The Effect of Small Doses of Fructose and Its Epimers on Glycemic Control: A Systematic Review and Meta-Analysis of Controlled Feeding Trials

Abstract

Objective: Contrary to the concerns that fructose may have adverse metabolic effects, an emerging literature has shown that small doses (≤10 g/meal) of fructose and its low-caloric epimers (allulose, tagatose, and sorbose) decrease the glycemic response to high glycemic index meals. Whether these acute reductions manifest as sustainable improvements in glycemic control is unclear. Our objective was to synthesize the evidence from controlled feeding trials that assessed the effect of small doses of fructose and its low-caloric epimers on glycemic control. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library through April 18, 2018. We included controlled feeding trials of ≥1 week that investigated the effect of small doses (≤50 g/day or ≤10% of total energy intake/day) of fructose and its low-caloric epimers on HbA1c, fasting glucose, and fasting insulin. Two independent reviewers extracted data and assessed risk of bias. Data were pooled using the generic inverse variance method and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the Cochran Q statistic and quantified using the I2 statistic. Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessed the certainty of the evidence. Results: We identified 14 trial comparisons (N = 337) of the effect of fructose in individuals with and without diabetes, 3 trial comparisons (N = 138) of the effect of allulose in individuals without diabetes, 3 trial comparisons (N = 376) of the effect of tagatose mainly in individuals with type 2 diabetes, and 0 trial comparisons of the effect of sorbose. Small doses of fructose and tagatose significantly reduced HbA1c (MD = −0.38% (95% CI: −0.64%, −0.13%); MD = −0.20% (95% CI: −0.34%, −0.06%)) and fasting glucose (MD = −0.13 mmol/L (95% CI: −0.24 mmol/L, −0.03 mmol/L)); MD = −0.30 mmol/L (95% CI: −0.57 mmol/L, −0.04 mmol/L)) without affecting fasting insulin (p > 0.05). Small doses of allulose did not have a significant effect on HbA1c and fasting insulin (p > 0.05), while the reduction in fasting glucose was of borderline significance (p = 0.05). The certainty of the evidence of the effect of small doses of fructose and allulose on HbA1c, fasting glucose, and fasting insulin was graded as low. The certainty of the evidence of the effect of tagatose on HbA1c, fasting glucose, and fasting insulin was graded as moderate. Conclusions: Our results indicate that small doses of fructose and tagatose may improve glycemic control over the long term. There is a need for long-term randomized controlled trials for all four sugars to improve our certainty in the estimates.

Effect of fructose and its epimers on postprandial carbohydrate metabolism: A systematic review and meta-analysis

“…Our allulose findings partly align with a recent systematic review and meta-analysis. Although small doses of allulose (8e15 g/ day) failed to reduce HbA 1c in otherwise healthy participants and those who were overweight/obese, the reduction in fasting glucose was approaching significance [76,83,88]. Given that these individuals did not present with hyperglycemia, significant reductions in HbA 1c would not be expected.…”

“…Several systematic reviews and meta-analyses have been conducted to assess the effect of fructose on glycemic control. Two meta-analyses showed that small doses of fructose (up to 50 g/day or 10% of total energy intake/day) in isocaloric exchange for other carbohydrates reduced HbA 1c by~0.4% [82,83]. Evans et al [26] showed that fructose doses of 15 ge100 g isocalorically exchanged for glucose or sucrose in acute trials reduced postprandial glucose and insulin responses without a negative impact on triglycerides, in those with and without type 2 diabetes.…”

Dietary Fructose and Risk of Metabolic Syndrome in Chinese Residents Aged 45 and Above: Results From the China National Nutrition and Health Survey

“…According to the systematic reviews and meta-analysis, high doses of fructose (≥ 100 g/day) increases serum TG concentration (10,32), low to middle doses of fructose (0 ~ 90 g/day) have a bene t effect in HbA1c (13,33). But fructose did not increase the risk of hypertension and type 2 diabetes (12,34), also, it did not affect serum HDL-C concentration (32) and cause weight gain when it was substituted for other carbohydrate in diets providing similar calories (35).…”

“…Some of them concluded that intakes of fructose were associated with increased risk of obesity, dyslipidemia, and hypertension (8)(9)(10). However, some of them found that a certain dose of fructose has no adverse or even some positive effects on fasting glucose, blood pressure, and blood lipids (11)(12)(13)(14)(15). Most of the studies included in these meta-analyses were interventional studies with high-dose fructose intake.…”

The technological challenges of reducing the sugar content of foods

“…Allulose is absorbed in the stomach, with peak plasma concentrations of allulose occurring within an Sugar reduction technical challenges hour and the vast majority excreted unchanged in the urine. Allulose has been found to have no impact on blood glucose levels (Noronha et al 2018a); it raises neither blood glucose nor insulin levels in healthy individuals or when consumed by individuals with type 2 diabetes (Noronha et al 2018b). Allulose is nearly calorie-freeit is labelled in the US, for example as having 90% fewer calories than sugar (FDA 2018).…”