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.

An Oat ß-Glucan Beverage Reduces LDL Cholesterol and Cardiovascular Disease Risk in Men and Women with Borderline High Cholesterol: A Double-Blind, Randomized, Controlled Clinical Trial.

BACKGROUND: High-molecular-weight (MW) oat ß-glucan (OBG), consumed at 3-4 g/d, in solid foods reduces LDL cholesterol by a median of ∼6.5%. OBJECTIVES: We evaluated the effect of a beverage providing 3 g/d high-MW OBG on reduction of LDL cholesterol (primary endpoint) when compared with placebo. METHODS: We performed a parallel-design, randomized clinical trial at a contract research organization; participants, caregivers, and outcome assessors were blinded to treatment allocation. Participants with LDL cholesterol between 3.0 and 5.0 mmol/L, inclusive [n = 538 screened, n = 260 ineligible, n = 23 lost, n = 48 withdrawn (product safety); n = 207 randomly assigned, n = 7 dropped out, n = 9 withdrawn (protocol violation); n = 191 analyzed; n = 72 (37.7%) male, mean ± SD age: 43.3 ± 14.3 y, BMI: 29.7 ± 5.2 kg/m2], were randomly assigned to consume, 3 times daily for 4 wk, 1 g OBG (n = 104, n = 96 analyzed) or rice powder (Control, n = 103, n = 95 analyzed) mixed into 250 mL water. Treatment effects were assessed as change from baseline and differences analyzed using a 2-sided t test via ANOVA with baseline characteristics as covariates. RESULTS: After 4 wk, change from baseline least-squares-mean LDL cholesterol on OBG (-0.195 mmol/L) was less than on Control (0.012 mmol/L) by mean: 0.207 mmol/L (95% CI: 0.318, 0.096 mmol/L; P = 0.0003); the following secondary endpoints were also reduced as follows: total cholesterol (TC) (0.226 mmol/L; 95% CI: 0.361, 0.091 mmol/L; P = 0.001), TC:HDL cholesterol ratio (0.147; 95% CI: 0.284, 0.010; P = 0.036), non-HDL cholesterol (0.194 mmol/L; 95% CI: 0.314, 0.073 mmol/L; P = 0.002), and Framingham cardiovascular disease (CVD) risk (0.474; 95% CI: 0.900, 0.049, P = 0.029). Changes in HDL cholesterol, triglycerides, glucose, and insulin did not differ between treatment groups (P > 0.05). Lipid treatment effects were not significantly modified by age, sex, BMI, or hypertension treatment. There were no major adverse events, but both treatments transiently increased gastrointestinal symptoms. CONCLUSIONS: Consuming a beverage containing 1 g high-MW OBG 3 times daily for 4 wk significantly reduced LDL cholesterol by ∼6% and CVD risk by ∼8% in healthy adults with LDL cholesterol between 3 and 5 mmol/L.This trial was registered at clinicaltrials.gov as NCT03911427.

Effect of viscous fiber supplementation on obesity indicators in individuals consuming calorie-restricted diets: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Dietary fiber has played a consistent role in weight management, with efficacy potentially attributed to increased viscous fiber consumption. PURPOSE: To summarize the effects of viscous fiber on body weight and other anthropometric parameters, along with a calorie-deficient diet, through a systematic review and meta-analysis. METHODS: MEDLINE, EMBASE, and the Cochrane library were searched through July 24, 2019 for randomized controlled trials that assessed the effect of viscous fiber supplementation as part of a restricted calorie diet for ≥ 4 weeks relative to comparator diets. Data were pooled using the generic inverse-variance method with random-effects models and expressed as mean differences with 95% confidence intervals. Inter-study heterogeneity was assessed using Cochran's Q and quantified with I2. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the overall certainty of evidence. RESULTS: Findings from 15 studies (n = 1347) showed viscous fiber supplementation significantly decreased body weight (- 0.81 kg [- 1.20, - 0.41]; p < 0.0001), BMI (- 0.25 kg/m2 [- 0.46, - 0.05]; p = 0.01), and body fat (- 1.39% [- 2.61, - 0.17]; p = 0.03), compared to control. No effect on waist circumference was found. The certainty of evidence was graded as "moderate" for body weight, BMI, and body fat based on downgrades for imprecision. Waist circumference was graded "low" for downgrades of inconsistency and imprecision. CONCLUSION: Viscous fiber within a calorie-restricted diet significantly improved body weight and other markers of adiposity in overweight adults and those with additional risk factors for cardiovascular disease. This trial is registered at www.clinicaltrials.gov as NCT03257449. REGISTRATION: ClinicalTrials.gov identifier: NCT03257449.

Co-administration of viscous fiber, Salba-chia and ginseng on glycemic management in type 2 diabetes: a double-blind randomized controlled trial.

PURPOSE: Viscous dietary fiber, functional seeds and ginseng roots have individually been proposed for the management of diabetes. We explored whether their co-administration would improve glycemic control in type 2 diabetes beyond conventional therapy. METHODS: In a randomized, double-blind, controlled trial conducted at two academic centers (Toronto, Canada and Zagreb, Croatia), individuals with type 2 diabetes were assigned to either an active intervention (10 g viscous fiber, 60 g white chia seeds, 1.5 g American and 0.75 g Korean red ginseng extracts), or energy and fiber-matched control (53 g oat bran, 25 g inulin, 25 g maltodextrose and 2.25 g wheat bran) intervention for 24 weeks, while on conventional standard of care. The prespecified primary endpoint was end difference at week 24 in HbA1c, following an intent-to-treat analysis adjusted for center and baseline. RESULTS: Between January 2016 and April 2018, 104 participants (60M:44F; mean ± SEM age 59 ± 0.8 years; BMI 29.0 ± 0.4 kg/m2; HbA1c 7.0 ± 0.6%) managed with antihyperglycemic agent(s) (n = 98) or lifestyle (n = 6), were randomized (n = 52 test; n = 52 control). At week 24, HbA1c levels were 0.27 ± 0.1% lower on test compared to control (p = 0.03). There was a tendency towards an interaction by baseline HbA1c (p = 0.07), in which a greater reduction was seen in participants with baseline HbA1c > 7% vs ≤ 7% (- 0.56 ± 0.2% vs 0.03 ± 0.2%). Diet and body weight remained unchanged. The interventions were well tolerated with no related adverse events and with high retention rate of 84%. CONCLUSIONS: Co-administration of selected dietary and herbal therapies was well-tolerated and may provide greater glycemic control as add-on therapy in type 2 diabetes. Registration: Clinicaltrials.gov NCT02553382 (registered on September 17, 2015).

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.

Efficacy and safety of American ginseng (Panax quinquefolius L.) extract on glycemic control and cardiovascular risk factors in individuals with type 2 diabetes: a double-blind, randomized, cross-over clinical trial.

PURPOSE: Despite the lack of evidence, a growing number of people are using herbal medicine to attenuate the burden of diabetes. There is an urgent need to investigate the clinical potential of herbs. Preliminary observations suggest that American ginseng (Panax quinquefolius [AG]) may reduce postprandial glycemia. Thus, we aimed to evaluate the efficacy and safety of AG as an add-on therapy in individuals with type 2 diabetes (T2DM) controlled by conventional treatment. METHODS: 24 individuals living with T2DM completed the study (F:M = 11:13; age = 64 ± 7 year; BMI = 27.8 ± 4.6 kg/m2; HbA1c = 7.1 ± 1.2%). Utilizing a double-blind, cross-over design, the participants were randomized to receive either 1 g/meal (3 g/day) of AG extract or placebo for 8 weeks while maintaining their original treatment. Following a ≥ 4-week washout period, the participants were crossed over to the opposite 8-week treatment arm. The primary objective was HbA1c, and secondary endpoints included fasting blood glucose and insulin, blood pressure, plasma lipids, serum nitrates/nitrites (NOx), and plasominogen-activating factor-1 (PAI-1). Safety parameters included liver and kidney function. RESULTS: Compared to placebo, AG significantly reduced HbA1c (- 0.29%; p = 0.041) and fasting blood glucose (- 0.71 mmol/L; p = 0.008). Furthermore, AG lowered systolic blood pressure (- 5.6 ± 2.7 mmHg; p < 0.001), increased NOx (+ 1.85 ± 2.13 µmol/L; p < 0.03), and produced a mean percent end-difference of - 12.3 ± 3.9% in LDL-C and - 13.9 ± 5.8% in LDL-C/HDL. The safety profiles were unaffected. CONCLUSIONS: AG extract added to conventional treatment provided an effective and safe adjunct in the management of T2DM. Larger studies using physiologically standardized ginseng preparations are warranted to substantiate the present findings and to demonstrate therapeutic effectiveness of AG. CLINICALTRIALS. GOV IDENTIFIER: NCT02923453.

The effects of gelled konjac glucomannan fibre on appetite and energy intake in healthy individuals: a randomised cross-over trial.

Konjac glucomannan (KGM) is a viscous dietary fibre that can form a solid, low-energy gel when hydrated and is commonly consumed in a noodle form (KGM-gel). Increased meal viscosity from gel-forming fibres have been associated with prolonged satiety, but no studies to date have evaluated this effect with KGM-gel. Thus, our objective was to evaluate subsequent food intake and satiety of KGM-gel noodles when replacing a high-carbohydrate preload, in a dose-response manner. Utilising a randomised, controlled, cross-over design, sixteen healthy individuals (twelve females/four males; age: 26·0 (sd 11·8) years; BMI: 23·1 (sd 3·2) kg/m2) received 325 ml volume-matched preloads of three KGM-gel noodle substitution levels: (i) all pasta with no KGM-gel (1849 kJ (442 kcal), control), half pasta and half KGM-gel (1084 kJ (259 kcal), 50-KGM) or no pasta and all KGM-gel (322 kJ (77 kcal), 100-KGM). Satiety was assessed over 90 min followed by an ad libitum dessert. Compared with control, cumulative energy intake was 47 % (-1761 kJ (-421 kcal)) and 23 % (-841 kJ (-201 kcal)) lower for 100-KGM and 50-KGM, respectively (both P<0·001), but no differences in subsequent energy intake was observed. Ratings of hunger were 31 % higher (P=0·03) for 100-KGM when compared with control, and were 19 % lower (P=0·04) for fullness and 28 % higher (P=0·04) for prospective consumption when comparing 100-KGM to 50-KGM. Palatability was similar across all treatments. Replacement of a high-carbohydrate preload with low-energy KGM-gel noodles did not promote additional food intake despite large differences in energy. The energy deficit incurred from partial KGM-gel substitution may have relevance in weight loss regimens, and should be further evaluated beyond the healthy population.

Co-administration of a konjac-based fibre blend and American ginseng (Panax quinquefolius L.) on glycaemic control and serum lipids in type 2 diabetes: a randomized controlled, cross-over clinical trial.

PURPOSE: Use of polypharmacy in the treatment of diabetes is the norm; nonetheless, optimal control is often not achieved. Konjac-glucomannan-based fibre blend (KGB) and American ginseng (AG) have individually been shown to improve glycaemia and CVD risk factors in type 2 diabetes. The aim of this study was to determine whether co-administration of KGB and AG could improve diabetes control beyond conventional treatment. METHOD: Thirty-nine participants with type 2 diabetes (6.5 > A1c < 8.4%) were enrolled between January 2002 and May 2003 at the Risk Factor Modification Centre at St Michaels Hospital in a randomized, placebo-controlled, crossover trial with each intervention lasting 12-weeks. Medications, diet and lifestyle were kept constant. Interventions consisted of 6 g of fibre from KGB together with 3 g of AG (KGB and AG) or wheat bran-based, fibre-matched control. Primary endpoint was the difference in HbA1c levels at week 12. RESULTS: Thirty participants (18M:12F; age: 64 ± 7 years; BMI: 28 ± 5 kg/m2; HbA1c: 7.0 ± 1.0%) completed the study, and consumed 5.5 and 4.9 g/day of fibre from KGB and wheat bran control, respectively, and 2.7 g/day of AG. At week 12, HbA1c levels were 0.31% lower on the KGB and AG compared to control (p = 0.011). Mean (±SEM) plasma lipids decreased on the KGB and AG vs control by 8.3 ± 3.1% in LDL-C (p = 0.002), 7.5 ± 2.4% in non-HDL-C (p = 0.013), 5.7 ± 1.9% in total-C (p = 0.012), 4.1 ± 2.1% in total-C:HDL-C ratio (p = 0.042), 9.0 ± 2.3% in ApoB (p = 0.0005) and 14.6 ± 4.2% in ApoB:ApoA1 ratio (p = 0.049). CONCLUSIONS: Co-administration of KGB and AG increases the effectiveness of conventional therapy through a moderate but clinically meaningful reduction in HbA1c and lipid concentrations over 12 weeks in patients with type 2 diabetes. CLINICAL TRIALS REGISTRATION: NCT02806349 ( https://clinicaltrials.gov/ ).

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.

The effect of oat ß-glucan on LDL-cholesterol, non-HDL-cholesterol and apoB for CVD risk reduction: a systematic review and meta-analysis of randomised-controlled trials.

Oats are a rich source of ß-glucan, a viscous, soluble fibre recognised for its cholesterol-lowering properties, and are associated with reduced risk of CVD. Our objective was to conduct a systematic review and meta-analysis of randomised-controlled trials (RCT) investigating the cholesterol-lowering potential of oat ß-glucan on LDL-cholesterol, non-HDL-cholesterol and apoB for the risk reduction of CVD. MEDLINE, Embase, CINAHL and Cochrane CENTRAL were searched. We included RCT of ≥3 weeks of follow-up, assessing the effect of diets enriched with oat ß-glucan compared with controlled diets on LDL-cholesterol, non-HDL-cholesterol or apoB. Two independent reviewers extracted data and assessed study quality and risk of bias. Data were pooled using the generic inverse-variance method with random effects models and expressed as mean differences with 95 % CI. Heterogeneity was assessed by the Cochran's Q statistic and quantified by the I 2-statistic. In total, fifty-eight trials (n 3974) were included. A median dose of 3·5 g/d of oat ß-glucan significantly lowered LDL-cholesterol (-0·19; 95 % CI -0·23, -0·14 mmol/l, P<0·00001), non-HDL-cholesterol (-0·20; 95 % CI -0·26, -0·15 mmol/l, P<0·00001) and apoB (-0·03; 95 % CI -0·05, -0·02 g/l, P<0·0001) compared with control interventions. There was evidence for considerable unexplained heterogeneity in the analysis of LDL-cholesterol (I 2=79 %) and non-HDL-cholesterol (I 2=99 %). Pooled analyses showed that oat ß-glucan has a lowering effect on LDL-cholesterol, non-HDL-cholesterol and apoB. Inclusion of oat-containing foods may be a strategy for achieving targets in CVD reduction.

Post-prandial glucose and insulin responses of hummus alone or combined with a carbohydrate food: a dose-response study.

OBJECTIVES: Pulses are low glycemic index (GI) foods and have been associated with reduced risk of heart disease, diabetes and some cancers. However the blood glucose and insulin responses of hummus, a food containing chickpea, have not been thoroughly tested. METHODS: Ten healthy subjects each consumed 11 breakfast study meals in randomized order over a period of 15 weeks. Hummus was consumed alone at three doses (2.7 g, 10.8 g and 25 g available carbohydrate [avCHO] portions) and with 50 g avCHO from white bread at three doses (2.7 g, 5.4 g and 10.8 g avCHO portions). The responses elicited by hummus alone were compared with 25 g avCHO portions of white bread, while those after hummus plus white bread were compared with 50 g avCHO from white bread. Plasma glucose and serum insulin responses were monitored over two hours and the GI and insulin index (II) calculated using standard methodology. RESULTS: The GI and II of hummus were 15 ± 3 and 52 ± 13, respectively, and were significantly lower than white bread (P < 0.05). The glucose and insulin incremental area under the curve (IAUC) for hummus alone were significantly lower than white bread except for insulin IAUC of hummus 25 g avCHO. The peak rise of blood glucose and insulin after hummus were significantly lower than after white bread. Glucose and insulin IAUC after adding hummus to bread did not differ significantly from white bread alone. However the blood glucose 45 min after adding 25 g avCHO from hummus to white bread was significantly lower while at 120 min it was significantly higher than after white bread alone. CONCLUSIONS: This study demonstrated that, similar to chickpeas, hummus has a very low GI and II. Postprandial glucose responses were 4 times less than that of white bread and did not compromise insulin levels.

Randomized clinical trial in healthy individuals on the effect of viscous fiber blend on glucose tolerance when incorporated in capsules or into the carbohydrate or fat component of the meal.

BACKGROUND/OBJECTIVE: Addition of viscous fiber to foods has been shown to significantly reduce postprandial glucose excursions. However, palatability issues and the variability in effectiveness due to different methods of administration in food limits it use. This study explores the effectiveness of a viscous fiber blend (VFB) in lowering postprandial glycemia using different methods of incorporation. METHODS: Two acute, randomized, controlled studies were undertaken: Study 1: Twelve healthy individuals (mean ± SD, age: 36 ± 13 years, body mass index [BMI]: 27 ± 4 kg/m(2)) consumed 8 different breakfasts. All meals consisted of 50 g of available carbohydrate from white bread (WB) and 10 g margarine. Zero, 1, 2, or 4 g of the VFB was baked into WB or mixed with the margarine. Study 2: Thirteen healthy individuals (mean ± SD, age: 39 ± 17 years, BMI: 25 ± 5 kg/m(2)) consumed 6 test meals, consisting of 50 g of available carbohydrate from WB. Six capsules containing either cornstarch or VFB were taken at 4 different time points during the glucose tolerance test. After obtaining a fasting finger-prick blood sample, volunteers consumed the test meal over a 10-minute period. Additional blood samples were taken at 15, 30, 45, 60, 90, and 120 minutes from the start of the meal. For study 2, an additional fasting sample was obtained at -30 minutes. RESULTS: Study 1: Irrespective of VFB dose, glucose levels were lower at 30 and 45 minutes when VFB was mixed into the margarine compared to the control (p < 0.05). Incremental areas under the curve were significantly lower compared to control when 4 g of VFB was mixed into the margarine. Study 2: There was no effect of the VFB on postprandial glucose levels when administered in capsules. CONCLUSION: Incorporation of VFB into margarine was more effective in lowering postprandial glycemia than when the VFB was baked into bread and no effect when given in capsules.

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.

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).

Gastrointestinal Tolerability and Acute Glycemic Response of Oligosaccharides and Polysaccharides from Cellulose and Xylan in Healthy Adults: Two Double-Blinded, Randomized, Controlled, Cross-over Trials.

OBJECTIVE: The aim of this study was to investigate the gastrointestinal tolerability, glycemic and insulinemic responses of Plant Fiber Extract (PFE), a mixture comprising of oligosaccharides and polysaccharides derived from cellulose and xylan. METHODS: Two double-blind, randomized, controlled, cross-over trials were conducted in healthy adults. In the first trial, participants (n = 29) consumed either 25, 35 or 45 g per day of PFE or resistant maltodextrin (Control) for 14 days. The occurrence and severity of gastrointestinal (GI) symptoms, stool parameters, and safety outcomes were evaluated with a combination of surveys and blood analysis respectively. In the second trial (n = 20), the post-prandial glycemic and insulinemic responses after the ingestion of 20 g of PFE diluted in water or incorporated into chocolate chips was measured and then compared to that of glucose and regular chocolate, respectively. RESULTS: For all timepoints (0, 7 and 14 days), within any given dose group, there was no statistically significant difference in the GI symptoms score between PFE and Control. Further, for each test product (PFE or Control), no difference was observed in the same dose group from days 0 and 14. Stool consistency score and number of participants experiencing loose or watery stools was similar between products. No serious adverse events were reported and neither PFE nor Control significantly altered blood or urine safety parameters. The glycemic and insulinemic responses after PFE ingestion in comparison to glucose were 12% and 8% respectively. The glycemic and insulinemic responses after consuming chocolate containing PFE were 20% of that of regular chocolate. CONCLUSION: PFE was well-tolerated by healthy volunteers in doses up to 45 g/day and it elicited comparatively low glycemic and insulinemic responses when consumed alone or when incorporated into a food product.

The effects of fructose intake on serum uric acid vary among controlled dietary trials.

Hyperuricemia is linked to gout and features of metabolic syndrome. There is concern that dietary fructose may increase uric acid concentrations. To assess the effects of fructose on serum uric acid concentrations in people with and without diabetes, we conducted a systematic review and meta-analysis of controlled feeding trials. We searched MEDLINE, EMBASE, and the Cochrane Library for relevant trials (through August 19, 2011). Analyses included all controlled feeding trials ≥ 7 d investigating the effect of fructose feeding on uric acid under isocaloric conditions, where fructose was isocalorically exchanged with other carbohydrate, or hypercaloric conditions, and where a control diet was supplemented with excess energy from fructose. Data were aggregated by the generic inverse variance method using random effects models and expressed as mean difference (MD) with 95% CI. Heterogeneity was assessed by the Q statistic and quantified by I(2). A total of 21 trials in 425 participants met the eligibility criteria. Isocaloric exchange of fructose for other carbohydrate did not affect serum uric acid in diabetic and nondiabetic participants [MD = 0.56 µmol/L (95% CI: -6.62, 7.74)], with no evidence of inter-study heterogeneity. Hypercaloric supplementation of control diets with fructose (+35% excess energy) at extreme doses (213-219 g/d) significantly increased serum uric acid compared with the control diets alone in nondiabetic participants [MD = 31.0 mmol/L (95% CI: 15.4, 46.5)] with no evidence of heterogeneity. Confounding from excess energy cannot be ruled out in the hypercaloric trials. These analyses do not support a uric acid-increasing effect of isocaloric fructose intake in nondiabetic and diabetic participants. Hypercaloric fructose intake may, however, increase uric acid concentrations. The effect of the interaction of energy and fructose remains unclear. Larger, well-designed trials of fructose feeding at "real world" doses are needed.

'Catalytic' doses of fructose may benefit glycaemic control without harming cardiometabolic risk factors: a small meta-analysis of randomised controlled feeding trials.

Contrary to concerns that fructose may have adverse metabolic effects, there is evidence that small, 'catalytic' doses ( ≤ 10 g/meal) of fructose decrease the glycaemic response to high-glycaemic index meals in human subjects. To assess the longer-term effects of 'catalytic' doses of fructose, we undertook a meta-analysis of controlled feeding trials. We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library. Analyses included all controlled feeding trials ≥ 7 d featuring 'catalytic' fructose doses ( ≤ 36 g/d) in isoenergetic exchange for other carbohydrates. Data were pooled by the generic inverse variance method using random-effects models and expressed as mean differences (MD) with 95 % CI. Heterogeneity was assessed by the Q statistic and quantified by I 2. The Heyland Methodological Quality Score assessed study quality. A total of six feeding trials (n 118) met the eligibility criteria. 'Catalytic' doses of fructose significantly reduced HbA1c (MD - 0·40, 95 % CI - 0·72, - 0·08) and fasting glucose (MD - 0·25, 95 % CI - 0·44, - 0·07). This benefit was seen in the absence of adverse effects on fasting insulin, body weight, TAG or uric acid. Subgroup and sensitivity analyses showed evidence of effect modification under certain conditions. The small number of trials and their relatively short duration limit the strength of the conclusions. In conclusion, this small meta-analysis shows that 'catalytic' fructose doses ( ≤ 36 g/d) may improve glycaemic control without adverse effects on body weight, TAG, insulin and uric acid. There is a need for larger, longer ( ≥ 6 months) trials using 'catalytic' fructose to confirm these results.

Decreasing the RAG:SAG ratio of granola cereal predictably reduces postprandial glucose and insulin responses: a report of four randomised trials in healthy adults.

Dietary starch contains rapidly (RAG) and slowly available glucose (SAG). To establish the relationships between the RAG:SAG ratio and postprandial glucose, insulin and hunger, we measured postprandial responses elicited by test meals varying in the RAG:SAG ratio in n 160 healthy adults, each of whom participated in one of four randomised cross-over studies (n 40 each): a pilot trial comparing six chews (RAG:SAG ratio 2·4-42·7) and three studies comparing a test granola (TG1-3, RAG:SAG ratio 4·5-5·2) with a control granola (CG1-3, RAG:SAG ratio 54·8-69·3). Within studies, test meals were matched for fat, protein and available carbohydrate. Blood glucose, serum insulin and subjective hunger were measured for 3 h. Data were subjected to repeated-measures analysis of variance (ANOVA). The relationships between the RAG:SAG ratio and postprandial end points were determined by regression analysis. In the pilot trial, 0-2 h glucose incremental areas under the curve (iAUC0-2; primary end point) varied across the six chews (P = 0·014) with each 50 % reduction in the RAG:SAG ratio reducing relative glucose response by 4·0 %. TGs1-3 elicited significantly lower glucose iAUC0-2 than CGs1-3 by 17, 18 and 17 %, respectively (similar to the 15 % reduction predicted by the pilot trial). The combined means ± sem (n 120) for TC and CG were glucose iAUC0-2, 98 ± 4 v. 118 ± 4 mmol × min/l (P < 0·001), and insulin iAUC0-2, 153 ± 9 v. 184 ± 11 nmol × h/l (P < 0·001), respectively. Neither postprandial hunger nor glucose or hunger increments 2 h after eating differed significantly between TG and CG. We concluded that TGs with RAG:SAG ratios <5·5 predictably reduced glycaemic and insulinaemic responses compared with CGs with RAG:SAG ratios >54. However, compared with CG, TG did not reduce postprandial hunger or delay the return of glucose or hunger to baseline.

Viscosity rather than quantity of dietary fibre predicts cholesterol-lowering effect in healthy individuals.

The well-documented lipid-lowering effects of fibre may be related to its viscosity, a phenomenon that has been understudied, especially when fibre is given against the background of a typical North American (NA) diet. In this three-arm experiment, we compared the lipid-lowering effect of low-viscosity wheat bran (WB), medium-viscosity psyllium (PSY) and a high-viscosity viscous fibre blend (VFB), as part of a fibre intervention aimed at increasing fibre intake to recommended levels within the context of a NA diet in apparently healthy individuals. Using a randomised cross-over design, twenty-three participants (twelve males and eleven females; age 35 (SD 12) years; LDL-cholesterol (C) 2.9 (SEM 0.6) mmol/l) consuming a typical NA diet received a standard, fibre-enriched cereal, where approximately one-third of the fibre was either a low-viscosity (570 centipoise (cP)) WB, medium-viscosity (14,300 cP) PSY or a high-viscosity (136,300 cP) novel VFB, for 3 weeks separated by washout periods of ≥ 2 weeks. There were no differences among the treatments in the amount of food consumed, total dietary fibre intake, reported physical activity and body weight. Final intake of the WB, PSY and VFB was 10.8, 9.0 and 5.1 g, respectively. Reduction in LDL-C was greater with the VFB compared with the medium-viscosity PSY (-12.6 (SEM 3.5) %, P = 0.002) and low-viscosity WB (-14.6 (SEM 4.2) %, P = 0.003). The magnitude of LDL-C reduction showed a positive association with fibre apparent viscosity (r - 0.41, P = 0.001). Despite the smaller quantity consumed, the high-viscosity fibre lowered LDL-C to a greater extent than lower-viscosity fibres. These data support the inclusion of high-viscosity fibre in the diet to reduce plasma lipids among apparently healthy individuals consuming a typical NA diet.

Neither low salivary amylase activity, cooling cooked white rice, nor single nucleotide polymorphisms in starch-digesting enzymes reduce glycemic index or starch digestibility: a randomized, crossover trial in healthy adults.

BACKGROUND: It was suggested that low salivary-amylase activity (SAA) and cooling or stir-frying cooked starch decreases its digestibility and glycemic index. OBJECTIVE: We determined the effects of SAA, cooling, and single-nucleotide polymorphisms (SNPs) in the salivary amylase (AMY1), pancreatic amylase (AMY2A, AMY2B), maltase-glucoamylase (MGAM), and sucrase-isomaltase (SI) genes on starch digestibility and glycemic index of cooked polished rice. METHODS: Healthy subjects [pilot, n = 12; main, n = 20 with low-SAA (<50 U/mL), and n = 20 with high-SAA (>105 U/mL)] consumed test meals containing 25 g (pilot) or 50 g (main) available carbohydrate at a contract research organization using open-label (pilot) or assessor-blinded (main), randomized, crossover, Latin-square designs (trial registration: NCT03667963). Pilot-trial test meals were dextrose, freshly cooked polished rice, cooked rice cooled overnight, stir-fried hot rice, or stir-fried cold rice. Main-trial test meals were dextrose, dextrose plus 10 g lactulose, plain hot rice, or plain cold rice. In both trials, blood glucose was measured fasting and at intervals over 2 h. In the main trial, breath hydrogen was measured fasting and hourly for 6 h to estimate in vivo starch digestibility. Data were analyzed by repeated-measures ANOVA for the main effects of temperature and stir-frying (pilot trial) or the main effects of SAA and temperature (main trial) and their interactions. Effects of 24 single nucleotide polymorphisms (SNPs) were assessed separately. Means were considered to be equivalent if the 95% CI of the differences were within ±20% of the comparator mean for glucose response/glycemic index or ±7% for digestibility. RESULTS: Pilot: neither temperature nor stir-frying significantly affected glucose incremental AUC (primary endpoint, n = 12). Main: mean ± SEM glycemic index (primary endpoint, n = 40) was equivalent for low-SAA compared with high-SAA (73 ± 3 vs. 75 ± 4) and cold rice compared with hot rice (75 ± 3 vs. 70 ± 3). Estimated starch digestibility (n = 39) was equivalent for low-SAA compared with high-SAA (95% ± 1% vs. 92% ± 1%) and hot rice compared with cold rice (94% ± 1% vs. 93% ± 1%). No meaningful associations were observed between genotypes and starch digestibility or glycemic index for any of the SNPs. CONCLUSIONS: The results do not support the hypotheses that low-SAA, cooling, and common genetic variations in starch-digesting enzymes affect the glycemic index or in vivo carbohydrate digestibility of cooked polished rice. This trial was registered at clinicaltrials.gov as NCT03667963.