Effect of lifelong added sugars consumption at human relevant levels on food intake and body composition of C57BL6 mice

Dr Louie, Chun Yu Jimmy   (Principal Investigator (PI))

Dr Li Edmund Tsze Shing   (Co-Investigator)

Professor Chan Chi Bun   (Co-Investigator)

Dr Wan Jennifer Man Fan   (Co-Investigator)

24

2017-01-01

2018-12-31

150000

Effect of lifelong added sugars consumption at human relevant levels on food intake and body composition of C57BL6 mice

added sugars, adiposity, life cycle, metabolic health, obesity, sucrose

NutritionEndocrinology

Physical Sciences (P)

201607159003

Seed Fund for Basic Research for New Staff

2016

Completed

The effect of sugars on health has been a controversial topic. Some researchers argue that high added sugars intake is the main factor behind the current obesity epidemic (1, 2), while others argue that calorie intake from sugars is no different from calories from other macronutrients in terms of their effect on energy balance (3). The recent guidelines from the World Health Organization (4), recommending a limit of 50% of energy intake) of individual types of sugars, in particular fructose, have been shown to impair metabolic health (e.g. increase triglyceride level, induces non-alcoholic fatty liver diseases, increases visceral fat deposition), many of these studies were short-term studies which aimed at examining the potential metabolic pathways behind such changes, thus requiring supraphysiological doses of sugars to induce a large impairment in metabolic health in a relatively short time frame. Results from these studies, while useful for the understanding of the potential mechanism behind such metabolic impairment, are not directly translatable into human relevant advices. This has been the main point of controversy in the debate about the effects of sugars on metabolic health. Furthermore, fructose is rarely used in isolation as a sweetening agent in our foods. Instead dietary added fructose come mainly from high fructose corn syrup (~55% fructose + 45% glucose) or sucrose (a disaccharide consisting of 50:50 mix of fructose and glucose). Since fructose is absorbed and metabolized differently from glucose, findings from studies using fructose as the sole source of added sugars bear little resemblance of the real world situation in humans. Last but not least, most if not all animal studies examining the effects of sugars on health and metabolism compared a sugar-containing diet with one that replaces all sugars with starch (e.g. corn starch or maltodextrin). In the modern world, humans rarely consume a diet void of added sugars – reports around the world suggest that on average humans consumed between 12 – 18% added sugars daily (5), with 5% or less consuming a diet that has less than 5% calorie from added sugars (6). This further adds to the irrelevance of the results of prior animal studies to advice for humans. Experimental evidence from human studies came mainly from short-term feeding trials, e.g. (7). While the short-term trials usually use normal dietary doses of sugars, unfortunately, short-term studies do not provide strong enough evidence to examine the long-term effect. Results from observational/population-based studies were also often used to support the argument that high sugars intake may be associated with ill health, however the evidence remains inconclusive (8-10). It is also important to note that results from observational studies do not support conclusions related to causation. To better inform our understanding on the causative effects (or lack thereof) of long-term sugars consumption on metabolic health, it is important to use an experimental design. A life-long dietary intervention with human relevant consumption level of added sugars is only feasible in laboratory animals with a relatively short lifespan, such as mice (~2 years). The main objective of the proposed study is to investigate the effect(s) of chronic added sugars (in the form of sucrose) consumption, at human relevant levels (10% vs. 25%), on ad libitum dietary intake and body composition of male mice (C57BL/6). The % calorie from sucrose is set at 10% and 25% to ensure our results are easily related to the two most commonly used dietary added sugars advice for humans, i.e. <10% calorie from added sugars from the World Health Organization (4); and <25% calories from added sugars for better nutrient intake from the US Institute of Medicine (11). This study will directly test the hypothesis that ‘lifelong consumption of added sugars, at human relevant levels, will induce over-eating and impaired glucose metabolism, as well as increase adiposity compared with a low added sugars diet’. It will also test a secondary hypothesis that ‘reverting to a low added sugars diet from a high added sugars diet will reverse some if not all of these adverse effects’. Our life-long observational design also allows us to test another secondary hypothesis that ‘chronic added sugars consumption will lower the life expectancy of mice compared with a low added sugars diet’. References: 1. Bray GA, Nielsen SJ, 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(4):537-43. 2. Ludwig DS, Peterson KE, Gortmaker SL. Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospective, observational analysis. The Lancet. 2001;357(9255):505-8. 3. Kahn R, Sievenpiper JL. Dietary Sugar and Body Weight: Have We Reached a Crisis in the Epidemic of Obesity and Diabetes?: We Have, but the Pox on Sugar Is Overwrought and Overworked. Diab Care. 2014;37(4):957-62. 4. World Health Organization. Guideline: Sugars intake for adults and children. Geneva, Switzerland: World Health Organization, 2015. 5. Newens KJ, Walton J. A review of sugar consumption from nationally representative dietary surveys across the world. J Hum Nutr Diet. 2016;29(2):225-40. 6. Lei L, Rangan AM, Flood VM, Louie JCY. Dietary intake and food sources of added sugar in the Australian population. Br J Nutr. 2016;115(5):868-77. 7. Raatz SK, Johnson LK, Picklo MJ. Consumption of Honey, Sucrose, and High-Fructose Corn Syrup Produces Similar Metabolic Effects in Glucose-Tolerant and -Intolerant Individuals. The Journal of Nutrition. 2015;145(10):2265-72. 8. Gyllenhammer LE, Weigensberg MJ, Spruijt-Metz D, Allayee H, Goran MI, Davis JN. Modifying influence of dietary sugar in the relationship between cortisol and visceral adipose tissue in minority youth. Obesity. 2014;22(2):474-81. 9. Tasevska N, Park Y, Jiao L, Hollenbeck A, Subar AF, Potischman N. Sugars and risk of mortality in the NIH-AARP Diet and Health Study. The American Journal of Clinical Nutrition. 2014;99(5):1077-88. 10. Kell KP, Cardel MI, Bohan Brown MM, Fernández JR. Added sugars in the diet are positively associated with diastolic blood pressure and triglycerides in children. The American Journal of Clinical Nutrition. 2014;100(1):46-52. 11. Institute of Medicine Panel on Macronutrients. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC, USA: National Academy Press, 2005.