Non-alcoholic fatty liver disease (NAFLD), a condition ranging from uncomplicated liver steatosis to steatohepatitis (NASH) and potentially to end-stage diseases such as cirrhosis or hepatocarcinoma [
1], is the most common cause of liver disease worldwide [
2,
3]. The prevalence of liver steatosis in Italy has been reported to be within the 35–40 % range in the general population [
4‐
6], with sharp increases in overweight and obese subjects (67 and 91 %, respectively [
7]). Whereas the concomitant presence of liver steatosis, obesity and insulin resistance is a common clinical finding, there is still ongoing research to elucidate the pathogenetic mechanisms involved [
8,
9]; for example, whether NAFLD is a cause or consequence of insulin resistance [
10]. However, accumulating evidence confirms not only a correlation between NAFLD and the metabolic syndrome [
8,
11,
12] but also the association of NAFLD with an increased cardiovascular risk [
13]. Intrahepatic oxidative stress is also known to be one of the critical factors that may determine progression of NAFLD to more severe conditions involving liver inflammation and fibrosis [
12]. Therefore, from the standpoint of the primary care physician, monitoring the presence of liver steatosis in subjects with signs of metabolic syndrome (particularly abdominal obesity, elevated triglycerides and abnormal fasting glycaemia) should be normal clinical practice, with the aim of taking preventive measures against the development of more severe stages of NAFLD. Since the usual biochemical parameters (alanine transaminase [ALT], aspartate transaminase [AST], γ-glutamyl transpeptidase [γGT]) may be within normal ranges in patients with uncomplicated steatosis, their use as a screening test would probably result in underestimation of the presence of NAFLD, whereas imaging techniques such as liver ultrasonography (USG) are a potentially more sensitive tool for diagnosis of liver steatosis [
3,
14]. According to recent guidelines [
3], the therapeutic approach to liver steatosis is mostly focused on lifestyle interventions, including weight reduction, dietary modification and aerobic physical exercise [
3]. A weight loss of at least 7 % has been shown to improve steatosis and also to reduce parameters of necroinflammation [
15]. However, actual long-term compliance of subjects with NAFLD to lifestyle intervention protocols is usually reported to be unsatisfactory. Reinforcing the ‘motivation to change’ in these subjects seems to be a critical factor, and strategies of targeted behavioural counselling, to provide these subjects not only with motivation but also with tools to monitor improvements and therefore to sustain the lifestyle changes, have been proposed for evaluation in clinical trials [
16]. In a similar perspective, with the aim of improving the subjective and objective results of lifestyle changes in subjects with liver steatosis, and therefore to possibly reinforce their motivation to compliance, the present study has observed the effects of a nutraceutical product as an adjunct to the standard diet and exercise regimen. Since silymarin has consistently been shown to improve parameters related to insulin resistance [
17‐
20], we have observed the efficacy and tolerability of a nutraceutical based on a new formulation of silymarin which provides, at the recommended daily posology, a high dosage of the active ingredient silibinin, together with vitamin E. The clinical use of oral formulations containing silymarin or silibinin has been documented in several clinical trials conducted in patients with ASH or NASH [
17‐
20]. Vitamin E, when used at a high dosage (800 IU), has also been shown to improve several inflammatory parameters in patients with NASH [
21]. The specific aim of the present study was to observe whether, in subjects with a less advanced stage of NAFLD (steatosis), a moderate regimen of diet and exercise, plus a combination of a relatively low dosage of vitamin E (60 IU) and a new formulation of silymarin (by its antioxidant activities) could provide additional clinical improvements.