A systematic review and meta-analysis of controlled feeding trials
No restriction was placed on language. RESULTS Search results A total of 4, eligible reports were identified with the search; of these, 4, were determined to be irrelevant on review of the titles and abstracts. Oleomargarine Act requires prominent labeling of colored oleomargarine, to distinguish it from butter. Metabolic effects of fructose supplementation in diabetic individuals. Long-term effects of dietary fructose on carbohydrate metabolism in non-insulin-dependent diabetes mellitus. Sensitivity analyses did not alter the effect estimate or degree of heterogeneity for fasting insulin, and meta-regression revealed no statistically significant subgroup effects Supplementary Fig.
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Subgroup analyses revealed no significant effect modification for glycated blood proteins, fasting glucose, or insulin. Although Livesey and Taylor 31 in their earlier meta-analysis found that the improvement in HbA 1c was dependent on the degree of dysglycemia, fructose dose, and follow-up, we did not find that these conditions altered any of the outcomes, nor in a separate analysis did we see any effect of fructose dose, follow-up, or comparator on triglycerides in type 2 diabetes with the same subgroup criteria There was, however, evidence of significant interstudy heterogeneity across most subgroup categories.
These may be related to real biological differences between study populations or to methodological differences between trials that were not assessed in our a priori subgroup analyses. A number of potential mechanisms have been proposed to explain the improvements in glycemia seen with the consumption of fructose.
One possibility is that the addition of fructose to the diet may help control postprandial glycemic excursions. The resulting fructoseP is able to displace fructoseP from its binding site on the glucokinase regulatory protein, allowing increased translocation of glucokinase from the nucleus to the cytosol, where it is active. Both these mechanisms may be operating. Although it appears that isocaloric fructose feeding benefits glycemia, a dose threshold for harm must also be considered because fructose, more than other sources of carbohydrate, may increase serum triglycerides.
We therefore must consider the possible adverse effects of substituting fructose for other carbohydrates at high doses. There are currently no meta-analyses investigating the effect of fructose on LDL. A number of limitations complicate the interpretation of these aggregate analyses. Second, several studies included participants who were receiving insulin or oral hypoglycemic agents, treatments that in themselves would be expected to influence glycemia.
Third, given the small number of trials included in each stratum, meta-regression may have been underpowered to detect true differences. Fourth, a significant amount of unexplainable heterogeneity was detected in both primary and subgroup analyses, although our random-effects model did account for this heterogeneity. These deficiencies were especially of concern in the context of the small sample sizes, with most of the trials having 15 or fewer participants.
Finally, because only published trials were included, publication bias remains a possibility for all outcomes, although we noted statistical evidence of publication bias only for fasting glucose. The harm-reduction approach to fructose taken by diabetes associations 2 , 7 , 8 , which is based on possible adverse serum lipid effects, may need to be reconciled with a possible glycemic benefit.
These conclusions, however, are limited by the short follow-up, small sample size, and poor quality of most trials included in our meta-analysis, as well as the large degree of unexplained significant heterogeneity. Larger, longer, and higher-quality trials of controlled fructose feeding that also weigh any possible glycemic benefit against adverse metabolic effects are required for definitive confirmation of these findings.
None of the sponsors had a role in any aspect of the current study, including design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
No other potential conflicts of interest relevant to this article were reported. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. September Volume 41, Issue 9. We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Skip to main content. Diabetes Care Jul; 35 7: Data extraction Reports that met the inclusion criteria were each independently reviewed and extracted by at least two investigators with a standardized form.
RESULTS Search results A total of 4, eligible reports were identified with the search; of these, 4, were determined to be irrelevant on review of the titles and abstracts. Figure 1 Flowchart of literature search for the effect of fructose on glycemic end points fasting glucose, fasting insulin, and glycated blood proteins [HbA 1c and glycated albumin].
View inline View popup Download powerpoint. Table 1 Characteristics of experimental trials included in the meta-analysis. Download figure Open in new tab Download powerpoint. Figure 2 Forest plot of controlled feeding trials investigating the effect of isocaloric exchange of fructose for other carbohydrate on A glycated blood proteins HbA 1c and glycated albumin , B fasting glucose, and C fasting insulin.
Publication bias Supplementary Figs. Footnotes Clinical trial reg. The World Health Report Life in the 21st Century: A Vision for All. Geneva, World Health Organization, Canadian Diabetes Association clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes ; Height, predictors of C-peptide and cancer risk in men. Int J Epidemiol ; National estimates of dietary fructose intake increased from to in the United States. J Nutr ; Intakes and food sources of fructose in the United States.
Am J Clin Nutr ; 58 Suppl: Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr ; Nutrition recommendations and interventions for diabetes: Diabetes Care ; 31 Suppl.
S61 — S78 pmid: Evidence-based nutritional approaches to the treatment and prevention of diabetes mellitus. Nutr Metab Cardiovasc Dis ; Metabolic effects of dietary sucrose and fructose in type II diabetic subjects. Diabetes Care ; Osei K , Bossetti B. Dietary fructose as a natural sweetener in poorly controlled type 2 diabetes: Diabet Med ; 6: Metabolic effects of fructose as a natural sweetener in the physiologic meals of ambulatory obese patients with type II diabetes.
Am J Med ; Metabolic effects of fructose supplementation in diabetic individuals. Fructose and insulin sensitivity in patients with type 2 diabetes. J Intern Med ; Effets metaboliques de la consommation quotidienne pendant un an de saccharose ou de fructose par des diabetiques.
Médecine et Nutrition ; Metabolic effects of dietary fructose and sucrose in types I and II diabetic subjects. JAMA ; Cochrane Handbook for Systematic Reviews of Interventions. Oxford, UK , Cochrane Collaboration , Accessed on 15 May Preferred reporting items for systematic reviews and meta-analyses: PLoS Med ; 6: Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. Meta-analyses involving cross-over trials: Metabolic effects of dietary fructose in diabetic subjects.
Lack of detectable deleterious effects on metabolic control of daily fructose ingestion for 2 mo in NIDDM patients. Long-term effects of dietary fructose on carbohydrate metabolism in non-insulin-dependent diabetes mellitus.
Metabolism ; Catalytic amounts of fructose may improve glucose tolerance in subjects with uncontrolled non-insulin-dependent diabetes. Clin Nutr ; Metabolic effects of dietary fructose in insulin dependent diabetes of adults. Acta Med Scand Suppl ; Effect of dietary fructose on triglyceride transport and glucoregulatory hormones in hypertriglyceridemic men.
Metabolic consequence of two-week fructose feeding in diabetic subjects. Diabetes Care ; 9: The effects of one month high fructose intake on plasma glucose and lipid levels in non-insulin-dependent diabetes.
Diabet Med ; 4: Lipid metabolism in non-insulin-dependent diabetes: Center for Drug Evaluation and Research. Rockville, Md , U. Oral antihyperglycemic therapy for type 2 diabetes: Livesey G , Taylor R. Fructose consumption and consequences for glycation, plasma triacylglycerol, and body weight: Diabetes Care ; 6: Food labels are to list the most important nutrients in an easy-to-follow format.
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