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

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Published Online: Jan 13th 2014 European Endocrinology 2014;10(1):51–60 DOI:
Authors: Adrian I Cozma, John L Sievenpiper
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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.


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.


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 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

Animal Models
The biologic plausibility supporting a link between fructose and cardiometabolic diseases arises from the unique metabolism of fructose. Fructose, unlike glucose, bypasses phophofructokinase, allowing it to enter glycolysis as an unregulated substrate for de novo lipogenesis (DNL) inducing a metabolic syndrome phenotype. The systemic effects of fructose-induced uric acid elevation mediated by intracellular adenosine triphosphate depletion may further modulate this phenotype.26 Fructose may also accelerate the development of obesity by uncoupling hormonal regulation of food intake through a lack of stimulation of insulin and leptin and impaired suppression of ghrelin.27 Animal models support these mechanisms. It is well established that excess fructose feeding in animal studies induces a metabolic syndrome phenotype with obesity, insulin resistance, hypertension, and dyslipidemia.28–31

The ability to extrapolate from animal models, however, is limited by supraphysiologic doses (%60 % of total energy intake), and the differences in carbohydrate metabolism between animals and humans. Whereas DNL can contribute >50 % of fatty acids in rodents, this proportion is much lower in humans.32 Two carefully conducted reviews of isotopic tracer studies in humans showed that <1 % of fructose is converted to triglycerides (DNL), while the conversion to glucose (~41 %), lactate (~28 %), and glycogen (>15 %) are much higher.33,34 These estimates, however, depend on the feeding state and will likely be higher under conditions of overfeeding and excess calories.35

Although a DNL-mediated mechanism of fructose may not be quantitatively signifcant in humans, there is evidence from experimental studies in humans to support a uric acid mediated mechanism36 and impaired satiety signaling involving insulin, leptin, and ghrelin.19,20 Whether these mechanisms will translate into downstream increases in obesity, diabetes, and cardiometabolic complications at population levels of exposure, however, remains unclear.

Ecologic Studies
Ecologic studies are frequently cited as the next line of evidence strongly supporting the link between sugars and cardiometabolic disease. This link has been extensively reviewed among various indigenous populations, in which the introduction of sugar has led to a transition from healthy individuals absent of chronic disease to a population with excessive rates of obesity and cardiometabolic diseases.26

A similar association has been shown in two recent ecologic analyses for the prevalence of type 2 diabetes. One study of 43 countries and the other of 175 countries showed a significant association with the availability of HFCS37 and total sugars,38 respectively. The prevalence of diabetes was 20 % higher in countries that use HFCS compared with countries that do not37 and increased by 1.1 % for every 150 kcal/ person/day increase in total sugar availability.38 Although these studies did attempt to control for some potential confounders, residual confounding cannot be ruled out, as a number of important confounders were not addressed. The estimates were also based on the pooling of heterogeneous measurements of exposure (both for the availability of HFCS or sugars and the potential confounders for which adjustments were made) and disease incidence.

There are, however, some disparities in the ecologic data. From 1980 to 2003, total nutritive sweeteners declined 16 % in Australia (see Figure 2). Despite this decline, there was a threefold increase in the prevalence of obesity among adults and children, in line with other developed world populations. This fnding, was coined the ‘Australian Paradox’.39 The same paradox has been seen in the UK,39 the US, and Canada. Over the last decade, the reductions in the intake of total added sugars25 have not resulted in a decrease of obesity or diabetes in the US.40

These con”icting results highlight a limitation of ecologic studies of fructose. Even after adjustments, it can be diffcult to conclude whether the associations seen with fructose are caused by fructose, excess energy, or an interaction with other dietary and lifestyle factors associated with obesity and cardiometabolic risk. One reason may be the reliance on cross-sectional or passive inaccurate surveillance.41

In the case of the US, over the last decade, the reduction in added sugars has been accompanied by reciprocal increases in protein, fat, and other carbohydrates.25 These limitations open all ecologic analyses to ‘ecologic fallacy’ and reinforce the need to rely on higher-level evidence for drawing inferences.

Evidence from Prospective Cohort Studies
Among observational studies, prospective cohort studies offer the highest quality design. Several large prospective cohort studies have investigated sugars in relation to diabetes and other cardiometabolic outcomes (see Table 2). Results have differed based on whether sugars are measured as total sugars (fructose, sucrose, and or HFCS) or SSBs.

Total Sugars
Type 2 Diabetes Mellitus
None of the available cohort studies have found a signifcant positive association between total sugar and T2DM (see Table 2). The results have been equally inconclusive for the data regarding individual sugars.42–46

Other Cardiometabolic Outcomes
A similar lack of a consistent relation has been shown between total sucrose or fructose and other related cardiometabolic outcomes. No association has been shown with hypertension47 or coronary heart disease (CHD).48 Results have been mixed for gout.49–51 Under conditions where positive associations were seen, comparisons were between the highest and the lowest intakes of total fructose. There were no associations seen at levels of exposure equivalent to or below the 50th percentile for fructose intake in the US.22

Sugar-sweetened Beverages
Type 2 Diabetes Mellitus and the Metabolic Syndrome
The prospective cohort evidence has more consistently shown an association with SSBs in relation to the metabolic syndrome and T2DM (see Table 2). A systematic review and meta-analysis of the available prospective cohort studies showed evidence of a signifcant association between SSBs and the risk for both T2DM and the metabolic syndrome, comparing the highest level of exposure with the lowest level of exposure of SSBs.52 There was, however, evidence of heterogeneity among the effect estimates. The reasons for this heterogeneity remain unexplained. One factor may relate to the small effect sizes and differing levels of exposure when comparing the highest with the lowest intakes. None of the studies showed signifcant associations at levels of exposure equivalent to or below the 50th percentile for added sugars or fructose intake in the US.22,25 The authors also preferred studies reporting energy unadjusted models providing the rationale that it is on the “causal pathway” between the exposure (SSBs) and the outcome (the metabolic syndrome or diabetes). Because energy is intrinsic to all caloric foods, this lack of adjustment complicates interpretation (especially where there may be important collinearity with other highly palatable caloric foods). Adjustments also differed among the studies for body mass index (BMI), family history of diabetes, smoking, physical activity, and various other dietary factors associated with the metabolic syndrome and diabetes.

Other Cardiometabolic Outcomes
The relationship with the metabolic syndrome and diabetes is supported by other prospective cohort studies that have shown a signifcant relation of SSBs with related cardiometabolic outcomes. A World Health Organization (WHO) commissioned systematic review and meta-analysis showed that SSBs increased the risk for overweight and obesity comparing the highest with the lowest intakes in children.53 Individually, large cohort studies have also shown increases in BMI54 and a higher risk for hypertension,55 gout,50 CHD,56 and stroke57 comparing the highest with lowest intakes of SSBs. As is the case for the metabolic syndrome and diabetes, these associations, however, have not been sustained at levels of intake equivalent to or below the 50th percentile for added sugars or fructose intake in the US.22,25 These associations do remain signifcant after adjustment for energy, although the effect estimates are smaller in these models. The one exception has been for BMI in children and adolescents.22,58

The reason for the different fndings when assessing the intake of total and individual sugars versus that of SSBs remains unclear. A lower satiety potential and inadequate compensation of energy from SSBs may lead to increased energy intake and weight gain with attendant cardiometabolic complications.52 On the other hand, the contribution of total sugar intake from nutrient dense fruits and vegetables as well as whole grain products, both of which have been associated with weight loss and improved metabolic outcomes in large prospective cohort studies59–61 and randomized dietary trials,62,63 may offset any adverse metabolic effects attributable to sugars. A more compelling reason may relate to collinearity between SSBs intake and various other lifestyle factors. For example, people who have high intakes of SSBs tend to eat more calories, exercise less, and smoke more,55 whereas the opposite is true for people with high intakes of total fructose.47 A high intake of SSBs is also associated with a high intake of red meat, processed meat, refned grains, French fries, sweets, and desserts, each of which have been shown to lead to weight gain60 and increase diabetes risk.61,64,65 Analyses that have taken advantage of this collinearity by combining these foods using dietary patterns analyses have shown that a Western dietary pattern characterized by the high intakes of these foods is more associated with weight gain and diabetes risk than SSBs alone even after adjustment for SSBs.66,67

Evidence from Controlled Dietary Trials
Sugar-related Interventions
Well-conducted dietary trials, controlling for both known and unknown confounders, provide the highest level of evidence for addressing the controversy of whether there are adverse effects of sugar intake. Careful inspection of these trials show contrasting effects between isocaloric trials, in which sugars are provided in isocaloric exchange for other macronutrients (energy-matched comparison) and hypercaloric trials, in which energy from sugars are added to or displaced from background diets compared with the background diets alone (a nonenergy matched comparison).

Glycemic Control
Isocaloric trials have not shown consistent evidence of differences between the effects of sugars and those of other macronutrients on glycemic control. A relatively large database of small trials exists of the effect of sucrose in isocaloric exchange for other carbohydrates on glycemic control. Only one shorter-term trial showed that high sucrose feeding (16 % total energy) raised day-long but not fasting blood glucose compared with low-sucrose feeding under energy-matched conditions in people with T2DM,68 while all remaining trials did not show signifcant effects on any indices of glycemic control for up to 52 weeks at large intakes up to 220 g/day in people with and without diabetes.69–77 Larger and longer trials have also failed to show consistent differences in glycemic effects between diets high and low in sugars in the CArbohydrate Ratio Management in European National diets (CARMEN) trial78 or between high and low carbohydrates (including sugars) in The Pounds Lost Trial.78–80

Few hypercaloric trials have assessed the effect of sugar on glycemic control. Two small feeding trials in people with diabetes and one larger trial in people without diabetes, in which diets were supplemented with small to moderate amounts of extra energy from sucrose (24 g/day to ~72 g/day) compared with a low-calorie sweetener, have failed to show adverse effects on glycemic control for up to 22 months.76,81,82 One trial, however, showed that overfeeding of carbohydrates, including sugars, sugar-sweetened foods, and beverages, at 50 % above energy requirements increased insulin without affecting fasting blood glucose compared with the baseline diet alone (without the excess energy) in lean and obese subjects at 2 weeks.83 These data suggest that a higher level of overfeeding may be required to provoke adverse glycemic effects. Nevertheless, it is unclear whether this isolated effect on insulin would have been true if this high level of overfeeding had been restricted to sucrose.

Other Cardiometabolic Risk Factors
Isocaloric trials, using energy-matched comparisons, have not shown any consistent evidence of an adverse effect of sugars in exchange for other macronutrients on a range of cardiometabolic risk factors. In overweight adolescents, a 1,500 kcal restricted snack diet containing calorie-free sodas achieved equal weight loss and changes in BMI as an isocaloric snack diet containing regular sodas.84 The CARMEN trial showed no differences in bodyweight, body fat, or blood lipids between the high-sugar diet and high-complex carbohydrate at 6 months.78 Similarly, no differences in bodyweight, fat, and ectopic fat distribution, changes were reported in The Pounds Lost Trial when comparing the higher carbohydrate diet (in which sugars were higher) with the lower carbohydrate diet (in which sugars were lower).79,80 Furthermore, isocaloric exchange of SSBs with milk showed no effect on bodyweight or body fat in a 4-month trial in children85 or 6-month trial in adults.86 The high intakes of SSBs (1 L/day providing 106 g/day sugars) in isocaloric exchange for milk, however, did increase ectopic liver, visceral fat, blood pressure, and triglycerides in the trial in adults.86 With few exceptions,68–70,87 smaller isocaloric trials of sucrose feeding up to 220 g/day have not shown signifcant differences in bodyweight, lipids, or any other cardiometabolic risk factors for up to 22 months in people with and without diabetes.71–76,88–91

A World Health Organization (WHO)-commissioned systematic review synthesized the available evidence in relation to bodyweight from the isocaloric trials published through December 2011. The conclusion was that sugars in isocaloric exchange with other sources of carbohydrate do not affect bodyweight.37 The same lack of a consistent effect would appear to apply to downstream metabolic complications. Further investigation, however, is required to understand the effect of SSBs in isocaloric exchange for milk on ectopic liver, visceral fat, blood pressure, and triglycerides.

In contrast with the results from isocaloric trials, adverse metabolic outcomes have been consistently reported in hypercaloric trials in which background diets are supplemented with sugar from SSBs providing excess energy at high doses. An earlier systematic review and meta-analysis of such trials, supplementing excess energy from SSBs compared with calorie-free control beverages, showed evidence of weight gain over 3 to 52 weeks of follow-up.92 The weight gain achieved, however, showed a linear dose response that was directly proportional to the degree of energy supplementation.90 A similar fnding was subsequently reported among children who had their diets supplemented with excess energy from SSBs (250 mL/day providing 104 Kcal/day) compared with calorie-free beverages for 18 months in the Double-blind, Randomized Intervention Study in Kids (DRINK).93 Smaller hypercaloric trials in which diets have been supplemented with sucrose in mixed forms (added to both solids and liquids) have shown mixed signals.76,81,82,94 Similarly, systematic reviews and meta-analyses90 and a subsequent large intervention trial95 have shown a weight decreasing effect of displacing energy from SSBs but only in some high-risk groups. In addition to a decrease in bodyweight, two small intervention trials of displacing energy from sucrose from usual intakes also showed decreases in triglycerides.73,77 Although another larger trial did not show a weight-decreasing effect of displacing energy from added sugars along with increasing dietary fber, it did show an improvement in insulin sensitivity over 16 weeks.96 When the available evidence from both the energy supplementation and displacement trials was synthesized in the most recent WHO-commissioned systematic review, the conclusion was that sugars are a determinant of bodyweight in so far as they supplement or displace energy in ad libitum diets.37 The same appears to apply to the observed downstream adverse metabolic effects.

In the absence of a macronutrient comparator supplementing or displacing the same amount of excess energy in the available hypercaloric trials, it is diffcult to disentangle whether the results are attributable to excess energy or sugar. In this regard, the overfeeding of carbohydrates (including sugars, sugar-sweetened foods, and beverages) compared with fats at 50 % above energy requirements resulted in similar weight gain.83 Displacement of energy from SSBs may also not offer any advantages over general weight loss strategies, as seen in the Choose Healthy Options Consciously Everyday (CHOICE) trial.97 These data support the idea that total energy is the critical component.

Taken together, the available trial data suggest a signal for harm when sugars and SSBs contribute excess energy to diets. The same has not been found to be true when sugars and SSBs replace starch, other macronutrients, or some snacks under energy-matched conditions. The one exception has been where large quantities of SSBs are provided in isocaloric substitution for milk. Further research is required to clarify whether sugars and SSBs have different effects than other commonly consumed sources of energy that are likely to replace them under free-living conditions.

Fructose Interventions
Several systematic reviews and meta-analyses, including a series ( identifer: NCT01363791) funded by the Canadian Institute of Health Research (CIHR), have been undertaken to investigate whether the consumption of fructose, as the main metabolic actor, predisposes individuals to weight gain and increase cardiometabolic risk, beyond that which would be expected with other sources of carbohydrate in controlled feeding trials. Collectively, these reviews have synthesized a large database of over 50 trials in over 1,000 participants. Consistent with the effect seen for sugar-related interventions, fructose has been shown to have differential effects in isocaloric and hypercaloric trials across a range of cardiometabolic endpoints.

Glycemic Control
In support of the early interest in fructose as an alternative sweetener in diabetes.73,98 isocaloric trials have provided evidence of a glycemic beneft of fructose (see Figure 3). A recent systematic review and meta-analysis of 18 controlled feeding trials in diabetes showed an improvement in long-term glycemic control when replacing an equal amount of other carbohydrate with fructose.99 At a median fructose dose of 60 g/day, which is near the mean intake in the general population,22 fructose in isocaloric exchange for other carbohydrates led to a clinically signifcant reduction in glycated hemoglobin (HbA1c) of ~0.53 %, a reduction equivalent to the lower limit of effcacy expected for oral hypoglycemic agents.99 These results confrm the results of an earlier meta-analysis of controlled feeding trials of the effect of fructose at intakes from 0 to %90 g/day in isocaloric exchange for other carbohydrates on HbA1c in people with and without diabetes.100

Similar glycemic advantages have been seen for fruit as an important source of fructose. A randomized controlled feeding trial showed that naturally occurring fructose from fruit at a dose equivalent to the median dose of fructose used across isocaloric feeding trials (~60 g/day) had a nonsignifcant tendency to decrease fasting blood glucose and signifcantly decreased bodyweight without adverse effects on lipids, blood pressure, uric acid, or insulin resistance compared with a low-fructose control diet under matched hypocaloric feeding conditions in overweight humans.62 Improvements in glycemic control seen in a RCT investigating the effect of a 6-month low glycemic index (GI) diet compared with a high-cereal fber diet in people with T2DM were also found to be attributable to low GI fruit as a source of small doses of fructose in T2DM.17,63 The improvements in glycemic control seen in this trial were nearly identical to those seen in a small systematic review and meta-analysis of six controlled feeding trials of fructose at a level (22.5–36 g/day) obtainable from fruit.101

The mechanisms by which fructose alone or as part of fruit may improve glycemic control is unclear. One explanation may relate to the ability of fructose to lower the GI of the diet.98 Another mechanism may relate to the ability of fructose to improve the metabolic handling of glucose derived from pure glucose and starch. An emerging body of evidence from elegant stable isotope and clamp studies in humans indicates that low-dose fructose may beneft glycemic control through a ‘catalytic’ mechanism, whereby fructose, through its metabolite fructose-1-P, increases the hepatic disposal of coingested glucose by increasing glucokinase activity.102,103 These effects have been shown to translate into decreases of ~15-30 % in the acute postprandial glycemic responses to coingested glucose and high-GI meals.104–106 This ability to lower the postprandial glycemic response to carbohydrate-rich meals may explain the reduction in HbA1c seen secondary to low-GI fruit in our recent RCT, as the low-GI fruit increase (2.2 servings/day) was equivalent to a ‘catalytic’ increase in fructose.63,107 A dose threshold for beneft, however, may lie above 10 g/day. Our systematic review and meta-analysis showed improvements in glycemic control at doses up to 100 g/day.99 There is currently insuffcient evidence to conclude that fructose benefts glycemic control. Fructose may only have beneft in so far as it does not contribute to a positive energy balance.

Other Cardiometabolic Risk Factors
A beneft of fructose on glycemic control must be weighed against its overall effects on cardiometabolic risk. Aggregate analyses of the available controlled feeding trials again show differences along the lines of isocaloric and hypercaloric trials (see Figure 3). Fructose in isocaloric exchange for other carbohydrates (even under positive energy balance or in fluid form) does not harm other cardiometabolic risk factors and even benefts blood pressure,108–110 the same is not true in hypercaloric trials. Aggregate analyses of hypercaloric trials show that diets 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 population22 compared with the same diets alone (without the excess energy) increase bodyweight and uric acid,109,110 as well as fasting triglycerides, postprandial triglycerides, and markers of nonalcoholic fatty liver disease (NAFLD) (unpublished data). Formal tests of interaction suggest that these adverse cardiometabolic effects are more attributable to the excess energy than fructose. There was a subset of fve isocaloric trials included in our systematic reviews and meta-analyses111–116 that used excess energy diets (positive energy balance) in both the fructose and glucose comparison arms. If we restrict our meta-analyses to these trials, then there was no evidence of harm and even a possible blood pressure beneft. The suggestion is that diets supplemented with fructose providing excess energy do not differ from diets supplemented with excess energy from glucose as long as the comparison is matched for the excess energy. Two earlier meta-analyses, however, suggested possible high-dose thresholds for harm for the effect of fructose on fasting (>60 g/ day114 and >100 g/day97) and postprandial (>50 g/day97 triglycerides under energy-matched conditions.

Taken together, the available trial evidence suggests that moderate fructose levels of intake under energy neutral, weight-maintaining conditions does not have adverse effects on cardiometabolic risk factors with possible advantages for glycemic control and blood pressure. Low-GI fruit, as an important source of fructose, may have particular advantages under these conditions. A signal for harm does emerge when fructose is provided at high doses or contributes excess energy to diets. The increase in cardiometabolic risk factors provoked by fructose providing excess energy, however, does not differ from that seen with glucose providing excess energy, suggesting that excess energy is driving the observed effects.

Summary and Concluding Remarks
While there are data to suggest a role for sugars in the epidemic of diabetes, much of the current available evidence arises from lowquality observational studies, animal models, and overfeeding trials featuring high-intake levels. Prospective cohort studies have failed to show a consistent relation of fructose-containing sugars with weight gain or diabetes risk. Although signifcant associations have been shown comparing the highest with the lowest levels of intake of SSBs, these associations are small, do not hold at moderate levels of intake, and are subject to collinearity effects. SSBs may be a marker for an overall unfavorable Western dietary pattern and lifestyle. As many of the metabolic consequences of a diet high in fructose-containing sugars in humans can also be observed with high-fat or high-glucose feeding, it is possible that excess calories may be the main culprit in the development of the metabolic syndrome.118 Thus, it is important to distinguish between isocaloric trials in which fructose-containing sugars are exchanged isocalorically for other carbohydrates from hypercaloric trials in which fructose-containing sugars supplement diets providing excess energy at high doses. Systematic reviews and meta-analyses of the highest level of evidence from controlled feeding trials have not shown evidence of harm of fructose-containing sugars in isocaloric trials with possible advantages for glycemic control in the case of fructose interventions, especially where these interventions provide small doses of fructose at a level obtainable from fruit. Nevertheless, hypercaloric trials have consistently shown adverse effects, which appear more attributable to the excess energy than the fructose-containing sugars. Translation of these data is limited by the small sample sizes, short duration, and poor study quality of the available trials.

There remains a lack of consistent evidence to suggest that fructose, sucrose, or HFCS at moderate doses is directly related to the development of diabetes and other cardiometabolic diseases, although there is potentially cause for concern where fructose is provided at high doses or contributes excess energy to diets. Many questions remain unanswered. High-quality trials are needed to assess the role of fructose-containing sugars in free exchange with foods likely to replace them in the diet in the development of diabetes and cardiometabolic diseases.

Article Information:

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.


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:


The publication of this article was supported by The Coca-Cola Company. The views and opinions expressed are those of the authors.




  1. International Diabetes Federation. Global burden. IDF Diabetes Atlas. 5th edition. 2011. Available at: diabetesatlas/5e/the-global-burden
  2. International Diabetes Federation. IDF Diabetes Atlas. Update 2012. Available at: Update2012.
  3. Eckel RH, Alberti KG, Grundy SM, Zimmet PZ, The metabolic syndrome, Lancet, 2010;375(9710):181–3.
  4. 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;79:537–43.
  5. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report, Circulation, 2002;106:3143.
  6. Nishida UR, Kumanyika S, Shetty P, The Joint WHO/FAO Expert Consultation on diet, nutrition and the prevention of chronic diseases: process, product and policy implications, Public Health Nutr, 2004;7:245–50.
  7. Lichtenstein AH, Appel LJ, Brands M, et al., Diet and Lifestyle Recommendations Revision 2006: A Scienti!c Statement From the American Heart Association Nutrition Committee, Circulation, 2006;114:82–96.
  8. Genest, R McPherson, J Frohlich, et al., 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult – 2009 recommendations, Can J Cardiol, 2009;25:567–79.
  9. U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2010. 7th Edition, Washington, DC: U.S. Government Printing Of!ce, December 2010.
  10. Anderson TJ, Gregoire J, Hegele RA et al., 2012 Update of the Canadian Cardiovascular Society: Guidelines for the Diagnosis and Treatment of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult, Can J Cardiol, 2013;29:151– 67.
  11. CHEP 2013 Full Report. Available at: images/CHEP_2013/2013_CompleteCHEPRecommendations_ EN_HCP1009.pdf.
  12. Lenfant C, Chobanian AV, Jones DW, et al., Seventh report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7): Complete Report, Hypertension, 2003;42:1206–52.
  13. Institute of Medicine (IOM), Dietary reference intakes for energy,carbohydrate, !ber, fat, fatty acids, cholesterol, protein, and amino acids. Washington, DC, National Academy Press, 2002.
  14. Johnson RK, Appel LJ, Brands M, et al., Dietary Sugars Intake and Cardiovascular Health: A Scienti!c Statement From the American Heart Association, Circulation, 2009;120:1011–20.
  15. Miller M, Stone NJ, Ballantyne C, et al., Triglycerides and Cardiovascular Disease: A Scienti!c Statement From the American Heart Association, Circulation, 2011;123:2292–333.
  16. . Mann JI, Evidence-based nutrition: Does it differ from evidencebased medicine?, Ann Med, 2010;42:475–86.
  17. Bantle JP, Wylie-Rosett J, Albright AL, et al., Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association, Diabetes Care, 2008;31 Suppl 1:S61–78.
  18. Dworatzek PD, Arcudi K, Gougeon R, et al., Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada: Nutrition Therapy, Can J Diabetes, 2013;37:S45–S55.
  19. Melanson KJ, Zukley L, Lowndes J, et al., Effects of high-fructose corn syrup and sucrose consumption on circulating glucose, insulin, leptin, and ghrelin and on appetite in normal-weight women, Nutrition, 2007;23:103–12.
  20. Stanhope KL, Havel PJ, Endocrine and metabolic effects on consuming beverages sweetened with fructose, glucose, sucrose, or high-fructose corn syrup, Am J Clin Nutr, 2008;88:1733S–1737S.
  21. Lowndes J, Kawiecki D, Pardo S, et al., The effects of four hypocaloric diets containing different levels of sucrose or high fructose corn syrup on weight loss and related parameters, Nutr J, 2012;11:55.
  22. 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–35S.
  23. Ng SW, Slining MM, Popkin MM, Use of caloric and noncaloric sweeteners in US consumer packaged foods, 2005–2009, J Acad Nutr Diet, 2012;112:1828–3
  24. Bray GA, Energy and fructose from beverages sweetened with sugar or high-fructose corn syrup pose a health risk for some people, Adv Nutr, 2013;4(2):220–25.
  25. Welsh JA, Sharma AJ, Grellinger L, Vos MB, Consumption of added sugars is decreasing in the United States, Am J Clin Nutr, 2011;94:726–734.
  26. Johnson RJ, Perez-Pozo SE, Sautin YY, et al., Hypothesis: could excessive fructose intake and uric acid cause type 2 diabetes?, Endocr Rev, 2009;30:96–116.
  27. Shapiro A, Mu W, Roncal C, et al., Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding, Am J Physiol Regul Integr Comp Physiol, 2008;295:R1370–75.
  28. Maiztegui B, Borelli MI, Raschia MA, et al., Islet adaptive changes to fructose-induced insulin resistance: beta-cell mass, glucokinase, glucose metabolism, and insulin secretion, J Endocrinol, 2009;200:139–49.
  29. Mielke JG, Taghibiglou C, Liu L, et al., A biochemical and functional characterization of diet-induced brain insulin resistance, J Neurochem, 2005;93:1568–78.
  30. Rizkalla SW, Boillot J, Tricottet V, et al., Effects of chronic dietary fructose with and without copper supplementation on glycaemic control, adiposity, insulin binding to adipocytes and glomerular basement membrane thickness in normal rats, Br J Nutr, 1993;70:199–209.
  31. Thorburn AW, Storlien LH, Jenkins AB, et al., Fructose-induced in vivo insulin resistance and elevated plasma triglyceride levels in rats, Am J Clin Nutr, 1989;49:1155–63.
  32. Sievenpiper JL, de Souza RJ, Kendall CW, et al., Is fructose a story of mice but not men?, J Am Diet Assoc, 2011;111:219–20; author reply 20–22.
  33. Sun SZ, Empie MW, Fructose metabolism in humans – what isotopic tracer studies tell us, Nutr Metab, 2012;9(1):89.
  34. Tappy L, Lê KA, Metabolic effects of fructose and the worldwide increase in obesity, Physiol Rev, 2010;90(1):23–46.
  35. Gross LS, Li L, Ford ES, Liu S, Increased consumption of re!ned carbohydrates and the epidemic of type 2 diabetes in the United States: an ecologic assessment, Am J Clin Nutr, 2004;79:774–9.
  36. Perez-Pozo SE, Schold J, Nakagawa T, et al., Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response, Int J Obes (Lond), 2010;34:454–61.
  37. Goran MI, Ulijaszek SJ, Ventura EE, High fructose corn syrup and diabetes prevalence: A global perspective, Glob Public Health, 2012;8:55–64.
  38. Basu S, Yoffe P, Hills N, Lustig RH, The relationship of sugar to population-level diabetes prevalence: an econometric analysis of repeated cross-sectional data, PloS One, 2013;8(2):e57873. 39. Barclay AW, Brand-Miller J, The Australian paradox: a substantial decline in sugars intake over the same timeframe that overweight and obesity have increased, Nutrients, 2012;3:491–504.
  39. Centers for Disease Control and Prevention 2011—Total added sugars, have not resulted in a decrease of obesity or diabetes in the US (Centers for Disease Control and Prevention 2011). Available at: maps_diabetesobesity_trends.pdf.
  40. Rizkalla SW, Health implications of fructose consumption: A review of recent data, Nutr Metab, 2010;7:82.
  41. Montonen J, Jarvinen R, Knekt P, et al., Consumption of sweetened beverages and intakes of fructose and glucose predict type 2 diabetes occurrence, J Nutr, 2007;137:1447–54.
  42. Hodge AM, English DR, O’Dea K, et al., Glycemic index and dietary !ber and the risk of type 2 diabetes, Diabetes Care, 2004;27:2701–6.
  43. Janket SJ, Manson JE, Sesso H, et al., A prospective study of sugar intake and risk of type 2 diabetes in women, Diabetes Care, 2003;26:1008–15.
  44. Meyer KA, Kushi LH, Jacobs DR, Jr, et al., Carbohydrates, dietary !ber, and incident type 2 diabetes in older women, Am J Clin Nutr, 2000;71:921–30.
  45. Colditz GA, Manson JE, Stampfer MJ, et al., Diet and risk of clinical diabetes in women, Am J Clin Nutr, 1992;55:1018–23.
  46. Forman JP, Choi H, Curhan GC, et al., Fructose and vitamin C intake do not in"uence risk for developing hypertension, J Am Soc Nephrol, 2009;20:863–71.
  47. Liu S, Willett WC, Stampfer MJ, et al., A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women, Am J Clin Nutr, 2000;71:1455–61.
  48. Sun SZ, Flickinger B, Williamson-Hughes P, Empie M, Lack of association between dietary fructose and hyperuricemia risk in adults, Nutr Metab, 2010;7:16.
  49. Choi HK, Willett W, Curhan G. Fructose-rich beverages and risk of gout in women, JAMA, 2010;304:2270–78.
  50. Choi HK, Curhan G, Soft drinks, fructose consumption, and the risk of gout in men: prospecive cohort study, BMJ, 2008;336(7639):309–12.
  51. Malik VS, Popkin BM, Bray GA, et al., Sugar-sweetened beverages and risk of metabolic syndrome and type 2 diabetes: a metaanalysis, Diabetes Care, 2010;33, 2477–483.
  52. 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;345:e7492.
  53. 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; 292:927–34.
  54. Cohen L, Curhan G, Forman J, Association of sweetened beverage intake with incident hypertension, J Gen Intern Med, 2012;27(9):1127–34.
  55. de Koning L, Malik VS, Kellogg MD, et al., Sweetened beverage consumption, incident coronary heart disease, and biomarkers of risk in men, Circulation, 2012;125:1735–41.
  56. Bernstein AM, de Koning L, Flint AJ, et al., Soda consumption and the risk of stroke in men and women, Am J Clin Nutr, 2012;95:1190–99.
  57. Forshee RA, Anderson PA, Storey ML, Sugar-sweetened beverages and body mass index in children and adolescents: a meta-analysis, Am J Clin Nutr, 2008;87(6):1662–71. Erratum in: Am J Clin Nutr, 2009;89(1):441–2.
  58. Ye EQ, Chacko SA, Chou EL, et al., Greater whole-grain intake is associated with lower risk of type 2 diabetes, cardiovascular disease, and weight gain, J Nutr, 2012;142(7):1304–13.
  59. Mozaffarian D, Hao T, Rimm EB, et al., Changes in diet and lifestyle and long-term weight gain in women and men, N Engl J Med, 2011;364(25):2392–404.
  60. Fung TT, Pereira MA, Liu S, et al., Whole-grain intake and the risk of type 2 diabetes: a prospective study in men, Am J Clin Nutr, 2002;76(3):535–540.
  61. Madero M, Jalal D, Rivard C, et al., The effect of two energyrestricted diets, a low-fructose diet versus a moderate natural fructose diet, on weight loss and metabolic syndrome parameters: A randomized controlled trial, Metabolism, 2011;60:1551–9.
  62. Jenkins DJ, Kendall CW, Sievenpiper JL, et al., The relation of low glycaemic index fruit consumption to glycaemic control and risk factors for coronary heart disease in type 2 diabetes, Diabetologia, 2011;54(2):271–9.
  63. Pan A, Sun Q, Bernstein AM, et al., Red meat consumption and risk of type 2 diabetes: 3 cohorts of US adults and an updated meta-analysis, Am J Clin Nutr, 2011;94(4):1088–96.
  64. Halton TL, Liu S, Manson JE, et al., Potato and french fry consumption and risk of type 2 diabetes in women, Am J Clin Nutr, 2006;83(2):284–90.
  65. Schulze MB, Manson JE, Willett WC, Hu FB, Dietary patterns and changes in body weight in women, Obesity, 2006;14:1444–53.
  66. Schulze MB, Manson JE, Willett WC, et al., Dietary pattern, in"ammation, and incidence of type 2 diabetes in women, Am J Clin Nutr, 2005;82:675–84.
  67. Coulston AM, Donner CC, Williams R, et al., Metabolic effects of added dietary sucrose in individuals with noninsulin-dependent diabetes mellitus (NIDDM), Metabolism, 1985;34(10):962–6.
  68. Claesson AL, Ernersson A, Lindström T, Nystrom FH, Two weeks of overfeeding with candy, but not peanuts, increases insulin levels and body weight, Scand J Clin Lab Invest, 2009;69(5):598–605.
  69. Malerbi DA, Duarte AL, Wajchenberg BL, Metabolic effects of dietary sucrose and fructose in type II diabetic subjects, Diabetes Care, 1996;19:1249–56.
  70. Blayo A, Rizkalla S, Bruzzo F, Slama G, Effets Metaboliques de la Consommation Quotidienne Pednant un an de Saccharose ou de Fructose par des Diabetiques, Med Nut, 1990;26:909–13.
  71. Cooper PL, Simpson RW, Sucrose versus saccharin as an added sweetener in non-insulin-dependent diabetes: short- and medium-term metabolic effects, Diabet Med, 1988;5:676–80.
  72. Bantle JP, Thomas JW, Metabolic effects of dietary fructose and sucrose in types I and II diabetic subjects, JAMA, 1986;256(23):3241–6.
  73. Peterson DB, Gerring S, Darling P, et al., Sucrose in the diet of diabetic patients–just another carbohydrate?, Diabetologia, 1986;29(4):216–20.
  74. Jellish WS, Abraira C. Graded sucrose/carbo- hydrate diets in overtly hypertriglyceridemic diabetic patients, Am J Med, 1984;77:1015–22.
  75. Huttunen JK, Mäkinen KK, Scheinin A, Turku sugar studies XI. Effects of sucrose, fructose and xylitol diets on glucose, lipid and urate metabolism, Acta Odontol Scand, 1976;34(6):345–51.
  76. Mann JI, Hendricks DA, Truswell AS, Manning E, Effects on serumlipids in normal men of reducing dietary sucrose or starch for !ve months, Lancet, 1970;1(7652):870–72.
  77. Saris WH, Astrup A, Prentice AM, et al., Randomized controlled trial of changes in dietary carbohydrate/fat ratio and simple vs complex carbohydrates on body weight and blood lipids: the CARMEN study. The Carbohydrate Ratio Management in European National diets, Int J Obes Relat Metab Disord, 2000;24:1310–18.
  78. de Souza RJ, Bray GA, Carey VJ, et al., Effects of 4 weight-loss diets differing in fat, protein, and carbohydrate on fat mass, lean mass, visceral adipose tissue, and hepatic fat: results from the POUNDS LOST trial, Am J Clin Nutr, 2012;95:614–25.
  79. Sacks FM, Bray GA, Carey VJ, et al., Comparison of weightloss diets with different compositions of fat, protein, and carbohydrates, N Engl J Med, 2009;360:859–73.
  80. Colagiuri S, Miller JJ, Edwards RA, Metabolic effects of adding sucrose and aspartame to the diet of subjects with non-insulindependent diabetes mellitus, Am J Clin Nutr, 1989;50:474–8.
  81. Chantelau EA, Gösseringer G, Sonnenberg GE, Berger M, Moderate intake of sucrose does not impair metabolic control in pump-treated diabetic out-patients, Diabetologia,1985;28:204–7.
  82. Horton TJ, Drougas H, Brachey A, et al., Fat and carbohydrate overfeeding in humans: different effects on energy storage, Am J Clin Nutr, 1995 62(1):19–29.
  83. Williams CL, Strobino BA, Brotanek J, Weight control among obese adolescents: a pilot study, Int J Food Sci Nutr, 2007;58(3):217–30.
  84. Albala C, Ebbeling CB, Cifuentes M, et al., Effects of replacing the habitual consumption of sugar-sweetened beverages with milk in Chilean children, Am J Clin Nutr, 2008;88:605–11.
  85. Maersk M, Belza A, Stødkilde-Jørgensen H, et al., Sucrosesweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study, Am J Clin Nutr, 2012;95:283–9.
  86. Poppitt SD, Keogh GF, Prentice AM, et al., Long-term effects of ad libitum low-fat, high-carbohydrate diets on body weight and serum lipids in overweight subjects with metabolic syndrome, Am J Clin Nutr, 2002;75(1):11–20.
  87. Roberts AM, Effects of a sucrose-free diet on the serum-lipid levels of men in Antarctica, Lancet, 1973;1(7814):1201–4.
  88. Mann JI, Truswell AS, Manning EB, Effects on serum lipids of reducing dietary sucrose or starch for 22 weeks in normal men, S Afr Med J, 1972;46(25):827–34.
  89. Nikkilä EA, Kekki M, Effects of dietary fructose and sucrose on plasma triglyceride metabolism in patients with endogenous hypertriglyceridemia, Acta Med Scand Suppl, 1972;542:221–7.
  90. Kaufmann NA, Poznanski R, Blondheim SH, Stein Y, Effect of fructose, glucose, sucrose and starch on serum lipids in carbohydrate induced hypertriglyceridemia and in normal subjects, Isr J Med Sci, 1966;2(6):15–26.
  91. Mattes RD, Kaiser KA, Allison DB, Nutritively sweetened beverage consumption and body weight: a systematic review and metaanalysis of randomized experiments, Obes Rev, 2011;12:346–65.
  92. de Ruyter JC, Olthof MR, Seidell JC, Katan MB, A trial of sugar-free or sugar-sweetened beverages and body weight in children, N Engl J Med, 2012;367:1397–1406.
  93. Raben A, Vasilaras TH, Møller AC, Astrup A, Sucrose compared with arti!cial 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(4):721–9.
  94. Ebbeling CB, Feldman HA, Chomitz VR., A randomized trial of sugar-sweetened beverages and adolescent body weight, N Engl J Med, 2012;367:1407–16.
  95. Hasson RE, Adam TC, Davis JN, et al., Randomized controlled trial to improve adiposity, in"ammation, and insulin resistance in obese African-American and Latino youth, Obesity (Silver Spring), 2012;20:811– 18.
  96. Tate DF, Lyons E, Stevens J, et al., Replacing caloric beverages with water or diet beverages for weight loss in adults: main results of the Choose Healthy Options Consciously Everyday (CHOICE) randomized clinical trial, Am J Clin Nutr, 2012;95:555–63.
  97. Jenkins DJ, Wolever TM, Taylor RH, et al., Glycemic index of foods: a physiological basis for carbohydrate exchange, Am J Clin Nutr, 1981;34:362–6.
  98. Cozma AI, Sievenpiper JL, de Souza RJ, et al., Effect of fructose on glycemic control in diabetes: a systematic review and meta-analysis of controlled feeding trials, Diabetes Care, 2012;35:1611–20.
  99. 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.
  100. Sievenpiper JL, Chiavaroli L, de Souza RJ, et al., ‘Catalytic’ doses of fructose may bene!t glycaemic control without harming cardiometabolic risk factors: a small meta-analysis of randomised controlled feeding trials, Br J Nutr, 2012;108:418–23.
  101. Hawkins M, Gabriely I, Wozniak R, et al., Fructose improves the ability of hyperglycemia per se to regulate glucose production in type 2 diabetes, Diabetes, 2002;51:606–14.
  102. Petersen KF, Yu C, Cline GW, Shulman GI, Stimulating effects of low-dose fructose on insulin-stimulated hepatic glycogen synthesis in humans, Diabetes, 2001;50(6):1263–8.
  103. Heacock PM, Hertzler SR, Wolf BW, Fructose prefeeding reduces the glycemic response to a high-glycemic index, starchy food in humans, J Nutr, 2002;132:2601–4.
  104. Moore MC, Mann SL, Cherrington AD, Acute fructose administration improves oral glucose tolerance in adults with type 2 diabetes, Diabetes Care, 2001;24(11):1882–7.
  105. Moore MC, Mann SL, Davis SN, Acute fructose administration decreases the glycemic response to an oral glucose tolerance test in normal adults, J Clin Endocrinol Metab, 2000;85(12): 4515–19.
  106. Jenkins DJ, McKeown-Eyssen G, Josse RG, et al., Effect of a lowglycemic index or a high-cereal !ber diet on type 2 diabetes: a randomized trial, JAMA, 2008;300(23):2742–53.
  107. Ha V, Sievenpiper JL, de Souza RJ, et al., Effect of fructose on blood pressure: a systematic review and meta-analysis of controlled feeding trials, Hypertension, 2012;59:787–95.
  108. Sievenpiper JL, de Souza RJ, Mirrahimi A, et al., Effect of fructose on body weight in controlled feeding trials: a systematic review and meta-analysis, Ann Intern Med, 2012;156:291–304.
  109. Wang DD, Sievenpiper JL, de Souza RJ, et al., The effects of fructose intake on serum uric acid vary among controlled dietary trials, J Nutr, 2012;142(5):916–23.
  110. Beck-Nielsen H, Pedersen O, Lindskov HO, Impaired cellular insulin binding and insulin sensitivity induced by high-fructose feeding in normal subjects, Am J Clin Nutr, 1980;33:273–8.
  111. Stanhope KL, Schwarz JM, Keim NL, et al., Consuming fructosesweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans, J Clin Invest, 2009;119:1322–34.
  112. Ngo Sock ET, Lê KA, Ith M, et al., Effects of a short-term overfeeding with fructose or glucose in healthy young males, Br J Nutr, 2010;103:939–43.
  113. Silbernagel G, Machann J, Unmuth S, Effects of 4-week very-highfructose/ glucose diets on insulin sensitivity, visceral fat and intrahepatic lipids: An exploratory trial, Br J Nutr, 2011;106:79–86.
  114. Stanhope KL, Bremer AA, Medici V, Consumption of fructose and high fructose corn syrup increase postprandial triglycerides, LDL-cholesterol, and apolipoprotein-B in young men and women, J Clin Endocrinol Metab, 2011;96(10):E1596–1605.
  115. Stanhope KL, Bremer AA, Vink RG, et al., Metabolic responses to prolonged consumption of glucose- and fructose-sweetened beverages are not associated with postprandial or 24-h glucose and insulin excursions, Am J Clin Nutr, 2011;94:112–19.
  116. Sievenpiper JL, Carleton AJ, Chatha S, et al., 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;32:1930–37.
  117. Tappy L, Lê KA, Tran C, Paquot N, Fructose and metabolic diseases: new !ndings, new questions, Nutrition, 2010;26: 1044–1049.
  118. Paynter NP, Yeh HC, Voutilainen S, et al., Coffee and sweetened beverage consumption and the risk of type 2 diabetes mellitus: the atherosclerosis risk in communities study, Am J Epidemiol, 2006;164:1075–84.
  119. 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(5):480–88.
  120. Bazzano LA, Li TY, Joshipura KJ, Hu FB, Intake of fruit, vegetables, and fruit juices and risk of diabetes in women, Diabetes Care, 2008;31:1311–17.
  121. Lutsey PL, Steffen LM, Stevens J, Dietary intake and the development of the metabolic syndrome:the Atherosclerosis Risk in Communities study, Circulation, 2008;117(6):754–61.
  122. Palmer JR, Boggs DA, Krishnan S., Sugar-sweetened beverages and incidence of type 2 diabetes mellitus in African American women, Arch Intern Med, 2008;168:1487–92.
  123. Nettleton JA, Lutsey PL, Wang Y, et al., Diet soda intake and risk of incident metabolic syndrome and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA), Diabetes Care, 2009;32(4):688–94.
  124. Odegaard AO, Koh WP, Arakawa K, et al., Soft Drink and Juice Consumption and Risk of Physician-diagnosed Incident Type 2 Diabetes: The Singapore Chinese Health Study, Am J Epidemiol, 2010;171(6):701–8. CozmaSievenpiperREPRINT.

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