Prof.dr. Frans J Kok. Nutrition & Health Perspectives over the Life course

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Prof.dr. Frans J Kok Nutrition & Health Perspectives over the Life course

Midlife Early life Midlife Late life

Double Burden of Malnutrition

Global population in 2015 and 2060

Modern Science and Technology Diet Individual biology at multi-level Topol EJ. Cell 2014

Late life Midlife Early life nutrition

Early life HIGH BURDEN OF UNDERNUTRITION Low Calories Protein Intake Big Five problem nutrients iron, vitamin A, iodine, zinc, folic acid Bhutta ZA. Lancet 2013

Early life REDUCED GROWTH IN CHILDREN UNDER 5 YEARS 10-20% 20-40% > 40% Stunted obesity FAO 2013

Early life Malnutrition responsible for half of child deaths anaemia, blindness, birth defects stunting, cognitive & motor impairment

Death of 1 million children per year can be prevented by 10 proven nutrition interventions. SAM = Severe Acute Malnutrition (WHZ < -3SD) MAM = Moderate Acute Malnutrition (WHZ < -2SD and >= -3SD) Bhutta et al. Lancet 2013

Early life 1000 days have a lifelong impact

Early life Cognitive Iron builds a better brain

Early life IRON SUPPLEMENTATION IMPROVES MENTAL DEVELOPMENT RTC 6000 pregnant women 4600 live births Chang S. Pediatrics 2013 Chang S. Pediatrics 2011

Early life We are neglecting adolescent girls' nutrition

Early life Chromosome Histone modification DNA-methylation Epigenetics

Early life Hungry Harvest Domingues-Salas P. Nat Commun 2014

Late life Early life Midlife nutrition

Midlife Obesity 2015. Lancet series

Midlife 5% weight loss only Calories count Johnston BC. JAMA 2014 Sacks FM. N Engl J Med 2009

Midlife

Midlife unhealthy week healthy week

Midlife UNHEALTHY CHANGES IN BODY unhealthy month PARAMETERS worse blood lipids high blood pressure higher heart rate increased insulin increased belly fat high liver enzymes lower fitness

Midlife Conclusions n=1 Self-experiment Experiment is scientifically designed: within-person variation, controlled protocol No scientific conclusions: chance-findings, repeated experiments with more subjects for valid outcomes However. A clear trend in the findings: small but adverse changes, which can be restored

Midlife BMI=36.2 BMI=22.8 Excess belly fat

Midlife STRESSED FAT CELLS LEAD TO INFLAMMATION infiltrated immune cells immune cells release signals Chawla A. Nature Rev Immunol 2012 stressed fat cell

Midlife immune cell adipocyte Johnson AR. Immunol Rev 2012

Midlife Wageningen Belly Fat study design Wageningen Belly Fat study design N = 40 N = 40 N = 30 Western diet Targeted diet Control usual diet -30% caloric restriction no caloric restriction

Midlife BODY WEIGHT & LIVER FAT DECREASED usual diet Western diet Targeted diet Control - 6.3 kg - 8.4 kg + 0.8 kg - 48 % - 57 % + 24 %

Change in SAT (log2 cm 2 ) Change in VAT (log2 cm 2 ) Change in VAT/SAT ratio (log2) Body fat distribution Western-type diet: n=28 Targeted diet: n=26 Control group: n=16 Subcutaneous adipose tissue mass Visceral adipose tissue mass

Insulin sensitivity Baseline Change after 12 weeks p-value HOMA-IR Western-type diet group Targeted diet group Control group 3.8 ± 3.1 3.5 ± 2.1 3.0 ± 1.4-1.3 ± 2.3 a -1.0 ± 1.5 a 0.1 ± 1.5 b 0.006 QUICKI * Western-type diet group Targeted diet group Control group 0.33 ± 0.04 0.33 ± 0.03 0.33 ± 0.02 0.01 ± 0.03 a,b 0.02 ± 0.03 a 0.00 ± 0.02 b 0.014 *Quantitative insulin sensitivity check index 31

HDL cholesterol Targeted diet group Western-type diet group Lipids Lipids Phospholipids Phospholipids X Large HDL (particle concentration) Cholesterol Cholesterol esters Cholesterol Cholesterol esters X Large HDL (particle concentration) Free cholesterol Free cholesterol Lipids Triglycerides Triglycerides Lipids Phospholipids Phospholipids Large HDL (particle concentration) Cholesterol Cholesterol esters Cholesterol Cholesterol esters Large HDL (particle concentration) Free cholesterol Free cholesterol Triglycerides Lipids Lipids Triglycerides Phospholipids Phospholipids Medium HDL (particle concentration) Cholesterol Cholesterol esters Cholesterol Cholesterol esters Medium HDL (particle concentration) Free cholesterol Free cholesterol Lipids Triglycerides Triglycerides Lipids Phospholipids Phospholipids Small HDL (particle concentration) Cholesterol Cholesterol esters Free cholesterol Cholesterol Cholesterol esters Free cholesterol Small HDL (particle concentration) 32 Triglycerides Triglycerides

Midlife Wageningen Belly Fat study Wageningen Belly Fat study

Diet Individual biology at multi-level Topol EJ. Cell 2014

Midlife Integrating multi-level data Topol EJ. Cell 2014

Midlife One size fits all

Midlife Early life 117 years old Late life nutrition

Late life Theory of aging programmed damage López-Otín C. Cell 2013

Late life physiological integrity The aging process organ function quality of life disease risk atherosclerosis carcinogenesis osteoporosis cognitive decline sarcopenia

Late life Aging brain Cognitive decline Dementia

Late life 30% OF ALZHEIMER CASES DUE TO LIFESTYLE normal Alzheimer Norton S. Lancet Neurol 2014

Late life INTERVENTION KEEPS THE MIND 'SHARP' total score executive functioning Z-score 1y 2y 1y 2y processing speed memory 1y 2y 1y 2y 2 year RCT, at-risk elderly aged 60-77 y, n=591 intervention, n=599 control 2 year RCT, 1190 elderly aged 60-77 y Ngandu T. Lancet 2015

Late life MIXED RESULTS ON COGNITION Durga J. Lancet 2007 van de Rest O. Neurology 2008 Van der Zwaluw N. Neurology 2014

Late life B-VITAMIN REDUCES LOSS OF GRAY MATTER reduced loss of gray matter before after 2 year RCT, Douaud 156 elderly, G. PNAS 2013 77 y, intervention B12, B6 & Folic acid 3.2% less loss Douaud G. PNAS 2013

Late life STROOP TEST STUDIES BRAIN CONNECTIVITY YELLOW BLUE ORANGE BLACK RED GREEN PURPLE YELLOW RED ORANGE GREEN BLACK BLUE RED PURPLE GREEN BLUE ORANGE Taya F. Front Syst Neurosci 2015

Late life USE IT OR LOSE IT muscle mass fat mass man 25 years man 63 years

Late life muscle mass (%) MUSCLE LOSS WITH AGING 50 25-50% 20-30 40-50 60-70 80-90 age (yrs) Short K, Nair S. 2000

Late life type 2 muscle fibers Exercise training gives muscle strength

Late life Exercise & protein beneficial for elderly 1.5 change in lean body mass (kg) 1.0 0.5 0.0 Placebo Protein -0.5 Tieland M. J Am Med Dir Assoc 2012

Late life 1 kg muscle mass loss in 7 days

Late life PROTEIN ENRICHED FOODS IMPROVED MUSCLE STRENGTH 6 month RCT - 120 elderly patients - 77 y -Cater with Care versus Standard Care

Late life Jankovic N. Am J Epidemiol 2014