Assessment of Carbohydrate Availability, Fermentability, and Food Energy Value in Humans Using Measurements of Breath Hydrogen.

Measurements in humans of their breath hydrogen is sometimes used to assess the availability, fermentability, and food energy value of carbohydrates that, to an unknown extent, resists small intestinal digestion and fermentation in the large intestine. Here I outline that the method is utterly flawed and conclude that it is unsuitable for making claims as to the availability, fermentability, and food energy value of carbohydrates. More traditional methods, although more demanding of time and effort, can be used. Otherwise further development of methodology is essential to avoid undue risk of bias.

Effect of low glycaemic index or load dietary patterns on glycaemic control and cardiometabolic risk factors in diabetes: systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To inform the update of the European Association for the Study of Diabetes clinical practice guidelines for nutrition therapy. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Embase, and the Cochrane Library searched up to 13 May 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials of three or more weeks investigating the effect of diets with low glycaemic index (GI)/glycaemic load (GL) in diabetes. OUTCOME AND MEASURES: The primary outcome was glycated haemoglobin (HbA1c). Secondary outcomes included other markers of glycaemic control (fasting glucose, fasting insulin); blood lipids (low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-HDL-C, apo B, triglycerides); adiposity (body weight, BMI (body mass index), waist circumference), blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP)), and inflammation (C reactive protein (CRP)). DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed risk of bias. Data were pooled by random effects models. GRADE (grading of recommendations assessment, development, and evaluation) was used to assess the certainty of evidence. RESULTS: 29 trial comparisons were identified in 1617 participants with type 1 and 2 diabetes who were predominantly middle aged, overweight, or obese with moderately controlled type 2 diabetes treated by hyperglycaemia drugs or insulin. Low GI/GL dietary patterns reduced HbA1c in comparison with higher GI/GL control diets (mean difference −0.31% (95% confidence interval −0.42 to −0.19%), P<0.001; substantial heterogeneity, I2=75%, P<0.001). Reductions occurred also in fasting glucose, LDL-C, non-HDL-C, apo B, triglycerides, body weight, BMI, systolic blood pressure (dose-response), and CRP (P<0.05), but not blood insulin, HDL-C, waist circumference, or diastolic blood pressure. A positive dose-response gradient was seen for the difference in GL and HbA1c and for absolute dietary GI and SBP (P<0.05). The certainty of evidence was high for the reduction in HbA1c and moderate for most secondary outcomes, with downgrades due mainly to imprecision. CONCLUSIONS: This synthesis suggests that low GI/GL dietary patterns result in small important improvements in established targets of glycaemic control, blood lipids, adiposity, blood pressure, and inflammation beyond concurrent treatment with hyperglycaemia drugs or insulin, predominantly in adults with moderately controlled type 1 and type 2 diabetes. The available evidence provides a good indication of the likely benefit in this population. STUDY REGISTRATION: ClinicalTrials.gov NCT04045938.

Dietary Glycaemic Index Labelling: A Global Perspective.

The glycaemic index (GI) is a food metric that ranks the acute impact of available (digestible) carbohydrates on blood glucose. At present, few countries regulate the inclusion of GI on food labels even though the information may assist consumers to manage blood glucose levels. Australia and New Zealand regulate GI claims as nutrition content claims and also recognize the GI Foundation's certified Low GI trademark as an endorsement. The GI Foundation of South Africa endorses foods with low, medium and high GI symbols. In Asia, Singapore's Healthier Choice Symbol has specific provisions for low GI claims. Low GI claims are also permitted on food labels in India. In China, there are no national regulations specific to GI; however, voluntary claims are permitted. In the USA, GI claims are not specifically regulated but are permitted, as they are deemed to fall under general food-labelling provisions. In Canada and the European Union, GI claims are not legal under current food law. Inconsistences in food regulation around the world undermine consumer and health professional confidence and call for harmonization. Global provisions for GI claims/endorsements in food standard codes would be in the best interests of people with diabetes and those at risk.

Dietary Fibre Consensus from the International Carbohydrate Quality Consortium (ICQC).

Dietary fibre is a generic term describing non-absorbed plant carbohydrates and small amounts of associated non-carbohydrate components. The main contributors of fibre to the diet are the cell walls of plant tissues, which are supramolecular polymer networks containing variable proportions of cellulose, hemicelluloses, pectic substances, and non-carbohydrate components, such as lignin. Other contributors of fibre are the intracellular storage oligosaccharides, such as fructans. A distinction needs to be made between intrinsic sources of dietary fibre and purified forms of fibre, given that the three-dimensional matrix of the plant cell wall confers benefits beyond fibre isolates. Movement through the digestive tract modifies the cell wall structure and may affect the interactions with the colonic microbes (e.g., small intestinally non-absorbed carbohydrates are broken down by bacteria to short-chain fatty acids, absorbed by colonocytes). These aspects, combined with the fibre associated components (e.g., micronutrients, polyphenols, phytosterols, and phytoestrogens), may contribute to the health outcomes seen with the consumption of dietary fibre. Therefore, where possible, processing should minimise the degradation of the plant cell wall structures to preserve some of its benefits. Food labelling should include dietary fibre values and distinguish between intrinsic and added fibre. Labelling may also help achieve the recommended intake of 14 g/1000 kcal/day.

Fructose ingestion: dose-dependent responses in health research.

Many hypotheses of disease risk and prevention depend on inferences about the metabolic effects of fructose; however, there is inadequate attention to dose dependency. Fructose is proving to have bidirectional effects. At moderate or high doses, an effect on any one marker may be absent or even the opposite of that observed at very high or excessive doses; examples include fasting plasma triglyceride, insulin sensitivity, and the putative marker uric acid. Among markers, changes can be beneficial for some (e.g., glycated hemoglobin at moderate to high fructose intake) but adverse for others (e.g., plasma triglycerides at very high or excessive fructose intake). Evidence on body weight indicates no effect of moderate to high fructose intakes, but information is scarce for high or excessive intakes. The overall balance of such beneficial and adverse effects of fructose is difficult to assess but has important implications for the strength and direction of hypotheses about public health, the relevance of some animal studies, and the interpretation of both interventional and epidemiological studies. By focusing on the adverse effects of very high and excessive doses, we risk not noticing the potential benefits of moderate to higher doses, which might moderate the advent and progress of type-2 diabetes, cardiovascular disease, and might even contribute to longevity. A salutary rather than hyperbolic examination of the evidence base needs to be undertaken.

Coronary Heart Disease and Dietary Carbohydrate, Glycemic Index, and Glycemic Load: Dose-Response Meta-analyses of Prospective Cohort Studies.

OBJECTIVE: To clarify the role of dietary carbohydrate, glycemic index (GI), and glycemic load (GL) in progression from health to coronary heart disease (CHD) by determining disease-nutrient risk relation (RR) values needed for intake ranges within jurisdictions and across the globe. METHODS: We performed a literature search of MEDLINE and EMBASE for prospective cohort studies that used truly valid dietary instruments in heathy adults published from January 1, 2000, to June 5, 2018. Relevant observations were extracted by 2 reviewers independently. We used dose-response meta-analysis accounting for nonindependence of results within studies. Bradford-Hill criteria were used to assess causality. RESULTS: Eligible studies had a mean follow-up of 11 years (range, 5-19 years), were conducted in North America, Europe, and East Asia, and yielded combined RRs of 1.44 (95% CI, 1.25-1.65) per 65 g/d GL (11 studies) and 1.24 (95% CI, 1.12-1.38) per 10 U GI (10 studies) (glucose scale). The CHD-carbohydrate RR on GI was 1.66 (95% CI, 1.23-2.25) per 98 g/d of carbohydrates per 10 units GI. The 65 g/d GL, 10 U GI, and 98 g/d carbohydrate values corresponded to oral intakes from the 10th to the 90th percentiles within sampled populations. Inconsistencies were minor (I 2 ≤20%), as were small-study effects (P=.61 for GL and P=.26 for GI). Funnel plots were symmetric. Cubic spline dose-response meta-analysis yielded RRs as follows: across the global range for GL (55-290 g/d), 5.5 (95% CI, 3.1-9.8) (I 2 =0); for GI (47-82 U), 2.71 (95% CI, 1.47-4.40) (I 2 =0); and for the CHD-carbohydrate dependence on GI (50-80 U), 4.57 (95% CI, 1.86-11.4) (I 2 =16%). Bradford-Hill criteria indicated that these relations were probably causal. CONCLUSION: Strong and probably causal CHD-GL and GI RRs exist within populations. The RRs were remarkably higher across global exposures. The results support the consideration of these markers of carbohydrate food quality in dietary guidelines for general populations. TRIAL REGISTRATION: PROSPERO Identifier: CRD42013004504.

Dietary Glycemic Index and Load and the Risk of Type 2 Diabetes: Assessment of Causal Relations.

While dietary factors are important modifiable risk factors for type 2 diabetes (T2D), the causal role of carbohydrate quality in nutrition remains controversial. Dietary glycemic index (GI) and glycemic load (GL) have been examined in relation to the risk of T2D in multiple prospective cohort studies. Previous meta-analyses indicate significant relations but consideration of causality has been minimal. Here, the results of our recent meta-analyses of prospective cohort studies of 4 to 26-y follow-up are interpreted in the context of the nine Bradford-Hill criteria for causality, that is: (1) Strength of Association, (2) Consistency, (3) Specificity, (4) Temporality, (5) Biological Gradient, (6) Plausibility, (7) Experimental evidence, (8) Analogy, and (9) Coherence. These criteria necessitated referral to a body of literature wider than prospective cohort studies alone, especially in criteria 6 to 9. In this analysis, all nine of the Hill's criteria were met for GI and GL indicating that we can be confident of a role for GI and GL as causal factors contributing to incident T2D. In addition, neither dietary fiber nor cereal fiber nor wholegrain were found to be reliable or effective surrogate measures of GI or GL. Finally, our cost-benefit analysis suggests food and nutrition advice favors lower GI or GL and would produce significant potential cost savings in national healthcare budgets. The high confidence in causal associations for incident T2D is sufficient to consider inclusion of GI and GL in food and nutrient-based recommendations.

Dietary Glycemic Index and Load and the Risk of Type 2 Diabetes: A Systematic Review and Updated Meta-Analyses of Prospective Cohort Studies.

Published meta-analyses indicate significant but inconsistent incident type-2 diabetes(T2D)-dietary glycemic index (GI) and glycemic load (GL) risk ratios or risk relations (RR). It is nowover a decade ago that a published meta-analysis used a predefined standard to identify validstudies. Considering valid studies only, and using random effects dose-response meta-analysis(DRM) while withdrawing spurious results (p < 0.05), we ascertained whether these relationswould support nutrition guidance, specifically for an RR > 1.20 with a lower 95% confidence limit>1.10 across typical intakes (approximately 10th to 90th percentiles of population intakes). Thecombined T2D-GI RR was 1.27 (1.15-1.40) (p < 0.001, n = 10 studies) per 10 units GI, while that forthe T2D-GL RR was 1.26 (1.15-1.37) (p < 0.001, n = 15) per 80 g/d GL in a 2000 kcal (8400 kJ) diet.The corresponding global DRM using restricted cubic splines were 1.87 (1.56-2.25) (p < 0.001, n =10) and 1.89 (1.66-2.16) (p < 0.001, n = 15) from 47.6 to 76.1 units GI and 73 to 257 g/d GL in a 2000kcal diet, respectively. In conclusion, among adults initially in good health, diets higher in GI or GLwere robustly associated with incident T2D. Together with mechanistic and other data, thissupports that consideration should be given to these dietary risk factors in nutrition advice.Concerning the public health relevance at the global level, our evidence indicates that GI and GLare substantial food markers predicting the development of T2D worldwide, for persons ofEuropean ancestry and of East Asian ancestry.

Glycemic response and health--a systematic review and meta-analysis: the database, study characteristics, and macronutrient intakes.

BACKGROUND: Reduction of dietary glycemic response has been proposed as a means of reducing the risk of diabetes and coronary heart disease. Its role in health maintenance and management, alongside unavailable carbohydrate (eg, fiber), is incompletely understood. OBJECTIVE: We aimed to assess the evidence relating the glycemic impact of foods to a role in health maintenance and management of disease. DESIGN: We searched the literature for relevant controlled dietary intervention trials on glycemic index (GI) according to inclusion and exclusion criteria, extracted the data to a database, and synthesized the evidence via meta-analyses and meta-regression models. RESULTS: Among literature to January 2005, 45 relevant publications were identified involving 972 subjects with good health or metabolic disease. With small reductions in GI (<10 units), increases in available carbohydrate, energy, and protein intakes were found in all studies combined. Falling trends in energy, available carbohydrate, and protein intakes then occurred with progressive reductions in GI. Fat intake was essentially unchanged. Unavailable carbohydrate intake was generally higher for intervention diets but showed no trend with GI (falling or rising). Among studies reporting on GI, variation in glycemic load was approximately equally explained by variation in GI and variation in available carbohydrate intake. An exchange of available and unavailable carbohydrate (approximately 1 g/g) was evident in these studies. CONCLUSIONS: Among GI studies, observed reductions in glycemic load are most often not solely due to substitution of high for low glycemic carbohydrate foods. Available carbohydrate intake is a confounding factor. The role of unavailable carbohydrate remains to be accounted for.

Glycemic response and health--a systematic review and meta-analysis: relations between dietary glycemic properties and health outcomes.

BACKGROUND: Reduction of dietary glycemic response has been proposed as a means of reducing the risk of diabetes and coronary heart disease. The impact of glycemic response on markers of health remains to be elucidated. OBJECTIVE: We assessed the evidence relating the glycemic impact of foods to measures relevant for health maintenance and management of disease. DESIGN: This was a systematic review and synthesis of interventional evidence from literature reported on glycemic index and markers of health through the use of meta-analyses and meta-regression models. RESULTS: Data from 45 relevant publications were found to January 2005. Lower glycemic index (GI) diets reduced both fasting blood glucose and glycated proteins independently of variance in available and unavailable carbohydrate intakes. Elevated unavailable carbohydrate added to improvements in both blood glucose and glycated protein control. These effects were greater in persons with poor fasting blood glucose control. No effects were seen on fasting insulin<100 pmol/L; above this, study numbers were few but consistent with prevention of hyperinsulinemia in some but not all overweight persons. Insulin sensitivity according to a variety of measurement methods was improved by lower GI, higher unavailable carbohydrate interventions in persons with type 2 diabetes, in overweight and obese persons, and in all studies combined. Fasting triacylglycerol in addition to body weight reduction related more to glycemic load than to GI. Glycemic load reduction by >17 g glucose equivalents/d was associated with reduced body weight. CONCLUSIONS: Consumption of reduced glycemic response diets are followed by favorable changes in the health markers examined. The case for the use of such diets looks compelling. Unavailable carbohydrate intake is equally important.

Accuracy of the Atwater factors and related food energy conversion factors with low-fat, high-fiber diets when energy intake is reduced spontaneously.

BACKGROUND: Systems to calculate metabolizable energy (ME) in foods and diets are often based on Atwater factors. The accuracy of these factors with low-fat diets high in fiber is unknown when food intake is reduced spontaneously. OBJECTIVE: The objective was to evaluate the accuracy of Atwater factors and other systems for calculating ME available from low-fat, high-fiber diets when food intake was reduced spontaneously. DESIGN: The ME contents of a high-fat, low-fiber diet and 2 low-fat diets, one high in fruit and vegetable fiber and the other high in cereal fiber, were determined in a randomized parallel study in humans (n = 27) and compared with various factorial and empirical models for calculating ME. RESULTS: Food intakes decreased with both the high fruit and vegetable fiber and cereal fiber diets. The difference between ME calculated by using Atwater and similar factors and determined ME values was up to 4% for the refined diet and up to 11% for the low-fat, high-fiber diets. Various factorial and empirical systems for calculating food energy failed to reflect the results of the direct determinations. CONCLUSION: Atwater factors were inaccurate with low-fat, high-fiber diets. Although modified Atwater factors may be accurate under standardized conditions of zero-nitrogen and zero-energy balance, they overestimate energy availability from high-fiber fruit and vegetable and cereal diets when food intake is reduced spontaneously in addition to when intake is reduced voluntarily.

Availability, fermentability, and energy value of resistant maltodextrin: modeling of short-term indirect calorimetric measurements in healthy adults.

BACKGROUND: Determination of the metabolizable (ME) and net metabolizable (NME) energy of total carbohydrate requires estimation of its available (AC) and fermentable (FC) carbohydrate content. Modeling of indirect calorimetric observations (respiratory gas exchange) and breath hydrogen would appear to make it possible to estimate noninvasively these nutritional quantities and the approximate time-course of availability. OBJECTIVE: We assessed the time-course of metabolism and energy availability from resistant maltodextrin (RMD) by modeling of respiratory gases after a single oral dose. DESIGN: Seventeen healthy adults (13 M, 4 F; aged 25-46 y) were randomly assigned to treatments (water, maltodextrin, or RMD) in a multiple-crossover, single-blinded trial with > or = 7 d washout. We monitored 8-h nitrogen-corrected oxygen and carbon dioxide exchanges and breath hydrogen. All treatment groups took low-carbohydrate meals at 3 and 6 h. RESULTS: Indirect calorimetry alone provided only qualitative information about the nutritional values of carbohydrate. In contrast, modeling of gaseous exchanges along with the use of central assumptions showed that 17 +/- 2% of RMD was AC and 40 +/- 4% was FC. As compared with 17 kJ gross energy/g RMD, mean (+/- SE) energy values were 7.3 +/- 0.6 kJ ME/g and 6.3 +/- 0.5 kJ NME/g. The fiber fraction of RMD provided 5.2 +/- 0.7 kJ ME/g and 4.1 +/- 0.6 kJ NME/g. CONCLUSIONS: Modeling with the use of this noninvasive and widely available respiratory gas-monitoring technique yields nutritional values for carbohydrate that are supported by enzymatic, microbial, and animal studies and human fecal collection studies. Improvement in this approach is likely and testable across laboratories.

Health potential of polyols as sugar replacers, with emphasis on low glycaemic properties.

Abstract Polyols are hydrogenated carbohydrates used as sugar replacers. Interest now arises because of their multiple potential health benefits. They are non-cariogenic (sugar-free tooth-friendly), low-glycaemic (potentially helpful in diabetes and cardiovascular disease), low-energy and low-insulinaemic (potentially helpful in obesity), low-digestible (potentially helpful in the colon), osmotic (colon-hydrating, laxative and purifying) carbohydrates. Such potential health benefits are reviewed. A major focus here is the glycaemic index (GI) of polyols as regards the health implications of low-GI foods. The literature on glycaemia and insulinaemia after polyol ingestion was analysed and expressed in the GI and insulinaemic index (II) modes, which yielded the values: erythritol 0, 2; xylitol 13, 11; sorbitol 9, 11; mannitol 0, 0; maltitol 35, 27; isomalt 9, 6; lactitol 6, 4; polyglycitol 39, 23. These values are all much lower than sucrose 65, 43 or glucose 100, 100. GI values on replacing sucrose were independent of both intake (up to 50 g) and the state of carbohydrate metabolism (normal, type 1 with artificial pancreas and type 2 diabetes mellitus). The assignment of foods and polyols to GI bands is considered, these being: high (> 70), intermediate (> 55-70), low (> 40-55), and very low (< 40) including non-glycaemic; the last aims to target particularly low-GI-carbohydrate-based foods. Polyols ranged from low to very low GI. An examination was made of the dietary factors affecting the GI of polyols and foods. Polyol and other food GI values could be used to estimate the GI of food mixtures containing polyols without underestimation. Among foods and polyols a departure of II from GI was observed due to fat elevating II and reducing GI. Fat exerted an additional negative influence on GI, presumed due to reduced rates of gastric emptying. Among the foods examined, the interaction was prominent with snack foods; this potentially damaging insulinaemia could be reduced using polyols. Improved glycated haemoglobin as a marker of glycaemic control was found in a 12-week study of type 2 diabetes mellitus patients consuming polyol, adding to other studies showing improved glucose control on ingestion of low-GI carbohydrate. In general some improvement in long-term glycaemic control was discernible on reducing the glycaemic load via GI by as little as 15-20 g daily. Similar amounts of polyols are normally acceptable. Although polyols are not essential nutrients, they contribute to clinically recognised maintenance of a healthy colonic environment and function. A role for polyols and polyol foods to hydrate the colonic contents and aid laxation is now recognised by physicians. Polyols favour saccharolytic anaerobes and aciduric organisms in the colon, purifying the colon of endotoxic, putrefying and pathological organisms, which has clinical relevance. Polyols also contribute towards short-chain organic acid formation for a healthy colonic epithelium. Polyol tooth-friendliness and reduced energy values are affirmed and add to the potential benefits. In regard to gastrointestinal tolerance, food scientists and nutritionists, physicians, and dentists have in their independent professional capacities each now described sensible approaches to the use and consumption of polyols.

Is there a dose-response relation of dietary glycemic load to risk of type 2 diabetes? Meta-analysis of prospective cohort studies.

BACKGROUND: Although much is known about the association between dietary glycemic load (GL) and type 2 diabetes (T2D), prospective cohort studies have not consistently shown a positive dose-response relation. OBJECTIVE: We performed a comprehensive examination of evidence on the dose response that links GL to T2D and sources of heterogeneity among all prospective cohort studies on healthy adults available in the literature. DESIGN: We conducted a systematic review of all prospective cohort studies and meta-analyses to quantify the GL-T2D relation both without and with adjustment for covariates. RESULTS: Among 24 prospective cohort studies identified by August 2012, the GL ranged from ∼60 to ∼280 g per daily intake of 2000 kcal (8.4 MJ). In a fully adjusted meta-analysis model, the GL was positively associated with RR of T2D of 1.45 (95% CI: 1.31, 1.61) for a 100-g increment in GL (P < 0.001; n = 24 studies; 7.5 million person-years of follow-up). Sex (P = 0.03), dietary instrument validity (P < 0.001), and ethnicity (European American compared with other; P = 0.04) together explained 97% of the heterogeneity among studies. After adjustment for heterogeneities, we used both funnel and trim-and-fill analyses to identify a negligible publication bias. Multiple influence, cumulative, and forecast analyses indicated that the GL-T2D relation tended to have reached stability and to have been underestimated. The relation was apparent at all doses of GL investigated, although it was statistically significant only at >95 g GL/2000 kcal. CONCLUSION: After we accounted for several sources of heterogeneity, findings from prospective cohort studies that related the GL to T2D appear robust and consistently indicate strong and significantly lower T2D risk in persons who consume lower-GL diets. This review was registered at http://www.crd.york.ac.uk/PROSPERO as CRD42011001810.

Interventions to lower the glycemic response to carbohydrate foods with a low-viscosity fiber (resistant maltodextrin): meta-analysis of randomized controlled trials.

BACKGROUND: The glycemic response to diet has been linked with noncommunicable diseases and is reduced by low-palatable, viscous, soluble fiber (1). Whether a palatable, low-viscous, soluble fiber such as resistant maltodextrin (RMD) has the same effect is unclear. OBJECTIVE: The objective was to assess evidence on the attenuation of the blood glucose response to foods by < or = 10 g RMD in healthy adults. DESIGN: We conducted a systematic review of randomized, placebo-controlled trials with the use of fixed- and random-effects meta-analyses and meta-regression models. RESULTS: We found data from 37 relevant trials to April 2007. These trials investigated the attenuation of the glycemic response to rice, noodles, pastry, bread, and refined carbohydrates that included 30-173 g available carbohydrate. RMD was administered in drinks or liquid foods or solid foods. Placebo drinks and foods excluded RMD. Percentage attenuation was significant, dose-dependent, and independent of the amount of available carbohydrate coingested. Attenuation of the glycemic response to starchy foods by 6 g RMD in drinks approached approximately 20%, but when placed directly into foods was approximately 10% -- significant (P < 0.001) by both modes of administration. Study quality analyses, funnel plots, and trim-and-fill analyses uncovered no cause of significant systematic bias. Studies from authors affiliated with organizations for-profit were symmetrical without heterogeneity, whereas marginal asymmetry and significant heterogeneity arose among studies involving authors from nonprofit organizations because of some imprecise studies. CONCLUSIONS: A nonviscous palatable soluble polysaccharide can attenuate the glycemic response to carbohydrate foods. Evidence of an effect was stronger for RMD in drinks than in foods.

Fructose consumption and consequences for glycation, plasma triacylglycerol, and body weight: meta-analyses and meta-regression models of intervention studies.

BACKGROUND: The glycemic response to dietary fructose is low, which may improve concentrations of glycated hemoglobin (HbA(1c), a marker of dysglycemia). Meanwhile, adverse effects on plasma triacylglycerol (a marker of dyslipidemia) and body weight have been questioned. Such effects are reported inconsistently. OBJECTIVE: We aimed to evaluate the effect of fructose on these health markers, particularly examining treatment dose and duration, and level of glycemic control. DESIGN: A literature search was conducted for relevant randomized and controlled intervention studies of crystalline or pure fructose (excluding high-fructose corn syrup), data extraction, meta-analyses, and modeling using meta-regression. RESULTS: Fructose intake < 90 g/d significantly improved HbA(1c) concentrations dependent on the dose, the duration of study, and the continuous severity of dysglycemia throughout the range of dysglycemia. There was no significant change in body weight at intakes <100 g fructose/d. Fructose intakes of <50 g/d had no postprandially significant effect on triacylglycerol and those of or=100 g fructose/d, the effect on fasting triacylglycerol depended on whether sucrose or starch was being exchanged with fructose, and the effect was dose-dependent but was less with increasing duration of treatment. Different health types and sources of bias were examined; they showed no significant departure from a general trend. CONCLUSIONS: The meta-analysis shows that fructose intakes from 0 to >or=90 g/d have a beneficial effect on HbA(1c). Significant effects on postprandial triacylglycerols are not evident unless >50 g fructose/d is consumed, and no significant effects are seen for fasting triacylglycerol or body weight with intakes of