Polyphenol-Rich Beverage Consumption Affecting Parameters of the Lipid Metabolism in Healthy Subjects.

Polyphenols are a diverse and widely distributed class of secondary metabolites, which possess numerous beneficial properties including a modulation of glucose and lipid metabolism. This placebo-controlled human intervention study was performed to explore effects of polyphenol-rich beverage (PRB) uptake on lipid metabolism, as well as DNA integrity. In this case, 36 healthy men were randomly divided to consume either 750 mL of a PRB (containing 51% chokeberry, cranberry, and pomegranate) or a placebo drink daily for eight weeks. Only PRB consumption was found to decrease fat and protein intakes significantly compared to the preceding one-week washout period. During the intervention with PRB an increased fat-free mass was shown after four weeks, whereas a significant elevation in body weight and leptin was observed in placebo group. Blood lipids were not significantly altered after PRB consumption, while triglyceride levels increased after placebo drink intake. In platelets, a significant inhibition of phosphodiesterase (PDE) activity was observed, more pronounced in test group. Consuming the PRB decreased total DNA strand breaks in whole blood as well as H2O2-induced breaks in isolated lymphocytes. Overall, our study suggested beneficial effects on lipid metabolism by reduced energy intake, modulation of biomarkers such as PDE activity and improved DNA integrity associated with PRB consumption.

Effects of two consecutive mixed meals high in palmitic acid or stearic acid on 8-h postprandial lipemia and glycemia in healthy-weight and overweight men and postmenopausal women: a randomized controlled trial.

PURPOSE: Palmitic and stearic acids have different effects on fasting serum lipoproteins. However, the effects on postprandial lipemia and glycemia are less clear. Also, the effects of a second meal may differ from those of the first meal. Therefore, we studied the effects of two consecutive mixed meals high in palmitic acid- or stearic acid-rich fat blends on postprandial lipemia and glycemia. METHODS: In a randomized, crossover study, 32 participants followed 4-week diets rich in palmitic or stearic acids, At the end of each dietary period, participants consumed two consecutive meals each containing ± 50 g of the corresponding fat blend. RESULTS: Postprandial concentrations of triacylglycerol (diet-effect: - 0.18 mmol/L; p = 0.001) and apolipoprotein B48 (diet-effect: - 0.68 mg/L; p = 0.002) were lower after stearic-acid than after palmitic-acid intake. Consequently, total (iAUC0-8 h) and first meal (iAUC0-4 h) responses were lower after stearic-acid intake (p ≤ 0.01). Second meal responses (iAUC4-8 h) were not different. Postprandial changes between the diets in non-esterified fatty acids (NEFA) and C-peptide differed significantly over time (p < 0.001 and p = 0.020 for diet*time effects, respectively), while those for glucose and insulin did not. The dAUC0-8 h, dAUC0-4 h, and dAUC4-8 h for NEFA were larger after stearic-acid intake (p ≤ 0.05). No differences were observed in the iAUCs of C-peptide, glucose, and insulin. However, second meal responses for glucose and insulin (iAUC4-8 h) tended to be lower after stearic-acid intake (p < 0.10). CONCLUSION: Consumption of the stearic acid-rich meals lowered postprandial lipemia as compared with palmitic acid. After the second stearic acid-rich meal, concentrations of C-peptide peaked earlier and those of NEFA decreased more. Clinical trial registry This trial was registered at clinicaltrials.gov as NCT02835651 on July 18, 2016.

Consumption of a dark roast coffee blend reduces DNA damage in humans: results from a 4-week randomised controlled study.

PURPOSE: To determine the DNA protective effects of a standard coffee beverage in comparison to water consumption. METHODS: The single-blind, randomised controlled study with parallel design included healthy women (n = 50) and men (n = 50) recruited from the general Central European population. The subjects were randomised in a coffee and a control group, with stratification for sex and body mass index. The study comprised two periods of 4 weeks: a preconditioning period, with daily consumption of at least 500 ml water but no coffee, nor tea, nor any other caffeine-containing product. During the subsequent intervention period the coffee group consumed 500 ml of freshly brewed dark roast coffee blend per day, the control group consumed water instead. On the last day of each period, blood was drawn and analysed by comet assay (single-cell gel electrophoresis) to assess the level of DNA damage (strand breakage). RESULTS: At the end of the intervention period the mean level of DNA strand breaks in the coffee group has decreased in comparison to the control group [difference in means 0.23% TI (tail intensity), p = 0.028]. The mean change from baseline (delta value) was - 23% in the coffee group (p = 0.0012). Effects of coffee intake were similar for men and women. During intervention, neither group showed any significant change in body weight or calorie intake. CONCLUSIONS: Our results indicate that regular consumption of a dark roast coffee blend has a beneficial protective effect on human DNA integrity in both, men and women.

Monitoring urinary mercapturic acids as biomarkers of human dietary exposure to acrylamide in combination with acrylamide uptake assessment based on duplicate diets.

The present human intervention study investigated the relation between the intake of acrylamide (AA) in diets with minimized, low, and high AA contents and the levels of urinary exposure biomarkers. As biomarkers, the mercapturic acids, N-acetyl-S-(carbamoylethyl)-L-cysteine (AAMA), and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) were monitored. The study was performed with 14 healthy male volunteers over a period of 9 days, under controlled conditions excluding any inadvertent AA exposure. Dietary exposure to AA was measured by determining AA contents in duplicates of all meals consumed by the volunteers. The study design included an initial washout period of 3 days on AA-minimized diet, resulting in dietary AA exposure not exceeding 41 ng/kg bw/d. Identical washout periods of 2 days each followed the AA exposure days (day 4, low exposure, and day 7, high exposure). At the respective AA intake days, volunteers ingested 0.6-0.8 (low exposure) or 1.3-1.8 (high exposure) µg AA/kg bw/d with their food. Both low and high AA intakes resulted in an AAMA output within 72 h corresponding to 58 % of the respective AA intake. At the end of the initial 3-day washout period, an AAMA baseline level of 93 ± 31 nmol/d was recorded, suggestive for an assumed net AA baseline exposure level of 0.2-0.3 µg AA/kg bw/d.

Polyphenols in foods: a potential strategy for preventing and managing the postprandial hyperglycemic response.

Type 2 diabetes mellitus (T2DM) is a significant health risk worldwide, and effective management strategies are needed. Polyphenols exhibit diverse biological functions, are abundant in various plants, and influence carbohydrate digestion and absorption. This review provides a comprehensive overview of clinical evidence regarding the relationship between dietary polyphenols and the postprandial hyperglycemic response. Human intervention studies have demonstrated the benefits of polyphenol-rich foods in improving glucose and insulin metabolism, underscoring their role in preventing T2DM. These findings highlight the potential of polyphenol-rich foods for managing hyperglycemia and mitigating T2DM risk and provide insight into effective dietary strategies for glycemic control and overall health.

A grape seed and bilberry extract reduces blood pressure in individuals at risk of developing type 2 diabetes: the PRECISE study, a double-blind placebo-controlled cross-over intervention study.

Background: Type 2 Diabetes Mellitus (T2DM) is a major risk factor for the development of cardiometabolic diseases. T2DM prevention is largely based on weight-loss and whole diet changes, but intervention with dietary plant bioactives may also improve metabolic health. Objective: To assess whether supplementation with bilberry and grape seed extract for 12 weeks improves cardiometabolic outcomes in individuals at risk of developing T2DM, and to determine whether individual treatment response is associated with differences in gut microbiota composition and levels of phenolic metabolites in blood and feces. Methods: In the randomized, double-blind, placebo-controlled, cross-over PRECISE intervention study, 14 participants, aged ≥45 years, with a BMI >28 kg/m2, and having an increased risk of T2DM, received a supplement containing 250 mg of bilberry plus 300 mg of grape seed extract, or 550 mg of a control extract, per day, for 12 weeks each. Blood samples were obtained for the assessment of HbA1c, fasting glucose, oral glucose tolerance tests, insulin, glucagon levels, total, LDL and HDL cholesterol, and phenolic acids. We also assessed advanced glycation end products in the skin, ambulatory 24 hours blood pressure, 7-day dietary intake by weighed food diaries, fecal levels of phenolic metabolites using LC-MS/MS and gut microbiota composition using 16S rRNA gene sequencing analysis. Results: The combined bilberry and grape seed extract did not affect glucose and cholesterol outcomes, but it decreased systolic and diastolic ambulatory blood pressure by 4.7 (p < 0.001) and 2.3 (p = 0.0009) mmHg, respectively. Eight out of fourteen participants were identified as blood pressure 'responders'. These responders had higher levels of phenylpropionic and phenyllactic acids in their fecal samples, and a higher proportional abundance of Fusicatenibacter-related bacteria (p < 0.01) in their baseline stool samples. Conclusion: Long-term supplementation with bilberry and grape seed extract can improve systolic and diastolic blood pressure in individuals at risk of T2DM. Individual responsiveness was correlated with the presence of certain fecal bacterial strains, and an ability to metabolize (epi)catechin into smaller phenolic metabolites.Clinical trial registry number: Research Registry (number 4084).

Dietary stearic acid and palmitic acid do not differently affect ABCA1-mediated cholesterol efflux capacity in healthy men and postmenopausal women: A randomized controlled trial.

BACKGROUND: The saturated fatty acid stearic acid (C18:0) lowers HDL cholesterol compared with palmitic acid (C16:0). However, the ability of HDL particles to promote cholesterol efflux from macrophages (cholesterol efflux capacity; CEC) may better predict coronary heart disease (CHD) risk than HDL cholesterol concentrations. OBJECTIVE: We examined effects of exchanging dietary palmitic acid for stearic acid on ATP-binding cassette transporter A1 (ABCA1)-mediated CEC, and other conventional and emerging cardiometabolic risk makers. DESIGN: In a double-blind, randomized, crossover study with two 4-week isocaloric intervention periods, 34 healthy men and postmenopausal women (61.5 ± 5.7 years, BMI: 25.4 ± 2.5 kg/m2) followed diets rich in palmitic acids or stearic acids. Difference in intakes was 6% of daily energy. ABCA1-mediated CEC was measured from J774 macrophages to apolipoprotein (apo)B-depleted serum. RESULTS: Compared with the palmitic-acid diet, the stearic-acid diet lowered serum LDL cholesterol (-0.14 mmol/L; p = 0.010), HDL cholesterol (-0.09 mmol/L; p=<0.001), and apoA1 (-0.05 g/L; p < 0.001). ABCA1-mediated CEC did not differ between diets (p = 0.280). Cholesteryl ester transfer protein (CETP) mass was higher on stearic acid (0.11 mg/L; p = 0.003), but CETP activity was comparable. ApoB100 did not differ, but triacylglycerol concentrations tended to be higher on stearic acid (p = 0.100). Glucose concentrations were comparable. Effects on insulin and C-peptide were sex-dependent. In women, the stearic-acid diet increased insulin concentrations (1.57 µU/mL; p = 0.002), while in men, C-peptide concentrations were lower (-0.15 ng/mL; p = 0.037). Interleukin 6 (0.15 pg/mL; p = 0.039) and tumor necrosis factor alpha (0.18 pg/mL; p = 0.005), but not high-sensitivity C-reactive protein, were higher on stearic acid. Soluble intracellular adhesion molecule (9 ng/mL; p = 0.033), but not soluble vascular cell adhesion molecule and endothelial-selectin concentrations decreased after stearic-acid consumption. CONCLUSIONS: As expected, stearic-acid intake lowered LDL cholesterol, HDL cholesterol, and apoA1. Insulin sensitivity in women and low-grade inflammation might be unfavorably affected by stearic-acid intake. However, palmitic-acid and stearic-acid intakes did not differently affect ABCA1-mediated CEC. CLINICAL TRIAL REGISTRY: This trial was registered at clinicaltrials.gov as NCT02835651.

Absorption, Pharmacokinetics, and Urinary Excretion of Pyridines After Consumption of Coffee and Cocoa-Based Products Containing Coffee in a Repeated Dose, Crossover Human Intervention Study.

SCOPE: The present study assesses the absorption, pharmacokinetics, and urinary excretion of coffee pyridines and their metabolites after daily regular exposure to specific dosages of coffee or cocoa-based products containing coffee (CBPCC), considering different patterns of consumption. METHODS AND RESULTS: In a three-arm, crossover, randomized trial, 21 volunteers are requested to randomly consume for 1 month: one cup of espresso coffee per day, three cups of espresso coffee per day, or one cup of espresso coffee plus two CBPCC twice per day. The last day of the one-month treatment, blood and urine samples are collected for 24 h. Trigonelline, N-methylpyridinium, N-methylnicotinamide, and N-methyl-4-pyridone-5-carboxamide are quantified. Trigonelline and N-methylpyridinium absorption curves and 24-h urinary excretion reflect the daily consumption of different servings of coffee or CBPCC, showing also significant differences in main pharmacokinetic parameters. Moreover, inter-subject variability due to sex and smoking is assessed, showing sex-related differences in the metabolism of trigonelline and smoking-related ones for N-methylpyridinium. CONCLUSION: The daily exposure to coffee pyridines after consumption of different coffee dosages in a real-life setting is established. This data will be useful for future studies aiming at evaluating the bioactivity of coffee-derived circulating metabolites in cell experiments, mimicking more realistic experimental conditions.

Metabolic tracking of isoflavones in soybean products and biosamples from healthy adults after fermented soybean consumption.

Fermentation may enhance the nutritional properties of foods by increasing metabolite bioactivity or bioavailability. This study explored the effect of fermentation on isoflavone bioavailability and metabolism. Isoflavone metabolites were tracked in foods and biospecimens of healthy adults after fermented soybean (FS) or non-fermented soybean (NFS) consumption in a randomized, controlled, crossover intervention study. The change in soybean isoflavones caused by fermentation resulted in faster absorption and higher bioavailability after consumption of FS. Although the urinary level of total isoflavone metabolites was similar after the consumption of the two diets, urinary genistein 7-O-sulfate was derived as a discriminant metabolite for the FS diet by partial least squares discriminant analysis. This study suggests that an isoflavone conjugate profile might be a more appropriate marker than total isoflavone levels for discriminating between the consumption of FS and NFS diets.

Consumption of anthocyanin-rich beverages affects Nrf2 and Nrf2-dependent gene transcription in peripheral lymphocytes and DNA integrity of healthy volunteers.

Recently, we demonstrated that the consumption of a bolus of bilberry extract modulates the transcription of Nrf2-regulated genes in peripheral blood lymphocytes (PBL) of healthy volunteers, accompanied by decreased DNA-damage. In the present study, we addressed the question whether consumption of consumer-relevant amounts of anthocyanin-rich beverages can achieve similar effects. The impact of three different anthocyanin-rich beverages on Nrf2-dependent gene transcription as well as and the status of DNA-damage in whole blood was investigated. After a polyphenol-reduced diet, five healthy male subjects consumed a bolus (700 mL) of respective test beverages with blood sampling up to 8 h after intake. All beverages affected the transcription of Nrf2, HO-1 and NQO-1, but showed different potencies and persistence of effects. Consumption of red fruit juice significantly reduced total DNA strand breaks (with formamidopyrimidine-DNA-glycosylase-(fpg) treatment) after 8 h in blood samples of the volunteers, suggesting antioxidant and DNA protective effects, albeit transcript levels of Nrf2-dependent genes had reached the basal state. The amount of basic DNA strand breaks (damage without oxidative DNA strand breaks) remained unchanged during the monitoring period. In contrast, a beverage prepared from grape skin extract significantly increased basic and total DNA strand breaks 2 h after intake, underlining the necessity of further investigations regarding composition, safety and consumer´s acceptance of respective products to exclude undesired adverse effects. Consumption of a bolus of anthocyanin-rich beverages affected Nrf2 and Nrf2-dependent gene transcription in human PBL and DNA integrity, which is indicative for systemic effects.

Habitual Intakes, Food Sources and Excretions of Phosphorus and Calcium in Three German Study Collectives.

Phosphorus intake in Europe is far above recommendations. We present baseline data from three human intervention studies between 2006 and 2014 regarding intake and excretion of phosphorus and calcium. All subjects documented their nutritional habits in weighed dietary records. Fasting blood samples were drawn, and feces and urine were quantitatively collected. Dietary phosphorus intake was estimated based on weighed dietary records and urine phosphorus excretions. Food sources were identified by allocation to defined food product groups. Average phosphorus consumption was 1338 mg/day and did not change from 2006 to 2014, while calcium intake decreased during this period (1150 to 895 mg/day). The main sources for phosphorus intake were bread/cereal products, milk/milk products and meat/meat products/sausage products and the main sources of calcium intake included milk/milk products/cheese, bread/cereal products and beverages. There was no difference between estimated phosphorus intake from the weighed dietary records and urine phosphorus excretion. In conclusion, we demonstrated constant phosphorus intakes far above the recommendations and decreasing calcium intakes below the recommendations in three German collectives from 2006 to 2014. Furthermore, we could show in case of usual intakes that an estimated phosphorus intake from urine phosphorus excretion is similar to the calculated intake from weighed dietary records.

Oral administration of nasturtium affects peptide YY secretion in male subjects.

SCOPE: Nasturtium plants contain the glucosinolate glucotropaeolin and its corresponding breakdown product benzyl isothiocyanate (BITC), the latter being intensively studied with regard to cancer chemoprevention and anti-inflammatory properties. In addition, recent research has shown that isothiocyanates are able to activate the release of several gut hormones in vitro and in rodent studies. Here, we tested the effects of a dietary nasturtium administration on circulating levels of gut hormones in humans. METHODS AND RESULTS: Metabolically healthy males (n = 15) received a single oral dose of 10 g freeze-dried nasturtium leaf material suspended in water or only water (control). Blood samples were taken every hour and serum concentrations of insulin, C-peptide, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and peptide (PYY) were analyzed. Oral nasturtium intake resulted in an increased release of PYY over a time period of 6 h whereas circulating levels of other hormones were not changed. CONCLUSION: Given the finding that nasturtium consumption enhances secretion of PYY, a key hormone involved in energy regulation, special diets containing nasturtium, or supplementation with nasturtium or BITC might be considered in the treatment of obesity.

Bioavailability and metabolism of benzyl glucosinolate in humans consuming Indian cress (Tropaeolum majus L.).

SCOPE: Benzyl isothiocyanate (BITC), which occurs in Brassicales, has demonstrated chemopreventive potency and cancer treatment properties in cell and animal studies. However, fate of BITC in human body is not comprehensively studied. Therefore, the present human intervention study investigates the metabolism of the glucosinolate (GSL) glucotropaeolin and its corresponding BITC metabolites. Analyzing BITC metabolites in plasma and urine should reveal insights about resorption, metabolism, and excretion. METHODS AND RESULTS: Fifteen healthy men were randomly recruited for a cross-over study and consumed 10 g freeze-dried Indian cress as a liquid preparation containing 1000 µmol glucotropaeolin. Blood and urine samples were taken at several time points and investigated by LC-ESI-MS/MS after sample preparation using SPE. Plasma contained high levels of BITC-glutathione (BITC-GSH), BITC-cysteinylglycine (BITC-CysGly), and BITC-N-acetyl-L-cysteine (BITC-NAC) 1-5 h after ingestion, with BITC-CysGly appearing as the main metabolite. Compared to human plasma, the main urinary metabolites were BITC-NAC and BITC-Cys, determined 4-6 h after ingestion. CONCLUSION: This study confirms that consumption of Indian cress increases the concentration of BITC metabolites in human plasma and urine. The outcome of this human intervention study supports clinical research dealing with GSL-containing innovative food products or pharmaceutical preparations.

Marginal Ascorbate Status (Hypovitaminosis C) Results in an Attenuated Response to Vitamin C Supplementation.

Inadequate dietary intake of vitamin C results in hypovitaminosis C, defined as a plasma ascorbate concentration ≤23 µmol/L. Our objective was to carry out a retrospective analysis of two vitamin C supplementation studies to determine whether supplementation with 50 mg/day vitamin C is sufficient to restore adequate ascorbate status (≥50 µmol/L) in individuals with hypovitaminosis C. Plasma ascorbate data from 70 young adult males, supplemented with 50 or 200 mg/day vitamin C for up to six weeks, was analyzed. Hypovitaminosis C status was identified based on plasma ascorbate being ≤23 µmol/L and the response of these individuals to vitamin C supplementation was examined. Of the participants consuming 50 mg/day vitamin C for up to six weeks, those with hypovitaminosis C at baseline achieved plasma concentrations of only ~30 µmol/L, whereas the remainder reached ~50 µmol/L. Participants who consumed 200 mg/day vitamin C typically reached saturating concentrations (>65 µmol/L) within one week, while those with hypovitaminosis C required two weeks to reach saturation. Regression modelling indicated that the participants' initial ascorbate status and body weight explained ~30% of the variability in the final ascorbate concentration. Overall, our analysis revealed that supplementation with 50 mg/day vitamin C, which resulted in a total dietary vitamin C intake of 75 mg/day, was insufficient to achieve adequate plasma ascorbate concentrations in individuals with hypovitaminosis C. Furthermore, increased body weight had a negative impact on ascorbate status.

The capsaicin analog nonivamide decreases total energy intake from a standardized breakfast and enhances plasma serotonin levels in moderately overweight men after administered in an oral glucose tolerance test: a randomized, crossover trial.

SCOPE: Since bolus administration of capsaicin has been shown to reduce appetite and ad libitum energy intake, this study elucidated the satiating effect of the less pungent capsaicin analog, nonivamide, on subjective feelings of hunger, ad libitum food intake, and satiating hormones in moderately overweight male subjects. METHODS AND RESULTS: Following a randomized, crossover design, 24 male subjects (BMI 27.5 ± 1.53 kg/m(2) ) received either 75 g glucose in 300 mL water (control treatment, CT) or the same glucose solution supplemented with 0.15 mg nonivamide (nonivamide treatment, NT). Ratings of hunger were assessed before and 2 h after each intervention by means of visual analog scales. Ad libitum energy and macronutrient intakes from a standardized breakfast 2 h postintervention were calculated. Plasma glucose, insulin, peptide YY (3-36), glucagon-like peptide 1, and serotonin were quantified in blood samples drawn before and 15, 30, 60, 90, and 120 min after each intervention. NT reduced subjective feelings of hunger and ad libitum energy and carbohydrate intakes from a standardized breakfast compared to CT. Plasma analysis revealed higher mean plasma glucagon-like peptide 1 and serotonin concentrations after NT versus CT. CONCLUSION: Addition of 0.15 mg nonivamide to a glucose solution reduced ad libitum energy intake from a standardized breakfast in moderately overweight men.