Control Drink Research Articles

Acute effects of whey protein, alone and mixed with other macronutrients, on blood pressure and heart rate in older men

BackgroundCaloric supplements are increasingly used by older people, aiming to increase their daily protein intake. These high caloric drinks, rich in glucose and whey-protein in particular, may result in potential harmful decreases in blood pressure (BP). The effect of ingesting whey-protein with glucose and fat on BP is unknown. It has also been assumed that the maximum fall in systolic blood pressure occurs within 2 h of a meal.MethodsThis study aimed to determine in older men, the effects of whey-protein, alone and mixed with other macronutrients, on systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR) in older men for 3 h. Thirteen older men (age 75 ± 2yrs; body mass index (BMI) 25.6 ± 0.6 kg/m2) ingested a drink on separate study days: (i) 70 g whey-protein (P280); (ii) 14 g whey-protein, 28 g carbohydrate, 12.4 g fat (M280); (iii) 70 g whey-protein, 28 g carbohydrate, 12.4 g fat (M504); or (iv) a non-caloric control drink (C).ResultsSBP decreased after all three nutrient drinks compared to the C, with the greatest reduction after the M504 drink (P = 0.008). Maximal decreases in SBP (C: -14 ± 2 mmHg, P280: -22 ± 2 mmHg, M280: -22 ± 4 mmHg, M504: -24 ± 3 mmHg) occurred about 2 h after drink ingestion and this fall was sustained thereafter (120-180 min: P280 and M504 vs. C P < 0.05). Maximum DBP decreases and HR increases occurred after M504, with no differences between the effects of the P280 and M280 drinks.ConclusionsThe effects of whey-protein containing drinks to lower BP and increase HR appear to be primarily dependent on their energy content rather than macronutrient composition and may persist for at least 3 h after ingestion,. Pure whey-protein drinks may represent the best approach to maximize protein intake without increasing the potential for deleterious BP falls in older people.Trial registrationACTRN12614000846628, 14/03/2019.

The impact of alcohol priming on craving and motivation to drink: a meta-analysis.

An initial dose of alcohol can motivate-or prime-further drinking and may precipitate (re)lapse and bingeing. Lab-based studies have investigated the alcohol priming effect; however, heterogeneity in designs has resulted in some inconsistent findings. The aims of this meta-analysis were to (i) determine the pooled effect size for motivation to drink following priming, measured by alcohol consumption and craving, and (ii) examine whether design characteristics influenced any priming effect. Literature searches of PsycINFO, PubMed and Scopus in October 2020 (updated October 2021) identified lab-based alcohol priming studies that assessed effect of priming on motivation to drink. A tailored risk-of-bias tool assessed quality of lab-based studies. Random effects meta-analyses were computed on outcome data from 38 studies comparing the effect of a priming dose of alcohol against control on subsequent alcohol consumption/self-reported craving. Study characteristics that might have affected outcomes were design type (within/between-participant), dose of prime, time of motivation assessment, type of control drink (placebo alcohol/soft drink). Relative to control, alcohol had a small-to-moderate priming effect on subsequent alcohol consumption (standardised mean difference [SMD] = 0.336 [95% CI, 0.171, 0.500]) and craving (SMD = 0.431 [95% CI, 0.306, 0.555]). Aspects of study design differentially affected consumption and craving. The size of the priming dose had no effect on consumption, but larger doses were sometimes associated with greater craving (with craving generally following the blood alcohol curve). Alcohol priming effects for consumption, but not craving, were smaller when compared with placebo, relative to soft drink, control. Lab-based alcohol priming studies are a valid paradigm from which to investigate the impact of acute intoxication on alcohol motivation. Designs are needed that assess the impact of acute consumption on motivation to drink in more varied and realistic ways.

Purple grape juice improves performance of recreational runners, but the effect is genotype dependent: a double blind, randomized, controlled trial

BackgroundWe examined the influence of superoxide dismutase 3 (SOD3) Arg213Gly and Peroxisome Proliferator-Activated α-Receptor (PPARα) 7G/C polymorphisms to a single dose of purple grape juice supplementation on time-to-exhaustion running test, redox balance and muscle damage in recreational runners.MethodsForty-seven male recreational runners performed a running test until exhaustion after supplementation with grape juice or a control drink. Serum total antioxidant capacity (TAC), malondialdehyde (MDA), plasma nitrite (NO), creatine kinase (CK) and lactate dehydrogenase (LDH) were measured pre and post exercise. Also, polymorphisms were analyzed in DNA extracted from the oral mucosa.ResultsGrape juice improved the time-to-exhaustion. When analyzed by genotype, the recreational runners with GG+CG genotypes of the SOD3 gene had greater time-to-exhaustion than the CC genotype, but was no different for the PAPRα gene. A slight difference was noted in TAC, since the CC genotype of the SOD3 gene showed higher TAC values in the post-exercise compared to the baseline and with pre-exercise, but these values did not increase compared to the CG+GG group, respectively. The SOD3 and PPARα genes were similar at all times for the other biochemical variables.ConclusionThe ergogenic effect of grape juice was genotype-dependent for SOD3 Arg213Gly. However, biochemical redox balance markers did not explain this difference.

Grapefruit Juice Flavanones Modulate the Expression of Genes Regulating Inflammation, Cell Interactions and Vascular Function in Peripheral Blood Mononuclear Cells of Postmenopausal Women.

Grapefruit is a rich source of flavanones, phytochemicals suggested excreting vasculoprotective effects. We previously showed that flavanones in grapefruit juice (GFJ) reduced postmenopausal women’s pulse-wave velocity (PWV), a measure of arterial stiffness. However, mechanisms of flavanone action in humans are largely unknown. This study aimed to decipher molecular mechanisms of flavanones by multi-omics analysis in PBMCs of volunteers consuming GFJ and flavanone-free control drink for 6 months. Modulated genes and microRNAs (miRNAs) were identified using microarrays. Bioinformatics analyses assessed their functions, interactions and correlations with previously observed changes in PWV. GFJ modified gene and miRNA expressions. Integrated analysis of modulated genes and miRNA-target genes suggests regulation of inflammation, immune response, cell interaction and mobility. Bioinformatics identified putative mediators of the observed nutrigenomic effect (STAT3, NF-κB) and molecular docking demonstrated potential binding of flavanone metabolites to transcription factors and cell-signaling proteins. We also observed 34 significant correlations between changes in gene expression and PWV. Moreover, global gene expression was negatively correlated with gene expression profiles in arterial stiffness and hypertension. This study revealed molecular mechanisms underlying vasculoprotective effects of flavanones, including interactions with transcription factors and gene and miRNA expression changes that inversely correlate with gene expression profiles associated with cardiovascular risk factors.Clinical Trial Registration[ClinicalTrials.gov], identifier [NCT01272167].

Preferences for oral rehydration drinks among healthy individuals in Ghana: A single-blind, cross-sectional survey to inform implementation of an enterally based resuscitation protocol for burn injury

BackgroundEnterally based resuscitation for major burn injuries has been suggested as a simple, operationally superior, and effective resuscitation strategy for use in austere contexts. However, key information to support its implementation is lacking, including palatability and acceptability of widely available rehydration drinks. MethodsWe performed a single-blinded, cross-sectional survey of 60 healthy children (5–14 years), adults (15–54 years) and older adults (≥55 years) to determine palatability and overall acceptability of five oral rehydration solutions (ORS) and a positive control drink (Sprite Zero®) in Ghana. Quantitative data were described and differences between our control drink and the others across age groups were visually examined with Likert plots. Qualitative responses were analyzed using a content analysis framework. ResultsTwenty participants in each age group completed the study. Participants were as young as 5 years and as old as 84 years. Nearly two thirds of the sample identified as male (n = 38, 63% of all participants). The positive control was reported to taste ‘good or ‘very good’ by the majority of participants (89%) followed by lemon-flavored ORS (78%) and orange-flavored ORS (78%). Conversely, homemade and low-osmolarity ORS were reported to taste ‘good’ or ‘very good’ by only 20% and 15% of participants, respectively. There were no major taste differences across the age groups. However, children more frequently reported positively (i.e., tastes ‘good’ or ‘very good’) about flavored and sweet drinks than did adults and older adults. When faced with the hypothetical situation of being critically injured and needing resuscitation, participants tended to be more agreeable to consuming all the drinks, even low-osmolarity and homemade ORS. ConclusionsThese findings can be used to support the development of protocols that may be more acceptable among patients undergoing enterally based resuscitation, thus improving the effectiveness of the treatment. Specifically, enterally based resuscitation should likely include citrus-flavored ORS when available, given superior palatability and the fact that different flavor additives for patients of different ages do not seem necessary.

Does acute alcohol consumption increase risk-taking while gambling? A systematic review and meta-analysis.

To estimate the effect of acute alcohol consumption on risk-taking while gambling, examine blood alcohol concentration as a moderator and explore possible moderators of this effect. A systematic review and meta-analysis was completed. A Boolean search strategy was used to identify studies that included (a) alcohol consumption as an independent variable; (b) a gambling or risk-taking task; (c) a control or placebo comparison; (d) human participants; and (e) English publications. Descriptive information, sample characteristics and experimental data were extracted from each study. Searched databases included: PsycINFO, Web of Science, Medline, Cochrane Library and ProQuest Dissertations and Theses. Included as participants were experiments that compared the effects of alcohol and non-alcoholic or placebo beverages on risk-taking while gambling. Comprehensive Meta-Analysis version 3.3.070 was used. Standardized mean differences of risk-taking while gambling between the experimental and control conditions were calculated when studies did not report effect sizes. Random-effects models were used for overall effect and meta-regressions while mixed-effects models were used for subgroup analyses. Twenty articles containing 47 alcohol versus control comparisons met inclusion criteria. The overall Hedges'g for the difference between groups consuming alcohol and groups consuming a placebo or non-alcoholic drink control was 0.03, 95% confidence interval (CI) = -0.07, 0.12, p = 0.60, indicating no significant difference. Larger effect sizes were found for studies using non-alcoholic control drinks (Hedges' g = 0.30, 95% CI = 0.01, 0.58) compared to placebo beverages (Hedges' g = -0.03, 95% CI = -0.13, 0.06), Cochran's Q= 4.67, p = 0.03. Finding that acute alcohol consumption had no reliable effect on risk-taking while gambling was consistent with existing animal research. No support was found for the relation between alcohol dose and risk-taking. The significantly larger effect size for experiments using non-alcoholic versus placebo beverages suggests the potential role of expectancy effects.

Co-pigmentation with catechin derived from Indonesian gambier increases the stability of black rice anthocyanin in isotonic sports drinks during one-month storage in 4°C

Anthocyanins are water-soluble pigments, which are found abundantly in plants. However, anthocyanins are unstable and break due to several factors. The stability of anthocyanins could be increased by applying co-pigmentation with the addition of flavonoids, polyphenols, alkaloids, amino acids, organic acids, or self-association. This study aimed to observe the effect of co-pigmentation with catechin from Indonesian gambier (Uncaria gambir) to enhance the stability and antioxidant activity of black rice anthocyanin in isotonic sports drink during storage. Anthocyanins extracted from black rice (30 mg/L) were used for isotonic sports drink formulation. The addition of 0.1 μg/L catechins to the drink with catechin: drink ratio (1:1) significantly increased antioxidant activity (89.30±1.12%). In a storage period of one month at room temperature (25oC), anthocyanin content and antioxidant activity in isotonic sports drinks showed a significant decrease than that at 4oC. Catechin co-pigmentation in the drinks increased anthocyanin stability and antioxidant activity compared to that of control (drinks without catechin). In conclusion, co-pigmentation with catechin derived from Indonesian gambier could be applied to enhance the stability and antioxidant activity of black rice anthocyanin in isotonic sports drink during storage at cold temperature (4oC) for one month.

Fermented Carrot Pulp Regulates the Dysfunction of Murine Intestinal Microbiota.

It was the focus of attention that probiotic control drink was packed with prebiotic nutrients and lactic acid bacteria. So, this study is aimed at revealing that the fermented carrot pulp regulation and protection function to the intestinal microecological disorders usually induced by antibiotic treatment. First, we study on lactobacillus fermentation conditions and effects on the secondary metabolism of fermented carrot juice, get its phenolic acids up, and get its flavonoids down. Then, establishment of the dysbacteriosis mouse model was used to validate the fermented carrot pulp prevention and treatment of intestinal microbiota imbalance. After the antibiotic treatment, the mice showed impotence, laziness, slow movement, weight loss, thin feces, dull hair, and anal redness, while the mice in the control group were all normal in terms of the mental state, diet, weight, and bowl movement. Along with the treatment, the abnormal conditions of the mice in the model group and natural recovery group improved in different degrees, indicating that the fermentation treatment is of help to the intestinal microbiota recovery. The fermentation-treated group of mice recovered close to normal that the diarrhea disappeared, and the weight gain, mental state, and the feces became normal. The serum antioxidant (SOD, GSH, and MDA) levels of the mice were checked. The superoxide dismutase (SOD) levels and glutathione (GSH) levels in the ordinary fermentation-treated group and probiotic fermentation-treated group were significantly increased compare to the natural recovery group. The malondialdehyde (MDA) levels showed great differences between the fermentation-treated groups and the blank group. At last, the 16sRNA analysis revealed that the microbiota richness and diversity in probiotic fermentation (J) are much higher than those in the model group (H), ordinary fermentation group (I), and blank group (G). Groups J and I are of significantly higher antioxidant level than group H; however, only the glutathione (GSH) level in group J increased dramatically but not those in the other three groups. Antibiotic treatment-induced mouse intestinal microecological disorder reduce the microbiota richness and diversity. Prebiotics fermented carrot pulp treatment can help in the recovery from the microbiota richness and diversity level prior to the antibiotic treatment, which suggests it can regulate and protect the murine intestinal microbiome.

Acute effects of energy drink consumption on left and right ventricular function - a 2-dimensional speckle tracking echocardiographic study.

Aim Energy drinks (ED) contain high levels of caffeine and taurine and are associated with several cardiovascular effects. We investigated acute effects of consuming low caffeine and taurine content ED on left ventricular (LV) and right ventricular (RV) function assessed by conventional and two-dimensional speckle tracking echocardiography.Material and methods In this crossover study, 34 healthy adults, age 19-48 yrs, drank an ED containing 53.25 milligrams of caffeine, 284 mg of taurine, or an equal volume of control drink (CD) on two separate sessions, 7-10 days apart. Standard echocardiographic and speckle tracking imaging were performed before and 60 min after consumption of the study beverages.Results Compared to CD, ED caused a significant increase in tricuspid annular plane systolic excursion (p=0.04) and RV systolic wave velocity (p=0.01) with no effect on global longitudinal strain when compared to CD. LV systolic function was not altered, but mitral early diastolic velocity by tissue Doppler imaging was significantly higher (p=0.031), and early diastolic strain rate, as measured by speckle tracking echocardiography, was significantly lower (p=0.022).Conclusion Reduced caffeine and taurine content ED does not affect LV systolic function, but increases RV longitudinal contractility and improves LV early diastolic filling.

Dietary Nitrate Supplementation Does Not Alter Exercise Efficiency at High Altitude - Further Results From the Xtreme Alps Study.

IntroductionNitrate supplementation in the form of beetroot juice (BRJ) ingestion has been shown to improve exercise tolerance during acute hypoxia, but its effect on exercise physiology remains unstudied during sustained terrestrial high altitude exposure. We hypothesized that performing exercise at high altitude would lower circulating nitrate and nitrite levels and that BRJ ingestion would reverse this phenomenon while concomitantly improving key determinants of aerobic exercise performance.MethodsTwenty seven healthy volunteers (21 male) underwent a series of exercise tests at sea level (SL, London, 75 m) and again after 5–8 days at high altitude (HA, Capanna Regina Margherita or “Margherita Hut,” 4,559 m). Using a double-blind protocol, participants were randomized to consume a beetroot/fruit juice beverage (three doses per day) with high levels of nitrate (∼0.18 mmol/kg/day) or a nitrate-depleted placebo (∼11.5 μmoles/kg/day) control drink, from 3 days prior to the exercise trials until completion. Submaximal constant work rate cycle tests were performed to determine exercise efficiency and a maximal incremental ramp exercise test was undertaken to measure aerobic capacity, using breath-by-breath pulmonary gas exchange measurements throughout. Concentrations of nitrate, nitrite and nitrosation products were quantified in plasma samples collected at 5 timepoints during the constant work rate tests. Linear mixed modeling was used to analyze data.ResultsAt both SL and HA, plasma nitrate concentrations were elevated in the nitrate supplementation group compared to placebo (P < 0.001) but did not change throughout increasing exercise work rate. Delta exercise efficiency was not altered by altitude exposure (P = 0.072) or nitrate supplementation (P = 0.836). V̇O2peak decreased by 24% at high altitude (P < 0.001) and was lower in the nitrate-supplemented group at both sea level and high altitude compared to placebo (P = 0.041). Dietary nitrate supplementation did not alter other peak exercise variables or oxygen consumption at anaerobic threshold. Circulating nitrite and S-nitrosothiol levels unexpectedly rose in a few individuals right after cessation of exercise at high altitude.ConclusionWhilst regularly consumed during an 8 days expedition to terrestrial high altitude, nitrate supplementation did not alter exercise efficiency and other exercise physiological variables, except decreasing V̇O2peak. These results and those of others question the practical utility of BRJ consumption during prolonged altitude exposure.

Efficacy of L-Arabinose in Lowering Glycemic and Insulinemic Responses: The Modifying Effect of Starch and Fat.

L-arabinose is a bio-active compound derived from the side-streams of plant food processing. L-arabinose lowers glycemic and insulinemic responses when added to simple water-based sugary liquids. However, the effect in more complex foods, including fat and starch, is inconsistent. This study assessed the effect of fat or starch in a sugary drink on the efficacy of L-arabinose. Twenty-three healthy volunteers (12 female/11 male; aged 24 ± 3 years; BMI 23 ± 3 kg/m2) participated in a randomised cross-over trial with six drinks: control: 50 g sucrose in water; fat: control + 22 g oil; starch: control + 50 g starch; and all three with and without the addition of 5 g L-arabinose. The addition of L-arabinose to the control drink lowered glucose and insulin peaks by 15% and 52%; for the fat drink by 8% and 45%; and for the starch drink by 7% and 29%. For all three drinks, adding L-arabinose increased glucagon-like peptide 1 (GLP-1) responses and lowered Glucose-dependent insulinotropic polypeptide (GIP) responses. Despite adding large quantities of starch and fat to sugary drinks, L-arabinose significantly lowered postprandial glycemic and insulinemic responses in healthy subjects. These findings suggest that L-arabinose can be functional in more complex foods; however, the factors affecting its efficacy in solid food matrices need to be studied in more detail.

SYNBIOTIC FUNCTIONAL DRINK FROM COW MILK FERMENTED WITH KEFIR AND SUPPLEMENTED WITH INULIN

Increasing awareness on health has increased demand for healthy food confirmed by raising market sales of functional food. This study aims to develop a new synergetic drink from cow milk fermented by kefir grains and supplemented by inulin. Firstly, the inulin was isolated from dahlia flower tuber while fresh cow milk was incubated with kefir grains to produce kefir probiotic drink. Next, inulin with different concentrations was added to the probiotic drink and was fermented for 48 hours at room temperature generating a symbiotic functional drink. Analysis of antimicrobial properties revealed that synbiotic drinks have antimicrobial activity and the colony unit bacteria was met the standard to be claimed as a probiotic supplement. The microbiology and physicochemical properties of kefir synbiotic drink were analyzed and the result showed better properties than the control. There was no significant difference in taste between control and kefir enriched inulin drink assessed by the panelist. Only kefir synbiotic drink supplemented by inulin of 3 and 5% determined has a significant difference in aroma. Based on that kefir enriched inulin drink has the potency to be used as a functional drink that has a synergistic combination of prebiotics and probiotics.

Binge Drinking, Alone or With Cannabis, During Adolescence Triggers Different Effects on Immediate Visual Memory in Men and Women.

Background: This study examines the interaction between a history of binge drinking (BD), alone or with cannabis consumption, and the effects of acute alcohol exposure on immediate visual memory (IVM) (faces memory task, scenes memory task and IVM-IQ) in adolescents of both sexes.Method: Two hundred and ninety adolescents, grouped into refrainers, binge drinkers and subjects with a history of simultaneous BD/Cannabis co-use, received a risk dose of alcohol or a control drink.Results: Consumption Pattern (refrainers vs. binge drinkers vs. BD/Cannabis consumers) was not significant, while Treatment (acute alcohol vs. control drink) was significant in both sexes. Also, male binge drinkers' performance in the faces memory task was poorer than that of refrainers and BD/Cannabis consumers who consumed the control drink. BD/Cannabis consumers performed this task as capably as refrainers. In women, binge drinkers performed better than refrainers in scene memory and IVM-IQ tests when given alcohol, and binge drinkers performed worse than refrainers after consuming the control drink.Conclusions: Acute alcohol consumption worsens IVM. Cannabis exerts a buffering effect in men. A cognitive tolerance effect is observed in women. Exposure during adolescence to alcohol, alone or with cannabis, can trigger different cognitive effects in men and women that could endure into adulthood.

Acute and short-term effects of Lactobacillus paracasei subsp. paracasei 431 and inulin intake on appetite control and dietary intake: A two-phases randomized, double blind, placebo-controlled study

This study aims to examine the acute and short-term effects of prebiotics, probiotics, and their combination on appetite, energy intake and satiety related hormones in two phases. The first phase was a randomized, double blind, placebo controlled crossover study. Prebiotic (16 g inulin), probiotic (Lactobacillus paracasei subsp. paracasei 431 (L. casei 431) (>106 cfu/ml), synbiotic (their combination) and control (16 g maltodextrin) dairy drinks were consumed by 16 healthy men with a standard breakfast on four separate test days, and the following satiety responses and ad libitum food intake at lunch and over 24 h were assessed. In the second phase, the effects of 21 days of synbiotic (n = 10) or control (n = 11) drink consumption on appetite sensation, energy intake, serum glucose, insulin, peptide YY, ghrelin, obestatin and adiponectin concentration were assessed in a randomized double-blind placebo-controlled design. In the first phase, energy intake values during ad libitum lunch were the lowest in the prebiotic drink, followed by probiotic, synbiotic and control drinks, respectively (p = 0.017); also the rest of the day and 24-h dietary energy intake was lower by prebiotic and probiotic drinks compared to the control drink (p < 0.05 for each). For short-term effects, no significant difference in anthropometric measurements, hunger-satiety scores and serum glucose, insulin, PYY, ghrelin, obestatin and adiponectin concentrations were recorded. Despite the potential of prebiotics and probiotics to reduce energy intake, further studies are required for a better understanding of their role in satiety related mechanisms.

The effects of 6-month hydrogen-rich water intake on molecular and phenotypic biomarkers of aging in older adults aged 70 years and over: A randomized controlled pilot trial.

In this randomized controlled pilot trial, we investigated the effects of a 6-month intake of hydrogen-rich water (HRW) on several molecular and phenotypic biomarkers of aging in older adults aged 70years and over. Forty older adults (20 women) were randomly allocated in a parallel-group design to receive 0.5L per day of HRW (15ppm of hydrogen) or control drink (0ppm of hydrogen) during a 6-month intervention period. The biomarkers assessed at baseline and 6-month follow up were molecular markers in the blood (DNA and chromosomes, nutrient sensing, protein, and lipid metabolism, oxidative stress and mitochondria, cell senescence, inflammation), brain metabolism, cognitive functioning, physical function and body composition, resting blood pressure, facial skin features, sleep outcomes, and health-related quality of life. The mean age, weight, and height of study participants were 76.0±5.6years, 78.2±16.1kg, height 167.5±11.5cm, respectively. A significant treatment vs. time interaction was found for telomere length (P=0.049), with the length increased after HRW intervention (from 0.99±0.15 at baseline to 1.02±0.26 at follow up) and decreased after drinking control water (from 0.92±0.27 to 0.79±0.15). A marker of DNA methylation (Tet methylcytosine dioxygenase 2, TET2) expression at 6-month follow-up increased in both groups, yet the degree of elevation was significantly higher in HRW (from 0.81±0.52 at baseline to 1.62±0.66 at follow up) comparing to the control water (from 1.13±0.82 to 1.76±0.87) (P=0.040). A strong trend for treatment vs. time interaction was found for a degree of DNA methylation (P=0.166), with the methylation increased in the HRW group (from 120.6±39.8ng at baseline to 126.6±33.8ng at follow up) and decreased after taking control water (from 133.6±52.9ng to 121.2±38.4ng). HRW was superior to control water to increase brain choline and NAA levels in the left frontal grey matter, brain creatine at the right parietal white matter, and brain NAA at the right parietal mesial grey matter (P<0.05). No significant differences were found between interventions for other outcomes (P>0.05), except for a significantly improved chair stand performance after HRW intervention compared to the control water (P=0.01). Owing to pleiotropic mechanisms of hydrogen action, this simple biomedical gas could be recognized as a possible anti-aging agent that tackles several hallmarks of aging, including loss of function and telomere length shortening. The study was registered at ClinicalTrials.gov (NCT04430803).

Biotechnological interventions of in vitro propagation and production ofvaluable secondary metabolites in Stevia rebaudiana.

Plant cell and tissue culture makes provision of a sustainable and nature-friendly strategy for the production of secondary metabolites, and modern progress in gene editing and genome engineering provides novel possibilities to improve both the qualitative and quantitative aspects of such phytochemicals. The ever-expanding quest for plant-based medicine to treat diabetes facilitates large-scale cultivation of Stevia rebaudiana to enhance the yield of its much-coveted low-calorie sweetener glycosides. The potential to process stevia as a "natural" product should enhance the acceptance of steviosides as a natural calorie-free sweetener especially suitable for use in diabetic and weight control drinks and foods. Besides sweetener agents, S. rebaudiana is a potent source of many antioxidant compounds and is used to cure immunodeficiencies, neurologic disorders, inflammation, diabetes mellitus, Parkinson's disease, and Alzheimer's disease. This comprehensive review presents the research outcomes of the many biotechnological interventions implicated to upscale the yield of steviol glycosides and its derivatives in in vitro cell, callus, tissue, and organ cultures with notes on the use of bioreactor and genetic engineering in relation to the production of these valuable compounds in S. rebaudiana. KEY POINTS: • Critical and updated assessment on sustainable production of steviol glycosides from Stevia rebaudiana. • In vitro propagation of S. rebaudiana and elicitation of steviol glycosides production. • Genetic fidelity and diversity assessment of S. rebaudiana using molecular markers.

Effect of the consumption of hesperidin in orange juice on the transcriptomic profile of subjects with elevated blood pressure and stage 1 hypertension: A randomized controlled trial (CITRUS study)

Hesperidin exerts cardiovascular beneficial effects, but its mechanisms of action remain undefined. In a previous study we demonstrated that a single dose and a 12-week treatment of hesperidin decreased systolic blood pressure. The aim of this study was to ascertain the action mechanisms of hesperidin consumption in subjects with elevated blood pressure or with stage 1 hypertension, by determining their transcriptomic profile after a single dose or a 12-week treatment. For transcriptomic analysis, peripheral blood mononuclear cells were obtained from 37 subjects with elevated blood pressure and stage 1 hypertension from CITRUS study who were randomized to receive for 12 weeks: control drink (CD; n=11), OJ (containing 345mg of hesperidin; n=15) or EOJ (containing 600mg of hesperidin; n=11). Before starting the 12-weeks treatment, a single dose study with a 6h of follow-up in each group was performed. After the single dose consumption, EOJ versus OJ, downregulated DHRS9 gene which is related with insulin resistance. Compared to CD, 12-week treatment of EOJ downregulated 6 proinflammatory genes while after OJ consumption only 1 proinflammatory gene was downregulated. Moreover, 12-week treatment of EOJ versus OJ, downregulated acute coronary syndrome gene related (SELENBP1). A single dose consumption of EOJ could protect from insulin resistance. Moreover, EOJ decrease the expression of proinflammatory genes after 12-week treatment providing a possible mechanism of action on inflammation pathway.

Exogenous ketosis increases blood and muscle oxygenation but not performance during exercise in hypoxia.

Available evidence indicates that elevated blood ketones are associated with improved hypoxic tolerance in rodents. From this perspective, we hypothesized that exogenous ketosis by oral intake of the ketone ester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE) may induce beneficial physiological effects during prolonged exercise in acute hypoxia. As we recently demonstrated KE to deplete blood bicarbonate, which per se may alter the physiological response to hypoxia, we evaluated the effect of KE both in the presence and absence of bicarbonate intake (BIC). Fourteen highly trained male cyclists performed a simulated cycling race (RACE) consisting of 3-h intermittent cycling (IMT180') followed by a 15-min time-trial (TT15') and an all-out sprint at 175% of lactate threshold (SPRINT). During RACE, fraction of inspired oxygen ([Formula: see text]) was gradually decreased from 18.6% to 14.5%. Before and during RACE, participants received either 1) 75 g of ketone ester (KE), 2) 300 mg/kg body mass bicarbonate (BIC), 3) KE+BIC, or 4) a control drink in addition to 60 g of carbohydrates/h in a randomized, crossover design. KE counteracted the hypoxia-induced drop in blood ([Formula: see text]) and muscle oxygenation by ∼3%. In contrast, BIC decreased [Formula: see text] by ∼2% without impacting muscle oxygenation. Performance during TT15' and SPRINT were similar between all conditions. In conclusion, KE slightly elevated the degree of blood and muscle oxygenation during prolonged exercise in moderate hypoxia without impacting exercise performance. Our data warrant to further investigate the potential of exogenous ketosis to improve muscular and cerebral oxygenation status, and exercise tolerance in extreme hypoxia.

Hesperidin in orange juice improves human endothelial function in subjects with elevated blood pressure and stage 1 hypertension: A randomized, controlled trial (Citrus study)

In a randomized, parallel, double-blind, placebo-controlled trial, participants with elevated blood pressure and stage 1 hypertension (n = 159) received 500 mL/day of control drink, orange juice (OJ), or hesperidin-enriched OJ (EOJ) for 12-weeks, and their ischaemic reactive hyperemia (IRH) was assessed at baseline and after 4, 8, and 12-weeks. Two dose–response studies were nested within the sustained-consumption study: at baseline and after 12-weeks, a single dose of 500 mL was administered. All treatments increased postpandrial IRH, and a higher increase was obtained with EOJ. Moreover, hs-CRP and IL6 increased but not after EOJ. After 12 weeks of sustained consumption: IRH values after EOJ increased versus control group; EOJ treatment increased DSP and decreased IEX-1 gene expression in PBMCs; and IRH directly correlated to NO and inversely to MPO and IEX1. Thus, hesperidin in OJ improves human endothelial function, lower inflammatory status at systemic level and changes at transcriptomic level might account for the increased IRH observed.

Effects of Hesperidin Consumption on the Cardiovascular System in Pre- and Stage 1 Hypertensive Subjects: Targeted and Non-Targeted Metabolomic Approaches (CITRUS Study).

The aim of the present work is to determine new biomarkers of the biological effects of hesperidin in orange juice (OJ) applying a non-targeted metabolomics approach validated by targeted metabolomics analyses of compliance biomarkers. Plasma/serum and urine targeted (HPLC-MS/MS) and untargeted (1 H-NMR) metabolomics signatures are explored in a subsample with pre- and stage-1 hypertension subjects of the CITRUS study (N=159). Volunteers received 500mL day-1 of control drink, OJ, or hesperidin-enriched OJ (EOJ) for 12-weeks. A 6-h postprandrial study is performed at baseline. Targeted analyses reveals plasma and urine hesperetin 7-O-β-d-glucuronide as the only metabolite differing between OJ and EOJ groups after 12-weeks consumption, and in urine is correlated with a decreased systolic blood pressure level. The non-targeted approach shows that after single dose and 12-weeks consumption of OJ and EOJ change several metabolites related with an anti-inflammatory and antioxidant actions, lower blood pressure levels and uremic toxins. Hesperetin 7-O-β-d-glucuronide can be a candidate marker for distinguishing between the consumption of different hesperidin doses at 12-weeks consumption as well as a potential agent mediating blood pressure reduction. Moreover, changes in different endogenous metabolites can explain the mechanisms of action and the biological effects of hesperidin consumption.