베타인 HCl

Meal Effects Confound Attempts to Counteract Rabeprazole-Induced Hypochlorhydria Decreases in Atazanavir Absorption.

1. Pharm Res. 2017 Mar;34(3):619-628. doi: 10.1007/s11095-016-2090-2. Epub 2016 Dec 27. Meal Effects Confound Attempts to Counteract Rabeprazole-Induced Hypochlorhydria Decreases in Atazanavir Absorption. Faber KP(1), Wu HF(1), Yago MR(1), Xu X(2), Kadiyala P(2), Frassetto LA(3)(4), Benet LZ(5)

The use of betaine HCl to enhance dasatinib absorption in healthy volunteers with rabeprazole-induced hypochlorhydria.

2. AAPS J. 2014 Nov;16(6):1358-65. doi: 10.1208/s12248-014-9673-9. Epub 2014 Oct 2. The use of betaine HCl to enhance dasatinib absorption in healthy volunteers with rabeprazole-induced hypochlorhydria. Yago MR(1), Frymoyer A, Benet LZ, Smelick GS, Frassetto LA, Ding X, Dean B, Salphati L, Budha

The effectiveness and safety of the active form of folate on biochemical parameters in women of childbearing age: A systematic review and meta-analysis.

1. Medicine (Baltimore). 2025 Dec 12;104(50):e46564. doi: 10.1097/MD.0000000000046564. The effectiveness and safety of the active form of folate on biochemical parameters in women of childbearing age: A systematic review and meta-analysis. Xie M(1)(2)(3)(4), Qing X(1), Huang H(1), Zhang J(2)(3)(4). Author information: (1)Department of Obstetrics and Gynecology, Chengdu Qingbaijiang District People's Hospital, Chengdu, China. (2)Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China. (3)The Joint Laboratory for Reproductive Medicine of Sichuan University, The Chinese University of Hong Kong, Chengdu, China. (4)Reproductive Endocrinology and Regulation Laboratory, West China Second University Hospital, Sichuan University, Chengdu, China. 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 studies and the short duration of treatment, more RCTs with high-quality, long-term duration and pregnancy outcomes are needed for further validation. Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc. DOI: 10.1097/MD.0000000000046564 PMCID: PMC12708167 PMID: 41398893 [Indexed for MEDLINE] Conflict of interest statement: The authors have no funding and conflicts of interest to disclose.

Antioxidant Treatment and the Chance to Conceive in Men Seeking Fertility Care: The SUMMER Randomized Clinical Trial.

2. JAMA Netw Open. 2025 Sep 2;8(9):e2532405. doi: 10.1001/jamanetworkopen.2025.32405. Antioxidant Treatment and the Chance to Conceive in Men Seeking Fertility Care: The SUMMER Randomized Clinical Trial. de Ligny WR(1)(2), de Bruin JP(2), Smits RM(1), Goovaerts IGF(3), Peeters K(3), Nap AW(1), Boxmeer JC(4), Donker RB(5), Schoonenberg M(6), Koks CAM(7), van Rumste MME(8), Visser J(9), Gielen SCJP(10), Boomsma CM(11), Smeenk JMJ(12), van Oppenraaij RHF(13), Cox T(14), Janse F(15), Muller LT(16), Brink-van der Vlugt JJ(17), Braat DDM(1), Fleischer K(6). Author information: (1)Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, the Netherlands. (2)Department of Obstetrics and Gynecology, Jeroen Bosch Hospital, 's-Hertogenbosch, the Netherlands. (3)Center of Reproductive Medicine, Antwerp University Hospital, Edegem, Belgium. (4)Center of Reproductive Medicine, Voorburg Reinier de Graaf, Voorburg, the Netherlands. (5)Department of Obstetrics and Gynecology, Slingeland Hospital, Doetinchem, the Netherlands. (6)Nij Geertgen Center for Reproductive Medicine, Elsendorp, the Netherlands. (7)Department of Obstetrics and Gynecology, Máxima Medical Center, Veldhoven, the Netherlands. (8)Department of Obstetrics and Gynecology, Catharina Hospital, Eindhoven, the Netherlands. (9)Department of Obstetrics and Gynecology, Amphia Hospital, Breda, the Netherlands. (10)Department of Obstetrics and Gynecology, Franciscus Hospital, Rotterdam, the Netherlands. (11)Department of Obstetrics and Gynecology, Bravis Hospital, Roosendaal, the Netherlands. (12)Department of Obstetrics and Gynecology, Elisabeth TweeSteden Hospital, Tilburg, the Netherlands. (13)Department of Obstetrics and Gynecology, Maasstad Hospital, Rotterdam, the Netherlands. (14)Department of Obstetrics and Gynecology, Medisch Centrum Kinderwens, Leiderdorp, the Netherlands. (15)Department of Obstetrics and Gynecology, Rjinstate Hospital, Arnhem, the Netherlands. (16)Department of Obstetrics and Gynecology, Bernhoven Hospital, Uden, the Netherlands. (17)Nij Barrahûs Center for Reproductive Medicine, Wolvega, the Netherlands. 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] years) were included in the data analysis, of whom 591 were in the antioxidant supplement group and 580 were in the placebo group. Ongoing pregnancy rate within 6 months was not significantly different between the 2 groups (193 of 571 [33.8%] vs 208 of 555 [37.5%]; adjusted odds ratio [AOR], 0.85 [95% CI, 0.66-1.09]; P = .20). Within the window of optimal treatment effect between 4 and 6 months (considering a spermatogenesis cycle of 72 days), ongoing pregnancy rate was significantly lower in the antioxidant supplement group compared with the placebo group (69 of 446 [15.5%] vs 95 of 442 [21.5%]; AOR, 0.66 [95% CI, 0.47-0.94]; P = .02). There were no significant between-group differences for the secondary outcomes. CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that ongoing pregnancy rates did not improve with the antioxidant supplement compared with a placebo. Therefore, the investigators do not support its use in men seeking fertility care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03337360. DOI: 10.1001/jamanetworkopen.2025.32405 PMCID: PMC12464787 PMID: 40996763 [Indexed for MEDLINE] Conflict of interest statement: Conflict of Interest Disclosures: Dr de Ligny reported receiving an unrestricted research grant and study medications from Goodlife Pharma BV during the conduct of the study and educational support from Ferring outside the submitted work. Dr de Bruin reported receiving an unrestricted research grant from Goodlife Pharma BV during the conduct of the study. Dr Smits reported receiving an unrestricted research grant from Goodlife Pharma BV during the conduct of the study. Dr van Rumste reported receiving personal fees from Ferring BV and Merck Group outside the submitted work. Dr Smeenk reported receiving grants from Merck BV, Ferring BV, and Goodlife Pharma BV outside the submitted work. Dr Fleischer reported receiving an unrestricted research grant from Goodlife Pharma BV during the conduct of the study. No other disclosures were reported.

Betaine Supplementation Improves 60 km Cycling Time Trial Performance and One-Carbon Metabolism in Cyclists During Recovery.

3. Nutrients. 2025 Aug 26;17(17):2765. doi: 10.3390/nu17172765. Betaine Supplementation Improves 60 km Cycling Time Trial Performance and One-Carbon Metabolism in Cyclists During Recovery. Nieman DC(1), Sakaguchi CA(1), Williams JC(1), Lawson J(2), Lambirth KC(2). Author information: (1)Human Performance Laboratory, Appalachian State University, North Carolina Research Campus, Kannapolis, NC 28081, USA. (2)College of Computing and Informatics, University of North Carolina at Charlotte, Kannapolis, NC 28081, USA. 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 metabolism pathway during the 24 h recovery period. DOI: 10.3390/nu17172765 PMCID: PMC12430687 PMID: 40944155 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Effect of inulin supplementation on fecal and blood metabolome in alcohol use disorder patients: A randomised, controlled dietary intervention.

4. Clin Nutr ESPEN. 2025 Apr;66:361-371. doi: 10.1016/j.clnesp.2025.01.046. Epub 2025 Jan 27. Effect of inulin supplementation on fecal and blood metabolome in alcohol use disorder patients: A randomised, controlled dietary intervention. Amadieu C(1), Ahmed H(2), Leclercq S(3), Koistinen V(4), Leyrolle Q(1), Stärkel P(5), Bindels LB(6), Layé S(7), Neyrinck AM(8), Kärkkäinen O(9), De Timary P(10), Hanhineva K(4), Delzenne NM(11). Author information: (1)Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium; Université de Bordeaux, INRAE, Bordeaux INP, NutriNeurO, UMR 1286, F-33000 Bordeaux, France. (2)Food Sciences Unit, Department of Life Technologies, University of Turku, Turku, Finland. (3)Laboratory of Nutritional Psychiatry, Institute of Neuroscience, UCLouvain, Université catholique de Louvain, Brussels, Belgium. (4)Food Sciences Unit, Department of Life Technologies, University of Turku, Turku, Finland; School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. (5)Department of Gastro-enterology, Cliniques Universitaires Saint Luc, Brussels, Belgium. (6)Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium; WELBIO Department, WEL Research Institute, Wavre, Belgium. (7)Université de Bordeaux, INRAE, Bordeaux INP, NutriNeurO, UMR 1286, F-33000 Bordeaux, France. (8)Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium. (9)School of Pharmacy, University of Eastern Finland, Kuopio, Finland. (10)Department of Adult Psychiatry, Cliniques Universitaires Saint-Luc and Institute of Neuroscience, UCLouvain, Université catholique de Louvain, Brussels, Belgium. (11)Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium. Electronic address: nathalie.delzenne@uclouvain.be. 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. Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved. DOI: 10.1016/j.clnesp.2025.01.046 PMID: 39864520 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest VK, OK and KH are founders of Afekta Technologies Ltd. The other authors report no financial interests or potential conflicts of interest.

Use of a Micronutrient Cocktail to Improve Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Adults with Obesity: A Randomized, Double-Blinded Pilot Clinical Trial.

5. Medicina (Kaunas). 2024 Aug 21;60(8):1366. doi: 10.3390/medicina60081366. Use of a Micronutrient Cocktail to Improve Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Adults with Obesity: A Randomized, Double-Blinded Pilot Clinical Trial. Perva IT(1)(2)(3), Simina IE(1)(3), Bende R(4)(5), Motofelea AC(6), Chirita Emandi A(1)(2), Andreescu N(1)(2), Sima A(7)(8), Vlad A(7)(9), Sporea I(4)(5), Zimbru C(10), Tutac PC(11), Puiu M(1)(2), Niculescu MD(1)(12). Author information: (1)Department of Microscopic Morphology, Genetics Discipline, Center of Genomic Medicine, "Victor Babeș" University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania. (2)Regional Center of Medical Genetics Timiș, Clinical Emergency Hospital for Children "Louis Țurcanu", Iosif Nemoianu Street N°2, 300011 Timisoara, Romania. (3)Department of Medical Genetics, Asociatia Oncohelp, 300239 Timișoara, Romania. (4)Department of Gastroenterology and Hepatology, "Victor Babeș" University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania. (5)Center of Advanced Research in Gastroenterology and Hepatology, "Victor Babeș" University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania. (6)Department of Internal Medicine, "Victor Babeș" University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania. (7)Department of Internal Medicine II, Division of Diabetes, Nutrition and Metabolic Diseases, "Victor Babeș" University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania. (8)Center for Research in Preventive Medicine, Faculty of Medicine, "Victor Babeș" University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania. (9)Center for Molecular Research in Nephrology and Vascular Disease, "Victor Babeș" University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania. (10)Department of Automation and Applied Informatics, Politehnica University Timișoara, 300223 Timișoara, Romania. (11)Toxicology and Molecular Biology Department, "Pius Brinzeu" Clinical Emergency County Hospital, 300723 Timisoara, Romania. (12)Advanced Nutrigenomics LLC, Durham, NC 27703, USA. 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. DOI: 10.3390/medicina60081366 PMCID: PMC11356300 PMID: 39202647 [Indexed for MEDLINE] Conflict of interest statement: Author Mihai Dinu Niculescu was employed by the company Advanced Nutrigenomics LLC. The remaining authors have not identified any potential conflicts of interest. The company has not received any direct benefit from this study or article. Niculescu has kindly provided his expertise in developing the study outline and throughout the entire process.

Betaine supplementation modulates betaine concentration by methylenetetrahydrofolate reductase genotype, but has no effect on amino acid profile in healthy active males: A randomized placebo-controlled cross-over study.

6. Nutr Res. 2024 Jul;127:63-74. doi: 10.1016/j.nutres.2024.05.003. Epub 2024 May 23. Betaine supplementation modulates betaine concentration by methylenetetrahydrofolate reductase genotype, but has no effect on amino acid profile in healthy active males: A randomized placebo-controlled cross-over study. Zawieja E(1), Drabińska N(2), Jeleń H(2), Szwengiel A(3), Durkalec-Michalski K(4), Chmurzynska A(5). Author information: (1)Department of Human Nutrition and Dietetics, Poznań University of Life Sciences, Poznań, Poland. (2)Food Volatilomics and Sensomics Group, Faculty of Food Science and Nutrition, Poznań University of Life Sciences, Poznań, Poland. (3)Department of Food Technology of Plant Origin, Poznań University of Life Sciences, Poznań, Poland. (4)Department of Sports Dietetics, Poznań University of Physical Education, Poznań, Poland. (5)Department of Human Nutrition and Dietetics, Poznań University of Life Sciences, Poznań, Poland. Electronic address: agata.chmurzynska@up.poznan.pl. 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. Copyright © 2024 Elsevier Inc. All rights reserved. DOI: 10.1016/j.nutres.2024.05.003 PMID: 38876040 [Indexed for MEDLINE]

Effects of Acute Beetroot Juice and Sodium Nitrate on Selected Blood Metabolites and Response to Transient Ischemia: A Crossover Randomized Clinical Trial.

7. J Nutr. 2024 Feb;154(2):491-497. doi: 10.1016/j.tjnut.2023.12.018. Epub 2023 Dec 16. Effects of Acute Beetroot Juice and Sodium Nitrate on Selected Blood Metabolites and Response to Transient Ischemia: A Crossover Randomized Clinical Trial. Jurga J(1), Samborowska E(2), Zielinski J(3), Olek RA(4). Author information: (1)Doctoral School, Poznan University of Physical Education, Poznan, Poland. (2)Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland. (3)Department of Athletics, Strength, and Conditioning, Poznan University of Physical Education, Poznan, Poland. (4)Department of Athletics, Strength, and Conditioning, Poznan University of Physical Education, Poznan, Poland. Electronic address: olek@awf.poznan.pl. 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. Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.tjnut.2023.12.018 PMID: 38110180 [Indexed for MEDLINE]

The Effect of Choline and Resistance Training on Strength and Lean Mass in Older Adults.

8. Nutrients. 2023 Sep 6;15(18):3874. doi: 10.3390/nu15183874. The Effect of Choline and Resistance Training on Strength and Lean Mass in Older Adults. Lee CW(1), Lee TV(2), Galvan E(3), Chen VCW(4), Bui S(5), Crouse SF(6), Fluckey JD(6), Smith SB(7), Riechman SE(6). Author information: (1)Department of Health and Human Performance, Nursing and Counseling, University of Houston-Victoria, Victoria, TX 77901, USA. (2)Life Sciences Department, Pierce College, Woodland Hills, CA 91367, USA. (3)School of Osteopathic Medicine in Arizona, A.T. Still University, Mesa, AZ 85206, USA. (4)Department of Integrative Health and Exercise Science, Georgian Court University, Lakewood, NJ 08701, USA. (5)Department of Health and Human Performance, Utah Tech University, St. George, UT 84770, USA. (6)Department of Kinesiology and Sport Management, Texas A&M University, College Station, TX 77843, USA. (7)Department of Animal Science, Texas A&M University, College Station, TX 77843, USA. 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. DOI: 10.3390/nu15183874 PMCID: PMC10534351 PMID: 37764658 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Effects of betaine supplementation on inflammatory markers: a systematic review and meta-analysis of randomised controlled trials.

9. Int J Food Sci Nutr. 2023 Nov;74(7):721-729. doi: 10.1080/09637486.2023.2257906. Epub 2023 Nov 15. Effects of betaine supplementation on inflammatory markers: a systematic review and meta-analysis of randomised controlled trials. Xu J(1), Nie Z(1), Qiu X(1), Zhang J(1), Han S(1). Author information: (1)Department of Nutrition and Toxicology, School of Public Health, Hangzhou Normal University, Hangzhou, Zhejiang, P.R. China. 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. DOI: 10.1080/09637486.2023.2257906 PMID: 37733077 [Indexed for MEDLINE]

The effects of betaine supplementation on fluid balance and heat tolerance during passive heat stress in men.

10. Physiol Rep. 2023 Aug;11(16):e15792. doi: 10.14814/phy2.15792. The effects of betaine supplementation on fluid balance and heat tolerance during passive heat stress in men. Willingham BD(1)(2), Rentería LI(2), Ragland TJ(2)(3), Ormsbee MJ(2)(4). Author information: (1)Department of Kinesiology, Coastal Carolina University, Conway, South Carolina, USA. (2)Institute of Sports Sciences & Medicine, Nutrition, and Integrative Physiology, Florida State University, Florida, USA. (3)Department of Kinesiology and Health, Rutgers University, New Brunswick, New Jersey, USA. (4)Discipline of Biokinetics, Exercise, and Leisure Sciences, University of KwaZulu-Natal, Durban, South Africa. 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. DOI: 10.14814/phy2.15792 PMCID: PMC10442523 PMID: 37604644 [Indexed for MEDLINE] Conflict of interest statement: All other authors have no competing interests to declare.

Betaine supplementation improves CrossFit performance and increases testosterone levels, but has no influence on Wingate power: randomized crossover trial.

11. J Int Soc Sports Nutr. 2023 Dec;20(1):2231411. doi: 10.1080/15502783.2023.2231411. Betaine supplementation improves CrossFit performance and increases testosterone levels, but has no influence on Wingate power: randomized crossover trial. Zawieja E(1), Durkalec-Michalski K(2)(3), Sadowski M(1), Główka N(2), Chmurzynska A(1). Author information: (1)Poznan University of Life Sciences, Department of Human Nutrition and Dietetics, Poznań, Poland. (2)Poznan University of Physical Education, Department of Sports Dietetics, Poznań, Poland. (3)Charles University, Department of Physiology and Biochemistry, Faculty of Physical Education and Sport, Prague, Czech Republic. 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. DOI: 10.1080/15502783.2023.2231411 PMCID: PMC10327519 PMID: 37409757 [Indexed for MEDLINE] Conflict of interest statement: No potential conflict of interest was reported by the author(s).

Effects of Nutrition Interventions on Athletic Performance in Soccer Players: A Systematic Review.

12. Life (Basel). 2023 May 28;13(6):1271. doi: 10.3390/life13061271. Effects of Nutrition Interventions on Athletic Performance in Soccer Players: A Systematic Review. Aguinaga-Ontoso I(1)(2), Guillen-Aguinaga S(1), Guillen-Aguinaga L(3), Alas-Brun R(1), Guillen-Grima F(1)(2)(4). Author information: (1)Departament of Health Sciences, Public University of Navarra, 31008 Pamplona, Spain. (2)Area of Epidemiology and Public Health, Healthcare Research Institute of Navarre (IdiSNA), 31008 Pamplona, Spain. (3)Department of Nursing, Suldal Hospital, 4230 Sands, Norway. (4)Department of Preventive Medicine, Clínica Universidad de Navarra, 31008 Pamplona, Spain. 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. DOI: 10.3390/life13061271 PMCID: PMC10301089 PMID: 37374054 Conflict of interest statement: The authors declare no conflict of interest.

Different choline supplement metabolism in adults using deuterium labelling.

13. Eur J Nutr. 2023 Jun;62(4):1795-1807. doi: 10.1007/s00394-023-03121-z. Epub 2023 Feb 25. Different choline supplement metabolism in adults using deuterium labelling. Böckmann KA(1), Franz AR(2)(3), Shunova A(2), Minarski M(2), Wiechers C(2), Poets CF(2), Bernhard W(2). Author information: (1)Department of Neonatology, Faculty of Medicine, Eberhard Karls University, Calwer Straße 7, 72076, Tübingen, Germany. katrin.boeckmann@med.uni-tuebingen.de. (2)Department of Neonatology, Faculty of Medicine, Eberhard Karls University, Calwer Straße 7, 72076, Tübingen, Germany. (3)Center for Pediatric Clinical Studies, Eberhard Karls University, Tübingen, Germany. 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 Clinical Studies), DRKS00020498. © 2023. The Author(s). DOI: 10.1007/s00394-023-03121-z PMCID: PMC10195734 PMID: 36840817 [Indexed for MEDLINE] Conflict of interest statement: The authors declare that they have no conflict of interest to disclose. Trial Registration: This trial was registered at https://drks.de/drks_web/ trial ID DRKS00020498.

Effects of low-dose B vitamins plus betaine supplementation on lowering homocysteine concentrations among Chinese adults with hyperhomocysteinemia: a randomized, double-blind, controlled preliminary clinical trial.

14. Eur J Nutr. 2023 Jun;62(4):1599-1610. doi: 10.1007/s00394-023-03087-y. Epub 2023 Jan 30. Effects of low-dose B vitamins plus betaine supplementation on lowering homocysteine concentrations among Chinese adults with hyperhomocysteinemia: a randomized, double-blind, controlled preliminary clinical trial. Lu XT(#)(1)(2), Wang YN(#)(3), Mo QW(4), Huang BX(1)(2), Wang YF(5), Huang ZH(1), Luo Y(1), Maierhaba W(1), He TT(1), Li SY(1), Huang RZ(1), Yang MT(1), Liu XZ(1), Liu ZY(1)(2), Chen S(1)(2), Fang AP(1)(2), Zhang XG(6), Zhu HL(7)(8). Author information: (1)Department of Nutrition, School of Public Health, Sun Yat-sen University, 74 Zhong Shan Road 2, Guangzhou, 510080, Guangdong, China. (2)Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China. (3)Department of VIP Medical Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. (4)Medical Examination Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. (5)BYHEALTH Institute of Nutrition and Health, No.3 Kehui 3Rd Street, No.99 Kexue Avenue Central, Guangzhou, 510663, Guangdong, China. (6)BYHEALTH Institute of Nutrition and Health, No.3 Kehui 3Rd Street, No.99 Kexue Avenue Central, Guangzhou, 510663, Guangdong, China. zhangxg2@by-health.com. (7)Department of Nutrition, School of Public Health, Sun Yat-sen University, 74 Zhong Shan Road 2, Guangzhou, 510080, Guangdong, China. zhuhl@mail.sysu.edu.cn. (8)Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China. zhuhl@mail.sysu.edu.cn. (#)Contributed equally 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. DOI: 10.1007/s00394-023-03087-y PMCID: PMC9886420 PMID: 36717385 [Indexed for MEDLINE] Conflict of interest statement: The authors declare that they have no conflict of interest.

The Impacts of Combined Blood Flow Restriction Training and Betaine Supplementation on One-Leg Press Muscular Endurance, Exercise-Associated Lactate Concentrations, Serum Metabolic Biomarkers, and Hypoxia-Inducible Factor-1α Gene Expression.

15. Nutrients. 2022 Nov 27;14(23):5040. doi: 10.3390/nu14235040. The Impacts of Combined Blood Flow Restriction Training and Betaine Supplementation on One-Leg Press Muscular Endurance, Exercise-Associated Lactate Concentrations, Serum Metabolic Biomarkers, and Hypoxia-Inducible Factor-1α Gene Expression. Machek SB(1)(2), Harris DR(1), Zawieja EE(3), Heileson JL(1)(4), Wilburn DT(1), Radziejewska A(3), Chmurzynska A(3), Cholewa JM(5), Willoughby DS(1)(6). Author information: (1)Department of Health, Human Performance, and Recreation, Robbins College of Health and Human Sciences, Baylor University, Waco, TX 76706, USA. (2)Kinesiology Department, College of Health Sciences and Human Services, California State University, Monterey Bay, Seaside, CA 93955, USA. (3)Department of Human Nutrition and Dietetics, The Poznań University of Life Sciences, 60-637 Poznań, Poland. (4)Nutrition Services Division, Walter Reed National Military Medical Center, Bethesda, MD 20814, USA. (5)Exercise Physiology Department, University of Lynchburg, Lynchburg, VA 24501, USA. (6)School of Exercise and Sport Science, Mayborn College of Health Sciences, University of Mary Hardin-Baylor, Belton, TX 76513, USA. 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. DOI: 10.3390/nu14235040 PMCID: PMC9739923 PMID: 36501070 [Indexed for MEDLINE] Conflict of interest statement: S.B.M. is registered as a B3 BFR Certified Coach under B3 Sciences (Frisco, TX, USA).