A randomized, open-label, parallel pilot study investigating metabolic product kinetics of the novel ketone ester, bis-hexanoyl (R)-1,3-butanediol, over one week of ingestion in healthy adults.

Introduction: Bis-hexanoyl (R)-1,3-butanediol (BH-BD) is a novel ketone ester that, when consumed, is hydrolyzed into hexanoic acid (HEX) and (R)-1,3-butanediol (BDO) which are subsequently metabolized into beta-hydroxybutyrate (BHB). Methods: We undertook a randomized, parallel, open-label study in healthy adults (n = 33) to elucidate blood BHB, HEX and BDO concentrations for 8 h following consumption of three different serving sizes (SS) of BH-BD (12.5, 25 and 50 g/day) before (Day 0) and after 7 days of daily BH-BD consumption (Day 7). Results: Maximal concentration and area under the curve of all metabolites increased proportionally to SS and were greatest for BHB followed by BDO then HEX on both Day 0 and 7. Metabolite half-life tended to decrease with increasing SS for BHB and HEX. Time to peak concentration increased with increasing SS for BHB and BDO on both days. In vitro incubation of BH-BD in human plasma demonstrated BH-BD undergoes rapid spontaneous hydrolysis. Conclusion: These results demonstrate that orally ingested BH-BD is hydrolyzed into products that appear in the plasma and undergo conversion to BHB in a SS dependent manner, and that metabolism of BH-BD neither becomes saturated at serving sizes up to 50 g nor displays consistent adaptation after 7 days of daily consumption.

The probiotic Bacillus subtilis BS50 decreases gastrointestinal symptoms in healthy adults: a randomized, double-blind, placebo-controlled trial

Abstract: Durable spore-forming probiotics are increasingly formulated into foods, beverages, and dietary supplements. To help meet this demand, the safety and efficacy of daily supplementation of Bacillus subtilis BS50 for 6 weeks was investigated in a randomized, double-blind, placebo-controlled, parallel clinical trial of 76 healthy adults. Before and during supplementation, gastrointestinal symptoms were recorded daily using a multi-symptom questionnaire. Clinical chemistry, hematology, plasma lipids, and intestinal permeability and inflammation markers were measured at baseline and end of study. Compared to placebo, 2 × 109 colony-forming units (CFU) BS50 per day increased the proportion of participants showing improvement from baseline to week 6 in the composite score for bloating, burping, and flatulence (47.4% vs. 22.2%), whereby the odds of detecting an improvement were higher with BS50 (OR [95% CI]: 3.2 [1.1, 8.7], p = .024). Analyses of individual gastrointestinal symptoms indicate that BS50 increased the proportion of participants showing an improvement at week 6 compared to placebo for burping (44.7% vs. 22.2%, p = .041) and bloating (31.6% vs. 13.9%, p = .071), without affecting other symptoms. There were no clinically meaningful changes in clinical chemistry, hematology, plasma lipids and intestinal permeability and other inflammation markers. In conclusion, the results suggest that dietary supplementation of 2 × 109 CFU Bacillus subtilis BS50 per day is a well-tolerated and safe strategy to alleviate gas-related gastrointestinal symptoms in healthy adults. ABBREVIATIONS: AE adverse event; BHD bowel habits diary; BMI body mass index; BSS Bristol Stool Scale; CFU colony-forming unit; CRP C-reactive protein; FGID functional gastrointestinal disorder; GI gastrointestinal; GITQ Gastrointestinal Tolerance Questionnaire; GLP-1 glucagon-like peptide 1; GSRS Gastrointestinal Symptom Rating Scale; HDL-C high-density lipoprotein-cholesterol; IBS irritable bowel syndrome; IL-10 interleukin-10; ITT intent-to-treat; LBP lipopolysaccharide binding protein; LDL-C low-density lipoprotein-cholesterol; PP per protocol; PYY peptide YY; TG triglyceride; total-C total cholesterol.

Beverage Containing Dispersible Yeast ß-Glucan Decreases Cold/Flu Symptomatic Days After Intense Exercise: A Randomized Controlled Trial.

In this double-blind, randomized, placebo-controlled parallel study, we examined the effect of dairy-based beverages (250 mL/day) containing 250 mg of dispersible baker's yeast ß-glucan (Wellmune) compared to a macronutrient- and calorie-matched control on upper respiratory tract infection (URTI) in marathon runners. Healthy adults running in the 2017 Austin Marathon consumed either ß-glucan (N = 132) or control (N = 225) for the 45 days prior to, day of, and 45 days after the marathon (91 days total). Participants completed a daily online survey assessing compliance, training status, and URTI symptoms. URTI occurrence and severity were evaluated using the Jackson Index and confirmed by the study physician. No significant differences in average duration and number of URTI episodes were found between ß-glucan and control. However, those who completed the study per protocol on the ß-glucan beverage reported significantly fewer URTI symptomatic days (3.43 ± 6.44 days, max 27 days) compared to those on control beverage (3.84 ± 6.84 days, max 49 days). Total URTI severity was significantly lower for ß-glucan (4.52 ± 1.61) compared to control (5.60 ± 2.23). Specifically, lower (p < .05) severity ratings for nasal discharge and sore throat were reported for ß-glucan compared to control. Average missed postmarathon workout days due to URTI were significantly less for ß-glucan (0.09 ± 0.38 days, max 2 days) compared to control (0.36 ± 1.40 days, max 10 days). Overall, consumption of dairy-based beverages containing dispersible yeast ß-glucan decreased URTI symptomatic days, severity of specific URTI symptoms, and missed postmarathon workout days due to URTI, without affecting duration and number of URTI episodes.

Soluble and Insoluble Yeast ß-Glucan Differentially Affect Upper Respiratory Tract Infection in Marathon Runners: A Double-Blind, Randomized Placebo-Controlled Trial.

In a previous study, consumption of a dairy beverage incorporating insoluble ß-glucan decreased upper respiratory tract infection (URTI) symptomatic days and severity in marathon runners. In this report, we extended our previous findings by presenting data on a dairy beverage containing soluble ß-glucan and URTI in marathon runners. Healthy adults running in the 2017 Austin Marathon consumed dairy beverages (250 mL/day) containing 250 mg of insoluble (n = 69) or soluble (n = 76) baker's yeast ß-glucan (Wellmune®) or placebo (n = 133) for the 45 days before, day of, and 45 days after the marathon (91 days total). Participants completed a daily online survey assessing compliance and URTI symptoms, which were evaluated using the Jackson Index and confirmed by the study physician. Total severity of URTI was significantly lower in the insoluble yeast ß-glucan group compared to the placebo group, but was not different between the soluble yeast ß-glucan group and placebo group. Severity ratings for nasal discharge were significantly lower in both the insoluble and soluble yeast ß-glucan groups compared to the placebo group. Additionally, severity rating for sore throat was lower in the insoluble, but not the soluble yeast ß-glucan group compared to the placebo group. The insoluble yeast ß-glucan group, but not the soluble yeast ß-glucan group also reported fewer URTI symptomatic days compared to the placebo group. The results suggest that soluble and insoluble yeast ß-glucan, incorporated into a food matrix, differentially affected exercise-induced URTI in marathon runners.

A Commercially Available Portion-Controlled Diet Program Is More Effective for Weight Loss than a Self-Directed Diet: Results from a Randomized Clinical Trial.

OBJECTIVE: To examine changes in weight and related outcomes in response to a commercial weight loss program compared to a self-directed diet in adults with overweight or obesity. DESIGN: Participants were randomly assigned [stratified by body mass index (BMI) and age] to a commercial weight loss program (n = 38) or to a self-directed Dietary Approaches to Stop Hypertension (DASH) diet (n = 40) for a 16-week period. Daily energy intake goals were 1,500 kcal/d for men and 1,200 kcal/d for women, except for the first week of the commercial program (1,000 kcal/d). This study was registered at http://ClinicalTrials.gov (NCT03017443). PARTICIPANTS: Primarily Caucasian (71%) women (n = 61) and men (n = 17) from the greater metropolitan area of the city of Chicago, IL, USA. with a mean baseline BMI of 34.4 kg/m2, body weight of 95.7 kg, and age of 50.4 years. RESULTS: Data = mean (95% CI). At week 16, the commercial program group lost significantly more body weight [-5.9 (-7.5, -4.3) kg vs. -1.8 (-2.9, -0.8) kg; or -6.4 vs. -1.8% of initial body weight, respectively], fat mass [-4.4 (-5.7, -3.1) kg vs. -1.2 (-2.1, -0.4) kg] and total body circumference (chest + waist + hip + upper arm + thigh) [-16.9 (-21.5, -12.3) cm vs. -5.8 (-9.0, -2.6) cm] (p < 0.01 for all). Additionally, more participants in the commercial program group lost a clinically meaningful amount of weight, defined as ≥5% of initial body weight, at week 16 (58% vs. 13%, p < 0.001). CONCLUSION: The commercial program resulted in greater weight loss and improvements in body composition/anthropometric parameters compared to a self-directed DASH diet over a 16-week period. Some important limitations were that no objective measurements of dietary intake or physical activity were collected to potentially ascertain the independent or combined effects of these components on weight loss (or lack thereof). Additionally, future research is warranted in order to understand the effects of this program, and similar programs, on longer term changes in body weight, in particular weight loss maintenance, as weight regain is common following the cessation of a structured weight loss intervention.

Cashew consumption reduces total and LDL cholesterol: a randomized, crossover, controlled-feeding trial.

Background: Cashews are the third most-consumed tree nut in the United States and are abundant with monounsaturated fatty acids and polyunsaturated fatty acids, which are associated with reduced cardiovascular disease risk. Although a qualified Food and Drug Administration health claim exists for nuts and heart health, cashews have been exempt from its use because cashews exceed the disqualifying amount of saturated fatty acids. Approximately one-third of the saturated fat in cashews is stearic acid, which is relatively neutral on blood lipids, thereby suggesting that cashews could have effects that are similar to those of other nuts. However, clinical data on cashews and blood lipids have been limited.Objective: We investigated the effect of reasonable intakes of cashews on serum lipids in adults with or at risk of high LDL cholesterol.Design: In a randomized, crossover, isocaloric, controlled-feeding study, 51 men and women (aged 21-73 y) with a median LDL-cholesterol concentration of 159 mg/dL (95% CI: 146, 165 mg/dL) at screening consumed typical American diets with cashews (28-64 g/d; 50% of kilocalories from carbohydrate, 18% of kilocalories from protein, and 32% of kilocalories from total fat) or potato chips (control; 54% of kilocalories from carbohydrate, 18% of kilocalories from protein, and 29% of kilocalories from total fat) for 28 d with a ≥2-wk washout period.Results: Consumption of the cashew diet resulted in a significantly greater median change from baseline (compared with the control, all P < 0.05) in total cholesterol [-3.9% (95% CI: -9.3%, 1.7%) compared with 0.8% (95% CI: -1.5%, 4.5%), respectively], LDL cholesterol [-4.8% (95% CI: -12.6%, 3.1%) compared with 1.2% (95% CI: -2.3%, 7.8%), respectively], non-HDL cholesterol [-5.3% (95% CI: -8.6%, 2.1%) compared with 1.7% (95% CI: -0.9%, 5.6%), respectively], and the total-cholesterol:HDL-cholesterol ratio [-0.0% (95% CI: -4.3%, 4.8%) compared with 3.4% (95% CI: 0.6%, 5.2%), respectively]. There were no significant differences between diets for HDL cholesterol and triglyceride.Conclusions: In comparison with a control diet, the incorporation of cashews into typical American diets decreases total cholesterol and LDL cholesterol. Results from this study provide support that the daily consumption of cashews, when substituted for a high-carbohydrate snack, may be a simple dietary strategy to help manage total cholesterol and LDL cholesterol. This study was registered at clinicaltrials.gov as NCT02769741.

Sugar-sweetened product consumption alters glucose homeostasis compared with dairy product consumption in men and women at risk of type 2 diabetes mellitus.

BACKGROUND: Dietary patterns characterized by high intakes of fruits and vegetables, whole grains, low-fat dairy products, and low glycemic load have been associated with lower type 2 diabetes mellitus (T2DM) risk. In contrast, dietary patterns that include high intakes of refined grains, processed meats, and high amounts of added sugars have been associated with increased T2DM risk. OBJECTIVE: This randomized, 2-period crossover trial compared the effects of dairy and sugar-sweetened product (SSP) consumption on insulin sensitivity and pancreatic ß-cell function in men and women at risk of the development of T2DM who habitually consume sugar-sweetened beverages. METHODS: In a randomized, controlled crossover trial, participants consumed dairy products (474 mL/d 2% milk and 170 g/d low-fat yogurt) and SSPs (710 mL/d nondiet soda and 108 g/d nondairy pudding), each for 6 wk, with a 2-wk washout between treatments. A liquid meal tolerance test (LMTT) was administered at baseline and the end of each period. RESULTS: Participants were 50% female with a mean age and body mass index of 53.8 y and 32.2 kg/m(2), respectively. Changes from baseline were significantly different between dairy product and SSP conditions for median homeostasis model assessment 2-insulin sensitivity (HOMA2-%S) (1.3 vs. -21.3%, respectively, P = 0.009; baseline = 118%), mean LMTT disposition index (-0.03 vs. -0.36, respectively, P = 0.011; baseline = 2.59), mean HDL cholesterol (0.8 vs. -4.2%, respectively, P = 0.015; baseline = 44.3 mg/dL), and mean serum 25-hydroxyvitamin D [25(OH)D] (11.7 vs. -3.3, respectively, P = 0.022; baseline = 24.5 µg/L). Changes from baseline in LMTT Matsuda insulin sensitivity index (-0.10 vs. -0.49, respectively; baseline = 4.16) and mean HOMA2-ß-cell function (-2.0 vs. 5.3%, respectively; baseline = 72.6%) did not differ significantly between treatments. CONCLUSION: These results suggest that SSP consumption is associated with less favorable values for HOMA2-%S, LMTT disposition index, HDL cholesterol, and serum 25(OH)D in men and women at risk of T2DM vs. baseline values and values during dairy product consumption. This trial was registered at clinicaltrials.gov as NCT01936935.

Corn oil improves the plasma lipoprotein lipid profile compared with extra-virgin olive oil consumption in men and women with elevated cholesterol: results from a randomized controlled feeding trial.

BACKGROUND: Restricted intakes of saturated and trans-fatty acids is emphasized in heart-healthy diets, and replacement with poly- and monounsaturated fatty acids is encouraged. OBJECTIVE: To compare the effects of polyunsaturated fatty acid-rich corn oil (CO) and monounsaturated fatty acid-rich extra-virgin olive oil (EVOO) on plasma lipids in men and women (N = 54) with fasting low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL and <200 mg/dL and triglycerides (TG) ≤350 mg/dL. METHODS: In a double-blind, randomized, crossover design (21-day treatments, 21-day washout between), 4 tablespoons/day CO or EVOO were provided in 3 servings study product/day (muffin, roll, yogurt) as part of a weight-maintenance diet (∼35% fat, <10% saturated fat, <300 mg cholesterol). Subjects ate breakfast at the clinic every weekday throughout the study. Lunches, dinners, and snacks (and breakfasts on weekends) were provided for consumption away from the clinic. RESULTS: Baseline mean (standard error) lipids in mg/dL were: LDL-C 153.3 (3.5), total cholesterol (total-C) 225.7 (3.9), non-high-density lipoprotein (non-HDL)-C 178.3 (3.7), HDL-C 47.4 (1.7), total-C/HDL-C 5.0 (0.2), and TG 124.8 (7.2). CO resulted in significantly larger least-squares mean % changes (all P < .001 vs EVOO) from baseline in LDL-C -10.9 vs -3.5, total-C -8.2 vs -1.8, non-HDL-C -9.3 vs -1.6, and total-C/HDL-C -4.4 vs 0.5. TG rose a smaller amount with CO, 3.5 vs 13.0% with EVOO (P = .007). HDL-C responses were not significantly different between conditions (-3.4 vs -1.7%). CONCLUSION: Consumption of CO in a weight-maintenance, low saturated fat and cholesterol diet resulted in more favorable changes in LDL-C and other atherogenic lipids vs EVOO.

Effects of prescription omega-3-acid ethyl esters on fasting lipid profile in subjects with primary hypercholesterolemia.

This double-blind, randomized crossover study investigated the effects of 6 weeks of treatment with prescription omega-3-acid ethyl esters (POM3, 4 g/day) versus placebo (soy oil) on low-density lipoprotein cholesterol (LDL-C) and other aspects of the fasting lipid profile in 31 men and women with primary, isolated hypercholesterolemia (LDL-C 130-220 mg/dL and triglycerides less than 150 mg/dL while free of lipid-altering therapies). Mean ± standard error of the mean baseline concentrations of total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), very-low-density lipoprotein cholesterol, and triglycerides were 229 ± 3, 146 ± 3, 60 ± 2, 23 ± 2, and 113 ± 8 mg/dL, respectively. POM3 produced a modest increase from baseline in LDL-C (3.4%) versus the placebo response (-0.7%, P = 0.010). Significant changes (P < 0.05) for POM3 (placebo-corrected) were observed for very-low-density lipoprotein cholesterol (-18.8%), triglycerides (-18.7%), and HDL-C (3.3%). Nuclear magnetic resonance-determined very-low-density lipoprotein particle concentration and size and HDL particle concentration decreased significantly more with POM3 versus placebo, whereas LDL and HDL particle sizes increased significantly more with POM3 versus placebo. Total cholesterol, non-HDL-C, apolipoproteins A1 and B, and LDL particle concentration responses did not differ between treatments. These results did not confirm the hypothesis that POM3 treatment would lower LDL-C in primary, isolated hypercholesterolemia. Effects on other variables were consistent with prior results in mixed dyslipidemia.

Whole-grain ready-to-eat oat cereal, as part of a dietary program for weight loss, reduces low-density lipoprotein cholesterol in adults with overweight and obesity more than a dietary program including low-fiber control foods.

OBJECTIVE: Weight loss and consumption of viscous fibers both lower low-density lipoprotein (LDL) cholesterol levels. We evaluated whether or not a whole-grain, ready-to-eat (RTE) oat cereal containing viscous fiber, as part of a dietary program for weight loss, lowers LDL cholesterol levels and improves other cardiovascular disease risk markers more than a dietary program alone. DESIGN: Randomized, parallel-arm, controlled trial. SUBJECTS/SETTING: Free-living, overweight and obese adults (N=204, body mass index 25 to 45) with baseline LDL cholesterol levels 130 to 200 mg/dL (3.4 to 5.2 mmol/L) were randomized; 144 were included in the main analysis of participants who completed the trial without significant protocol violations. INTERVENTION: Two portions per day of whole-grain RTE oat cereal (3 g/day oat b-glucan) or energy-matched low-fiber foods (control), as part of a reduced energy ( approximately 500 kcal/day deficit) dietary program that encouraged limiting consumption of foods high in energy and fat, portion control, and regular physical activity. MAIN OUTCOME MEASURES: Fasting lipoprotein levels, waist circumference, triceps skinfold thickness, and body weight were measured at baseline and weeks 4, 8, 10, and 12. RESULTS: LDL cholesterol level was reduced significantly more with whole-grain RTE oat cereal vs control (-8.7+/-1.0 vs -4.3+/-1.1%, P=0.005). Total cholesterol (-5.4+/-0.8 vs -2.9+/-0.9%, P=0.038) and non-high-density lipoprotein-cholesterol (-6.3+/-1.0 vs -3.3+/-1.1%, P=0.046) were also lowered significantly more with whole-grain RTE oat cereal, whereas high-density lipoprotein and triglyceride responses did not differ between groups. Weight loss was not different between groups (-2.2+/-0.3 vs -1.7+/-0.3 kg, P=0.325), but waist circumference decreased more (-3.3+/-0.4 vs -1.9+/-0.4 cm, P=0.012) with whole-grain RTE oat cereal. Larger reductions in LDL, total, and non-high-density lipoprotein cholesterol levels and waist circumference were evident as early as week 4 in the whole-grain RTE oat cereal group. CONCLUSIONS: Consumption of a whole-grain RTE oat cereal as part of a dietary program for weight loss had favorable effects on fasting lipid levels and waist circumference.

Beneficial effects of resistant starch on laxation in healthy adults.

OBJECTIVE: This randomized, double-blind crossover trial evaluated the effects of a type 3 novel resistant starch (RS) versus wheat bran (WB) on faecal weight, frequency, and consistency in healthy adults. METHODS: Following a 14-day baseline period during which subjects (n=14) consumed low-fibre (<2 g) test products, participants were assigned to receive 25 g RS or WB fibre daily for 14 days, then crossed over to the opposite treatment after a 7-day washout. RESULTS: Daily faecal output increased from 128.8+/-68.7 g at baseline to 164.2+/-88.4 g with RS and 194.5+/-92.0 g with WB (both P<0.02 versus baseline). No significant differences among the three conditions were observed for bowel movement frequency. Faecal consistency ratings were increased with WB (P=0.001), but unchanged with RS. CONCLUSIONS: Dietary RS and WB increase faecal output in healthy adults.

Lipid-altering effects of different formulations of hydroxypropylmethylcellulose.

BACKGROUND: Hydroxypropylmethylcellulose (HPMC), a viscous, soluble dietary fiber, has been shown to be efficacious for lowering total and low-density lipoprotein cholesterol (LDL-C) concentrations. The relative effects of various dosages and viscosities of HPMC have not been fully evaluated. OBJECTIVE: To examine the lipid-altering effects of several formulations of HPMC. METHODS: In this randomized, double-blind pilot study, 165 men and women with primary hypercholesterolemia consumed a control product (snack bar or drink mix) or an HPMC-containing test bar or drink for 4 weeks. HPMC-containing products delivered 3, 5, or 10g of HPMC of low, moderate, moderately high, or high viscosity (9 HPMC groups, each with ∼15 subjects). RESULTS: Data from drink and bar groups were combined because there was no evidence of a vehicle effect. The resulting analysis included data from the control and 6 HPMC dose and viscosity combinations. All HPMC groups showed LDL-C reductions ranging from 6.1 to 13.3% (P < .05 vs. baseline for 6 of the 7 groups), compared with a nonsignificant reduction (1.9%) in the control group. Changes in total and non-high-density lipoprotein cholesterol paralleled those for LDL-C. Concentrations of high-density lipoprotein cholesterol, triglycerides, apolipoprotein B, and high-sensitivity C-reactive protein were not significantly altered. CONCLUSION: This pilot study provides preliminary evidence to support the efficacy of various formulations of HPMC for reducing cholesterol carried by atherogenic particles in men and women with primary hypercholesterolemia. Additional research will be required to more clearly define the roles of viscosity and dosage on the lipid-altering effects of HPMC.

Effects of a reduced-glycemic-load diet on body weight, body composition, and cardiovascular disease risk markers in overweight and obese adults.

BACKGROUND: Lowering the dietary glycemic load and increasing protein intake may be advantageous for weight management. OBJECTIVE: This randomized controlled trial was designed to evaluate the effects of an ad libitum reduced-glycemic-load (RGL) diet on body weight, body composition, and cardiovascular disease (CVD) risk markers in overweight and obese adults during an initial weight-loss phase (12 wk) and a weight-loss maintenance phase (weeks 24-36). DESIGN: Subjects were assigned to RGL (n = 43) or low-fat, portion-controlled (control; n = 43) diet groups. The RGL group was instructed to eat until satisfied, maintaining a low carbohydrate intake during weeks 0-2 and adding low-glycemic-index carbohydrate thereafter. Control subjects were instructed to reduce fat intake and decrease portion sizes, with a targeted energy deficit of 500 to 800 kcal/d. RESULTS: The RGL group had lost significantly more weight than did the control group at week 12 (-4.9 and -2.5 kg, respectively; P = 0.002), but the 2 groups did not differ significantly at week 36 (-4.5 and -2.6 kg, respectively; P = 0.085). Changes in fat mass differed between the groups at week 12 (-1.9 and -0.9 kg, respectively; P = 0.016) but not at week 36 (-2.0 and -1.3 kg, respectively; P = 0.333). At the end of the study, no differences were found in responses for CVD risk markers except a larger mean change in HDL cholesterol in the RGL group than in the control group (3.8 and 1.9 mg/dL, respectively; P = 0.037). CONCLUSION: These findings provide evidence that an ad libitum RGL diet is a reasonable alternative to a low-fat, portion-controlled eating plan for weight management.