studies[8,26-28,38-45] used only dry extract of Silybum marianum, which contains silymarin or silymarin alone, two[34,35] used silymarin associated with vitamin E and three[19,36,37] studies used silybin with vitamin E and phosphatidylcholine. All articles evaluated ALT, however the study by Velussi et al[26] only evaluated liver enzymes in the baseline, four[16,43-45] did not evaluate AST and eight[27-29,36,39,42-44] did not evaluate γGT.…”

Section: Resultsmentioning

confidence: 99%

“…Twelve studies[8,26-28,38-45] used only dry extract of Silybum marianum, which contains silymarin or silymarin alone, two[34,35] used silymarin associated with vitamin E and three[19,36,37] studies used silybin with vitamin E and phosphatidylcholine. All articles evaluated ALT, however the study by Velussi et al[26] only evaluated liver enzymes in the baseline, four[16,43-45] did not evaluate AST and eight[27-29,36,39,42-44] did not evaluate γGT. Six studies[26-28,36,37,39] did not report data on adverse effects, six[8,19,34,35,41,45] did not identify any of these effects, four[40-43] performed specific evaluation and only one[39] described that serious adverse events were not observed and that side effects were similar in frequency and uncommon in both groups.…”

Section: Resultsmentioning

confidence: 99%

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Effect of silymarin on biochemical indicators in patients with liver disease: Systematic review with meta-analysis

Avelar

Pereira

Costa

et al. 2017

WJG

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AIMTo evaluate the effect of silymarin on the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transpeptidase (γGT) in patients with liver diseases.METHODSA systematic review with meta-analysis of ramdomized and controlled clinical trials was performed, evaluating the effects of sylimarin in patients with hepatic diseases, published by January 31, 2016. Clinical trials were sought on the basis of The Cochrane Central Register of Controlled Trials in the Cochrane Library, PubMed/Medline, Scopus, Web of Science, Lilacs and Clinical Trials. The trials with adult and elderly patients of both sexes, with Liver Diseases who took oral silymarin supplementation, as extract or isolated, as well as Silymarin combined with other nutrients, were included. The trials should provide information about the intervention, such as dosages and detailing of the product used, besides the mean and standard deviation of serum levels of ALT, AST and γGT of the baseline and at the end of the intervention.RESULTSAn amount of 10904 publications were identified. From those, only 17 were included in the systematic review and 6 in the meta-analysis, according to the used selection criteria. In this meta-analysis, the results indicated a reduction of 0.26 IU/mL (95%CI: -0.46-0.07, P = 0.007) at the level of ALT and 0.53 IU/mL (95%CI: -0.74-0.32, P = 0.000) at the serum levels of AST after using the silymarin, both, statistically significant, but with no clinical relevance. There was no significant change in the γGT levels. Subgroup analyzes were also performed for the biochemical markers in relation to the type of intervention, whether silymarin isolated or associated with other nutrients and the time of intervention (whether ≥ 6 mo or < 6 mo). Significant differences were not found. The evaluated studies presented a high degree of heterogeneity and low methodological quality in the carried out analysis.CONCLUSIONSilymarin minimally reduced, but without clinical relevance, the serum levels of ALT and AST. It is necessary to carry out studies with more appropriate methodological designs.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Effect of silymarin on biochemical indicators in patients with liver disease: Systematic review with meta-analysis

Avelar

Pereira

Costa

et al. 2017

WJG

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“…Furthermore, silibinin has been shown to ameliorate insulin resistance in HepG2 cells partially through targeting IRS‐1/PI3K/Akt pathway . From a clinical point of view, two small randomized clinical trials reported that supplementation of silibinin combined with phosphatidylcholine and vitamin E in patients with NAFLD may improve insulin resistance and liver histology as well as liver enzymes and lipid profile . Consistently, a silymarin‐vitamin E complex has been recently shown to reduce liver steatosis in a small uncontrolled clinical trial .…”

Section: Silymarin/silibininmentioning

confidence: 90%

Natural antioxidants for non‐alcoholic fatty liver disease: molecular targets and clinical perspectives

Salomone¹,

Godos

Zelber‐Sagi

2015

Liver International

211

140

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Non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease (NAFLD), is emerging as a main health problem in industrialized countries. Lifestyle modifications are effective in the treatment of NAFLD; however, the long-term compliance is low. Therefore, several pharmacological treatments have been proposed but none has shown significant efficacy or long-term safety. Natural polyphenols are a heterogeneous class of polyphenolic compounds contained in vegetables, which are being proposed for the treatment of different metabolic disorders. Although the beneficial effect of these compounds has traditionally related to their antioxidant properties, they also exert several beneficial effects on hepatic and extra-hepatic glucose and lipid homeostasis. Furthermore, natural polyphenols exert antifibrogenic and antitumoural effects in animal models, which appear relevant from a clinical point of view because of the association of NASH with cirrhosis and hepatocellular carcinoma. Several polyphenols, such anthocyanins, curcumin and resveratrol and those present in coffee, tea, soy are available in the diet and their consumption can be proposed as part of a healthy diet for the treatment of NAFLD. Other phenolic compounds, such as silymarin, are commonly consumed worldwide as nutraceuticals or food supplements. Natural antioxidants are reported to have beneficial effects in preclinical models of NAFLD and in pilot clinical trials, and thus need clinical evaluation. In this review, we summarize the existing evidence regarding the potential role of natural antioxidants in the treatment of NAFLD and examine possible future clinical applications.Keywords fibrosis -NASH -nutraceuticals -oxidative stress -polyphenols Abbreviations ACC, acetyl coenzyme A carboxylase; ACN, anthocyanins; AKT, serine-threonine protein kinase; AMPK, adenosine monophosphate-activated protein kinase; CD36, cluster of differentiation 36; CHREBP, carbohydrate-responsive element-binding protein; COX-2, cyclooxygenase 2; CYP2E1, cytochrome P450 2E1; CYP4A1, cytochrome P450 4A1; DJ-1, protein deglycase-1; EC-SOD, extracellular superoxide dismutase; EGCG, epigallocatechin gallate; ERK, extracellular receptor kinase; FA, fatty acid; FAS, fatty acid synthase; FFA, free fatty acid; GGT, gamma glutamyl transferase; GRP-78, 78 kDa glucose-regulated protein; GSH, glutathione; HDL, high density lipoprotein; HFD, high fat diet; HMG-CoA, 3-Hydroxy-3-Methyl-Glutaryl-CoA; HSC, hepatic stellate cell; ICAM-1, intercellular cell adhesion molecule type 1; IRS-1, insulin receptor substrate-1; JNK, Jun Nterminal kinase; LDL, low density lipoprotein; MCP-1, monocyte chemoattractant protein-1; NAD, nicotinamide adenine dinucleotide; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; NFkB, nuclear factor kappa B; NRF2, nuclear respiratory factor 2; PDGF-BB, platelet-derived growth factor-BB; PGC-1a, proliferator-activated receptor-gamma coactivator-1alpha; PI3K, phosphoinositide 3-kinase; PPAR-a, peroxisome pro...

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“…However, this improvement was not accompanied by ALT reduction . Similarly, in a non‐randomized controlled trial among 20 NAFLD patients, MD improved the fatty liver index (FLI), but not liver enzymes . Conversely, in a quasi‐randomized trial, which evaluated the influence of different diets on liver enzymes, 259 obese diabetic patients have been assigned to either a diet recommended by the American Diabetes Association (50‐55% carbohydrate of mixed glycaemic index, 30% fat and 15‐20% protein), a low glycemic index (LGI) diet (50‐55% LGI carbohydrate, 30% fat, 15‐20% protein), or a modified (so that all foods will have low glycemic index) MD (35% LGI carbohydrate, 45% fats high in MUFA content, 20% protein), and found that despite the similar caloric content, the most significant reduction in ALT levels occurred in the modified MD arm at 6 and 12 months of follow‐up, even after adjustment for weight loss …”

Section: The Association Between the MD Pattern As A Whole And Nafldmentioning

confidence: 99%

The Mediterranean dietary pattern as the diet of choice for non‐alcoholic fatty liver disease: Evidence and plausible mechanisms

Zelber‐Sagi

Salomone²,

Mlynarsky

2017

Liver International

203

162

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Non-alcoholic fatty liver disease (NAFLD) has become a major global health burden, leading to increased risk for cirrhosis, hepatocellular carcinoma, type-2 diabetes and cardiovascular disease. Lifestyle intervention aiming at weight reduction is the most established treatment. However, changing the dietary composition even without weight loss can also reduce steatosis and improve metabolic alterations as insulin resistance and lipid profile. The Mediterranean diet (MD) pattern has been proposed as appropriate for this goal, and was recommended as the diet of choice for the treatment of NAFLD by the EASL-EASD-EASO Clinical Practice Guidelines. The MD has an established superiority in long term weight reduction over low fat diet, but it improves metabolic status and steatosis even without it.However, the effect on liver inflammation and fibrosis was tested only in few observational studies with positive results. Furthermore, considering the strong association between NAFLD and diabetes and CVD, the MD has a highly established advantage in prevention of these diseases, demonstrated in randomized clinical trials. The individual components of the MD such as olive oil, fish, nuts, whole grains, fruits, and vegetables, have been shown to beneficially effect or negatively correlate with NAFLD, while consumption of components that characterize a Western dietary pattern as soft drinks, fructose, meat and saturated fatty acids have been shown to have detrimental association with NAFLD. In this review we will cover the epidemiological evidence and the plausible molecular mechanisms by which the MD as a whole and each of its components can be of benefit in NAFLD.

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Effects of Mediterranean diet supplemented with silybin–vitamin E–phospholipid complex in overweight patients with non-alcoholic fatty liver disease

Cited by 75 publications

References 44 publications

Effect of silymarin on biochemical indicators in patients with liver disease: Systematic review with meta-analysis

Effect of silymarin on biochemical indicators in patients with liver disease: Systematic review with meta-analysis

Natural antioxidants for non‐alcoholic fatty liver disease: molecular targets and clinical perspectives

The Mediterranean dietary pattern as the diet of choice for non‐alcoholic fatty liver disease: Evidence and plausible mechanisms

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