To the Editor:
Ryan and colleagues [
[1]
] found that a Mediterranean diet pattern reduced liver steatosis and improved insulin sensitivity in an insulin resistant population with non-alcoholic fatty liver disease (NAFLD), compared to current dietary advice. We suggest that lower body iron stores induced by components of the Mediterranean diet may be involved in this beneficial effect. In this setting, it has been proposed that the balance between the average bio-availability of dietary iron and the overall effects of inhibitors and enhancers of iron absorption may lead to lower iron stores in people consuming a Mediterranean dietary pattern [[2]
].In fact, it has been reported that elderly men from Crete, in the Mediterranean south of Europe had consistently lower levels of indicators of oxidative stress and iron status than elderly men from Zutphen in the north of Europe [
[3]
]. In particular, serum ferritin, a good marker of the iron stored in the body, were 2-fold lower in men from Crete than in men from Zutphen (69.8 μg/L and 134.2 μg/L, respectively).Mounting evidence suggests a link between serum ferritin, insulin resistance, and NAFLD [
[4]
]. Body iron excess has frequently been found in patients with metabolic syndrome [[5]
], with serum ferritin showing a linear increase with the increasing number of metabolic syndrome features [[5]
]. Moreover, it has been suggested that the relation between serum ferritin and most of metabolic syndrome features might be mediated by the presence of NAFLD at population-based level [[6]
]. Excessive hepatic iron accumulation in NAFLD can be 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 [[7]
].One of the largest studies evaluating iron and liver histology in NAFLD demonstrated that elevated serum ferritin identified NAFLD patients with more advanced disease [
[8]
]. Previous studies have shown a benefit of iron reduction therapy on NAFLD severity and insulin sensitivity [[9]
]. Furthermore, iron depletion by phlebotomy has been recently found to impact liver histology, which is considered the gold standard for evaluating the efficacy of liver disease treatment. A small phase II study of phlebotomy carried out to achieve near-iron depletion (serum ferritin ⩽50 μg/L) demonstrated statistically significant reductions in the NAFLD activity score (NAS), transaminases, serum ferritin, and hepatic iron concentration [[10]
]. Although not statistically significant, improvements in steatosis, lobular inflammation, hepatocyte ballooning, and fibrosis were all in the predicted direction. Of note, these beneficial effects were reached in patients with a relatively mild overall degree of iron overload and liver disease at baseline (mean NAS = 3.8).Therefore, lower body iron stores induced by dietary components of Mediterranean diet could be involved in the beneficial action of this dietary pattern. It is important in future studies to include assessment of the dietary intervention on iron status and also to investigate the particular effects of iron depletion.
Conflict of interest
The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
References
- The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease.J Hepatol. 2013; 59: 138-143
- Mediterranean diet, lower body iron stores and metabolic syndrome.Int J Clin Pract. 2011; 65: 1110
- Oxidative stress, and iron and antioxidant status in elderly men: differences between the Mediterranean south (Crete) and northern Europe (Zutphen).Eur J Cardiovasc Prev Rehabil. 2007; 14: 495-500
- Ferritin, metabolic syndrome and NAFLD: elective attractions and dangerous liaisons.J Hepatol. 2007; 46: 549-552
- Prevalence of body iron excess in the metabolic syndrome.Diabetes Care. 2005; 28: 2061-2063
- NAFLD and hyperinsulinemia are major determinants of serum ferritin levels.J Hepatol. 2007; 46: 700-707
- Increased hepatic iron concentration in non-alcoholic steatohepatitis is associated with increased fibrosis.Gastroenterology. 1998; 114: 311-318
- Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with non-alcoholic fatty liver disease.Hepatology. 2012; 55: 77-85
- Venesection for non-alcoholic fatty liver disease unresponsive to lifestyle counselling – a propensity score-adjusted observational study.QJM. 2011; 104: 141-149
- Phase II clinical trial of phlebotomy for non-alcoholic fatty liver disease.Aliment Pharmacol Ther. 2013; 37: 720-729
Article info
Publication history
Published online: May 28, 2013
Accepted:
March 27,
2013
Received:
March 17,
2013
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© 2013 European Association for the Study of the Liver. Published by Elsevier B.V.
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