Establishing a Common Nutritional Vocabulary - From Food Production to Diet.

Informed policy and decision-making for food systems, nutritional security, and global health would benefit from standardization and comparison of food composition data, spanning production to consumption. To address this challenge, we present a formal controlled vocabulary of terms, definitions, and relationships within the Compositional Dietary Nutrition Ontology (CDNO, www.cdno.info) that enables description of nutritional attributes for material entities contributing to the human diet. We demonstrate how ongoing community development of CDNO classes can harmonize trans-disciplinary approaches for describing nutritional components from food production to diet.

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.

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.

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.

Characterization of the nutrient profile of processed red raspberries for use in nutrition labeling and promoting healthy food choices.

BACKGROUND: Red raspberries (Rubus idaeus L.) contain varied nutrients and phytochemicals important for healthy aging. Processing berries extends their shelf-life and culinary applications, although information on nutritional content among processed forms are limited. OBJECTIVE: The main objective of the project was to conduct a market basket study to characterize nutrient content and variation in processed red raspberry (RRB) products (i.e., individually quick frozen (IQF), purée, concentrates). Secondary objectives were to provide new data to the USDA nutrient composition database on processed RRB, which is now complete, and to evaluate RRB forms relative to regulatory (US FDA) criteria for food labeling based on Dietary Reference Intake (DRI) recommendations expressed as % Daily Values (DV). METHODS: Processed raspberry product samples were obtained in 2017 from retail outlets, processing plants and distributors, in and outside the USA. Samples were analyzed by pre-qualified laboratories using pre-approved AOAC methods and validated HPLC methods. RESULTS: Nutrient variance in domestic compared to imported product was observed, but on average IQF and purée with seeds are excellent sources of dietary fiber based on FDA criteria of providing ≥20% DV, IQF and purée are good (10-19% DV) sources of copper, thiamin, riboflavin and folate, and all forms were excellent or good sources of vitamin C and manganese. IQF and puréed red raspberries may also be considered a valuable fruit source of lutein/zeaxanthin. CONCLUSIONS: Processed RRB are nutrient rich options for including in a diet for healthy aging.

An exploratory study of red raspberry (Rubus idaeus L.) (poly)phenols/metabolites in human biological samples.

Red raspberry (Rubus idaeus L.) contains a variety of polyphenols including anthocyanins and ellagitannins. Red raspberry polyphenols absorbed in different forms (parent compounds, degradants or microbial metabolites) are subject to xenobiotic metabolism in the intestine, liver, and/or kidney, forming methylate, glucuronide, and sulfate conjugated metabolites. Upon acute exposure, (poly)phenol/metabolite presence in the blood depends mainly on intestinal absorption, enterohepatic circulation, and metabolism by resident microbiota. However, chronic exposure to red raspberry polyphenols may alter metabolite patterns depending on adaptions in the xenobiotic machinery and/or microbiota composition. Understanding the metabolic fate of these compounds and their composition in different biological specimens relative to the exposure time/dose will aid in designing future health benefit studies, including the mechanism of action studies. The present exploratory study applied ultra-high performance liquid chromatography (UHPLC) coupled with quadrupole time-of-flight (QTOF) and triple quadrupole (QQQ) mass spectrometries to characterize red raspberry polyphenols in fruit and then their appearance, including metabolites in human biological samples (plasma, urine and breast milk) after the chronic intake of red raspberries. The results suggested that the most abundant polyphenols in red raspberries included cyanidin 3-O-sophoroside, cyanidin 3-O-glucoside, sanguiin H6 and lambertianin C. Sixty-two (poly)phenolic compounds were tentatively identified in the plasma, urine and breast milk samples after the intake of red raspberries. In general, urine contained the highest content of phenolic metabolites; phase II metabolites, particularly sulfated conjugates, were mainly present in urine and breast milk, and breast milk contained fewer parent anthocyanins compared to urine and plasma.