Brain activity and connectivity changes in response to nutritive natural sugars, non-nutritive natural sugar replacements and artificial sweeteners.

INTRODUCTION: The brain plays an important regulatory role in directing energy homeostasis and eating behavior. The increased ingestion of sugars and sweeteners over the last decades makes investigating the effects of these substances on the regulatory function of the brain of particular interest. We investigated whole brain functional response to the ingestion of nutrient shakes sweetened with either the nutritive natural sugars glucose and fructose, the low- nutritive natural sugar replacement allulose or the non-nutritive artificial sweetener sucralose. METHODS: Twenty healthy, normal weight, adult males underwent functional MRI on four separate visits. In a double-blind randomized study setup, participants received shakes sweetened with glucose, fructose, allulose or sucralose. Resting state functional MRI was performed before and after ingestion. Changes in Blood Oxygen Level Dependent (BOLD) signal, functional network connectivity and voxel based connectivity by Eigenvector Centrality Mapping (ECM) were measured. RESULTS: Glucose and fructose led to significant decreased BOLD signal in the cingulate cortex, insula and the basal ganglia. Glucose led to a significant increase in eigen vector centrality throughout the brain and a significant decrease in eigen vector centrality in the midbrain. Sucralose and allulose had no effect on BOLD signal or network connectivity but sucralose did lead to a significant increase in eigen vector centrality values in the cingulate cortex, central gyri and temporal lobe. DISCUSSION: Taken together our findings show that even in a shake containing fat and protein, the type of sweetener can affect brain responses and might thus affect reward and satiety responses and feeding behavior. The sweet taste without the corresponding energy content of the non-nutritive sweeteners appeared to have only small effects on the brain. Indicating that the while ingestion of nutritive sugars could have a strong effect on feeding behavior, both in a satiety aspect as well as rewarding aspects, non-nutritive sweeteners appear to not have these effects. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov under number NCT02745730.

The acute effect of black tea consumption on resistance artery endothelial function in healthy subjects. A randomized controlled trial.

BACKGROUND & AIMS: Black tea is a main source of flavonoids in the Western diet and has been associated with reduced risk for cardiovascular disease, possibly through lowering blood pressure. These effects may be mediated through improving endothelial function of resistance arteries. The aim of this study was therefore to examine the acute impact of black tea on forearm resistance artery endothelial function in healthy, normotensive middle-aged subjects. METHODS: Twenty middle-aged men and women (age-range 45-75 years) were recruited into a double-blind, randomized, placebo-controlled crossover intervention study. Forearm resistance artery blood flow (FBF, measured using venous occlusion plethysmography) in response to incremental doses of acetylcholine, sodium nitroprusside and L-NG-monomethyl arginine were determined 2 h after consumption of either black tea containing ∼400 mg flavonoids (equivalent to 2-3 cups of tea) or a taste- and color-matched placebo. RESULTS: The mean FBF-response to acetylcholine after tea consumption was 23% higher compared to the response after placebo (95% CI: -20%, +88%), but this difference did not reach statistical significance (P = 0.32). No significant differences in the FBF-responses to sodium nitroprusside and L-NG-monomethyl arginine were found between the tea and placebo interventions (P = 0.96 and 0.74, respectively). Correcting FBF for changes in blood pressure did not alter the outcomes. CONCLUSIONS: We found no evidence that acute intake of black tea significantly altered endothelium-dependent vasodilation of forearm resistance arteries in healthy middle-aged subjects. Interventions with a longer duration of tea ingestion are required to further explore the (long-term) impact of tea flavonoids on blood pressure regulatory mechanisms. This trial was registered at clinicaltrials.gov as NCT02328339.

Impact of flavonoid-rich black tea and beetroot juice on postprandial peripheral vascular resistance and glucose homeostasis in obese, insulin-resistant men: a randomized controlled trial.

BACKGROUND: Insulin-stimulated muscle blood flow facilitates plasma glucose disposal after a meal, a mechanism that is impaired in obese, insulin-resistant volunteers. Nitrate- or flavonoid-rich products, through their proposed effects on nitric oxide, may improve postprandial blood flow and, subsequently, glucose disposal. To investigate whether a single dose of nitrate-rich beetroot juice or flavonoid-rich black tea lowers postprandial muscle vascular resistance in obese volunteers and alters postprandial glucose or insulin concentrations. METHOD: In a randomised, controlled, cross-over study, 16 obese, insulin-resistant males consumed 75 g glucose, which was combined with 100 ml black tea, beetroot juice or control (water). Peripheral vascular resistance (VR), calculated as mean arterial pressure divided by blood flow, was assessed in the arm and leg conduit arteries, resistance arteries and muscle microcirculation across 3 h (every 30-min) after the oral glucose load. RESULTS: During control, we found no postprandial response in VR in conduit, resistance and microvessels (all P > 0.05). Black tea decreased VR compared to control in conduit, resistance and microvessels (all P < 0.05). Beetroot juice decreased postprandial VR in resistance vessels, but not in conduit artery and microvessels. Although postprandial glucose response was similar after all interventions, postprandial insulin response was attenuated by ~29 % after tea (P < 0.0005), but not beetroot juice. CONCLUSIONS: A single dose of black tea decreased peripheral VR across upper and lower limbs after a glucose load which was accompanied by a lower insulin response. Future studies in insulin-resistant subjects are warranted to confirm the observed effects and to explore whether long-term regular tea consumption affects glucose homeostasis. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov on 30(th) November 2012 (NCT01746329).

Plant-rich mixed meals based on Palaeolithic diet principles have a dramatic impact on incretin, peptide YY and satiety response, but show little effect on glucose and insulin homeostasis: an acute-effects randomised study.

There is evidence for health benefits from 'Palaeolithic' diets; however, there are a few data on the acute effects of rationally designed Palaeolithic-type meals. In the present study, we used Palaeolithic diet principles to construct meals comprising readily available ingredients: fish and a variety of plants, selected to be rich in fibre and phyto-nutrients. We investigated the acute effects of two Palaeolithic-type meals (PAL 1 and PAL 2) and a reference meal based on WHO guidelines (REF), on blood glucose control, gut hormone responses and appetite regulation. Using a randomised cross-over trial design, healthy subjects were given three meals on separate occasions. PAL2 and REF were matched for energy, protein, fat and carbohydrates; PAL1 contained more protein and energy. Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and peptide YY (PYY) concentrations were measured over a period of 180 min. Satiation was assessed using electronic visual analogue scale (EVAS) scores. GLP-1 and PYY concentrations were significantly increased across 180 min for both PAL1 (P= 0·001 and P< 0·001) and PAL2 (P= 0·011 and P= 0·003) compared with the REF. Concomitant EVAS scores showed increased satiety. By contrast, GIP concentration was significantly suppressed. Positive incremental AUC over 120 min for glucose and insulin did not differ between the meals. Consumption of meals based on Palaeolithic diet principles resulted in significant increases in incretin and anorectic gut hormones and increased perceived satiety. Surprisingly, this was independent of the energy or protein content of the meal and therefore suggests potential benefits for reduced risk of obesity.

Effects of black tea on body composition and metabolic outcomes related to cardiovascular disease risk: a randomized controlled trial.

UNLABELLED: There is increasing evidence that tea and its non-caffeine components (primarily flavonoids) contribute to cardiovascular health. Randomized controlled trials have shown that tea can improve cardiovascular disease risk factors. We have previously reported a non-caffeine associated beneficial effect of regular black tea consumption on blood pressure and its variation. OBJECTIVE: To explore the non-caffeine associated effects of black tea on body weight and body fat distribution, and cardiovascular disease related metabolic outcomes. DESIGN: regular tea-drinking men and women (n = 111; BMI 20-35 kg m(-2)) were recruited to a randomized controlled double-blind 6 month parallel-designed trial. Participants consumed 3 cups per day of either powdered black tea solids (tea) or a flavonoid-free flavour- and caffeine-matched placebo (control). Body weight, waist- and hip-circumference, endothelial function and plasma biomarkers were assessed at baseline, 3 months and 6 months. RESULTS: Compared to control, regular ingestion of black tea over 3 months inhibited weight gain (-0.64 kg, p = 0.047) and reduced waist circumference (-1.88 cm, P = 0.035) and waist-to-hip ratio (-0.03, P = 0.005). These effects were no longer significant at 6 months. There were no significant effects observed on fasting glucose, insulin, plasma lipids or endothelial function. CONCLUSION: Our study suggests that short-term regular ingestion of black tea over 3 months can improve body weight and body fat distribution, compared to a caffeine-matched control beverage. However, there was no evidence that these effects were sustained beyond 3 months.

Theaflavins from black tea, especially theaflavin-3-gallate, reduce the incorporation of cholesterol into mixed micelles.

Tea is one of the most widely consumed beverages in the world and may be associated with reduced heart disease rates. Theaflavins, which are formed in the production of black tea, have been suggested being responsible for the blood-cholesterol-lowering (BCL) effects of tea. We hypothesized that the effect of theaflavins on BCL could be through interference in the formation of dietary mixed micelles, which could result in reduced intestinal cholesterol absorption. Micelles were produced by mixing oleic acid, bile acids, lyso-phosphatidylcholine, and cholesterol. Theaflavin-treated micelles/particles were analyzed using electron microscopy (cryo-TEM), high-performance liquid chromatography (HPLC) analysis, and light-scattering particle size measurements. A dose-dependent inhibitory effect of theaflavins on the incorporation of (14)C-labeled cholesterol into micelles and a theaflavin-dependent increase in particle size was found. These particles consisted of insoluble large multilamellar vesicles with onion-like structures. Ultracentrifugation and HPLC analysis revealed that the pellets contained mainly theaflavin-3-gallate, while the remaining theaflavins were found to be present in the supernatant. Using purified theaflavin subtypes confirmed that mainly theaflavin-3-gallate is responsible for multilamellar vesicle formation. These results show that theaflavins can play a role in decreased intestinal cholesterol absorption via inhibition of micelle formation.

Metabonomics approach to determine metabolic differences between green tea and black tea consumption.

The purpose of this study was to compare the effects of black and green tea consumption on human metabolism. Seventeen healthy male volunteers consumed black tea, green tea, or caffeine in a randomized crossover study. Twenty-four-hour urine and blood plasma samples were analyzed by NMR-based metabonomics, that is, high-resolution 1H NMR metabolic profiling combined with multivariate statistics. Green and black tea consumption resulted in similar increases in urinary excretion of hippuric acid and 1,3-dihydroxyphenyl-2-O-sulfate, both of which are end products of tea flavonoid degradation by colonic bacteria. Several unidentified aromatic metabolites were detected in urine specifically after green tea intake. Interestingly, green and black tea intake also had a different impact on endogenous metabolites in urine and plasma. Green tea intake caused a stronger increase in urinary excretion of several citric acid cycle intermediates, which suggests an effect of green tea flavanols on human oxidative energy metabolism and/or biosynthetic pathways.

Nuclear magnetic resonance spectroscopic based studies of the metabolism of black tea polyphenols in humans.

Epidemiological studies indicate that a high intake of flavonoids is associated with an improved health status. Tea is one of the most abundant sources of flavonoids in the human diet. The bioavailability and biotransformation of tea flavonoids are, however, not clearly understood. The aim of the present study was to investigate the metabolism of black tea via a nonspecific screening method. (1)H nuclear magnetic resonance (NMR) spectroscopy was used to obtain nonselective profiles of urine samples collected from three human volunteers before and after a single dose of black tea. The complex spectroscopic profiles were interpreted with the use of pattern recognition techniques. Hippuric acid was confirmed as the major urinary black tea metabolite. One previously unknown metabolite was detected and identified as 1,3-dihydroxyphenyl-2-O-sulfate (sulfate conjugate of pyrogallol) using HPLC directly coupled to mass spectrometry and (1)H NMR spectroscopy. This study shows that NMR-pattern recognition studies can be used for the discovery of unknown flavonoid metabolites in humans.

Consumption of both black tea and green tea results in an increase in the excretion of hippuric acid into urine.

BACKGROUND: A major portion of the catechins in green tea is not absorbed in the small intestine. Bacteria in the colon convert nonabsorbed catechins into simpler phenolic compounds, which may also be absorbed. During the production of black tea, most catechins are polymerized to complex molecules called thearubigins. Little is known about the microbial degradation of these complex polyphenols, but hippuric acid has been identified as a major excretion product associated with black tea consumption. OBJECTIVE: To investigate whether green tea and black tea have the same metabolic fate in humans. DESIGN: Seventeen healthy male volunteers were studied with a randomized, full-crossover design. Each intervention period lasted 4 d, ie, a 2-d run-in period with a low-polyphenol diet followed by a 2-d treatment period. Volunteers consumed a daily dose of 6 g green tea solids, 6 g black tea solids, or 360 mg caffeine. Intervention periods were separated by a 10-d washout period. Twenty-four-hour urine samples were collected during the second day of each treatment period. Hippuric acid was analyzed with HPLC-tandem mass spectrometry. RESULTS: The mean excretion of urinary hippuric acid during black tea and green tea consumption was 3.75 +/- 0.28 mmol/24 h and 4.22 +/- 0.28 mmol/24 h, respectively (95% CI for the difference: -0.37 to +1.30 mmol/24 h). The hippuric acid excretion during the control treatment was much lower (1.89 +/- 0.28 mmol/24 h; P < 0.0001, compared with both black tea and green tea). CONCLUSION: The ingestion of either green tea or black tea results in a major increase in the excretion of hippuric acid into urine.

NMR-based metabonomic studies on the biochemical effects of epicatechin in the rat.

Flavonoid consumption via tea drinking has been attributed a number of potential health benefits including cancer prevention, anti-inflammatory action, and cardioprotectant activity. Although the predominant flavonoids in fresh leaf and green tea are known to be flavan-3-ols and flavan-3-O-gallates ("the catechins"), the biochemical effects of tea polyphenol consumption on living systems are generally poorly understood. Metabonomic methods utilizing (1)H NMR spectroscopy of biofluids and principal component analysis (PCA) have been applied to investigate the bioavailability and metabolic responses of rats to a single dose of 22 mg of epicatechin (EC) dissolved in water. Urine samples were collected twice daily (0-8 and 8-24 h) from male Sprague-Dawley rats (n = 10) prior to dosing and for 2 days after dosing. A series of subtle urinary biochemical effects were evident from the (1)H NMR spectra showing that EC was both bioavailable and biochemically active. The identifiable biochemical effects associated with EC dosing included decreased urinary concentrations of taurine, citrate, dimethylamine, and 2-oxoglutarate. These effects were predominately seen within the first 8 h after dosing. EC metabolites were also observed in the urine during this time period. PCA of later time points after dosing (24-32 and 32-48 h) showed that the effects of EC were reversible. This is the first in vivo study demonstrating the overall endogenous metabolic effects of EC consumption and shows the bioavailability of EC via metabolic effects and excretion of EC metabolites.

Glutathione and glutathione S-transferases A1-1 and P1-1 in seminal plasma may play a role in protecting against oxidative damage to spermatozoa.

OBJECTIVE: To study the levels of glutathione, glutathione S-transferase A1-1, and glutathione S-transferase P1-1 in seminal fluid of fertile and subfertile men. DESIGN: Retrospective case-control study. SETTING: Departments of gastroenterology, obstetrics and gynecology, and epidemiology and biostatistics in a university medical center. PATIENT(S): Twenty-five subfertile men visiting the fertility clinic and 25 fertile men from midwife practices were recruited. INTERVENTION(S): Collection of semen of subfertile and fertile men. MAIN OUTCOME MEASURE(S): Plasma levels of glutathione and glutathione S-transferases A1-1 and P1-1 in relation to seminal characteristics. RESULT(S): Glutathione, glutathione S-transferase A1-1, as well as glutathione S-transferase P1-1 were found in considerable amounts in seminal fluid of subfertile and fertile men. No differences between groups were found for glutathione S-transferases A1-1 and P1-1. Also, no associations with sperm count, motility, or morphology could be detected. Fertile men had significantly higher glutathione levels as compared with the case of subfertile men. Associations of glutathione with sperm motility quality (r(s) = 0.321) and abnormal sperm morphology (r(s) = -0.496) were found. CONCLUSION(S): The presence of glutathione S-transferases A1-1 and P1-1 in seminal fluid suggests a role in the protection against (oxidative) damage of spermatozoa, whereas glutathione may play a role in male fertility.