Research

Betaine

62 peer-reviewed studies curated from PubMed and Semantic Scholar.

6
Meta-analyses
2
Systematic reviews
33
RCTs
21
Other studies
Meta-analyses (10%)
Systematic reviews (3%)
RCTs (53%)
Observational (6%)

Studies

Sorted by quality and recency

2025·JAMA network open·Wiep R de Ligny, Jan Peter de Bruin, Roos M Smits, et al

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

RCTn = 1,171Sexual Health

The SUMMER randomized clinical trial assessed the effect of an antioxidant supplement (Impryl) on semen quality and pregnancy rates in men seeking fertility care. The study found no significant improvement in ongoing pregnancy rates with the supplement compared to placebo, and a lower pregnancy rate within the optimal treatment window.

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2024·Nutrition research (New York, N.Y.)·Elham Sharifi-Zahabi, Sepideh Soltani, Sahar Asiaei, et al

Higher dietary choline intake is associated with increased risk of all-cause and cause-specific mortality: A systematic review and dose-response meta-analysis of cohort studies.

Meta-analysisn = 482,778

This meta-analysis of six cohort studies with 482,778 participants investigated the association of dietary choline and betaine with mortality. It found that each 100 mg/day increase in choline intake was associated with a 6% increase in all-cause mortality and an 11% increase in cardiovascular disease mortality. Betaine intake was not associated with all-cause mortality but showed a significant relationship with stroke mortality at doses of 50 to 250 mg/day.

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2024·Nutrients·Caleigh M Sawicki, Lorena S Pacheco, Sona Rivas-Tumanyan, et al

Association of Gut Microbiota-Related Metabolites and Type 2 Diabetes in Two Puerto Rican Cohorts.

Meta-analysisn = 1,669Nutrition Gut Health

Meta-analysis of two Puerto Rican cohorts examining associations between gut microbiota-related metabolites and cardiometabolic risk factors. Higher plasma betaine was associated with lower fasting glucose, HbA1c, HOMA-IR, fasting insulin, and a lower incidence of type 2 diabetes. L-carnitine was associated with lower fasting glucose and HbA1c, while TMAO was associated with higher fasting glucose and triglycerides.

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2024·Journal of sports sciences·Emilia Zawieja, Steven Machek, Nelo Eidy Zanchi, et al

Effects of chronic betaine supplementation on exercise performance: Systematic review and meta-analysis.

Meta-analysisn = 317Physical Performance

Systematic review and meta-analysis of 17 studies with 317 participants on chronic betaine supplementation's effects on exercise performance. Betaine significantly enhances muscular strength, particularly lower body strength, and improves vertical jumping performance.

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2024·Ageing research reviews·Emilia Zawieja, Agata Chmurzynska

Betaine and aging: A narrative review of findings, possible mechanisms, research perspectives, and practical recommendations.

Systematic reviewLongevity Inflammation Joint Bone Health Physique Brain Health

This systematic review analyzes current literature on the impact of betaine on aging. Betaine may counteract aging-related changes by increasing methylation potential, reducing homocysteine concentrations, enhancing mitochondrial function, reducing oxidative stress, and attenuating inflammation. It may also promote anabolic signaling pathways and improve muscle strength, with potential effects on bone remodeling and adipose tissue metabolism.

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2023·International journal of food sciences and nutrition·Jiaoyang Xu, Zizheng Nie, Xinyi Qiu, et al

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

Meta-analysisn = 277Inflammation

This meta-analysis assessed the effects of betaine supplementation on inflammatory markers based on 6 RCTs with 7 intervention trials involving 277 participants. Betaine supplementation led to a slight reduction in IL-1β levels but produced a small, nonsignificant reduction in CRP, IL-6, and TNF-α levels. The analysis does not provide sufficient evidence to conclude that betaine supplementation improved the inflammation state.

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2022·Nutrients·Xiaoting Lu, Rongzhu Huang, Shuyi Li, et al

Associations between Serum Betaine, Methyl-Metabolizing Genetic Polymorphisms and Risk of Incident Type 2 Diabetes: A Prospective Cohort Study in Community-Dwelling Chinese Adults.

Cohort studyn = 1,565

Prospective cohort study of 1565 Chinese adults examining associations between serum betaine, methyl-metabolizing genetic polymorphisms, and risk of type 2 diabetes. Higher serum betaine and certain genetic mutations were associated with a lower risk of developing type 2 diabetes over a median follow-up of 8.9 years.

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2021·Critical Reviews in Food Science and Nutrition·D. Ashtary-Larky, R. Bagheri, M. Ghanavati, et al

Effects of betaine supplementation on cardiovascular markers: A systematic review and Meta-analysis

Meta-analysisHeart Health

This systematic review and meta-analysis evaluated the effects of betaine supplementation on cardiovascular disease markers. Betaine supplementation significantly affected concentrations of betaine, total cholesterol, LDL, homocysteine, dimethylglycine, and methionine, but did not affect triglycerides, HDL, fasting blood glucose, C-reactive protein, liver enzymes, or blood pressure. A lower dose of betaine (<4 g/d) was beneficial for homocysteine levels without adverse lipid effects.

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2021·The British journal of nutrition·Damoon Ashtary-Larky, Reza Bagheri, Grant M Tinsley, et al

Betaine supplementation fails to improve body composition: a systematic review and meta-analysis.

Meta-analysisPhysique -

This systematic review and meta-analysis assessed the effects of betaine supplementation on body composition indices such as body mass, BMI, body fat percentage, fat mass, and fat-free mass. Betaine supplementation failed to significantly affect these indices, showing no beneficial effects on body composition.

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2026·The American journal of clinical nutrition·Isis Trujillo-Gonzalez, David A Horita, Julie Stegall, et al

Choline and betaine concentrations in plasma discriminate levels of dietary choline intake in healthy adults: analysis of a double-blind randomized crossover controlled feeding study.

RCTNutrition

Double-blind, randomized, crossover feeding study tested whether plasma concentrations of choline and its metabolites could discriminate between low and adequate dietary choline intake. Plasma choline and betaine concentrations were highly responsive to dietary choline intake, with strong discrimination for plasma choline and betaine. Fibroscan identified increased liver fat in response to low choline intake in some participants.

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2025·International journal of molecular sciences·José López-López, José M Reuss, Teresa Vinuesa-Aumedes, et al

Rapid Reduction of Pro-Inflammatory Cytokines with an Oral Topical Composition Comprising Olive Oil, Trimethylglycine and Xylitol: A Randomized Double-Blind Controlled Trial.

RCTInflammation

This randomized double-blind controlled trial assessed the effect of a novel oral topical composition comprising olive oil, trimethylglycine, and xylitol on salivary cytokines in periodontally healthy normal and overweight/pre-obese individuals. Significant reductions in pro-inflammatory cytokines IL-1β and TNF-α were observed in the intervention group, suggesting a potential strategy for reducing inflammation in overweight/pre-obese patients.

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2024·Medicina (Kaunas, Lithuania)·Iulia Teodora Perva, Iulia Elena Simina, Renata Bende, et al

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.

RCTn = 155

A randomized, double-blind, placebo-controlled pilot clinical trial assessed the impact of a micronutrient cocktail on liver parameters in adults with obesity and metabolic syndrome. The treatment group showed significant reductions in CAP and TE scores, indicating improved liver fat content and fibrosis.

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2023·European journal of nutrition·Xiao-Ting Lu, Yi-Na Wang, Qi-Wan Mo, et al

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.

RCTn = 100Heart Health

RCT of 100 Chinese adults with hyperhomocysteinemia testing low-dose B vitamins plus betaine supplementation for 12 weeks. The supplement group showed a significant reduction in plasma homocysteine concentrations compared to placebo, indicating a positive effect on heart health.

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2021·Alcohol (Fayetteville, N.Y.)·J A Kable, C D Coles, C L Keen, et al

The impact of micronutrient supplementation in alcohol-exposed pregnancies on reaction time responses of preschoolers in Ukraine.

RCTMental Clarity

RCT in Ukraine examining the impact of maternal micronutrient supplementation, including MVM and choline, on reaction time in preschoolers exposed to prenatal alcohol. Boys whose mothers received MVM showed improved reaction times, while choline supplementation increased response speed in males without PAE history. Females did not show the same benefits and were more adversely impacted by PAE.

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2020·The American journal of clinical nutrition·B. Fu, M. Hullar, T. Randolph, et al

Associations of plasma trimethylamine N-oxide, choline, carnitine, and betaine with inflammatory and cardiometabolic risk biomarkers and the fecal microbiome in the Multiethnic Cohort Adiposity Phenotype Study.

Cross-sectionaln = 1,653Inflammation Heart Health

Cross-sectional analysis of 1653 participants in the Multiethnic Cohort Study examining associations of TMAO and its precursors with inflammatory and cardiometabolic risk biomarkers. Higher TMAO and carnitine levels, and lower betaine levels, were linked to greater insulin resistance. Choline was associated with adverse cardiometabolic risk profiles. TMAO was also associated with specific bacterial taxa in the fecal microbiome.

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2019·PLoS medicine·Philip T James, Ousubie Jawla, Nuredin I Mohammed, et al

A novel nutritional supplement to reduce plasma homocysteine in nonpregnant women: A randomised controlled trial in The Gambia.

RCTn = 298Nutrition

RCT in nonpregnant women in The Gambia testing a novel drink powder containing betaine, folic acid, vitamin B12, and vitamin B2 against a micronutrient tablet and no intervention. The drink powder reduced plasma homocysteine by 23.6% compared to controls, showing potential for future use in preconception trials.

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2015·Journal of inherited metabolic disease·Martina Huemer, Viktor Kožich, Piero Rinaldo, et al

Newborn screening for homocystinurias and methylation disorders: systematic review and proposed guidelines.

Systematic review

Systematic review on newborn screening for homocystinurias and methylation disorders. Recommends early treatment with diet, betaine, and/or pyridoxine for CBS deficiency and betaine for severe MTHFR deficiency. Discusses screening methods and evidence for various metabolic disorders.

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2012·Fish physiology and biochemistry·Neeraj Kumar, S B Jadhao, N K Chandan, et al

Methyl donors potentiates growth, metabolic status and neurotransmitter enzyme in Labeo rohita fingerlings exposed to endosulfan and temperature.

RCTn = 270Physical Performance Stress

A 2-month study on Labeo rohita fingerlings examined the effects of dietary methyl donors (choline, betaine, and lecithin) on growth and metabolic status under endosulfan and elevated temperature stress. Methyl donors improved growth performance and stress mitigation, with significant differences in weight gain and enzyme activities compared to control.

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2025·Nutrients·David C Nieman, Camila A Sakaguchi, James C Williams, et al

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

RCTn = 21Physical Performance Recovery

This study examined the effects of 2 weeks of betaine supplementation (3 g/d) versus placebo on 60 km cycling performance and one-carbon metabolism in 21 non-elite cyclists. Betaine supplementation modestly improved cycling performance and influenced the one-carbon metabolism pathway during recovery, but had no effect on gut permeability.

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2024·Nutrition research (New York, N.Y.)·Emilia Zawieja, Natalia Drabińska, Henryk Jeleń, et al

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.

RCTn = 20Nutrition

Randomized placebo-controlled cross-over study on betaine supplementation in healthy active males. Betaine supplementation increased betaine concentration and decreased homocysteine levels, with greater effects in MTHFR T-allele carriers. No significant changes were observed in amino acid or choline concentrations.

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2023·Journal of the International Society of Sports Nutrition·Emilia Zawieja, Krzysztof Durkalec-Michalski, Marcin Sadowski, et al

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

RCTn = 43Physical Performance Mens Health

Randomized crossover trial evaluating the effects of three weeks of betaine supplementation on CrossFit performance, muscle power, body composition, and hormone levels in 43 practitioners. Betaine improved CrossFit performance and increased testosterone levels, but had no effect on Wingate power or body composition.

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2023·Nutrients·Michaela Minarski, Christoph Maas, Christine Heinrich, et al

Choline and Betaine Levels in Plasma Mirror Choline Intake in Very Preterm Infants.

RCTn = 34Nutrition

This secondary analysis of an RCT investigated the relationship between enteral choline intake and plasma choline, betaine, and phosphatidylcholine concentrations in very low birth weight infants. Plasma choline and betaine levels correlated with enteral choline intake, but the intake was insufficient to achieve physiological concentrations, suggesting a need to optimize maternal choline status and milk fortification.

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2023·Physiological reports·Brandon D Willingham, Liliana I Rentería, Tristan J Ragland, et al

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

RCTn = 11

A double-blind, placebo-controlled, crossover study examined the effects of betaine supplementation on fluid balance and heat tolerance in 11 young, recreationally active men. After a 7-day loading period and during passive heat exposure, betaine did not improve markers of fluid balance or heat tolerance compared to placebo.

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2022·Nutrients·Steven B Machek, Dillon R Harris, Emilia E Zawieja, et al

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.

RCTn = 18Physical Performance -

RCT comparing the effects of betaine supplementation versus placebo on one-leg press performance, lactate concentrations, and exercise-associated biomarkers in 18 recreationally trained males. No significant differences were found in total repetitions completed, but betaine showed higher serum IGF-1 levels compared to placebo, suggesting anabolic potential.

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2022·Orphanet journal of rare diseases·Apolline Imbard, Artemis Toumazi, Sophie Magréault, et al

Efficacy and pharmacokinetics of betaine in CBS and cblC deficiencies: a cross-over randomized controlled trial.

RCTn = 11

This study is a prospective, randomized, crossover clinical trial comparing two doses of betaine (100 mg/kg/day vs. 250 mg/kg/day) in children with pnrCBS or cblC deficiencies. The study found that tHcy concentrations were equivalent for both dosages after one month. However, higher doses of betaine increased methionine and SAM concentrations, which could benefit cblC patients but may be harmful to pnrCBS patients with pre-existing hypermethioninemia.

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2021·Stroke·Chongke Zhong, Zian Lu, Bizhong Che, et al

Choline Pathway Nutrients and Metabolites and Cognitive Impairment After Acute Ischemic Stroke.

Observationaln = 617Brain Health

The study investigated the relationship between circulating choline, betaine, and trimethylamine N-oxide with cognitive impairment in 617 acute ischemic stroke patients. Higher plasma levels of choline and betaine were inversely associated with cognitive impairment, while trimethylamine N-oxide was positively associated with cognitive impairment as evaluated by the Mini-Mental State Examination.

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2021·European journal of neurology·Mengyuan Miao, Jigang Du, Bizhong Che, et al

Circulating choline pathway nutrients and depression after ischemic stroke.

Observationaln = 612Mood

This study explored the associations between plasma choline and betaine levels and depression after ischemic stroke in 612 participants. Patients with higher levels of choline and betaine had a lower risk of poststroke depression, indicating a protective effect of these nutrients.

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2021·Journal of the International Society of Sports Nutrition·H. Nobari, M. Kargarfard, V. Minasian, et al

The effects of 14-week betaine supplementation on endocrine markers, body composition and anthropometrics in professional youth soccer players: a double blind, randomized, placebo-controlled trial

RCTn = 29Hormone Health Physique

Double-blind, randomized, placebo-controlled trial evaluating the effects of 14-week betaine supplementation on endocrine markers, body composition, and anthropometrics in professional youth soccer players. Betaine supplementation increased testosterone levels and T/C ratio, with no negative effects on growth and potential attenuation of testosterone reductions due to intense training.

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2021·Journal of the International Society of Sports Nutrition·Hadi Nobari, Jason M Cholewa, Alfonso Castillo-Rodríguez, et al

Effects of chronic betaine supplementation on performance in professional young soccer players during a competitive season: a double blind, randomized, placebo-controlled trial.

RCTn = 29Physical Performance Inflammation

Double-blind, randomized, placebo-controlled trial of 29 young professional soccer players assessing the effects of 14-week betaine supplementation (2 g/day) on performance. Betaine supplementation increased predicted 1-RM, VO, and repeated sprint ability, suggesting it is a useful nutritional strategy to improve and maintain performance during a competitive soccer season.

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2021·Journal of the International Society of Sports Nutrition·Hadi Nobari, Jason M Cholewa, Jorge Pérez-Gómez, et al

Effects of 14-weeks betaine supplementation on pro-inflammatory cytokines and hematology status in professional youth soccer players during a competition season: a double blind, randomized, placebo-controlled trial.

RCTn = 29Inflammation Immunity

This double-blind, randomized, placebo-controlled trial investigated the effects of 14 weeks of betaine supplementation on pro-inflammatory cytokines and hematology status in 29 professional youth soccer players. Betaine supplementation prevented an increase in pro-inflammatory cytokines and white blood cell counts, suggesting it may help regulate the immune response during a competitive soccer season.

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2021·Journal of dietary supplements·Hunter S Waldman, Andrea R Bryant, Matthew J McAllister

Effects of Betaine Supplementation on Markers of Metabolic Flexibility, Body Composition, and Anaerobic Performance in Active College-Age Females.

RCTn = 23Physique Physical Performance

RCT investigating the effects of betaine supplementation on metabolic flexibility, body composition, and anaerobic performance in active college-age females. The study found that betaine supplementation led to significant increases in fat-free mass and improvements in performance metrics such as mean power output and perceived exertion during exercise.

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2020·Nutrients·E. Smeets, R. Mensink, J. Hoeks, et al

Effects of Beetroot Powder with or without L-Arginine on Postprandial Vascular Endothelial Function: Results of a Randomized Controlled Trial with Abdominally Obese Men

RCTn = 18Heart Health -

RCT with 18 abdominally obese men comparing the effects of beetroot powder with or without L-arginine on postprandial vascular endothelial function after a high-fat meal. No significant differences were observed in postprandial FMD levels, though there was a non-significant trend towards a more beneficial response with beetroot-containing meals.

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2016·Pharmaceutical research·Kathleen Panter Faber, Hsin-Fang Wu, Marc R Yago, et al

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

RCT

Randomized, single-dose, 3 period, crossover study in healthy volunteers examining the effect of betaine hydrochloride on atazanavir absorption during rabeprazole-induced hypochlorhydria. Betaine HCl restored 13% of atazanavir concentration and 12% of AUC lost due to rabeprazole, but did not sufficiently mitigate the loss of atazanavir exposure.

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2014·The AAPS journal·Marc R Yago, Adam Frymoyer, Leslie Z Benet, et al

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

RCT

Randomized, single-dose, three-way crossover study in healthy volunteers to assess if betaine hydrochloride (BHCl) can enhance dasatinib absorption under rabeprazole-induced hypochlorhydric conditions. BHCl significantly increased dasatinib Cmax and AUC0-∞, restoring them to levels comparable to dasatinib alone.

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2014·Journal of animal physiology and animal nutrition·M Nezamidoust, M Alikhani, G R Ghorbani, et al

Responses to betaine and inorganic sulphur of sheep in growth performance and fibre growth.

RCT

The study examined the effects of betaine and inorganic sulphur supplementation on growth performance and wool production in ewes and lambs. Betaine plus sulphate supplementation increased wool growth rate, wool yield, staple length, and wool sulphur concentration in ewes, but had no significant effect on lambs. Plasma methionine concentration increased in ewes with the combined treatment.

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2014·Nutricion hospitalaria·Guilherme Teixeira Araújo, Fernanda Domenici, Jorge Elias, et al

Betaine: a potential agent for the treatment of hepatopathy associated with short bowel syndrome.

RCT

A prospective, unicentric, non-placebo controlled trial evaluated the efficacy of betaine for treating hepatopathy associated with short bowel syndrome. Betaine supplementation for three months decreased hepatic fat percentage but did not significantly reduce inflammatory proteins or hepatic lesion markers. Side effects included transient diarrhea and nausea.

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2005·PLoS medicine·Margreet R Olthof, Trinette van Vliet, Petra Verhoef, et al

Effect of homocysteine-lowering nutrients on blood lipids: results from four randomised, placebo-controlled studies in healthy humans.

RCTn = 151Heart Health

Four placebo-controlled, randomised intervention studies examined the effect of betaine, folic acid, and phosphatidylcholine on blood lipid concentrations in healthy humans. Betaine supplementation increased blood LDL cholesterol and triacylglycerol concentrations, potentially counteracting its homocysteine-lowering benefits. Phosphatidylcholine slightly increased triacylglycerol concentrations, while folic acid had no effect on lipid concentrations.

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2005·Research in veterinary science·B H Ali, A A Al-Qarawi, H M Mousa

Stress associated with road transportation in desert sheep and goats, and the effect of pretreatment with xylazine or sodium betaine.

RCTStress -

The study investigates the effects of road transportation stress on desert sheep and goats and the influence of pretreatment with xylazine and sodium betaine. Transportation stress increased plasma cortisol and glucose levels and decreased magnesium levels. Xylazine significantly ameliorated stress effects, while sodium betaine had variable and insignificant effects.

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2018·The Journal of Clinical Endocrinology & Metabolism·Ana María Grizales, M. Patti, Alexander P Lin, et al

Metabolic Effects of Betaine: A Randomized Clinical Trial of Betaine Supplementation in Prediabetes

RCTn = 27Nutrition

A 12-week, randomized, double-masked, placebo-controlled trial assessed the metabolic effects of oral betaine in 27 obese participants with prediabetes. Betaine supplementation resulted in a significant increase in plasma dimethylglycine levels and reduced insulin area under curve after oral glucose compared to placebo, but did not improve insulin sensitivity or glycemia significantly. Serum total cholesterol levels increased after betaine treatment.

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2018·Journal of the International Society of Sports Nutrition·J. Cholewa, A. Hudson, Taylor Cicholski, et al

The effects of chronic betaine supplementation on body composition and performance in collegiate females: a double-blind, randomized, placebo controlled trial

RCTn = 23Physique Physical Performance -

This double-blind, randomized, placebo-controlled trial investigated the effects of chronic betaine supplementation on body composition and performance in 23 untrained collegiate females. The study found that betaine supplementation may enhance reductions in fat mass but did not significantly affect absolute strength gains compared to placebo.

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2012·Animal : an international journal of animal bioscience·I Fernández-Fígares, M Lachica, A Martín, et al

Impact of dietary betaine and conjugated linoleic acid on insulin sensitivity, protein and fat metabolism of obese pigs.

RCTn = 20

RCT studying the effects of betaine and conjugated linoleic acid (CLA) on insulin sensitivity, protein, and fat metabolism in obese pigs. Betaine and CLA altered serum lipids and hormones, indicating a nutrient partitioning effect, but had weak detrimental effects on blood lipids. Serum insulin increased with CLA and betaine + CLA, but insulin resistance indices were unaffected.

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2008·Journal of animal science·I Fernández-Fígares, J A Conde-Aguilera, R Nieto, et al

Synergistic effects of betaine and conjugated linoleic acid on the growth and carcass composition of growing Iberian pigs.

RCTn = 20Physique

An experiment on growing Iberian pigs tested the effects of dietary betaine, CLA, or both on growth and carcass composition. Betaine + CLA increased average daily gain and protein, water, and lean deposition compared to control. The study suggests a synergistic effect of betaine and CLA on growth performance.

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2006·The Journal of nutrition·Ursula Schwab, Anneli Törrönen, Esa Meririnne, et al

Orally administered betaine has an acute and dose-dependent effect on serum betaine and plasma homocysteine concentrations in healthy humans.

RCTn = 10

This study assessed the pharmacokinetics of orally administered betaine and its acute effect on plasma homocysteine concentrations in 10 healthy volunteers. Betaine had an immediate and dose-dependent effect on serum betaine concentration, with single doses of 3 and 6 g lowering plasma homocysteine concentrations, unlike the 1-g dose.

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2002·The American journal of clinical nutrition·Ursula Schwab, Anneli Törrönen, Leena Toppinen, et al

Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects.

RCTn = 42Nutrition

RCT of 42 obese subjects on a hypoenergetic diet, comparing betaine supplementation (6 g/d) to placebo for 12 weeks. Betaine decreased plasma homocysteine concentrations but did not significantly affect body weight, body composition, or resting energy expenditure compared to placebo.

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2024·Redox Biology·Zhijun Yang, Si-Yu Huang, Kai-Yi Zhong, et al

Betaine alleviates cognitive impairment induced by homocysteine through attenuating NLRP3-mediated microglial pyroptosis in an m6A-YTHDF2-dependent manner

Animal studyBrain Health

The study investigates the effects of betaine on cognitive impairment induced by homocysteine in SD rats. Betaine supplementation attenuated cognitive impairment and inhibited microglial activation, reducing oxidative stress and inflammation. Mechanistically, betaine inhibited microglial pyroptosis via the NLRP3/caspase-1/GSDMD pathway in an m6A-YTHDF2-dependent manner.

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2023·Diagnostics·K. Sarkisova, E. Fedosova, A. Shatskova, et al

Maternal Methyl-Enriched Diet Increases DNMT1, HCN1, and TH Gene Expression and Suppresses Absence Seizures and Comorbid Depression in Offspring of WAG/Rij Rats

Animal studyBrain Health Mood

The study investigated the effects of a maternal methyl-enriched diet (MED) on gene expression and absence seizures with comorbid depression in WAG/Rij rat offspring. MED, containing choline, betaine, folic acid, vitamin B12, L-methionine, and zinc, suppressed seizures and depression symptoms, associated with increased expression of DNMT1, HCN1, and TH genes in specific brain regions.

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2021·Frontiers in Pharmacology·Wang Yajun, Cui Jin, Zhengrong Gu, et al

Betaine Attenuates Osteoarthritis by Inhibiting Osteoclastogenesis and Angiogenesis in Subchondral Bone

Animal studyJoint Bone Health

The study evaluated the effects of betaine on ACLT-induced osteoarthritis in mice. Betaine decreased MMP-13 and Col X-positive cells, prevented cartilage proteoglycan loss, and improved subchondral bone remodeling. It also inhibited osteoclastogenesis and angiogenesis in subchondral bone, suggesting a positive effect on joint health.

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2021·Gut Microbes·Jingjing Du, Peiwen Zhang, Jia Luo, et al

Dietary betaine prevents obesity through gut microbiota-drived microRNA-378a family

Animal studyGut Health Physique Nutrition

The study investigates the role of betaine supplementation in preventing high-fat diet-induced obesity and metabolic syndrome in mice. Betaine improved gut microbiota dysbiosis and increased anti-obesity strains, contributing to the regulation of glucose and lipid metabolism through the gut microbiota-derived miR-378a/YY1 regulatory axis.

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2020·Journal of hazardous materials·Xin Hu, Dahui Li, Y. Qiao, et al

Salt tolerance mechanism of a hydrocarbon-degrading strain: Salt tolerance mediated by accumulated betaine in cells.

Study

The study investigates the salt tolerance mechanism of Rhodococcus sp. HX-2, which degrades diesel oil in high salt conditions. Betaine accumulation in cells was identified as the main mechanism for salt resistance, with exogenous betaine enhancing cell growth and diesel degradation. The study highlights the potential of this strain for bioremediation in saline environments.

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2019·Animals : an Open Access Journal from MDPI·Wenchao Liu, Yilin Yuan, Chenyu Sun, et al

Effects of Dietary Betaine on Growth Performance, Digestive Function, Carcass Traits, and Meat Quality in Indigenous Yellow-Feathered Broilers under Long-Term Heat Stress

Animal studyn = 240

The study evaluated the effects of dietary betaine on growth performance, digestive function, carcass traits, and meat quality in indigenous yellow-feathered broilers under long-term heat stress. Betaine supplementation partially alleviated the adverse effects of heat stress on these parameters, improving body weight gain, feed intake, nitrogen retention, trypsin activity, and carcass yield.

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1998·Acta odontologica Scandinavica·E Söderling, A Le Bell, V Kirstilä, et al

Betaine-containing toothpaste relieves subjective symptoms of dry mouth.

RCTn = 13

Double-blind crossover study with 13 subjects with chronic dry mouth symptoms comparing betaine-containing toothpaste to regular toothpaste. The betaine toothpaste significantly relieved subjective symptoms of dry mouth, though no significant changes were observed in microbiologic variables or oral mucosa appearance.

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2023·Molecules·D. Dobrijević, K. Pastor, Nataša Nastić, et al

Betaine as a Functional Ingredient: Metabolism, Health-Promoting Attributes, Food Sources, Applications and Analysis Methods

Review

This narrative review discusses betaine as a functional ingredient, covering its dietary sources, metabolic pathways, health-promoting properties, and applications in food products. It also highlights extraction procedures and detection methods, as well as gaps in the existing scientific literature.

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2022·Animals : an Open Access Journal from MDPI·W. A. Abd El-Ghany, D. Babazadeh

Betaine: A Potential Nutritional Metabolite in the Poultry Industry

Review

This review article discusses the role of dietary betaine supplementation in the poultry industry, focusing on its effects on performance, carcass traits, osmoregulatory, anticoccidial, immune-modulatory, and heat-stress alleviation activities. Betaine is suggested as a promising feed additive due to its ability to improve feed conversion ratio, body weight, and reduce body fat in poultry.

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2021·European journal of pharmacology·Cheng Wang, Cheng Ma, Lihong Gong, et al

Preventive and therapeutic role of betaine in liver disease: A review on molecular mechanisms.

Review

This narrative review summarizes the molecular mechanisms by which betaine improves liver diseases, including chemical or drug-induced liver injury, nonalcoholic fatty liver disease, alcoholic fatty liver disease, liver fibrosis, hepatitis B, and hepatitis C. The review highlights betaine's role in inhibiting inflammatory response, improving insulin resistance, reducing endoplasmic reticulum stress, alleviating liver oxidative stress, increasing autophagy, remodeling intestinal flora, and regulating epigenetic modification.

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2021·Biology·M. Arumugam, Matthew C. Paal, T. Donohue, et al

Beneficial Effects of Betaine: A Comprehensive Review

ReviewBrain Health Heart Health Gut Health Inflammation

This comprehensive review focuses on the biological and beneficial effects of dietary betaine, highlighting its role as a therapeutic agent for liver diseases, including alcohol-induced and metabolic-associated liver disease. Betaine is shown to protect against hepatic steatosis, apoptosis, and liver injury, and also has neuroprotective and myocardial function-preserving roles.

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2020·Nutrients·Brandon D. Willingham, Tristan J Ragland, M. Ormsbee

Betaine Supplementation May Improve Heat Tolerance: Potential Mechanisms in Humans

Review

The paper reviews the potential mechanisms by which betaine supplementation may improve heat tolerance. It discusses betaine's role in reducing oxidative damage, stabilizing protein conformations, and maintaining gut membrane integrity under stress. While animal and cell culture studies suggest benefits, human data are limited and speculative.

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2019·Molecules·Hui Shi, Xiao-Long Wang, Hong-Feng Quan, et al

Effects of Betaine on LPS-Stimulated Activation of Microglial M1/M2 Phenotypes by Suppressing TLR4/NF-κB Pathways in N9 Cells

In vitroInflammation Brain Health

In vitro study investigating the anti-inflammatory effects of betaine on LPS-activated microglial cells. Betaine mitigated pro-inflammatory cytokine production, increased anti-inflammatory cytokines, and promoted microglial conversion from M1 to M2 phenotype by inhibiting the TLR4/NF-κB pathways.

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2019·European Journal of Pharmacology·M. Vesković, D. Mladenović, M. Milenkovic, et al

Betaine modulates oxidative stress, inflammation, apoptosis, autophagy, and Akt/mTOR signaling in methionine‐choline deficiency‐induced fatty liver disease

Animal studyInflammation

The study examined the effects of betaine on oxidative stress, inflammation, apoptosis, and autophagy in methionine-choline deficient diet-induced non-alcoholic fatty liver disease in mice. Betaine reduced liver transaminases, inflammatory infiltration, hepatosteatosis, and serum LDL levels, while increasing HDL levels. It also improved antioxidative defense and modulated cytokine expression, apoptosis, and autophagy markers, coinciding with increased Akt/mTOR signaling.

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2001·The American journal of gastroenterology·M F Abdelmalek, P Angulo, R A Jorgensen, et al

Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot study.

Studyn = 10

Pilot study of betaine anhydrous in 10 adult patients with nonalcoholic steatohepatitis (NASH) over 12 months. Significant improvements in serum aminotransferase levels and histological markers of liver disease activity were observed. Betaine was well tolerated with transitory GI adverse events in some patients.

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2013·Nutrients·R. Obeid

The Metabolic Burden of Methyl Donor Deficiency with Focus on the Betaine Homocysteine Methyltransferase Pathway

ReviewEnergy Nutrition

The paper reviews the metabolic impact of methyl donor deficiency, focusing on the betaine homocysteine methyltransferase pathway. It discusses the roles of dietary methyl donors like methionine, folate, betaine, and choline in energy metabolism and protein synthesis, and how deficiencies can lead to metabolic disturbances. Betaine supplementation is noted to lower post-methionine load homocysteine levels.

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1996·The Journal of pharmacology and experimental therapeutics·M. Miñana, Carlos Hermenegildo, M. Llsansola, et al

Carnitine and choline derivatives containing a trimethylamine group prevent ammonia toxicity in mice and glutamate toxicity in primary cultures of neurons.

Animal study

The study assessed the ability of carnitine and other trimethylamine-containing compounds to prevent ammonia toxicity in mice and glutamate toxicity in primary neuronal cultures. Carnitine, betaine, trimethylamine-N-oxide, choline, acetylcholine, carbachol, and acetylcarnitine were found to prevent ammonia toxicity in mice and glutamate toxicity in neurons, with varying degrees of protection.

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2018·Orphanet Journal of Rare Diseases·A. Gales, M. Masingue, S. Millecamps, et al

Adolescence/adult onset MTHFR deficiency may manifest as isolated and treatable distinct neuro-psychiatric syndromes

Case reportn = 2Brain Health

Case report of two adult siblings with MTHFR deficiency who experienced focal epilepsy as a first disease manifestation. Metabolic treatment with B9, B12, and betaine stopped seizures and allowed discontinuation of anti-epileptic drugs. Review of 24 cases showed improvement with metabolic treatment.

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