Food and Obesity. Professor Mike Lean. Human Nutrition, University of Glasgow. Zurich June 14 th 2018

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1 Food and Obesity Professor Mike Lean Human Nutrition, University of Glasgow Zurich June 14 th 2018

2 Disclosures: Research/conference support and advisory boards: (Novo Nordisk, Orexigen, Janssen, Cambridge Weight Plan) Medical consultancy for Counterweight Ltd I have shares costing 10 in Eat Balanced Ltd I have never tasted any cola drink, or owned a TV Acknowlegments to paper co-authors: Sue Roberts (Tufts) Arne Astrup (Copenhagen)

3 What is obesity? Obesity is defined as a disease process characterised by excessive body fat accumulation with multiple organ-specific consequences. SIGN 2010

4 Who is affected by obesity? BMI >30 Age Age Age % 9% 3% Age Data from EUROSTAT 2014

5 Considerations To guide individuals for prevention or treatment of obesity. To guide population-directed recommendations. Foods/ food groups/ meals/ complete diet/ psycho-social context : Energy balance and body weight/ fat mass Metabolic complications of obesity - eg Type 2 Diabetes (obesity disease process, not just BMI>30) Physical complications of obesity (eg sleep apnea is aggravated by late night eating and by alcohol) Can advice apply to all? Equally? Or do some identifiable subgroups need different advice even be disadvantaged by general advice?

6 Four elements of obesity & weight management

7 Change in energy stores = EI EE Obesity, (disease process of excess body-fat accumulation), develops (only, and inescapably) if foods provide a net excess of calories above energy expended over time. Individuals with obesity have higher energy expenditure, and metabolic rate falls with food restriction and weight loss.

8 Relatively low RMR or 24hEE predicts greater weight gain Ravussin et al NEJM 1988

9 Metabolic rate and 24h EE change with changes in body weight Leibel et al Am J Clin Nutr 1995

10 Generally non-contentious factors affecting obesity and energy balance Obesity, (disease process of excess body-fat accumulation), develops if foods provide a net excess of calories above energy expended over time. Individuals with obesity have higher energy expenditure, and metabolic rate falls with food restriction and weight loss. Reaching energy-balance and weight stability depends on food supply, social/ cultural influences on food choices/ eating, and habitual PA. Obesity pandemic cannot be explained by changes in physiology/genes. Global per capita food supply has risen by 450 kcal/day, with cheaper oils and animal products, SSBs, and larger portion-sizes, more available food, and increased eating via reduced sleep, stress, screens/tv. Social marketing has normalised new behaviours, such as consuming energy-dense sweet snacks and drinks between meals. Occupational PA has all but disappeared, and the leisure industry promotes inactivity more than physical activity.

11 Data from UN FAO,

12 Rising per-capita food consumption in US Cereals fats and sugar Fats Drenowski, Am J Prev Med 2004

13 Energetic impacts of nutrients On a mixed diet c.10% of metabolisable energy must be expended on digestion and storage (Westerterp 2004) Metabolisable calories available to the body (kcal/g) All fats 9 Alcohol 7 Proteins 4 Digestible carbohydrates (including sugars) 3.75 Soluble dietary fibre (fermentable) 2 Insoluble dietary fibre (non-fermentable) 0

14 Energetic impacts of nutrients On a mixed diet c.10% of metabolisable energy must be expended on digestion and storage (Westerterp 2004) Metabolisable calories available to the body (kcal/g) Diet-induced thermogenesis (SDA) All fats 9 0-3% Alcohol % Proteins % Digestible carbohydrates (including sugars) % Soluble dietary fibre (fermentable) 2 - Insoluble dietary fibre (non-fermentable) 0 -

15 Excess total fat and calorie intake if foods contain more fat Subjects ate similar weights of food on 3 diets, unaware of different fat contents On high fat diet they went into positive energy and fat balance. Stubbs et al, 1995

16 Gluttony or sloth? Failures of a willpower-centric view of obesity National behavioural recommendations for weight management are largely based on application of willpower and poorly accepted as they are seen as difficult and ineffective Uniquely for major diseases causing multiple pathologies, the prevailing perception of obesity as a cost to healthcare and burden on society, rather than disabling & distressing Insufficient investment in effective treatments for obesity, thus numerous profitable nonevidence-based approaches are promoted, with inflated claims to meet popular desire for easy weight control Intense media coverage of commercial treatments that are not evidence-based or are minimally effective contribute to mass confusion and undermine professional advice The view that food companies are not responsible for the obesity epidemic leaves them free to create and promote an increasing variety of tempting obesogenic products Less obesogenic food products tend to be more expensive per calorie, which is a barrier to population shifts towards healthier eating habits Willpower centricity leads to an underdevelopment of population directed measures that can avoid individual accountability Government funding for obesity treatment is less than for other diseases relative to numbers of resulting disabilities or deaths

17 Eat less or move more? RCTs find little effect on weight loss: Increasing PA is hard with obesity. More value for prevention, reducing appetite, so energy balance at lower weight. Possible PA threshold for energy balance that most do not meet. Regulated zone Mayer, 1956 Tsofliou Lean et al, 2003

18 Special effect foods: are all calories equal? Certain foods are widely portrayed as having special importance for obesity: as causes eg. SSBs, added sugar, refined grains, or as protective (eg dairy foods, yogurt and cheese, nuts). These are useful markers of diets and lifestyles which promote or protect against obesity, but they do not of themselves have unique properties to affect energy balance. Confusion between diet composition for fitness, general or cardiovascular health, and for a healthy/normal weight The word healthy has no meaning for foods (Buckton et al 2015)

19 Food craving and eating "addiction" Assertions that certain foods or nutrients (eg chocolate, sugar) are addictive like specific chemicals (nicotine, caffeine, cocaine or alcohol) are not supported by evidence for addiction. While people find specific foods more desirable, evidence does not support true addictions to specific foods. Instead, normal physiological addiction to eating can be focussed or corrupted. The impact of adding caffeine, known to be addictive, on consumptions of foods and drinks is unclear.

20 Two Brain Centres Are Involved in Regulating Hunger and Food Cravings Mesolimbic Reward System 1-3 Controls motivation, reward, & reinforcement associated with survival activities (eg, eating, reproduction) Involved in cravings in response to food-related cues Dopamine & opioid signaling play important roles, altered in obesity Mesolimbic reward system can override the hypothalamic hunger system increasing the consumption of highly palatable foods 4 Hypothalamic Hunger System 5 Integrates peripheral signals of hunger, fullness, & fat stores to modulate feeding behavior and energy balance Appetite suppression by leptin [adipose], Appetite stimulation by ghrelin [stomach, duodenum]). Signals can be altered in obesity (eg, leptin resistance) 1. Morton GJ et al. Nature. 2006;443: Billes SK et al. Pharmacol Res. 2014;84: Reichelt AC, et al. Br J Pharmacol. 2015;172: Volkow ND et al. Obes Rev. 2013;14: Yu JH et al. Diabetes Metab J. 2012;36:

21

22 Specific foods and obesity: the example of sugar Sugar provides 3.75 kcal/g, and has a relatively low GI. Not essential to human diets, but aids palatability Consumption, particularly in sweetened drinks between meals and in snack foods combined with fat (9 kcal/g), has risen with rising rates of obesity

23 Dietary sugars and body weight: systematic review and metaanalyses of randomised controlled trials and cohort studies (Te Morenga L, Mallard S, Mann J. BMJ 2012) Overweight/obesity in children associated with sugar-sweetened beverages consumption (not free sugars)

24 Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies (Te Morenga L 1, Mallard S, Mann J. BMJ 2012) Effect of increasing free sugars on measures of body fatness in adults: <1kg Funnel plot of randomised ad libitum trials in adults: evidence of publication bias In studies comparing increased intake (higher sugars) with usual intake (lower sugars).

25 Dietary sugars and body weight: systematic review and metaanalyses of randomised controlled trials and cohort studies (Te Morenga L, Mallard S, Mann J. BMJ 2012) Iso-energetic exchanges of free sugars with other carbohydrates or other macronutrient sources No effect on body weight So any effect is to do with patterns of eating and drinking (not the sugars)

26 Specific foods and obesity: the example of sugar Conclusions Among free living people involving ad libitum diets, intake of free sugars or sugar sweetened beverages is a determinant of body weight. The change in body fatness that occurs with modifying intakes seems to be mediated via changes in energy intakes, since isoenergetic exchange of sugars with other carbohydrates was not associated with weight change.

27 Adiposity adjustment In diet research Prospective associations of beverage consumption with RR of incident type 2 diabetes * Unadjusted for adiposity. Adjusted for adiposity: SSB association reduced 5% (using BMI). (Imamura et al. BMJ 2015)

28 SSBs and BMI-adjusted risk of diabetes in EPIC-Interact (Europe) Romaguera-Bosch et al. Diabetologia 56:1520, 2013

29 Association between SSB & T2DM attenuated by adiposity: reduced ORs (black bars) and increased p values (grey) Data from Scottish Health Survey, n = 5187 Yi Jing, Thang Han, Majid Alkhalaf, Michael Lean, Eur J Nutr 2018

30 Reducing dietary carbohydrate or fat? RCTs and meta-analyses demonstrate minimal or no overall differences in long-term effects on body weight between high- and low-carbohydrate/fat diets When small differences are seen they favour lower carb/ lower glycaemic load

31 EI EE = change in energy stores Under metabolic ward conditions, weight change is determined dietary energy, irrespective of nutrient composition: Weight loss is entirely predicted by calorie deficit Fat/ Carbohydrate content is unimportant A calorie is a calorie Bortz W, 1967, 1968

32

33

34 Medical weight loss in primary care for overweight & obese non-diabetic reduces all risk factors at 1-2 years (Naude et al meta-analysis 2014)

35 Meta-analysis of controlled feeding experiments High carb vs Low carb diets effects on Body Fat Guo & Hall 2017

36 Meta-analyses of the meta-analyses of low vs high carb diets 3-year citations & - AMSTAR Quality - Difference in weight loss rho = -0.9, p = rho = -0.9, p = Churuangsuk et al 2018

37 Low Carbohydrate diets deplete body glycogen stores, so cause extra weight loss by water loss 19 subjects Prolonged heavy arm & leg exercise, Then 3-day low-carb diet. Then 4-day carbohydrate-rich diet: Body weight increased 2.4 kg Total body water increased 2.2 kg Arm/leg muscle glycogen increased 4.5/2.6 to 19.9/16.9 g/kg Total glycogen stored c.500 g Therefore 3-4 g of water is stored with each gram glycogen 2 kg difference Olsson and Saltin, 1970 Acta Physiol Scand 80(1) 11 18

38 Carbohydrate/ cereal/ gluten avoidance?? Risk of thiamine deficiency, beri-beri (McKenna Lean et al BMJ 2013) Healthy bowel needs a healthy microbiome, which depends on carbohydrate

39 Low-Carb vs High-Carb diets for T2DM Body Weight HbA1c No significant effects for LDLc, HDLc, TC, BP, or attrition rate. TG fell 0.13mmol/l more on LCD (A-M Aas, at DNSG 2017)

40 To maintain weight loss, behaviours must counteract environment and physiology Obesogenic Environment Physical environment Food environment Educational environment Cultural environment Social environment Social Marketing (normalised behaviours) The obesity epidemic Biology& Physiology Satiety signals - fall with weight loss (Leptin, PYY, CCK, amylin, insulin, GLP-1) Orexigenic signals - rise with weight loss (ghrelin) Metabolic Rate - falls with energy restriction & with weight loss Leslie et al 2007; Sumithran et al 2011; Maclean 2011; Leibel et al 1995;

41 Meta-analysis of non-surgical trials with 1-year follow-up: BEST RESULTS WITH MOST RAPID WEIGHT LOSS VLCD/ TDR reliably achieves 15kg weight loss 15 kg 80 studies, n = 26,455, 69% completers (Franz et al JADA 2007)

42 Copenhagen Weight Loss in Knee Osteoarthritis trial: more liberal TDR allowed more patients to do well Little difference in weight loss 415kcal VLED vs. 810kcal LED weeks (D) 1500kcal/d part food/part formula [average one formula meal daily] (E) Knee exercises group (C) Control no intervention Body Weight (kg) weeks 810kcal/d 98.0 liquid formula 415kcal/d liquid formula weeks 1200kcal Part food/part formula 2 meals /day ) D = structured food/formula maintenance programme Time (weeks) n=96 per group n=64 per group (Christensen, Bliddal et al, secondary care, dietitian managed)

43 DIRECT: Results: weight changes over 12 months kg +1.0 kg +1.9 kg 830 kcal: 61%E CHO 13% fat, 26% protein Food-based diet +/- meal replacements 50%E carbohydrate, 35% fat, 15% protein

44 DiRECT: Remissions by 12m weight loss: entire study population 86.1% 57.1% 0% 6.7% 33.9% 10 kg loss: 73% are in remission None 0-5 kg 5-10 kg kg 15 kg Weight loss at 12 months HbA1c <48 mmol/mol, off anti-diabetes drugs for >2 months Lean et al Lancet 2017

45 Personalised dietary management, based on genetic or metabolic status??

46 Individual differences in response to GL - in RCT Median split of insulin secretion 30 min after a 75 g OGTT Pittas et al. Diabetes Care 2005;28:12:2939 Low GL High GL

47 DiOGenes 2017: Subjects With Prediabetes + Low FPI Regain Less Weight On A Low CHO/ LowGI Diet Variables: Fasting Plasma Glucose + Fasting Plasma Insulin Favors High CHO/GI Diet Favors Low CHO/GI Diet *P < 0.05 vs. zero # P < 0.05 vs glycemic/insulin groups 53

48 19/06/ Enterotypes and personalized nutrition Prevotella type Bacteroides type Diet Whole grain fiber (e.g. arabinoxylans, beta-glucans) Carbohydrate modulation/acarbose (e.g. bifidogenic prebiotics) Effect Weight-loss Improved glycemic response Improved glycemic response Improved bile-acid metabolism...weight-loss?

49 Large 12m RCT (Low v High Carb) No evidence to support personalised nutrition Gardner et al JAMA 2018

50 Achieving Low Glycaemic Load Diets: -- Reduce total carbohydrate or Choose slow-release low GI carbohydrates or Combine with other foods and nutrients eg. Fats Amylose-rich non-digestible carbohydrate Legumes = Traditional diets - Mediterranean, Nordic, Japanese etc.

51 Evolution, weight cycling and paleo diets Modern so-called paleo diets: meat and dairy foods, eliminating grains, beans, soy, some vegetable oils and sugar were unlikely to have been usual for human ancestors

52 Neanderthal man.brutish and short Omnivore Huge capacity for starch digestion

53 Tsimane hunter-gatherer tribe, in Bolivia, have no heart disease or diabetes High (72% E) carbohydrate diet 15,00-17,000 steps per day Kaplan et al. Lancet 2017

54 What policy actions are required? Tax SSBs? Reduce sweetness? Tax fats? Act against misleading marketing Enforce EU Unfair Commercial Practices Laws (Lean, BMJ 2008) Control advertising and event sponsoring Safe cycling and walking paths Green environments

55 Take-Home Messages 1. The balance between calorie intake and calorie expenditure determines body weight and fat changes. Foods affect total energy consumption by modifying appetite, or energy expenditure via diet-induced thermogenesis. 2. Overweight people generally consume more food energy (calories) than thinner people to maintain their higher body weight. 3. Hierarchy of metabolisable calories/g: fats=9, alcohol=7, protein=4, digestible carbohydrates (including sugars)=3.75, soluble dietary fibre c.2 4. Any calorie restriction diet plan which an individual is able to adhere to will cause weight loss; but different dietary patterns influence adherence to different degrees in different people. Both Art and Science are important. 5. Weight loss maintenance is harder than weight loss, as it requires a permanent new normal lower-calorie eating. higher-calorie lifestyle, within the same food/ physical/ social/ cultural educational environments.

56 Best bet? Current evidence favours moderately low glycemic-load Mediterranean or Nordic diets, but individuals may do better with Japanese style etc. Well-conducted RCTs (eg N of 1 crossover design: BMJ 2015) to evaluate the preferences and responses of free-living individuals in real-life settings have not yet been conducted.

57 Basic Copyright Notice & Disclaimer 2018 This presentation is copyright protected. All rights reserved. You may download or print out a hard copy for your private or internal use. You are not permitted to create any modifications or derivatives of this presentation without the prior written permission of the copyright owner. This presentation is for information purposes only and contains non-binding indications. Any opinions or views expressed are of the author and do not necessarily represent those of Swiss Re. Swiss Re makes no warranties or representations as to the accuracy, comprehensiveness, timeliness or suitability of this presentation for a particular purpose. Anyone shall at its own risk interpret and employ this presentation without relying on it in isolation. In no event will Swiss Re be liable for any loss or damages of any kind, including any direct, indirect or consequential damages, arising out of or in connection with the use of this presentation.

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