Year: 2009
Type: article
Abstract: Sirs, Loomba et al.1 report that metformin leads to improvements in liver histology and serum alanine transaminase levels in a subset of patients with non-alcoholic steatohepatitis (NASH) probably by its effects in causing weight loss. We suggest that part of the metformin action might be related to the higher body iron stores often found in such patients. Mounting evidence highlights that moderate elevations in body iron stores, much lower than those seen in hereditary haemochromatosis, are associated with insulin resistance.2 In particular, hyperferritinaemia and increased iron stores have been frequently observed in patients with the metabolic syndrome3 and NASH.4, 5 It has been hypothesized that excessive hepatic iron accumulation in NASH is one of the potential cofactors involved in the enhanced oxidative stress, which triggers liver cell necrosis and activation of hepatic stellate cells, both leading to fibrosis.4 Iron depletion by phlebotomy was found to be beneficial in improving insulin resistance in patients with non-alcoholic fatty liver disease and hyperferritinaemia6 and reducing transaminase activities in NASH.7 Furthermore, in women with polycystic ovary syndrome, it has been shown that metformin, increasing insulin sensitivity, may decrease intestinal iron absorption.8 Increased iron stores may contribute to insulin resistance by reducing hepatic insulin extraction and metabolism9 and by decreasing glucose uptake in muscle.10 On the other hand, insulin can stimulate intestinal iron absorption.8 Therefore, it is possible that metformin induces a decrease in iron absorption, thus breaking the vicious cycle of insulin resistance, increased intestinal iron absorption and further worsening of insulin sensitivity. This would lead to improvements in liver histology and serum alanine transaminase levels in patients with NASH, especially in the subset with elevated body iron stores. Declaration of personal interests: None.
Authors: L. Mascitelli, F. Pezzetta, M. R. Goldstein
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2055129724