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Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies

BMJ 2013; 346 doi: https://doi.org/10.1136/bmj.e7492 (Published 15 January 2013) Cite this as: BMJ 2013;346:e7492

Re: Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies

We read with interest the high-quality systematic review by Te Morengo et al. [1]. Although the conclusion that sugars in isocaloric exchange with other sources of carbohydrate do not affect body weight is well supported by the available evidence and agrees well with the effect of sugars on other related cardiometabolic endpoints, the conclusion that sugars are a determinant of body weight from ad libitum trials requires some attention.

A large database of feeding trials have studied the effect of sugars in isocaloric exchange for other sources of carbohydrate. We have conducted a series of systematic reviews and meta-analyses of these trials in relation to the effect of fructose (the presumed culprit) on cardiometabolic risk factors (ClinicalTrials.gov identifier: NCT01363791). In agreement with the present systematic review [1], pooled analyses have shown that fructose in isocaloric exchange for other carbohydrates does not increase body weight [2]. The same is also true for fasting lipids [3] and uric acid [4], as well as postprandial lipids and non-alcoholic fatty liver disease (NAFLD) [unpublished data] with benefits seen for glycemic control [5] and blood pressure [6]. In these syntheses, fructose was no worse than other sources of carbohydrate (even under positive energy balance, at large doses well above the mean level of fructose intake [7],or in fluid form) as long as the comparisons remain matched for energy. As more trials have become available, earlier signals for harm in relation to fasting (>60 g/day [3] and >100 g/day [8]) and postprandial (>50 g/day [8]) triglycerides at high-dose thresholds have not been replicated [unpublished data].

The authors interpreted the ad libitum trials as providing evidence for harm [1]. In the absence of an effect under conditions of isocaloric exchange of sugars with other sources of carbohydrate, it was concluded that changes in body fatness are mediated through the ability of sugars in ad libitum trials (defined as, “no strict control of food intake”) to increase energy intake rather than any metabolic effects particular to sugars. The problem is whether the design of these trials allows this inference to be drawn. A true ad libitum design should allow for the free selection of study foods (sugary foods and beverages) not just the background diets. The trials in question required that the participants consume all sugary study foods and beverages providing excess energy or eliminate these foods while not strictly controlling the food intake of the background diets. The comparator was the background diets alone [1]. In the absence of a macronutrient comparator providing or displacing the same amount of excess energy, this design is necessarily an imbalanced, hypercaloric (more calories in the sugar arm) design which makes it difficult to conclude that sugary foods and beverages more than any other caloric foods lead to greater overall caloric intake and weight gain. This is the interpretation we adopted with our systematic reviews and meta-analyses of the effect of fructose on cardiometabolic risk factors. As with the present review [1], we found a consistent signal for harm in hypercaloric trials in which diets were supplemented with fructose providing excess energy (+18-97% energy) at extreme doses (+104-250 g/day) well above the 95th-percentile for intake in the population [7] compared with the same diets alone (without the excess energy). Under these conditions, pooled analyses showed clinically important increases in body weight and uric acid [2,3], as well as in fasting triglycerides, postprandial triglycerides, markers of non-alcoholic fatty liver disease (NAFLD), glucose, and insulin [unpublished data]. When the excess energy from fructose in these trials, however, was matched with excess energy from glucose, the signal for harm disappeared [2-6]. That is, fructose did not behave differently than glucose as a source of excess energy. The implication is that the observed adverse effects of sugars and fructose on body weight and cardiometabolic risk may be more attributable to the provision of excess energy rather than the sugar itself.

Before one can conclude that fructose-containing sugars uniquely lead to an increase in overall energy intake, weight gain and greater cardiometabolic risk, evidence of a meaningful effect of sugars on energy intake and weight gain beyond that of other commonly consumed forms of energy (such as refined grains, salty snacks, or processed meats) must first be established. As the decrease in energy from one food will tend to be compensated by the increases in energy from another food to maintain energy balance under free living, ad libitum conditions, it is important to compare fructose-containing sugars with those foods likely to replace these sugars in the diet. True ad libitum trials which compare fructose-containing sugars with other sources of energy under free living, “real world” conditions are urgently needed.

References
1. Te Morenga L, Mallard S, Mann J. Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies. BMJ 2013;346:e7492
2. Sievenpiper JL, de Souza RJ, Mirrahimi A, Yu ME, Carleton AJ, Chiavaroli L, DiBuono M, Jenkins AL, Leiter LA, Wolever TWS, Beyene J, Kendall CWC, Jenkins DJA. Effect of fructose feeding on body weight: systematic review and meta-analyses of controlled feeding trials. Ann Intern Med 2012;156, 291-304
3. Sievenpiper JL, Carleton AJ, Chatha S, Jiang HY, de Souza RJ, Beyene J, Kendall CW, Jenkins DJ. Heterogeneous effects of fructose on blood lipids in individuals with type 2 diabetes: systematic review and meta-analysis of experimental trials in humans. Diabetes Care. 2009;32:1930-7
4. Wang DD, Sievenpiper JL, de Souza RJ, Chiavaroli L, Ha V, Cozma AI, Mirrahimi A, Yu ME, Carleton AJ, DiBuono M, Jenkins AL, Leiter LA, Wolever TWS, Beyene J, Kendall CWC, Jenkins DJA. The effects of fructose intake on serum uric acid vary among controlled dietary trials. J Nutr. 2012;142:916-23.
5. Cozma AI, Sievenpiper JL, de Souza RJ, Chiavaroli L, Ha V, Wang DD, Mirrahimi A, Yu ME, Carleton AJ, DiBuono M, Jenkins AL, Leiter LA, Wolever TWS, Beyene J, Kendall CWC, Jenkins DJA. Effect of Fructose on Glycemic control in Diabetes: A Systematic Review and Meta-Analysis of Controlled Feeding Trials. Diabetes Care. 2012;35:1611-20.
6. Ha V, Sievenpiper JL, de Souza RJ, Chiavaroli L, Wang DD, Cozma AI, Mirrahimi A, Yu ME, Carleton AJ, DiBuono M, Jenkins AL, Leiter LA, Wolever TWS, Beyene J, Kendall CWC, Jenkins DJA. Effect of Fructose on Blood Pressure: A Systematic Review and Meta-Analysis of Controlled Feeding Trials. Hypertension. 2012;59:787-95.
7. Marriott BP, Cole N, Lee E. National estimates of dietary fructose intake increased from 1977 to 2004 in the united states. J Nutr. 2009;139:1228S-1235S.
8. Livesey G, Taylor R. Fructose consumption and consequences for glycation, plasma triacylglycerol, and body weight: meta-analyses and meta-regression models of intervention studies. Am J Clin Nutr. 2008;88:1419-37.

Competing interests: I have received research support from the Canadian Institutes of health Research (CIHR), Calorie Control Council, The Coca-Cola Company (investigator initiated, unrestricted grant), Pulse Canada, and International Nut Council. I have also received travel funding, speaker fees, and/or honoraria from The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH), Canadian Diabetes Association (CDA), Calorie Control Council, Diabetes and Nutrition Study Group (DNSG) of the European Association for the Study of Diabetes (EASD), International Life Sciences Institute (ILSI) North America, ILSI Brazil, Abbott Laboratories, Pulse Canada, and The Coca-Cola Company. My wife is an employee of Unilever Canada.

24 February 2013
John L Sievenpiper
Knowledge Synthesis Lead
Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital
#6137-61 Queen Street East, Toronto, ON, M5C 2T2, CANADA