A practical guide for lifestyle modification in NAFLD

Transcription

1 A practical guide for lifestyle modification in NAFLD Shira Zelber-Sagi R.D. Ph.D Dept. of Gastroenterology Tel Aviv Medical Center School of Public Health, Haifa University Israel

2 The mission for today Macronutrients & NAFLD Total calories Different types of fat Carbohydrates and sugars Dietary patterns Coffee Obesogenic diet

3 Sobrecases H., Diabetes & Metabolism 2010 Hyper-caloric diets Overfeeding with saturated fat or fructose influences liver fat within days & prior to weight gain! 65% increased E 30% increased E

4 Dietary fats Amount and composition Independently of body fatness

5 MRI Effect of hyper-caloric high-fat diets PUFA compared with SFAs Double-blind RCT, 7 weeks 39 normal-weight Body weight modestly increased, not different between groups Dietary intake change PUFA SFA P Energy, kcal 632± ± Fat, E% 5±6 5± Rosqvist F., Diabetes 2014 SFAs palm oil n-6 PUFAs (sunflower oil)

6 Effect of iso-caloric high-fat diets PUFAs compared with SFAs RCT, 10 weeks 67 obese Body weight modestly increased, not different between groups Bjermo H., Am J Clin Nutr 2012

7 Effects of iso-caloric diets MUFA compared with a standard high carbohydrate diet RCT, 8-weeks 45 type-2 diabetes patients high-carbohydrate (52% vs. 40%) high-mufa diet (28% vs. 16%/ kcal) CHO -4% MUFA -29% MUFA -25% Body weight remained -6% stable Bozzetto L., Diabetes Care 2012

8 The Mediterranean is superior to low fat diet in RCTs Clinical High outcomes Olive oil 4 tbsp/day nuts handful/day Fish 3 /wk Diabetes Legumes 3 /wk Fruits &Vegetables Fat - 40% /kcal, mostly CVD MUFA and ω3 PUFA NAFLD Low in Metabolic profile Soda drinks Sweets Red Blood and processed pressure meats Carbohydrate- 40% /kcal Lipid profile glucose CRP Salas-Salvadó J., Ann Intern Med 2014 Ryan MC., Journal of Hepatology 2013 Nordmann AJ., The American Journal of Medicine 2011 Estruch R., N Engl J Med 2013

9 The Mediterranean diet improves hepatic steatosis Nutrient Mediterranean Diet Low Fat Diet Fat Carbohydrate Olive oil & nuts Fish & meat 40% /kcal MUFA and ω3 PUFA 40% /kcal Daily Fish 3/w, meat 3/w 30% /kcal ω6 PUFA 50% /kcal None Fish 2/week, meat daily -39% -7% RCT 12 NAFLD patients 6-week diets 1-2 kg weight loss Ryan MC, Journal of Hepatology 2013

10 Mechanism of the benefit of the Mediterranean diet in NAFLD Lipid metabolism MUFAs Increases hepatocyte fatty acid oxidation Reduces hepatic lipogenesis Decreases serum triglycerides levels Inflammation Anti-inflammatory effect Suppression of pro-inflammatory cytokines ω3 PUFA Insulin sensitivity Improves insulin sensitivity Paniagua JA., J Am Coll Nutr 2007; Paniagua JA., Diabetes Care, 2007; Fung T., Circulation 2009

11 Omega-3 supplementation in NAFLD Double-blind RCTs Author Supplement mg/day Duration (M) Sample Steatosis NASH Fibrosis Argo CK, J of Hepatology EPA & DHA NASH Yes No No Sanyal AJ, Gastroenterology EPA NASH No No No Scorletti E, Hepatology EPA & DHA NAFLD Yes - No fibrosis scores Nobili V, Arch Dis Child or 500 DHA 6 60 children NAFLD Yes - - Fish oil had no independent effect on glucose or insulin levels in most studies

12 Omega-3 supplementation in NAFLD Decreases liver fat (B1) Practice guidelines Journal of Hepatology 2016 The optimal dose required has not been determined It is possible that DHA and EPA have different effects Not recommended by the EASL (2016) or AASLD (2012) guidelines for the specific treatment of NAFLD/ NASH 3 g/d is the American Heart Association s upper dose for triglyceride reduction & safe dose by the FDA Nobili V., Critical Reviews in Clinical Laboratory Sciences 2016 Kris-Etherton PM., Circulation 2002

13 Fish consumption and risk of hepatocellular carcinoma: meta-analysis Eleven studies Cohort or case control highest vs. lowest category NCC nested case control PCC population-based case control HCC hospital-based case control Min Gao., Cancer Causes Control 2015 Fish consumption was associated with 35 % reduction in HCC risk

14 n-3 polyunsaturated fatty acids, and risk of hepatocellular carcinoma: meta-analysis Eleven studies cohort or case control n-3 PUFA n-3 polyunsaturated fatty acids may lower cancer risk by suppressing mutations inhibiting cellular proliferation inducing cell apoptosis decreased production of free radicals and ROS Effect on insulin sensitivity n-6 alpha-linolenic acid (ALA) Animal models- purified n-3 fatty acids has slowed the growth of HCC Min Gao., Cancer Causes Control 2015

15 Lustig RH., NATURE 2012 Added sweeteners pose dangers to health that justify controlling them like alcohol

16 NAFLD according to beverages consumption in the Framingham cohort CT in 2634 participants None Consumers 1 serving/mo- <1 serving/wk 1 serving/wk- <1 serving/d 1 servings/d p for trend Sugar-sweetened beverages 1 (Ref) 1.16 ( ) 1.32 ( ) 1.61 ( ) 0.04 Diet soda 1 (Ref) 1.02 ( ) 1.12 ( ) 0.91 ( ) 0.52 Adjusted for: energy intake, macronutrients intake and BMI Ma J., Journal of Hepatology 2015

17 Sucrose-sweetened beverages increase liver fat 47 overweight subjects Randomized to 4 different test drinks 1 L/d for 6 mo P = 0.01 Regular Cola Milk Carbohydrate (g/l) Fat (g/l) % Milk Water Energy (kcal/d) Cola Diet cola Maersk M., Am J Clin Nutr 2012

18 3 2.5 The good and the bad nutrients for HCC Prospective cohort studies Independent of BMI ,206 Europeans Fedirko V., Annals of Oncology ,296 Japanese Sawada N., Gastroenterology Americans (NHNES) Ioannou GN., Hepatology Total sugar Fibers n-3 rich fish EPA DHA Cholesterol per 50 g/day per 10 g/day Q g/d Q5 511 mg/day

19 Increased Intake of Vegetables, But Not Fruit, Reduces Risk for Hepatocellular Carcinoma: A Meta-analysis Cohort and case-control studies 19 studies involving 1,290,045 participants and 3912 cases of HCC The inverse association did not change regardless of history of hepatitis, alcohol smoking, or energy intake Forest plot of vegetable intake and HCC risk for high vs. low consumption The risk of HCC decreases by 8% for every 100 g/d increase in vegetable intake Yang Y., Gastroenterology 2014

20 Advanced-Glycation End-Products (AGEs) glycotoxins Reaction of sugars (glucose and mainly fructose) with fat, amino acids, proteins and nucleic acids Exogenic AGEs from processed food Serum levels correlate with the amount ingested Protein peptide Associated with metabolic alterations Oxidative stress Insulin resistance & DM Cardiovascular disease Associated with liver damage Steatosis NASH Activation of HSCs HCC Sugar molecule Zelber-Sagi S., submitted Iwamoto K., J Gastroenterol 2008 Hyogo H., J Gastroenterol Hepatol 2007 Yilmaz Y., Clinical Biochemistry 2009 Moy KA., Hepatology 2013

21 AGE content in common foods and beverages Food Sprite Cereal (granola) Cake Beverage Orange juice Classic Coca Cola Duck skin (roasted) Diet Coke Cooking condition Temperature C Content, g/cup Carbohydrate Time min AGEs content Fold increase post/before cooking X4 X59 X101 AGEs, units/cup Units/g of food postcooking ,400 8, ,400 6,259,000 9,500 Koschinsky T, Proc. Natl. Acad. Sci. USA 1997

22 To achieve a lower AGE diet, try the following Limit the amount of grilled and fried meats Reduce the cooking temperature Cut down on processed foods - exposed to a high cooking temperature Get more fruits and veggies - contain antioxidants

23 Alcohol and NAFLD

24 Roles of alcohol consumption in fatty liver: A longitudinal study 5297 Japanese individuals follow-up from 2004 to 2006 Fatty liver assessed by ultrasonography Men Women Moriya A., Journal of Hepatology 2015

25 Alcohol and the incidence of Hepatocellular Carcinoma in Patients with NASH 195 NASH-Cirrhosis patients, follow-up 3.2 years social alcohol intake, no more than two alcoholic drinks daily or three to six drinks daily on weekends, increased HCC risk Factors Associated with HCC in Ascha MS., HEPATOLOGY 2010

26 EASL guidelines regarding alcohol intake in NAFLD patients Strictly keep alcohol below the risk threshold (30 g, men; 20 g, women) In epidemiological surveys, moderate alcohol intake (namely, wine) below the risk threshold is associated with lower prevalence of NAFLD, NASH and even lower fibrosis at histology Total abstinence is mandatory in NASH-cirrhosis to reduce the HCC risk European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) and European Association for the Study of Obesity (EASO) Journal of Hepatology 2016

27 Coffee? Polyphenols Salomone F., Liver international 2015 Zelber-Sagi S., Liver international 2015 Anti-oxidative Anti-fibrogenic Anti-tumoral

28 Summary of studies on coffee and NAFLD Author Type of coffee Sample Steatosis Fibrosis Zelber-Sagi S All caffeinated coffee types 347 No Yes Bambha K Caffeinated and decaffcoffee 782 No Yes Anty R Regular coffee but not espresso Yes Birerdinc A Caffeine intake 41,658 Yes - Molloy JW Regular coffee 306 No Yes Catalano D Only espresso coffee 245 Yes -

29 Coffee intake & reduced incidence of liver cancer and death from chronic liver disease Prospective cohort study, 215,000 men and women 18-year follow up Hepatocellular carcinoma Chronic Liver Disease mortality Regular coffee (cups/day) RR (95% CI) Regular coffee (cups/day) RR (95% CI) Never 1.00 (Ref) Never 1.00 (Ref) < (0.88, 1.48) < (0.92, 1.41) (0.67, 1.11) (0.69, 1.04) (0.46, 0.84) (0.42, 0.69) 4 P trend 0.59 (0.35, 0.99) P trend 0.29 (0.17, 0.50) < Adjusted for: age, sex, ethnicity, education, BMI alcohol intake, smoking and diabetes Setiawan VW., Gastroenterology 2015

30 If you don't move you get fatty liver!

31 Effect of aerobic exercise training dose on liver fat 48 overweight adults, RCT, 8 weeks training Different variations of intensity and volume Control 50% VO2 peak, 60 min, 4 d/week 70% VO2 peak, 45 min, 3 d/week 50% VO2 peak, 4 5 min, 3 d/week Keating SE, J of Hepatology 2015

32 Both Resistance Training and Aerobic Training Reduce Hepatic Fat Content RCT Hepatic fat content 31 sedentary adults with type 2 diabetes & NAFLD 4-month aerobic/ resistance training 3 times/week Absolute reductions -33% -26% Bacchi E, Hepatology 2013 Relative reductions

33 Lifestyle modification & weight reduction

34 Weight Loss Through Lifestyle Modification Reduces Features of Nonalcoholic Steatohepatitis Weight-loss and changes in the fibrosis status in those with fibrosis in baseline Prospective study of 293 patients with histologically proven NASH Lifestyle changes intervention over 52 weeks Repeated liver biopsies Vilar-Gomez E., Gastroenterology 2015

35 Weight loss pyramid Weight loss 10% Fibrosis Weight loss 7% NASH Weight loss 5% Ballooning/ inflammation Weight loss 3% Steatosis Vilar-Gomez E., Gastroenterology 2015 & multiple other sources

36 Algorithm for lifestyle changes in NAFLD Obese or over-weight patient 5-10% moderate weight reduction Normal weight patient Weight maintenance (reduce weight gain) Energy restriction Nutrients Physical activity Hypo-caloric diet Tailored for the patients needs and preferences Zelber-Sagi S., Therap Adv Gastroenterol 2016 Practice guidelines Journal of Hepatology 2016 Carbohydrates Reduce added sugar Avoid sugar sweetened beverages Fats Reduce saturated/trans fat Increase n-3 PUFA & MUFA Dietary patterns Minimize processed food Adjust macronutrient composition to Mediterranean diet (B1) Aerobic 3/w (~150 min/w) Resistance 2/w Life-long behavioral strategies to facilitate adherence

37 EASL EASD EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease Recommendations Unhealthy lifestyles play a role in the development and progression of NAFLD. The assessment of dietary and physical activity habits is part of comprehensive NAFLD screening Structured programs aimed at lifestyle changes towards healthy diet and habitual physical activity are advisable in NAFLD In overweight/obese NAFLD, a 7 10% weight loss is the target of most lifestyle interventions, and results in improvement of liver enzymes and histology Dietary recommendations should consider energy restriction and exclusion of NAFLD-promoting components (processed food, and food and beverages high in added fructose). The macronutrient composition according to the Mediterranean diet Both aerobic exercise and resistance training effectively reduce liver fat. The choice of training should be tailored based on patients preferences to be maintained in the long-term Grading of evidence A C B B B Grading of recommen dations Journal of Hepatology 2016

38 My special tips Eat dark chocolate Cocoa polyphenols exert an antioxidant activity in NASH patients APT 2016 Don t eat Oreo cookies "America's favorite cookie is just as addictive as cocaine -- at least for lab rats. And just like most humans, rats go for the middle first

39 The $1,000,000 Question Which diet is best for achieving or maintaining weight loss? Reduced-calorie diets result in clinically meaningful weight loss regardless of which macronutrients they emphasize Limiting energy intake- deficit of kcal/day Ad libitum- no formal energy deficit, but lower calorie intake is achieved by restriction of particular food groups Jensen MD., 2013 AHA/ACC/TOS Guideline, Circulation 2013

40 Obligatory components of an effective lifestyle intervention 51 good quality RCTs Behavioral strategies to facilitate adherence Diet moderate caloric restriction Jensen MD, 2013 AHA/ACC/TOS Guideline, Circulation 2013

41 Obligatory components of an effective lifestyle intervention Behavioral strategies to facilitate adherence Weight Loss Maintenance Life-long challenge Diet moderate caloric restriction Jensen MD, 2013 AHA/ACC/TOS Guideline, Circulation 2013

42 Oren Shibolet Zamir Halpern Izabel Zvibel Sigal Fishman Hanny Yeshua Revital Kariv Manfred Green Muriel Webb Shiri Sherf Naomi Fliss