An Improved Validated Method for the Determination of Short-Chain Fatty Acids in Human Fecal Samples by Gas Chromatography with Flame Ionization Detection (GC-FID).

Short-chain fatty acids (SCFAs) are metabolites produced by the gut microbiota through the fermentation of non-digestible carbohydrates. Recent studies suggest that the gut microbiota composition, diet and metabolic status play an important role in the production of SCFAs. The primary objective of this study was to develop a simplified method for SCFA analysis in human fecal samples by gas chromatography with flame ionization detection (GC-FID). The secondary objective was to apply the method to fecal samples collected from a clinical trial. The developed GC-FID method showed excellent linearity (R2 > 0.99994), with a limit of detection (LOD) ranging from 0.02 to 0.23 µg/mL and a limit of quantification (LOQ) ranging from 0.08 to 0.78 µg/mL. Recovery for the method ranged between 54.24 ± 1.17% and 140.94 ± 2.10%. Intra- and inter-day repeatability ranged from 0.56 to 1.03 and from 0.10 to 4.76% RSD, respectively. Nine SCFAs were identified and quantified (acetic, propionic, iso-butyric, butyric, iso-valeric, valeric, 4-methyl valeric, hexanoic and heptanoic acids) in freeze-dried fecal samples. The clinical trial compared participants with prediabetes mellitus and insulin resistance (IR-group, n = 20) to metabolically healthy participants (reference group, R-group, n = 9) following a 4-week intervention of a daily red raspberry smoothie (RRB, 1 cup fresh-weight equivalent) with or without fructo-oligosaccharide (RRB + FOS, 1 cup RRB + 8 g FOS). The statistical analysis (Student's t-test, ANCOVA) was performed on PC-SAS 9.4 (SAS Institute). Acetic acid was higher in the R-group compared to the IR-group at baseline/week 0 (p = 0.14). No significant changes in fecal SCFA content were observed after 4 weeks of either RRB or RRB + FOS.

Characterization and Pharmacokinetic Profile of Herbs and Spices' Phytochemicals over 24 h after Consumption in Overweight/Obese Adults.

SCOPE: This study aims to characterize the phytochemicals in commonly consumed herbs/spices (H/S) in the United States and their pharmacokinetic profile (PK) over 24 h in humans after consumption. METHOD AND RESULTS: The clinical trial is a randomized, single-blinded, four-arm, 24 h, multi-sampling, single-center crossover design (Clincaltrials.gov NCT03926442) conducted in obese/overweight adults (n = 24, aged 37 ± 3 years, BMI = 28.4 ± 0.6 kg m-2 ). Study subjects consume a high-fat high-carbohydrate meal with salt and pepper (control) or the control meal with 6 g of three different H/S mixtures (Italian herb: rosemary, basil, thyme, oregano, and parsley in the same ratio; cinnamon; and pumpkin pie spice containing cinnamon, ginger, nutmeg, and allspice, the ratio is unknown). Three H/S mixtures are analyzed and 79 phytochemicals are tentatively identified and quantified. Following H/S consumption, 47 metabolites are tentatively identified and quantified in plasma samples. The PK data suggest that some metabolites appear in blood as early as 0.5 h while others can extend up to 24 h. CONCLUSION: Phytochemicals from H/S include in a meal are absorbed and undergo phase I and phase II metabolism and/or catabolized to phenolic acids peaking at different times.

Phytochemical Composition and Health Benefits of Figs (Fresh and Dried): A Review of Literature from 2000 to 2022.

With their rich history dating back 6000 years, figs are one of the oldest known plants to mankind and are a classical fruit in the Mediterranean diet. They possess a diverse array of bioactive components, including flavonoids, phenolic acids, carotenoids, and tocopherols, which have been used for centuries in traditional medicine for their health-promoting effects addressing gastrointestinal, respiratory, inflammatory, metabolic, and cardiovascular issues. This review summarizes the updated information on the phenolic composition, antioxidant capacity and other functional properties of fresh and dried figs cultivated in various parts of the world, highlighting variation in phenolic composition based on cultivar, harvesting time, maturity stage, processing, and fig parts. Additionally, the review delves into the bio-accessibility and bio-availability of bioactive components from figs and their potential influence on cardiovascular health, diabetes, obesity, and gut/digestive health. Data suggest that the intake of figs regularly in the diet, alone or with other dried fruits, increases select micronutrient intake and is associated with higher diet quality, respectively. Research in animal and human models of health and disease risk provide preliminary health benefits data on figs and their extracts from fig parts; however, additional well-controlled human studies, particularly using fig fruit, will be required to uncover and verify the potential impact of dietary intake of figs on modern day health issues.

Avocado Consumption for 12 Weeks and Cardiometabolic Risk Factors: A Randomized Controlled Trial in Adults with Overweight or Obesity and Insulin Resistance.

BACKGROUND: Diets emphasizing unsaturated fat and high fiber are associated with reducing cardiometabolic risk factors. Avocados are rich in MUFA and PUFA fats and fiber. OBJECTIVES: Assess replacement of carbohydrate energy with avocado energy for 12 wk on glucose homeostasis and cardiometabolic risk factors in self-selecting free-living adults who are overweight or with obesity and have insulin resistance. METHODS: In a single-center, randomized, 2-arm, controlled, 12-wk parallel trial, adults [n = 93; male/female: 39/54; mean ± SD age: 42 ± 12 y; BMI: 32.6 ± 3.9 (in kg/m2);  HOMA-IR: 2.7 ± 1.7] were counseled to exchange avocado (AV) or control food (C; low fat, low fiber, energy matched) for carbohydrate food in their usual diet for 12 wk. The primary outcome was the change in Matsuda Insulin Sensitivity Index (MISI) after 12-wk interventions. Secondary outcomes were changes in fasting and post-oral glucose tolerance test glycemic variables, fasting lipids, endothelial activation and inflammation markers. Automated Self-Administered 24-h Dietary Assessment Tool captured weekly dietary intake. Intervention effects were mainly determined by ANCOVA using PC-SAS version 9.4. RESULTS: Dietary total, MUFA, and PUFA fat; fiber; and vegetable intake were higher in the AV group compared with the C group (P < 0.05), and no change in body weight or composition was observed (P > 0.05). Differences between the changes in MISI after AV compared with C were not different (Δ0-12 wk, P = 0.1092). Differences in fasting insulin (Δ0-12 wk, P = 0.0855) and improved glycated hemoglobin (Δ0-12 wk, P = 0.0632) after AV compared with C were suggested. C-reactive protein was significantly lower after AV compared with C at 12 wk (P = 0.0418). Select biomarkers of endothelial activation and lipoproteins by NMR were also influenced by AV compared with C food intake. CONCLUSIONS: Avocado intake was associated with a healthier dietary pattern and trends favoring improved glucose control and reduced biomarkers of cardiometabolic risk when replacing avocado energy for carbohydrate energy in free-living adults who are overweight or with obesity and have insulin resistance. This trial was registered at clinicaltrials.gov as NCT02695433.

Red Raspberry and Fructo-Oligosaccharide Supplementation, Metabolic Biomarkers, and the Gut Microbiota in Adults with Prediabetes: A Randomized Crossover Clinical Trial.

BACKGROUND: Evidence suggests that the gut microbiota and cardiometabolic status are associated, suggesting dietary interventions that alter the microbiota may affect metabolic health. OBJECTIVES: We investigated whether supplementation with (poly)phenol-dense red raspberries (RRB), alone or with a fructo-oligosaccharide (FOS) prebiotic, would improve biomarkers of cardiometabolic risk in individuals with prediabetes (PreDM) and insulin resistance (IR) and whether the effects are related to modulation of the gut microbiota. METHODS: Adults with PreDM-IR (n = 26; mean ± SEM age, 35 ± 2 years; fasting glucose, 5.7 ± 0.1 mmol/L; HOMA-IR, 3.3 ± 0.3) or who were metabolically healthy (reference group; n = 10; age, 31 ± 3 years; fasting glucose, 5.1 ± 0.2 mmol/L; HOMA-IR, 1.1 ± 0.1) participated in a randomized crossover trial with two 4-week supplementation periods, in which they consumed either RRB (125 g fresh equivalents) daily or RRB + 8g FOS daily, separated by a 4-week washout. The primary outcome variable was the change in the gut microbiota composition, assessed by shotgun sequencing before (baseline) and at the end of each supplementation period. Secondary outcomes were changes in glucoregulation, lipid metabolism, anti-inflammatory status, and anthropometry. The trial is registered at ClinicalTrials.gov, NCT03049631. RESULTS: In PreDM-IR, RRB supplementation reduced hepatic-IR (-30.1% ± 14.6%; P = 0.04) and reduced plasma total and LDL cholesterol [-4.9% ± 1.8% (P = 0.04) and -7.2% ± 2.3% (P = 0.003), respectively] from baseline. Adding FOS (RRB + FOS) improved ß-cell function [insulin secretion rate, +70.2% ± 32.8% (P = 0.02); Disposition Index, +94.4% ± 50.2% (P = 0.04)], but had no significant effect on plasma cholesterol compared to baseline. RRB increased Eubacterium eligens (2-fold) and decreased Ruminococcus gnavus (-60% ± 34%), whereas RRB + FOS increased Bifidobacterium spp. (4-fold) and decreased Blautia wexlerae (-23% ± 12%) from baseline (all P values ≤ 0.05). R. gnavus was positively correlated with hepatic-IR, and E. eligens and Bifidobacterium catenulatum were negatively correlated with cholesterol concentrations (P ≤ 0.05). CONCLUSIONS: Increased Bifidobacterium spp., concurrently with reduced R. gnavus, was associated with metabolic improvements in adults with PreDM-IR, warranting further research on the mechanisms involved in (poly)phenol/FOS-microbial interactions with host metabolism.

Endothelial Function and Postprandial Glucose Control in Response to Test-Meals Containing Herbs and Spices in Adults With Overweight/Obesity.

Objectives: Herbs and Spices (H/S) contain bioactive compounds with purported health benefits. This study investigated the effect of H/S intake on indicators of vascular and metabolic health over 24 h using a test-meal challenge paradigm in adults with overweight or obesity. Methods: In a randomized, single-blinded, 4-arm, 24 h, multi-sampling, crossover clinical trial, adults (n = 25) aged 36.6 ± 3.1 years with BMI 28.5 ± 0.6 kg/m2 (mean ± SEM) consumed a high-fat, high-carbohydrate challenge meal (~810 kcal) with salt/pepper only (control) or control with one of three different H/S combinations: Italian herb (rosemary, basil, thyme, oregano, and parsley), cinnamon, or pumpkin pie spice mix (cinnamon, ginger, nutmeg, and allspice) on four separate visits at least 3 days apart. Meals provided 35% of subjects' energy to maintain weight and ~1 g H/S per 135 kcal of the meal. Flow-mediated dilation (FMD) and blood samples were collected at 0, 1, 2, 4, 5.5, 7, and 24 h for endpoint analysis (additional blood draw at 0.5 h for insulin/glucose). Mixed-model analysis of repeated measures via PROC MIXED PC-SAS 9.4 was performed on the primary outcome (FMD) and secondary outcome variables. This study was registered at ClinicalTrials.gov (NCT03926442). Results: Italian herb and pumpkin spice meals significantly increased %FMD at 24 h compared to the control meal (P = 0.048 and P = 0.027, respectively). The cinnamon meal reduced postprandial glycemia (Δ) compared to control (P = 0.01), and pumpkin pie spice mix and cinnamon meals reduced postprandial insulin at 0.5 h compared to the control meal (P = 0.01 and P = 0.04, respectively). IL-6 and triglycerides increased in response to all meals (Time, P < 0.0001) but were not significantly different between meals. Conclusions: The test-meal challenge study design coupled with multiple sampling over 24 h provides insights into time-course bioactivity of H/S on vascular function and metabolic indices in overweight/obese adults. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03926442.

Watermelon and L-Citrulline in Cardio-Metabolic Health: Review of the Evidence 2000-2020.

PURPOSE OF REVIEW: Watermelon (Citrullus lanatus) distinctively contains L-citrulline and L-arginine, precursors of nitric oxide (NO), along with polyphenols and carotenoids suggesting a role in cardio-metabolic health. The goal of this paper is to review the preclinical and clinical trial evidence published from 2000 to 2020 to assess watermelon intake and L-citrulline, as a signature compound of watermelon, on cardiovascular and metabolic outcomes, and to identify future directions important for establishing dietary guidance and therapeutic recommendations actionable by health care professionals, patients, and the general public. RECENT FINDINGS: Watermelon and L-citrulline supplementation reduced blood pressure in human trials. Evidence for benefits in lipids/lipoprotein metabolism is emerging based on human literature and consistently reported in animal models. A role for watermelon intake in body weight control, possibly through satiety mechanisms, warrants further research. Likewise, improved glucose homeostasis in chemically and diet-induced animal models of diabetes is apparent, though limited data are available in humans. Emerging areas include brain and gut health indicated by NO bioavailability in all tissues, and evidence suggesting improvements in gut barrier function and altered microbial composition after watermelon intake that may influence metabolite pools and physiological function. Watermelon fruit contains unique vaso- and metabolically-active compounds. Accumulating evidence supports regular intake for cardio-metabolic health. Future research to determine the amount and frequency of watermelon/citrulline intake for desired outcomes in different populations requires attention to advance preventative and therapeutic strategies for optimal health and disease risk reduction.

Pharmacokinetic Evaluation of Red Raspberry (Poly)phenols from Two Doses and Association with Metabolic Indices in Adults with Prediabetes and Insulin Resistance.

This study aimed to investigate pharmacokinetic variables of two doses of red raspberry (RR) (poly)phenols and their association with metabolic indices in adults with prediabetes and insulin resistance (preDM-IR) compared to metabolically healthy adults (reference). Thirty-two adults (preDM-IR, n = 21; reference, n = 11) consumed three meals containing 0 g (control), 125 g, or 250 g of frozen RR on three separate days in random order. Plasma (poly)phenolic metabolites and metabolic indices were characterized over a 0-8 h period and again at 24 h. Twenty-four metabolites were significantly increased by RR interventions in all subjects (p < 0.05). Individuals with preDM-IR compared to reference had a lower capacity to generate several metabolites, including 4'-hydroxy-3'-methoxycinnamic acid and hydroxymethoxycinnamic acid isomer, both negatively correlated with postprandial insulin concentrations (p < 0.05). The results suggest that RR (poly)phenols are metabolized in a dose-related manner, and further research is required to understand their role in insulin management.

Addition of Orange Pomace Attenuates the Acute Glycemic Response to Orange Juice in Healthy Adults.

BACKGROUND: Fiber is an important part of a healthy diet and is known to attenuate postprandial glycemia. Orange pomace (OP) is a by-product of orange juice (OJ) production and is a rich source of fiber. OBJECTIVE: Two separate studies determined the impact of added OP to 100% OJ on postprandial glycemic response compared with sugar-matched OJ or whole orange fruit (WOF). METHODS: Study 1 included 17 adults [65% female, age 39.3 ± 3.1 y, and BMI (in kg/m2) 24.6 ± 0.7], and study 2 included 45 different adults (47% female, age 25.1 ± 4.3 y, and BMI 22.5 ± 1.6). Studies were conducted at separate locations using a randomized, 3-arm, crossover design to test the glycemic response to sugar-matched OJ, OJ with 5 g fiber from OP (OPF), or WOF. The primary outcomes were 2-h glucose incremental area under the curve (iAUC) in study 1, analyzed by repeated measures ANOVA, and maximum glucose concentration (Cmax) in study 2, analyzed using PROC MIXED (ANCOVA). Glucose and insulin concentrations were measured at fasting and multiple time points over 2 h after test product consumption (study 1, serum; study 2, plasma). RESULTS: In study 1, glucose iAUC was not significantly lower in OPF compared to the OJ or WOF (825 ± 132 compared with 920 ± 132 and 760 ± 132 mg · min · dL-1, respectively, P = 0.57 for both). In study 2, glucose iAUC was significantly lower in WOF compared with OPF and OJ (689 ± 70.7 compared with 892 ± 70.7 and 974 ± 70.7 mg · min · dL-1, P = 0.02 and 0.001, respectively). Data from both studies indicated OPF reduced Cmax compared with OJ and that the reductions were comparable to WOF (study 1: OPF, 115 ± 4.06 compared with OJ, 124 ± 4.06 and WOF, 114 ± 4.06 mg · dL-¹, P = 0.002 and 0.75, respectively; study 2: OPF, 128 ± 1.92 compared with OJ, 136 ± 1.92 and WOF, 125 ± 1.92 mg · dL-¹, P = 0.001 and 0.28, respectively). CONCLUSION: Data from both studies demonstrated no significant effect of OPF on postprandial iAUC compared with OJ. However, adding OP into OJ attenuates the postprandial glucose Cmax, and the responses were comparable to WOF in healthy adults.

Strawberry Consumption, Cardiometabolic Risk Factors, and Vascular Function: A Randomized Controlled Trial in Adults with Moderate Hypercholesterolemia.

BACKGROUND: Certain fruits, such as strawberries, may impart cardiometabolic benefits due to their phytochemical content. OBJECTIVES: Study aims were to assess the effects of strawberry intake on cardiometabolic risk factors and vascular endothelial function in adults with moderate hypercholesterolemia. METHODS: This study was a randomized, controlled, double-blinded, 2-arm, 2-period (4-wk/period) crossover trial. Adults (n = 34; male/female 1:1; mean ± SEM age, 53 ± 1 y; BMI, 31 ± 1 kg/m2;  LDL cholesterol, 133 ± 3 mg/dL) were randomly allocated to 1 of 2 study sequences in a 1:1 ratio. Participants drank study beverages twice daily containing freeze-dried strawberry powder (2 × 25 g) or energy-, volume-matched control powder for 4 wk separated by a 4-wk washout. The primary outcome variable was the difference in fasting LDL cholesterol after 4-wk interventions. Secondary outcomes were metabolic markers, inflammation, quantitative (poly)phenolic metabolomics, flow-mediated dilation (FMD), and blood pressure (BP), with the latter (FMD, BP) also assessed acutely at 1 h and 2 h after a 50-g bolus strawberry or control beverage. Mixed-model analysis of repeated measures via PROC MIXED, PC-SAS was performed on primary and secondary outcome variables. RESULTS: LDL cholesterol did not differ after the 4-wk interventions (P > 0.05), nor did fasting total cholesterol, triglycerides, glucose, insulin, high-sensitivity C-reactive protein, FMD, or BP (all P > 0.05). Significant intervention-by-hour interaction for FMD (P = 0.03) and BP (P = 0.05) revealed increased FMD at 1 h after strawberry compared with control by 1.5 ± 0.38% (P = 0.0008) and attenuated systolic BP at 2 h by 3.1 ± 0.99 mmHg (P = 0.02). Select phenolic metabolites increased significantly (P < 0.05) in blood following strawberry consumption while others decreased, including 3-(4-methoxyphenyl)propanoic acid-3-O-glucuronide, which was significantly correlated with increased FMD (P < 0.05). CONCLUSION: Strawberries may improve vascular health, independent of other metabolic changes. The effect may be related to changes in microbial-derived phenolic metabolites after strawberry consumption influencing endothelial function. Data support inclusion of strawberries in a heart-healthy diet in adults with moderate hypercholesterolemia.This trial was registered at clinicaltrials.gov as NCT02612090.

Comprehensive Characterization of Bile Acids in Human Biological Samples and Effect of 4-Week Strawberry Intake on Bile Acid Composition in Human Plasma.

Primary bile acids (BAs) and their gut microbial metabolites have a role in regulating human health. Comprehensive characterization of BAs species in human biological samples will aid in understanding the interaction between diet, gut microbiota, and bile acid metabolism. Therefore, we developed a qualitative method using ultra-high performance liquid chromatography (UHPLC) coupled with a quadrupole time-of-flight (Q-TOF) to identify BAs in human plasma, feces, and urine samples. A quantitative method was developed using UHPLC coupled with triple quadrupole (QQQ) and applied to a previous clinical trial conducted by our group to understand the bile acid metabolism in overweight/obese middle-aged adults (n = 34) after four weeks strawberry vs. control intervention. The qualitative study tentatively identified a total of 81 BAs in human biological samples. Several BA glucuronide-conjugates were characterized for the first time in human plasma and/or urine samples. The four-week strawberry intervention significantly reduced plasma concentrations of individual secondary BAs, deoxycholic acid, lithocholic acid and their glycine conjugates, as well as glycoursodeoxycholic acid compared to control (p < 0.05); total glucuronide-, total oxidized-, total dehydroxyl-, total secondary, and total plasma BAs were also lowered compared to control (p < 0.05). The reduced secondary BAs concentrations suggest that regular strawberry intake modulates the microbial metabolism of BAs.

Improved metabolic function and cognitive performance in middle-aged adults following a single dose of wild blueberry.

PURPOSE: Research has demonstrated cognitive benefits following acute polyphenol-rich berry consumption in children and young adults. Berry intake also has been associated with metabolic benefits. No study has yet examined cognitive performance in middle-aged adults. We investigated the relationships among cognitive and metabolic outcomes in middle-aged adults following wild blueberry (WBB) consumption. METHODS: Thirty-five individuals aged 40-65 years participated in a randomized, double blind, cross-over study. Participants consumed a breakfast meal and 1-cup equivalent WBB drink or matched placebo beverage on two occasions. Participants completed cognitive tasks and had blood drawn before and at regular intervals for 8 h after each meal/treatment. Changes in episodic memory and executive function (EF) were assessed alongside plasma levels of glucose, insulin, and triglyceride. RESULTS: Analysis of the memory-related Auditory Verbal Learning Task (AVLT) word recognition measure revealed a decrease in performance over the test day after placebo intake, whereas performance after WBB was maintained. For the AVLT word rejection measure, participants identified more foils following WBB in comparison to placebo. Benefits were also observed for EF on the Go/No-Go task with fewer errors following WBB intake on cognitively demanding invalid No-Go trials in comparison to placebo. Furthermore, in comparison to placebo, response times were faster for the Go/No-Go task, specifically at 4 h and 8 h following WBB treatment. We also observed reduced post-meal glucose and insulin, but not triglyceride, concentrations in comparison to placebo over the first 2 h following ingestion. Though the addition of Age, BMI, glucose and insulin as covariates to the analysis reduced the significant effect of beverage for AVLT word rejection, metabolic outcomes did not interact with treatment to predict cognitive performance with the exception of one isolated trend. CONCLUSIONS: This study indicated acute cognitive benefits of WBB intake in cognitively healthy middle-aged individuals, particularly in the context of demanding tasks and cognitive fatigue. WBB improved glucose and insulin responses to a meal. Further research is required to elucidate the underlying mechanism by which WBB improves cognitive function.

Varying roles of glucoregulatory function measures in postprandial cognition following milk consumption.

PURPOSE: Past work suggests milk consumption may facilitate cognition in children and college students with higher fasting glucose compared to other beverages (e.g., fruit juice). However, no studies have evaluated this phenomenon in adults, or considered other measures of glucoregulatory function. This open-label study assessed the role of glucoregulatory function in postprandial cognition after milk intake in adults. We hypothesized participants with lower fasting or post-consumption plasma glucose following a glucose excursion challenge (glucose response) would demonstrate better cognition following beverages of higher (juice) versus lower (milk) or no (water) glycemic content. METHODS: Forty-four nondiabetic, overnight-fasted adults attended three laboratory visits, ingesting 237 mL of 2% fat milk, apple juice, or water at each visit in a randomized, counterbalanced, crossover design. Participants completed cognitive testing (CNS Vital Signs) at baseline and 30, 90, and 150 min post-ingestion; primary outcomes were CNS Vital Signs composite scores. Fasting and post-consumption plasma glucose levels were assessed, with glucose response indexed as the change in plasma glucose from baseline to 30 min after juice (ΔGlucose). RESULTS: Mixed modeling revealed participants with higher fasting glucose demonstrated better complex attention after water versus juice at 30 min, but better performance after juice versus water at 150 min (p = 0.02). Participants with a larger ΔGlucose demonstrated better processing speed (p = 0.01) 30 min after milk versus water; this effect also reversed at 150 min. CONCLUSION: Different methods of measuring glucoregulatory function reveal its differing roles in postprandial cognition. Time since ingestion may also determine which beverages best optimize cognition.

Blueberry phenolics are associated with cognitive enhancement in supplemented healthy older adults.

Blueberries (BB) contain an array of bioactive phenolic compounds that may play a protective role against various age-related diseases. Here we explored the metabolic fate of BB phenolics and their relationship to cognitive function after chronic (90 days) supplementation of freeze-dried BB (24 g d-1, equivalent to 1 cup of fresh BB) or control in a randomized, double-blind, parallel study with 38 healthy older adults (60-75 years). Blood samples were collected at fasting (t = 0 h) and 2 h after a breakfast meal on days 0 (no treatment), 45, and 90, and a battery of cognitive tests was also conducted on these days. Hippuric acid, phloroglucinaldehyde, syringic acid, ferulic acid-glucuronide, cyanidin-3-O-galactoside, cyanidin-3-O-glucoside, malvidin-3-O-galactoside, malvidin-3-O-glucoside, peonidin-3-O-xyloside, peonidin glucuronide, and petunidin-3-O-glucoside concentrations were significantly altered after 90 days of BB consumption compared to control. Stepwise regression was used to assess the relationship between significantly altered concentrations of plasma phenolics and observed improvements in cognition. Among participants in the BB group, changes in switch errors on the task-switching test (TST) from day 0 to 90 were associated with changes in postprandial levels of plasma ferulic acid-glucuronide, syringic acid, and malvidin-3-galactoside (R2 = 0.521, p < 0.05). Changes in repetition errors on the California Verbal Learning Test (CVLT-II) from day 0 to 90 were associated with changes in postprandial levels of ferulic acid-glucuronide, syringic acid, and hippuric acid (R2 = 0.807, p < 0.001). These findings demonstrate that the addition of easily achievable quantities of BB to the diets of older adults significantly alters levels of circulating phenolic compounds which are related to improvements in cognition.

Pharmacokinetic Characterization of (Poly)phenolic Metabolites in Human Plasma and Urine after Acute and Short-Term Daily Consumption of Mango Pulp.

Pharmacokinetic (PK) evaluation of polyphenolic metabolites over 24 h was conducted in human subjects (n = 13, BMI = 22.7 ± 0.4 kg/m2) after acute mango pulp (MP), vitamin C (VC) or MP + VC test beverage intake and after 14 days of MP beverage intake. Plasma and urine samples were collected at different time intervals and analyzed using targeted and non-targeted mass spectrometry. The maximum concentrations (Cmax) of gallotannin metabolites were significantly increased (p < 0.05) after acute MP beverage intake compared to VC beverage alone. MP + VC beverage non-significantly enhanced the Cmax of gallic acid metabolites compared to MP beverage alone. Pyrogallol (microbial-derived metabolite) derivatives increased (3.6%) after the 14 days of MP beverage intake compared to 24 h acute MP beverage intake (p < 0.05). These results indicate extensive absorption and breakdown of gallotannins to galloyl and other (poly)phenolic metabolites after MP consumption, suggesting modulation and/or acclimation of gut microbiota to daily MP intake.

Functional Deficits in Gut Microbiome of Young and Middle-Aged Adults with Prediabetes Apparent in Metabolizing Bioactive (Poly)phenols.

BACKGROUND: Gut microbiota metabolize select dietary (poly)phenols to absorbable metabolites that exert biological effects important in metabolic health. Microbiota composition associated with health/disease status may affect its functional capacity to yield bioactive metabolites from dietary sources. Therefore, this study assessed gut microbiome composition and its related functional capacity to metabolize fruit (poly)phenols in individuals with prediabetes and insulin resistance (PreDM-IR, n = 26) compared to a metabolically healthy Reference group (n = 10). METHODS: Shotgun sequencing was used to characterize gut microbiome composition. Targeted quantitative metabolomic analyses of plasma and urine collected over 24 h were used to assess microbial-derived metabolites in response to a (poly)phenol-rich raspberry test drink. RESULTS: PreDM-IR compared to the Reference group: (1) enriched Blautia obeum and Blautia wexlerae and depleted Bacteroides dorei and Coprococcus eutactus. Akkermansia muciniphila and Bacteroides spp. were depleted in the lean PreDM-IR subset; and (2) impaired microbial catabolism of select (poly)phenols resulting in lower 3,8-dihydroxy-urolithin (urolithin A), phenyl-γ-valerolactones and various phenolic acids concentrations (p < 0.05). Controlling for obesity revealed relationships with microbial species that may serve as metagenomic markers of diabetes development and therapeutic targets. CONCLUSIONS: Data provide insight from multi-omics approaches to advance knowledge at the diet-gut-disease nexus serving as a platform for devising dietary strategies to improve metabolic health.

Plasma and Urinary (Poly)phenolic Profiles after 4-Week Red Raspberry (Rubus idaeus L.) Intake with or without Fructo-Oligosaccharide Supplementation.

Red raspberries (RRB) are high in anthocyanin- and ellagitannin- type (poly)phenols. This study aimed to investigate the effect of 4-week RRB supplementation on (poly)phenolic metabolism in adults with prediabetes and insulin-resistance (PreDM-IR); and whether adding fructo-oligosaccharides (FOS), prebiotics, would augment the microbial metabolites of RRB (poly)phenols. In a randomized crossover clinical trial, subjects (n = 35: PreDM-IR, n = 25; healthy Reference group, n = 10) consumed 1 cup RRB (fresh weight equivalence) per day and RRB with 8 g FOS per day each for 4 weeks in random order separated by 4-week washout. Plasma and urinary (poly)phenolic metabolites were characterized after (0-24h) consuming a RRB-based test drink (2 cups RRB) at baseline/week 0 and again after 4-week supplementations. A total of 123 (poly)phenolic metabolites were quantified. After 4-week RRB supplementation, several metabolite groups were significantly increased (p < 0.05), including urolithins, phenyl-γ-valerolactones, and phenolic acids. Supplementing FOS with RRB for 4 weeks enhanced benzoic acid derivatives compared to the baseline (p < 0.05). Specific effects of supplementation by metabolic status indicated 4-week RRB supplementation significantly increased microbial metabolites that were lower in PreDM-IR group. Our results suggest alterations in the capacity of PreDM-IR group to metabolize and render bioavailable raspberry-derived (poly)phenols when consumed regularly.

Pharmacokinetic Parameters of Watermelon (Rind, Flesh, and Seeds) Bioactive Components in Human Plasma: A Pilot Study to Investigate the Relationship to Endothelial Function.

This study aimed to investigate the metabolic fate of bioactive components in watermelon and explore their effect on endothelial function. Six healthy overweight/obese (BMI: 28.7 ± 1.6 kg/m2) adults received 100 kcal of watermelon flesh (WF), rind (WR), seeds (WS), or control meal. l-Citrulline, arginine, and (poly)phenolic metabolites were characterized in plasma over 24 h using UHPLC-MS. Endothelial function was assessed using a flow mediated dilation (FMD) technique over 7 h. Maximum concentration (Cmax) and area under the curve (AUC0-8h) of l-citrulline were significantly higher after WF- and WR-containing test meals compared to control (p < 0.05). Likewise, several individual phenolic metabolites in plasma had significantly higher Cmax after WR, WF, or WS intake compared to control. FMD responses were not different among test meals. Our results provide insights on circulating metabolites from watermelon flesh, seed, and rind and lay the foundation for future clinical trials on vascular benefits of watermelon.

Assessing consumers' understanding of the term "Natural" on food labeling.

The objective of this study was to gain a better understanding of how consumers' interpret the term "natural" by assessing food choice based on labels describing attributes of a product associated with the term "natural"; to assess food intake of chosen food, and; to determine factors that influence food choice and intake. A randomized, single-visit pilot study was conducted where participants (n = 105) were presented with seven identical bowls of granola each bearing a different descriptive label. Participants were asked to choose and eat the granola (ad libitum) that coincided with what was closest to their view of "natural." Food choice, intake amount, demographics, self-health perception, label use, dietary restraint, and mindfulness were measured. "Organic" (31%), "Made with real grains" (17%), and "No preservatives" (15%) were the top three chosen labels. These choices related to concerns about environment and processing, personal health, and additives and preservatives, respectively (P = 0.049). Income level and age were significantly associated with choice (P = 0.003). Defining the term "natural" for use on food labels will require follow-up researchacrosseconomically diverse populations and age groups to understand expectations of food products bearing the term "natural."