Industrialized Food Components and Obesity Risk. Kylie Kavanagh, VMS MS MPH Department of Pathology

Transcription

1 Industrialized Food Components and Obesity Risk Kylie Kavanagh, VMS MS MPH Department of Pathology

2 Overview Role of science in policy development Components versus calories Past lessons (trans fat) Present issue (added sugars) Future challenges (??) Benchtop/Preclinical Science Clinical Evidence Scientists TRANSLATIONAL SCIENCE Animal Research Proof of Concept Safety Evaluation Clinicians 2

3 Public Health Models 3

4 Obese Primates

5 Obese Primates Schmidt et al., Int J Obesity 2017

6 Study Goals The problem with cohort studies of people: Conflicting evidence Need to evaluate effects that are independent of variability in body weight. Our objectives: Evaluate the effect of dietary ingredients on health in the absence of weight gain

7 Individual Determinants of Obesity Nutrition Behavior Environment Genes Ingredients Caloric intake Macro / Micronutrient 7

8 Individual Determinants of Obesity Nutrition Behavior Environment Genes 8 Jorgensen and Kavanagh, unpublished data

9 Individual Determinants of Obesity Nutrition Behavior Environment Genes Althoff et al., Nature

10 Individual Determinants of Obesity Contribution to Waist Size Nutrition Behavior Environment Genes Everything Else Genes Althoff et al., Nature

11 Nutritional history Industrialization of food CDC March 2018

12 The obesity epidemic Fast food industry uses trans-fat % obesity before 1960 in TFA from 1911 to mid- 1960s High Fructose Corn syrup process derived and implemented Trans fat GRAS revoked

13 Trans Fatty Acids Sources of TFAs: Natural sources - milk, butter, beef fat Made from industrial processing: - margarine, shortenings, and frying fat

14 Trans Fatty Acids

15 kg Calorie controlled Trans fat intake x 7% Baseline 6 Years 6.5 2% CONTROL TRANS FAT Kavanagh et al, Obesity 2007

16 Body Fat Distribution Trans, 6.13kg Cis, 6.09kg Kavanagh et al, Obesity 2007

17 Grams of fat 33% more AU 23% more Body Fat Cis, Distribution 6.09kg Trans, 6.13kg 250 INTRA-ABDOMINAL FAT Cis, 6.09kg 2 FAT RATIO CONTROL TRANS FAT 0 CONTROL TRANS FAT Kavanagh et al, Obesity 2007

18 % of Baseline Glucose % of Baseline Glucose Vulnerable periods Pregnancy Lactation Adulthood Gp 1 Gp 2 Gp 3 Gp 4 CIS CIS CIS TRANS CIS CIS CIS TRANS CIS TRANS TRANS CIS Gp 1 Gp 2 Gp 3 Gp 4 Kavanagh et al, Nutr Res

19 Controversy Chowdhury 2014, Ann Intern Med Micha 2014, BMJ

20 Lessons learned from Trans-fat A natural product mimicked by industrialization Naïve motivation for development and dissemination Science converged to document health effects Labeling required in 2003 Safe status revoked in 2015 WHO recommends global elimination by 2023 A 20 year timeline 20

21 Fructose Should we really be worried?

22 Fructose Syrup, made from corn easy to use and make Intake is about 8-15% of total calories, 75% of products have added sugar Encouraged by farm subsidies for corn Currently supplies nearly half of the sweeteners in our diet Soda missing! Duffey and Popkin, 2008 Am J Clin Nutr

23 Fructose controversy Is it the ingredient or just the excess calories? Glucose 45% Fructose 55% Glucose 50% Fructose 50% Van Horn L et al. Circulation 2010

24 Fructose Is Biologically Different Intestinal lumen Blood Intestinal cell Small intestine has a limited capacity for uptake Energy, insulin and sodium independent Does not stimulate insulin release Increases liver glucose output

25 Intrigue

26 Fructose in Monkeys High fructose diets fed for < 7yrs 15% develop Type 2 diabetes after a median of 3.7 years 55% less calories fed to maintain weight stability High Fructose Control CHO % of calories in diet Sucrose % of calories in diet 24 2 Fructose % of calories in diet 24 <0.5 Fat % of calories in diet Protein % of calories in diet 14 18

27 Liver Injury With Fructose Calories fed to maintain weight stability ALT Baseline 6-weeks % Change p-value Control % High Fructose % ALP Control % High Fructose % GGT Control % High Fructose % Kavanagh et al, 2013 Am J Clin Nutr

28 Grade 0 (Control) Liver Histological Score Grade 3 (High Fructose) Liver Injury With Fructose Control High Fructose Kavanagh et al, 2013 Am J Clin Nutr

29 Portal Plasma LPS (EU/mL) Intestinal bacterial circulate with fructose diets Control High Fructose Portal sampling for bacteria was 31% higher with high fructose feeding Kavanagh et al, 2013 Am J Clin Nutr

30 Fecal Bacterial Analysis No differences BUT it was only 6 weeks Kavanagh et al, 2013 Am J Clin Nutr

31 Fructose fat AND fibrosis Fibrosis Score (# area collagen) r=0.48, p= Steatosis Score (log # lipid droplets) Steatosis Score (log # lipid droplets) r=0.68, p< Duration of HFr Consumption (years) Cydylo..Kavanagh, Obesity

32 Why does the liver matter? Low difference in liver fat Naukkarinen et al, 2015 Diabetologia High difference in liver fat 32

33 Take home message Trans-fat makes you abdominally obese and insulin resistant Fructose induces microbial translocation (inflammation) and promotes fatty/fibrotic liver Neither ingredient is necessary

34 Science and the fructose environment Added sugars labeling is under debate Public pressure needs to continue No forecast GRAS status on fructose-syrups The science is clear but only really implicated fructose 1990 onwards 34

35 The future Many things but

36 Dietary Emulsifiers Theme- not a required ingredient Carboxymethocellulose and polysorbate-80 FDA safe, used < 2% by weight in food products as a stabilizer Used in packaged, ready to eat foods, beverages Cani and Everard, Trends Endocrinol Metab 2015 Chassaing et al. Nature

37 Emulsification of the intestinal surface Replicates what is seen in older adults and those with increased risk for colon cancer DNA content of mucosa (Ln[ng/uL]) Young p=0.03 Old Mucosal 16S gene (AU) Young p=0.06 Old 37

38 Emulsification of the intestinal surface Fasting Glucose (mg/dl) Old - Chow Diet Baseline 8-Week Old - Western Diet *p=0.03 Young - Western Diet Goblet Cells (#/100 m) r=-0.46, p< Ln Mucosal 16s Gene Count (AU) 38

39 Please ask questions and THANK YOU for your interest and support