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Beta-alanine is a nonessential amino acid that is commonly used to improve exercise performance. It could influence the buffering of hydrogen ions produced during intense exercise and delay fatigue, providing a substrate for increased synthesis of intramuscular carnosine. This systematic review evaluates the effects of beta-alanine supplementation on maximal intensity exercise in trained, young, male individuals. Six databases were searched on August 10, 2023, to identify randomized, double-blinded, placebo-controlled trials investigating the effect of chronic beta-alanine supplementation in trained male individuals with an age range of 18–40 years. Studies evaluating exercise performance through maximal or supramaximal intensity efforts falling within the 0.5–10 min duration were included. A total of 18 individual studies were analyzed, employing 18 exercise test protocols and 15 outcome measures in 331 participants. A significant (p =.01) result was observed with an overall effect size of 0.39 (95% confidence interval [CI] [0.09, 0.69]), in favor of beta-alanine supplementation versus placebo. Results indicate significant effects at 4 weeks of supplementation, effect size 0.34 (95% CI [0.02, 0.67], p =.04); 4–10 min of maximal effort, effect size 0.55 (95% CI [0.07, 1.04], p =.03); and a high beta-alanine dosage of 5.6–6.4 g per day, effect size 0.35 (95% CI [0.09, 0.62], p =.009). The results provide insights into which exercise modality will benefit the most, and which dosage protocols and durations stand to provide the greatest ergogenic effects. This may be used to inform further research, and professional or recreational training design, and optimization of supplementation strategies. [ABSTRACT FROM AUTHOR]

Objectives: Dietary strategies to improve arachidonic acid:eicosapentaenoic acid (AA:EPA) ratios are of interest due to potential reductions in inflammation and oxidative stress following exercise. The aim of this study was to investigate the impact of a novel dietary intervention, that is, the ingestion of 30 g of dark chocolate, on blood lipid profiles and gut microbiota composition in elite male soccer players. Methods: Professional male soccer players were randomly assigned to the experimental group (DC) provided with 30 g of dark chocolate or to the control group (WC), provided with 30 g of white chocolate, for 30 days. Before and after intervention, blood, fecal sample, and anthropometry data were collected. For each outcome, two-way repeated-measure analysis of variance was used to identify differences between baseline and endpoint (Week 4), considering treatment (dark chocolate, white chocolate) as intersubjects' factors. Metagenomic analysis was performed following the general guidelines, which relies on the bioBakery computational environment. Results: DC group showed increased plasma polyphenols (from 154.7 ± 18.6 μg gallic acid equivalents/ml to 185.11 ± 57.6 μg gallic acid equivalents/ml, Δ pre vs. post = +30.41 ± 21.50) and significant improvements in lipid profiles: total cholesterol (Δ −32.47 ± 17.18 mg/dl DC vs. Δ −2.84 ± 6.25 mg/dl WC, Time × Treatment interaction p <.001), triglycerides (Δ −6.32 ± 4.96 mg/dl DC vs. Δ −0.42 ± 6.47 mg/dl WC, Time × Treatment interaction p <.001), low-density lipoprotein (Δ −18.42 ± 17.13 mg/dl vs. Δ −2.05 ± 5.19 mg/dl WC, Time × Treatment interaction p <.001), AA/EPA ratio (Δ −5.26 ± 2.35; −54.1% DC vs. Δ −0.47 ± 0.73, −6.41% WC, Time × Treatment interaction p <.001) compared with WC group. In addition, 4 weeks of intervention showed a significant increase in high-density lipoprotein concentration in DC group (Δ + 3.26 ± 4.49 mg/dl DC vs. Δ −0.79 ± 5.12 mg/dl WC). Microbial communities in the DC group maintained a slightly higher microbial stability over time (exhibiting lower within-subject community dissimilarity). Conclusion: Ingesting 30 g of dark chocolate over 4 weeks positively improved AA:EPA ratio and maintained gut microbial stability. Dark chocolate ingestion represents an effective nutritional strategy to improve blood lipid profiles in professional soccer players. What Are the Findings? Ingesting 30 g of dark chocolate for 4 weeks positively influences blood lipid AA: EPA ratio while maintaining gut microbial stability. What This Study Adds? Dietary intake of specific foods such as dark chocolate represents an alternative strategy to support the health and recovery of elite soccer players. WhatImpact Might This Have on Clinical Practice in the Future? From a clinical and translational perspective, dark chocolate ingestion positively modulates favorable blood lipid profiles and polyunsaturated fatty acid metabolism while maintaining gut microbial stability. Dark chocolate ingestion may be considered as an effective nutritional strategy in elite sport environments during periods of high-intensity training and congested competitions. Further research is required to determine functional outcomes associated with the observed improvements in blood lipid profiles. [ABSTRACT FROM AUTHOR]

Purpose: To determine the acute response of lactate supplementation on athletic performance. Method: Fifteen athletes under the age of 15 performed the following 4 sessions in a nonrandomized order: (1) familiarization, (2) control, (3) participants ingested calcium lactate (21.5 mg·kg−1 body mass), and (4) participants ingested a placebo (PLA, calcium carbonate, 21.5 mg·kg−1 body mass). The capsules were randomly offered and consumed 60 minutes before the physical tests. To assess the physical performance, the athletes executed squat jump, countermovement squat jump, 20-m linear sprint, change of direction test, and running anaerobic sprint test. Results: There were no significant differences between conditions for squat jump, countermovement jump, change of direction, and minimum power obtained in the running anaerobic sprint test (P >.05). Conversely, we observed a worse performance (P <.05) in the 20-m linear sprint test in the PLA and lactate conditions compared with control (P <.05). The lactate condition worsened performance during running anaerobic sprint test for peak power, mean power, and fatigue index compared with control and PLA (P <.05). Conclusions: Calcium lactate supplementation worsened repetitive running sprint ability and 20-m sprint performance. However, lactate supplementation does not affect jump or agility capacity. Therefore, calcium lactate supplementation seems to be an ineffective strategy to improve anaerobic and neuromuscular performance in soccer players 15 years of age or less. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate the effectiveness of the combination of protein supplementation and resistance training (RT), compared with RT alone or combined with a placebo, in improving gait speed. Methods: We searched PubMed, Web of Science, Cochrane Library, and SPORTDiscus databases, and 18 randomized controlled trials with 1,147 older participants were included for meta-analysis. Data were pooled as the effect sizes (Hedges' g) with 95% confidence interval (CI) of the gait speed (in meters per second). The random-effect meta-analysis, subgroup analyses, meta-regression, and sensitivity analysis were conducted. Results: The combination of protein supplementation and RT significantly improved gait speed (Hedges' g: 0.52 m/s, 95% confidence interval [0.17, 0.86], p =.005; I2 = 86.5%) compared with the RT alone. The subgroup analyses revealed that the significant improvement in gait speed postprotein intervention plus RT was observed only in participants who consumed protein after RT (Hedges' g: 0.90 m/s, 95% confidence interval [0.46, 1.33], p =.001; I2 = 79.6%). The pooled result did not significantly change after excluding any single study at one time or excluding smaller studies with large effect sizes. Conclusions: Protein supplementation combined with RT could significantly improve the gait speed of older adults compared with RT alone. This positive effect is more pronounced in people who consume protein after RT. [ABSTRACT FROM AUTHOR]

Athletes, both amateur and professional, often resort to the consumption of nutritional supplements without professional supervision and without being aware of the risks they may entail. We conducted an exhaustive literature search to determine the most common substances found as contaminants in dietary supplements. For each substance, we analyzed its mechanism of action, clinical indication, health risk, and putative use as doping agent. In addition, we evaluated the current regulation of these supplements. Contamination of nutritional supplements (accidental or intentional), especially with steroids and stimulants, is a hazardous situation. The prolonged consumption of these products without being aware of their composition can cause serious health risks and, in the case of professional athletes, a possible sanction for doping. [ABSTRACT FROM AUTHOR]

Carbohydrate (CHO) supplementation during endurance exercise can improve performance. However, it is unclear whether low glycemic index (GI) CHO leads to differential ergogenic and metabolic effects compared with a standard high GI CHO. This study investigated the ergogenic and metabolic effects of CHO supplementation with distinct GIs, namely, (a) trehalose (30 g/hr), (b) isomaltulose (30 g/hr), (c) maltodextrin (60 g/hr), and (d) placebo (water). In this double-blind, crossover, counterbalanced, placebo-controlled study, 13 male cyclists cycled a total of 100 min at varied exercise intensity (i.e., 10-min stages at 1.5, 2.0, and 2.5 W/kg; repeated three times plus two 5-min stages at 1.0 W/kg before and after the protocol), followed by a 20-min time trial on four separated occasions. Blood glucose and lactate (every 20 min), heart rate, and ratings of perceived exertion were collected throughout, and muscle biopsies were taken before and immediately after exercise. The results showed that trehalose improved time-trial performance compared with placebo (total work done 302 ± 39 vs. 287 ± 48 kJ; p =.01), with no other differences between sessions (all p ≥.07). Throughout the 100-min protocol, blood glucose was higher with maltodextrin compared with the other supplements at all time points (all p <.05). Heart rate, ratings of perceived exertion, muscle glycogen content, blood glucose, and lactate were not different between conditions when considering the 20-min time trial (all p >.05). Trehalose supplementation throughout endurance exercise improved cycling performance and appears to be an appropriate CHO source for exercise tasks up to 2 hr. No ergogenic superiority between the different types of CHO was established. [ABSTRACT FROM AUTHOR]

Whey protein ingestion during recovery from exercise increases myofibrillar but not muscle connective protein synthesis rates. It has been speculated that whey protein does not provide sufficient glycine to maximize postexercise muscle connective protein synthesis rates. In the present study, we assessed the impact of coingesting different amounts of collagen with whey protein as a nutritional strategy to increase plasma glycine availability during recovery from exercise. In a randomized, double-blind, crossover design, 14 recreationally active men (age: 26 ± 5 years; body mass index: 23.8 ± 2.1 kg·m−2) ingested in total 30 g protein, provided as whey protein with 0 g (WHEY), 5 g (WC05); 10 g (WC10), and 15 g (WC15) of collagen protein immediately after a single bout of resistance exercise. Blood samples were collected frequently over 6 hr of postexercise recovery to assess postprandial plasma amino acid kinetics and availability. Protein ingestion strongly increased plasma amino acid concentrations (p <.001) with no differences in plasma total amino acid availability between treatments (p >.05). The postprandial rise in plasma leucine and essential amino acid availability was greater in WHEY compared with the WC10 and WC15 treatments (p <.05). Plasma glycine and nonessential amino acid concentrations declined following whey protein ingestion but increased following collagen coingestion (p <.05). Postprandial plasma glycine availability averaged −8.9 ± 5.8, 9.2 ± 3.7, 23.1 ± 6.5, and 39.8 ± 11.0 mmol·360 min/L in WHEY, WC05, WC10, and WC15, respectively (incremental area under curve values, p <.05). Coingestion of a small amount of collagen (5 g) with whey protein (25 g) is sufficient to prevent the decline in plasma glycine availability during recovery from lower body resistance-type exercise in recreationally active men. [ABSTRACT FROM AUTHOR]

There has been an increase in the use of commercially available multi-ingredient preworkout supplements (MIPS); however, there are inconsistencies regarding the efficacy of MIPS in resistance-trained women. Purpose: To determine the effect of varying doses of MIPS compared with caffeine only (C) and a placebo (PL) on resistance-training performance in trained women. Methods: Ten women (21.5 [2.3] y) completed 1-repetition-maximum tests at baseline for leg press and bench press. A within-group, double-blind, and randomized design was used to assign supplement drinks (ie, PL, C, MIPS half scoop [MIPS-H], and MIPS full scoop [MIPS-F]). Repetitions to failure were assessed at 75% and 80% to 85% of 1-repetition maximum for bench and leg press, respectively. Total performance volume was calculated as load × sets × repetitions for each session. Data were analyzed using a 1-way repeated-measures analysis of variance and reported as means and SDs. Results: There were no differences in repetitions to failure for bench press (PL: 14.4 [3.2] repetitions, C: 14.4 [2.9] repetitions, MIPS-H: 14.2 [2.6] repetitions, MIPS-F: 15.1 [3.1] repetitions; P =.54) or leg press (PL: 13.9 [7.8] repetitions, C: 10.8 [5.9] repetitions, MIPS-H: 13.1 [7.1] repetitions, MIPS-F: 12.4 [10.7] repetitions; P =.44). Furthermore, there were no differences in total performance volume across supplements for bench press (PL: 911.2 [212.8] kg, C: 910.7 [205.5] kg, MIPS-H: 913.6 [249.3] kg, MIPS-F: 951.6 [289.6] kg; P =.39) or leg press (PL: 4318.4 [1633.6] kg, C: 3730.0 [1032.5] kg, MIPS-H: 4223.0 [1630.0] kg, MIPS-F: 4085.5 [2098.3] kg; P =.34). Conclusions: Overall, our findings suggest that caffeine and MIPS do not provide ergogenic benefits for resistance-trained women in delaying muscular failure. [ABSTRACT FROM AUTHOR]

The use of dietary supplements by patients with chronic liver disease is prevalent and rising. Despite the known risks of dietary supplements, including hepatotoxicity, adulteration, and contamination, patients with chronic liver disease often turn to dietary supplements to support their liver and/or overall health but are not necessarily empowered with the information or guidance from their liver practitioner to do so. This article provides practitioners with a framework for balancing the risks and benefits of dietary supplements in patients with chronic liver disease, offering examples of independent resources and certifications to use this framework in clinical practice. We offer 3 common clinical scenarios to highlight how the use of this framework can improve communication and decision-making in clinical practice. By adapting principles from Integrative Medicine, this article advocates for a patient-centered approach to dietary supplements in patients with chronic liver disease, encouraging open dialogue between clinicians and their patients to facilitate informed decision-making and personalized care.

BACKGROUND: 2-Fucosyllactose (2-FL) is an oligosaccharide contained in human milk and possesses prebiotic and anti-inflammatory effects, which may alleviate skeletal muscle atrophy under caloric restriction. This study evaluated the impacts of 12 weeks of 2-FL supplementation in conjunction with exercise (10,000 steps/day, 5 days/week) and energy-reduced (-300 kcals/day) dietary interventions on changes in body composition and health-related biomarkers. METHODS: A total of 41 overweight and sedentary female and male participants (38.0 ± 13 years, 90.1 ± 15 kg, 31.6 ± 6.6 kg/m2, 36.9 ± 7% fat) took part in a randomized, double-blind, and placebo-controlled study. The participants underwent baseline assessments and were then assigned to ingest 3 g/day of a placebo (PLA) or Momstamin 2-F while initiating the exercise and weight-loss program. Follow-up tests were performed after 6 and 12 weeks. Data were analyzed using general linear model statistics with repeated measures and mean changes from baseline values with 95% confidence intervals (CIs). RESULTS: No group × time × sex interaction effects were observed, so group × time effects are reported. Participants in both groups saw comparable reductions in weight. However, those with 2-FL demonstrated a significantly greater reduction in the percentage of body fat and less loss of the fat-free mass. Additionally, there was evidence that 2-FL supplementation promoted more favorable changes in resting fat oxidation, peak aerobic capacity, IL-4, and platelet aggregation, with some minimal effects on the fermentation of short-chain fatty acids and monosaccharides in fecal samples. Moreover, participants perceptions regarding some aspects of the functional capacity and ratings of the quality of life were improved, and the supplementation protocol was well tolerated, although a small, but significant, decrease in BMC was observed. CONCLUSIONS: The results support contentions that dietary supplementation of 2-FL (3 g/d) can promote fat loss and improve exercise- and diet-related markers of health and fitness in overweight sedentary individuals initiating an exercise and weight-loss program. Further research is needed to explore the potential health benefits of 2-FL supplementation in both healthy and elderly individuals (Registered clinical trial #NCT06547801).

BACKGROUND: Undernutrition during pregnancy increases the risk of giving birth to a small vulnerable newborn. Small-quantity lipid-based nutrient supplements (SQ-LNSs) contain both macro- and micronutrients and can help prevent multiple nutritional deficiencies. OBJECTIVES: We examined the effects of SQ-LNSs provided during pregnancy compared with 1) iron and folic acid or standard of care (IFA/SOC) or 2) multiple micronutrient supplements (MMSs) and identified characteristics that modified the estimates of effects of SQ-LNSs on birth outcomes. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 4 randomized controlled trials of SQ-LNSs provided during pregnancy (n = 5273). We generated study-specific and subgroup estimates of SQ-LNS compared with IFA/SOC or MMS and pooled the estimates. In sensitivity analyses, we examined whether the results differed depending on methods for gestational age dating, birth anthropometry, or study design. RESULTS: SQ-LNSs (compared with IFA/SOC) increased birth weight [mean difference: +49 g; 95% confidence interval (CI): 26, 71 g] and all birth anthropometric z-scores (+0.10-0.13 standard deviation); they reduced risk of low birth weight by 11%, newborn stunting by 17%, newborn wasting by 11%, and small head size by 15%. Only 2 trials compared SQ-LNSs and MMSs; P values for birth outcomes were >0.10 except for head circumference (e.g., z-score for gestational age: +0.11; 95% CI: -0.01, 0.23). Effect estimates for SQ-LNSs compared with IFA/SOC were greater among female infants and, for certain outcomes, among mothers with body mass index

Hazardous alcohol consumption is highly prevalent for men who have sex with men (MSM). The 4 treatments currently approved by the Food and Drug Administration for alcohol use are reaching an alarmingly low percentage of people who would benefit from a reduction in their alcohol use. There is increasing interest in alternative methods of treatment, such as herbal supplements, to address hazardous drinking. However, research on the acceptability of alternative pharmacotherapies among MSM remains limited. We examined the prevalence and correlates of expressing interest in using herbal supplements for alcohol treatment among MSM with hazardous alcohol consumption. We conducted a secondary data analysis from a cross-sectional study of MSM who use alcohol, conducted from March 2015 to July 2017 in San Francisco, California, to assess the overall prevalence of interest in using herbal supplements to help reduce alcohol consumption. Associations between expressing interest in herbal supplements and demographic, social, and clinical characteristics were examined using bivariate and multivariable logistic regression models. One-third (66/200, 33%) of the participants expressed interest in an herbal supplement for reducing alcohol consumption. In the multivariable analyses, weekly binge drinking (adjusted odds ratio [aOR] 2.85, 95% CI 1.17-6.93), interest in abstaining from alcohol use (aOR 5.04, 95% CI 1.46-17.40), higher severity of alcohol dependence score (aOR 1.22, 95% CI 1.04-1.41), and interest in naltrexone (aOR 3.22, 95% CI 2.12-4.91) were independently associated with higher odds of being interested in using an herbal supplement to reduce alcohol consumption, adjusting for age, race or ethnicity, and education. We found that MSM who have hazardous drinking habits, more severe alcohol dependence, and interest in pharmacotherapy were more likely to express interest in using an herbal supplement for reducing alcohol consumption. To our knowledge, this is the first study that has evaluated correlates of interest in herbal supplements for alcohol use among MSM. As researchers implement novel alcohol treatment studies, they should focus on recruitment efforts among MSM with a motivation to reduce their alcohol use patterns.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is a common, yet underdiagnosed, gut condition caused by gut dysbiosis. A previous study has shown the potential of herbal therapy, providing equivalent results to rifaximin. OBJECTIVES: The objective of this study was to assess how the use of an oral botanical regimen may modulate the gut microbiome, facial erythema, and intestinal permeability in those with SIBO. METHODS: This was an open-label prospective study of adults that had lactulose breath test-confirmed SIBO. Participants received a 10-week oral supplementation of a Biocidin liquid tincture and GI Detox+. If participants were found to be non-responsive to treatment after 10 weeks with a persistently positive lactulose breath test, a third oral supplement, Olivirex, was administered for an additional 4 weeks. Lactulose breath tests were administered at baseline, weeks 6, 10, and 14 to assess for SIBO status. A high-resolution photographic analysis system was utilized to analyze changes in facial erythema. Stool sample collections and venipuncture were performed to analyze the gut microbiome and intestinal permeability. RESULTS: A total of 33 subjects were screened with breath testing, and 19 subjects were found to have SIBO. Three of the subjects withdrew during the screening period prior to baseline, and sixteen subjects enrolled. Four subjects dropped out after baseline. Hydrogen-dominant SIBO was the most common subtype of SIBO, followed by methane and hydrogen sulfide. The botanical regimen was most effective for hydrogen- and hydrogen sulfide-dominant SIBO, leading to negative breath test results at week 10 in 42.8% and 66.7% of participants, respectively. Compared to baseline, supplementation with the botanical regimen led to positive shifts in short-chain fatty acid-producing bacteria such as A. muciniphila, F. prausnitzii, C. eutectus, and R. faecis by 31.4%, 35.4%, 24.8%, and 48.7% percent at week 10, respectively. The mean abundance of Firmicutes decreased by 20.2%, Bacteroides increased by 30%, and the F/B ratio decreased by 25.4% at week 10 compared to baseline. At week 10, there was a trending 116% increase in plasma LPS/IgG (p = 0.08). There were no significant changes in plasma zonulin, DAO, histamine, DAO/histamine, LPS/IgG, LPS/IgA, or LPS/IgM. Facial erythema was not statistically different at week 6, but at week 10, there was a 20% decrease (p = 0.001) in redness intensity. Among the patients that extended to week 14, there was no statistical change in erythema. CONCLUSIONS: Supplementation with an antimicrobial botanical supplemental regimen may have therapeutic potential in hydrogen and hydrogen-sulfide subtypes of SIBO. Furthermore, the botanical supplemental regimen may reduce facial erythema, increase SCFA-producing bacteria, decrease the F/B ratio, and modulate markers of intestinal permeability.

BACKGROUND: Prenatal fish intake is a key source of omega-3 (ω-3) polyunsaturated fatty acids needed for brain development, yet intake is generally low, and studies addressing associations with autism spectrum disorder (ASD) and related traits are lacking. OBJECTIVE: This study aimed to examine associations of prenatal fish intake and ω-3 supplement use with both autism diagnosis and broader autism-related traits. METHODS: Participants were drawn from 32 cohorts in the Environmental influences on Child Health Outcomes Cohort Consortium. Children were born between 1999 and 2019 and part of ongoing follow-up with data available for analysis by August 2022. Exposures included self-reported maternal fish intake and ω-3/fish oil supplement use during pregnancy. Outcome measures included parent report of clinician-diagnosed ASD and parent-reported autism-related traits measured by the Social Responsiveness Scale (SRS)-second edition (n = 3939 and v3609 for fish intake analyses, respectively; n = 4537 and n = 3925 for supplement intake analyses, respectively). RESULTS: In adjusted regression models, relative to no fish intake, fish intake during pregnancy was associated with reduced odds of autism diagnosis (odds ratio: 0.84; 95% confidence interval [CI]: 0.77, 0.92), and a modest reduction in raw total SRS scores (β: -1.69; 95% CI: -3.3, -0.08). Estimates were similar across categories of fish consumption from any or less than once per week to more than twice per week. For ω-3 supplement use, relative to no use, no significant associations with autism diagnosis were identified, whereas a modest relation with SRS score was suggested (β: 1.98; 95% CI: 0.33, 3.64). CONCLUSIONS: These results extend previous work by suggesting that prenatal fish intake, but not ω-3 supplement use, may be associated with lower likelihood of both autism diagnosis and related traits. Given the low-fish intake in the United States general population and the rising autism prevalence, these findings suggest the need for better public health messaging regarding guidelines on fish intake for pregnant individuals.

BackgroundObesity and consumption of high-fat diets (HFD) are associated with intestinal permeabilization and increased paracellular transport of endotoxins, which can promote neuroinflammation. Inflammation can affect the hypothalamic pituitary adrenal (HPA) axis, which controls responses to stress and downregulates the brain-derived neurotrophic factor (BDNF), which can promote anxiety and depression, conditions frequently found in obesity. We previously showed that consumption of anthocyanins (AC) mitigate HFD-induced insulin resistance, intestinal permeability, and inflammation.ObjectivesThis study investigated if a dietary supplementation with a cyanidin- and delphinidin-rich extract (CDRE) could counteract HFD/obesity-induced hippocampal inflammation in mice.MethodsC57BL/6J male mice were fed for 14 wk on one of the following diets: 1) a control diet containing 10% total calories from fat (C), 2) a control diet supplemented with 40 mg AC/kg body weight (BW) (CAC), 3) a HFD containing 60% total calories from fat (lard) (HF), or 4) the HFD supplemented with 2, 20, or 40 mg AC/kg BW (HFA2, HFA20, and HFA40, respectively). In plasma and in the hippocampus, parameters of neuroinflammation and the underlying cause (endotoxemia) and consequences (alterations to the HPA and BDNF downregulation) were measured.ResultsConsumption of the HFD caused endotoxemia. Accordingly, hippocampal Tlr4 mRNA levels were 110% higher in the HF group, which were both prevented by CDRE supplementation. Consumption of the HFD also caused: 1) microgliosis and increased expression of genes involved in neuroinflammation, that is, Iba-1, Nox4, Tnfα, and Il-1β, 2) alterations of HPA axis regulation, that is, with low expression of mineralocorticoid (MR) and glucocorticoid (GR) receptors; and 3) decreased Bdnf expression. Supplementation of HFD-fed mice with CDRE mitigated neuroinflammation, microgliosis, and MR and BDNF decreases.ConclusionsCDRE supplementation mitigates the negative effects associated with HFD consumption and obesity in mouse hippocampus, in part by decreasing inflammation, improving glucocorticoid metabolism, and upregulating BDNF.

Despite the abundance of research investigating the efficacy of caffeine supplementation on exercise performance, the physiological and biochemical responses to caffeine supplementation during intermittent activities are less evident. This study investigated the acute effects of caffeine supplementation on measures of exercise performance, ratings of perceived exertion, and biomarkers of oxidative stress induced by an acute bout of sprint interval training. In a randomized crossover design, 12 healthy males (age: 26 ± 4 years, height: 177.5 ± 6 cm, body mass: 80.7 ± 7.6 kg) ingested 6 mg/kg of caffeine or placebo 60 min prior to performing sprint interval training (12 × 6 s "all-out sprints" interspersed by 60 s of rest). Performance scores and ratings of perceived exertion were assessed after every sprint. Blood samples were collected before supplementation, prior to and following each sprint, and 5 and 60 min after the last sprint. Caffeine had no effect on any performance measures, ratings of perceived exertion, or biomarkers of oxidative stress (p >.05). In conclusion, caffeine supplementation does not improve performance or decrease oxidative stress after an acute bout of sprint interval training. [ABSTRACT FROM AUTHOR]

Nitrate ( NO 3 − ) has properties that can improve muscle function, leading to improvements in metabolic cost of exercise as well as enhance force production. Gymnastics is a whole-body sport, involving events that demand a high level of strength and fatigue resistance. However, the effect of NO 3 − supplementation on both upper- and lower-body function in gymnasts is unknown. This study examined the effect of acute beetroot juice (BRJ) supplementation on isokinetic strength and endurance of the upper- and lower-body in highly trained international-level male gymnasts. In a double-blind, randomized crossover design, 10 international-level male gymnasts completed two acute supplementation periods, consuming either 2 × 70 ml NO 3 − -rich (∼12.8 mmol/L of NO 3 − ) or NO 3 − -depleted (PLA) BRJ. Maximal strength of the upper-leg and upper-arm at 60°/s, 120°/s, 180°/s, and 300°/s, and muscular endurance (50 repeated isokinetic contractions at 180°/s) were assessed. Plasma NO 3 − (BRJ: 663 ± 164 μM, PLA: 89 ± 48 μM) and nitrite ( NO 2 − ) concentrations (BRJ: 410 ± 137 nmol/L, PLA: 125 ± 36 nmol/L) were elevated following BRJ compared to PLA (both p <.001). Maximal strength of knee and elbow extensors and flexors did not differ between supplements (p >.05 for all velocities). Similarly, fatigue index of knee and elbow extension and flexion was not different between supplements (all p >.05). Acute BRJ supplementation, containing ∼12.8 mmol/L of NO 3 − , increased plasma NO 3 − and NO 2 − concentrations, but did not enhance isokinetic strength or fatigue resistance of either upper or lower extremities in international-level male gymnasts. [ABSTRACT FROM AUTHOR]

There is a lack of evidence on the additional benefits of combining caffeine (CAF) and creatine (CRE) supplementation on anaerobic power and capacity. Thus, the aim of the present study was to test the effects of combined and isolated supplementation of CAF and CRE on anaerobic power and capacity. Twenty-four healthy men performed a baseline Wingate anaerobic test and were then allocated into a CRE (n = 12) or placebo (PLA; n = 12) group. The CRE group ingested 20 g/day of CRE for 8 days, while the PLA group ingested 20 g/day of maltodextrin for the same period. On the sixth and eighth days of the loading period, both groups performed a Wingate anaerobic test 1 hr after either CAF (5 mg/kg of body mass; CRE + CAF and PLA + CAF conditions) or PLA (5 mg/kg of body mass of cellulose; CRE + PLA and PLA + PLA conditions) ingestion. After the loading period, changes in body mass were greater (p <.05) in the CRE (+0.87 ± 0.23 kg) than in the PLA group (+0.13 ± 0.27 kg). In both groups, peak power was higher (p =.01) in the CAF (1,033.4 ± 209.3 W) than in the PLA trial (1,003.3 ± 204.4 W), but mean power was not different between PLA and CAF trials (p >.05). In conclusion, CAF, but not CRE ingestion, increases anaerobic power. Conversely, neither CRE nor CAF has an effect on anaerobic capacity. [ABSTRACT FROM AUTHOR]

Introduction: The acute and isolated ingestion of sodium bicarbonate (NaHCO3) and caffeine (CAF) improves performance and delays fatigue in high-intensity tasks. However, it remains to be elucidated if the coingestion of both dietary supplements stimulates a summative ergogenic effect. This study aimed to examine the effect of the acute coingestion of NaHCO3 and CAF on repeated-sprint performance. Methods: Twenty-five trained participants (age: 23.3 [4.0] y; sex [female/male]: 12/13; body mass: 69.6 [12.5] kg) participated in a randomized, double-blind, placebo (PLA) -controlled, crossover study. Participants were assigned to 4 conditions: (1) NaHCO3 + CAF, (2) NaHCO3, (3) CAF, or (4) PLA. Thus, they ingested 0.3 g/kg of NaHCO3, 3 mg/kg of CAF, or PLA. Then, participants performed 4 Wingate tests (Wt), consisting of a 30-second all-out sprint against an individualized resisted load, interspersed by a 1.5-minute rest period between sprints. Results: Peak (Wpeak) and mean (Wmean) power output revealed a supplement and sprint interaction effect (P =.009 and P =.049, respectively). Compared with PLA, NaHCO3 + CAF and NaHCO3 increased Wpeak performance in Wt 3 (3%, P =.021) and Wt 4 (4.5%, P =.047), while NaHCO3 supplementation increased mean power performance in Wt 3 (4.2%, P =.001). In Wt 1, CAF increased Wpeak (3.2%, P =.054) and reduced time to Wpeak (−8.5%; P =.008). Plasma lactate showed a supplement plus sprint interaction (P <.001) when NaHCO3 was compared with CAF (13%, P =.031) and PLA (23%, P =.021). Conclusion: To summarize, although the isolated ingestion of CAF and NaHCO3 improved repeated-sprint performance, the coingestion of both supplements did not stimulate a synergic ergogenic effect. [ABSTRACT FROM AUTHOR]

Purpose: To examine the impact of oral contraceptive (OC) phases on performance, physiological, and subjective responses to prolonged, intensive exercise when carbohydrate (CHO) stores are reduced. Methods: Ten well-trained female cyclists using monophasic OC completed 4 identical trials (>150 min) under conditions of in-trial 60-g·h−1 CHO supplementation (CHO+) or placebo (CHO−) during the sugar- (SUG) and active-pill (ACT) phases of their OC cycle. Each trial comprised two 400-kcal time trials (TT) separated by 1 hour of submaximal cycling at first ventilatory threshold. Results: Change in completion time from TT1 to TT2 was minimized in CHO+ compared with CHO− (4.06 [2.55] vs 6.08 [5.33] min; P =.019, effect size = −0.36). An interaction effect of OC and CHO was observed for time to complete TT (P =.006), mean TT power (P =.002), mean TT heart rate (P =.002), and posttrial emotional balance (P =.020) and negative emotional state (P =.033). In ACT, mean TT power and heart rate were higher in CHO+ when compared with CHO−, resulting in faster TTs in CHO+ and improved posttrial emotional well-being. When CHO was not supplemented, TT power and heart rate were higher in SUG when compared with ACT, resulting in faster TTs in SUG and improved posttrial emotional balance. Conclusion: CHO depletion during ACT negatively influenced TT performance and emotional well-being when compared with SUG. Irrespective of OC pill phase, CHO supplementation should be prioritized to sustain performance and improve postexercise recovery–stress balance. [ABSTRACT FROM AUTHOR]

Previous studies showed that collagen peptide supplementation along with resistance exercise enhance muscular recovery and function. Yet, the efficacy of collagen peptide supplementation in addition to standard nutritional practices in athletes remains unclear. Therefore, the objective of the study was to compare the effects of combined collagen peptide (20 g) and whey protein (25 g) supplementation with a similar daily protein dose (45 g) of whey protein alone on indices of muscle damage and recovery of muscular performance during eccentric exercise training. Young fit males participated in a 3-week training period involving unilateral eccentric exercises for the knee extensors. According to a double-blind, randomized, parallel-group design, before and after training, they received either whey protein (n = 11) or whey protein + collagen peptides (n = 11). Forty-eight hours after the first training session, maximal voluntary isometric and dynamic contraction of the knee extensors were transiently impaired by ∼10% (Ptime <.001) in whey protein and whey protein + collagen peptides, while creatine kinase levels were doubled in both groups (Ptime <.01). Furthermore, the training intervention improved countermovement jump performance and maximal voluntary dynamic contraction by respectively 8% and 10% (Ptime <.01) and increased serum procollagen type 1N-terminal peptide concentration by 10% (Ptime <.01). However, no differences were found for any of the outcomes between whey and whey protein + collagen peptides. In conclusion, substituting a portion of whey protein for collagen peptide, within a similar total protein dose, improved neither indices of eccentric muscle damage nor functional outcomes during eccentric training. [ABSTRACT FROM AUTHOR]

Bile acids (BA) are among the most abundant metabolites produced by the gut microbiome. Primary BAs produced in the liver are converted by gut bacterial 7-α-dehydroxylation into secondary BAs, which can differentially regulate host health via signaling based on their varying affinity for BA receptors. Despite the importance of secondary BAs in host health, the regulation of 7-α-dehydroxylation and the role of diet in modulating this process is incompletely defined. Understanding this process could lead to dietary guidelines that beneficially shift BA metabolism. Dietary fiber regulates gut microbial composition and metabolite production. We tested the hypothesis that feeding mice a diet rich in a fermentable dietary fiber, resistant starch (RS), would alter gut bacterial BA metabolism. Male and female wild-type mice were fed a diet supplemented with RS or an isocaloric control diet (IC). Metabolic parameters were similar between groups. RS supplementation increased gut luminal deoxycholic acid (DCA) abundance. However, gut luminal cholic acid (CA) abundance, the substrate for 7-α-dehydroxylation in DCA production, was unaltered by RS. Further, RS supplementation did not change the mRNA expression of hepatic BA producing enzymes or ileal BA transporters. Metagenomic assessment of gut bacterial composition revealed no change in the relative abundance of bacteria known to perform 7-α-dehydroxylation. P. ginsenosidimutans and P. multiformis were positively correlated with gut luminal DCA abundance and increased in response to RS supplementation. These data demonstrate that RS supplementation enriches gut luminal DCA abundance without increasing the relative abundance of bacteria known to perform 7-α-dehydroxylation.

BackgroundGestational nutrition can protect against adverse neurodevelopmental outcomes.ObjectivesWe developed a short tool for collecting maternal nutritional intake during pregnancy to facilitate research in this area and compared its retrospective use to prospectively-collected food frequency questionnaires (FFQ).MethodsMaternal nutritional intake was retrospectively assessed using three versions (full interview, full self-administered online, and shortened interview) of the Early Life Exposure Assessment Tool (ELEAT) among participants of the MARBLES pregnancy cohort study of younger siblings of autistic children. Retrospective responses were compared with responses to supplement questions and the validated 2005 Block FFQ prospectively collected in MARBLES during pregnancies 2-7 years prior. ELEAT nutrient values were calculated using reported food intake frequencies and nutrient values from the USDA nutrient database. Correlations between retrospectively- and prospectively-reported intake were evaluated using Kappa coefficients, Youden's J, and Spearman Rank Correlation Coefficients (rs).ResultsMARBLES FFQ dietary intakes were compared among 54 women who completed the ELEAT full form including 12 online, and among 23 who completed the ELEAT short form. Correlations across most foods were fair to moderate. Most ELEAT quantified nutrient values were moderately correlated (rs = 0.3-0.6) with those on the Block FFQ. Supplement questions in both MARBLES and the ELEAT were completed by 114 women. Kappas were moderate for whether or not supplements were taken, but modest for timing. Correlations varied by version and child diagnosis or concerns, and were higher when mothers completed the ELEAT when their child was 4 years old or younger.ConclusionsWith recall up to several years, ELEAT dietary and supplement module responses were modestly to moderately reliable and produced nutrient values moderately correlated with prospectively-collected measures. The ELEAT dietary and vitamin supplements modules can be used to rank participants in terms of intake of several nutrients relevant for neurodevelopment.

BACKGROUND: Dietary supplement (DS) use is common and increasing among older adults, though much data available on use frequencies are from surveys and performed cross-sectionally. This paper sought to assess the frequency and pattern of dietary supplement use among older adults over time. METHODS: A secondary analysis of data from the AAA LongROAD study, a longitudinal prospective cohort study of older adult drivers, using data from baseline and the first two years of follow up included a total of 2990 drivers aged 65-79 years recruited at five study sites across the US from July 2015 to March 2017. Participants underwent baseline and annual evaluations, which included a brown bag medication review. DS were identified and categorized according to type and key components. Prevalence and pattern of DS use over time and relationship to demographics were measured with frequency and Chi squared analyses. RESULTS: 84% of participants took at least one dietary supplement during the 2-year study period, and 55% of participants continually reported use. DS accounted for approximately 30% of the total pharmacologic-pill burden in all years. Participants who were White non-Hispanic, female, 75-79 years of age at baseline, and on more non-supplement medications took significantly more dietary supplements (P

Agricultural systems are under increasing pressure from declining environmental conditions, a growing population, and changes in consumer preferences, resulting in widespread malnutrition-related illnesses. Improving plant nutritional content through biotechnology techniques such as synthetic biology is a promising strategy to help combat hidden hunger caused by the lack of affordable and healthy foods in human diets. Production of compounds usually found in animal-rich diets, such as vitamin D or omega-3 fatty acids, has been recently demonstrated in planta. Here, we review recent biotechnological approaches to biofortifying plants with vitamins, minerals, and other metabolites, and summarise synthetic biology advances that offer the opportunity to build on these early biofortification efforts.

Probiotics are typically marketed as foods and dietary supplements, categories for products intended to maintain health in generally healthy populations and which, unlike drugs, cannot claim to treat or cure disease. This review addresses the existing evidence that probiotics are beneficial to healthy people. Our approach was to perform a descriptive review of efficacy evidence that probiotics can prevent urinary, vaginal, gastrointestinal, and respiratory infections, and improve risk factors associated with cardiovascular health or reduce antibiotic use. Other endpoints such as mental, dental, or immune health were not specifically addressed. We concluded that there is sufficient evidence of efficacy and safety for clinicians and consumers to consider using specific probiotics for some indications - such as the use of probiotics to support gut function during antibiotic use or to reduce the risk of respiratory tract infections - for certain people. However, we did not find a sufficiently high level of evidence to support unconditional, population-wide recommendations for other preventive endpoints we reviewed for healthy people. Although evidence for some indications is suggestive of the preventive benefits of probiotics, additional research is needed.

Iron is essential for life, but its imbalances can lead to severe health implications. Iron deficiency is the most common nutrient disorder worldwide, and iron disregulation in early life has been found to cause long-lasting behavioral, cognitive, and neural effects. However, little is known about the effects of dietary iron on gut microbiome function and metabolism. In this study, we sought to investigate the impact of dietary iron on the fecal metabolome and microbiome by using mice fed with three diets with different iron content: an iron deficient, an iron sufficient (standard), and an iron overload diet for seven weeks. Additionally, we sought to understand whether any observed changes would persist past the 7-week period of diet intervention. To assess this, all feeding groups were switched to a standard diet, and this feeding continued for an additional 7 weeks. Analysis of the fecal metabolome revealed that iron overload and deficiency significantly alter levels of peptides, nucleic acids, and lipids, including di- and tri-peptides containing branched-chain amino acids, inosine and guanosine, and several microbial conjugated bile acids. The observed changes in the fecal metabolome persist long after the switch back to a standard diet, with the cecal gut microbiota composition and function of each group distinct after the 7-week standard diet wash-out. Our results highlight the enduring metabolic consequences of nutritional imbalances, mediated by both host and gut microbiome, which persist after returning to original standard diets.

Congenital diarrheas and enteropathies (CODE) are a group of rare, heterogenous, monogenic disorders that lead to chronic diarrhea in infancy. Definitive treatment is rarely available, and supportive treatment is the mainstay. Nutritional management in the form of either specialized formulas, restrictive diet, or parenteral nutrition support in CODE with poor enteral tolerance is the cornerstone of CODE treatment and long-term growth. The evidence to support the use of specific diet regimens and nutritional approaches in most CODE disorders is limited due to the rarity of these diseases and the scant published clinical experience. The goal of this review was to create a comprehensive guide for nutritional management in CODE, based on the currently available literature, disease mechanism, and the PediCODE group experience. Enteral diet management in CODE can be divided into 3 distinct conceptual frameworks: nutrient elimination, nutrient supplementation, and generalized nutrient restriction. Response to nutrient elimination or supplementation can lead to resolution or significant improvement in the chronic diarrhea of CODE and resumption of normal growth. This pattern can be seen in CODE due to carbohydrate malabsorption, defects in fat absorption, and occasionally in electrolyte transport defects. In contrast, general diet restriction is mainly supportive. However, occasionally it allows parenteral nutrition weaning or reduction over time, mainly in enteroendocrine defects and rarely in epithelial trafficking and polarity defects. Further research is required to better elucidate the role of diet in the treatment of CODE and the appropriate diet management for each disease.

Deep learning-based mammographic evaluations could noninvasively assess response to breast cancer chemoprevention. We evaluated change in a convolutional neural network-based breast cancer risk model applied to mammograms among women enrolled in SWOG S0812, which randomly assigned 208 premenopausal high-risk women to receive oral vitamin D3 20 000 IU weekly or placebo for 12 months. We applied the convolutional neural network model to mammograms collected at baseline (n = 109), 12 months (n = 97), and 24 months (n = 67) and compared changes in convolutional neural network-based risk score between treatment groups. Change in convolutional neural network-based risk score was not statistically significantly different between vitamin D and placebo groups at 12 months (0.005 vs 0.002, P = .875) or at 24 months (0.020 vs 0.001, P = .563). The findings are consistent with the primary analysis of S0812, which did not demonstrate statistically significant changes in mammographic density with vitamin D supplementation compared with placebo. There is an ongoing need to evaluate biomarkers of response to novel breast cancer chemopreventive agents.

Vitamin B12 is critical for hematopoiesis and myelination. Deficiency can cause neurologic deficits including loss of coordination and cognitive decline. However, diagnosis relies on measurement of vitamin B12 in the blood, which may not accurately reflect the concentration in the brain. Using programmable phage display, we identified an autoantibody targeting the transcobalamin receptor (CD320) in a patient with progressive tremor, ataxia, and scanning speech. Anti-CD320 impaired cellular uptake of cobalamin (B12) in vitro by depleting its target from the cell surface. Despite a normal serum concentration, B12 was nearly undetectable in her cerebrospinal fluid (CSF). Immunosuppressive treatment and high-dose systemic B12 supplementation were associated with increased B12 in the CSF and clinical improvement. Optofluidic screening enabled isolation of a patient-derived monoclonal antibody that impaired B12 transport across an in vitro model of the blood-brain barrier (BBB). Autoantibodies targeting the same epitope of CD320 were identified in seven other patients with neurologic deficits of unknown etiology, 6% of healthy controls, and 21.4% of a cohort of patients with neuropsychiatric lupus. In 132 paired serum and CSF samples, detection of anti-CD320 in the blood predicted B12 deficiency in the brain. However, these individuals did not display any hematologic signs of B12 deficiency despite systemic CD320 impairment. Using a genome-wide CRISPR screen, we found that the low-density lipoprotein receptor serves as an alternative B12 uptake pathway in hematopoietic cells. These findings dissect the tissue specificity of B12 transport and elucidate an autoimmune neurologic condition that may be amenable to immunomodulatory treatment and nutritional supplementation.

Objectives: White spot lesions are more susceptible to staining agents due to their porous structure. This study examines the impact of white spot lesion treatments on discoloration caused by pediatric supplements. Method and materials: Three treatments (fluoride, casein phosphopeptide-amorphous calcium phosphate [CPP-ACP], resin infiltration), a control, and their respective syrup-based subgroups (iron and black elderberry syrups) were established, each with eight teeth. Artificial white spot lesions were induced, and weekly applications of fluoride varnish, daily applications of CPP-ACP paste, or a single resin infiltration procedure were performed on the white spot lesions within the treatment groups over 4 weeks. Simultaneously, samples were exposed daily to iron or black elderberry syrups. Spectrophotometer measurements were taken at baseline, after demineralization (T0), and after 1 (T1), 2 (T2), and 4 weeks (T4). ΔE00 values were calculated. Statistical analysis was conducted using a three-way mixed-design ANOVA, with the significance level set at P = .05. Results: At T4, ΔE00 values from all groups exceeded the clinical acceptability limit of 1.8. At T2 and T4, the ΔE00 values obtained from the black elderberry syrup subgroups were significantly higher (P < .001). At T4, the highest ΔE00 values were seen in the CPP-ACP groups (P < .001). The lowest ΔE00 values at T2 and T4 were observed in the resin infiltration groups (P < .05). Conclusions: Supplements containing ferrous sulfate and black elderberry extract caused color changes in white spot lesions that exceeded the clinical acceptability limit. Resin infiltration of white spot lesions provides advantages over remineralization treatments, particularly in minimizing discoloration induced by pediatric supplements. [ABSTRACT FROM AUTHOR]

Purpose: Transmeridian travel is common for elite athletes participating in competitions and training. However, this travel can lead to circadian misalignment wherein the internal biological clock becomes desynchronized with the light–dark cycle of the new environment, resulting in performance decrement and potential negative health consequences. Existing literature extensively discusses recommendations for managing jet lag, predominantly emphasizing light-based interventions to synchronize the internal clock with the anticipated time at the destination. Nevertheless, visually impaired (VI) athletes may lack photoreceptiveness, diminishing or nullifying the effectiveness of this therapy. Consequently, this invited commentary explores alternative strategies for addressing jet lag in VI athletes. Conclusions: VI athletes with light perception but reduced visual acuity or visual fields may still benefit from light interventions in managing jet lag. However, VI athletes lacking a conscious perception of light should rely on gradual shifts in behavioral factors, such as meal timing and exercise, to facilitate the entrainment of circadian rhythms to the destination time. Furthermore, interventions like melatonin supplementation may prove useful during and after travel. In addition, it is recommended that athlete guides adopt phase-forward or phase-back approaches to synchronize with the athlete, aiding in jet-lag management and optimizing performance. [ABSTRACT FROM AUTHOR]

This study assessed the effect of combined jump training and collagen supplementation on bone mineral density (BMD) in elite road-race cyclists. In this open-label, randomized study with two parallel groups, 36 young (21 ± 3 years) male (n = 8) and female (n = 28) elite road-race cyclists were allocated to either an intervention (INT: n = 18) or a no-treatment control (CON: n = 18) group. The 18-week intervention period, conducted during the off-season, comprised five 5-min bouts of jumping exercise per week, with each bout preceded by the ingestion of 15 g hydrolyzed collagen. Before and after the intervention, BMD of various skeletal sites and trabecular bone score of the lumbar spine were assessed by dual-energy X-ray absorptiometry, along with serum bone turnover markers procollagen Type I N propeptide and carboxy-terminal cross-linking telopeptide of Type I collagen. BMD of the femoral neck decreased in CON (from 0.789 ± 0.104 to 0.774 ± 0.095 g/cm2), while being preserved in INT (from 0.803 ± 0.058 to 0.809 ± 0.066 g/cm2; Time × Treatment, p <.01). No differences between treatments were observed for changes in BMD at the total hip, lumbar spine, and whole body (Time × Treatment, p >.05 for all). Trabecular bone score increased from 1.38 ± 0.08 to 1.40 ± 0.09 in CON and from 1.46 ± 0.08 to 1.47 ± 0.08 in INT, respectively (time effect: p <.01), with no differences between treatments (Time × Treatment: p =.33). Serum procollagen Type I N propeptide concentrations decreased to a similar extent in CON (83.6 ± 24.8 to 71.4 ± 23.1 ng/ml) and INT (82.8 ± 30.7 to 66.3 ± 30.6; time effect, p <.001; Time × Treatment, p =.22). Serum carboxy-terminal cross-linking telopeptide of Type I collagen concentrations did not change over time, with no differences between treatments (time effect, p =.08; Time × Treatment, p =.58). In conclusion, frequent short bouts of jumping exercise combined with collagen supplementation beneficially affects femoral neck BMD in elite road-race cyclists. [ABSTRACT FROM AUTHOR]

The present randomized study investigated the effect of acute supplementation of 800 mg/kg of ketone monoester ingestion (KE) or placebo (PL) and 210 mg/kg of NaHCO3 co-ingestion on cycling performance of WorldTour cyclists during a road cycling stage simulation. Twenty-eight cyclists participated in the study (27.46 ± 4.32 years; 1.80 ± 0.06 m; 69.74 ± 6.36 kg). Performance, physiological, biochemical, and metabolism outcomes, gut discomfort, and effort perceived were assessed during a road cycling simulation composed of an 8-min time-trial (TT) performance + 30-s TT + 4.5 hr of outdoor cycling + a second 8-min TT + a second 30-s TT. Greater absolute and relative mean power during the first 8-min TT (F = 5.067, p =.033, η p 2 =.163 , F = 5.339, p =.029, η p 2 =.170 , respectively) was observed after KE than after PL (KE: 389 ± 34, PL: 378 ± 44 W, p =.002, d = 0.294 and KE: 5.60 ± 0.42, PL: 5.41 ± 0.44 W/kg, p =.001, d = 0.442). Additionally, greater concentration of β-hydroxybutyrate blood concentration (F = 42.195, p <.001, η p 2 =.619) was observed after KE than after PL during the first steps of the stage (e.g., after warm-up KE: 1.223 ± 0.642, PL: 0.044 ± 0.058 mM, p <.001, d = 2.589), although the concentrations returned to near baseline after 4.5 hr of outdoor cycling. Moreover, higher values of anion gap were observed (F = 2.333, p =.026, η p 2 =.080) after KE than after PL ingestion, after the warm-up and after the first 8-min and 30-s TT. Additionally, lower concentrations of HCO 3 − were reported in the KE condition after warm-up and after the first 8-min and 30-s TT. During the initial phase of the stage simulation, acute supplementation with KE + NaHCO3 co-ingestion enhanced 8-min TT cycling performance (3.1%) in WorldTour cyclists with a concomitant hyperketonaemia. [ABSTRACT FROM AUTHOR]

ObjectiveThe aim of this study was to examine associations between empirically derived dietary pattern scores and cognition, as well as risk of cognitive decline, over an average of 4.6 (± 0.3) years in older men.Materials and methodsThis analysis was conducted as part of the Osteoporotic Fractures in Men (MrOS) prospective cohort study. Diet was assessed at Visit 1 (3/2000-4/2002) by food frequency questionnaire, and dietary patterns (Western and Prudent) were derived by factor analysis. The analytic cohort comprised 4231 community-dwelling American men who were aged 65 years or more. Cognitive function was assessed with the Modified Mini-Mental State exam (3MS) and the Trails B test at Visit 1 and at Visit 2 (3/2005-5/2006). Associations between dietary pattern score and cognition and risk of cognitive decline were estimated using mixed effects regression models. Model 1 was adjusted for age, clinic site and total energy intake (TEI). Model 2 was further adjusted for calcium and vitamin D supplement use, body mass index (BMI), physical activity, smoking, diabetes and hypertension (Western diet group) and education, calcium and vitamin D supplement use, depression, BMI, physical activity, smoking and stroke (Prudent diet group).ResultsAdherence to the Western dietary pattern was associated with higher 3MS scores and shorter Trails B test time at Visit 1 in Model 2. Adherence to the Prudent dietary pattern was associated with higher 3MS scores in Model 1 but not Model 2. There were no independent associations between dietary pattern scores and risk of cognitive decline 4.6 (± 0.3) years later at Visit 2.ConclusionThe results do not support a robust protective effect of the Prudent dietary pattern on cognition in the MrOS cohort. Associations between the Western dietary pattern and better cognitive scores should be interpreted with caution. Further research is needed to understand the complex interactions between dietary patterns and cognition in older men.

BackgroundDespite mixed evidence regarding the safety and efficacy of natural products, many are marketed for pain and related symptoms. Use of these products is prevalent among veterans, who have disproportionately high rates of chronic pain. To date, however, there is limited research on veterans' beliefs and attitudes about natural products and their communication with healthcare providers about their natural product use.ObjectiveTo explore how veterans experiencing chronic pain make decisions about natural product use, to investigate veterans' beliefs about the safety and efficacy of these products, and to examine veterans' experiences discussing natural products with their providers.DesignQualitative sub-study conducted as a supplement to a pragmatic randomized controlled trial for chronic pain management.ParticipantsTwenty veterans experiencing chronic pain who reported using natural products for pain management or related health concerns.ApproachQualitative interviews with veterans were conducted over the phone and audio-recorded. Interviews were guided by an original semi-structured interview guide and qualitative data were analyzed using a template-based rapid analysis technique.Key resultsVeterans with chronic pain may perceive natural products as safer than pharmaceutical products and may prefer to use natural products. Talking with providers about natural products is important to veterans, who would like information regarding the safety and potential for interaction of natural products with pharmaceutical products. However, veterans were frequently disappointed with these conversations. Veterans felt their providers demonstrated biases against natural products, which negatively impacted patient-provider relationships.ConclusionsVeterans wish to have more productive conversations with providers about natural products. They value providers' open-mindedness towards natural products and transparency about limitations in their knowledge. Suggestions for how providers and healthcare systems might better support veterans interested in natural products are discussed.

AbstractAlthough numerous studies have demonstrated the impact of microbiome manipulation on human health, research on the microbiome's influence on female health remains relatively limited despite substantial disease burden. In light of this, we present a selected review of clinical trials and preclinical studies targeting both the vaginal and gut microbiomes for the prevention or treatment of various gynecologic conditions. Specifically, we explore studies that leverage microbiota transplants, probiotics, prebiotics, diet modifications, and engineered microbial strains. A healthy vaginal microbiome for females of reproductive age consists of lactic acid-producing bacteria predominantly of the Lactobacillus genus, which serves as a protective barrier against pathogens and maintains a balanced ecosystem. The gut microbiota's production of short-chain fatty acids, metabolism of primary bile acids, and modulation of sex steroid levels have significant implications for the interplay between host and microbes throughout the body, ultimately impacting reproductive health. By harnessing interventions that modulate both the vaginal and gut microbiomes, it becomes possible to not only maintain homeostasis but also mitigate pathological conditions. While the field is still working toward making broad clinical recommendations, the current studies demonstrate that manipulating the microbiome holds great potential for addressing diverse gynecologic conditions.Lay summaryManipulating the microbiome has recently entered popular culture, with various diets thought to aid the microbes that live within us. These microbes live in different locations of our body and accordingly help us digest food, modulate our immune system, and influence reproductive health. The role of the microbes living in and influencing the female reproductive tract remains understudied despite known roles in common conditions such as vulvovaginal candidiasis (affecting 75% of females in their lifetime), bacterial vaginosis (25% of females in their lifetime), cervical HPV infection (80% of females in their lifetime), endometriosis (6-10% of females of reproductive age), and polycystic ovary syndrome (10-12% of females of reproductive age). Here, we review four different approaches used to manipulate the female reproductive tract and gastrointestinal system microbiomes: microbiota transplants, probiotics, prebiotics, and dietary interventions, and the use of engineered microbial strains. In doing so, we aim to stimulate discussion on new ways to understand and treat female reproductive health conditions.

Herbal medicines are used by patients with IBD despite limited evidence. We present a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating treatment with herbal medicines in active ulcerative colitis (UC). A search query designed by a library informationist was used to identify potential articles for inclusion. Articles were screened and data were extracted by at least two investigators. Outcomes of interest included clinical response, clinical remission, endoscopic response, endoscopic remission, and safety. We identified 28 RCTs for 18 herbs. In pooled analyses, when compared with placebo, clinical response rates were significantly higher for Indigo naturalis (IN) (RR 3.70, 95% CI 1.97-6.95), but not for Curcuma longa (CL) (RR 1.60, 95% CI 0.99-2.58) or Andrographis paniculata (AP) (RR 0.95, 95% CI 0.71-1.26). There was a significantly higher rate of clinical remission for CL (RR 2.58, 95% CI 1.18-5.63), but not for AP (RR 1.31, 95% CI 0.86-2.01). Higher rates of endoscopic response (RR 1.56, 95% CI 1.08-2.26) and remission (RR 19.37, 95% CI 2.71-138.42) were significant for CL. CL has evidence supporting its use as an adjuvant therapy in active UC. Research with larger scale and well-designed RCTs, manufacturing regulations, and education are needed.

Glucosinolates are plant-specialized metabolites that can be hydrolyzed by glycosyl hydrolases, called myrosinases, creating a variety of hydrolysis products that benefit human health. While cruciferous vegetables are a rich source of glucosinolates, they are often cooked before consumption, limiting the conversion of glucosinolates to hydrolysis products due to the denaturation of myrosinases. Here we screen a panel of glycosyl hydrolases for high thermostability and engineer the Brassica crop, broccoli (Brassica oleracea L.), for the improved conversion of glucosinolates to chemopreventive hydrolysis products. Our transgenic broccoli lines enabled glucosinolate hydrolysis to occur at higher cooking temperatures, 20 °C higher than in wild-type broccoli. The process of cooking fundamentally transforms the bioavailability of many health-relevant bioactive compounds in our diet. Our findings demonstrate the promise of leveraging genetic engineering to tailor crops with novel traits that cannot be achieved through conventional breeding and improve the nutritional properties of the plants we consume.

The complex role of the gut microbiome in the pathogenesis of gastrointestinal (GI) disorders is an emerging area of research, and there is considerable interest in understanding how diet can alter the composition and function of the microbiome. Prebiotics and probiotics have been shown to beneficially modulate the gut microbiome, which underlies their potential for benefit in GI conditions. Formulating specific recommendations for the public regarding these dietary supplements has been difficult due to the significant heterogeneity between strains, doses, and duration of treatment investigated across studies, as well as safety concerns with administering live organisms. This review aims to summarize the existing evidence for the use of prebiotics and probiotics in various GI disorders, paying special attention to strain-specific effects that emerged and any adverse effects noted.

PurposeChronic inflammation is integral to myeloproliferative neoplasm (MPN) pathogenesis. JAK inhibitors reduce cytokine levels, but not without significant side effects. Nutrition is a low-risk approach to reduce inflammation and ameliorate symptoms in MPN. We performed a randomized, parallel-arm study to determine the feasibility of an education-focused Mediterranean diet intervention among patients with MPN.Experimental designWe randomly assigned patients with MPN to either a Mediterranean diet or standard U.S. Dietary Guidelines for Americans (USDA). Groups received equal but separate education with registered dietician counseling and written dietary resources. Patients were prospectively followed for feasibility, adherence, and symptom burden assessments. Biological samples were collected at four timepoints during the 15-week study to explore changes in inflammatory biomarkers and gut microbiome.ResultsThe Mediterranean diet was as easy to follow for patients with MPN as the standard USDA diet. Approximately 80% of the patients in the Mediterranean diet group achieved a Mediterranean Diet Adherence Score of ≥8 throughout the entire active intervention period, whereas less than 50% of the USDA group achieved a score of ≥8 at any timepoint. Improvement in symptom burden was observed in both diet groups. No significant changes were observed in inflammatory cytokines. The diversity and composition of the gut microbiome remained stable throughout the duration of the intervention.ConclusionsWith dietician counseling and written education, patients with MPN can adhere to a Mediterranean eating pattern. Diet interventions may be further developed as a component of MPN care, and potentially incorporated into the management of other hematologic conditions.SignificanceDiet is a central tenant of management of chronic conditions characterized by subclinical inflammation, such as cardiovascular disease, but has not entered the treatment algorithm for clonal hematologic disorders. Here, we establish that a Mediterranean diet intervention is feasible in the MPN patient population and can improve symptom burden. These findings warrant large dietary interventions in patients with hematologic disorders to test the impact of diet on clinical outcomes.

This systematic meta-review evaluated the effects of exercise with and without protein interventions on muscle strength and function in older adults with sarcopenic obesity. PubMed, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, Scopus, and SPORTDiscus databases were searched through February 2021 for relevant systematic reviews and meta-analyses with aerobic, resistance, and/or combined training interventions with and without protein supplementation in older adults ≥ 65 years with sarcopenic obesity. This meta-review showed that exercise with and without protein supplementation improved body composition (i.e., decreased percentage body fat) and functional outcomes (i.e., gait speed and grip strength). Because the current literature is limited, determining the effects of exercise and combined protein supplementation in this population requires further investigation. In the meantime, protein recommendations should align with general sarcopenia recommendations. Based upon available findings, tentative exercise recommendations to optimize health outcomes in this population are proposed. [ABSTRACT FROM AUTHOR]

Resistance training alongside proper protein intake is an important tool to mitigate the deleterious effects of the aging process on skeletal muscle tissue. However, it is not completely elucidated whether adding protein supplementation provides further improvements on body composition outcomes of older adults during resistance training programs. The present narrative review aimed to describe the most recent evidence regarding the effects of protein supplementation on both lean body mass and fat mass of older adults and to provide insight into how health professionals may use this information to properly design nutritional programs for this population. While individuals with previous training experience, not meeting daily protein requirement, or displaying frailty symptoms may experience some benefits, protein supplementation does not seem to provide further improvements in untrained and healthy subjects. Aspects such as the age of the individuals and the different characteristics of the supplementation protocols must be considered when making evidence-based decisions regarding this topic. [ABSTRACT FROM AUTHOR]

OBJECTIVE: n-3 fatty acid consumption during pregnancy is recommended for optimal pregnancy outcomes and offspring health. We examined characteristics associated with self-reported fish or n-3 supplement intake. DESIGN: Pooled pregnancy cohort studies. SETTING: Cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) consortium with births from 1999 to 2020. PARTICIPANTS: A total of 10 800 pregnant women in twenty-three cohorts with food frequency data on fish consumption; 12 646 from thirty-five cohorts with information on supplement use. RESULTS: Overall, 24·6 % reported consuming fish never or less than once per month, 40·1 % less than once a week, 22·1 % 1-2 times per week and 13·2 % more than twice per week. The relative risk (RR) of ever (v. never) consuming fish was higher in participants who were older (1·14, 95 % CI 1·10, 1·18 for 35-40 v.

Cancer therapy, including immunotherapy, is inherently limited by chronic inflammation-induced tumorigenesis and toxicity within the tumor microenvironment. Thus, stimulating the resolution of inflammation may enhance immunotherapy and improve the toxicity of immune checkpoint inhibition (ICI). As epoxy-fatty acids (EpFAs) are degraded by the enzyme soluble epoxide hydrolase (sEH), the inhibition of sEH increases endogenous EpFA levels to promote the resolution of cancer-associated inflammation. Here, we demonstrate that systemic treatment with ICI induces sEH expression in multiple murine cancer models. Dietary omega-3 polyunsaturated fatty acid supplementation and pharmacologic sEH inhibition, both alone and in combination, significantly enhance anti-tumor activity of ICI in these models. Notably, pharmacological abrogation of the sEH pathway alone or in combination with ICI counter-regulates an ICI-induced pro-inflammatory and pro-tumorigenic cytokine storm. Thus, modulating endogenous EpFA levels through dietary supplementation or sEH inhibition may represent a unique strategy to enhance the anti-tumor activity of paradigm cancer therapies.

Cholera is a global health problem with no targeted therapies. The Ca2+-sensing receptor (CaSR) is a regulator of intestinal ion transport and a therapeutic target for diarrhea, and Ca2+ is considered its main agonist. We found that increasing extracellular Ca2+ had a minimal effect on forskolin-induced Cl- secretion in human intestinal epithelial T84 cells. However, extracellular Mg2+, an often-neglected CaSR agonist, suppressed forskolin-induced Cl- secretion in T84 cells by 65% at physiological levels seen in stool (10 mM). The effect of Mg2+ occurred via the CaSR/Gq signaling that led to cAMP hydrolysis. Mg2+ (10 mM) also suppressed Cl- secretion induced by cholera toxin, heat-stable E. coli enterotoxin, and vasoactive intestinal peptide by 50%. In mouse intestinal closed loops, luminal Mg2+ treatment (20 mM) inhibited cholera toxin-induced fluid accumulation by 40%. In a mouse intestinal perfusion model of cholera, addition of 10 mM Mg2+ to the perfusate reversed net fluid transport from secretion to absorption. These results suggest that Mg2+ is the key CaSR activator in mouse and human intestinal epithelia at physiological levels in stool. Since stool Mg2+ concentrations in patients with cholera are essentially zero, oral Mg2+ supplementation, alone or in an oral rehydration solution, could be a potential therapy for cholera and other cyclic nucleotide-mediated secretory diarrheas.

Microbial chemoautotroph-heterotroph interactions may play a pivotal role in the cycling of carbon in the deep ocean, reminiscent of phytoplankton-heterotroph associations in surface waters. Nitrifiers are the most abundant chemoautotrophs in the global ocean, yet very little is known about nitrifier metabolite production, release, and transfer to heterotrophic microbial communities. To elucidate which organic compounds are released by nitrifiers and potentially available to heterotrophs, we characterized the exo- and endometabolomes of the ammonia-oxidizing archaeon Nitrosopumilus adriaticus CCS1 and the nitrite-oxidizing bacterium Nitrospina gracilis Nb-211. Nitrifier endometabolome composition was not a good predictor of exometabolite availability, indicating that metabolites were predominately released by mechanisms other than cell death/lysis. Although both nitrifiers released labile organic compounds, N. adriaticus preferentially released amino acids, particularly glycine, suggesting that its cell membranes might be more permeable to small, hydrophobic amino acids. We further initiated co-culture systems between each nitrifier and a heterotrophic alphaproteobacterium, and compared exometabolite and transcript patterns of nitrifiers grown axenically to those in co-culture. In particular, B vitamins exhibited dynamic production and consumption patterns in nitrifier-heterotroph co-cultures. We observed an increased production of vitamin B2 and the vitamin B12 lower ligand dimethylbenzimidazole by N. adriaticus and N. gracilis, respectively. In contrast, the heterotroph likely produced vitamin B5 in co-culture with both nitrifiers and consumed the vitamin B7 precursor dethiobiotin when grown with N. gracilis. Our results indicate that B vitamins and their precursors could play a particularly important role in governing specific metabolic interactions between nitrifiers and heterotrophic microbes in the ocean.

Background: Childhood vitamin A deficiency leads to increased morbidity and mortality. Human milk is the only source of vitamin A for exclusively breastfed infants. Dried Moringa oleifera leaf powder (moringa) is a good food source of provitamin A and other carotenoids. Its effect during lactation on human milk vitamin A and carotenoid content is unclear. Objectives: Our objective was to investigate the effect of maternal moringa consumption on human milk retinol and carotenoid concentrations and maternal and infant vitamin A status. Methods: We conducted a 3-month pilot single-blinded cluster-randomized controlled trial in breastfeeding mother-infant pairs (n = 50) in Kenya. Mothers received corn porridge with (20 g/d) or without moringa with complete breast expressions and maternal and infant serum collected at enrollment (infant

BACKGROUND: DATATOP was a study of early Parkinsons disease (PD) conducted in the 1980 s, before mandatory folic acid fortification in the United States. Our analysis of its baseline serum samples revealed a geometric mean vitamin B12 of 369 pg/mL and homocysteine (tHcy) of 9.5μmol/l. We also found that low B12 predicted greater worsening of ambulatory capacity (AC) and elevated tHcy (>15μmol/L) predicted greater declines in cognitive function. OBJECTIVE: We sought to measure B12 and tHcy in contemporary trial participants with early PD who had not started dopaminergic treatment and to determine whether these analytes were associated with clinical progression. METHODS: We measured B12 and tHcy from baseline and end-of-study blood samples from three recent clinical trials. RESULTS: Baseline geometric mean B12 levels for these studies ranged from 484- 618 pg/ml and for tHcy ranged from 7.4- 10μmol/L. Use of B12-containing supplements ranged from 41- 61%, and those taking supplements had higher B12 and lower tHcy. Those who began levodopa, but were not taking B12-supplements, had greater end-of-study tHcy. There was no association of baseline tHcy > 15μmol/L with annualized change in Montreal Cognitive Assessment and no association of baseline B12 tertiles with change in AC. CONCLUSIONS: In these longitudinal trials, B12 levels were higher than for DATATOP, due in large part to increased B12-supplement intake, while tHcy levels were similar. Initiation of levodopa was associated with increases of tHcy in those not taking a B12-containing supplement. These smaller studies did not replicate prior findings of low B12 and elevated tHcy with features of progression, possibly due to higher baseline B12.