Gut microbial metabolism drives transformation of MSH2-deficient colon epithelial cells.

The etiology of colorectal cancer (CRC) has been linked to deficiencies in mismatch repair and adenomatous polyposis coli (APC) proteins, diet, inflammatory processes, and gut microbiota. However, the mechanism through which the microbiota synergizes with these etiologic factors to promote CRC is not clear. We report that altering the microbiota composition reduces CRC in APC(Min/+)MSH2(-/-) mice, and that a diet reduced in carbohydrates phenocopies this effect. Gut microbes did not induce CRC in these mice through an inflammatory response or the production of DNA mutagens but rather by providing carbohydrate-derived metabolites such as butyrate that fuel hyperproliferation of MSH2(-/-) colon epithelial cells. Further, we provide evidence that the mismatch repair pathway has a role in regulating ß-catenin activity and modulating the differentiation of transit-amplifying cells in the colon. These data thereby provide an explanation for the interaction between microbiota, diet, and mismatch repair deficiency in CRC induction. PAPERCLIP:

Cross-linked phosphorylated RS4 wheat starch reduces glucose and insulin responses after 3 days of pre-feeding in healthy adults: an acute, double-blind, randomized controlled clinical trial.

When this project was designed, there was no evidence that adding resistant starch to available carbohydrate (avCHO) reduced glycaemic and insulinaemic responses (GIR). We compared GIR elicited by a cookie containing cross-linked phosphorylated RS4 wheat starch (Fibersym®) (RS4XL) versus an avCHO-matched control-cookie (CC) after n = 15 adults had consumed RS4XL or CC daily for 3-days using a double-blind, randomised, cross-over design. The difference in glucose iAUC over 0-2 h (primary endpoint) (mmol × min/L) after RS4XL, (mean ± SEM) 106 ± 16, versus CC, 124 ± 16, was not significant (p = 0.087). However, RS4XL reduced 0-90 min glucose iAUC (72 ± 9 vs 87 ± 9, p = 0.022), peak glucose concentration (6.05 ± 0.36 vs 6.57 ± 0.31 mmol/L, p = 0.017) and 0-2 h insulin iAUC (189 ± 21 vs 246 ± 24 nmol × h/L, p = 0.020). These results show that RS4XL reduced postprandial glycaemic and insulinaemic responses when added to avCHO, but do not prove that the products of its colonic fermentation are required for this effect.

Canned Beans Decrease Serum Total and LDL Cholesterol in Adults with Elevated LDL Cholesterol in a 4-wk Multicenter, Randomized, Crossover Study.

BACKGROUND: Practical risk reduction strategies are needed to address cardiovascular disease. Beans can decrease LDL cholesterol; however, research into different daily amounts and varieties is warranted. OBJECTIVES: To examine the effects of canned beans (daily rotation of black, navy, pinto, dark red kidney, white kidney) in 1-cup (1CB, 180 g) and ½-cup (½CB, 90 g) daily amounts compared with a 1-cup white rice (WR) control on serum lipid and glycemic biomarkers in adults with elevated LDL cholesterol. METHODS: Adults [n = 73, mean ± SD age: 48.1 ± 14.2 y; BMI (in kg/m2): 25.9 ± 4.22; fasting serum LDL cholesterol: 3.0-5.0 mmol/L] consumed 1CB, ½CB, and WR for 4-wk treatment periods separated by ≥4-wk washouts in a multicenter, randomized, crossover study. Fasting serum LDL cholesterol (primary outcome) and other lipids and glycemic biomarkers (secondary outcomes) were measured on study days 1 and 29 of each treatment period with study day 29 values compared using repeated-measures ANCOVA, including study day 1 values as covariates. RESULTS: Treatment completion was n = 66 for 1CB, n = 68 for ½CB, and n = 64 for WR. Total cholesterol on study day 29 was lower for 1CB (P = 0.04) but not ½CB (P = 0.77) compared with WR (-5.46%, -2.74%, -0.65% changes from study day 1, respectively) and did not differ between 1CB and ½CB (P = 0.17). LDL cholesterol on study day 29 was also lower for 1CB (P = 0.002) but not ½CB (P = 0.30) compared with WR (-8.08%, -3.84%, +0.49% changes from study day 1, respectively) and did not differ between 1CB and ½CB (P = 0.11). Other lipids and glycemic biomarkers did not differ among treatments. CONCLUSIONS: Consumption of 1 cup (180 g) of canned beans of multiple varieties decreased total and LDL cholesterol in adults with elevated LDL cholesterol, supporting a practical strategy for cardiovascular disease risk reduction. This trial was registered at clinicaltrials.gov as NCT03830970.

Impact of oat processing on glycaemic and insulinaemic responses in healthy humans: a randomised clinical trial.

Oats can be processed in a variety of ways ranging from minimally processed such as steel-cut oats (SCO), to mildly processed such as large-flake oats (old fashioned oats, OFO), moderately processed such as instant oats (IO) or highly processed in ready-to-eat oat cereals such as Honey Nut Cheerios (HNC). Although processing is believed to increase glycaemic and insulinaemic responses, the effect of oat processing in these respects is unclear. Thus, we compared the glycaemic and insulinaemic responses elicited by 628 kJ portions of SCO, OFO, IO and HNC and a portion of Cream of Rice cereal (CR) containing the same amount of available-carbohydrate (23 g) as the oatmeals. Healthy males (n 18) and females (n 12) completed this randomised, cross-over trial. Blood was taken fasting and at intervals for 3 h following test-meal consumption. Glucose and insulin peak-rises and incremental AUC (iAUC) were subjected to repeated-measures ANOVA using Tukey's test (two-sided P<0·05) to compare individual means. Glucose peak-rise (primary endpoint, mean (sem) mmol/l) after OFO, 2·19 (sem 0·11), was significantly less than after CR, 2·61 (sem 0·13); and glucose peak-rise after SCO, 1·93 (sem 0·13), was significantly less than after CR, HNC, 2·49 (sem 0·13) and IO 2·47 (sem 0·13). Glucose iAUC was significantly lower after SCO than CR and HNC. Insulin peak rise was similar among the test meals, but insulin iAUC was significantly less after SCO than IO. Thus, the results show that oat processing affects glycaemic and insulinaemic responses with lower responses associated with less processing.

The effect of small doses of fructose and allulose on postprandial glucose metabolism in type 2 diabetes: A double-blind, randomized, controlled, acute feeding, equivalence trial.

AIM: To assess and compare the effect of small doses of fructose and allulose on postprandial blood glucose regulation in type 2 diabetes. METHODS: A double-blind, multiple-crossover, randomized, controlled, acute feeding, equivalence trial in 24 participants with type 2 diabetes was conducted. Each participant was randomly assigned six treatments separated by >1-week washouts. Treatments consisted of fructose or allulose at 0 g (control), 5 g or 10 g added to a 75-g glucose solution. A standard 75-g oral glucose tolerance test protocol was followed with blood samples at -30, 0, 30, 60, 90 and 120 minutes. The primary outcome measure was plasma glucose incremental area under the curve (iAUC). RESULTS: Allulose significantly reduced plasma glucose iAUC by 8% at 10 g compared with 0 g (717.4 ± 38.3 vs. 777.5 ± 39.9 mmol × min/L, P = 0.015) with a linear dose response gradient between the reduction in plasma glucose iAUC and dose (P = 0.016). Allulose also significantly reduced several related secondary and exploratory outcome measures at 5 g (plasma glucose absolute mean and total AUC) and 10 g (plasma glucose absolute mean, absolute and incremental maximum concentration [Cmax ], and total AUC) (P < .0125). There was no effect of fructose at any dose. Although allulose showed statistically significant reductions in plasma glucose iAUC compared with fructose at 5 g, 10 g and pooled doses, these reductions were within the pre-specified equivalence margins of ±20%. CONCLUSION: Allulose, but not fructose, led to modest reductions in the postprandial blood glucose response to oral glucose in individuals with type 2 diabetes. There is a need for long-term randomized trials to confirm the sustainability of these improvements.

Effect of vitamin D supplementation on oral glucose tolerance in individuals with low vitamin D status and increased risk for developing type 2 diabetes (EVIDENCE): A double-blind, randomized, placebo-controlled clinical trial.

AIMS: Low serum 25-hydroxyvitamin-D (25(OH)D) concentrations are associated with insulin resistance, ß-cell dysfunction and type 2 diabetes. We conducted a 24-week double-blind, randomized, placebo-controlled trial to examine the effect of 28 000 IU of vitamin D3 once weekly on plasma glucose after a 2 hour-75 g oral glucose tolerance test (2hrPC glucose), insulin sensitivity and ß-cell function. STUDY DESIGN AND METHODS: A total of 71 participants with serum 25(OH)D ≤65 nmol/L, impaired fasting glucose and elevated glycated hemoglobin were randomly assigned to receive 28 000 IU of vitamin D3 (VitD; n = 35) or placebo (n = 36) in cheese once weekly for 24 weeks. The primary outcome was the change in 2hPC glucose. Secondary outcomes were fasting glucose, fasting and postprandial insulin, indices of insulin sensitivity and ß-cell function, glycated hemoglobin and lipid profile. Participants underwent an oral glucose tolerance test to determine 2hPC glucose. RESULTS: Mean baseline serum 25(OH)D was 48.1 and 47.6 nmol/L in the VitD and placebo groups, respectively. Serum 25(OH)D significantly increased to 98.7 nmol/L (51 nmol/L increase; P < .0001) in the VitD group. No significant differences in fasting ( P = .42) or 2hPC glucose ( P = .55) or other indices of glucose metabolism, including ß-cell function and insulin sensitivity, were observed between groups. A subgroup analysis of individuals with 25(OH)D < 50 nmol/L and prediabetes did not change these results. The VitD group exhibited a significant reduction in LDL cholesterol (-0.27 vs 0.01 mmol/L, P = .03). CONCLUSION: Weekly doses of vitamin D3 in individuals with suboptimal vitamin D levels who were at risk for type 2 diabetes did not improve oral glucose tolerance or markers of glycaemic status.

Relation of total sugars, fructose and sucrose with incident type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Sugar-sweetened beverages are associated with type 2 diabetes. To assess whether this association holds for the fructose-containing sugars they contain, we conducted a systematic review and meta-analysis of prospective cohort studies. METHODS: We searched MEDLINE, Embase, CINAHL and the Cochrane Library (through June 2016). We included prospective cohort studies that assessed the relation of fructose-containing sugars with incident type 2 diabetes. Two independent reviewers extracted relevant data and assessed risk of bias. We pooled risk ratios (RRs) using random effects meta-analyses. The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Fiffeen prospective cohort studies (251 261 unique participants, 16 416 cases) met the eligibility criteria, comparing the highest intake (median 137, 35.2 and 78 g/d) with the lowest intake (median 65, 9.7 and 25.8 g/d) of total sugars, fructose and sucrose, respectively. Although there was no association of total sugars (RR 0.91, 95% confidence interval [CI] 0.76-1.09) or fructose (RR 1.04, 95% CI 0.84-1.29) with type 2 diabetes, sucrose was associated with a decreased risk of type 2 diabetes (RR 0.89, 95% CI 0.80-0.98). Our confidence in the estimates was limited by evidence of serious inconsistency between studies for total sugars and fructose, and serious imprecision in the pooled estimates for all 3 sugar categories. INTERPRETATION: Current evidence does not allow us to conclude that fructose-containing sugars independent of food form are associated with increased risk of type 2 diabetes. Further research is likely to affect our estimates. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01608620.

Neuromuscular adaptations to sprint interval training and the effect of mammalian omega-3 fatty acid supplementation.

PURPOSE: Sprint interval training (SIT) stimulates rapid metabolic adaptations within skeletal muscle but the nature of neuromuscular adaptions is unknown. Omega-3 polyunsaturated fatty acids (N-3 PUFA) are suggested to enhance neuromuscular adaptations to exercise. METHODS: We measured the neuromuscular adaptations to SIT (Study-1) and conducted a placebo-controlled randomized double blinded study to determine the effect of N-3 PUFA supplementation on neuromuscular adaptations to SIT (Study-2). In Study-1, seven active men (24.4 ± 2.6 years, VO2 peak 43.8 ± 8.7 ml kg min-1) completed 2-weeks of SIT with pre- and post-training 10 km cycling time trials (TT). In Study-2, 30 active men (24.5 ± 4.2 years, VO2 peak 41.0 ± 5.1 ml kg min-1) were randomly assigned to receive N-3 PUFA (2330 mg day-1) (n = 14) or olive oil (n = 16) during 2-weeks of SIT with pre- and post-training TTs. Four week post-training, a SIT session and TT were also performed. Change in neuromuscular function was assessed from resting twitches, quadriceps maximal voluntary contraction (MVC) force, and potentiated twitch force (Q tw). RESULTS: Study-1 showed that SIT did not elicit significant neuromuscular adaptations. Study-2 showed that N-3 PUFA supplementation had no significant effect on neuromuscular adaptations. Training caused lower MVC force [mean ± SD; N-3 PUFA -9 ± 11%, placebo -9 ± 13% (p < 0.05 time)] and Q tw peripheral fatigue [N-3 PUFA -10 ± 19%, placebo -14 ± 13% (p < 0.05 time)]. TT time was lower after training in all groups [Study-1 -10%, Study-2 N-3 PUFA -8%, placebo -12% (p < 0.05 time)]. CONCLUSION: Two weeks of SIT improved TT performance in the absence of measurable neuromuscular adaptations. N-3 PUFA supplementation had no significant effect on SIT training adaptations.

Short-chain fatty acids affect cystic fibrosis airway inflammation and bacterial growth.

The hypoxic environment of cystic fibrosis airways allows the persistence of facultative anaerobic bacteria, which can produce short-chain fatty acids (SCFAs) through fermentation. However, the relevance of SCFAs in cystic fibrosis lung disease is unknown. We show that SCFAs are present in sputum samples from cystic fibrosis patients in millimolar concentrations (mean±sem 1.99±0.36 mM).SCFAs positively correlated with sputum neutrophil count and higher SCFAs were predictive for impaired nitric oxide production. We studied the effects of the SCFAs acetate, propionate and butyrate on airway inflammatory responses using epithelial cell lines and primary cell cultures. SCFAs in concentrations present in cystic fibrosis airways (0.5-2.5 mM) affected the release of granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor and interleukin (IL)-6. SCFAs also resulted in higher IL-8 release from stimulated cystic fibrosis transmembrane conductance regulator (CFTR) F508del-mutant compared to wild-type CFTR-corrected bronchial epithelial cells. At 25 mM propionate reduced IL-8 release in control but not primary cystic fibrosis epithelial cells. Low (0.5-2.5 mM) SCFA concentrations increased, while high (25-50 mM) concentrations decreased inducible nitric oxide synthase expression. In addition, SCFAs affected the growth of Pseudomonas aeruginosa in a concentration- and pH-dependent manner.Thus, our data suggest that SCFAs contribute to cystic fibrosis-specific alterations of responses to airway infection and inflammation.

Total fructose intake and risk of hypertension: a systematic review and meta-analysis of prospective cohorts.

OBJECTIVES: Although most controlled feeding trials have failed to show an adverse effect of fructose on blood pressure, concerns continue to be raised regarding the role of fructose in hypertension. To quantify the association between fructose-containing sugar (high-fructose corn syrup, sucrose, and fructose) intake and incident hypertension, a systematic review and meta-analysis of prospective cohort studies was undertaken. METHODS: MEDLINE, EMBASE, CINAHL and the Cochrane Library (through February 5, 2014) were searched for relevant studies. Two independent reviewers reviewed and extracted relevant data. Risk estimates were aggregated comparing the lowest (reference) quintile with highest quintile of intake using inverse variance random effect models and expressed as risk ratios (RR) with 95% confidence intervals (CIs). Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I(2) statistic). The Newcastle-Ottawa Scale assessed study quality. Clinicaltrials.gov NCT01608620. RESULTS: Eligibility criteria were met by 3 prospective cohorts (n = 37,375 men and 185,855 women) with 58,162 cases of hypertension observed over 2,502,357 person-years of follow-up. Median fructose intake was 5.7-6.0% total energy in the lowest quintile and 13.9-14.3% total energy in the highest quintile. Fructose intake was not associated with incident hypertension (RR = 1.02, 95% CI, 0.99-1.04), with no evidence of heterogeneity (I(2) = 0%, p = 0.59). Spline curve modeling showed a U-shaped relationship with a negative association at intakes ≤50th percentile (∼10% total energy) and a positive association at higher intakes. CONCLUSIONS: Total fructose intake was not associated with an increased risk of hypertension in 3 large prospective cohorts of U.S. men and women.

Ketone production and excretion even during mild hyperglycemia and the impact of sodium-glucose co-transporter inhibition in type 1 diabetes.

AIMS: We aimed to determine if ketone production and excretion are increased even at mild fasting hyperglycemia in type 1 diabetes (T1D) and if these are modified by ketoacidosis risk factors, including sodium-glucose co-transporter inhibition (SGLTi) and female sex. METHODS: In secondary analysis of an 8-week single-arm open-label trial of empagliflozin (NCT01392560) we evaluated ketone concentrations during extended fasting and clamped euglycemia (4-6 mmol/L) and mild hyperglycemia (9-11 mmol/L) prior to and after treatment. Plasma and urine beta-hydroxybutyrate (BHB) concentrations and fractional excretion were analyzed by metabolomic analysis. RESULTS: Forty participants (50 % female), aged 24 ± 5 years, HbA1c 8.0 ± 0.9 % (64 ± 0.08 mmol/mol) with T1D duration of 17.5 ± 7 years, were studied. Increased BHB production even during mild hyperglycemia (median urine 6.3[3.5-13.6] vs. 3.5[2.2-7.0] µmol/mmol creatinine during euglycemia, p < 0.001) was compensated by increased fractional excretion (0.9 % [0.3-1.6] vs. 0.4 % [0.2-0.9], p < 0.001). SGLTi increased production and attenuated the increased BHB fractional excretion (decreased to 0.3 % during mild hyperglycemia, p < 0.001), resulting in higher plasma concentrations (increased to 0.21 [0.05-0.40] mmol/L, p < 0.001), particularly in females (interaction p < 0.001). CONCLUSIONS: Even mild hyperglycemia is associated with greater ketone production, compensated by urinary excretion, in T1D. However, SGLTi exaggerates production and partially reduces compensatory excretion, particularly in women.

Age, dietary fiber, breath methane, and fecal short chain fatty acids are interrelated in Archaea-positive humans.

Recent attention has focused on the significance of colonic Archaea in human health and energy metabolism. The main objectives of this study were to determine the associations among the number of fecal Archaea, body mass index (BMI), fecal short chain fatty acid (SCFA) concentrations, and dietary intakes of healthy humans. We collected demographic information, 3-d diet records, and breath and fecal samples from 95 healthy participants who were divided into 2 groups: detectable Archaea (>10(6) copies/g; Arch+ve) and undetectable Archaea. Dietary intakes, BMI, and fecal SCFAs were similar in both groups. The mean number of Archaea 16S rRNA gene copies detected in Arch+ve participants' feces was 8.9 ± 0.2 log/g wet weight. In Arch+ve participants, there were positive correlations between breath methane and age (r = 0.52; P = 0.001), total dietary fiber (TDF) intake (r = 0.57; P = 0.0003), and log number of fecal Archaea 16S rRNA gene copies (r = 0.35; P = 0.03). In the Arch+ve group, negative correlations were observed between TDF/1000 kcal and fecal total SCFA (r = -0.46; P ≤ 0.01) and between breath methane and fecal total SCFA (r = -0.42; P = 0.01). Principal component analysis identified a distinct Archaea factor with positive loadings of age, breath methane, TDF, TDF/1000 kcal, and number of log Archaea 16S rRNA gene copies. The results suggest that colonic Archaea is not associated with obesity in healthy humans. The presence of Archaea in humans may influence colonic fermentation by altering SCFA metabolism and fecal SCFA profile.

Increasing the viscosity of oat ß-glucan beverages by reducing solution volume does not reduce glycaemic responses.

The soluble fibre (1 → 3)(1 → 4)-ß-D-glucan attenuates postprandial glycaemic responses when administered in solution. This attenuating effect is strengthened when solution viscosity is increased by increasing the ß-glucan dose or molecular weight (MW). The effect of varying solution viscosity by changing solution volume, without changing the ß-glucan dose or MW, on glycaemic responses was determined. A total of fifteen healthy subjects received six 50 g oral glucose beverages prepared with or without 4 g of high-MW (HMW, 580,000 g/mol) or low-MW (LMW, 145,000 g/mol) ß-glucan, with a beverage volume of 250 or 600 ml. Postprandial plasma glucose concentration was measured over 2 h, and the peak blood glucose rise (PBGR) and the incremental area under the glycaemic response curve (AUC) were calculated. Subjects served as their own controls. The physico-chemical properties of the beverages were measured to examine their relationship with glycaemic response results. The HMW ß-glucan beverage was more viscous and achieved greater reductions in PBGR than the glucose beverage with LMW ß-glucan (P < 0·05). At the same MW, the 250 and 600 ml ß-glucan beverages differed in viscosity (>9-fold difference) but not in PBGR (P > 0·05). No differences in AUC were detected among the beverages (P = 0·147). The effects of ß-glucan on glycaemic response were altered by changes in beverage viscosity achieved through changes in MW but not in volume. Therefore, ß-glucan dose and MW are the most vital characteristics for optimising the bioactivity of ß-glucan solutions with respect to glycaemic response.

Preoperative carbohydrate loading in patients undergoing coronary artery bypass or spinal surgery.

BACKGROUND: Surgical stress creates a state of insulin resistance which may contribute to the development of hyperglycemia and, subsequently, postoperative complications. Consumption of an oral carbohydrate supplement before surgery may improve insulin sensitivity and reduce hyperglycemia. In this trial, we investigated the effects of carbohydrate supplementation on insulin resistance in coronary artery bypass graft and spinal decompression and fusion surgical patients. METHODS: Twenty-six patients undergoing coronary artery bypass graft and 12 undergoing spine surgery were randomized to receive 800 mL of an oral carbohydrate supplement the evening before and 400 mL 2 hours before surgery (CHO) or to fasting per standard hospital protocol (FAST). Baseline and postoperative measurements of insulin sensitivity were assessed using the short insulin tolerance test and homeostasis model assessment (HOMA). Interleukin-6, C-reactive protein, and free fatty acid levels were determined at baseline, postoperatively, and 24, 48, and 72 hours after surgery. Adiponectin was measured at baseline. Subjective feelings of well-being were measured immediately before surgery, and intra- and postoperative outcomes were documented. RESULTS: Postoperative insulin sensitivity did not differ significantly between the FAST and CHO groups whether measured by the short insulin tolerance test (rate of disappearance of blood glucose: 0.29%/min vs 0.38%/min; 99% confidence interval [CI] for difference, -0.17 to 0.32, P = 0.41) or HOMA (insulin resistance at values >1: 2.3 vs 3.3; 99% CI for difference, -0.8 to 2.8, P = 0.14). Circulating blood glucose levels after surgery in the CHO group, 6.2 mmol/L, tended to be lower than the FAST group, 6.9 mmol/L (99% CI for difference, -1.7 to 0.25, P = 0.05) and postoperative ß-cell function, measured by HOMA-ß (impaired ß-cell function at values <100%), tended to be higher in the CHO group, 87%, vs 47.5% in the FAST group (99% CI for difference, -9.4 to 88.4), but these differences were not significant. Adiponectin levels were not different between groups at baseline, and levels of free fatty acid, interleukin-6 and C-reactive protein were not affected by treatment. CONCLUSIONS: Preoperative carbohydrate loading did not improve postoperative insulin sensitivity. However, the observed postoperative blood glucose levels and ß-cell function as well as secondary outcomes warrant further study to reevaluate traditional fasting practices in surgical patients.

Effect of fructose on body weight in controlled feeding trials: a systematic review and meta-analysis.

BACKGROUND: The contribution of fructose consumption in Western diets to overweight and obesity in populations remains uncertain. PURPOSE: To review the effects of fructose on body weight in controlled feeding trials. DATA SOURCES: MEDLINE, EMBASE, CINAHL, and the Cochrane Library (through 18 November 2011). STUDY SELECTION: At least 3 reviewers identified controlled feeding trials lasting 7 or more days that compared the effect on body weight of free fructose and nonfructose carbohydrate in diets providing similar calories (isocaloric trials) or of diets supplemented with free fructose to provide excess energy and usual or control diets (hypercaloric trials). Trials evaluating high-fructose corn syrup (42% to 55% free fructose) were excluded. DATA EXTRACTION: The reviewers independently reviewed and extracted relevant data; disagreements were reconciled by consensus. The Heyland Methodological Quality Score was used to assess study quality. DATA SYNTHESIS: Thirty-one isocaloric trials (637 participants) and 10 hypercaloric trials (119 participants) were included; studies tended to be small (<15 participants), short (<12 weeks), and of low quality. Fructose had no overall effect on body weight in isocaloric trials (mean difference, -0.14 kg [95% CI, -0.37 to 0.10 kg] for fructose compared with nonfructose carbohydrate). High doses of fructose in hypercaloric trials (+104 to 250 g/d, +18% to 97% of total daily energy intake) lead to significant increases in weight (mean difference, 0.53 kg [CI, 0.26 to 0.79 kg] with fructose). LIMITATIONS: Most trials had methodological limitations and were of poor quality. The weight-increasing effect of fructose in hypercaloric trials may have been attributable to excess energy rather than fructose itself. CONCLUSION: Fructose does not seem to cause weight gain when it is substituted for other carbohydrates in diets providing similar calories. Free fructose at high doses that provided excess calories modestly increased body weight, an effect that may be due to the extra calories rather than the fructose. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research. (ClinicalTrials.gov registration number: NCT01363791).

The importance of molecular weight in determining the minimum dose of oat ß-glucan required to reduce the glycaemic response in healthy subjects without diabetes: a systematic review and meta-regression analysis.

To determine the minimum amount of oat ß-glucan (OBG) required to reduce glycaemic responses (MinDose), we conducted a systematic review and meta-regression analysis of acute, crossover, single-meal feeding trials that examined the effects of adding OBG or oat bran to a carbohydrate-containing test-meal versus a control test-meal containing an equivalent amount of available-carbohydrate (avCHO) from the same or similar source. Medline, Embase, and Cochrane Library were searched up to 18 August 2021. The primary outcome was glucose incremental-area-under-the-curve (iAUC). Secondary outcomes included insulin iAUC, and glucose and insulin incremental peak-rise (iPeak). Two independent reviewers extracted data. Results were expressed as ratio-of-means (RoM) with 95% confidence intervals (CIs). Linear associations were assessed by random effects meta-regression. MinDose was defined as the dose at which the upper 95% CI of the regression line cut the line of no effect (i.e., RoM = 1). Fifty-nine comparisons (n = 340) were included; 57 in healthy subjects without diabetes and two in subjects with diabetes; 24 high-MW (>1000 kg/mol), 22 medium-MW (300-1,000 kg/mol), and 13 low-MW (<300 kg/mol). In healthy subjects without diabetes the associations between OBG dose and glucose iAUC and iPeak were linear (non-linear p value >0.05). MinDoses for glucose iAUC for high-MW, medium-MW and low-MW OBG, respectively, were estimated to be 0.2 g, 2.2 g and 3.2 g per 30 g avCHO; MinDoses for glucose iPeak were less than those for iAUC. Insufficient data were available to assess MinDose for insulin, however, there was no evidence of a disproportionate increase in insulin. More high-quality trials are needed to establish MinDose in individuals with diabetes.

Minimal Effective Dose of Beans Required to Elicit a Significantly Lower Glycemic Response Than Commonly Consumed Starchy Foods: Predictions Based on In Vitro Digestion and Carbohydrate Analysis.

Beans elicit lower glycemic responses (GRs) than other starchy foods, but the minimum effective dose (MED) to reduce GR is unknown. We sought to determine the MED of beans compared to common starchy foods. Overnight-fasted healthy volunteers consumed »c (phase 1, n = 24) or ½c (phase 2, n = 18) of black, cranberry, great northern, kidney, navy and pinto beans and corn, rice, pasta and potato (controls), with blood glucose measured before and for 2 h after eating. GRs (incremental areas under the curves, iAUCs) after beans were consumed were compared to those of controls by ANOVA followed by Dunnett's test. To qualify for MED, beans had to elicit an effective reduction in GR, defined as a statistically significant reduction in iAUC of ≥20% (i.e., a relative glycemic response, RGR, ≤80). Outcomes from in vitro digestion were compared with in vivo RGR. Both doses of all six beans effectively reduced GR versus all four starchy controls, except for »c and ½c cranberry and pinto vs. corn, »c great northern and navy vs. corn and »c navy and pinto vs. potato. MED criteria were met for 18 comparisons of the »c servings, with four of the remaining six met by the ½c servings. The overall mean ± SEM RGR vs. controls was similar for the »c and ½c servings: 53 ± 4% and 56 ± 3%, respectively. By multiple regression analysis, RGR = 23.3 × RDS + 8.3 × SDS - 20.1 × RS + 39.5 × AS - 108.2 (rapidly digested starch, p < 0.001; slowly digested starch, p = 0.054; resistant starch, p = 0.18; available sugars, p = 0.005; model r = 0.98, p = 0.001). RGR correlated with in vitro glucose release (r = 0.92, p < 0.001). The MED of beans is » cup. For n = 30 comparisons (n = 24 beans vs. controls, n = 6 controls vs. each other), an effective reduction in GR was predicted from in vitro carbohydrate analysis with 86% sensitivity and 100% specificity.

Fructose-containing food sources and blood pressure: A systematic review and meta-analysis of controlled feeding trials.

Whether food source or energy mediates the effect of fructose-containing sugars on blood pressure (BP) is unclear. We conducted a systematic review and meta-analysis of the effect of different food sources of fructose-containing sugars at different levels of energy control on BP. We searched MEDLINE, Embase and the Cochrane Library through June 2021 for controlled trials ≥7-days. We prespecified 4 trial designs: substitution (energy matched substitution of sugars); addition (excess energy from sugars added); subtraction (excess energy from sugars subtracted); and ad libitum (energy from sugars freely replaced). Outcomes were systolic and diastolic BP. Independent reviewers extracted data. GRADE assessed the certainty of evidence. We included 93 reports (147 trial comparisons, N = 5,213) assessing 12 different food sources across 4 energy control levels in adults with and without hypertension or at risk for hypertension. Total fructose-containing sugars had no effect in substitution, subtraction, or ad libitum trials but decreased systolic and diastolic BP in addition trials (P<0.05). There was evidence of interaction/influence by food source: fruit and 100% fruit juice decreased and mixed sources (with sugar-sweetened beverages [SSBs]) increased BP in addition trials and the removal of SSBs (linear dose response gradient) and mixed sources (with SSBs) decreased BP in subtraction trials. The certainty of evidence was generally moderate. Food source and energy control appear to mediate the effect of fructose-containing sugars on BP. The evidence provides a good indication that fruit and 100% fruit juice at low doses (up to or less than the public health threshold of ~10% E) lead to small, but important reductions in BP, while the addition of excess energy of mixed sources (with SSBs) at high doses (up to 23%) leads to moderate increases and their removal or the removal of SSBs alone (up to ~20% E) leads to small, but important decreases in BP in adults with and without hypertension or at risk for hypertension. Trial registration: Clinicaltrials.gov: NCT02716870.

Barley cultivar, kernel composition, and processing affect the glycemic index.

Barley has a low glycemic index (GI), but it is unknown whether its GI is affected by variation in carbohydrate composition in different cultivars and by food processing and food form. To examine the effect of these factors on GI, 9 barley cultivars varying in amylose and ß-glucan content were studied in 3 experiments in separate groups of 10 healthy participants. In Expt. 1, 3 barley cultivars underwent 2 levels of processing: hull removal [whole-grain (WG)] and bran, germ, and crease removal [white pearled (WP)]. GI varied by cultivar (CDC Fibar vs. AC Parkhill, [mean ± SEM]: 26 ± 3 vs. 53 ± 4, respectively; P < 0.05) and pearling (WG vs. WP: 26 ± 4 vs. 35 ± 3, respectively; P < 0.05) with no cultivar × pearling interaction. In Expt. 2, the GI of 7 WG cultivars ranged from 21 ± 4 to 36 ± 8 (P = 0.09). In Expt. 3, WG and WP AC Parkhill and Celebrity cultivars were ground and made into wet pasta. The GI of AC Parkhill pasta (69 ± 3) was similar to that of Celebrity pasta (64 ± 4) but, unlike in Expt. 1, the GI of WP pasta (61 ± 3) was less than that of WG pasta (72 ± 4) (P < 0.05). Pooled data from Expts. 1 and 2 showed that GI was correlated with total fiber (r = -0.75, P = 0.002) but not with measures of starch characteristics. We conclude that the GI of barley is influenced by cultivar, processing, and food form but is not predicted by its content of amylose or other starch characteristics.

Glycemic index predicts individual glucose responses after self-selected breakfasts in free-living, abdominally obese adults.

The degree to which an individual's glycemic response to a meal is determined by the glycemic index (GI) and other components of the meal remains unclear, especially when meals are not consumed in a highly controlled research setting. To address this question, we analyzed data collected during the run-in period of a clinical trial. Free-living, nondiabetic adults (n = 57) aged 53.9 ± 9.8 y (mean ± SD) with a BMI of 33.9 ± 5.3 kg/m(2) and waist circumference of 109 ± 11 cm underwent a 75-g oral glucose tolerance test (OGTT) and, on a separate day, wore a continuous glucose-monitoring system (CGMS) for 24 h during which time they recorded all foods consumed. The protein, fat, and available carbohydrate (avCHO) content and GI of the breakfast meals were calculated from the food records and the incremental areas under the glycemic response curves (iAUC) for 2 h after breakfast (iAUC(breakfast)) were calculated from CGMS data. Values for iAUC(breakfast), avCHO, fat, fiber, and BMI were normalized by log-transformation. The ability of participant characteristics and breakfast composition to predict individual iAUC(breakfast) responses was determined using step-wise multiple linear regression. A total of 56% of the variation in iAUC(breakfast) was explained by GI (30%; P < 0.001), iAUC after the OGTT (11%; P < 0.001), avCHO (11%; P < 0.001), and waist circumference (3%; P = 0.049); the effects of fat, protein, dietary fiber, age, sex, and BMI were not significant. We concluded that, in free-living, abdominally obese adults, GI is a significant determinant of individual glycemic responses elicited by self-selected breakfast meals. In this study, GI was a more important determinant of glycemic response than carbohydrate intake.