Welcome Aboard the Sweet Titanic: Added Sugars, Cancer, Heart Disease and Diabetes Dead Ahead

Welcome Aboard the Sweet Titanic: Added Sugars, Cancer, Heart Disease and Diabetes Dead Ahead? A. Paul Chous, MA, OD, FAAO, CDE Tacoma, WA

Essential Questions: Do added sugars increase the risk of diabetes, cardiovascular disease and cancer? Are some added sugars metabolically more damaging? Why should eye doctors care?

I. US sugar consumption over the last 50 years a. net increase of 450 kcal per capita per day b. concomitant increases in obesity, diabetes, metabolic syndrome, cancer and heart disease c. These associations are also co-mingled with decreased rates of physical activity, increasing environmental toxins, increasing mean indoor ambient temperatures, an aging population, misguided public health focus on reducing dietary fats, and improved ability to diagnose d. Added sugar (sucrose) consumption and fructose consumption

II Is a Calorie Really Just a Calorie? a. what is a calorie? b. Hypothesis: The metabolic effects of calories from various foodstuffs are independent of their total energy content c. Significance of advanced glycation endproducts (AGES) -biomarkers of glucose toxicity -implicated in all diabetes complications, but multiple other diseases as well (AMD, glaucoma, cataract in the eye) - formed by high temperature + low humidity cooking -inhibit SIRT1 gene, shortening lifespan d. Simple sugars stored in carbohydrates contribute to increased production of intermediate metabolites that promote disease 1. glucose – advanced glycation endproducts (AGEs) 2. fructose – 99% first-pass hepatic metabolism produces uric acid, small/dense atherogenic LDL-cholesterol, insulin resistance

III. Sugar and Cancer a. some studies show significant increase in risk of colon, breast, and pancreatic cancers b. Dietary sugar intake associated with increased cancer mortality c. Warburg Hypothesis: cancer cells preferentially perform anaerobic glycolysis and have increased insulin receptors to facilitate high metabolic rate d. Mechanism of increased cancer risk: -glucose inhibits vitamin C and promotes hypoxia inducible factor (HIF) requisite for tumor growth (HIF also implicated in neovascular AMD) -Glucose and fructose inhibit beta catenin signaling that renders cancer cells ‘immortal’ -added sugars increase obesity & diabetes, major risk factor for multiple cancers via insulin-like growth factor signaling due to excess insulin - Reducing Risk: reduce sugar intake; possible benefits of metformin; use of a pyruvate analog that prevents ATP production via anaerobic glycolysis (2-bromopyruvate)

IV. Diabetes a. Is increased sugar consumption causally related to increased incidence of diabetes mellitus? b. Each 150 kcal/day percapita increase in added sugars increases population prevalence of DM 1.1% 1. 3.5 million additional cases of T2DM per can of sugar-sweetened beverage in the US 2. WHO recommendations: < 25 g added sugars/day c. High fructose corn syrup (HFCS) is metabolized by the liver, yielding excess uric acid, NAFLD, NO and is causally linked to T2DM - multiple studies linking hyperuricemia to T2DM -glucose is not harmless: polyol pathway of aerobic glycolysis yields fructose and produces AGEs outside of the liver d. Reducing Risk: keep added sugars < 40 grams/day (ideally < 25 g); eat foods with fewer AGEs; prevent AGE formation with curcumin and benfotiamine (lipid soluble thiamine analog); increase macular pigment with xanthophyll rich diet that increases macular pigment - low MPOD implicated in diabetes, diabetic retinopathy, but also…

V. Sugar and Cardiovascular Disease a. meta-analysis of 39 RCTs shows added sugars increase triglycerides, LDL cholesterol and blood pressure after all controls b. Dose increases risk: nearly 3-fold increased risk of death when > 25% of calories come from added sugars*NHANES data c. low sugar intake improves HDL cholesterol, TGs in both men and women and LDL-C in women e. Fructose appears worse than glucose by fostering small, dense, highly Atherogenic LDL-C, NAFLD and hepatic insulin resistance; also Raises hsCRP > glucose f. Sugar accelerates cell aging by shortening telomeres g. Sugar increases serum AGEs that predict CV mortality in type 2 diabetes

VI Conclusion: Is dietary sugar consumption linked to CV disease, diabetes and cancer? Is it linked to ocular disease? YES a. the problem of mono versus multifactorial causality b. practical strategies: keep carbs < 30 grams/meal; keep daily added sugars < 25grams; substitute whole plant foods and lean protein for processed carbs/snack foods/soda; avoid AGEs in food preparation; avoid HFCS c. Food companies disguise added sugars: (56 names) – read labels!