Several foods with fructose-containing sugars have harmful effects on glycemic control and add unneeded energy to the diet, but these effects may be mediated by energy and food source, according to a review published in BMJ.

Researchers conducted a systematic literature review and meta-analysis of controlled intervention studies to determine how fructose-containing sugars (fructose, sucrose, high fructose corn syrup, honey, syrups) within various food sources affect glycemic control in individuals with and without diabetes. Studies from Medline, Embase, and the Cochrane Central Register of Controlled Studies through April 25, 2018 were included in the review if they lasted ≥7 days and compared the effect of diets with fructose-containing foods to control diets (diets free of or with lower levels of fructose-containing sugars) with outcome measures of glycemic control (fasting glucose, fasting insulin, and glycated hemoglobin [HbA1c]) in individuals with and without diabetes.

The researchers prespecified 4 study designs based on control of energy: substitution studies (food sources compared under energy-matched conditions), addition studies (excess energy added to background diets), subtraction studies (food sources lessened or removed from background diets), and ad libitum studies (food sources compared without strict control). Studies that assessed meal replacements, interventions of rare sugars that contained fructose (eg, isomaltulose or melzitose), or low-calorie epimers of fructose (eg, allulose, tagatose, sorbose) were excluded.

Upon screening 4442 reports, 118 reports of controlled interventions were selected for review, which yielded a total of 155 study comparisons in 5086 participants. No serious risk of bias was detected among the included studies.

A significant beneficial effect of total fructose-containing sugars on HbA1c was observed for all food sources in substitution studies (30 study comparisons: mean difference, -0.22%; P <.01; substantial heterogeneity [I2, 82%; P <.001]). Fruit as a sole food source, however, accounted for 30% of this weighted benefit of significantly decreased HbA1c (6 study comparisons: mean difference, -0.19%; P =.02; substantial heterogeneity [I2, 78%; P <.001]).

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Total fructose-containing sugars had no effect on fasting blood glucose except in addition studies (P <.001). In general, fruit, fruit drinks, sweetened chocolate, added sweeteners, and mixed sources of fructose-containing sugars showed no significant effect on fasting blood glucose.

Total fructose-containing sugars, regardless of food source, had a harmful effect on fasting blood insulin levels in addition studies (23 study comparisons: mean difference, 4.68 pmol/L; P <.01; substantial heterogeneity [I2, 58%; P <.001]) and ad libitum studies (4 study comparisons: mean difference, 7.24 pmol/L; P =.04; no evidence of heterogeneity [I2, 0%, P =.46]).

The researchers noted several limitations to their systematic review and meta-analysis, including a substantial amount of unexplained heterogeneity in all analyses for the substitution and addition studies for HbA1c, fasting blood glucose, and fasting blood insulin.

The researchers discussed that as dietary guidelines shift in focus to foods and dietary patterns, these review findings can be used to guide recommendations on important food sources of fructose-containing sugars to help prevent and manage diabetes. “More large, high quality studies using a greater variety of food sources of fructose-containing sugars are required to assess the durability of these effects and understand whether certain food sources with an apparent signal for benefit, such as fruit, might even have advantages for [glycemic] control,” said the researchers.

Some authors declared financial conflicts of interest with this study. Please refer to original reference for a full list of authors’ disclosures.

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Choo VL, Viguiliouk E, Mejia SB, et al. Food sources of fructose-containing sugars and glycaemic control: systematic review and meta-analysis of controlled intervention studies [published online November 21, 2018]. BMJ. doi:10.1136/bmj.k4644