1 www.diogenes-eu.org Contract no. FP6-2005-513946

The Diogenes Study – Food Research in the service of HEALTH

Thomas Meinert Larsen Associate Professor Department of Human Nutrition Centre for Advanced Food Technology Faculty of Life Sciences University of Copenhagen

WORK SHOP: ”Food Research and Food Production – priority setting weith smart specialisation strategies” Brussels, Belgium, October 13, 2011

2 www.diogenes-eu.org

DiOGenes

The basics

•  34 partners, in 14 European countries •  Includes 3 food industry multinationals and 5 SMEs •  € 20.1 million total budget, of which € 14.5 million EU

funding •  5-year project, started 1st January 2005 •  Co-ordinator: University of Maastricht, The Netherlands

•  Executive Director: Prof. Wim HM Saris

DG Research European Commission

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FOOD QUALITY AND SAFETY

DiOGenes Diet, Obesity and Genes

External Advisory Group

Project Board Project Coordinator

General Assembly Project Secretariat

PM

DIDT

DIDT Coordinator

RTD lines Coordinator

RTD2 RTD3 RTD4 RTD5 RTD1

: Optimizing GI and Protein content of the diet: RCT Intervention : Identification gene-nutrients weight regulation/predictors weight variation : Epidemiological approach to assess current risk of weight gain/data Hub : Lifestyle and psycho-social aspects of food intake : To develop food products that support weight management : Dissemination, Innovation, Demonstration, Training

RTD1

DIDT

RTD2

RTD3

RTD4

RTD5

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The DiOGenes research lines

RTD 3 Population studies

RTD 5 Food technology

RTD 1 Diet intervention

RTD 2 Genetics/Transcriptomics/ Proteomics/Metabolomics

Data Hub

RTD 6

An Integrated Project of the EU 6th Framework Programme for

Research and Technological Development (2005-2009) Co-ordinator Wim Saris, University of Maastricht

RTD 4 Psychological predictors & behaviour

Slide 5

Can protein and glycemic index be used as tools to help regulate body weight ?

Starting weight

Time

Natural course of weight gain

Increasing success

Body weight (kg)

Weight loss phase

Weight maintenance phase

years months

Slide 6

Total Fat (E%) 25-35

Total Carbohydrate (E%) 55-60

Total Protein (E%) 10-20

Total Saturated Fat (E%) <10

Total Monounsaturated Fat (E%) 5-15

Total Polyunsaturated Fat (E%) 5-10

Added Sugar (E%) <10

WHAT IS IN THE CURRENT DIETARY GUIDELINES ?

”Based on best available

evidence”

7 www.diogenes-eu.org Contract no. FP6-2005-513946

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The Clinical Evidence of GI - RCTs GIycemic index Duration n Diets Body weight

change (LGI vs. others)

Ad libitum Raben et al. (1997) 2 weeks 20 nw High-sucrose (LGI) vs. high-starch (HGI) Increase

Bouche et al. (2002) 5 weeks 11 ow LGI vs. HGI NS (FM decrease)

Ebbeling et al. (2003) 6 months 16 ob LGL vs. energy-restricted LF BMI + FM decrease

Sloth et al. (2004) 10 weeks 45 ow Low-GI vs. HGI NS

McMillan-Price et al. (2006) 12 weeks 129 ow + ob LGI, HC vs. HGI, HC vs. LGI, HP vs. HGI, HP NS

Moses et al. (2006) 26 weeks 62 nw (pregnant) LGI vs. high-fibre, moderate-to-high GI Decrease (birth weight)

Energy-restricted Wolever et al. (1992) 6 weeks 6 ow + ob LGI vs. HGI foods NS

Slabber et al. (1994) 12 weeks 30 ow + ob LGI vs. HGI NS

Slabber et al. (1994) 12 weeks 16 ow + ob LGI vs. HGI Decrease

Agus et al. (2000) 6 days 10 ow + ob LGI vs. HGI NS

Spieth et al. (2000) 4 months 107 ow LGI vs. LF Decrease

Raatz et al. (2005) 12 weeks 29 ob HGI vs. LGI vs. HF NS

Thompson et al. (2005) 48 weeks 90 ob HGI, high-dairy vs. LGI, high-dairy NS

BMI: body mass index, FM: fat mass, HC: high-carbohydrate, HF: high-fat, HGI: high-glycemic index, LF: low-fat, LGI: low-glycemic index, LGL: low-glycemic load, NS: non-significant, nw: normal-weight, ob: obese, ow: overweight

No clear / consistent picture…. maybe too small sample size

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The Clinical Evidence of HP - RCTs

No clear / consistent picture…. maybe too small sample size

High protein High protein

High protein

High protein

Low GI (& GL)

High fat Low GI Low GI

Low GI

Low carb

High Protein

A number of the most known (and used) diets already take us of high protein (and low GI) as a central element

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Diogenes takes use of the most reliable scientific methods:

Intervention

Cohort Case-Control

Cross-sectional studies Correlation studies

DIOGENES-RCT WP1

DIOGENES-EPI WP3

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Diogenes diet intervention Multicentre trial in 8 European cities

Copenhagen (Astrup A, Larsen TM) Maastricht (van Baak M, Saris W) Berlin (Pfeiffer A) Cambridge (Jebb S) Prague (Kunesova M) Pamplona (Martinez JA) Sofia (Hanjieva S) Heraklion (Kafatos A)

The study is registered with www.ClinicalTrials.gov number NCT00390637

13 www.diogenes-eu.org Contract no. FP6-2005-513946

•  Family (adult + child)

•  One adult with BMI > 27 (preferably higher)�

•  Healthy

•  1-3 children (preferably iso-BMI > 25)

•  Adults obtain > 8% weight loss during 8 w LCD

Inclusion criteria

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Weight loss on 8 week LCD

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Diet Composition, ad libitum (Targeted)

∆ of 15 GI units

LP/LGI LP/HGI HP/LGI HP/HGI Control

Protein E% 13 (8-18) 13 (8-18) 25 (20-30) 25 (20-30) 15 (10-20)

CHO + fibre E% 60 (55-65) 60 (55-65) 48 (43-53) 48 (43-53) 60 (55-65)

Fat E% 27 (22-32) 27 (22-32) 27 (22-32) 27 (22-32) 25 (20-30)

Glycemic index low high low high medium

∆ of 15 GI units

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Low protein, high GI

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Details on methodology published in: Larsen TM, Dalskov S, van Baak M et al. Obes Rev 2010; 11(1):76-91. Moore CS, Lindroos AK, Kreutzer M et al. Obes Rev 2010; 11(1):67-75.

Study design

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Diogenes diet intervention

Shop model - shopping 1-2 times weekly to aim at 100% food supply - control the macronutrient composition at every session

Dietary guidance - individual / group meetings with the dietician (8 sessions) - written information about the specific intervention diet - no specific emphasis on physical activity

19 New England Journal of Medicine, published online Nov 25, 2010.

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Patient flow

COMPLETERS: 548 Subjects

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Major end-point: Drop-out rate Assignment to: HP vs. LP diets

associated with 20.0% lower drop out rate,

p=0.05.

Assignment to: LGI vs. HGI diets

associated with 22.6% lower drop-out rate,

p<0.02.

Drop-out/Randomised (%)

LP/LGI 44/150 (29.3)ab

LP/HGI 58/155 (37.4) b

HP/LGI 35/159 (22.0) a

HP/HGI 48/155 (31.0) ab

CTR 40/154 (26.0) ab

Overall 225/773 (29.1)

The superscripts a and b are indicating if two groups are significantly different (p<0.05) in a logistic regression model after adjustment for centre, centre type (shop/intervention), gender, BMI at post-LCD, BW loss during LCD, family type, and age at screening. This is the case if they do not share a common letter

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Compliance to Glycemic Index (shop centres)

50525456586062646668

baseline 4 weeks 26 weeks

LP/LGILP/HGIHP/LGIHP/HGIcontrol

* * *

* * *

~8 units

FOOD Diaries: All 8 centres: 5 GI units difference

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Compliance to dietary protein intake as assessed by 24 hour urinary nitrogen excretion

FOOD Diaries: All 8 centres: 5.4 E% difference

Pre-LCD

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Results: Body weight changes

• Overall weight regain was relatively low (0.56 kg), and that the overall weight loss in completers as therefore quite high (10.6 kg)

• Completers analysis (N=548) (kg, mean, 95% CI);

LP/LGI (N=106): 0.3 (-0.74, 1.40) LP/HGI (N=97): 1.7 (0.48, 2.87) HP/LGI (N=124): -0.4 (-1.70, 0.93) HP/HGI (N= 107): 0.6 (-0.65, 1.78) CTR (N=114): 0.8 (-0.17, 1.86) Overall group difference p-value: 0.01 (ANCOVA)

• The assignment to LP and HGI diets completer analysis (N=548), linear regression model) produced higher weight regain of LP: 1.14 kg (0.23,2.06) (p=0.02) HGI: 1.09 (0.18, 2.00) (p=0.02)

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Completers at Week 26

ITT

In an ITT-analysis (N=773, mixed linear model) the weight regain was 0.93 kg (95 % CI: 0.31; 1.55, p=0.003) lower by HP than LP, and 0.95 kg (0.33; 1.57, p=0.003) lower by LGI than HGI diets.

* P < 0.05 for difference from 0;

# P < 0.01 HP vs other diets, no effect of GI or protein*GI interaction; gender and initial weight as covariates

SHOP CENTRES (N=204, at 6 month): Better weight maintenance in high protein groups

0

0.5

1

1.5

2

2.5

3

3.5

4

1 2 3 4 5

weig

ht

ch

an

ge (

kg

)

LP/LGI LP/HGI HP/LGI control HP/HGI

*

*

*

# # ~1.8 kg

Van Baak, M et al. Abstract, ECO 2008. Manuscript with 1y data in preparation

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HP/LGI diet the most promising for weight control in children

Papadaki et al. Pediatrics, vol 126, no. 5, November 2010

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Conclusions from Diogenes-RCT

•  A low GI diet high in calories from protein prevented weight regain after a 12 % weight loss.

•  The high-protein/low GI diet was

associated with lower drop out rate

The Diogenes cohort (RTD 3.1)

•  89432 participants (37125 men and 52307 women) •  Originated from 5 EPIC cohorts (Germany, Italy, the Netherlands, UK

and Denmark)  with baseline dietary information

 repeated anthropometric measures of weight and waist circumference

 Free of prevalent diabetes, cancer and CHD at baseline •  Baseline age 53 (20-78) years

• mean follow-up time of 6.5 (1.9-12.5) years

Overall aim •  To investigate the associations between diet (with main focus on protein and

GI/GL) and subsequent changes in weight or waist circumference in a large prospective cohort study

Intake of animal or plant protein (per 150 kcal) and yearly weight changes (g/y)

Adjusted for baseline age, height, weight, follow-up time, changes in smoking status, education, physical activity, and HRT and menopause status (women)

Overall est: Animal protein 56 g/y (95 %CI: 27 to 86) per 150 kcal

Overall est: Plant protein 18 g/y (95 %CI: -39 to 96) per 150 kcal

Halkjær et al. Int J Obes (Lond)2011:35:1104-13.

Protein from food groups and yearly changes in weight or waist circumference

Weight changes (g/year) Waist changes (cm/year)

Per 150 kcal Estimate (95% CI) Estimate (95% CI)

Protein from

Red/proc meat 81.0 (46.8 to 115.3) 0.11 (0.04-0.17)

Poultry 114.9 (49.8 to 180.0) 0.04 (-0.05 to 0.13)

Fish 40.8 (-16.9 to 98.5) -0.08 (-0.15 to -0.0)

Dairy 13.2 (-26.2 to 52.7) -0.05 (-0.08 to -0.02)

Estimates are summed estimates based on the random effects meta-analysis model (overall sum for men and women)

Halkjær et al. Int J Obes (Lond)2011:35:1104-13.

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Additional challenges & obstacles

ROME 2006

Dias 33

Potential environmental effects of 1 kg

of food or drinks

Is a high protein diet environmentally

sustainable?

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Can we increase recommendations for protein intake, given the global environmental constraints?

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Next steps for research ? •  Resolve conflicting evidence •  Is the HP/LGI diet effective in the long term (> 1 year) ?

•  Weight change and risk of T2D & CVD ?�

•  Is the HP/LGI diet safe in the long term ? •  Effects on kidney, bone, cancer etc. ?�

•  Can the HP/LGI be maintained in the long term (>1 year) ? •  Is it palatable enough? •  Is it compatible with local traditions/cuisine?�

•  Is HP/LGI diet compatible with visions of environmental sustainability? •  Can vegetable sources of protein replace animal sources? •  Can technological development lower the environmental impact of � producing animal sources of protein?

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Acknowledgements

….DIOGENES Partners ….Dieticians & other technical staff ….all the food sponsors. ….and the study participants (for their patience)

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Thank you for your attention