TABLE OF CONTENTS. Editorial Sugar sweetened beverages: A missing piece of the obesity puzzle?

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1 Oct (Vol. 2, Issue 2, pages 1 19) TABLE OF CONTENTS Editorial Board Editor in Chief Jean Pierre Després Québec, Canada Associate Editors Philip Barter Sydney, Australia Bryan Brewer Washington DC, USA Peter Libby Boston, USA Managing Editor Isabelle Lemieux Québec, Canada Editorial Office Assistant Diana Vincze Québec, Canada Editorial Sugar sweetened beverages: A missing piece of the obesity puzzle? By Jean Pierre Després, PhD, FAHA Luc F. Van Gaal, MD, PhD pages 2 5 Global dimensions of sugary beverages and programmatic and policy solutions By Barry M. Popkin, PhD pages 6 9 Soft drinks and obesity: the evidence By George A. Bray, MD pages Sugar sweetened soft drink consumption and risk of type 2 diabetes and cardiovascular risk By Frank B. Hu, MD, PhD pages 15 18

2 Oct (Vol. 2, Issue 2, pages 2 5) EDITORIAL SUGAR SWEETENED BEVERAGES: A MISSING PIECE OF THE OBESITY PUZZLE? By Jean Pierre Després, PhD, FAHA Centre de recherche de l Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC, Canada; Division of Kinesiology, Department of Social and Preventive Medicine, Université Laval, Québec, QC, Canada jean pierre.despres@criucpq.ulaval.ca By Luc F. Van Gaal, MD, PhD Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Antwerp, Belgium luc.van.gaal@uza.be Every week there is an article published in the lay press on the current epidemic of obesity and on the wave of overweight/obese children who are at very high risk of beginning their young adult lives with diabetes or at least with their share of cardiovascular disease risk factors. For instance, it is really sad to note that type 2 diabetes has now struck the pediatric population [1]. Obesity is a complex condition as it is quite heterogeneous both in terms of etiology and related complications [2 4]. With the exception of rare genetic causes of obesity and endocrine diseases [5], most common forms of obesity are polygenic [6]. Thus, several susceptibility genes interact with permissive environmental factors leading to weight gain, body fat accumulation and eventually obesity [7, 8]. Obesity obviously results from an imbalance between caloric intake and energy expenditure [9, 10]. There is a debate, however, on the respective roles of increased caloric intake vs. reduced physical activity/exercise as the main driving force behind the epidemic of obesity observed over the last century [11]. On the energy intake part of the equation, it appears that we have recently moved from a technical discussion on the role of the macronutrient composition of the diet (such as the high fat diet which was a popular culprit in the eighties) to some key qualitative aspects of our nutritional habits [12]. For instance, it is now fairly well accepted that a low consumption of fruits and vegetables combined with excessive consumption of animal meat and of refined foods with a high energy density (not only rich in fat but also in refined sugar) are factors which promote obesity [12]. However, until recently, little attention had been given to calories consumed in liquid forms. There is now evidence that sugar sweetened beverages have a low satiety potential [13, 14] and that increased consumption 2

3 of sugar sweetened beverages are not associated with a compensatory reduction in the caloric intake from solid foods [15, 16]. Thus, calories from sugar sweetened beverages essentially add to daily caloric intake. Although numerous factors contribute to the epidemic of obesity, limiting the intake of sugar sweetened beverages could contribute to reduce daily caloric intake (even without other adjustments in eating habits) [17]. In a world where dieting is sometimes a sport very difficult to practice with problems of adherence and compliance, approaches to limit the intake of sugarsweetened beverages could represent a very simple recommendation which could have significant clinical and public health implications. This issue of the CMReJournal addresses this original question which identifies a new and potentially important target in our battle against the obesity epidemic. Three international experts cover different angles of the topic. In his paper, George Bray reviews the evidence available on the association between the consumption of sugar sweetened beverages and obesity. Results from acute and shortterm studies are discussed. In addition, results from the few meta analyses available are presented. Bray concludes that there is indeed evidence of a relationship between the consumption of sugarsweetened beverages and obesity and identifies fructose as a potentially important mediator of their deleterious effects on cardiometabolic risk variables. Recent evidence suggests that fructose may promote intra abdominal (visceral) fat accumulation and liver fat deposition [18], two phenotypes associated with the presence of insulin resistance and the metabolic syndrome [2 4]. Clearly, further mechanistic studies are needed to examine this important question. In his paper, Frank Hu reviews the key epidemiological data on the relationship between consumption of sugar sweetened beverages and risk of type 2 diabetes and cardiovascular disease. Hu also reaches the conclusion that consumption of sugar sweetened beverages increases risk of both diabetes and cardiovascular disease in a manner which may be partly independent from body weight gain. The latter finding is also concordant with the results of metabolic studies highlighting the potentially deleterious effects of fructose on cardiometabolic risk. Thus, there is evidence that sugar sweetened beverages have deleterious effects on adiposity and the risk of both diabetes and cardiovascular disease. In the paper introducing the issue, Popkin provides data showing that the consumption of sugar sweetened beverages has increased over the last few decades, a phenomenon which must be a source of concern as it contributes to increase total caloric intake. Popkin endorses the position of Bray and Hu on the hazards of a high consumption of sugarsweetened beverages and moves on to propose possible solutions. His proposal to consider taxation of sugar sweetened beverages has been the topic of another paper that he recently co signed with Dr. Kelly Brownell as the leading author in the NEJM [13]. The mechanics of how to possibly apply such tax is further discussed in this recent paper [13]. Furthermore, he suggests that regulations should be put in place so that vending machines selling sugar sweetened beverages in schools to vulnerable populations and in the workplace should be banned. Of course, actions should also be taken to make sure that children have easy access to safe water. 3

4 In the current epidemic of type 2 diabetes and considering that patients with type 2 diabetes are younger than ever because of their obesity, a robust action plan should be put in place to battle the epidemic of obesity underlying the huge prevalence figures reached by this metabolic disease (type 2 diabetes) which have been suggested to limit our ability to successfully battle cardiovascular disease in the 21 st century. The question is complex as numerous societal, individual and biological factors are at interplay. However, on top of all the appropriate nutritional guidance that our patients should receive, it appears that a focus on the consumption of sugar sweetened beverages may represent a simple initial step in an attempt to reduce caloric intake. Thus, limiting the consumption of sugar sweetened beverages represents one element of a healthy lifestyle to prevent or manage obesity and its related complications. References 1. Rosenbloom AL, Joe JR, Young RS, et al. Emerging epidemic of type 2 diabetes in youth. Diabetes Care 1999; 22: Després JP and Lemieux I. Abdominal obesity and metabolic syndrome. Nature 2006; 444: Després JP, Lemieux I, Bergeron J, et al. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol 2008; 28: Van Gaal LF, Mertens IL and De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature 2006; 444: O'Rahilly S and Farooqi IS. Human obesity as a heritable disorder of the central control of energy balance. Int J Obes (Lond) 2008; 32 Suppl 7: S Rankinen T, Zuberi A, Chagnon YC, et al. The human obesity gene map: the 2005 update. Obesity (Silver Spring) 2006; 14: Bouchard C, Tremblay A, Després JP, et al. The response to long term overfeeding in identical twins. N Engl J Med 1990; 322: Bouchard C, Després JP and Mauriège P. Genetic and nongenetic determinants of regional fat distribution. Endocr Rev 1993; 14: Doucet E and Tremblay A. Food intake, energy balance and body weight control. Eur J Clin Nutr 1997; 51: Hill JO. Understanding and addressing the epidemic of obesity: an energy balance perspective. Endocr Rev 2006; 27: Jeffery RW and Utter J. The changing environment and population obesity in the United States. Obes Res 2003; 11 Suppl: 12S 22S. 12. Gidding SS, Lichtenstein AH, Faith MS, et al. Implementing American Heart Association pediatric and adult nutrition guidelines: a scientific statement from the American Heart Association Nutrition Committee of the Council on Nutrition, Physical Activity and Metabolism, Council on Cardiovascular Disease in the Young, Council on Arteriosclerosis, Thrombosis and Vascular Biology, Council on Cardiovascular Nursing, Council on Epidemiology and Prevention, and Council for High Blood Pressure Research. Circulation 2009; 119: Brownell KD, Farley T, Willett WC, et al. The public health and economic benefits of taxing sugar sweetened beverages. N Engl J Med 2009; 360: Mourao DM, Bressan J, Campbell WW, et al. Effects of food form on appetite and energy intake in lean and obese young adults. Int J Obes (Lond) 2007; 31:

5 15. De Castro JM. The effects of the spontaneous ingestion of particular foods or beverages on the meal pattern and overall nutrient intake of humans. Physiol Behav 1993; 53: Harnack L, Stang J and Story M. Soft drink consumption among US children and adolescents: nutritional consequences. J Am Diet Assoc 1999; 99: Mattes RD and Popkin BM. Nonnutritive sweetener consumption in humans: effects on appetite and food intake and their putative mechanisms. Am J Clin Nutr 2009; 89: Stanhope KL, Schwarz JM, Keim NL, et al. Consuming fructose sweetened, not glucose sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest 2009; 119:

6 Oct (Vol. 2, Issue 2, pages 6 9) GLOBAL DIMENSIONS OF SUGARY BEVERAGES AND PROGRAMMATIC AND POLICY SOLUTIONS By Barry M. Popkin, PhD University of North Carolina, Chapel Hill, NC, USA popkin@unc.edu Overview Over the past half century, there has been a rapid expansion in the consumption of caloric beverages, particularly those sweetened with some type of sugar. These dynamics have been driven partly by our preference for sweetened products and our desire for more options other than water and unsweetened tea and coffee and small amounts of milk and alcohol in our daily consumption patterns. At the same time, modern manufacturing, marketing and food distribution systems coupled with global subsidies of sugar have created very cheap Key Points There is a marked increase across the globe in consumption of caloric beverages, particularly sugar sweetened beverages (SSB s). For hundreds of thousands of year, man has consumed water alone (with only breast milk consumption for a few years of early life). Water is essential for life; we die in 2 4 days without water. For reasons unknown, we developed independent of our hunger mechanism, a separate thirst mechanism. Thus, when over the last 10 12,000 years we have developed caloric beverages we did not reduce food intake when we consumed them. However, this became important and detrimental to global health only in the past years. Globally, we have increased by hundreds of kcals per day our intake of SSB s in the past few decades. This unprecedented increase in intake of caloric beverages for which our body does not compensate by reducing food intake has been critical for global increased energy intake and subsequently added weight gain and central adiposity. Countries throughout the world are beginning to take actions to reduce intake of SSB s. Taxation, removal of vending machines from public facilities, promotion of water consumption, eliminating marketing of these products on TV and other media are some of the regulations and policies being implemented. alternatives to water, milk and alcohol that have captured very large segments of demand for beverages. Modern beverage companies have found ways to increase our total beverage intake. Sweetness Preference As I show in my book, sweetness preference has been with us for many thousands of years [1]. Furthermore, for hundreds of thousands of years, primates and mammals have showed a preference for sweet fruit. In the past half century, we have increasingly sweetened our food supply. Studies from places as diverse as the US, Mexico, Australia and South Africa have shown large increases in sugar intake, be it in the form of honey, a range of sugars from cane and beets, fruit juice concentrate, high 6

7 fructose corn syrup or the myriad other types of caloric sweeteners. The book provides the references used in my research on the global dimension of caloric sweeteners and the increases in all countries of sugar intake in the past several decades [1]. Beverages with Calories and Their Unique Biology Our biology is also very much a product of our need for water intake in some form. We die in 2 4 days if we consume no water whereas we take months to die with no food consumption. Food was highly seasonal for much of our development. It was very important for us to consume food when available and at the same time we had to consume water daily. For reasons and mechanisms we do not fully understand, we do not reduce food intake when we consume water or any other beverage. This is linked in unclear ways back to our evolution. So when Figure 1: Beverage history timeline. we drink a beverage be it water, beer, wine, milk, fruit juice or some sugar sweetened beverage we do not reduce our food intake. This lack of compensation is hard to explain; however, it is critical in understanding how the recent global increase in caloric beverage consumption is affecting our net energy balance, abdominal obesity and metabolic conditions [2]. Figure 1 shows the history of our experience with beverages. Increases in the Intake of Caloric Beverages In essence, what most nations in the world have seen is a remarkable increase in the consumption of caloric beverages. Some of this increase is healthy as with increased intake of milk. Unfortunately, much of it is whole milk, which contains excessive saturated fat. However, most nations have experienced a marked increase in sugary beverages. In Mexico, consumption of caloric beverages doubled from , with much of this intake in the form of juices with sugar added, whole milk 7

8 or sugar sweetened fruit and soft drinks as shown in Figure 2 [3]. I detail some of this history in my book [1]. Programmatic Actions A few countries to date have created beverage guidance panels and begun to attempt to shift beverages back to healthier options. Mexico stands out for taking on this task in a most systematic way. Research in Figure 2: Beverage consumption trends in Mexico, Mexico and the US (unpublished 20 year study of the effect of price changes on diet, weight dynamics and metabolic outcomes from CARDIA) shows that taxation of caloric beverages is linked with significant improvements in health [3, 4]. Program and policy actions across the globe are attempting in a range of ways to reduce consumption of sugary beverages. Nevertheless, there has been little rigorous evaluation of these options to date. Taxation is one of the prime targets for caloric beverages. In Mexico and unpublished US research, we show that sugar sweetened beverages are very sensitive to food prices. Applying an excise tax based either on the number of grams of sugar (any form of caloric sweetener in water) or the numbers of ounces would provide the clearest way to increase prices and significantly reduce intake of these sugary beverages. The Mexican panel wanted to couple a sugary beverage tax with one on the fat content of milk in order to enhance water and reduce fat milk intake. Regulations are another important option. France banned all vending machines from its schools as did Singapore, among other countries. France, Sweden and a few other countries have banned sugary beverage advertisement from media to which children and teens are exposed. There is strong evidence that any approach that changes the norms of society by banning advertisements of all sorts, keeping consumption of sugar sweetened beverages out of schools and 8

9 public places and providing inexpensive healthy options such as potable water, chilled in hot climates, is important. This option has worked for tobacco and can work for sugar sweetened beverages. Summary Sugar sweetened beverages in the area of cardiometabolic risk represent the low hanging fruit that is closest to tobacco as an item with no benefits and huge health costs. Consumption of all caloric beverages, particularly those we would call sugar sweetened beverages, have become a major component of the diet of most nations. Furthermore, due to the lack of dietary compensation when they are drunk, they have added considerably to the globe s problems of excess energy intake relative to energy expenditure. The major options for addressing this situation involve governmental actions. Education will not work, as the funding of the sugar and beverage sectors is in the tens of billions of dollars globally. Taxation, regulation in public facilities and regulation of media are the major options countries have other than completely banning these products. References 1. Popkin BM. The World Is Fat The Fads, Trends, Policies, and Products That Are Fattening The Human Race. New York: Avery Penguin Group, Wolf A, Bray GA and Popkin BM. A short history of beverages and how our body treats them. Obes Rev 2008; 9: Barquera S, Hernandez Barrera L, Tolentino ML, et al. Energy intake from beverages is increasing among Mexican adolescents and adults. J Nutr 2008; 138: Rivera JA, Munoz Hernandez O, Rosas Peralta M, et al. [Beverage consumption for a healthy life: recommendations for the Mexican population]. Salud Publica Mex 2008; 50:

10 Oct (Vol. 2, Issue 2, pages 10 14) SOFT DRINKS AND OBESITY: THE EVIDENCE George A. Bray, MD Pennington Biomedical Research Center, Baton Rouge, LA, USA Introduction Obesity has become an epidemic problem. It affects both children and adults. Recent data from the National Health and Nutrition Examination Survey [1] showed that the prevalence of obesity in children has continued to rise and is now 18%. This extra fat requires the intake of more food energy over time than is needed by the body. Thus, any form of energy that we ingest may play a role in the development of obesity. These extra calories are of particular concern for the childhood obesity epidemic, because children have limited responsibility for Key Points Intake of sugar sweetened beverages has continued to rise, and the fructose they contain, either from sugar (sucrose) or high fructose corn syrup has been associated with higher energy intake, an increase in body weight, a risk of developing metabolic syndrome and gout in men. Fructose in single doses increases thermogenesis, blood pressure and triglycerides, particularly in men. Sugar sweetened beverages or fructose itself increase blood pressure and hepatic lipid production in healthy individuals over a 10 week period. Mechanisms for these effects of sugar sweetened beverages may reflect reduced caloric compensation of liquid calories and increased production of uric acid during hepatic metabolism of fructose. their caloric intake. With this focus on children, I have reviewed the data on the effects of fructose on acute and intermediate metabolic responses and on the effects of beverage intake on energy intake and weight gain. The possibility that calorie containing beverages might have a strong relationship in the development of obesity was highlighted in a paper which showed that the growing use of highfructose corn syrup between 1970 and 1990 paralleled the rising prevalence of obesity in the period between 1970 and 2000 [2 4]. Acute Studies Several studies have examined the effects of single doses of fructose vs. glucose on energy expenditure, serum lipids and blood pressure. From these studies it is clear that fructose increases thermogenesis more than glucose, that it increases triglycerides and increases blood pressure. A 75 g oral load of glucose or fructose was given to 17 volunteers and metabolic changes followed for 4 hours. Fructose stimulated oxygen consumption more than glucose but produced a much smaller 10

11 stimulation of insulin [5]. Fructose increased the respiratory quotient more than glucose, a finding that may imply increase de novo lipogenesis. Blockade of the sympathetic nervous system with propanolol, a beta adrenergic blocking drug, reduced oxidation of both fructose and glucose by about 40%. Of interest, both obese and diabetic patients had a similar stimulation of oxygen uptake after infusion of glucose which was smaller than the response to fructose [6]. To evaluate the effect of fructose on lipids, 17 obese men (n=9) and women (n=8) with a body mass index (BMI) >30 kg/m 2 were admitted to the Clinical and Translational Research Center for a cross over study lasting 24 hours in where mixed meals and beverages with 30% fructose or 30% glucose were given to healthy volunteers and blood samples drawn periodically. The area under the curve of insulin, leptin, and triglycerides were measured. The rise in plasma glucose was smaller after fructose, but the rise in triglycerides and lactate larger. Insulin and leptin both showed a lower response to fructose than to glucose. These responses in lipids are seen primarily in men with no response or only small responses in women [7]. The response of blood pressure to fructose was examined in 15 healthy men who drank 500 ml volumes of water (placebo) or 60 g of fructose or glucose on 3 occasions. Blood pressure, metabolic rate and autonomic nervous system activity were measured for 2 hours. Administration of fructose was associated with an increase in both systolic and diastolic blood pressure. Blood pressure did not rise after either glucose or water [8]. Intermediate Length Studies A number of studies comparing sucrose, artificially sweetened beverages, fructose or glucose have been reported. In one 10 week study, 41 overweight men and women entered a 10 week parallel arm study. One group of 21 adults received 3.4 MJ (813 kcal) of sugar containing beverages and were compared with 20 others who received beverages sweetened with aspartame, containing about 1 MJ (240 kcal) and no sugar. For their other foods, the subjects could select freely from foods at a kiosk run by the study group. After 10 weeks, energy intake had increased by 1.6 MJ/day and sucrose to 28% of intake in the group receiving the sugar containing beverages. Protein and fat intake declined. Body weight and fat mass increased by 1.6 and 1.3 kg respectively in the sugar group and decreased by 1.0 and 0.3 kg in the aspartame sweetened group. Blood pressure increased by 3.8/4.1 mmhg in the sugar consuming group but did not change in the other group. Concentrations of several inflammatory markers were also changed. In the group consuming sucrose, haptoglobin increased by 13%, transferrin by 5% and C reactive protein by 6%. In the group receiving the aspartame sweetened beverages, haptoglobin decreased by 16%, C reactive protein decreased by 26% and transferrin was basically unchanged with a small 2% fall [9, 10]. In a study of similar length, fructose and glucose were compared when added to the diet as 25% of calories for 10 weeks, 8 weeks as out patients and 2 weeks as in patients at the end of the study. Thirty two men and women had a diet with 15% protein, 30% fat and 55% carbohydrate. Fifteen received 25% of calories in glucose beverages and 17 in fructose beverages. Intra abdominal (visceral) fat increased by 14% in the fructose consuming group compared to about 5% in the control group with no significant change in body weight or subcutaneous fat. De novo lipogenesis increased and postprandial triglycerides increased, particularly at night [11]. 11

12 Meta Analyses of Beverage Consumption Several meta analyses on the effect of soft drink consumption on changes in energy intake or changes in body weight have been published. In the study by Vartanian et al. [12] the magnitude of the relationship between the beverage intake and body weight was expressed as the effect size or r value, which represents the magnitude of the relationship between the beverage intake and body weight. An effect size of 0.1 is small, of 0.25 is moderate and a value of 0.4 is large. They examined the effect size between soft drink consumption and BMI in 11 cross sectional studies and found a significant positive relationship in 2, but not in 9 others, and there were no studies where drinking beverages was associated with a significant reduction in BMI. Among longitudinal studies that have examined the association between soft drink consumption and change in body weight or BMI, one was positive, 2 were mixed and 4 showed no association. Of 7 experimental studies, 5 reported a positive association with weight. Overall, the effect size for body weight was smaller than for energy intake since soft drinks are only one source of calories. In cross sectional studies the effect size was only 0.06, in longitudinal studies it was 0.03 and in short experimental studies it was Calcium intake inversely related to soft drink consumption. One study showed that a 1 oz decrease in soft drink intake increased milk intake by 0.25 oz. A second meta analysis reported by Olsen and Heitmann [13] included some additional studies. A total of 14 prospective and 5 experimental studies were identified. The majority of the prospective studies found positive associations between intake of calorically sweetened beverages and obesity. Three experimental studies found positive effects of calorically sweetened beverages on body fat, but 2 did not find any effects. The third meta analysis examined the relation of beverage intake in children and adolescents [14]. This meta analysis included 2 randomized clinical trials and 8 longitudinal studies. In an erratum to their original paper, the predicted change in BMI for each serving per day change in sugar sweetened beverage consumption was 0.02 BMI units/day (95% CI: ). The overall estimate of the association was change in BMI during the time defined by the study for each serving per day change in sugar sweetened beverage consumption. Since the BMI unit change/day is a very small unit, it was converted to a yearly change which is 1.46 BMI units enough to explain much of the current epidemic of obesity. Association of Fructose Intake with Disease Risk As the quantity of fructose and sucrose/high fructose corn syrup in the diet has increased, the number of health related issues has increased. There is a report that consumption of soft drinks is associated with the metabolic syndrome [15] and gout in men [16]. There is also a suggestion that it is associated with the development of diabetes [17]. Potential Mechanisms for the Potential Detrimental Effects of Fructose Three main mechanisms have been suggested for the effects of fructose from either high fructose corn syrup or sucrose. The inadequate reduction in caloric intake when calorie sweetened beverages are ingested has been proposed as part of the mechanism for increased energy intake and obesity [4, 18]. 12

13 In acute feeding studies, sugar sweetened beverages fail to reduce energy intake, in contrast to water [19]. The metabolic pathway for fructose, in contrast to glucose, may account for the increased de novo lipogenesis and higher triglycerides [20]. Fructose is metabolized primarily in the liver where it is converted to fructose 1 phosphate from which it can readily become a substrate for the backbone of the triglyceride molecule. Third, the metabolism of fructose in the liver generates adenosine 5 phosphate that is a substrate for conversion to uric acid through a process which alters nitric oxide generation. The enhanced production of uric acid by the liver may contribute to the relation of uric acid to cardiovascular disease [21]. The rising consumption of calorie sweetened beverages provides an increasing amount of dietary fructose. Based on this review of the literature, I conclude that in the amounts now ingested, fructose is hazardous to the health of some people. References 1. Anderson SE and Whitaker RC. Prevalence of obesity among US preschool children in different racial and ethnic groups. Arch Pediatr Adolesc Med 2009; 163: Bray GA. Fructose: Is It Bad For Our Health? A commentary prepared for a joint ILSI North America/USDA Workshop: State of the Science on Dietary Sweeteners Containing Fructose Bray GA. Fructose: should we worry? Int J Obes (Lond) 2008; 32 Suppl 7: S Bray GA, Nielsen SJ and Popkin BM. Consumption of high fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr 2004; 79: Tappy L, Randin JP, Felber JP, et al. Comparison of thermogenic effect of fructose and glucose in normal humans. Am J Physiol 1986; 250: E Teff KL, Grudziak J, Townsend RR, et al. Endocrine and metabolic effects of consuming fructose and glucosesweetened beverages with meals in obese men and women: influence of insulin resistance on plasma triglyceride responses. J Clin Endocrinol Metab 2009; 94: Couchepin C, Le KA, Bortolotti M, et al. Markedly blunted metabolic effects of fructose in healthy young female subjects compared with male subjects. Diabetes Care 2008; 31: Brown CM, Dulloo AG, Yepuri G, et al. Fructose ingestion acutely elevates blood pressure in healthy young humans. Am J Physiol Regul Integr Comp Physiol 2008; 294: R Raben A, Vasilaras TH, Moller AC, et al. Sucrose compared with artificial sweeteners: different effects on ad libitum food intake and body weight after 10 wk of supplementation in overweight subjects. Am J Clin Nutr 2002; 76: Sorensen LB, Raben A, Stender S, et al. Effect of sucrose on inflammatory markers in overweight humans. Am J Clin Nutr 2005; 82: Stanhope KL, Schwarz JM, Keim NL, et al. Consuming fructose sweetened, not glucose sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest 2009; 119: Vartanian LR, Schwartz MB and Brownell KD. Effects of soft drink consumption on nutrition and health: a systematic review and meta analysis. Am J Public Health 2007; 97: Olsen NJ and Heitmann BL. Intake of calorically sweetened beverages and obesity. Obes Rev 2009; 10:

14 14. Forshee RA, Anderson PA and Storey ML. Sugar sweetened beverages and body mass index in children and adolescents: a meta analysis. Am J Clin Nutr 2008; 87: Dhingra R, Sullivan L, Jacques PF, et al. Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle aged adults in the community. Circulation 2007; 116: Choi HK and Curhan G. Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study. BMJ 2008; 336: Aeberli I, Zimmermann MB, Molinari L, et al. Fructose intake is a predictor of LDL particle size in overweight schoolchildren. Am J Clin Nutr 2007; 86: Johnson RJ, Perez Pozo SE, Sautin YY, et al. Hypothesis: could excessive fructose intake and uric acid cause type 2 diabetes? Endocr Rev 2009; 30: Mattes RD. Fluid energy Where's the problem? J Am Diet Assoc 2006; 106: Rolls BJ, Kim S and Fedoroff IC. Effects of drinks sweetened with sucrose or aspartame on hunger, thirst and food intake in men. Physiol Behav 1990; 48: Havel PJ. Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr Rev 2005; 63:

15 Oct (Vol. 2, Issue 2, pages 15 18) SUGAR SWEETENED SOFT DRINK CONSUMPTION AND RISK OF TYPE 2 DIABETES AND CARDIOVASCULAR RISK Frank B. Hu, MD, PhD Harvard School of Public Health and Harvard Medical School, Boston, MA, USA frank.hu@channing.harvard.edu In parallel with the increasing prevalence of Key Points obesity and type 2 diabetes, the consumption Sugar sweetened soft drinks are a major source of excess of sugar sweetened soft drinks in the US has calories and glycemic load in the diet. increased dramatically in the past several Epidemiologic studies have provided substantial evidence that regular consumption of soft drinks not only decades. There is substantial evidence that contributes to weight gain and obesity, but also increases higher intake of soft drinks is associated with risk of type 2 diabetes and the metabolic syndrome. increased risk of obesity in children and The deleterious effects of soft drinks on diabetes are not adults [1]. Sugar sweetened soft drinks may entirely explained by body weight. contribute to weight gain because of the low Emerging evidence suggests that soft drink consumption is also associated with increased risk of coronary heart satiety of liquid calories. In experimental disease. studies, intake of sugar sweetened beverages is not fully compensated by reductions in energy intake in subsequent meals, resulting in increased energy intake and positive energy balance. Emerging evidence also suggests that higher consumption of sugar sweetened soft drinks may raise the risk of developing type 2 diabetes and the metabolic syndrome. Soft drinks contain large amounts of simple sugars, which can induce higher glycemic and insulinemic responses. Soft drinks are an important source of glycemic load in the diet, which has been associated with the risk of developing type 2 diabetes and cardiovascular disease. Several epidemiologic studies have examined the relationship between soft drink consumption and risk of type 2 diabetes. Schulze et al. [2] conducted a prospective analysis of soft drink consumption and risk of weight gain and diabetes among 91,249 women who were followed from 1991 to 1999 in the Nurses Health Study II. During the follow up, 741 incident cases of type 2 diabetes were confirmed. After adjustment for potential confounders, women consuming 1 or more sugar sweetened soft drinks per day had a relative risk (RR) of type 2 diabetes of 1.83 (95% CI: ; p<0.001 for trend) compared with those who consumed less than 1 of these beverages per month (see Figure). The 15

16 RR for extreme categories, after further controlling for body mass index (BMI), was 1.41 (95% CI: ; p=0.008 for trend). This finding suggests that BMI accounted for about half of the excess risk. The results for sugar sweetened cola alone were similar to those for all sugar sweetened soft drinks (multivariate adjusted RR of diabetes for consumption 1/day compared with <1/month: 1.88, 95% CI: , p<0.001 for trend). This association was also attenuated after additional adjustment for BMI (RR: 1.46, 95% CI: , p=0.004 for trend). In addition, consumption of fruit punch was associated with increased diabetes risk (RR for 1 drink/day compared with <1 drink/month, 2.00; 95% CI: ; p=0.001). In the Black Women s Health Study, Palmer et al. [3] examined the association between sugarsweetened beverage consumption and risk of type 2 diabetes among 43,960 African American women who were followed from 1995 to During the follow up, 2,713 incident cases of type 2 diabetes were identified. After adjustment for confounding variables, the RR for 2 soft drinks/day was 1.24 (95% CI: ). For fruit drinks, the corresponding RR was 1.31 (95% CI: ). The association of diabetes with soft drink consumption was primarily mediated by BMI, whereas the association with fruit drink consumption appeared to be independent of body weight. Figure: Multivariate relative risks of type 2 diabetes according to sugarsweetened soft drink consumption in the Nurses Health Study II Multivariate relative risks were adjusted for age, alcohol (0, , , 10+ g/day), physical activity (quintiles), family history of diabetes, smoking (never, past, current), postmenopausal hormone use (never, ever), oral contraceptive use (never, past, current), intake (quintiles) of cereal fibre, magnesium, trans fat, polyunsaturated fat, saturated fat, and consumption of sugar sweetened soft drinks, diet soft drinks, fruit juice, and fruit punch (other than the main exposure, depending on model). The data was based on reference 2. 16

17 Dhingra and colleagues [4] examined soft drink consumption and risk of developing the metabolic syndrome in the Framingham Heart Study. In cross sectional analysis, individuals consuming 1 soft drink/day had a 50% greater prevalence of the metabolic syndrome [odds ratio (OR): 1.48; 95% CI: ] than those consuming <1 drink/day. In prospective analysis with 4 year follow up, consumption of 1 soft drink/day was associated with increased risk of developing the metabolic syndrome (RR: 1.44, 95% CI: ). Regular consumption of soft drinks was also associated with individual components of the metabolic syndrome, including increased waist circumference (RR: 1.30, 95% CI: ), impaired fasting glucose (RR: 1.25; 95% CI: ), higher blood pressure (RR: 1.18; 95% CI: ), hypertriglyceridemia (RR: 1.25; 95% CI: ), and low HDL cholesterol (RR: 1.32, 95% CI: ). In a recent analysis, Fung and colleagues [5] examined the relationship between sugar sweetened beverages and risk of coronary heart disease (CHD) among 88,520 subjects from the Nurses' Health Study. During 24 years of follow up, 3,105 incident cases of CHD (nonfatal myocardial infarction and fatal CHD) were documented. After adjusting for cardiovascular risk factors, the RRs (and 95% CIs) of CHD according to categories of cumulative average of sugar sweetened beverage consumption (<1/month, 1 4/months, 2 6/weeks, 1/day, and 2 servings/day) were 1.0, 0.96 ( ), 1.04 ( ), 1.23 ( ), and 1.35 ( ) (p<0.001 for trend). Additional adjustment for BMI, energy intake, and incident diabetes attenuated the associations, but they remained significant. Artificiallysweetened beverages were not significantly associated with CHD. This data provides mounting evidence that sugar sweetened beverages not only contribute to positive energy balance and obesity, but also to type 2 diabetes and cardiovascular risk. It appears that the deleterious effects of soft drinks are not entirely mediated through BMI. One potential explanation is that the high glycemic load of soft drinks increases insulin demand and in the long run, may lead to beta cell failure. Because high fructose corn syrups contained in soft drinks contain roughly 45% glucose and 55% fructose, the overall glycemic index of soft drinks is only moderate due to the low glycemic index of fructose. However, overall blood glucose response is not only determined by the glycemic index value of a food, but also by its amount of carbohydrate. Thus, the concept of glycemic load, which is the product of the glycemic index value of a food and its carbohydrate content, has been used to represent the quality and quantity of carbohydrates consumed. Because of their high sugar content, soft drinks are an important source of glycemic load in the US diet. Several large populationbased studies have documented an inverse association between dietary glycemic load values and HDL levels and a positive association with triglycerides [6]. Epidemiologic studies report that a higher dietary glycemic load, especially combined with low intake of cereal fibre, significantly elevates longterm risk of type 2 diabetes and CHD (6). Therefore, the detrimental effects of sugar sweetened beverages stem from both increased caloric intake and high glycemic load values. References 1. Malik VS, Schulze MB and Hu FB. Intake of sugar sweetened beverages and weight gain: a systematic review. Am J Clin Nutr 2006; 84:

18 2. Schulze MB, Manson JE, Ludwig DS, et al. Sugar sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle aged women. JAMA 2004; 292: Palmer JR, Boggs DA, Krishnan S, et al. Sugar sweetened beverages and incidence of type 2 diabetes mellitus in African American women. Arch Intern Med 2008; 168: Dhingra R, Sullivan L, Jacques PF, et al. Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle aged adults in the community. Circulation 2007; 116: Fung TT, Malik V, Rexrode KM, et al. Sweetened beverage consumption and risk of coronary heart disease in women. Am J Clin Nutr 2009; 89: Hu FB and Willett WC. Optimal diets for prevention of coronary heart disease. JAMA 2002; 288:

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