J. Alfredo Martínez Hernández Granada 18th sept 2013

Benefits and mechanisms of moderately high protein or

high fiber diets in body weight loss and maintenance:

The DIOGENES project

Departamento de Nutrición, Ciencias de la

Alimentación y Fisiología

Pamplona

Spain

INTRODUCCIÓN

High Prevalence

Public health Burden

Mortality cause

Hypertension, hiperinsulinemia, dislipidemias,

diabetes, cardiovascular diseases and cáncer

OBESITY PREVALENCE

Life quality impairments

Introducción

SPAIN 33% 11%

PORTUGAL 33% 9%

FRANCE 24% 7%

IRELAND 31% 8%

NETHERLANDS 29% 10%

U. K. 30% 12%

BELGIUM 31% 9%

DENMARK 31% 8%

SWEDEN 33% 7%

LUXEMBOURG 27% 9%

ITALY 30% 7% GREECE

35% 11%

GERMANY 35% 11%

AUSTRIA 32% 10%

FINLAND 33% 10%

33% OW

Genetics

Introducción

BODY FAT

EXCESS

OBESITY

DEFINICIÓN DE OBESIDAD

Environment

Lifestyle

+ + +

ENERGY

INTAKE

ENERGY

EXPENDITURE

Neuroendocrine

factors

- -

ADIPOSITY

Fatty acids

Metabolic Syndrome

Glucose Intolerance

Diabetes mellitus type II

Inflammation

Hypertension

Glucose

intolerance

Atherosclerosis

Insulin

Resistance

Endothelial

dysfunctions

Introducción

TRATAMIENTO DE LA OBESIDAD

Negative Energy

Balance

Weight and fat loss

RISK FACTORS IMPROVEMENT

Objetive

intake

Energy expenditure

Introducción

OBESITY TREATMENT

Nutritional therapies Lifestyle Adaptation

Physical Activity

programmes

Pharmacological approaches

Surgery

1º

2º

3º

Introducción

DIETS

Low Carb vs High

protein diets

High carb / low fat diets

GI

VLCD 400-1000 kcal

Products,………

Capsules, powders, teas…

Specific foods

Pinaapple,

cider,apple,berries,..…

Macronutrient distribution may

have a role in body weight loss and

maintenance as well as on

associated obesity manifestations

Hipótesis

LOW CALORIE DIETS

Fat losses

lean tissue maintenance

Macronutrient distribution

Food Composition

Proteins, 3 fatty acids,

glycemic index, fiber,

amino acids…

Risk factors

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1 2

Carbohydrates

Lípids

Proteíns

Body weight composition

DEXA, Bio-impedance

Energy expenditure

Indirect Calorimetry

Mitochondrial Oxidation

Breath tests for stable isotopes

Blood Sampling

Lipids, carbohydrates, leptin Energy

expenditure

Energy - 30%

DIET

Anthropometrics

Weight, stature, circumferences,……..

Material y Métodos

RESULTADOS:

Resultados

Labayen et al. 2004,Clin Nutr; 23:571-578

Net Lipid Oxidation

Resultados

Resultados

Labayen et al. 2004,Nutr Res; 24: 7-18

Efecto termogénico y utilización postprandial de nutrientes

Fat Balance

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

Day 0 Day 70

Fat

bala

nce (

kJ)

* P < 0.10

Resultados

EFECTS OF PROTEIN VS CARBOHYDRATE-RICH DIETS

ON FUEL UTILISATION IN OBESE WOMEN DURING

WEIGHT LOSS

Elmadfa I, Ankalm E, König JS (eds): Modern Aspects of Nutrition. Present knowledge

and future perspectives. Forum Nutr. Basel, Karger, 2003, vol 56: 168-170

Labayen I, Díez N, González A, Parra D, Martínez JA

Resultados

Labayen et al., 2003. Forum Nutr. 23: 168-170

Cambios en leptina y utilización de nutrientes

+51% (p<0.05) in leptin concentration in protein diet.

OXIDACIÓN DE PROTEÍNAS

0

0,2

0,4

0,6

0,8

1

1,2

1,4

1,6

1,8

2

Dieta HP Dieta HC

Tasa d

e o

xid

ació

n (

g/k

g*d

)

Inicio

Final

p=0.052

Resultados

HP Diet HC Diet

Basal

Final

Resultados

EFECTO SOBRE LA OXIDACIÓN MITOCONDRIAL:

Test en aliento 2-ceto[1-13C]isocaproato

25

27

29

31

33

35

37

Dieta control Dieta hiperproteíca

Inicio

Final

p=0.036

p=0.597

Tra

zer

Oxid

atio

n (

%)

Abete et al., 2008. Int J Food Sci Nutr; 1-13

Resultados

Control diet High protein diet

Basal

Final

Resultados

N=10

CONTROL

N=9

HIGH PROTEIN

N=8

LEGUMES

N=8

FATTY FISH

35 Men; Age: 387 years; BMI: 31,83,0 kg/m2

>Protein

<Carbohydrates

30%P; 33%CHO; 37%FAT

> Fiber

>Protein

19%P; 52%CHO; 30% FAT

> 3 Fatty acids

18.5%P; 51%CHO; 32%AG

Balanced Energy restricted

19%P; 51%CHO; 30%FAT

Resultados

Pérdida de peso durante el período de intervención nutricional

Abete et al., 2008. J Med Food; 12:100-108

-9

-8

-7

-6

-5

-4

-3

-2

-1

0

0 1 2 3 4 5 6 7 8

Dieta control

Dieta legumbres

Dieta pescado azul

Dieta hiperproteica

Pé

rdid

a d

e p

es

o (

%)

* *#

Energy restriction effect p<0,001

Weeks

Dier effect p=0,05

# p<0,05 legumes vs control

* p<0,05 Higher protein vs control

Resultados

Control diet

Legumes diet

Fatty fish diet

High protein diet

Wa

ist

Circ

um

fere

nc

e

(%)

-14

-12

-10

-8

-6

-4

-2

0

Dieta control Dieta legumbres

Dieta pescado

azul Dieta hiperproteica

* *

*

*

Fa

t M

ass

(%

)

-25

-20

-15

-10

-5

0

Dieta control Dieta legumbres

Dieta pescado

azul Dieta hiperproteica

* * * *

-7,6

-7,55

-7,5

-7,45

-7,4

-7,35

-7,3

Dieta control Dieta legumbres

Dieta pescado

azul

Dieta

hiperproteica

R

est

ing

en

erg

y

ex

pe

nd

itu

re (%

)

* * * *

Cambios observados tras el período de intervención nutricional

*P<0,05. Basal vs final Abete et al., 2008. J Med Food; 12:100-108

Resultados

Control diet Legume

diet Fatty fish

diet

High protein

diet Control diet Legume

diet Fatty fish

diet

High protein

diet

Control diet Legume

diet Fatty fish

diet

High protein

diet

Resultados

EVOLUCIÓN DE LA PERDIDA DE PESO

Resultados

Larsen et al, 2010. N Engl J Med; 363:2102-13

Background

PROYECTO DiOGenes: Diet, Obesity and Genes. 8 European countries

Nutritional Intervention

- PHASE I: Weight loss - 800 kcal for 8 weeks

- PHASE II: Mantenimiento Maintenance for 26 weeks .

1209 adults 938 PHASE I 773 adults in PHASE II

Resultados

Larsen et al, 2010. N Engl J Med; 363:2102-13

PHASE II: Weight Maintenance

773 adults with weight loss >8%

↑ Prot

↓ IG

Control ↑ Prot

↑ IG

↓ Prot

↑ IG

↓ Prot

↓ IG

N= 159 N= 155 N= 150 N= 154 N= 155

Protein = 25% E

GI= 58.0 vs 61.3

Protein = 13% E

IG = 58.2 vs 61.4

AD LIBITUM WITH NO ENERGY RESTRICTION !

26 weeks with monthly advice.

Resultados

Larsen et al, 2010. N Engl J Med; 363:2102-13

CAMBIOS EN PESO CORPORAL

Resultados

Resultados

Resultados

Possible interactions of dietary intake with genetic variability to affect disease risk.

Jenab MZ et al. Hum Genet (2009) 125: 507–525

Nutrition and genetic interactions

DEPARTAMENTO DE CIENCIAS DE LA ALIMENTACIÓN,

FISIOLOGÍA Y TOXICOLOGÍA

GOBIERNO DE NAVARRA Y UNIÓN EUROPEA

Agradecimientos

Resultados

Resultados

Resultados

DNA RNA PROTEINS

Transcription Translation

Gene Expression= f (DNA Environmental factors)

GENOTYPE PHENOTYPE

Regulatory Elements Estructural Functions

Proteins

Energy

Nutrients

NUTRIENT FUNCTIONS

Fatty Acids

Retinoids

Vitamin D

Glucose

Energy

Transcription mRNA DNA Proteíns

Translation

Amino acids

Iron

Selenium

Postranslation

Minerals

Vitamins

Gene expression – Nutritional control

Cascade

Kinases

Mechanisms : - Receptors (membrane/nucleus)

Nutrients

Nutrients

Nutrients &

Metabolites

- Metabolism intermediate

FT

- Transcription Factors (FT): affinity & concentrations

RE

Gene expression control: Mechanisms

Genetic make up can determine

unique nutritional requirements

and responses to different foods.

Based on:

- The sequencing of the human genome,

- subsequent analyses of human genetic variation,

-studies that associate gene variants with disease markers

-Impact of nutrition/nutrients on gene expression

Personalized Medicine and Nutrition

Epigenetic processes modulate gene activity and expression

without changes in the DNA nucleotide sequence

EPIGENETICS

Me

DNA Methylation

Histone Modifications DNA Packaging

around Nucleosomes

Me

Me

Chromatin Packaging

Alterations

Me

Me

Me

Me

Me

Me

Me

Me

Me Me

Me Me Ac Ac Ac

Ac

Epigenetic Modifications

Sullivan KE et al. Epigenetic regulation of tumor necrosis factor alpha.

Mol Cell Biol 2007, 27: 5147-5160.

TNF-α promoter methylation is tissue

specific

24 obese subjects

(BMI: 30.5 ± 1.5 kg/m2)

12 men 12 female

Serum: TNF-a Blood, PBMC: DNA

8-week hypocaloric diet

Weigh loss ≥ 5% of initial body

Responders Non-responders

Serum: TNF-a

Experimental design

TNF-a gene

% Methylation

Campion et al Obesity 2009

Weight Loss

Baseline TNF-a

Final TNF-a

Subjects less

methylated lose

more weight

Subjects with more

baseline TNF have

the promoter

more methylated

Subjects with the

promoter more

methylated decrease

less the TNF levels

Campion et al Obesity 2009

Results

CONCLUSIONES

Conclusiones

2) La utilización de lípidos tras la ingesta de una comida con

alto aporte proteico es significativamente mayor

comparada con una comida alta en hidratos de carbono.

1) La sustitución de hidratos de carbono por proteínas en el

contexto de una dieta hipocalórica favorece la pérdida

de peso y masa grasa (10% y 5.5%, respectivamente),

además de promover la oxidación endógena de lípidos

sin afectar al metabolismo proteico.

3) El aumento del contenido proteico a expensas de los

hidratos de carbono dentro de una dieta hipocalórica

produjo un aumento específico de la oxidación

mitocondrial, limitando el descenso del gasto energético

en reposo frente a la restricción calórica

4) Las dietas hiperproteicas pueden ser una estrategia

dietética a corto plazo más efectiva en cuanto a la

pérdida de peso, masa grasa, resistencia a la insulina,

control del apetito y descenso del gasto energético en

reposo.

Conclusiones

Conclusiones

5) La ingesta moderadamente alta de proteína y la

reducción del índice glucémico dentro de una dieta

habitual favorece el mantenimiento de peso, evitando la

recuperación del peso perdido y de la masa grasa

específicamente.

Genetics Genomics Epigenetics

Nutrition, perinatal programming and

disease

Nutrition and Health

Genetics Genomics Epigenetics

Nutrition, perinatal programming and

disease

CONCLUSIONES

Conclusiones

2) La utilización de lípidos tras la ingesta de una comida con

alto aporte proteico es significativamente mayor

comparada con una comida alta en hidratos de carbono.

1) La sustitución de hidratos de carbono por proteínas en el

contexto de una dieta hipocalórica favorece la pérdida

de peso y masa grasa (10% y 5.5%, respectivamente),

además de promover la oxidación endógena de lípidos

sin afectar al metabolismo proteico.

3) El aumento del contenido proteico a expensas de los

hidratos de carbono dentro de una dieta hipocalórica

produjo un aumento específico de la oxidación

mitocondrial, limitando el descenso del gasto energético

en reposo frente a la restricción calórica

4) Las dietas hiperproteicas pueden ser una estrategia

dietética a corto plazo más efectiva en cuanto a la

pérdida de peso, masa grasa, resistencia a la insulina,

control del apetito y descenso del gasto energético en

reposo.

Conclusiones

Conclusiones

5) La ingesta moderadamente alta de proteína y la

reducción del índice glucémico dentro de una dieta

habitual favorece el mantenimiento de peso, evitando la

recuperación del peso perdido y de la masa grasa

específicamente.

Abete I et al., Arch Med Res. 2009 May;40(4):306-10. 2009

Inflammatory state and stress condition in weight-lowering Lys109Arg LEPR gene polymorphism carriers.

Goyenechea E et al .(Diabetes Res; 2008) Goyenechea E et al .(Diabetes Res; 2008)

Enhanced short-term improvement of insulin response to a low-caloric diet in

obese carriers the Gly482Ser variant of the PGC-1alpha gene

Goyenechea E et al .(Diabetes Res; 2008) Goyenechea E et al .(Diabetes Res; 2008)

Enhanced short-term improvement of insulin response to a low-caloric diet in

obese carriers the Gly482Ser variant of the PGC-1alpha gene

Goyenechea E et al .(Diabetes Res; 2008)

Enhanced short-term improvement of insulin response to a low-caloric diet in

obese carriers the Gly482Ser variant of the PGC-1alpha gene

Goyenechea E et al .(Br. J Nutr. 2006)

Weight regain after slimming induced by an energy-restricted diet depends on interleukin-6 and

peroxisome-proliferator-activated-receptor-gamma2 gene polymorphisms

Goyenechea E et al .(Br. J Nutr. 2006)

Weight regain after slimming induced by an energy-restricted diet depends on interleukin-6 and

peroxisome-proliferator-activated-receptor-gamma2 gene polymorphisms

Goyenechea E et al .(Br. J Nutr. 2006)

Weight regain after slimming induced by an energy-restricted diet depends on interleukin-6 and

peroxisome-proliferator-activated-receptor-gamma2 gene polymorphisms

Goyenechea E et al .(Br. J Nutr. 2006)

Weight regain after slimming induced by an energy-restricted diet depends on interleukin-6 and

peroxisome-proliferator-activated-receptor-gamma2 gene polymorphisms

Crujeiras AB et al. (OMICS. 2008)

Differential expression of oxidative stress and inflammation related genes in peripheral blood mononuclear

cells in response to a low-calorie diet: a nutrigenomics study.

Crujeiras AB et al. (OMICS. 2008)

Differential expression of oxidative stress and inflammation related genes in peripheral blood mononuclear

cells in response to a low-calorie diet: a nutrigenomics study.

Crujeiras AB et al. (OMICS. 2008)

Crujeiras AB et al. (OMICS. 2008)

Differential expression of oxidative stress and inflammation related genes in peripheral blood mononuclear

cells in response to a low-calorie diet: a nutrigenomics study.

Sirtuin gene expression in human mononuclear cells is modulated by caloric restriction

Crujeiras AB et al. (Eur J Clin Invest 2008)

Crujeiras AB et al. (Eur J Clin Invest 2008)

Sirtuin gene expression in human mononuclear cells is modulated by caloric restriction

Crujeiras AB et al. (Eur J Clin Invest 2008)

Sirtuin gene expression in human mononuclear cells is modulated by caloric restriction

Goyenechea E et al. (Ann Nutr Metab. 2008)

A nutrigenomic inflammation-related PBMC-based approach to predict the weight-loss regain in obese subjects

Goyenechea E et al. (Ann Nutr Metab. 2008)

A nutrigenomic inflammation-related PBMC-based approach to predict the weight-loss regain in obese subjects

Goyenechea E et al. (J Nutrigenet Nutrigenomics. 2008)

Expression of two inflammation-related genes (RIPK3 and RNF216) in mononuclear cells is

associated with weight-loss regain in obese subjects.

Goyenechea E et al. (J Nutrigenet Nutrigenomics. 2008)

Expression of two inflammation-related genes (RIPK3 and RNF216) in mononuclear cells is

associated with weight-loss regain in obese subjects.

SPAIN 33% 11%

PORTUGAL 33% 9%

FRANCE 24% 7%

IRELAND 31% 8%

NETHERLANDS 29% 10%

U. K. 30% 12%

BELGIUM 31% 9%

DENMARK 31% 8%

SWEDEN 33% 7%

LUXEMBOURG 27% 9%

ITALY 30% 7% GREECE

35% 11%

GERMANY 35% 11%

AUSTRIA 32% 10%

FINLAND 33% 10%