The Role of Fructose, Sucrose, and High-fructose Corn Syrup in Diabetes

US Endocrinology 2013;9(2):128–38


Concerns are growing regarding the role of dietary sugars in the development of obesity and cardiometabolic diseases, including diabetes. Highfructose corn syrup (HFCS) and sucrose are the most important dietary sweeteners. Both HFCS and sucrose have overlapping metabolic actions with adverse effects attributed to their fructose moiety. Ecologic studies have linked the rise in fructose availability with the increases in obesity and diabetes worldwide. This link has been largely underpinned by animal models and select human trials of fructose overfeeding at high levels of exposure. Although prospective cohort studies have shown significant associations comparing the highest with the lowest levels of intake sugarsweetened beverages, these associations are small, do not hold at moderate levels of intake, and are subject to collinearity effects from related dietary and lifestyle factors. Most systematic reviews and meta-analyses from controlled feeding trials have shown that fructose-containing sugars in isocaloric exchange for other carbohydrates do not show evidence of harm and, in the case of fructose, may even have advantages for glycemic control, especially at small doses. Nevertheless, trials in which fructose-containing sugars supplement diets with excess energy have shown adverse effects, effects that appear more attributable to the excess energy than the sugar. There is no unequivocal evidence that fructose intake at moderate doses is directly related with adverse metabolic effects, although there is potentially cause for concern where fructose is provided at high doses or contributes excess energy to diets. Further investigation is warranted due to the significant knowledge gaps and weaknesses in existing research.
Acknowledgments: Aspects of this work were funded by a Canadian Institutes of Health Research (CIHR) Knowledge Synthesis Grant (funding reference number, 102078) and a research grant from the Calorie Control Council.
Keywords: Diabetes, fructose, high-fructose corn syrup, sucrose
Disclosure: Adrian Cozma, HBSc, has no conflicts of interest to declare. John Sievenpiper, MD, PhD, has received research support from the Canadian Institutes of Health Research (CIHR), Calorie Control Council, The Coca-Cola Company (investigator initiated, unrestricted grant), Pulse Canada. He has received travel funding, speaker fees, and/or honoraria from the American Heart Association (AHA), American Society for Nutrition (ASN), 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. He is on the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of both the Canadian Diabetes Association (CDA) and European Association for the study of Diabetes (EASD), as well as the American Society for Nutrition (ASN) writing panel for a scientific statement on the metabolic and nutritional effects of fructose, sucrose, and high-fructose corn syrup. His wife is an employee of Unilever Canada.
Received: March 15, 2013 Accepted April 28, 2013 Citation US Endocrinology 2013;9(2):128–38
Correspondence: John L Sievenpiper, MD, PhD, 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. E:
Support: The publication of this article was supported by The Coca-Cola Company. The views and opinions expressed are those of the authors.

The total number of people with diabetes worldwide is projected to double by 2030.1,2 Given the increasing prevalence of obesity, these fgures probably underestimate the future prevalence of diabetes. The risk for developing type 2 diabetes mellitus (T2DM) and premature cardiovascular disease are strongly linked to the metabolic syndrome, a condition characterized by excess central adiposity, elevated triglycerides, reduced high-density lipoprotein (HDL) cholesterol, hypertension, and impaired glucose tolerance.3
A number of dietary factors have been implicated in the development and progression of this cardiometabolic phenotype. Chief among them have been sugars containing fructose: fructose, sucrose, and high-fructose corn syrup (HFCS). Since a temporal relationship was frst demonstrated between the increasing availability of HFCS and the prevalence of overweight and obesity in the US nearly a decade ago,4a fructose-centric view of cardiometabolic diseases has emerged. We aim to review the scientifc evidence supporting the role of fructose-containing sugars in the epidemics of diabetes and its related cardiometabolic complications.

Current Dietary Advice Regarding Sugar Intake
Various dietary guidelines have addressed sugars (see Table 1). Most have focused on the reduction of added fructose-containing sugars to maintain a healthy bodyweight.5–14 Recent American Heart Association lipid guidelines15 and international diabetes guidelines16–18 have singled out fructose by setting upper thresholds for fructose intake based on putative adverse lipid effects, although the American Diabetes Association acknowledges that fructose produces a lower postprandial glucose response when it replaces sucrose or starch in the diet.17 The guidelines implicate all fructose-containing sugars. There is now broad scientifc consensus that sucrose and most forms of HFCS are nutritionally and metabolically equivalent.19–21 Differences in the thresholds for harm set by the different guidelines, however, re"ect some uncertainty in the evidence on which the guidelines are based.

Dietary Sugar Sources/Typical Intake Patterns
Sugars are found naturally in fruit and fruit products (fructose) and are added to foods mainly as sucrose (50 % bound fructose) or HFCS (42 % to 55 % free fructose) during preparation or processing to improve their palatability. HFCS is available at various fructose levels. HFCS 42, used in beverages, processed foods, cereals, and baked goods, comprises 42 % fructose and 53 % glucose. HFCS 90 comprises 90 % fructose and 10 % glucose. It is used in small quantities for specialized applications, but is primarily blended with HFCS to produce HFCS 55, which is used in soft drinks. The most important sources of fructose are nonalcoholic beverages (46 %) followed by grain products (17.3 %), and fruit and fruit products (13.4 %) (see Figure 1). The introduction of corn sweeteners in the early 1970s led to the progressive replacement of sucrose with HFCS in sugar-sweetened beverages (SSBs), so that the availability of sucrose (44 %) and HFCS (42 %) in the US market is roughly equal.22 The use of fruit sugar concentrate is also increasing.23

Although the availability of sugars has increased considerably over the last 50 years,24 total added sugar intake has begun to decrease over the last decade in the US. According to an analysis of the National Health and Nutrition Examination Survey (NHANES) III from 1999 to 2008 (n=42,316), the intake of added sugars in the US has decreased from 100.1 g/day (18.1 % energy) to 76.7 g/day (14.6 % energy), with a reduction in the intake of SSBs accounting for two-thirds of this reduction.25 The contribution of fructose to the diet has followed these trends. Total fructose intake is 49 g/day (9.1 % energy intake) at the 50th percentile and 87 g/day (14.6 % energy intake) at the 95th percentile.22 The highest intakes of fructose are among males 15–18y and 19–22y, each of whom consumes 75 g/day at the 50th percentile and 121 g/day and 134 g/ day, respectively, at the 95th percentile. On a per bodyweight basis, the highest intakes of fructose are in non-breast-fed infants and toddlers.22

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