State of the Science and Technology in Personalized Nutrition The nutritional systems biology

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Abner Cole
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1 State of the Science and Technology in Personalized Nutrition The nutritional Ben van systems Ommen biology solution in Type 2 Diabetes and Cardiovascular Desease prevention and therapy". Ben van Ommen

2 Personalized nutrition the questions - Are we different in our nutritional needs? - What is my optimal nutrition - What is my health? - What do I know about my health - How can I act upon it?

3 Different from the inside

4 Different from the outside

6 Oxidative processes metabolic processes Inflammatory processes Glucose control Lipid control Immune control Overarching processes Metabolic Crohns disease obesity Parkinson Multiple Sclerosis Inflammatory Bowel Syndrome COPD Osteo porosis Rheumatoid Arthritis Alzheimer allergies Ulcerative Colitis Sarcopeny Type 2 diabetes CVD disease areas Hypercholesterolemia Hypertension blood pressure Cognition mental health Intestinal health Lung health Bone health Joint health Muscle health vascular health Target areas liver health Vit D Vit E Vit C Pantothenic acid

7 So, who am I in this scheme and what should I eat to remain in optimal health? Me? blood pressure vascular health liver health Cognition mental health Joint health Oxidative Immune Target areas processes control Intestinal Inflammatory Glucose processes health control Overarching metabolic processes Lung processes Lipid health control Muscle Bone health health

75 g Glucose gut inflammation IBD adipose inflammation systemic inflammation Hepatic inflammation fibrosis endothelial inflammation ectopic lipid overload Cardiac dysfunction Visceral adiposity Fatty

10 75 g Glucose gut inflammation IBD adipose inflammation systemic inflammation Hepatic inflammation fibrosis endothelial inflammation ectopic lipid overload Cardiac dysfunction Visceral adiposity Fatty liver High cholesterol Heart failure Metabolically healthy dyslipidemia LDL elevated Myocardial infactions Hepatic IR Brain disorders High glucose Glucose toxicity Adipose IR β-cell gluc Ìrreversible process Reversible process Pathology Risk factor Muscle metabolic inflexibility systemic Insulin resistance β-cell failure Atherosclerosis Microvascular Hypertension The flexible phenotype: the system is a shock damageabsorber Retinopathy ( phenotypic flexibility ) Nephropathy Nakatsuji, Metabolism 2009 Stroke reversible irreversible

Phenotypic Flexibility as biomarker of health 134 biomarkers report on challenge responses in organs Brain Secondary messengers Trp, Tyr, Phe, Met Pancreas Disposition index C-peptide Insulin

ribulose / xylulose GIP, GLP-1 Indole-3-proprionic acid Metabolic challenge Matsuda index, HbA1C, HOMA-IR glucose, 1,5-anhydroglucitol Glutathione ratio, uric acid, vit E mannose, ribose, glycine,

11 Phenotypic Flexibility as biomarker of health 134 biomarkers report on challenge responses in organs Brain Secondary messengers Trp, Tyr, Phe, Met Pancreas Disposition index C-peptide Insulin Glucagon HOMA-B Blue = responding Green = not responding Back = could not be determined Liver Ketone bodies Central metabolism ALAT, ASAT, ALP, GGT CRP TG Liver IR index Liver IS index Gut Fructose, ribulose / xylulose GIP, GLP-1 Indole-3-proprionic acid Metabolic challenge Matsuda index, HbA1C, HOMA-IR glucose, 1,5-anhydroglucitol Glutathione ratio, uric acid, vit E mannose, ribose, glycine, pseudo uridine RQ measures Muscle Lactate, beta-alanine Muscle IR index Branched chain amino acids & derivatives 1-methylhistidine, 3-methylhistidine 4-hydroxyproline, 4-oxoproline Adipose tissue Glycerol, NEFA & specific FFA MG, DG Leptin, adiponectin Estimated SCD activity C16:1 FFA Adipose IR index Kidney Creatinin Asp, Glu, Orn, Urea Albumin Vasculature Cholesterol, HDL, LDL SAA, sicam, svcam PhenFlex challenge: - 75 g glucose - 60 g palmoic oil - 20 g protein

12 Personalized (Micro)nutrient Recommendations related to systems flexibility Liver Choline, carnitine Catechins? low grade inflammation vitd, VitE, Mg, ω-3 fatty acid, flavonoids, curcuminoids Vasculature vitc, K, cocoa flavanols, NO-producing nutrients, lycopene Pancreas Leucine, vitk, vitd, Mg

13 We can now quantify the individual processes and optimize these with personalized diets carotenoids Quercetin, Se, Zn, Omega 3/6 FA Stannols,fibre Carnitine, Choline, Low glycemic index polyphenols Antho cyanins epicathechins procyanidins

IS Low-fat diet improves liver IS Mediterranean diet improves systemic IS T2D subgroup glucose

14 Personalized? Type 2 diabetes subgroups react differently on different diets Mediterranean diet improves muscle IS Low-fat diet improves liver IS Mediterranean diet improves systemic IS T2D subgroup glucose respose to Oral Glucose Tolerance Test [Glucose] T2D (diagnosed) T2D (non-diagnosed) IGT & IFG IGT (muscle) IFG (liver) healthy time(min) Blanco-Rojo, Diabetologia, Oct 2015

Adipose insulin sensitivity Adipokine production Lipoprotein production Muscle insulin sensitivity Ketogenesis beta-oxidation Lipolysis Lipid flexibility * * * *** * ** Carnitine, choline Gut

15 Adipose insulin sensitivity Adipokine production Lipoprotein production Muscle insulin sensitivity Ketogenesis beta-oxidation Lipolysis Lipid flexibility * * * *** * ** Carnitine, choline Gut mediated inflammation Oxidative stress Nitrosative stress Chronic low grade inflammation NO formation * * ** ** * * * * * * ** * * * * * * * * * * * * * * * Carbohydrate flexibility * * * * Fiber, vitk, ** * * * Mg * * * * * * * * DHA, EPA, Se, Vit E gluconeogenesis insulin sensitivity incretin production bile production insulin sensitivity Disposition index Metabolic flexibility

16 Phenotypic flexibility of 50 healthy subjects in a health space Stress flexibility N-H Lipid flexibility L-N Age LOW FAT% NORMAL FAT% HIGH FAT%

17 So what`s the right diet for me? 17

18 From public Health dietary recommendations dietary recommendations are mostly based on epidemiology: associations of the masses

19 to a multitude of diet types based on a mix of science, fiction and commerce Dietary choices are based on the choice of the book

20 Information overflow? Misleading Information?

The real value of MY health data: how can this data work for

Doctors Schools & daycare Hospitals Research Infant formula

22 The real value of MY health data: how can this data work for me? Health Data Cooperative as legal entity that valorizes my own health data. COOPERATIVE Citizen-owned Citizen-controlled Developers Doctors Schools & daycare Hospitals Research Infant formula producers food industry Education Retail Health Service Providers Farmers market Government Ernst Hafen, ETH Zurich

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Sustained effort to continue newly established behavior Self pertetuating pattern

27 Four Behavioural changes phases Initial response Continued response maintenance habit Initial effort to change behavior Continue effort to establish behavior Sustained effort to continue newly established behavior Self pertetuating pattern of behavior Rothman (2009) Disentangling behavioural initiation and behavioural maintenance

Each person deserves the right method for the right phase Behavior Change Technique (93 different techniues) Initial response Continued response Maintenance Habit Prompt practice Stress management

28 Each person deserves the right method for the right phase Behavior Change Technique (93 different techniues) Initial response Continued response Maintenance Habit Prompt practice Stress management General communication skills training Environmental restructuring Model/demonstrate the behavior Goal setting (outcome) Relapse prevention/coping planning Facilitate social comparison Goal setting (behavior) Action planning Provide feedback on performance Barrier identification/problem solving Provide instruction Teach to use prompts/cues Provide normative information about others behavior Plan social support/social change

29 Example of individual approach based on 360 O Behavior Change Technique Initial response Continued response Maintenance Habit Prompt practice Stress management General communication skills training Environmental restructuring Model/demonstrate the behavior Goal setting (outcome) Relapse prevention/coping planning Facilitate social comparison Goal setting (behavior) Action planning Provide feedback on performance Barrier identification/problem solving Provide instruction Teach to use prompts/cues Provide normative information about others behavior Personalized selection of behavioural change sequences Lifestyle as medicine: behavioral Plan social support/social change

30 Bottomline The technology is there to come The science is good enough to introduce The data ownership is an issue Personalized will change society but society also needs to change Food services will replace food products

HOW TO DEFINE GOOD BIOMARKERS OF HEALTH? Suzan Wopereis

HOW TO DEFINE GOOD BIOMARKERS OF HEALTH? Suzan Wopereis My personal objective: identification of biomarkers of (optimal) health Biomarker Definition: a characteristic that is objectively measured and evaluated