Health effects of sugar Fifty shades of grey between «white and pure» and «black and deadly»
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1 Health effects of sugar Fifty shades of grey between «white and pure» and «black and deadly» Dublin, M Rothko, 1962
2 L Tappy, M.D. Department of Physiology, University of Lausanne Conflicts of interest - Consultant: Isis Pharmaceuticals, USA - Research support: Nestec AG, Switzerland; Ajinomoto Co Inc, Japan - Conference fees: Ferrero, Italy - Editor of a textbook «Dietary Sugars and Health» (TBP dec 2014)
3 What is special about sugar? Why suspect that sugar is responsible for metabolc diseases? Does dietary sugar make you fat?, how? Does sugar specifically favour abdominal obesity? Is an intervention aimed at reducing sugar intake efficient for body weight control? Does sugar cause insulin resistance? Does sugar increase blood lipids? Major open questions
4 What is sugar?
5 Glucose Fructose Sucrose Starch
6 Consumption of Fructose in the USA Average daily intake: 54.7 g/day (10.2 % total energy) 25 Fructose intake (% energy) SSB fruit juices dairy whole fruits vegetables sweets grains th 10th 25th 50th 75th 90th 95th percentile Data from NHANES III Vos et al, Medscape J Med > v.10(7); 2008
7 What is special about sugar? tableau à grignotter! Copyright de l'image Charline Chargelègue
8 Sugar is composed of glucose and fructose HFCS Fruits Honey sucrose starch sucrose maltose isomaltose dextrins sucrase maltase isomaltase glucoamylase glucose glucose fructose
9 All cells can use glucose as an energy substrate Most cells can use fatty acids Glucose Fatty acids gut Starch Lipids
10 Most cells cannot use fructose as an energy substrate Fructose has first to be converted into lactate, glucose, or fatty acids in the liver Ca. 5% energy loss Fructose Glucose Lactate Fructose gut Ca. 25 % energy loss Fatty acids Fructose conversion into glucose and fatty acids comes with some energy loss
11 Conversion into glucose and oxidation are the major fates for dietary fructose Protein+Lipid + 30g Fru Protein+Lipid + 30g Fru+ 30g Glu protein fat fructose glucose protein fat fructose glucose Theytaz et al, Nutrients, 2014 % Fructose released as CO2 42% 37% % Fructose released as blood glucose 30% 21% Fructose stimulates both hepatic and intestinal denovo lipogenesis (unquantified; most likely minor)
12 De novo lipogenesis is a minor pathway for fructose disposal Am J Clin Nutr December 1, 2001 vol. 74 no ; McDevitt et al De novo lipogenesis during controlled overfeeding with sucrose or glucose in lean and obese women Lean and obese women Overfeeding with + 50% energy as sucrose during 4 days 375 g carbohydrate/day 135 g sucrose/day Fat storage: 72 g/day De novo lipogenesis 1 : g/day % de novo-synthesized palmitate on VLDL 1 Calculated based on estimated VLDL production rates
13 Why suspect that sugar is responsible for metabolic diseases?
14 Nutritional recommendations for Sugars (09/2014) EFSA 2010: no adverse effect up to 20-25% total energy; no sufficient evidence for an upper limit IOM 2002: no more than 25% total energy as added sugars AHA 2013 : added sugar intake <36 g/j (men), or <29 g/j (women) WHO (consultation 2014): limit free sugar intake to max 5%) total energy intake UK (consultation 2014): limit free sugar intake to max 5%
15
16 X-XIIIe crusades Sugar plantations in colonies Sodas, ice cream New beverages: chocolate Tea, coffee, chocolate XVI-XVIIe Modified from Johnson R J et al. Am J Clin Nutr 2007;86:
17 High Sucrose/High Fructose diets in rodents Obesity Dyslipidemia NAFLD/NASH Insulin resistance / diabetes mellitus High fructose diet as animal model of metabolic diseases Not designed to compare fructose/sucrose to other substrate Not designed to assess substrate vs energy intake
18 Does dietary sugar make you fat? How? Bartolomé Esteban Murillo, Mangeurs de patisseries, ancienne pinacothèque de Munich, huile sur toile, entre 1670 et 1682
19 Epidemiological studies: added sugar or sweetened beverages and body weight (far from exhaustive!!!) Positive association with body weight Vartanian LR et al: Effects of soft drink consumption. Am J Public Health 97: , 2007 Schulze MB et al: Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women. JAMA 292: , 2004 Troiano RP: Energy and fat intakes of children. Am J Clin Nutr 72: 1343S-1353S, Welsh JA, Cogswell ME, Rogers S, Rockett H, Mei Z, and Grummer-Strawn LM. Overweight among lowincome preschool children Pediatrics 115: e , No positive association with body weight Blum JW et al: Beverage consumption patterns in elementary school aged children across a two-year period. J Am Coll Nutr 24: 93-98, 2005 Kvaavik E et al: The stability of soft drinks intake from adolescence to adult age and the association between long-term consumption of soft drinks and lifestyle factors and body weight. Public Health Nutr 8: , 2005 Rodriguez-Artalejo F, Garcia EL, Gorgojo L, Garces C, Royo MA, Martin Moreno JM, Benavente M, Macias A, and De Oya M. Consumption of bakery products, sweetened soft drinks and yogurt among children aged 6-7 years: association with nutrient intake and overall diet quality. Br J Nutr 89: , Maillard G et al. Macronutrient energy intake and adiposity IJO (12):
20 Association between sugar and body weight: specific effect of sugar or too much of everything? Sugar Sugar Sugar Sugar
21 Relationships between Changes in Food Consumption and Weight Changes Every 4 Years Study participants included 50,422 women in the Nurses' Health Study (NHS), followed for 20 years (1986 to 2006); 47,898 women in the Nurses' Health Study II (NHS II), followed for 12 years (1991 to 2003); and 22,557 men in the Health Professionals Follow-up Study (HPFS), followed for 20 years (1986 to 2006). Mozaffarian D et al. N Engl J Med 2011;364:
22 Is a fructose calorie different from another calorie? Energy balance concept 70 kg BW 0.5 kg glycogen = kcal 6 kg protein = kcal 7 kg fat = kcal Total energy: kcal Lipids LOx Nature morte. Peter Claesz Carbs COx Prot. Energy POx
23 Body weight gain always corresponds to a positive energy balance 100 kg BW 0.5 kg glycogen = kcal 8 kg protein = kcal 25 kg fat = kcal Total energy: kcal Lipids LOx Carbs COx Prot. Ox Energy expended
24 If sugar does promote weight gain, it must cause energy balance to become positive by either - Decreasing energy expenditure - Increasing energy intake
25 Effects of fructose on energy expenditure Fructose increases post-prandial thermogenesis in lean and obese subjects 0.60 Diet-induced thermogenesis after oral glucose or fructose G F G F G F NW Ob T2DM D Simonsen et al, AJP 1990
26 Thermic effect of fructose vs glucose
27 Effects of high fructose or high glucose diets on BMR
28 Fructose does not stimulate post-prandial satiety factors in blood Teff et al, JCEM 2004
29 Effects of sugar preloads on food intake kj consumed at buffet lunch 50 g glucose, 50 g fructose, aspartame or water drink Buffet lunch with food intake monitoring 2.25h later 6 non-obese male subjects Rodin et al, AJCN 1990
30 Studies having documented a satiating effect of fructose The slowing of gastric emptying: a regulatory capacity with implications for feeding. McHugh PR et al. Am J Physiol 1979, 236:R Effects of fructose and glucose pre-loads on subsequent food intake. Spitzer L and Rodin J, Appetite 1987;8: Metabolic effects of fructose and glucose: implication for food intake. Rodin J et al. Am J Clin Nutr 1988, 47: Comparative effects of fructose, aspartame, glucose and water preloads on calorie and macronutrient intake. Rodin J. Am J Clin Nutr 1990,51: Effects of glucose and fructose solutions on food intake and gastric emptying in nonobese women.guss JL et al. Am J Physiol 1994; 267: R
31 Does sugar specifically favour abdominal obesity? Manet; le bon bock
32 Effects of high Fructose vs Glucose diets on body fat in overweight subjects Stanhope et al, J Clin Invest 2009
33 Stanhope et al, J Clin Invest 2009
34 Is an intervention aimed at reducing sugar intake efficient for body weight control? Der Völler von Georg Emanuel Opiz
35 A Randomized Trial of Sugar-Sweetened Beverages and Adolescent Body Weight Cara B. Ebbeling et al, N Engl J Med 2012; 224 overweight and obese adolescents, high SSB consumers Mean age 15 years 1-year intervention to reduce SSB consumption (home delivery of noncaloric beverages, monthly motivational telephone calls with parents and three check-in visits with participants) Primary outcome: change in BMI at 2 years
36 A Randomized Trial of Sugar-Sweetened Beverages and Adolescent Body Weight Cara B. Ebbelinget al, N Engl J Med 2012; 367: Intervention Control Change in sugar intake (g/day) 1 year - 76 ± 4-37 ± 4 2 years - 64 ± 5-44 ± 5 Change in energy intake (kcal/day) 1 year ± ± 48 2 years ± ± 54 Change in BMI (kg/m2) 1 year ± ± years ± ± 0.28 BMI (kg/m2) baseline ± ± year ± ± years ± ± 5.51 Statistically different from controls
37 Intervention Control
38 Does sugar cause insulin resistance? Le Buveur de soda; Jorge Colomina
39 Effects of Short-Term Fructose Overfeeding on Whole-Body Insulin Sensitivity Faeh D et al. Diabetes 2005;54: Copyright 2011 American Diabetes Association, Inc.
40 Fructose overfeeding decreases hepatic insulin sensitivity % inhibition of Hepatic Glucose Output Hyperinsulinemiceuglycemic clamps at ca 30 mu/l insulin Control High Fructose Effects of a 6-days fructose overfeeding (+ 3g/kg/day) * % inhibition EGP Faeh et al, Diabetes 2005
41 High Fructose decreases hepatic insulin sensitivity Relationship with IHCL? Intrahepatic fat content (% control) HISI (% control) fructose added (g/kg/day) Lecoultre et al, Obesity 2013
42 Fructose overfeeding does not decrease wholebody (muscle) insulin sensitivity Hyperinsulinemiceuglycemic clamps at ca 100 mu/l insulin Hypercaloric (+15% energy) High fructose (+1.5g/kg/d) Lê et al, AJCN 2006
43
44 Does fructose significantly impairs glucose homeostasis? Oral glucose tolerance before/after overfeeding with glucose fructose Overweight females and males 10-week supplementation with fructose or glucose drinks (ca 30% total energy expenditure) Stanhope et al, J Clin Invest 2009
45 Does fructose significantly impairs glucose homeostasis? Oral glucose tolerance before/after overfeeding with glucose fructose Overweight females and males 10-week supplementation with fructose or glucose drinks (ca 30% total energy expenditure) but effects are modest even after very high fructose intake Stanhope et al, J Clin Invest 2009
46 Does Fructose increase blood lipids? Annibale Carracci: the butcher shop. Ca 1580
47 . Fructose increases fasting TG Effects of a 1 and 4 weeks overfeeding with 1.5g fructose/kg/day (ca + 15% energy) on fasting triglycerides in healthy males Lê K et al. Am J Clin Nutr 2006;84: by American Society for Nutrition
48 . Fructose ingestion increases post-prandial TG and impairs TG clearance after a meal Teff et al, JCEM 2004
49 Effects of excess fructose or excess energy? 1,4 1,2 1 0,8 0 0,6 0,4 0,2 + 30% Fr h.cal +30% Fat h.cal 30% Fr iso % Fr h.cal +30% Fat h.cal 30% Fr iso F Theytaz et al,in prep; Sobrecases et al, 2010 Egli et al, in prep
50 What is the amount of fructose required to increase fasting plasma TG? 1,6 1,4 1,2 1 0,8 0,6 0,4 0,2 0 * * 0 0,55 1,1 1,5 3 4 g/d fructose added to % +11% +15% +30% +40% weight-maintenance diet daily energy requirements as fructose * Fructose intake (% energy) 5th 10th 25th 50th 75th 90th 95th Calculated from Lê et al, AJCN 2006, Lê et al AJCN 2009, Aeberli et al AJCN 2011, Theytaz et al Abstract ASN 2012, and Egli et al abstract ADA 2012
51 Risk of coronary heart disease by triglyceride level in men and women - The Framingham Heart Study. [Adapted from Castelli WP. Epidemiology of triglycerides: a view from Framingham. Am J Cardiol 1992; F = fasting PP= postprandial F F PP Lecoultre et al, AJCN 2014, normal-weight M, + 4 g/kg/day for 6 days) Stanhope et al, JCI 2009: overweight M and F, +25% energy requirements for 10 weeks
52 What is special about sugar? Fructose Why suspect that sugar is responsible for metabolc diseases? Epidemiological studies and common sense Does dietary sugar make you fat?, how Yes, like any other substrate eaten in excess. May increase food intake due to hedonic properties Does sugar specifically favour abdominal obesity? Awaits confirmation by additionnal studies Is an intervention aimed at reducing sugar intake efficient for body weight control? Awaits studies Does sugar cause insulin resistance? Causes hepatic insulin resistance. Does not cause muscle insulin resistance independantly of body weight gain Does Fructose increase blood lipids? Increases fasting and postprandial lipoproteins
53 Open questions Added sugars vs total sugars Definition Analytical procedures in foods Animal models Comparaison between sugars and other substrate Effects of sugars and of liquid vs solid calories on food intake Long term effects of sugars Proinflammatory? Lipotoxicity? Are hypertriglyceridemia and hepatic insulin resistance normal adaptations or early pathological events? Deleterious effects of sugars: subpopulations?
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