Table 1.
Study | Group * | NAFLD Diagnosis | Substance | Duration | Results ** | Possible Mechanism |
---|---|---|---|---|---|---|
Loguercio et al. [29] (2012) | 138 patients with NAFLD (69 in treatment group) | Histology–liver biopsy | Realsil (94 mg of silybin and 194 mg of phosphatidylcholine) + 89.28 mg vitamin E acetate 50% (30 mg of α-tocopherol) | 12 months | Normalization of ALT and AST ↓: GGT, HOMA-IR, improvement in liver histology |
Antioxidant activity which may lead to decline in membrane lipid peroxidation and restoration of glutathione levels |
Wang et al. [31] (2022) | 260 patients with NAFLD (130 in the DSSG group) | B-ultrasound | DSSG in 12 g package, 2 packages/time, 3 times per day | 16 weeks | ↓: TC, TG, ALT, AST, GGT, FPG Improvement in B-USG |
Inhibition of lipid peroxidation; decline in NF-κB expression in liver |
Chen et al. [37] (2015) | 60 patients with NAFLD (30 in treatment group) | B-ultrasound | Dihydromyricetin in dose 150 mg twice a day | 3 months | ↑: Adiponectin ↓: ALT, AST, GGT, LDL-C, apo-B, HOMA-IR, TNF- α, CK-18, FGF-21 |
Prevention of hepatocyte apoptosis; regulation of antioxidant properties; decline in proinflammatory cytokine levels |
Zhang et al. [40] (2015) | 74 patients with NAFLD (1:1 with placebo) | USG | Anthocyanin in dose 80 mg in capsule, two capsules twice a day | 12 weeks | ↓: ALT, CK-18, myeloperoxidase, 2 h OGTT, plasma glucose and HOMA-IR | Antioxidant and anti-inflammatory properties; improvement in IR |
Medina-Urrutia et al. [43] (2020) | 25 patients with NAFLD | CT imaging | Milled chia seeds 25 g per day | 2 weeks of dietary stabilization and 8 weeks of chia supplementation | ↑: L: SAR, ALA plasma concertation, dietary fiber consumption ↓: VAF, BW, BMI, WC, TC, non-HDL, FFA |
Fiber may lead to improvements in intestinal barrier which may further promote intestinal transit slowdown, production of GLP-1, and favor the sensation of satiety |
Zamani et al. [48] (2018) | 85 patients with NAFLD (45 in treatment group) | USG | Zataria multiflora powder 700 mg twice a day | 12 weeks | ↓: Serum insulin, IR, SBP, DBP | IR, and serum TG levels improvements through increase in PPAR-γ expression; increase in adiponectin leads to gluconeogenesis decline |
Khonche et al. [58] (2019) | 120 patients (60 patients in treatment group) | USG | 2.5 mL standardized Nigella sativa seed oil every 12 h | 3 months | ↑: HDL-C ↓: Grade of hepatic steatosis, ALT, AST, TG, LDL-C |
PPAR-γ upregulation; anti-inflammatory, antifibrotic and antioxidant properties |
Musazadeh et al. [64] (2021) | 43 patients with NAFLD (22 in CSO group) | USG | Camelina sativa oil in dose 20 g per day + calorie restricted diet | 12 weeks | ↑: HDL-C ↓: hs-CRP, insulin, HOMA-IR, QUICKI, LPS, TAC, SOD, GSH-Px, MDA, 8-iso-PGF2α |
Omega-3 fatty acids in CSO may lead to induction of GLP-1; CSO leads to decrease in energy intake, and inflammation |
Arefhosseini et al. [69] (2022) | 40 overweight/obese females with NAFLD (21 in HCA group) | USG | Garcinia cambogia extract (HCA) in connection with calorie restriction diet | 8 weeks | ↑: HDL-C ↓: BW, WC, HC, FPG, LDL-C, TG, TG/HDL-c ratio |
Improvement in lipid profile due to suppression of ATP-citrate lyase and appetite; enhancement of glycogen deposition in the liver; anti-obesity properties due to regulation of serotonin levels, reduction in de novo lipogenesis, reduction in leptin, and insulin levels in plasma |
Ebrahimi-Mameghani [71] et al. (2014) | 55 NAFLD patients (29 in intervention group) | USG | Chlorella vulgaris 300 mg in tables per day + vitamin E 400 mg per day | 8 weeks | ↓: BW, liver enzymes, FPG, ALP, TG, TC, LDL-C | Possible effect related to BW reduction; improvements in glucose metabolism by boost of glucose uptake |
Cossiga et al. [76] (2019) | 49 NAFLD patients (26 in plant extracts supplementation group) | Transient elastography | Berberis aristata (588 mg), Elaeis guineensis (143 mg) and decaffeinated green coffee by Coffea canephora (67 mg) extracts in dose 1 table per day | 6 months | ↓: serum glucose, insulin, HOMA-IR, CAP | Modulation of serum insulin receptor levels by activation of protein kinase C; insulin sensitizing effect through the activation of AMPK |
Sakata et al. [81] (2013) | 17 patients with NAFLD (12 in green tea supplementation group) | USG and CT | Green tea in dose 700 mL per day, containing above 1 g catechin | 12 weeks | ↑: L: SAR ↓: BF, ALT, urinary 8-isoprostane excretion |
Decline in hepatic oxidation stress; inhibition of lipase which leads to decrease in glucose and fat absorption; improvements in liver lipid metabolism by increase in mRNA expression of peroxisomal, and mitochondrial β-oxidizing enzymes |
Amanat et al. [86] (2018) | 78 patients with NAFLD (41 in genistein group) | USG | Genistein in dose 250 mg per day | 8 weeks | ↓: Serum insulin, HOMA-IR, MDA, TNF-α, IL-6, WHR, BF, TG | Increase in glucose uptake by promotion of glucose transporter type 4 translocation to a membrane; activation of AMPK; upregulation of genes related to antioxidant properties by NF-κB and Nrf2 transcription factors |
Atefi et al. [90] (2022) | 53 females with NAFLD (27 in sesame oil group) | USG | Sesame oil supplementation in dose 30 mg per day + low-calorie diet | 12 weeks | ↓: BW, BMI, WC, fatty liver grade, AST, ALT | Inhibiting matrix metalloproteinases-2, 9 activities and upregulating PPAR-γ expression; antioxidant properties; reduction in lipogenic enzymes mRNA expression, and induction of mRNA expression of enzymes related to fatty acid oxidation, e.g., CoA dehydrogenases, acyl-CoA oxidase, or 3-hydroxyacyl CoA dehydrogenase |
Rezaei et al. [94] (2019) | 54 patients with NAFLD (26 in olive oil group) | USG | Olive oil in dose 20 g per day + recommendation of hypocaloric diet | 12 weeks | ↓: Fatty liver grade in USG, BW, WC, BP, AST, TG, fat mass | Antioxidant properties; action of omega-3 fatty acids; increase in post-prandial β-oxidation of fatty acids; improvements in IR |
Schweinlin et al. [101] (2018) | 36 patients with NAFLD (17 in oat enriched diet group) | FLI | Restricted diet + oat intake | 12 weeks | ↓: BMI, hepatorenal index, BP | Improvements in gut microbiota, which may be related to fiber intake |
Lee et al. [105] (2019) | 76 patients with NAFLD (27 in pinitol high dose group) | USG | Pinitol in dose 500 mg per day | 12 weeks | ↑: GSH-Px ↓: Liver fat amount, MDA, AST, ALT, GGT, postprandial TG |
Increase in liver antioxidant enzyme activities, e.g., GSH; decline in the rate of glutathione turnover |
Kazemi et al. [107] (2020) | 80 patients with NAFLD (1:1 with placebo) | Hepatic fibrosis grade based on FibroScan device and ALT level | Sumac powder in dose 2 g per day + calorie deficit diet | 12 weeks | ↑: QUICKI ↓: liver fibrosis score, ALT, AST, hs-CRP, MDA, FPG, HbA1c, HOMA-IR, serum insulin |
Inhibition of α-glucosidase and pancreatic α-amylase; suppression of lipogenic factor genes; stimulation of AMPK and lipolysis; increase in PPAR-γ gene expression |
Yan et al. [110] (2015) | 155 patients with NAFLD (55 in berberine group) | Proton magnetic resonance spectroscopy | Berberine in dose 500 mg 3 times per day + lifestyle intervention | 16 weeks | ↓: HFC, BW, WC, HOMA-IR, TC, TG, ALT | Mechanism is still unclear, but may be linked to expression of genes related to glucose and lipid metabolism such as CPT-1, GCK, or MTTP |
Amerikanou et al. [114] (2021) | 98 patients with NAFLD (41 in mastiha group) | LiverMultiScan technique | Mastiha in dose 350 mg three times per day | 6 months | Positive effects on intestinal microbiota, improvement in lipid metabolite levels Additionally, in severely obese subjects, ↓ liver fibrosis score, liver inflammation |
Reduction in expression of genes related to collagen (Col1a1 and Col4a1); decline in inflammatory and endotoxin-producing bacteria; increase in anti-inflammatory bacteria |
Abbreviations: 8-iso-PGF2α–8-iso-prostaglandin F2α, ALA—alpha linolenic acid, ALP—alkaline phosphatase, ALT—alanine aminotransferase, AMPK—5′-adenosine monophosphate-activated protein kinase, apo-B—apolipoprotein B, AST—aspartate aminotransferase, BF—body fat, BMI—body mass index, BP—blood pressure, BW—bodyweight, CAP—controlled attenuation parameter, CK-18—cytokeratin-18, CT—computed tomography, DBP—diastolic blood pressure, DSSG—Danshao Shugan Granules, FFA—free fatty acids, FGF21—fibroblast growth factor 21, FPG—fasting plasma glucose, GGT—γ-glutamyltranspeptidase, GLP-1—glucagon-like peptide-1, GSH-Px—glutathione peroxidase, HbA1c—glycated hemoglobin, HC—hip circumference, HCA—hydroxycitric acid, HDL-C—high density lipoprotein cholesterol, HFC—hepatic fat content, HOMA-IR—homeostasis model assessment of insulin resistance, hs-CRP—high sensitive C-reactive protein, IL-6—interleukin 6, LDL-C—low density lipoprotein cholesterol, L:SAR—liver to spleen attenuation ratio, IR—insulin resistance, LPS—lipopolysaccharide, MDA—malondialdehyde, NAFLD—non-alcoholic fatty liver disease, Nrf2—Nuclear factor erythroid 2-related factor 2, OGTT—oral glucose tolerance test, PPARγ—peroxisome proliferator activated receptor protein, QUICKI—quantitative insulin sensitivity check index, SBP—systolic blood pressure, SOD—Superoxide dismutase, TAC—total antioxidant capacity, TC—total cholesterol, TG—triglycerides, TNF-α—tumor necrosis factor alpha, USG—ultrasonography, VAF—visceral abdominal fat, WC—waist circumference, WHR—waist to hip ratio. * In the group column, the number of respondents analyzed was given, not the people who were included in the study and for various reasons were excluded from it during procedures. ** Changes shown in results column are significant.