Får vi for lidt protein? Fra Overlevelse til Sundhed

Får vi for lidt protein? Fra Overlevelse til Sundhed Arne Astrup, Head, professor, MD, Dr.Med.Sci. Department of Human Nutrition, University of Copenhagen

Conclusions from protein Summit, Charleston May 2007 There is adequate rationale to revisit protein intake recommendations and explore increasing the RDA. The recent DRI macronutrient report and Dietary Guidelines for Americans retained recommendations for minimum protein intakes on the basis of nitrogen balance. This approach is controversial and recognized by the National Academy of Science to have substantial practical limitations and problems. Thus, other methods and endpoints to define protein requirements should be considered.

Conclusions from protein Summit, Charleston May 2007 Endpoints including muscle mass, strength and metabolic function in relation to protein intake within the context of meeting other nutrients in the diet should be integrated into studies designed to determine dietary guidelines. The minimal amount of protein to avoid a progressive loss of muscle is likely to be well below the optimal level to maximize all aspects of muscle. Measures of body composition to assess muscle mass; determination of insulin sensitivity from oralglucose-tolerance curves to assess metabolic function of muscle; and dietary protein intake as an indicator of nutritional status are methods that should be validated and used in large epidemiological studies.

Conclusions from protein Summit, Charleston May 2007 Beneficial effects of protein intake above the current RDA recommendations include weight management, management/prevention of diabetes/insulin resistance, lipid control and the prevention of osteoporosis. Sarcopenia is a public health issue that will affect an increasingly significant proportion of the population in the near future. Consumption of adequate protein is an important factor in its prevention and/or treatment. Lean muscle mass builds strength and promotes active daily life and may ultimately improve overall health.

Conclusions from protein Summit, Charleston May 2007 Potential issues with high protein intake involve bone health, kidney stones, urea production among other conditions. The implication of dietary protein as a causative in these conditions is not definitively supported by scientific reports to date.

Weight Management facts and stats Role of protein in satiety Role of muscle mass in obesity prevention Thermogenic effect of protein High-protein diets and weight loss and regain Definition of high-protein inconsistent in studies; examples High-protein diets and renal function.

Energy Balance Equation Energy Stores = Energy Intake - Energy Expenditure 1% difference over 1 year ENERGY INTAKE ENERGY EXPENDITURE Intake = 1,000,000 kcal Expenditure 990,000 kcal Weight Gain = 1.2-1.7 kg

Components of Daily Energy Expenditure 100 SMR % of Daily Energy Expenditure Expenditure100 75 50 25 0 NEAT & Unrestricted Activity SPA Thermic effect of food Ventilated Hood Ventilated Hood Respiratory Chamber Respiratory Chamber Double Labelled Water Double Labelled Water Arousal BMR Methods

Measurement of energy expenditure: Respiration chamber

Energy expenditure (energy requirements) of normal weight, overweight and obese subjects 24-hour energy expenditure (kcal/day) 4000 3000 2000 1000 Normal weight Obesity 40 50 60 70 80 90 100 110 120 Body weight (kg) Moderate activity level Low activity level Underreporting bias Self-reported energy intake Astrup, Clin. Endocrinol. Metab.. 13: 1999, 109-120 120

Variability in Resting Metabolic Rate Percentage of Explained Variance 90 80 0 Within Subject Family FFM FM Age Sex Method T3, NA, UCP

R 2 235 kvinder og 78 mænd målt i respirationskammer på FHE ved forskellige forsøg. Å61

Relation between fat-free mass (FFM) and 24-h energy expenditure (EE) adjusted for differences in duration of exercise and spontaneious physical activity Klausen et al. Am J Clin Nutr 1997;65:895-907

Relation between fat mass (FM) and 24-h energy expenditure (EE) adjusted for differences in duration of exercise, spontaneious physical activity and FFM Klausen et al. Am J Clin Nutr 1997;65:895-907

Recommended Nutrient Content of a Weight-Reducing Diet Carbohydrate >55% Protein 15% Fat <30% 30% 8%-10% <10% 10% Saturated fatty acids Polyunsaturated fatty acids <15% Monounsaturated fatty acids Calories: 500-1000 kcal/d reduction Cholesterol: <300 mg/d Fiber: 20-30 g/d Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults The Evidence Report. Obes Res. 1998;6 (suppl 2).

Proposed Hierarchy of Satiety Protein leucine fructose fiber Carbohydrate mct sucrose Fat Need hypothesis-driven studies to determine differences

Effect on satiety How satisfied do you feel? Visual analogue scale (cm) 10 9 8 7 6 5 4 3 2 1 0 I cannot eat another bite I am completely empty 8 10 12 14 16 18 20 22 24 Time High-Protein meals Normal protein meals

Highly satiating effect of protein Animal model: Bensaid et al., Phys & Behav, 2002. Protein is more potent than carbohydrate for reducing appetite in rats. Bensaid et al., Phys & Behav, 2003. A high-protein diet enhances satiety without conditioned taste aversion in the rat. Humans: Latner & Schwartz, Appetite, 1999. The effects of a highcarbohydrate, high protein or balanced lunch upon later food intake and hunger ratings. Westerterp-Plantenga et al., AJCN, 1999. The appetizing effect of anaperitif in overweight and normal-weight humans. fat diets measured in a respiration chamber.

Measurementof energy expenditure: Respiration chamber

Measurementof energy expenditure: Respiration chamber

Thermogenic effect of protein

Thermogenic effect of protein vs. carbohydrate Identical parameters - Energy (to energy balance = 0) - Fat (30 energy-%) Intervention parameters -Protein vs Carbohydrate: 30 vs 10 protein-e% -PORK vs SOY: 20 E% pork vs 20 E% soy protein Mikkelsen et al. Am J Clin Nutr 2000;72:1135-41

Results 24 hour energy expenditure PORK: 13.11 ± 1.00 MJ/d a (3.9%) SOY: 12.86 ± 0.98 MJ/d b (1.9%) CARBO: 12.62 ± 0.98 MJ/d c BASELINE: 12.52 ± 1.06 MJ/d b,c Pork versus Soy: 1.9 % (P < 0.05) Mikkelsen et al. Am J Clin Nutr 2000;72:1135-41

Intervention studies: Does the effects of protein on appetite and energy expenditure translate into weight loss?

METHODS Subjects: 50 overweight and obese (25 in control group) men (n=12) and women (n=38) age: 19-55 years BMI: 26-34 kg/m 2 Free from illness (CVD, T2D etc.) One-year randomised dietary intervention, comparing an ad libitum fat-reduced diet (30% of energy) either high in protein (25% of energy, HP) or medium in protein (12% of energy, MP) Normal fat control group (only 6 months)

DIETARY INTERVENTION SUPERMARKET MODEL DIETARY COUNSELLING FREE LIVING 0 6 12 24 MONTH Anthropometry, DEXA & Blood samples Body weight Diet Registration Compliance Assessment

Protein versus Carbohydrate

SHOP MODEL: 6 months with all food provided for free

Skov et al. Int. J. Obes 1999;23:528-536

Skov et al. Int. J. Obes 1999;23:528-536

COMPLIANCE 24-h Urinary Nitrogen 18 (n=23) Medium-protein High-protein 16 (n=23) 24-h UN (g) 14 12 10 8 (n=22) (n=18) 6 0 1 2 3 4 5 6 7 8 9 10 11 12 Duration (month) Due A et al. Int J Obes 2004;28:1283-90.

Due A et al. Int J Obes 2004;28:1283-90. DROP OUT RATE Month 0-6 (Free provision of food): 2 subjects dropped out in each group (NS) Month 6-12 (dietary counseling): 7 (28%) in the MP group dropped out 2 (8%) in the HP group dropped out (p=0.07) Month 24 (follow up): 19 (76%) in the MP group and 14 (56%) in the HP group no longer attended (NS)

A randomized 6-month trial on two fat-reduced diets: Low protein versus high protein Weight loss and fat loss Skov et al. Int. J. Obes 1999;23:528-536

A randomized 12-month trial on Low protein versus high protein Body weight (kg) 90 LP seca HP seca C seca LP dxa HP dxa C dxa 80 0 0 10 20 30 40 50 60 70 80 90 100 110 Dietary intervention Follow-up Weight maintenance Duration (weeks) Skov AR et al. Int J Obes 2002; 23: 528-36

Proportion of subjects having lost and maintained >5 and 10 kg body weight after 6, 12 and 24 months of dietary intervention.

CHANGES IN WAIST 0 6 12 (cm) -2-4 -6-8 Medium-protein High-protein -10-12 P=0.004 P=0.0006 Due A et al. Int J Obes 2004;28:1283-90.

CHANGES IN INTRA-ABDOMINAL FAT (cm²) 0-5 -10-15 -20-25 -30-35 -40 6 12 P=0.002 P=0.03 Medium-protein High-protein Due A et al. Int J Obes 2004;28:1283-90.

Due A et al. Diabetes, Obesity and Metabolism, 2005, 7, 223-9.

Mean total plasma homocysteine at baseline and after 3 and 6 mo of the intervention 1 Low-protein group (n = 23) High-protein group (n = 23) Control group (n = 14) µmol/l Baseline 3 mo 10.9 ± 1.5 12.1 ± 2.3 10.8 ± 1.4 10.6 ± 0.7 9.7 ± 0.7 9.8 ± 1.0 6 mo 10.4 ± 0.8 9.6 ± 0.7 10.3 ± 1.0 1 x ± SEM. There were no significant differences between groups by ANOVA. Haulrik N, Toubro S, Dyerberg J, Stender S, Skov AR, Astrup A. Am J Clin Nutr 2002;76:1202-6.

A randomized 12-month trial on Low protein versus high protein Skov AR, Toubro S, Bülow J, Krabbe K, Parving HH, Astrup A. Int J Obes 1999;23:1170-1177.

A randomized 12-month trial on Low protein versus high protein Skov AR, Toubro S, Bülow J, Krabbe K, Parving HH, Astrup A. Int J Obes 1999;23:1170-1177.

A randomized 12-month trial on Low protein versus high protein: BMC 3 6 Duration of dietary intervention (months) Skov AR, Haulrik N, Toubro S, Mølgaard C, Astrup A. Obes. Res. 2002;10:432-8.

CONCLUSION A fat-reduced diet high in protein (25 E%) Is superior to a similar fat-reduced high-carbohydrate diet over 12 months to reduce body fat (-4.6 vs - 3.1 kg) and intra-abdominal fat mass. The high-protein diet did not have any adverse effect on risk factors of cardiovascular disease, osteoporosis, or renal function

Protein power

Low Carbohydrate vs Low Fat (Completers analysis) 0 Weight Loss (%) -5-10 Low-Fat Low Carb -15 0 3 6 9 12 Foster et al NEJM 2003; Months of Diet

RDI: At least 130 g carbohydrate/day Atkits: 50 g/d Adverse effects: Muscle cramps, headache, weakness, diarheea etc. No need to reduce carbohydrate intake that dramatic Astrup, Larsen, Harper. The Lancet. 2004; 364: 897-9.

Institute of Medicine, USA Despite the association between red meat and certain tumor types, no clear role for protein (in cancer) has yet emerged The current state of the literature, therefore, does not permit any recommendations of upper limit to be made on the basis of cancer risk

US recommendations AMDR (DRI, Institute of Medicine, USA) Protein: Adults: 10-35% Older children: 10-30% Smaller children: 10-20 %

Institute of Medicine, USA There is no evidence to suggest that the AMDR for protein should be at levels below the RDA for protein (~10 E%) for adults There is insufficient data to suggest an upper limit for an AMDR for protein To complement the AMDR for fat (20-35 E%), and carbohydrate (45-65E%) for adults, protein intakes may range from 10-35E% to ensure a nutritionally adequate diet

Discussion Points questions that remain to be answered Optimal protein (%) for weight control and inproved CV and T2D risks Protein sources Adverse effects (renal, bone, but more important cancer risk (BW vs. direct, dairy/red meat) Mechanism behind satiety/thermogenesis

Diet, Obesity and Genes European Commission 6 th framework: Food Quality & Safety Coordinator: Wim Saris (NUTRIM, Maastricht)

RTD Line 1: Dietary Intervention Budget: 3.7 mio. Dietary Intervention in whole families Ad libitum diet most effective against weight (re)gain Long-term (6/12 mo) large-scale intervention study (700 adults randomised plus 350-1050 children 1-3 children/family) Factorial Design (5 groups): Low GI High GI High/low Glycaemic Index High/normal Protein Control Normal protein 1 2 High protein 3 4 Control 5

Disclosures A receive honoraria for consulting and speakers fee from several food companies I sit in several advisory boards for food and weight control companies My department and research group receive funding from >100 food companies My university have files ~5 patents with me as a coinventor