Sugar-Loaded Beverages and the Impact on Cardiovascular Health. Christina M. Shay, PhD, MA

Sugar-Loaded Beverages and the Impact on Cardiovascular Health Christina M. Shay, PhD, MA 1

Presenter Disclosure Information Christina M. Shay, PhD, MA Sugar-Loaded Beverages and the Impact on Cardiovascular Health FINANCIAL DISCLOSURE: No relevant financial relationship exists Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 2

Objectives To gain an understanding of the scientific evidence supporting a role for sugar-loaded beverages in the development of cardiovascular disease and its risk factors To discuss predominant theories behind how sugar-loaded beverage consumption may adversely influence cardiovascular health independent of weight gain or obesity Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 3

January 2010

2020 Strategic Impact Goal By 2020 to improve the cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular diseases and stroke by 20%. 5

Define and Monitor CV Health Defined 7 Components of CV health Factors (clinical) and behaviors (lifestyle) Defined a continuum of CV health according to poor, intermediate and ideal Outlined standardized metrics to monitor the status of CV health of populations over time 6

Prevalence of Ideal Healthy Diet Score (%) Prevalence of Ideal Healthy Diet Score* by Sex and Age Group NHANES 2003-2008 100 75 Men Women 50 25 0 Young Age (20-39 Yrs) Middle Age (40-64 Yrs) Older Age (65+ Yrs) Shay et al. Circulation, 2012. 3:125(1):45-56. 7

Prevalence of Healthy Diet Score* by Sex and Age Group: NHANES (2003-2008) Females (12-17 yrs) Females (18-19 yrs) Males (12-17 yrs) Poor Intermediate Ideal Males (18-19 yrs) 0% 20% 40% 60% 80% 100% Prevalence *Poor: 0-1 Factors; Intermediate: 2-3 Factors; Ideal: 4-5 Factors Components: Fruits and vegetables >4.5 cup serv/day, fish>2 3.5 oz serv/week, sodium <1500 mg/day, sugar-sweetened beverages <450 kcal (36 oz)/week, whole grains >3serv/day 8

Prevalence of Attaining Individual Components of the Healthy Diet Score (Adults 20+ Years) NHANES 2003-2008 Prevalence (%) 0 10 20 30 40 50 60 70 80 90 100 Fruits & Vegetables Fish Males Females Whole Grains Sodium SSBs Score based on adherence to the following recommendations: fruits & vegetables > 4.5 cup serv/day, fish >2 3.5 oz serv/week, sodium <1500 mg/day, and whole grains >3 serv/day; sugar-sweetened beverages <450 kcal (36 oz) per week 9

Prevalence of Attaining Individual Components of the Healthy Diet Score (Adolescents 12-19 Years) NHANES 2003-2008 Prevalence (%) 0 10 20 30 40 50 60 70 80 90 100 Fruits & Vegetables Fish Males Females Whole Grains Sodium SSBs Score based on adherence to the following recommendations: fruits & vegetables > 4.5 cup serv/day, fish >2 3.5 oz serv/week, sodium <1500 mg/day, and whole grains >3 serv/day; sugar-sweetened beverages <450 kcal (36 oz) per week 10

Sugar Loaded Beverages & Cardiovascular Disease Risk Make Headlines!! Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 11

SLB + Weight Gain = CVD Risk? SLBs cause weight gain through Increased hunger Decreased satiety Decreased fullness (Ranawana, Henry. Int J Food Sci Nutr. 2011 Feb;62(1):71-81) Adding 1 can of soda per day to the diet would lead to a weight gain of 15 lb over 3 years or 5 lb in 1 year (Hall et al. Lancet. 2011;378(9793):826 37.) Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 12

Type 2 Diabetes Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 13

Multivariate relative risks of type 2 diabetes according to sugar-sweetened soft drink consumption Nurses Health Study II 1991-1999 RRs were adjusted for age, alcohol use, physical activity, family diabetes, smoking, postmenopausal hormone use, oral contraceptive use, cereal fiber intake, magnesium, trans fat, PUFA:SFA ratio Shultz MB et al. JAMA. 2004 Aug 25;292(8):927-34. 14

SLBs and Type 2 Diabetes Risk Forrest plot of studies evaluating SLB consumption and risk of type 2 diabetes mellitus, comparing extreme categories of intake (random effects estimate). Malik et al. Diabetes Care 2010, 33(11):2477 2483) 15

SLB and T2D Risk: More than obesity? Consumption of SSBs has been shown to: induce rapid spikes in blood glucose and insulin Excess insulin secretion Chronic exposure to elevated insulin levels Insulin Resistance & T2D Ludwig DS. JAMA. 2002;287(18):2414 23. 16

Dyslipidemia Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 17

Soft Drink Consumption and Risk of Developing Cardiometabolic Risk Factors of Metabolic Syndrome in Middle-Aged Adults in the Community Incidence of hypertriglyceridemia ( 1.7 mmol/l or on treatment) Soft Drink Consumption, Servings/d Incident, n No. at Risk * Age- and Sex- Adjusted OR (95% CI) Multivariable- Adjusted OR (95% CI) None 695 4258 Referent Referent 1 250 1317 1.24 (1.05 to 1.46) 1.35 (1.09 to 1.67) 2 148 807 1.20 (0.98 to 1.46) 1.09 (0.82 to 1.44) 1 398 2124 1.22 (1.07 to 1.41) 1.25 (1.04 to 1.51) Multivariable models adjust for baseline triglycerides, age, sex, physical activity index, smoking, dietary consumption of saturated fat, trans fat, fiber, magnesium, total calories, and glycemic index. Dhingra et al. Circulation. 2007 Jul 31;116(5):480-8. Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 18

Soft Drink Consumption and Risk of Developing Cardiometabolic Risk Factors of Metabolic Syndrome in Middle- Aged Adults in the Community Incidence of low HDL-C (<1.03 mmol/l, men ; <1.3 mmol/l, women or treatment) Soft Drink Consumption, Servings/d Incident, n No. at Risk * Age- and Sex-Adjusted OR (95% CI) Multivariable-Adjusted OR (95% CI) None 460 3878 Referent Referent 1 183 1201 1.28 (1.06 to 1.54) 1.38 (1.08 to 1.77) 2 96 684 1.13 (0.89 to 1.43) 1.21 (0.87 to 1.68) 1 279 1885 1.22 (1.04 to 1.44) 1.32 (1.06 to 1.64) Multivariable models adjust for baseline HDL, age, sex, physical activity index, smoking, dietary consumption of saturated fat, trans fat, fiber, magnesium, total calories, and glycemic index. Dhingra et al. Circulation. 2007 Jul 31;116(5):480-8. 19

Drinking caloric beverages increases the risk of adverse cardiometabolic outcomes in the Coronary Artery Risk Development in Young Adults (CARDIA) Study Estimated risk of incident risk factors associated with baseline quartile of beverage intake Risk Factor Sample size total (outcome) RR (95% CI) P for trend High TG 4 2627 (542) 1.06 (1.01,1.13) 0.033 High LDL 5 2640 (94) 1.18 (1.02,1.36) 0.018 Low HDL 6 1837 (252) 1.06 (0.97,1.16) 0.192 4 TG 150 mg/dl ( 1.7 mmol/l) or use of cholesterol-lowering medication. 5 LDL 130 mg/dl or use of cholesterol-lowering medication. 6 HDL <40 mg/dl [<1.04 mmol/l (men)], <50 mg/dl [<1.3 mmol/l (women)], or use of cholesterol-lowering medication. Adjustment for race, sex, CARDIA exam center, baseline age, weight, smoking status, energy from food, physical activity, energy from the 3 other beverages, and energy from alcohol Duffey et al. Am J Clin Nutr. 2010 Oct;92(4):954-9 Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 20

Hypertension Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 21

PREMIER Study An 18-Month Behavioral Intervention Trial A reduction in SSB of 1 serv/day was associated with a 1.8-mm Hg reduction in systolic BP and 1.1-mm Hg reduction in diastolic BP over 18 months Chen L et al. Circulation 2010;121:2398-2406 Copyright American Heart Association 22

Copyright restrictions may apply. Winkelmayer, W. C. et al. JAMA 2005;294:2330-2335 23

Does the adverse influence of SLBs on CVD risk factors translate into higher risk for CVD events? Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 24

Risk of Coronary Heart Disease per Serving of Sugar-Sweetened Beverages Health Professionals Follow-Up Study Prospective Study 42,883 Men Beverage Relative Risk for 1 Serving per Day (95% CI) P Total sugar-sweetened beverages 1.19 (1.11 1.28) <0.01 Colas 1.19 (1.09 1.31) <0.01 Carbonated noncolas 1.25 (1.04 1.51) 0.02 Fruit punches, lemonades, other noncarbonated fruit drinks 1.25 (1.08 1.46) <0.01 (de Koning et al. Circulation. 2012 Apr 10;125(14):1735-41.) Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 25

Sweetened Beverage Intake and CHD Risk in Women Nurses' Health Study, Prospective Study 88,520 Women (34-59 yrs) Beverage type RR (95% CI) P value Total sugar-sweetened beverages Multivariate-adjusted 1 1.32 (1.17, 1.48) <0.001 Multivariate-adjusted + diet 2 1.28 (1.14, 1.44) <0.001 Colas Multivariate-adjusted 1 1.40 (1.21, 1.63) <0.001 Multivariate-adjusted + diet 2 1.35 (1.15, 1.57) <0.001 Carbonated noncola Multivariate-adjusted 1 1.33 (0.91, 1.94) 0.24 Multivariate-adjusted + diet 2 1.27 (0.87, 1.86) 0.22 Fruit drinks and punch 3 Multivariate-adjusted 1 1.32 (1.02, 1.70) 0.04 Multivariate-adjusted + diet 2 1.33 (1.03, 1.71) 0.03 1 Adjusted for age, smoking, alcohol intake, family hx CVD, physical activity, aspirin use, menopausal status and postmenopausal hormone use, hx of hypertension and high blood cholesterol; 2Model 1+ Dietary quality; 3 Model 1 + fruit punch, lemonades, and other noncarbonated sweetened beverages. 26 (Fung et al. Am J Clin Nutr. 2009 Apr;89(4):1037-42)

American Beverage Association Responds [Observational studies] cannot show that drinking sugar-sweetened beverages causes increased risk for cardiovascular disease. It simply looks at associations between the two, which could be the result of numerous other confounding factors. http://www.ameribev.org/news--media/news-releases-- statements/more/255/ Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 27

How could sugarsweetened beverages elevate CVD risk beyond the influence of obesity? Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 28

American Beverage Association Responds When it comes to risk for heart disease, there is nothing unique about the calories from added sugars, or sugar-sweetened beverages for that matter. http://www.ameribev.org/news--media/newsreleases--statements/more/270/ Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 29

Potential Culprit: Fructose Foods and beverages in the US are typically sweetened with Sucrose (50% glucose, 50% fructose) High-fructose corn syrup (45% 58% glucose, 42% 55% fructose) Consumption is highest among 12 18 year-olds (12.1% of total calories). The largest sources of fructose was sugar-sweetened beverages (30%) followed by grains (22%) and fruit or fruit juice (19%). Vos et al. Medscape J Med. 2008 Jul 9;10(7):160. Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 30

Glucose vs. Fructose Objective: To assess the relative effects of providing 25% of energy requirements for 10 weeks in the form of glucose or fructose beverages in overweight and obese participants. Sample Sizes: Glucose: Male (n=7) Female (n=8) Fructose: Male (n=9) Female (n=8) Stanhope KL et al. J Clin Invest. 2009 May 1; 119(5): 1322 1334. Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 31

Increase in Abdominal Adiposity After Sugar Loaded Beverage Consumption Changes of total abdominal adipose tissue, SAT, and VAT volume in subjects after consuming glucose- or fructose-sweetened beverages for 10 weeks. *P < 0.05; **P < 0.01, Stanhope KL et al. J Clin Invest. 2009 May 1; 119(5): 1322 1334. 32

Changes in Blood Lipids After Sugar Loaded Beverage Consumption Mean ± SEM; + P < 0.05, ++ P < 0.01, +++ P < 0.001, ++++ P < 0.0001 Data summarized from Stanhope KL et al. J Clin Invest. 2009 May 1; 119(5): 1322 1334. 33

Post-Prandial Triglycerides After Sugar Loaded Beverage Consumption A. Glucose (n=14) B. Fructose (n=17) Stanhope KL et al. J Clin Invest. 2009 May 1; 119(5): 1322 1334. 34

Changes in Glucose Tolerance and Insulin Sensitivity After Sugar Loaded Beverage Consumption Mean ± SEM; + P < 0.05, ++ P < 0.01, +++ P < 0.001, ++++ P < 0.0001 Data summarized from Stanhope KL et al. J Clin Invest. 2009 May 1; 119(5): 1322 1334. 35

Oral Glucose Tolerance Test Stanhope KL et al. J Clin Invest. 2009 May 1; 119(5): 1322 1334. 36

Glucose vs. Fructose vs. HFCS Stanhope et al. J Clin Endo Met 96(10), 2011, p E1596 E1605 37

Potential Culprit: Uric Acid Fructose is metabolized in the liver which produces uric acid Serum uric acid has been suggested to be a potential intermediate step toward the development of CVD risk factors (Johnson RJ et al. Hypertension. 2005 Jan;45(1):18-20.) Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 38

Uric Acid Paradox Serum Uric Acid has antioxidant properties Excess SUA has deleterious effects: endothelial dysfunction proliferation of vascular smooth muscle cell increases platelet adhesiveness, oxidation of LDL- cholesterol and lipid peroxidation All these pathological processes might contribute to the development of CVD Iliesiu et al. Maedica (Buchar). 2010 July; 5(3): 186 192. Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 39

Serum Uric Acid Predicts the Development of Hypertension Author (year) Population Relative Risk Khan (1972) 10 000 males 2- fold relative risk at 5 years * Selby (1990) 2062 subjects 3-fold relative risk at 6 years * Hunt (1991) 1482 adults 2-fold relative risk at 7 years Jossa (1994) 619 males 1.2-fold relative risk at 12 years Taniguchi (2001) 6356 males 2-fold relative risk at 10 years * Masuo (2003) 433 males A 1.0 mg/dl change in uric acid predicts a 27 mm Hg increase in systolic BP at 5 years Nakanishi (2003) 2310 males 1.6-fold relative risk at 6 years * Alper (2004) 577 children Predicts diastolic hypertension at 11 years Sundström (2004) 3119 adults 1.5-fold relative risk at 4 years * *Highest tercile/quartile/quintile vs lowest tertile/quartile/quintile. Compared to 2 SD lower. Per difference of 1 mg/dl. (Johnson RJ et al. Hypertension. 2005 Jan;45(1):18-20.) 40

National Health and Nutrition Examination Surveys 1999-2004 Adolescents 12-18 years (N=4867) Nguyen et al. J Pediatr. 2009 Jun;154(6):807-13. 41

Bogalusa Heart Study Independent Childhood Predictors of Adult Systolic Blood Pressure Independent Variable Regression Coefficient PValue Race 2.36 0.002 Sex 5.95 <0.001 Childhood age 0.58 <0.001 Δ Age 0.59 <0.001 Childhood BMI 0.37 <0.001 Childhood SBP 0.48 <0.001 Childhood uric acid 0.63 0.067 Δ Uric acid 5.85 0.025 Δ uric acid indicates change in serum uric acid levels from childhood to adulthood; Δ age, change in age between baseline and follow-up. 334 whites, 243 blacks ages 5-17 years and as adults aged 18-35 years (Alper et al. Hypertension. 2005 Jan;45(1):34-8.) 42

Major biases affecting the feasibility of randomized controlled studies (RCTs), and the validity and transferability of their findings Intervention intensity and study design Type, number and frequency of SSB intake in the general population is difficult to measure and emulate in the setting of a clinical trial. Misclassification of SSB intake The wide range of SSBs (soft drinks, fruit drinks, energy drinks, vitamin water drinks) that differ in sugar added, especially in fructose and glucose amount, may have a different impact on outcome measures. Study duration Results from short-term trials are difficult to extrapolate to dietary alterations of longer durations because significant changes in body composition and metabolic structure accounting for cardiovascular risk occur slowly over time. Thus, a sufficient follow-up time is needed to effectively evaluate the causal role of SSBs to occurrence of cardiovascular diseases. Confounding by lifestyle factors affecting total energy intake Incomplete adjustment for neglected or imperfectly measured lifestyle factors may overestimate the strength of the associations Mucca et al. Intern Emerg Med. 2011 May 5. 43

Major Biases Type, number and frequency of SSB intake in the general population is difficult to measure Wide range of SSBs (soft drinks, fruit drinks, energy drinks, vitamin water drinks) that differ in amount and type of sugar added Incomplete adjustment or imperfectly measured lifestyle factors may influence the strength of the associations Mucca et al. Intern Emerg Med. 2011 May 5. Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 44

Conclusions Epidemiologic evidence suggests higher SSB consumption is associated with unfavorable levels of several cardiometabolic risk factors The precise mechanisms of these associations need further clarification To maintain or improve CV health, the American Heart Association recommends < 450 kcal (36 oz.) SLB per week for children and adults Sugar-Loaded Beverages and the Impact on Cardiovascular Health - Christina Shay, PhD, MA 45

Mucca et al. Intern Emerg Med. 2011 May 5. [Epub ahead of print] 46