Lifestyle and silymarin: a fight against liver damage in NAFLD associated - prediabetic disease

Abstract

Background Nonalcoholic fatty liver disease (NAFLD) is common in both prediabetic patients and healthy overweight individuals, yet it remains understudied. This study investigates the effects of hepatic steatosis on fibrosis and evaluates the major predictors of liver injury in prediabetes and whether this damage is reversible with Mediterranean diet and administration of the nutraceutical silymarin. Methods First, a case-control study was conducted in which 212 patients with prediabetes, not known to have NAFLD, and 126 healthy controls underwent clinical evaluation, transient elastography with measurement of liver stiffness (LS) and controlled attenuation parameter (CAP). Subsequently, the 212 prediabetic patients were enrolled into a prospective randomized interventional study: 104 were allocated to Mediterranean diet alone while 108 followed Mediterranean diet plus supplementation with silymarin (a flavonolignan complex isolated from Silybum marianum and Morus alba). The administered silymarin dose was 210 mg twice daily for 6 months. Clinical and instrumental evaluations were repeated at the end of the 6 month-study period. Prediabetics were genotyped for patatin like phospholipase domain containing 3 (PNPLA3). Results In the case-control study, 29% of prediabetic patients have significant fibrosis defined as LS ≥ 7.9 kPa vs only 3% of controls (p < 0.001). PNPLA3 genotype CG/GG are significantly associated with significant fibrosis LS ≥ 7.9 relative to CC genotype χ2(1) = 76.466, p < 0.001. Binomial regression analysis shows that increase in BMI, ALT and AST are significantly associated with increased likelihood of significant fibrosis (χ2(7) = 191.9, p < .001) prior to intervention. In the randomized interventional study, prediabetics following Mediterranean diet alone (group 1) experienced a significant regression of fibrosis and decrease in ALT, HbA1c, FBS after 6 months (p < 0.001); similar findings were observed in patients following Mediterranean diet plus silymarin regimen (group 2); group 2 had a significant decrease in HbA1c relative to group 1 (95% CI: 37.8–38.6 vs 39.5–40.3, p < 0.001). Conclusion PNPLA3 genotype CG/GG and elevated BMI are the major predictors of significant fibrosis in prediabetic patients prior to intervention in this study. Mediterranean diet either alone or with silymarin treatment for 6 months leads to significant regression of liver damage and improvement of the glycemic profile in prediabetic patients. Yet, as combination treatment of silymarin with Mediterranean diet shows significant reduction of HbA1c when compared to diet alone, this suggests that silymarin may exert an independent anti-glycemic action.

The effect of phytochemicals in prediabetic patients: A systematic review of randomized controlled trials

“…In their study, Colletta et al assessed the effect of silymarin on prediabetic patients. The findings of this study only showed the positive impact of silymarin on HbA1c (Colletta et al, 2020). However, it was the only study arm that examined silymarin in our review.…”

“…The main finding of this review is that from 31 arms, 21 arms had positive effects on at least one glycemic indices or one of the other cardiometabolic factors (Cicero et al, 2020; Colletta et al, 2020; Derosa, D'angelo, et al, 2020; Derosa, Maffioli, et al, 2020; Karandish et al, 2021; Karandish et al, 2022; Ming et al, 2021; Ribeiro et al, 2019; Thota et al, 2019; Thota et al, 2020; Wang et al, 2020; Yang et al, 2017; Yang, Liu, et al, 2020; Yari et al, 2021; Zhang et al, 2018). However, 10 arms had no effective results on any of the measured factors (Funamoto et al, 2019; Moreno‐Ulloa et al, 2018; Pollack et al, 2017; Shanobin et al, 2007; Yang et al, 2021; Yang, Ling, et al, 2020; Ye et al, 2021, 2015).…”

“…Out of 23 included studies, 15 articles were categorized as highquality studies (Cicero et al, 2020;Funamoto et al, 2019;Karandish et al, 2021;Karandish et al, 2022;Ming et al, 2021;Ribeiro et al, 2019;Thota et al, 2019;Wang et al, 2020;Yang et al, 2017Yang et al, , 2021Yari et al, 2021;Ye et al, 2015Ye et al, , 2021, three studies had fair quality Thota et al, 2020;, and three studies were categorized as low quality (Colletta et al, 2020;Moreno-Ulloa et al, 2018;Pollack et al, 2017).…”

A Molecular Insight into the Role of Antioxidants in Nonalcoholic Fatty Liver Diseases

“…Silymarin has the potential to regress NAFLD in patients under the Mediterranean diet than in the Mediterranean diet alone group. For instance, along with the Mediterranean diet, twice-daily administration of silymarin (210 mg) for 6 months has led to significant improvement in the glycemic profile and regression of liver damage (Colletta et al, [ 111 ]). Silymarin, vitamin C, vitamin E, and coenzyme Q10 and selenomethionine (Medronys epato®) contain a capsule twice a day for 45- and 90-days treatments that has histologically improved liver function and reduced the marker enzymes of liver toxicity (ALT, AST, ALP, and GGT) and lipid markers (total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and TG) in serum of NAFLD patients (Curcio et al, [ 112 ]).…”

Ionic liquid-based dispersive liquid-liquid followed high-performance liquid chromatography for the determination of Silychristin, Silydianin, Silybin, Silybin B, Isosilybin A, Isosilybin B in silbbum marianum seed

“…It is commonly used in the treatment of simple or alcoholic fatty liver acute and chronic hepatitis, and other diseases with abnormal liver function (11)(12)(13). However, the standard methods for the determination of SCN, SDN, SBA, SBB, ISBA, and ISBB in SMS have not been established in China.…”