Betaine HCl

PURPOSE: Clinically relevant pharmacokinetic interactions exist between gastric acid-reducing agents and certain weakly basic drugs that rely on acidic environments for optimal oral absorption. In this study, we examine whether the administration of betaine hydrochloride under fed conditions can enhance the absorption of atazanavir, an HIV-1 protease inhibitor, during pharmacologically-induced hypochlorhydria. METHODS: In this randomized, single-dose, 3 period, crossover study healthy volunteers received ritonavir-boosted atazanavir (atazanavir/ritonavir 300/100 mg) alone, following pretreatment with the proton pump inhibitor rabeprazole (20 mg twice daily), and with 1500 mg of betaine HCl after rabeprazole pretreatment. Atazanavir was administered with a light meal and gastric pH was monitored using the Heidelberg Capsule. RESULTS: Pretreatment with rabeprazole resulted in significant reductions in atazanavir Cmax (p < 0.01) and AUC0-last (p < 0.001) (71 and 70%, respectively), and modest decreases in ritonavir Cmax and AUClast (p < 0.01) (40% and 41%, respectively). The addition of betaine HCl restored 13% of ATV Cmax and 12% of AUClast lost due to rabeprazole. CONCLUSIONS: The co-administration of rabeprazole with atazanavir resulted in significant decreases in atazanavir exposure. The addition of betaine HCl did not sufficiently mitigate the loss of ATV exposure observed during RAB-induced hypochlorhydria. Meal effects lead to a marked difference in the outcome of betaine HCl on atazanavir exposure than we previously reported for dasatanib under fasting conditions.

Many orally administered, small-molecule, targeted anticancer drugs, such as dasatinib, exhibit pH-dependent solubility and reduced drug exposure when given with acid-reducing agents. We previously demonstrated that betaine hydrochloride (BHCl) can transiently re-acidify gastric pH in healthy volunteers with drug-induced hypochlorhydria. In this randomized, single-dose, three-way crossover study, healthy volunteers received dasatinib (100 mg) alone, after pretreatment with rabeprazole, and with 1500 mg BHCl after rabeprazole pretreatment, to determine if BHCl can enhance dasatinib absorption in hypochlorhydric conditions. Rabeprazole (20 mg b.i.d.) significantly reduced dasatinib Cmax and AUC0-∞ by 92 and 78%, respectively. However, coadministration of BHCl significantly increased dasatinib Cmax and AUC0-∞ by 15- and 6.7-fold, restoring them to 105 and 121%, respectively, of the control (dasatinib alone). Therefore, BHCl reversed the impact of hypochlorhydria on dasatinib drug exposure and may be an effective strategy to mitigate potential drug-drug interactions for drugs that exhibit pH-dependent solubility and are administered orally under hypochlorhydric conditions.

BACKGROUND: Low folate levels in women of childbearing age can cause various health issues. Additionally, low perinatal folate concentrations are a significant cause of neural tube defects. Currently, folic acid supplements mainly consist of folic acid and the active form of folate. Therefore, this systematic review and meta-analysis aimed to evaluate the effectiveness and safety of the active form of folate in women of childbearing age. METHODS: We searched the published literature in PubMed, Medline, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, and Wanfang. Randomized controlled trials (RCTs) were obtained to assess the effects of the active form of folate versus folic acid in women of childbearing age. The random or fixed effects model was used to analyze the data in meta-analysis. The results were expressed as standardized mean differences or risk ratios along with their corresponding 95% confidence intervals. RESULTS: Eleven RCTs were identified in our systematic review. The results indicated that the active form of folate supplementation might significantly increase plasma folate (P = .04), increase erythrocyte folate (P = .01), and decrease unmetabolized folic acid (P < .0001). Supplementation with the active form of folate might increase the subsequent pregnancy rates (P = .0005) and might decrease the incidence of adverse pregnancy outcomes (P = .0003) in women with a history of adverse pregnancy outcomes. However, there were no significant differences in homocysteine, vitamin B12, and betaine. In addition, subgroup analyses showed a significant increase in plasma folate and erythrocyte folate in the active form of folate supplementation group, specifically in subgroups with dosage ≥0.4 mg, intervention of the active form of folate supplementation versus the equimolar mass of folic acid, and intervention duration ≥12 weeks. CONCLUSION: Active form of folate supplementation might contribute to higher plasma folate, erythrocyte folate, and subsequent pregnancy rates, lower unmetabolized folic acid, and lower incidence of adverse pregnancy outcomes in women of childbearing age. Due to the limitation in the quality of involved stud

IMPORTANCE: Treatments for men seeking fertility care are limited. Antioxidant supplements have been widely studied as a new treatment option, but these studies have had conflicting results. OBJECTIVE: To assess whether treatment of men seeking fertility care with an antioxidant supplement can improve semen quality and pregnancy rates compared with a placebo. DESIGN, SETTING, AND PARTICIPANTS: The SUMMER trial was a multicenter, double-blind, placebo-controlled randomized clinical trial conducted in 21 hospitals and private fertility clinics in the Netherlands. Male patients in these centers were enrolled between May 2018 and February 2024, and follow-up of the primary outcome was completed in December 2024. Eligible participants were men aged 18 to 50 years with female partners aged 18 to 43 years, who sought fertility care and were advised to undergo expectant management, treatment with intrauterine insemination, in vitro fertilization (IVF), or intracytoplasmic sperm injection (ICSI). Couples treated with ovulation induction only or IVF for bilateral tubal pathology were excluded. The men were randomly assigned to receive an antioxidant supplement or a placebo. Intention-to-treat analysis was performed for all outcomes. INTERVENTIONS: The antioxidant supplement (Impryl) was a tablet to be taken daily for 6 months. It contained betaine (200 mg), L-cystine (200 mg), niacin (16 mg), zinc (10 mg), vitamin B6 (1.4 mg), vitamin B2 (1.4 mg), folic acid (400 µg), and vitamin B12 (2.5 µg). The placebo tablet and its packaging were identical to those of the antioxidant supplement. All participating couples received standard infertility care. MAIN OUTCOMES AND MEASURES: The primary outcome was ongoing pregnancy conceived within 6 months after randomization. Secondary outcomes included semen parameters, sperm DNA fragmentation, fertilization and embryo utilization rates after IVF or ICSI, biochemical and clinical pregnancy rates, first-trimester pregnancy loss, ectopic pregnancy rate, cumulative number of pregnancies, time to pregnancy, and adverse events. RESULTS: A total of 1171 men (median [IQR] age, 34 [31-38] years; female partners' median [IQR] age, 32 [30-35] year

BACKGROUND/OBJECTIVES: This study examined the effects of 2 weeks of betaine versus placebo supplementation (3 g/d) on 60 km cycling performance, gut permeability, and shifts in plasma metabolites. METHODS: Participants included 21 male and female non-elite cyclists. A randomized, placebo-controlled, double-blind, crossover design was used with two 2-week supplementation periods and a 2-week washout period. Supplementation periods were followed by a 60 km cycling time trial. Six blood samples were collected before and after supplementation (overnight fasted state), and at 0 h, 1.5 h, 3 h, and 24 h post-exercise. Five-hour urine samples were collected pre-supplementation and post-60 km cycling after ingesting a sugar solution containing lactulose 5 g, 13C mannitol 100 mg, and 12C mannitol 1.9 g in 450 mL water. Other outcome measures included plasma intestinal fatty acid binding protein-1 (I-FABP), muscle damage biomarkers (serum creatine kinase, myoglobin), serum cortisol, complete blood cell counts, and shifts in plasma metabolites using untargeted metabolomics. RESULTS: The time to complete the 60 km cycling bout differed significantly between the betaine and placebo trials (mean ± SE, 112.8 ± 2.3, 114.2 ± 2.6 min, respectively, (-1.41 ± 0.7 min) (effect size = 0.475, p = 0.042). No trial differences were found for I-FABP (interaction effect, p = 0.076), L:13CM (p = 0.559), the neutrophil/lymphocyte ratio (p = 0.171), serum cortisol (p = 0.982), serum myoglobin (p = 0.942), or serum creatine kinase (p = 0.694). Untargeted metabolomics showed that 214 metabolites exhibited significant trial treatment effects and 130 significant trial x time interaction effects. Betaine versus placebo supplementation was linked to significant increases in plasma betaine, dimethylglycine (DMG), sarcosine, methionine, S-adenosylhomocysteine (SAH), alpha-ketoglutaramate, and 5'methylthioadensone (MTA), and decreases in plasma carnitine and numerous acylcarnitines. CONCLUSIONS: Betaine supplementation modestly improved 60 km cycling performance but had no effect on gut permeability. The metabolomics data supported a strong influence of 2-week intake of betaine on the one-carbon meta

BACKGROUND AND AIMS: Alcohol Use Disorder (AUD) is a psychiatric disorder characterized notably by gut microbial dysbiosis and insufficient dietary fiber (DF) intake. This study aims to investigate the effect of DF placebo-controlled intervention in patients suffering from AUD during a three-week period of alcohol withdrawal, in order to discover microbial-derived metabolites that could be involved in metabolic and behavioral status. METHODS: A randomized, double-blind, placebo-controlled study was performed with 50 AUD patients supplemented with inulin (prebiotic DF) or maltodextrin (placebo) during 17 days. Fecal microbiota composition, plasma and fecal metabolomics (liquid chromatography coupled to mass spectrometry), blood markers of inflammation and hepatic alterations, and psychological assessment (questionnaires) were analyzed before and after the intervention. RESULTS: Fecal metabolomics revealed 14 metabolites significantly modified by inulin versus placebo treatment (increased N8-acetylspermidine and decreased indole-3-butyric acid, 5-amino valeric acid betaine (5-AVAB) and bile acids). Thirteen plasma metabolites differentiated both treatments (higher levels of long-chain fatty acids, medium-chain acylcarnitines and sphingomyelin species, and reduced 3-methylhistidine by inulin versus placebo). Fecal Lachnoclostridium correlated with 6 of the identified fecal metabolites, whereas plasma lipidic moieties positively correlated with fecal Ruminococcus torques group and Flavonifractor. Interestingly, parameters reflecting liver alterations inversely correlated with sphingomyelin (SM 36:2). CONCLUSIONS: Three weeks of inulin supplementation during alcohol withdrawal leads to specific and different changes in the plasma and fecal metabolome of AUD patients, some of these gut microbiota-related metabolites being correlated with liver function. TRIAL REGISTRATION: NCT03803709, https://clinicaltrials.gov/ct2/show/NCT03803709.

Background and Objectives: The goal of this study was to assess the impact of supplementation with a combination of nutrients on metabolic-dysfunction-associated steatotic liver disease (MASLD)-related liver parameters, and other parameters related to metabolic syndrome in adults with obesity. These measurements included anthropometric and lipid profiling, and FibroScan technology (controlled attenuation parameter (CAP) and transient elastography (TE) values). Materials and Methods: A double-blind, placebo-controlled pilot clinical trial was conducted over a three-month treatment period. Adults with metabolic syndrome and obesity were allocated to receive either a cocktail of nutrients with defined daily dosages (5-MTHF, betaine, alpha-linolenic acid, eicosapentaenoic acid, choline bitartrate, docosahexaenoic acid, and vitamin B12) or a placebo. The participants were evaluated at the start and the end of the three-month treatment period. Results: A total of 155 participants entered the study, comprising 84 in the treatment group and 71 in the placebo group. The administration of the nutritional supplement resulted in a notable reduction in both CAP and TE scores when compared to the placebo group. The treatment group exhibited a mean reduction in CAP of 4% (p < 0.05) and a mean reduction in TE of 7.8% (p < 0.05), indicative of a decline in liver fat content and fibrosis. Conclusions: The supplementation over a period of three months led to a significant amelioration of liver fibrosis and steatosis parameters in adults with metabolic syndrome and obesity. These findings suggest that this supplementation regimen could be a beneficial adjunct therapy for improving liver health in adults with obesity-induced MASLD.

Betaine supplementation is used by athletes, but its mechanism of action is still not fully understood. We hypothesized that betaine supplementation would increase betaine concentration and alter amino acid profiles in relation to MTHFR genotype and dose in physically active males. The study followed a randomized placebo-controlled cross-over design. Blood samples were collected before and after each supplementation period. Serum was analyzed for amino acid profile, homocysteine, betaine, choline, and trimethylamine N-oxide (TMAO) concentrations. For the washout analysis, only participants starting with betaine were included (n = 20). Statistical analysis revealed no differences in the amino acid profile after betaine supplementation. However, betaine concentration significantly increased after betaine supplementation (from 4.89 ± 1.59 µg/mL to 17.31 ± 9.21 µg/mL, P < .001), with a greater increase observed in MTHFR (C677T, rs180113) T-allele carriers compared to CC (P = .027). Betaine supplementation caused a decrease in homocysteine concentration (from 17.04 ± 4.13 µmol/L to 15.44 ± 3.48 µmol/L, P = .00005) and a non-significant increase in TMAO concentrations (from 0.27 ± 0.20 µg/ml to 0.44 ± 0.70 µg/ml, P = .053), but had no effect on choline concentrations. Serum betaine concentrations were not significantly different after the 21-day washout from the baseline values (baseline: 4.93 ± 1.87 µg/mL and after washout: 4.70 ± 1.70 µg/mL, P = 1.000). In conclusion, betaine supplementation increased betaine and decreased homocysteine concentrations, but did not affect the amino acid profile or choline concentrations in healthy active males. Betaine concentrations may be dependent on MTHFR genotype.

BACKGROUND: Modification of the nitrate (NO3)-nitrite (NO2)-nitric oxide (NO) pathway can be induced by oral intake of inorganic NO3 (NIT) or NO3-rich products, such as beetroot juice (BRJ). OBJECTIVES: The primary aim of this study was to evaluate the plasma changes in betaine, choline, trimethylamine (TMA), trimethylamine N-oxide (TMAO), and NO3/NO2 (NOx) concentrations over 4 h after single oral ingestion of NIT or BRJ. The flow-mediated skin fluorescence (FMSF) method was applied to measure the changes in nicotinamide adenine dinucleotide reduced form (NADH) in response to transient ischemia and reperfusion. We hypothesized that various sources of NO3 may differently affect endothelial and mitochondrial functions in healthy human subjects. METHODS: In a randomized crossover trial, 8 healthy young adults ingested 800 mg NO3 from either NIT or BRJ on 2 separate days with ≥3 d apart. Venous blood samples were collected every hour, and FMSF determination was applied bihourly. RESULTS: Plasma betaine and choline concentrations peaked at 1 h after BRJ ingestion, and remained significantly higher than baseline values at all time points (P < 0.001 and P < 0.001, compared to preingestion values). Over time, BRJ was more effective in increasing NOx compared with NIT (fixed-trial effect P < 0.001). Baseline fluorescence decreased after both NIT and BRJ consumption (fixed-time effect P = 0.005). Transient ischemia and reperfusion response increased because of NO3 consumption (fixed-time effect P = 0.003), with no differences between trials (P = 0.451; P = 0.912; P = 0.819 at 0, 2, and 4 h, respectively). CONCLUSIONS: Acute ingestion of BRJ elevated plasma betaine and choline, but not TMA and TMAO. Moreover, plasma NOx levels were higher in the BRJ trial than in the NIT trial. Various sources of NO3 positively affected endothelial and mitochondrial functions. This trial was registered at clinicaltrials.gov as NCT05004935.

Choline plays many important roles, including the synthesis of acetylcholine, and may affect muscle responses to exercise. We previously observed correlations between low choline intake and reduced gains in strength and lean mass following a 12-week resistance exercise training (RET) program for older adults. To further explore these findings, we conducted a randomized controlled trial. Three groups of 50-to-69-year-old healthy adults underwent a 12-week RET program (3x/week, 3 sets, 8-12 reps, 70% of maximum strength (1RM)) and submitted >48 diet logs (>4x/week for 12 weeks). Participants' diets were supplemented with 0.7 mg/kg lean/d (low, n = 13), 2.8 mg/kg lean/d (med, n = 11), or 7.5 mg/kg lean/d (high, n = 13) of choline from egg yolk and protein powder. The ANCOVA tests showed that low choline intake, compared with med or high choline intakes, resulted in significantly diminished gains in composite strength (leg press + chest press 1RM; low, 19.4 ± 8.2%; med, 46.8 ± 8.9%; high, 47.4 ± 8.1%; p = 0.034) and thigh-muscle quality (leg press 1RM/thigh lean mass; low, 12.3 ± 9.6%; med/high, 46.4 ± 7.0%; p = 0.010) after controlling for lean mass, protein, betaine, and vitamin B12. These data suggest that low choline intake may negatively affect strength gains with RET in older adults.

Several studies have suggested that betaine is closely related to inflammatory biomarkers that contribute to the development of metabolic diseases, but the effect remains controversial. This meta-analysis aimed to assess the effects of betaine supplementation on inflammatory markers based on randomised controlled trials (RCTs). PubMed, Web of Science and ResearchGate databases were searched up to March 2023. A total of 6 RCTs with 7 intervention trials involving 277 participants were included. Betaine supplementation led to a slight reduction in levels of circulating IL-1β of 0.65 pg/mL (95% CI, -1.23 to -0.06) with high heterogeneity (I2 = 95%). Betaine produced a small but nonsignificant reduction in levels of circulating CRP (0.33 mg/L; 95% CI, -1.79 to 1.14), IL-6 (0.47 pg/mL; 95% CI, -1.13 to 0.18) and TNF-α (0.25 pg/mL; 95% CI, -0.98 to 0.48). The present meta-analysis does not provide sufficient evidence to conclude that betaine supplementation improved the inflammation state.

INTRODUCTION: Consuming intracellular osmolytes, like betaine (BET), may attenuate symptoms of heat stress. The purpose of this study was to examine the effects of BET supplementation on fluid balance and heat tolerance after a 7-day loading period and during passive heat exposure. METHODS: A double-blind, placebo controlled, crossover study compared BET or placebo consumption (50 mg·kg-1 , twice daily) for 7 days in young, recreationally active men (N = 11). RESULTS: During the loading period, no significant interactions were found for any marker of fluid balance between or within conditions. During heat exposure, significant time effects but no condition x time interactions, were found for plasma characteristics (i.e., volume, osmolality, sodium, albumin, and total protein). Plasma volume was significantly increased by min 30 in both conditions (PLA: +6.9. ± 5.0%, BET: +10.2 ± 7.4%) and remained elevated for the remainder of the experimental trial, but was not significantly different between conditions. After 60 min of passive heat exposure, both conditions experienced a similar increase in core temperature (PLA: +0.32 ± 0.22°C, BET: +0.31 ± 0.21°C; p = 0.912). CONCLUSIONS: Supplemental BET did not improve markers of fluid balance or heat tolerance during 7 days of loading or during passive heat exposure. © 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.

BACKGROUND: Because betaine (BET) supplementation may improve muscular strength and endurance, it seems plausible that BET will also influence CrossFit performance (CF). PURPOSE: The aim of this study was to evaluate the effects of three weeks of BET supplementation on body composition, CF performance, muscle power in the Wingate anaerobic test (WAnT), and the concentrations of selected hormones. The secondary aims were to analyze the effectiveness of two different BET doses (2.5 and 5.0 g/d) and their interaction with the methylenetetrahydrofolate reductase (MTHFR) genotype. METHODS: The study was designed in a double-blinded randomized cross-over fashion. Forty-three CF practitioners completed the entire study. CF performance was measured using the Fight Gone Bad (FGB) workout and muscle power was evaluated in a 30-second WAnT. Body composition was determined by air-displacement plethysmography. Blood was drawn to assess hormone concentrations. The C677T single nucleotide polymorphism (rs180113) in the MTHFR gene was analyzed. RESULTS: FGB total improved with BET by 8.7 ± 13.6% (p < 0.001), but no significant changes were observed with placebo (- 0.4 ± 10.0%, p = 0.128). No changes were also observed in WAnT and body composition. After BET supplementation testosterone concentration increased by 7.0 ± 15.4% with BET (p = 0.046) (no change with placebo: 1.5 ± 19.6%, p = 0.884) but had no effect on concentrations of insulin-like growth factor or cortisol. Finally, there were no significant interactions between MTHFR genotype and BET dose in any outcome. CONCLUSIONS: BET supplementation may improve CF performance and increase testosterone concentration. However, there was no evidence of a difference between dosages (2.5 and 5.0 g/d) and MTHFR genotypes. The trial was registered on clinicaltrials.gov (NCT03702205) on 10 October 2018.

BACKGROUND: More than 270 million participants and 128,893 professional players play soccer. Although UEFA recommendations for nutrition in elite football exist, implementing these guidelines among professional and semiprofessional soccer players remains suboptimal, emphasizing the need for targeted and individualized nutritional strategies to improve adherence to established recommendations. METHODS: We conducted a comprehensive search in PubMed, Scopus, Web of Science, and clinical trial registers. Inclusion criteria focused on professional or semiprofessional soccer players, nutrition or diet interventions, performance improvement outcomes, and randomized clinical trial study types. We assessed quality using the Risk of Bias 2 (RoB 2) tool. We identified 16 eligible articles involving 310 participants. No nutritional interventions during the recovery period effectively improved recovery. However, several performance-based interventions showed positive effects, such as tart cherry supplementation, raw pistachio nut kernels, bicarbonate and mineral ingestion, creatine supplementation, betaine consumption, symbiotic supplements, and a high-carbohydrate diet. These interventions influenced various aspects of soccer performance, including endurance, speed, agility, strength, power, explosiveness, and anaerobic capacity. CONCLUSIONS: Specific strategies, such as solutions with bicarbonate and minerals, high carbohydrate diets, and supplements like creatine, betaine, and tart cherry, can enhance the performance of professional soccer players. These targeted nutritional interventions may help optimize performance and provide the competitive edge required in professional soccer. We did not find any dietary interventions that could enhance recovery.

BACKGROUND: Choline deficiency leads to pathologies particularly of the liver, brain and lung. Adequate supply is important for preterm infants and patients with cystic fibrosis. We analysed the assimilation of four different enterally administered deuterium-labelled (D9-) choline supplements in adults. METHODS: Prospective randomised cross-over study (11/2020-1/2022) in six healthy men, receiving four single doses of 2.7 mg/kg D9-choline equivalent each in the form of D9-choline chloride, D9-phosphorylcholine, D9-alpha-glycerophosphocholine (D9-GPC) or D9-1-palmitoyl-2-oleoyl-glycero-3-phosphoryl-choline (D9-POPC), in randomised order 6 weeks apart. Plasma was obtained at baseline (t = - 0.1 h) and at 0.5 h to 7d after intake. Concentrations of D9-choline and its D9-labelled metabolites were analysed by tandem mass spectrometry. Results are shown as median and interquartile range. RESULTS: Maximum D9-choline and D9-betaine concentrations were reached latest after D9-POPC administration versus other components. D9-POPC and D9-phosphorylcholine resulted in lower D9-trimethylamine (D9-TMAO) formation. The AUCs (0-7d) of plasma D9-PC concentration showed highest values after administration of D9-POPC. D9-POPC appeared in plasma after fatty acid remodelling, predominantly as D9-1-palmitoyl-2-linoleyl-PC (D9-PLPC), confirming cleavage to 1-palmitoyl-lyso-D9-PC and re-acylation with linoleic acid as the most prominent alimentary unsaturated fatty acid. CONCLUSION: There was a delayed increase in plasma D9-choline and D9-betaine after D9-POPC administration, with no differences in AUC over time. D9-POPC resulted in a higher AUC of D9-PC and virtually absent D9-TMAO levels. D9-POPC is remodelled according to enterocytic fatty acid availability. D9-POPC seems best suited as choline supplement to increase plasma PC concentrations, with PC as a carrier of choline and targeted fatty acid supply as required by organs. This study was registered at Deutsches Register Klinischer Studien (DRKS) (German Register for Clinical Studies), DRKS00020498, 22.01.2020. STUDY REGISTRATION: This study was registered at Deutsches Register Klinischer Studien (DRKS) (German Register for Clinic

PURPOSE: To test the hypothesis that daily supplementation with low-dose B vitamins plus betaine could significantly reduce plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia and free from background mandatory folic acid fortification. METHODS: One hundred apparently healthy adults aged 18-65 years with hyperhomocysteinemia were recruited in South China from July 2019 to June 2021. They were randomly assigned to either the supplement group (daily supplementation: 400 μg folic acid, 8 mg vitamin B6, 6.4 μg vitamin B12 and 1 g betaine) or the placebo group for 12 weeks. Fasting venous blood was collected at baseline, week 4 and week 12 to determine the concentrations of homocysteine, folate, vitamin B12 and betaine. Generalized estimation equations were used for statistical analysis. RESULTS: Statistically significant increments in blood concentrations of folate, vitamin B12 and betaine after the intervention in the supplement group indicated good participant compliance. At baseline, there were no significant differences in plasma homocysteine concentration between the two groups (P = 0.265). After 12-week supplementation, compared with the placebo group, there was a significant reduction in plasma homocysteine concentrations in the supplement group (mean group difference - 3.87; covariate-adjusted P = 0.012; reduction rate 10.1%; covariate-adjusted P < 0.001). In the supplement group, the decreased concentration of plasma homocysteine was associated with increments of blood concentrations of both folate (β = -1.680, P = 0.004) and betaine (β = -1.421, P = 0.020) after 12 weeks of supplementation. CONCLUSIONS: Daily supplementation with low-dose B vitamins plus betaine for 12 weeks effectively decreased plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov as NCT03720249 on October 25, 2018. Website: https://clinicaltrials.gov/ct2/show/NCT03720249 . © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.

The purpose of this investigation was to compare the impacts of a potential blood flow restriction (BFR)-betaine synergy on one-leg press performance, lactate concentrations, and exercise-associated biomarkers. Eighteen recreationally trained males (25 ± 5 y) were randomized to supplement 6 g/day of either betaine anhydrous (BET) or cellulose placebo (PLA) for 14 days. Subsequently, subjects performed four standardized sets of one-leg press and two additional sets to muscular failure on both legs (BFR [LL-BFR; 20% 1RM at 80% arterial occlusion pressure] and high-load [HL; 70% 1RM]). Toe-tip lactate concentrations were sampled before (PRE), as well as immediately (POST0), 30 min (POST30M), and 3 h (POST3H) post-exercise. Serum homocysteine (HCY), growth hormone (GH) and insulin-like growth factor-1 concentrations were additionally assessed at PRE and POST30M. Analysis failed to detect any significant between-supplement differences for total repetitions completed. Baseline lactate changes (∆) were significantly elevated from POST0 to POST30 and from POST30 to POST3H (p < 0.05), whereby HL additionally demonstrated significantly higher ∆Lactate versus LL-BFR (p < 0.001) at POST3H. Although serum ∆GH was not significantly impacted by supplement or condition, serum ∆IGF-1 was significantly (p = 0.042) higher in BET versus PLA and serum ∆HCY was greater in HL relative to LL-BFR (p = 0.044). Although these data fail to support a BFR-betaine synergy, they otherwise support betaine’s anabolic potential.