A total of 112 studies (42 reports) were included in the review: More than half (54%) of the studies were of cross-over design. A high proportion (35%) of these did not report randomisation. Most studies scored 1 or 2 on the 0 to 3 Jadad scale. Attrition was less than 20% in all studies. There were only two double blinded studies and one single blinded study.
HbA1c (eight studies comprising six cross-over and two parallel studies, totalling 106 participants, provided just 14 point estimates): Overall, the addition of fructose to the diet reduced HbA1c concentration regardless of the substitute used (glucose or starch). There was no data comparing fructose and sucrose. Fructose dose, duration of fructose treatment, and the severity of dysglycaemia interacted as a single determinant of the treatment effect size. Treatment effect was greatest in individuals with poor baseline glycaemic control (high HbA1c). Funnel plot and trim-and-fill analyses revealed no significant publication bias.
Fasting plasma triacylglycerol (FPTG) (60 studies, comprising 33 cross-over, 20 sequence, four sandwich and three parallel studies, totalling 589 participants): Overall, RCTs with 100g/day or less fructose had no significant effect on FPTG. Fructose intake up to 350g/day increased FPTG. Non-significant residual differences from a general trend with dose were reported for RCTs and studies in which randomisation was not reported (RCTs: ResD -0.09, 95% CI -0.39 to 0.21. Non-RCTs: ResD 0.06, 95% CI -0.14 to 0.28). There was evidence of statistical heterogeneity for RCTs (I2=0.93) and non-RCTs (I2=0.91). FPTG increased as fructose dose increased, but the size of the effect decreased with duration of treatment. Subgroups of males, females, healthy persons, type 1 diabetics, type 2 diabetics, hyperlipidaemics, normal weight, overweight and obese persons showed no significant departure from the general trend for the dose response. Funnel plots and trim-and-fill analyses revealed no significant publication bias.
Postprandial triacylglycerol (PPTG) (25 studies, comprising 17 cross-over, five sequence, two parallel and one sandwich studies, totalling 234 participants): There was a significant reduction in PPTG in studies that monitored PPTG for five hours or less (-0.02 mmol/L, 95% CI -0.03 to -0.01; 13 studies). There was evidence of significant heterogeneity (Χ2=0.001). In studies that monitored PPTG between six and 24 hours, there was no statistically significant evidence of a dose dependency effect (12 studies). Further studies are needed.
Body weight (19 studies, comprising 12 cross-over, three parallel, two sandwich and two sequence studies, totalling 246 participants): Fructose intakes of 100g/day or less did not have a significant effect on body weight. There was no evidence of statistical heterogeneity (I2=0%). There was no evidence of publication bias using funnel plots and trim-and-fill analyses. Data on the effect of fructose intakes greater than 100g/day on body weight were limited.
The sensitivity of combined effects to different ways of handing repeat measures was investigated. Heterogeneity was variably studied as appropriate across outcomes in terms of choice of control substitute, background diet, health state, baseline weight/BMI, age and gender of the participants, adaptation, mode of fructose ingestion, and study quality. The results were reported in the review.