Abstract
Liver lipid accumulation is a hallmark of non-alcoholic fatty liver disease (NAFLD), broadly associated with insulin resistance. Inositols (INS) are ubiquitous polyols implied in many physiological functions. They are produced endogenously, are present in many foods and in dietary supplements. Alterations in INS metabolism seems to play a role in diseases involving insulin resistance such as diabetes and polycystic ovary syndrome. Given its role in other metabolic syndromes, the hypothesis of an INS role as a supplement in NAFLD is intriguing. We performed a systematic review of the literature to find preclinical and clinical evidence of INS supplementation efficacy in NAFLD patients. We retrieved 10 studies on animal models assessing Myoinosiol or Pinitol deficiency or supplementation and one human randomized controlled trial (RCT). Overall, INS deficiency was associated with increased fatty liver in animals. Conversely, INS supplementation in animal models of fatty liver reduced hepatic triglycerides and cholesterol accumulation and maintained a normal ultrastructural liver histopathology. In the one included RCT, Pinitol supplementation obtained similar results. Pinitol significantly reduced liver fat, post-prandial triglycerides, AST levels, lipid peroxidation increasing glutathione peroxidase activity. These results, despite being limited, indicate the need for further evaluation of INS in NAFLD in larger clinical trials.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is the most important emerging liver disease, and its rising incidence in different countries seems to partly explain the new chronic liver disease pandemic.In Italy, the incidence of non-alcoholic fatty liver disease (NAFLD) is 18.5 per 1000 person/years, and due to the high number of risk factors in these patients, its prevalence can increase up to 70% in subgroups of patients affected by type 2 diabetes mellitus [1].Non-alcoholic fatty liver disease burden does weigh on the liver, but is burdened by a series of cardiovascular, neurological, and kidney complications, making the treatment of this disease crucial for the improvement of both survival and quality of life in these patients
A total of 11 studies were included in our systematic review
One of the mechanisms proposed for the underlying positive effects of INS supplements is based on the hypothesis that the increased availability of INS could intensify the insulin pathway through an enhanced signaling mediated by INS phosphoglycans (IPGs) [14,58]
Summary
Non-alcoholic fatty liver disease (NAFLD) is the most important emerging liver disease, and its rising incidence in different countries seems to partly explain the new chronic liver disease pandemic. Non-alcoholic fatty liver disease burden does weigh on the liver, but is burdened by a series of cardiovascular, neurological, and kidney complications, making the treatment of this disease crucial for the improvement of both survival and quality of life in these patients. Non-alcoholic fatty liver disease patients have an increased risk of developing non-alcoholic steatohepatitis (NASH), and liver fibrosis, liver cirrhosis, and hepatocellular carcinoma (HCC), albeit NAFLD, itself, being the third most common cause of liver transplantation [2]. Chronic kidney disease shows an association with NAFLD, and a more rapid decline of the glomerular filtration rate was present in NAFLD patients [5]
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