Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in Western countries leading to high morbidity and mortality and is strongly related to obesity (1). Indeed, metabolic syndrome and insulin resistance play a role in the pathogenesis of NAFLD, which involves intrahepatic triglyceride accumulation and inflammation (2). NAFLD is a consequence of genetic predisposition interacting with environmental and behavioral factors. Data within the literature strongly support the idea that it represents the hepatic feature of a multisystem disease together with type 2 diabetes, cardiovascular disease (CVD), chronic kidney disease and osteoporosis (3). Nevertheless, the exact mechanism of hepatic fat accumulation and the progression to nonalcoholic steatohepatitis (NASH) is not completely understood. Hepatic fat is closely related to cardiometabolic risk (4) and, in order to decrease intrahepatic lipid (IHL) content and improve NAFLD, lifestyle interventions involving both diet and physical activity are recommended (2). In particular, great attention is focused on Mediterranean diet, which seems to help in gradually improving the severity of NAFLD (5). A randomized, cross-over intervention study demonstrated that in just 6 weeks, an olive-oil rich Mediterranean diet can result in a 40% relative reduction in liver fat measured by magnetic resonance in the form of IHL% (6). NAFLD improvement was associated with increased insulin sensitivity and reduced circulating insulin concentrations, even without a change in body weight (6).
Mediterranean diet is characterized by a large intake of fruits, vegetables, whole grains, nuts, legumes and fish and low consumption of red meats with moderate alcohol intake, usually red wine consumed with meals (5). A large fraction of the dietary lipid content consists of monounsaturated fatty acids provided by extra-virgin olive oil (EVOO). The beneficial effects of EVOO may be attributed to phenolic compounds, tocopherol, carotenoids, which show antioxidant, antimicrobial and anti-inflammatory properties, preventing cellular injury and oxidative stress with subsequent positive effects on diseases risk (7,8). Animal models have demonstrated that EVOO and its phenols could regulate hepatic lipid metabolism by reducing the lipogenic pathway, and thus attenuating liver steatosis and collagen deposition (7,8). The largest study on the benefits of the Mediterranean diet was the seven countries study of CVDs that began in the 1950s and has spanned for over 50 years (9). It was an epidemiological study enrolling, at entry, 12,763 men from 16 population cohorts in eight nations of seven countries (Italy, USA, Japan, Netherlands, Greece, Yugoslavia and Finland). Cultural and dietary differences were evaluated in relation to incidence of CVD. Higher incidence and mortality rates from CVD were found in USA and northern Europe whilst Mediterranean countries and Japan showed lower mortality rates (9). In the same period, the Framingham Heart Study , another ongoing and long-lasting epidemiological study on CVD, started to document the natural history of CVD (10). Now the study is turning 70 years old and continues to provide valuable information regarding cardio-metabolic diseases.
A very recent study by Ma and collaborators, involving the second- and the third-generation cohorts of the Framingham Heart Study (11), demonstrated that improved diet quality led to a decrease in liver fat accumulation and consequently a reduced risk and severity of steatosis in adults. Moreover, it was suggested that adopting a healthier diet might blunt the genetic predisposition to NAFLD. In particular their focus was on the Mediterranean Diet assessed by Mediterranean-style diet score (MDS) and the Alternative Healthy Eating Index (AHEI) score. Greater adherence to these dietary patterns was associated with reduction in weight gain and hepatic fat together with lower incidence of CVD and decreased risk of death (11). Authors found that increased intake of fruits, legumes, vegetables, nuts, whole grains, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and reduction in red meat and trans-fat, was associated with lower risk of steatosis. Furthermore, Ma and collaborators strongly support a long-term diet-quality change that might induce improvements in liver fat accumulation reducing the risk of NAFLD (11). Liver fat deposition may be influenced by the consumption of fruits and vegetables rich in water and fiber, which help to decrease the energy intake by affecting satiety and, thus, avoiding weight gain (11). Moreover, high fiber consumption increases bacteria degrading fiber which may increase the production of short-chain fatty acids (SCFAs), including butyrate which may suppress inflammation reducing the possible onset and progression of NAFLD (11). Another hypothesis explaining the association between diet and reduced liver fat accumulation is independent of change in weight gain and is related to increased nut or legume consumption suggesting that nut intake may promote lipid oxidation and reduce ectopic visceral fat (10). Mediterranean diet interventions in non-Mediterranean countries may have additional challenges and need specific approaches (11). An English study on NAFLD patients found Mediterranean diet as an acceptable healthy eating model without associations between socio-demographic characteristics and adherence to dietary changes (12). The main issue for patients is to accept NAFLD as a disease, indeed successful nutritional changes are strongly related to patients’ knowledge about their condition. Indeed, the lack of early symptoms and the misperception of a long-term disease with severe outcome make difficult the intervention in this kind of patients. The role of clinicians, instead, is to give the message that NAFLD is treatable and even reversible if diet improvements are achieved. Moreover, it has been demonstrated that weight loss promotes the adoption and adherence to the diet (12).
Together with diet, physical activity is suggested in NAFLD prevention and treatment, data from literature reported that physical activity influences hepatic metabolism and is inversely associated with the onset of NAFLD and NASH (1). Exercise training induces significant improvement of hepatic and visceral fat accumulation, increased lipid oxidation and insulin sensitivity (13). Decreased hepatic fat content, adipose tissue and insulin resistance have been showed at similar extent with both aerobic and anaerobic resistance training (14). Unfortunately, it has not yet been established the optimal type, duration, and intensity of exercise training for patients with NAFLD so that clinical studies are needed to focus which are the best conditions of physical activity in order to obtain the best results in prevention of NAFLD (15). Even if a large number of studies support the efficacy of both diet-based approaches and physical activity for NAFLD prevention, further future investigations are needed to confirm scientific data and to explore the possible molecular mechanisms underlying the association between NAFLD, diet and physical activity.
The authors would like to thank Prof. Iain Halliday for commenting and making corrections to the paper.
Funding: This study was supported by the University Research Project Grant (Triennial Research Plan 2016-2018), Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Italy.
Conflicts of Interest: The authors have no conflicts of interest to declare.
- Berzigotti A, Saran U, Dufour JF. Physical activity and liver diseases. Hepatology 2016;63:1026-40. [Crossref] [PubMed]
- Armstrong MJ, Adams LA, Canbay A, et al. Extrahepatic complications of nonalcoholic fatty liver disease. Hepatology 2014;59:1174-97. [Crossref] [PubMed]
- Albhaisi S, Issa D, Alkhouri N. Non-alcoholic fatty liver disease: a pandemic disease with multisystem burden. Hepatobiliary Surg Nutr 2018;7:389-91. [Crossref] [PubMed]
- Lee JJ, Pedley A, Hoffmann U, et al. Visceral and Intrahepatic Fat Are Associated with Cardiometabolic Risk Factors Above Other Ectopic Fat Depots: The Framingham Heart Study. Am J Med 2018;131:684-92.e12. [Crossref] [PubMed]
- Trovato FM, Catalano D, Martines GF, et al. Mediterranean diet and non-alcoholic fatty liver disease: the need of extended and comprehensive interventions. Clin Nutr 2015;34:86-8. [Crossref] [PubMed]
- Ryan MC, Itsiopoulos C, Thodis T, et al. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol 2013;59:138-43. [Crossref] [PubMed]
- Jurado-Ruiz E, Varela LM, Luque A, et al. An extra virgin olive oil rich diet intervention ameliorates the nonalcoholic steatohepatitis induced by a high-fat "Western-type" diet in mice. Mol Nutr Food Res 2017;61. [PubMed]
- Trovato FM, Castrogiovanni P, Szychlinska MA, et al. Early effects of high-fat diet, extra-virgin olive oil and vitamin D in a sedentary rat model of non-alcoholic fatty liver disease. Histol Histopathol 2018;33:1201-13. [PubMed]
- The diet and all-causes death rate in the Seven Countries Study. Lancet 1981;2:58-61. [PubMed]
- Dawber TR, Meadors GF, Moore FE Jr. Epidemiological approaches to heart disease: the Framingham Study. Am J Public Health Nations Health 1951;41:279-81. [Crossref] [PubMed]
- Ma J, Hennein R, Liu C, et al. Improved Diet Quality Associates With Reduction in Liver Fat, Particularly in Individuals With High Genetic Risk Scores for Nonalcoholic Fatty Liver Disease. Gastroenterology 2018;155:107-17. [Crossref] [PubMed]
- Haigh L, Bremner S, Houghton D, et al. Barriers and Facilitators to Mediterranean Diet Adoption by Patients with Non-alcoholic Fatty Liver Disease in Northern Europe. Clin Gastroenterol Hepatol 2018. [Epub ahead of print]. [Crossref] [PubMed]
- Johnson NA, Sachinwalla T, Walton DW, et al. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology 2009;50:1105-12. [Crossref] [PubMed]
- Bacchi E, Negri C, Targher G, et al. Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 Randomized Trial). Hepatology 2013;58:1287-95. [Crossref] [PubMed]
- Trovato FM, Martines GF, Brischetto D, et al. Fatty liver disease and lifestyle in youngsters: diet, food intake frequency, exercise, sleep shortage and fashion. Liver Int 2016;36:427-33. [Crossref] [PubMed]