Download PDF
Semin Liver Dis 2015; 35(03): 318-337
DOI: 10.1055/s-0035-1562950
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Nonalcoholic Fatty Liver Disease Management: Dietary and Lifestyle Modifications

Vi Nguyen
1   Storr Liver Centre, Westmead Hospital and Westmead Millennium Institute, University of Sydney at Westmead Hospital, Sydney, Australia
,
Jacob George
1   Storr Liver Centre, Westmead Hospital and Westmead Millennium Institute, University of Sydney at Westmead Hospital, Sydney, Australia
› Author Affiliations
Further Information

Publication History

Publication Date:
17 September 2015 (online)

    Permissions and Reprints

Abstract

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of abnormalities that can range from bland liver fat (steatosis), to hepatic inflammation and liver injury (steatohepatitis). It is estimated that NAFLD will become the principal cause of liver disease in Western nations and the leading indication for liver transplantation. Advancements in disease recognition and management are therefore paramount. Although the development of new, reliable drug therapies is vital, lifestyle interventions remain the most effective treatment modality. In addition to weight loss as a primary measure of treatment success, there is growing recognition that other endpoints, including the prevention or delay of diabetes onset, reduced cardiovascular events, prevention of cancer, and improved overall mortality, are equally important outcomes that can be independently modified by lifestyle change. Moreover, NAFLD is inextricably part of a complex, systemic disease process that is linked with deeply entrenched maladaptive lifestyle behaviors. Thus, a holistic, multidisciplinary, and individualized approach to disease management will be the key to achieving any realistic population-level change.

Keywords

nonalcoholic fatty liver - nonalcoholic steatohepatitis - lifestyle intervention - dietary modification - macronutrients - exercise
 

  • References

  • 1 Argo CK, Caldwell SH. Epidemiology and natural history of non-alcoholic steatohepatitis. Clin Liver Dis 2009; 13 (4) 511-531
    CrossrefPubMedGoogle Scholar
  • 2 Bellentani S, Scaglioni F, Marino M, Bedogni G. Epidemiology of non-alcoholic fatty liver disease. Dig Dis 2010; 28 (1) 155-161
    CrossrefPubMedGoogle Scholar
  • 3 Ekstedt M, Franzén LE, Mathiesen UL , et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006; 44 (4) 865-873
    CrossrefPubMedGoogle Scholar
  • 4 White DL, Kanwal F, El-Serag HB. Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin Gastroenterol Hepatol 2012; 10 (12) 1342-1359.e2
    CrossrefPubMedGoogle Scholar
  • 5 Adams LA, Lymp JF, St Sauver J , et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005; 129 (1) 113-121
    CrossrefPubMedGoogle Scholar
  • 6 Lazo M, Hernaez R, Bonekamp S , et al. Non-alcoholic fatty liver disease and mortality among US adults: prospective cohort study. BMJ 2011; 343: d6891
    CrossrefPubMedGoogle Scholar
  • 7 Mahady SE, George J. Management of nonalcoholic steatohepatitis: an evidence-based approach. Clin Liver Dis 2012; 16 (3) 631-645
    CrossrefPubMedGoogle Scholar
  • 8 Avery L, Flynn D, van Wersch A, Sniehotta FF, Trenell MI. Changing physical activity behavior in type 2 diabetes: a systematic review and meta-analysis of behavioral interventions. Diabetes Care 2012; 35 (12) 2681-2689
    CrossrefPubMedGoogle Scholar
  • 9 Butryn ML, Webb V, Wadden TA. Behavioral treatment of obesity. Psychiatr Clin North Am 2011; 34 (4) 841-859
    CrossrefPubMedGoogle Scholar
  • 10 Boutelle KN, Kirschenbaum DS. Further support for consistent self-monitoring as a vital component of successful weight control. Obes Res 1998; 6 (3) 219-224
    CrossrefPubMedGoogle Scholar
  • 11 Renjilian DA, Perri MG, Nezu AM, McKelvey WF, Shermer RL, Anton SD. Individual versus group therapy for obesity: effects of matching participants to their treatment preferences. J Consult Clin Psychol 2001; 69 (4) 717-721
    CrossrefPubMedGoogle Scholar
  • 12 Wing RR, Tate DF, Gorin AA, Raynor HA, Fava JL. A self-regulation program for maintenance of weight loss. N Engl J Med 2006; 355 (15) 1563-1571
    CrossrefPubMedGoogle Scholar
  • 13 Moscatiello S, Di Luzio R, Bugianesi E , et al. Cognitive-behavioral treatment of nonalcoholic fatty liver disease: a propensity score-adjusted observational study. Obesity (Silver Spring) 2011; 19 (4) 763-770
    CrossrefPubMedGoogle Scholar
  • 14 Frith J, Day CP, Robinson L, Elliott C, Jones DE, Newton JL. Potential strategies to improve uptake of exercise interventions in non-alcoholic fatty liver disease. J Hepatol 2010; 52 (1) 112-116
    CrossrefPubMedGoogle Scholar
  • 15 Bellentani S, Dalle Grave R, Suppini A, Marchesini G ; Fatty Liver Italian Network. Behavior therapy for nonalcoholic fatty liver disease: the need for a multidisciplinary approach. Hepatology 2008; 47 (2) 746-754
    CrossrefPubMedGoogle Scholar
  • 16 Newton JL, Jones DE, Henderson E , et al. Fatigue in non-alcoholic fatty liver disease (NAFLD) is significant and associates with inactivity and excessive daytime sleepiness but not with liver disease severity or insulin resistance. Gut 2008; 57 (6) 807-813
    CrossrefPubMedGoogle Scholar
  • 17 Marchesini G, Nuccitelli G, Centis E , et al. Behavioral aspects of nonalcoholic fatty liver disease: diet, causes, and treatment. In Preedy VR, Watson RR, Martin CR, , Eds. Handbook of Behavior, Food and Nutrition. New York: Springer; 2011: 1833-1844
    CrossrefGoogle Scholar
  • 18 Byrne S, Cooper Z, Fairburn C. Weight maintenance and relapse in obesity: a qualitative study. Int J Obes Relat Metab Disord 2003; 27 (8) 955-962
    CrossrefPubMedGoogle Scholar
  • 19 Visram S, Crosland A, Cording H. Triggers for weight gain and loss among participants in a primary care-based intervention. Br J Community Nurs 2009; 14 (11) 495-501
    PubMedGoogle Scholar
  • 20 Phelan S, Hill JO, Lang W, Dibello JR, Wing RR. Recovery from relapse among successful weight maintainers. Am J Clin Nutr 2003; 78 (6) 1079-1084
    PubMedGoogle Scholar
  • 21 Knowler WC, Barrett-Connor E, Fowler SE , et al; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346 (6) 393-403
    CrossrefPubMedGoogle Scholar
  • 22 Lindström J, Louheranta A, Mannelin M , et al; Finnish Diabetes Prevention Study Group. The Finnish Diabetes Prevention Study (DPS): Lifestyle intervention and 3-year results on diet and physical activity. Diabetes Care 2003; 26 (12) 3230-3236
    CrossrefPubMedGoogle Scholar
  • 23 Sesso HD, Paffenbarger Jr RS, Lee IM. Physical activity and coronary heart disease in men: the Harvard Alumni Health Study. Circulation 2000; 102 (9) 975-980
    CrossrefPubMedGoogle Scholar
  • 24 Wei M, Kampert JB, Barlow CE , et al. Relationship between low cardiorespiratory fitness and mortality in normal-weight, overweight, and obese men. JAMA 1999; 282 (16) 1547-1553
    CrossrefPubMedGoogle Scholar
  • 25 Knowler WC, Fowler SE, Hamman RF , et al; Diabetes Prevention Program Research Group. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet 2009; 374 (9702) 1677-1686
    CrossrefPubMedGoogle Scholar
  • 26 Diabetes Prevention Program Research Group. The 10-year cost-effectiveness of lifestyle intervention or metformin for diabetes prevention: an intent-to-treat analysis of the DPP/DPPOS. Diabetes Care 2012; 35 (4) 723-730
    CrossrefPubMedGoogle Scholar
  • 27 Pan XR, Li GW, Hu YH , et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 1997; 20 (4) 537-544
    CrossrefPubMedGoogle Scholar
  • 28 Gong Q, Gregg EW, Wang J , et al. Long-term effects of a randomised trial of a 6-year lifestyle intervention in impaired glucose tolerance on diabetes-related microvascular complications: the China Da Qing Diabetes Prevention Outcome Study. Diabetologia 2011; 54 (2) 300-307
    CrossrefPubMedGoogle Scholar
  • 29 Li G, Zhang P, Wang J , et al. Cardiovascular mortality, all-cause mortality, and diabetes incidence after lifestyle intervention for people with impaired glucose tolerance in the Da Qing Diabetes Prevention Study: a 23-year follow-up study. Lancet Diabetes Endocrinol 2014; 2 (6) 474-480
    PubMedGoogle Scholar
  • 30 Kim D, Kim WR, Kim HJ, Therneau TM. Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States. Hepatology 2013; 57 (4) 1357-1365
    CrossrefPubMedGoogle Scholar
  • 31 Thoma C, Day CP, Trenell MI. Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: a systematic review. J Hepatol 2012; 56 (1) 255-266
    CrossrefPubMedGoogle Scholar
  • 32 Promrat K, Kleiner DE, Niemeier HM , et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 2010; 51 (1) 121-129
    CrossrefPubMedGoogle Scholar
  • 33 Eckard C, Cole R, Lockwood J , et al. Prospective histopathologic evaluation of lifestyle modification in nonalcoholic fatty liver disease: a randomized trial. Therap Adv Gastroenterol 2013; 6 (4) 249-259
    CrossrefPubMedGoogle Scholar
  • 34 Vilar Gomez E, Rodriguez De Miranda A, Gra Oramas B , et al. Clinical trial: a nutritional supplement Viusid, in combination with diet and exercise, in patients with nonalcoholic fatty liver disease. Aliment Pharmacol Ther 2009; 30 (10) 999-1009
    CrossrefPubMedGoogle Scholar
  • 35 Bugianesi E, Moscatiello S, Ciaravella MF, Marchesini G. Insulin resistance in nonalcoholic fatty liver disease. Curr Pharm Des 2010; 16 (17) 1941-1951
    CrossrefPubMedGoogle Scholar
  • 36 Marchesini G, Brizi M, Morselli-Labate AM , et al. Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med 1999; 107 (5) 450-455
    Google Scholar
  • 37 Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003; 348 (17) 1625-1638
    CrossrefPubMedGoogle Scholar
  • 38 Arem H, Moore SC, Park Y , et al. Physical activity and cancer-specific mortality in the NIH-AARP Diet and Health Study cohort. Int J Cancer 2014; 135 (2) 423-431
    CrossrefPubMedGoogle Scholar
  • 39 Kampert JB, Blair SN, Barlow CE, Kohl III HW. Physical activity, physical fitness, and all-cause and cancer mortality: a prospective study of men and women. Ann Epidemiol 1996; 6 (5) 452-457
    CrossrefPubMedGoogle Scholar
  • 40 Wen CP, Wai JP, Tsai MK , et al. Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet 2011; 378 (9798) 1244-1253
    CrossrefPubMedGoogle Scholar
  • 41 Ballard-Barbash R, Friedenreich CM, Courneya KS, Siddiqi SM, McTiernan A, Alfano CM. Physical activity, biomarkers, and disease outcomes in cancer survivors: a systematic review. J Natl Cancer Inst 2012; 104 (11) 815-840
    CrossrefPubMedGoogle Scholar
  • 42 Courneya KS. Exercise in cancer survivors: an overview of research. Med Sci Sports Exerc 2003; 35 (11) 1846-1852
    CrossrefPubMedGoogle Scholar
  • 43 Watson K, Baar K. mTOR and the health benefits of exercise. Semin Cell Dev Biol 2014; 36: 130-139
    CrossrefPubMedGoogle Scholar
  • 44 de Lorgeril M, Salen P. New insights into the health effects of dietary saturated and omega-6 and omega-3 polyunsaturated fatty acids. BMC Med 2012; 10: 50
    CrossrefPubMedGoogle Scholar
  • 45 Grosso G, Buscemi S, Galvano F , et al. Mediterranean diet and cancer: epidemiological evidence and mechanism of selected aspects. BMC Surg 2013; 13 (Suppl. 02) S14
    CrossrefPubMedGoogle Scholar
  • 46 de Lorgeril M, Salen P. The Mediterranean diet: rationale and evidence for its benefit. Curr Atheroscler Rep 2008; 10 (6) 518-522
    CrossrefPubMedGoogle Scholar
  • 47 Bamia C, Lagiou P, Buckland G , et al. Mediterranean diet and colorectal cancer risk: results from a European cohort. Eur J Epidemiol 2013; 28 (4) 317-328
    CrossrefPubMedGoogle Scholar
  • 48 Praud D, Bertuccio P, Bosetti C, Turati F, Ferraroni M, La Vecchia C. Adherence to the Mediterranean diet and gastric cancer risk in Italy. Int J Cancer 2014; 134 (12) 2935-2941
    CrossrefPubMedGoogle Scholar
  • 49 Bosetti C, Turati F, Dal Pont A , et al. The role of Mediterranean diet on the risk of pancreatic cancer. Br J Cancer 2013; 109 (5) 1360-1366
    CrossrefPubMedGoogle Scholar
  • 50 Turati F, Trichopoulos D, Polesel J , et al. Mediterranean diet and hepatocellular carcinoma. J Hepatol 2014; 60 (3) 606-611
    CrossrefPubMedGoogle Scholar
  • 51 Buckland G, Travier N, Cottet V , et al. Adherence to the Mediterranean diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study. Int J Cancer 2013; 132 (12) 2918-2927
    CrossrefPubMedGoogle Scholar
  • 52 Yang B, Ren XL, Fu YQ, Gao JL, Li D. Ratio of n-3/n-6 PUFAs and risk of breast cancer: a meta-analysis of 274135 adult females from 11 independent prospective studies. BMC Cancer 2014; 14: 105
    CrossrefPubMedGoogle Scholar
  • 53 Wang J, John EM, Ingles SA. 5-lipoxygenase and 5-lipoxygenase-activating protein gene polymorphisms, dietary linoleic acid, and risk for breast cancer. Cancer Epidemiol Biomarkers Prev 2008; 17 (10) 2748-2754
    CrossrefPubMedGoogle Scholar
  • 54 Ravnskov U, McCully KS, Rosch PJ. The statin-low cholesterol-cancer conundrum. QJM 2012; 105 (4) 383-388
    CrossrefPubMedGoogle Scholar
  • 55 Sacks FM, Pfeffer MA, Moye LA , et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996; 335 (14) 1001-1009
    CrossrefPubMedGoogle Scholar
  • 56 American Diabetes Association. Standards of medical care in diabetes—2013. Diabetes Care 2013; 36 (Suppl. 01) S11-S66
    CrossrefPubMedGoogle Scholar
  • 57 Harrison SA, Fecht W, Brunt EM, Neuschwander-Tetri BA. Orlistat for overweight subjects with nonalcoholic steatohepatitis: a randomized, prospective trial. Hepatology 2009; 49 (1) 80-86
    CrossrefPubMedGoogle Scholar
  • 58 Suzuki A, Lindor K, St Saver J , et al. Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease. J Hepatol 2005; 43 (6) 1060-1066
    CrossrefPubMedGoogle Scholar
  • 59 Solon-Biet SM, McMahon AC, Ballard JW , et al. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell Metab 2014; 19 (3) 418-430
    CrossrefPubMedGoogle Scholar
  • 60 Sørensen A, Mayntz D, Raubenheimer D, Simpson SJ. Protein-leverage in mice: the geometry of macronutrient balancing and consequences for fat deposition. Obesity (Silver Spring) 2008; 16 (3) 566-571
    CrossrefPubMedGoogle Scholar
  • 61 Kapahi P, Chen D, Rogers AN , et al. With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab 2010; 11 (6) 453-465
    CrossrefPubMedGoogle Scholar
  • 62 Fontana L, Partridge L, Longo VD. Extending healthy life span—from yeast to humans. Science 2010; 328 (5976) 321-326
    CrossrefPubMedGoogle Scholar
  • 63 Sacks FM, Bray GA, Carey VJ , et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med 2009; 360 (9) 859-873
    CrossrefPubMedGoogle Scholar
  • 64 Ioannou GN, Morrow OB, Connole ML, Lee SP. Association between dietary nutrient composition and the incidence of cirrhosis or liver cancer in the United States population. Hepatology 2009; 50 (1) 175-184
    CrossrefPubMedGoogle Scholar
  • 65 Sathiaraj E, Chutke M, Reddy MY , et al. A case-control study on nutritional risk factors in non-alcoholic fatty liver disease in Indian population. Eur J Clin Nutr 2011; 65 (4) 533-537
    CrossrefPubMedGoogle Scholar
  • 66 Volynets V, Küper MA, Strahl S , et al. Nutrition, intestinal permeability, and blood ethanol levels are altered in patients with nonalcoholic fatty liver disease (NAFLD). Dig Dis Sci 2012; 57 (7) 1932-1941
    CrossrefPubMedGoogle Scholar
  • 67 Musso G, Gambino R, De Michieli F , et al. Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology 2003; 37 (4) 909-916
    CrossrefPubMedGoogle Scholar
  • 68 Cortez-Pinto H, Jesus L, Barros H, Lopes C, Moura MC, Camilo ME. How different is the dietary pattern in non-alcoholic steatohepatitis patients?. Clin Nutr 2006; 25 (5) 816-823
    CrossrefPubMedGoogle Scholar
  • 69 Toshimitsu K, Matsuura B, Ohkubo I , et al. Dietary habits and nutrient intake in non-alcoholic steatohepatitis. Nutrition 2007; 23 (1) 46-52
    CrossrefPubMedGoogle Scholar
  • 70 Kang H, Greenson JK, Omo JT , et al. Metabolic syndrome is associated with greater histologic severity, higher carbohydrate, and lower fat diet in patients with NAFLD. Am J Gastroenterol 2006; 101 (10) 2247-2253
    CrossrefPubMedGoogle Scholar
  • 71 Kwon OW, Jun DW, Lee SM , et al. Carbohydrate but not fat is associated with elevated aminotransferases. Aliment Pharmacol Ther 2012; 35 (9) 1064-1072
    PubMedGoogle Scholar
  • 72 Da Silva HE, Arendt BM, Noureldin SA, Therapondos G, Guindi M, Allard JP. A cross-sectional study assessing dietary intake and physical activity in Canadian patients with nonalcoholic fatty liver disease vs healthy controls. J Acad Nutr Diet 2014; 114 (8) 1181-1194
    CrossrefPubMedGoogle Scholar
  • 73 Zelber-Sagi S, Nitzan-Kaluski D, Goldsmith R , et al. Long term nutritional intake and the risk for non-alcoholic fatty liver disease (NAFLD): a population based study. J Hepatol 2007; 47 (5) 711-717
    CrossrefPubMedGoogle Scholar
  • 74 Simonen P, Kotronen A, Hallikainen M , et al. Cholesterol synthesis is increased and absorption decreased in non-alcoholic fatty liver disease independent of obesity. J Hepatol 2011; 54 (1) 153-159
    PubMedGoogle Scholar
  • 75 Min HK, Kapoor A, Fuchs M , et al. Increased hepatic synthesis and dysregulation of cholesterol metabolism is associated with the severity of nonalcoholic fatty liver disease. Cell Metab 2012; 15 (5) 665-674
    CrossrefPubMedGoogle Scholar
  • 76 Simonen M, Männistö V, Leppänen J , et al. Desmosterol in human nonalcoholic steatohepatitis. Hepatology 2013; 58 (3) 976-982
    CrossrefPubMedGoogle Scholar
  • 77 Mozaffarian D, Katan MB, Ascherio A, Stampfer MJ, Willett WC. Trans fatty acids and cardiovascular disease. N Engl J Med 2006; 354 (15) 1601-1613
    CrossrefPubMedGoogle Scholar
  • 78 Mozaffarian D. Trans fatty acids - effects on systemic inflammation and endothelial function. Atheroscler Suppl 2006; 7 (2) 29-32
    PubMedGoogle Scholar
  • 79 Mozaffarian D, de Oliveira Otto MC, Lemaitre RN , et al. trans-Palmitoleic acid, other dairy fat biomarkers, and incident diabetes: the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr 2013; 97 (4) 854-861
    CrossrefPubMedGoogle Scholar
  • 80 Obara N, Fukushima K, Ueno Y , et al. Possible involvement and the mechanisms of excess trans-fatty acid consumption in severe NAFLD in mice. J Hepatol 2010; 53 (2) 326-334
    CrossrefPubMedGoogle Scholar
  • 81 Neuschwander-Tetri BA, Ford DA, Acharya S , et al. Dietary trans-fatty acid induced NASH is normalized following loss of trans-fatty acids from hepatic lipid pools. Lipids 2012; 47 (10) 941-950
    CrossrefPubMedGoogle Scholar
  • 82 Kris-Etherton PM, Lefevre M, Mensink RP, Petersen B, Fleming J, Flickinger BD. Trans fatty acid intakes and food sources in the U.S. population: NHANES 1999-2002. Lipids 2012; 47 (10) 931-940
    CrossrefPubMedGoogle Scholar
  • 83 Krauss RM, Eckel RH, Howard B , et al. AHA Dietary Guidelines: revision 2000: a statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation 2000; 102 (18) 2284-2299
    CrossrefPubMedGoogle Scholar
  • 84 Wang D, Wei Y, Pagliassotti MJ. Saturated fatty acids promote endoplasmic reticulum stress and liver injury in rats with hepatic steatosis. Endocrinology 2006; 147 (2) 943-951
    CrossrefPubMedGoogle Scholar
  • 85 Vessby B, Uusitupa M, Hermansen K , et al; KANWU Study. Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study. Diabetologia 2001; 44 (3) 312-319
    CrossrefPubMedGoogle Scholar
  • 86 Chowdhury R, Warnakula S, Kunutsor S , et al. Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis. Ann Intern Med 2014; 160 (6) 398-406
    PubMedGoogle Scholar
  • 87 Jakobsen MU, O'Reilly EJ, Heitmann BL , et al. Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies. Am J Clin Nutr 2009; 89 (5) 1425-1432
    CrossrefPubMedGoogle Scholar
  • 88 Mozaffarian D, Micha R, Wallace S. Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: a systematic review and meta-analysis of randomized controlled trials. PLoS Med 2010; 7 (3) e1000252
    CrossrefPubMedGoogle Scholar
  • 89 Rajaram S, Burke K, Connell B, Myint T, Sabaté J. A monounsaturated fatty acid-rich pecan-enriched diet favorably alters the serum lipid profile of healthy men and women. J Nutr 2001; 131 (9) 2275-2279
    PubMedGoogle Scholar
  • 90 Kris-Etherton PM, Pearson TA, Wan Y , et al. High-monounsaturated fatty acid diets lower both plasma cholesterol and triacylglycerol concentrations. Am J Clin Nutr 1999; 70 (6) 1009-1015
    PubMedGoogle Scholar
  • 91 Wheeler ML, Dunbar SA, Jaacks LM , et al. Macronutrients, food groups, and eating patterns in the management of diabetes: a systematic review of the literature, 2010. Diabetes Care 2012; 35 (2) 434-445
    CrossrefPubMedGoogle Scholar
  • 92 Schwingshackl L, Hoffmann G. Monounsaturated fatty acids and risk of cardiovascular disease: synopsis of the evidence available from systematic reviews and meta-analyses. Nutrients 2012; 4 (12) 1989-2007
    CrossrefPubMedGoogle Scholar
  • 93 Li ZZ, Berk M, McIntyre TM, Feldstein AE. Hepatic lipid partitioning and liver damage in nonalcoholic fatty liver disease: role of stearoyl-CoA desaturase. J Biol Chem 2009; 284 (9) 5637-5644
    CrossrefPubMedGoogle Scholar
  • 94 Bozzetto L, Prinster A, Annuzzi G , et al. Liver fat is reduced by an isoenergetic MUFA diet in a controlled randomized study in type 2 diabetic patients. Diabetes Care 2012; 35 (7) 1429-1435
    CrossrefPubMedGoogle Scholar
  • 95 Laaksonen DE, Nyyssönen K, Niskanen L, Rissanen TH, Salonen JT. Prediction of cardiovascular mortality in middle-aged men by dietary and serum linoleic and polyunsaturated fatty acids. Arch Intern Med 2005; 165 (2) 193-199
    CrossrefPubMedGoogle Scholar
  • 96 Djoussé L, Folsom AR, Province MA, Hunt SC, Ellison RC ; National Heart, Lung, and Blood Institute Family Heart Study. Dietary linolenic acid and carotid atherosclerosis: the National Heart, Lung, and Blood Institute Family Heart Study. Am J Clin Nutr 2003; 77 (4) 819-825
    PubMedGoogle Scholar
  • 97 Michas G, Micha R, Zampelas A. Dietary fats and cardiovascular disease: putting together the pieces of a complicated puzzle. Atherosclerosis 2014; 234 (2) 320-328
    CrossrefPubMedGoogle Scholar
  • 98 Simopoulos AP. Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases. Biomed Pharmacother 2006; 60 (9) 502-507
    CrossrefPubMedGoogle Scholar
  • 99 Parker HM, Johnson NA, Burdon CA, Cohn JS, O'Connor HT, George J. Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol 2012; 56 (4) 944-951
    CrossrefPubMedGoogle Scholar
  • 100 Hamazaki T, Okuyama H. The Japan Society for Lipid Nutrition recommends to reduce the intake of linoleic acid. A review and critique of the scientific evidence. World Rev Nutr Diet 2003; 92: 109-132
    PubMedGoogle Scholar
  • 101 Simopoulos AP. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med (Maywood) 2008; 233 (6) 674-688
    CrossrefPubMedGoogle Scholar
  • 102 Wu JH, Lemaitre RN, King IB , et al. Circulating omega-6 polyunsaturated fatty acids and total and cause-specific mortality: the Cardiovascular Health Study. Circulation 2014; 130 (15) 1245-1253
    CrossrefPubMedGoogle Scholar
  • 103 De Caterina R. n-3 fatty acids in cardiovascular disease. N Engl J Med 2011; 364 (25) 2439-2450
    CrossrefPubMedGoogle Scholar
  • 104 Roncaglioni MC, Tombesi M, Avanzini F , et al; Risk and Prevention Study Collaborative Group. n-3 fatty acids in patients with multiple cardiovascular risk factors. N Engl J Med 2013; 368 (19) 1800-1808
    CrossrefPubMedGoogle Scholar
  • 105 Joensen AM, Overvad K, Dethlefsen C , et al. Marine n-3 polyunsaturated fatty acids in adipose tissue and the risk of acute coronary syndrome. Circulation 2011; 124 (11) 1232-1238
    CrossrefPubMedGoogle Scholar
  • 106 Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico. Lancet 1999; 354 (9177) 447-455
    CrossrefPubMedGoogle Scholar
  • 107 Ghafoorunissa A, Ibrahim A, Natarajan S. Substituting dietary linoleic acid with alpha-linolenic acid improves insulin sensitivity in sucrose fed rats. Biochim Biophys Acta 2005; 1733 (1) 67-75
    CrossrefPubMedGoogle Scholar
  • 108 Lombardo YB, Chicco AG. Effects of dietary polyunsaturated n-3 fatty acids on dyslipidemia and insulin resistance in rodents and humans. A review. J Nutr Biochem 2006; 17 (1) 1-13
    CrossrefPubMedGoogle Scholar
  • 109 Wijendran V, Hayes KC. Dietary n-6 and n-3 fatty acid balance and cardiovascular health. Annu Rev Nutr 2004; 24: 597-615
    CrossrefPubMedGoogle Scholar
  • 110 Scorletti E, Bhatia L, McCormick KG , et al; WELCOME Study. Effects of purified eicosapentaenoic and docosahexaenoic acids in nonalcoholic fatty liver disease: results from the Welcome* study. Hepatology 2014; 60 (4) 1211-1221
    CrossrefPubMedGoogle Scholar
  • 111 Dasarathy S, Dasarathy J, Khiyami A , et al. Double-blind randomized placebo-controlled clinical trial of omega 3 fatty acids for the treatment of diabetic patients with nonalcoholic steatohepatitis. J Clin Gastroenterol 2015; 49 (2) 137-144
    CrossrefPubMedGoogle Scholar
  • 112 Sanyal AJ, Abdelmalek MF, Suzuki A, Cummings OW, Chojkier M ; EPE-A Study Group. No significant effects of ethyl-eicosapentanoic acid on histologic features of nonalcoholic steatohepatitis in a phase 2 trial. Gastroenterology 2014; 147 (2) 377-84.e1
    CrossrefPubMedGoogle Scholar
  • 113 Kurabayashi T, Okada M, Tanaka K ; The Niigata Epadel Study Group. Eicosapentaenoic acid effect on hyperlipidemia in menopausal Japanese women. Obstet Gynecol 2000; 96 (4) 521-528
    CrossrefPubMedGoogle Scholar
  • 114 Tanaka N, Sano K, Horiuchi A, Tanaka E, Kiyosawa K, Aoyama T. Highly purified eicosapentaenoic acid treatment improves nonalcoholic steatohepatitis. J Clin Gastroenterol 2008; 42 (4) 413-418
    CrossrefPubMedGoogle Scholar
  • 115 Tapsell LC, Gillen LJ, Patch CS , et al. Including walnuts in a low-fat/modified-fat diet improves HDL cholesterol-to-total cholesterol ratios in patients with type 2 diabetes. Diabetes Care 2004; 27 (12) 2777-2783
    CrossrefPubMedGoogle Scholar
  • 116 Fink A, Rüfer CE, Le Grandois J , et al. Dietary walnut oil modulates liver steatosis in the obese Zucker rat. Eur J Nutr 2014; 53 (2) 645-660
    CrossrefPubMedGoogle Scholar
  • 117 Garg A, Bantle JP, Henry RR , et al. Effects of varying carbohydrate content of diet in patients with non-insulin-dependent diabetes mellitus. JAMA 1994; 271 (18) 1421-1428
    CrossrefPubMedGoogle Scholar
  • 118 McLaughlin T, Abbasi F, Lamendola C, Yeni-Komshian H, Reaven G. Carbohydrate-induced hypertriglyceridemia: an insight into the link between plasma insulin and triglyceride concentrations. J Clin Endocrinol Metab 2000; 85 (9) 3085-3088
    CrossrefPubMedGoogle Scholar
  • 119 Hudgins LC, Hellerstein M, Seidman C, Neese R, Diakun J, Hirsch J. Human fatty acid synthesis is stimulated by a eucaloric low fat, high carbohydrate diet. J Clin Invest 1996; 97 (9) 2081-2091
    CrossrefPubMedGoogle Scholar
  • 120 Paniagua JA, Gallego de la Sacristana A, Romero I , et al. Monounsaturated fat-rich diet prevents central body fat distribution and decreases postprandial adiponectin expression induced by a carbohydrate-rich diet in insulin-resistant subjects. Diabetes Care 2007; 30 (7) 1717-1723
    CrossrefPubMedGoogle Scholar
  • 121 Feinman RD, Pogozelski WK, Astrup A , et al. Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition 2015; 31 (1) 1-13
    CrossrefPubMedGoogle Scholar
  • 122 Haufe S, Engeli S, Kast P , et al. Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects. Hepatology 2011; 53 (5) 1504-1514
    CrossrefPubMedGoogle Scholar
  • 123 Ryan MC, Abbasi F, Lamendola C, Carter S, McLaughlin TL. Serum alanine aminotransferase levels decrease further with carbohydrate than fat restriction in insulin-resistant adults. Diabetes Care 2007; 30 (5) 1075-1080
    CrossrefPubMedGoogle Scholar
  • 124 Assy N, Nasser G, Kamayse I , et al. Soft drink consumption linked with fatty liver in the absence of traditional risk factors. Can J Gastroenterol 2008; 22 (10) 811-816
    PubMedGoogle Scholar
  • 125 Ouyang X, Cirillo P, Sautin Y , et al. Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol 2008; 48 (6) 993-999
    CrossrefPubMedGoogle Scholar
  • 126 Elliott SS, Keim NL, Stern JS, Teff K, Havel PJ. Fructose, weight gain, and the insulin resistance syndrome. Am J Clin Nutr 2002; 76 (5) 911-922
    PubMedGoogle Scholar
  • 127 Fields M, Lewis CG, Lure MD. Responses of insulin to oral glucose and fructose loads in marginally copper-deficient rats fed starch or fructose. Nutrition 1996; 12 (7-8) 524-528
    CrossrefPubMedGoogle Scholar
  • 128 Martinez FJ, Rizza RA, Romero JC. High-fructose feeding elicits insulin resistance, hyperinsulinism, and hypertension in normal mongrel dogs. Hypertension 1994; 23 (4) 456-463
    CrossrefPubMedGoogle Scholar
  • 129 Lê KA, Ith M, Kreis R , et al. Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes. Am J Clin Nutr 2009; 89 (6) 1760-1765
    CrossrefPubMedGoogle Scholar
  • 130 Johnston RD, Stephenson MC, Crossland H , et al. No difference between high-fructose and high-glucose diets on liver triacylglycerol or biochemistry in healthy overweight men. Gastroenterology 2013; 145 (5) 1016-1025.e2
    CrossrefPubMedGoogle Scholar
  • 131 Ngo Sock ET, Lê KA, Ith M, Kreis R, Boesch C, Tappy L. Effects of a short-term overfeeding with fructose or glucose in healthy young males. Br J Nutr 2010; 103 (7) 939-943
    CrossrefPubMedGoogle Scholar
  • 132 Silbernagel G, Machann J, Unmuth S , et al. Effects of 4-week very-high-fructose/glucose diets on insulin sensitivity, visceral fat and intrahepatic lipids: an exploratory trial. Br J Nutr 2011; 106 (1) 79-86
    CrossrefPubMedGoogle Scholar
  • 133 Livesey G, Taylor R, Livesey H, Liu S. Is there a dose-response relation of dietary glycemic load to risk of type 2 diabetes? Meta-analysis of prospective cohort studies. Am J Clin Nutr 2013; 97 (3) 584-596
    CrossrefPubMedGoogle Scholar
  • 134 Ma XY, Liu JP, Song ZY. Glycemic load, glycemic index and risk of cardiovascular diseases: meta-analyses of prospective studies. Atherosclerosis 2012; 223 (2) 491-496
    CrossrefPubMedGoogle Scholar
  • 135 Thomas D, Elliott EJ. Low glycaemic index, or low glycaemic load, diets for diabetes mellitus. Cochrane Database Syst Rev 2009; (1) CD006296
    PubMedGoogle Scholar
  • 136 Valtueña S, Pellegrini N, Ardigò D , et al. Dietary glycemic index and liver steatosis. Am J Clin Nutr 2006; 84 (1) 136-142, quiz 268–269
    PubMedGoogle Scholar
  • 137 Micha R, Wallace SK, Mozaffarian D. Red and processed meat consumption and risk of incident coronary heart disease, stroke, and diabetes mellitus: a systematic review and meta-analysis. Circulation 2010; 121 (21) 2271-2283
    CrossrefPubMedGoogle Scholar
  • 138 Fung TT, van Dam RM, Hankinson SE, Stampfer M, Willett WC, Hu FB. Low-carbohydrate diets and all-cause and cause-specific mortality: two cohort studies. Ann Intern Med 2010; 153 (5) 289-298
    CrossrefPubMedGoogle Scholar
  • 139 Bernstein AM, Sun Q, Hu FB, Stampfer MJ, Manson JE, Willett WC. Major dietary protein sources and risk of coronary heart disease in women. Circulation 2010; 122 (9) 876-883
    CrossrefPubMedGoogle Scholar
  • 140 Bao Y, Han J, Hu FB , et al. Association of nut consumption with total and cause-specific mortality. N Engl J Med 2013; 369 (21) 2001-2011
    CrossrefPubMedGoogle Scholar
  • 141 Larsen TM, Dalskov SM, van Baak M , et al; Diet, Obesity, and Genes (Diogenes) Project. Diets with high or low protein content and glycemic index for weight-loss maintenance. N Engl J Med 2010; 363 (22) 2102-2113
    CrossrefPubMedGoogle Scholar
  • 142 Aller EE, Larsen TM, Claus H , et al. Weight loss maintenance in overweight subjects on ad libitum diets with high or low protein content and glycemic index: the DIOGENES trial 12-month results. Int J Obes 2014; 38 (12) 1511-1517
    CrossrefPubMedGoogle Scholar
  • 143 Shai I, Schwarzfuchs D, Henkin Y , et al; Dietary Intervention Randomized Controlled Trial (DIRECT) Group. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med 2008; 359 (3) 229-241
    CrossrefPubMedGoogle Scholar
  • 144 Serra-Majem L, Roman B, Estruch R. Scientific evidence of interventions using the Mediterranean diet: a systematic review. Nutr Rev 2006; 64 (2 Pt 2) S27-S47
    CrossrefPubMedGoogle Scholar
  • 145 Estruch R, Ros E, Salas-Salvadó J , et al; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 2013; 368 (14) 1279-1290
    CrossrefPubMedGoogle Scholar
  • 146 Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med 2003; 348 (26) 2599-2608
    CrossrefPubMedGoogle Scholar
  • 147 Sofi F, Cesari F, Abbate R, Gensini GF, Casini A. Adherence to Mediterranean diet and health status: meta-analysis. BMJ 2008; 337: a1344
    CrossrefPubMedGoogle Scholar
  • 148 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 (1) 138-143
    CrossrefPubMedGoogle Scholar
  • 149 Fraser A, Abel R, Lawlor DA, Fraser D, Elhayany A. A modified Mediterranean diet is associated with the greatest reduction in alanine aminotransferase levels in obese type 2 diabetes patients: results of a quasi-randomised controlled trial. Diabetologia 2008; 51 (9) 1616-1622
    CrossrefPubMedGoogle Scholar
  • 150 Trovato FM, Catalano D, Martines GF, Pace P, Trovato GM. Mediterranean diet and non-alcoholic fatty liver disease: the need of extended and comprehensive interventions. Clin Nutr 2015; 34 (1) 86-88
    CrossrefPubMedGoogle Scholar
  • 151 Kontogianni MD, Tileli N, Margariti A , et al. Adherence to the Mediterranean diet is associated with the severity of non-alcoholic fatty liver disease. Clin Nutr 2014; 33 (4) 678-683
    CrossrefPubMedGoogle Scholar
  • 152 Hung T, Sievenpiper JL, Marchie A, Kendall CW, Jenkins DJ. Fat versus carbohydrate in insulin resistance, obesity, diabetes and cardiovascular disease. Curr Opin Clin Nutr Metab Care 2003; 6 (2) 165-176
    CrossrefPubMedGoogle Scholar
  • 153 Keys A, Menotti A, Karvonen MJ , et al. The diet and 15-year death rate in the seven countries study. Am J Epidemiol 1986; 124 (6) 903-915
    PubMedGoogle Scholar
  • 154 Kromhout D ; Seven Countries Study Research Group. Food consumption patterns in the Seven Countries Study. Ann Med 1989; 21 (3) 237-238
    CrossrefPubMedGoogle Scholar
  • 155 Parola M, Muraca R, Dianzani I , et al. Vitamin E dietary supplementation inhibits transforming growth factor beta 1 gene expression in the rat liver. FEBS Lett 1992; 308 (3) 267-270
    CrossrefPubMedGoogle Scholar
  • 156 Harrison SA, Torgerson S, Hayashi P, Ward J, Schenker S. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 2003; 98 (11) 2485-2490
    CrossrefPubMedGoogle Scholar
  • 157 Sanyal AJ, Chalasani N, Kowdley KV , et al; NASH CRN. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 2010; 362 (18) 1675-1685
    CrossrefPubMedGoogle Scholar
  • 158 Lavine JE, Schwimmer JB, Van Natta ML , et al; Nonalcoholic Steatohepatitis Clinical Research Network. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA 2011; 305 (16) 1659-1668
    CrossrefPubMedGoogle Scholar
  • 159 Miller III ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005; 142 (1) 37-46
    CrossrefPubMedGoogle Scholar
  • 160 Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev 2008; (2) CD007176
    PubMedGoogle Scholar
  • 161 Dietrich M, Jacques PF, Pencina MJ , et al. Vitamin E supplement use and the incidence of cardiovascular disease and all-cause mortality in the Framingham Heart Study: Does the underlying health status play a role?. Atherosclerosis 2009; 205 (2) 549-553
    CrossrefPubMedGoogle Scholar
  • 162 Bjelakovic G, Gluud LL, Nikolova D , et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev 2014; 1: CD007470
    PubMedGoogle Scholar
  • 163 Durup D, Jørgensen HL, Christensen J, Schwarz P, Heegaard AM, Lind B. A reverse J-shaped association of all-cause mortality with serum 25-hydroxyvitamin D in general practice: the CopD study. J Clin Endocrinol Metab 2012; 97 (8) 2644-2652
    CrossrefPubMedGoogle Scholar
  • 164 Michaëlsson K, Baron JA, Snellman G , et al. Plasma vitamin D and mortality in older men: a community-based prospective cohort study. Am J Clin Nutr 2010; 92 (4) 841-848
    CrossrefPubMedGoogle Scholar
  • 165 Amer M, Qayyum R. Relationship between 25-hydroxyvitamin D and all-cause and cardiovascular disease mortality. Am J Med 2013; 126 (6) 509-514
    CrossrefPubMedGoogle Scholar
  • 166 Ju SY, Jeong HS, Kim H. Blood vitamin D status and metabolic syndrome in the general adult population: a dose-response meta-analysis. J Clin Endocrinol Metab 2014; 99 (3) 1053-1063
    PubMedGoogle Scholar
  • 167 Pittas AG, Chung M, Trikalinos T , et al. Systematic review: vitamin D and cardiometabolic outcomes. Ann Intern Med 2010; 152 (5) 307-314
    CrossrefPubMedGoogle Scholar
  • 168 Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab 2007; 92 (6) 2017-2029
    CrossrefPubMedGoogle Scholar
  • 169 Seida JC, Mitri J, Colmers IN , et al. Clinical review: Effect of vitamin D3 supplementation on improving glucose homeostasis and preventing diabetes: a systematic review and meta-analysis. J Clin Endocrinol Metab 2014; 99 (10) 3551-3560
    CrossrefPubMedGoogle Scholar
  • 170 Roth CL, Elfers CT, Figlewicz DP , et al. Vitamin D deficiency in obese rats exacerbates nonalcoholic fatty liver disease and increases hepatic resistin and Toll-like receptor activation. Hepatology 2012; 55 (4) 1103-1111
    CrossrefPubMedGoogle Scholar
  • 171 Manna P, Jain SK. Vitamin D up-regulates glucose transporter 4 (GLUT4) translocation and glucose utilization mediated by cystathionine-γ-lyase (CSE) activation and H2S formation in 3T3L1 adipocytes. J Biol Chem 2012; 287 (50) 42324-42332
    CrossrefPubMedGoogle Scholar
  • 172 Ding N, Yu RT, Subramaniam N , et al. A vitamin D receptor/SMAD genomic circuit gates hepatic fibrotic response. Cell 2013; 153 (3) 601-613
    CrossrefPubMedGoogle Scholar
  • 173 Fedirko V, Duarte-Salles T, Bamia C , et al. Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: a nested case-control study. Hepatology 2014; 60 (4) 1222-1230
    CrossrefPubMedGoogle Scholar
  • 174 Finkelmeier F, Kronenberger B, Köberle V , et al. Severe 25-hydroxyvitamin D deficiency identifies a poor prognosis in patients with hepatocellular carcinoma - a prospective cohort study. Aliment Pharmacol Ther 2014; 39 (10) 1204-1212
    CrossrefPubMedGoogle Scholar
  • 175 Sharifi N, Amani R, Hajiani E, Cheraghian B. Does vitamin D improve liver enzymes, oxidative stress, and inflammatory biomarkers in adults with non-alcoholic fatty liver disease? A randomized clinical trial. Endocrine 2014; 47 (1) 70-80
    Google Scholar
  • 176 Freedman ND, Park Y, Abnet CC, Hollenbeck AR, Sinha R. Association of coffee drinking with total and cause-specific mortality. N Engl J Med 2012; 366 (20) 1891-1904
    CrossrefPubMedGoogle Scholar
  • 177 Catalano D, Martines GF, Tonzuso A, Pirri C, Trovato FM, Trovato GM. Protective role of coffee in non-alcoholic fatty liver disease (NAFLD). Dig Dis Sci 2010; 55 (11) 3200-3206
    CrossrefPubMedGoogle Scholar
  • 178 Gutiérrez-Grobe Y, Chávez-Tapia N, Sánchez-Valle V , et al. High coffee intake is associated with lower grade nonalcoholic fatty liver disease: the role of peripheral antioxidant activity. Ann Hepatol 2012; 11 (3) 350-355
    PubMedGoogle Scholar
  • 179 Birerdinc A, Stepanova M, Pawloski L, Younossi ZM. Caffeine is protective in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2012; 35 (1) 76-82
    CrossrefPubMedGoogle Scholar
  • 180 Bambha K, Wilson LA, Unalp A , et al; Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). Coffee consumption in NAFLD patients with lower insulin resistance is associated with lower risk of severe fibrosis. Liver Int 2014; 34 (8) 1250-1258
    CrossrefPubMedGoogle Scholar
  • 181 Molloy JW, Calcagno CJ, Williams CD, Jones FJ, Torres DM, Harrison SA. Association of coffee and caffeine consumption with fatty liver disease, nonalcoholic steatohepatitis, and degree of hepatic fibrosis. Hepatology 2012; 55 (2) 429-436
    CrossrefPubMedGoogle Scholar
  • 182 Johnson S, Koh WP, Wang R, Govindarajan S, Yu MC, Yuan JM. Coffee consumption and reduced risk of hepatocellular carcinoma: findings from the Singapore Chinese Health Study. Cancer Causes Control 2011; 22 (3) 503-510
    CrossrefPubMedGoogle Scholar
  • 183 Schnabl B, Brenner DA. Interactions between the intestinal microbiome and liver diseases. Gastroenterology 2014; 146 (6) 1513-1524
    CrossrefPubMedGoogle Scholar
  • 184 Paolella G, Mandato C, Pierri L, Poeta M, Di Stasi M, Vajro P. Gut-liver axis and probiotics: their role in non-alcoholic fatty liver disease. World J Gastroenterol 2014; 20 (42) 15518-15531
    Google Scholar
  • 185 Eslamparast T, Poustchi H, Zamani F, Sharafkhah M, Malekzadeh R, Hekmatdoost A. Synbiotic supplementation in nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled pilot study. Am J Clin Nutr 2014; 99 (3) 535-542
    CrossrefPubMedGoogle Scholar
  • 186 Lim SS, Vos T, Flaxman AD , et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380 (9859) 2224-2260
    CrossrefPubMedGoogle Scholar
  • 187 Xu G, Sui X, Liu S , et al. Effects of insufficient physical activity on mortality and life expectancy in Jiangxi province of China, 2007-2010. PLoS ONE 2014; 9 (10) e109826
    CrossrefPubMedGoogle Scholar
  • 188 Franco OH, de Laet C, Peeters A, Jonker J, Mackenbach J, Nusselder W. Effects of physical activity on life expectancy with cardiovascular disease. Arch Intern Med 2005; 165 (20) 2355-2360
    CrossrefPubMedGoogle Scholar
  • 189 Hu FB, Sigal RJ, Rich-Edwards JW , et al. Walking compared with vigorous physical activity and risk of type 2 diabetes in women: a prospective study. JAMA 1999; 282 (15) 1433-1439
    CrossrefPubMedGoogle Scholar
  • 190 Lynch J, Helmrich SP, Lakka TA , et al. Moderately intense physical activities and high levels of cardiorespiratory fitness reduce the risk of non-insulin-dependent diabetes mellitus in middle-aged men. Arch Intern Med 1996; 156 (12) 1307-1314
    CrossrefPubMedGoogle Scholar
  • 191 Tanasescu M, Leitzmann MF, Rimm EB, Willett WC, Stampfer MJ, Hu FB. Exercise type and intensity in relation to coronary heart disease in men. JAMA 2002; 288 (16) 1994-2000
    CrossrefPubMedGoogle Scholar
  • 192 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 (4) 1105-1112
    CrossrefPubMedGoogle Scholar
  • 193 Shephard RJ, Johnson N. Effects of physical activity upon the liver. Eur J Appl Physiol 2015; 115 (1) 1-46
    CrossrefPubMedGoogle Scholar
  • 194 Perseghin G, Lattuada G, De Cobelli F , et al. Habitual physical activity is associated with intrahepatic fat content in humans. Diabetes Care 2007; 30 (3) 683-688
    CrossrefPubMedGoogle Scholar
  • 195 Goodpaster BH, Katsiaras A, Kelley DE. Enhanced fat oxidation through physical activity is associated with improvements in insulin sensitivity in obesity. Diabetes 2003; 52 (9) 2191-2197
    CrossrefPubMedGoogle Scholar
  • 196 Kemp BE, Mitchelhill KI, Stapleton D, Michell BJ, Chen ZP, Witters LA. Dealing with energy demand: the AMP-activated protein kinase. Trends Biochem Sci 1999; 24 (1) 22-25
    CrossrefPubMedGoogle Scholar
  • 197 Houten SM, Auwerx J. PGC-1alpha: turbocharging mitochondria. Cell 2004; 119 (1) 5-7
    CrossrefPubMedGoogle Scholar
  • 198 Lim JY, Oh MA, Kim WH, Sohn HY, Park SI. AMP-activated protein kinase inhibits TGF-β-induced fibrogenic responses of hepatic stellate cells by targeting transcriptional coactivator p300. J Cell Physiol 2012; 227 (3) 1081-1089
    CrossrefPubMedGoogle Scholar
  • 199 Zelber-Sagi S, Nitzan-Kaluski D, Goldsmith R , et al. Role of leisure-time physical activity in nonalcoholic fatty liver disease: a population-based study. Hepatology 2008; 48 (6) 1791-1798
    CrossrefPubMedGoogle Scholar
  • 200 Krasnoff JB, Painter PL, Wallace JP, Bass NM, Merriman RB. Health-related fitness and physical activity in patients with nonalcoholic fatty liver disease. Hepatology 2008; 47 (4) 1158-1166
    CrossrefPubMedGoogle Scholar
  • 201 Kistler KD, Brunt EM, Clark JM, Diehl AM, Sallis JF, Schwimmer JB ; NASH CRN Research Group. Physical activity recommendations, exercise intensity, and histological severity of nonalcoholic fatty liver disease. Am J Gastroenterol 2011; 106 (3) 460-468, quiz 469
    CrossrefPubMedGoogle Scholar
  • 202 St George A, Bauman A, Johnston A, Farrell G, Chey T, George J. Independent effects of physical activity in patients with nonalcoholic fatty liver disease. Hepatology 2009; 50 (1) 68-76
    CrossrefPubMedGoogle Scholar
  • 203 Hallsworth K, Fattakhova G, Hollingsworth KG , et al. Resistance exercise reduces liver fat and its mediators in non-alcoholic fatty liver disease independent of weight loss. Gut 2011; 60 (9) 1278-1283
    CrossrefPubMedGoogle Scholar
  • 204 Zelber-Sagi S, Buch A, Yeshua H , et al. Effect of resistance training on non-alcoholic fatty-liver disease a randomized-clinical trial. World J Gastroenterol 2014; 20 (15) 4382-4392
    CrossrefPubMedGoogle Scholar
  • 205 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 (4) 1287-1295
    CrossrefPubMedGoogle Scholar
  • 206 Slentz CA, Bateman LA, Willis LH , et al. Effects of aerobic vs. resistance training on visceral and liver fat stores, liver enzymes, and insulin resistance by HOMA in overweight adults from STRRIDE AT/RT. Am J Physiol Endocrinol Metab 2011; 301 (5) E1033-E1039
    CrossrefPubMedGoogle Scholar
  • 207 Davidson LE, Hudson R, Kilpatrick K , et al. Effects of exercise modality on insulin resistance and functional limitation in older adults: a randomized controlled trial. Arch Intern Med 2009; 169 (2) 122-131
    CrossrefPubMedGoogle Scholar
  • 208 Bateman LA, Slentz CA, Willis LH , et al. Comparison of aerobic versus resistance exercise training effects on metabolic syndrome (from the Studies of a Targeted Risk Reduction Intervention Through Defined Exercise - STRRIDE-AT/RT). Am J Cardiol 2011; 108 (6) 838-844
    CrossrefPubMedGoogle Scholar
  • 209 Baumgartner RN. Body composition in healthy aging. Ann N Y Acad Sci 2000; 904: 437-448
    PubMedGoogle Scholar
  • 210 Davison KK, Ford ES, Cogswell ME, Dietz WH. Percentage of body fat and body mass index are associated with mobility limitations in people aged 70 and older from NHANES III. J Am Geriatr Soc 2002; 50 (11) 1802-1809
    CrossrefPubMedGoogle Scholar
  • 211 Frontera WR, Hughes VA, Fielding RA, Fiatarone MA, Evans WJ, Roubenoff R. Aging of skeletal muscle: a 12-yr longitudinal study. J Appl Physiol (1985) 2000; 88 (4) 1321-1326
    CrossrefPubMedGoogle Scholar
  • 212 Elia M, Ritz P, Stubbs RJ. Total energy expenditure in the elderly. Eur J Clin Nutr 2000; 54 (Suppl. 03) S92-S103
    CrossrefPubMedGoogle Scholar
  • 213 Gale CR, Martyn CN, Cooper C, Sayer AA. Grip strength, body composition, and mortality. Int J Epidemiol 2007; 36 (1) 228-235
    CrossrefPubMedGoogle Scholar
  • 214 Hong HC, Hwang SY, Choi HY , et al. Relationship between sarcopenia and nonalcoholic fatty liver disease: the Korean Sarcopenic Obesity Study. Hepatology 2014; 59 (5) 1772-1778
    CrossrefPubMedGoogle Scholar
  • 215 Nomura T, Ikeda Y, Nakao S , et al. Muscle strength is a marker of insulin resistance in patients with type 2 diabetes: a pilot study. Endocr J 2007; 54 (5) 791-796
    CrossrefPubMedGoogle Scholar
  • 216 Ratziu V, Bellentani S, Cortez-Pinto H, Day C, Marchesini G. A position statement on NAFLD/NASH based on the EASL 2009 special conference. J Hepatol 2010; 53 (2) 372-384
    CrossrefPubMedGoogle Scholar
  • 217 Villareal DT, Banks M, Sinacore DR, Siener C, Klein S. Effect of weight loss and exercise on frailty in obese older adults. Arch Intern Med 2006; 166 (8) 860-866
    CrossrefPubMedGoogle Scholar
  • 218 Pattullo V, Duarte-Rojo A, Soliman W , et al. A 24-week dietary and physical activity lifestyle intervention reduces hepatic insulin resistance in the obese with chronic hepatitis C. Liver Int 2013; 33 (3) 410-419
    CrossrefPubMedGoogle Scholar
  • 219 Astell-Burt T, Feng X, Kolt GS. Is neighborhood green space associated with a lower risk of type 2 diabetes? Evidence from 267,072 Australians. Diabetes Care 2014; 37 (1) 197-201
    CrossrefPubMedGoogle Scholar
  • 220 Astell-Burt T, Feng X, Kolt GS. Green space is associated with walking and moderate-to-vigorous physical activity (MVPA) in middle-to-older-aged adults: findings from 203 883 Australians in the 45 and Up Study. Br J Sports Med 2014; 48 (5) 404-406
    CrossrefPubMedGoogle Scholar
  • 221 Astell-Burt T, Feng X, Mavoa S, Badland HM, Giles-Corti B. Do low-income neighbourhoods have the least green space? A cross-sectional study of Australia's most populous cities. BMC Public Health 2014; 14: 292
    CrossrefPubMedGoogle Scholar
  • 222 Parmenter K, Waller J, Wardle J. Demographic variation in nutrition knowledge in England. Health Educ Res 2000; 15 (2) 163-174
    CrossrefPubMedGoogle Scholar
  • 223 Wardle J, Steptoe A. Socioeconomic differences in attitudes and beliefs about healthy lifestyles. J Epidemiol Community Health 2003; 57 (6) 440-443
    CrossrefPubMedGoogle Scholar
  • 224 Academy of Medical Royal Colleges. Measuring up the medical profession's prescription for the nation's obesity crisis. London: Academy of Medical Royal Colleges; 2013
    Google Scholar
  • 225 Williams R, Aspinall R, Bellis M , et al. Addressing liver disease in the UK: a blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol, obesity, and viral hepatitis. Lancet 2014; 384 (9958) 1953-1997
    CrossrefPubMedGoogle Scholar