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Frontiers in Immunology 2018Betaine is known as trimethylglycine and is widely distributed in animals, plants, and microorganisms. Betaine is known to function physiologically as an important... (Review)
Review
Betaine is known as trimethylglycine and is widely distributed in animals, plants, and microorganisms. Betaine is known to function physiologically as an important osmoprotectant and methyl group donor. Accumulating evidence has shown that betaine has anti-inflammatory functions in numerous diseases. Mechanistically, betaine ameliorates sulfur amino acid metabolism against oxidative stress, inhibits nuclear factor-κB activity and NLRP3 inflammasome activation, regulates energy metabolism, and mitigates endoplasmic reticulum stress and apoptosis. Consequently, betaine has beneficial actions in several human diseases, such as obesity, diabetes, cancer, and Alzheimer's disease.
Topics: Animals; Anti-Inflammatory Agents; Betaine; Biomarkers; Endoplasmic Reticulum Stress; Energy Metabolism; Humans; Inflammation; Oxidation-Reduction; Oxidative Stress; Signal Transduction; Structure-Activity Relationship
PubMed: 29881379
DOI: 10.3389/fimmu.2018.01070 -
Journal of the International Society of... Aug 2018In recent years, a new class of dietary supplements called multi-ingredient pre-workout supplements (MIPS) has increased in popularity. These supplements are intended to... (Review)
Review
In recent years, a new class of dietary supplements called multi-ingredient pre-workout supplements (MIPS) has increased in popularity. These supplements are intended to be taken prior to exercise and typically contain a blend of ingredients such as caffeine, creatine, beta-alanine, amino acids, and nitric oxide agents, the combination of which may elicit a synergistic effect on acute exercise performance and subsequent training adaptations compared to single ingredients alone. Therefore, the purpose of this article was to review the theoretical rationale and available scientific evidence assessing the potential ergogenic value of acute and chronic ingestion of MIPS, to address potential safety concerns surrounding MIPS supplementation, and to highlight potential areas for future research. Though direct comparisons between formulations of MIPS or between a MIPS and a single ingredient are challenging and often impossible due to the widespread use of "proprietary blends" that do not disclose specific amounts of ingredients in a given formulation, a substantial body of evidence suggests that the acute pre-exercise consumption of MIPS may positively influence muscular endurance and subjective mood, though mixed results have been reported regarding the acute effect of MIPS on force and power production. The chronic consumption of MIPS in conjunction with a periodized resistance training program appears to augment beneficial changes in body composition through increased lean mass accretion. However, the impact of long-term MIPS supplementation on force production, muscular endurance, aerobic performance, and subjective measures is less clear. MIPS ingestion appears to be relatively safe, though most studies that have assessed the safety of MIPS are relatively short (less than eight weeks) and thus more information is needed regarding the safety of long-term supplementation. As with any dietary supplement, the use of MIPS carries implications for the athlete, as many formulations may intentionally contain banned substances as ingredients or unintentionally as contaminants. We suggest that athletes thoroughly investigate the ingredients present in a given MIPS prior to consumption. In conclusion, it appears that multi-ingredient pre-workout supplements have promise as an ergogenic aid for active individuals, though further information is required regarding long-term efficacy and safety in a wider variety of populations.
Topics: Amino Acids; Athletes; Athletic Performance; Betaine; Caffeine; Creatine; Dietary Supplements; Humans; Muscle Strength; Performance-Enhancing Substances; Physical Endurance; Sports Nutritional Physiological Phenomena; beta-Alanine
PubMed: 30089501
DOI: 10.1186/s12970-018-0247-6 -
Journal of Inherited Metabolic Disease Jan 2017Cystathionine beta-synthase (CBS) deficiency is a rare inherited disorder in the methionine catabolic pathway, in which the impaired synthesis of cystathionine leads to... (Review)
Review
Cystathionine beta-synthase (CBS) deficiency is a rare inherited disorder in the methionine catabolic pathway, in which the impaired synthesis of cystathionine leads to accumulation of homocysteine. Patients can present to many different specialists and diagnosis is often delayed. Severely affected patients usually present in childhood with ectopia lentis, learning difficulties and skeletal abnormalities. These patients generally require treatment with a low-methionine diet and/or betaine. In contrast, mildly affected patients are likely to present as adults with thromboembolism and to respond to treatment with pyridoxine. In this article, we present recommendations for the diagnosis and management of CBS deficiency, based on a systematic review of the literature. Unfortunately, the quality of the evidence is poor, as it often is for rare diseases. We strongly recommend measuring the plasma total homocysteine concentrations in any patient whose clinical features suggest the diagnosis. Our recommendations may help to standardise testing for pyridoxine responsiveness. Current evidence suggests that patients are unlikely to develop complications if the plasma total homocysteine concentration is maintained below 120 μmol/L. Nevertheless, we recommend keeping the concentration below 100 μmol/L because levels fluctuate and the complications associated with high levels are so serious.
Topics: Betaine; Cystathionine beta-Synthase; Homocysteine; Homocystinuria; Humans; Methionine; Pyridoxine
PubMed: 27778219
DOI: 10.1007/s10545-016-9979-0 -
The Cochrane Database of Systematic... Mar 2021Leg ulcers are open skin wounds that occur below the knee but above the foot. The majority of leg ulcers are venous in origin, occurring as a result of venous... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Leg ulcers are open skin wounds that occur below the knee but above the foot. The majority of leg ulcers are venous in origin, occurring as a result of venous insufficiency, where the flow of blood through the veins is impaired; they commonly arise due to blood clots and varicose veins. Compression therapy, using bandages or stockings, is the primary treatment for venous leg ulcers. Wound cleansing can be used to remove surface contaminants, bacteria, dead tissue and excess wound fluid from the wound bed and surrounding skin, however, there is uncertainty regarding the effectiveness of cleansing and the best method or solution to use.
OBJECTIVES
To assess the effects of wound cleansing, wound cleansing solutions and wound cleansing techniques for treating venous leg ulcers.
SEARCH METHODS
In September 2019 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) comparing wound cleansing with no wound cleansing, or RCTs comparing different wound cleansing solutions, or different wound cleansing techniques.
DATA COLLECTION AND ANALYSIS
We screened studies for their appropriateness for inclusion, assessed their risk of bias using the Cochrane 'Risk of bias' tool, and used GRADE methodology to determine the certainty of evidence. Two review authors undertook these tasks independently, using predetermined criteria. We contacted study authors for missing data where possible.
MAIN RESULTS
We included four studies with a total of 254 participants. All studies included comparisons between different types of cleansing solutions, and three of these reported our primary outcomes of complete wound healing or change in ulcer size over time, or both. Two studies reported the secondary outcome, pain. One study (27 participants), which compared polyhexamethylene biguanide (PHMB) solution with saline solution for cleansing venous leg ulcers, did not report any of the review's primary or secondary outcomes. We did not identify any studies that compared cleansing with no cleansing, or that explored comparisons between different cleansing techniques. One study (61 participants) compared aqueous oxygen peroxide with sterile water. We are uncertain whether aqueous oxygen peroxide makes any difference to the number of wounds completely healed after 12 months of follow-up (risk ratio (RR) 1.88, 95% confidence interval (CI) 1.10 to 3.20). Similarly, we are uncertain whether aqueous oxygen peroxide makes any difference to change in ulcer size after eight weeks of follow-up (mean difference (MD) -1.38 cm, 95% CI -4.35 to 1.59 cm). Finally, we are uncertain whether aqueous oxygen peroxide makes any difference to pain reduction, assessed after eight weeks of follow-up using a 0 to 100 pain rating, (MD 3.80, 95% CI -10.83 to 18.43). The evidence for these outcomes is of very low certainty (we downgraded for study limitations and imprecision; for the pain outcome we also downgraded for indirectness). Another study (40 participants) compared propyl betaine and polihexanide with a saline solution. The authors did not present the raw data in the study report so we were unable to conduct independent statistical analysis of the data. We are uncertain whether propyl betaine and polihexanide make any difference to the number of wounds completely healed, change in ulcer size over time, or wound pain reduction. The evidence is of very low certainty (we downgraded for study limitations and imprecision). The final study (126 participants) compared octenidine dihydrochloride/phenoxyethanol (OHP) with Ringer's solution. We are uncertain whether OHP makes any difference to the number of wounds healed (RR 0.96, 95% CI 0.53 to 1.72) or to the change in ulcer size over time (we were unable to conduct independent statistical analysis of available data). The evidence is of very low certainty (we downgraded for study limitations and imprecision). None of the studies reported patient preference, ease of use of the method of cleansing, cost or health-related quality of life. In one study comparing propyl betaine and polihexanide with saline solution the authors do not report any adverse events occurring. We are uncertain whether OHP makes any difference to the number of adverse events compared with Ringer's solution (RR 0.58, 95% CI 0.29 to 1.14). The evidence is of very low certainty (we downgraded for study limitations and imprecision).
AUTHORS' CONCLUSIONS
There is currently a lack of RCT evidence to guide decision making about the effectiveness of wound cleansing compared with no cleansing and the optimal approaches to cleansing of venous leg ulcers. From the four studies identified, there is insufficient evidence to demonstrate whether the use of PHMB solution compared with saline solution; aqueous oxygen peroxide compared with sterile water; propyl betaine and polihexanide compared with a saline solution; or OHP compared with Ringer's solution makes any difference in the treatment of venous leg ulcers. Evidence from three of the studies is of very low certainty, due to study limitations and imprecision. One study did not present data for the primary or secondary outcomes. Further well-designed studies that address important clinical, quality of life and economic outcomes may be important, based on the clinical and patient priority of this uncertainty.
Topics: Aged; Anti-Infective Agents, Local; Betaine; Bias; Biguanides; Confidence Intervals; Detergents; Disinfectants; Ethylene Glycols; Female; Humans; Hydrogen Peroxide; Imines; Male; Middle Aged; Pain Measurement; Pyridines; Randomized Controlled Trials as Topic; Ringer's Solution; Saline Solution; Varicose Ulcer; Wound Healing
PubMed: 33734426
DOI: 10.1002/14651858.CD011675.pub2 -
International Journal of Molecular... Aug 2021Polybetaines, that have moieties bearing both cationic (quaternary ammonium group) and anionic groups (carboxylate, sulfonate, phosphate/phosphinate/phosphonate groups)... (Review)
Review
Polybetaines, that have moieties bearing both cationic (quaternary ammonium group) and anionic groups (carboxylate, sulfonate, phosphate/phosphinate/phosphonate groups) situated in the same structural unit represent an important class of smart polymers with unique and specific properties, belonging to the family of zwitterionic materials. According to the anionic groups, polybetaines can be divided into three major classes: poly(carboxybetaines), poly(sulfobetaines) and poly(phosphobetaines). The structural diversity of polybetaines and their special properties such as, antifouling, antimicrobial, strong hydration properties and good biocompatibility lead to their use in nanotechnology, biological and medical fields, water remediation, hydrometallurgy and the oil industry. In this review we aimed to highlight the recent developments achieved in the field of biomedical applications of polybetaines such as: antifouling, antimicrobial and implant coatings, wound healing and drug delivery systems.
Topics: Animals; Anti-Infective Agents; Betaine; Drug Delivery Systems; Humans; Wound Healing
PubMed: 34502230
DOI: 10.3390/ijms22179321 -
European Journal of Nutrition Apr 2022Alcohol-associated liver disease (AALD) is one of most common chronic liver diseases. Hepatic steatosis is the earliest stage in AALD pathological spectrum, reversible... (Review)
Review
Alcohol-associated liver disease (AALD) is one of most common chronic liver diseases. Hepatic steatosis is the earliest stage in AALD pathological spectrum, reversible by alcohol abstinence. Untreated steatosis can progress to steatohepatitis, fibrosis and/or cirrhosis. Considering the difficulties in achieving complete abstinence, challenges in disease reversal at advanced stages, high costs of AALD management and lack of standardised prescribed medications for treatment, it is essential to explore low-cost natural compounds that can target AALD at an early stage and halt or decelerate disease progression. Betaine is a non-hazardous naturally occurring nutrient. Here, we address the mechanisms of alcohol-induced hepatic steatosis, the role of betaine in reversing the effects i.e., its action against hepatic steatosis in animal models and humans, and the associated cellular and molecular processes. Accordingly, the review discusses how betaine restores the alcohol-induced reduction in methylation potential by elevating the levels of S-adenosylmethionine and methionine. It details how betaine reinstates alcohol-induced alterations in the expressions and/or activities of protein phosphtase-2A, FOXO1, PPAR-α, AMPK, SREBP-1c, fatty acid synthase, diacylglycerol transferase-2, adiponectin and nitric oxide. Interrelationships between these factors in preventing de novo lipogenesis, reducing hepatic uptake of adipose-tissue-derived free fatty acids, promoting VLDL synthesis and secretion, and restoring β-oxidation of fatty acids to attenuate hepatic triglyceride accumulation are elaborated. Despite its therapeutic potential, very few clinical trials have examined betaine's effect on alcohol-induced hepatic lipid accumulation. This review will provide further confidence to conduct randomised control trials to enable maximum utilisation of betaine's remedial properties to treat alcohol-induced hepatic steatosis.
Topics: Animals; Betaine; Fatty Liver; Lipogenesis; Liver; Sterol Regulatory Element Binding Protein 1
PubMed: 34817678
DOI: 10.1007/s00394-021-02738-2 -
Biochimica Et Biophysica Acta Jun 2016Betaine is the trimethyl derivative of glycine and is normally present in human plasma due to dietary intake and endogenous synthesis in liver and kidney. Betaine is... (Review)
Review
BACKGROUND
Betaine is the trimethyl derivative of glycine and is normally present in human plasma due to dietary intake and endogenous synthesis in liver and kidney. Betaine is utilized in the kidney primarily as an osmoprotectant, whereas in the liver its primary role is in metabolism as a methyl group donor. In both organs, a specific betaine transporter mediates cellular uptake of betaine from plasma. The abundance of both betaine and the betaine transporter in liver greatly exceeds that of other organs.
SCOPE OF REVIEW
The remarkable contributions of betaine to normal human and animal health are summarized together with a discussion of the mechanisms and potential beneficial effects of dietary betaine supplements on liver disease.
MAJOR CONCLUSIONS
A significant amount of data from animal models of liver disease indicates that administration of betaine can halt and even reverse progression of the disruption of liver function. Betaine is well-tolerated, inexpensive, effective over a wide range of doses, and is already used in livestock feeding practices.
GENERAL SIGNIFICANCE
The accumulated data indicate that carefully controlled additional investigations in humans are merited. The focus should be on the long-term use of betaine in large patient populations with liver diseases characterized by development of fatty liver, especially non-alcoholic fatty liver disease and alcoholic liver disease.
Topics: Animals; Betaine; Humans; Kidney; Liver; Liver Diseases; Liver Diseases, Alcoholic; Non-alcoholic Fatty Liver Disease
PubMed: 26850693
DOI: 10.1016/j.bbagen.2016.02.001 -
Nutrients Jul 2017Studies implicate choline and betaine metabolite trimethylamine N-oxide (TMAO) in cardiovascular disease (CVD). We conducted a systematic review and random-effects... (Meta-Analysis)
Meta-Analysis Review
Studies implicate choline and betaine metabolite trimethylamine N-oxide (TMAO) in cardiovascular disease (CVD). We conducted a systematic review and random-effects meta-analysis to quantify a summary estimated effect of dietary choline and betaine on hard CVD outcomes (incidence and mortality). Eligible studies were prospective studies in adults with comprehensive diet assessment and follow-up for hard CVD endpoints. We identified six studies that met our criteria, comprising 18,076 incident CVD events, 5343 CVD deaths, and 184,010 total participants. In random effects meta-analysis, incident CVD was not associated with choline (relative risk (RR): 1.00; 95% CI: 0.98, 1.02) or betaine (RR: 0.99; 95% CI: 0.98, 1.01) intake. Results did not vary by study outcome (incident coronary heart disease, stroke, total CVD) and there was no evidence for heterogeneity among studies. Only two studies provided data on phosphatidylcholine and CVD mortality. Random effects meta-analysis did not support an association between choline and CVD mortality (RR: 1.09, 95% CI: 0.89, 1.35), but one study supported a positive association and there was significant heterogeneity (² = 84%, -value < 0.001). Our findings do not support an association between dietary choline/betaine with incident CVD, but call for further research into choline and CVD mortality.
Topics: Adult; Aged; Betaine; Cardiovascular Diseases; Choline; Diet; Female; Humans; Male; Middle Aged; Prospective Studies; Risk; Risk Factors
PubMed: 28686188
DOI: 10.3390/nu9070711 -
The Journal of Nutrition Oct 2020The metabolism of methionine and cysteine in the body tissues determines the concentrations of several metabolites with various biologic activities, including... (Review)
Review
The metabolism of methionine and cysteine in the body tissues determines the concentrations of several metabolites with various biologic activities, including homocysteine, hydrogen sulfide (H2S), taurine, and glutathione. Hyperhomocysteinemia, which is correlated with lower HDL cholesterol in blood in volunteers and animal models, has been associated with an increased risk for cardiovascular diseases. In humans, the relation between methionine intake and hyperhomocysteinemia is dependent on vitamin status (vitamins B-6 and B-12 and folic acid) and on the supply of other amino acids. However, lowering homocysteinemia by itself is not sufficient for decreasing the risk of cardiovascular disease progression. Other compounds related to methionine metabolism have recently been identified as being involved in the risk of atherosclerosis and steatohepatitis. Indeed, the metabolism of sulfur amino acids has an impact on phosphatidylcholine (PC) metabolism, and anomalies in PC synthesis due to global hypomethylation have been associated with disturbances of lipid metabolism. In addition, impairment of H2S synthesis from cysteine favors atherosclerosis and steatosis in animal models. The effects of taurine on lipid metabolism appear heterogeneous depending on the populations of volunteers studied. A decrease in the concentration of intracellular glutathione, a tripeptide involved in redox homeostasis, is implicated in the etiology of cardiovascular diseases and steatosis. Last, supplementation with betaine, a compound that allows remethylation of homocysteine to methionine, decreases basal and methionine-stimulated homocysteinemia; however, it adversely increases plasma total and LDL cholesterol. The study of these metabolites may help determine the range of optimal and safe intakes of methionine and cysteine in dietary proteins and supplements. The amino acid requirement for protein synthesis in different situations and for optimal production of intracellular compounds involved in the regulation of lipid metabolism also needs to be considered for dietary attenuation of atherosclerosis and steatosis risk.
Topics: Amino Acids, Sulfur; Animals; Atherosclerosis; Betaine; Cholesterol; Cysteine; Dietary Proteins; Dietary Supplements; Fatty Liver; Glutathione; Humans; Hydrogen Sulfide; Hyperhomocysteinemia; Lipid Metabolism; Methionine; Nutritional Requirements; Nutritional Status; Phosphatidylcholines; Sulfur; Sulfur Compounds; Taurine
PubMed: 33000164
DOI: 10.1093/jn/nxaa243 -
Molecules (Basel, Switzerland) Mar 2021Trimethylamine -oxide (TMAO), as a gut-derived metabolite, has been found to be associated with enhanced risk for atherosclerosis and cardiovascular disease. We...
Trimethylamine -oxide (TMAO), as a gut-derived metabolite, has been found to be associated with enhanced risk for atherosclerosis and cardiovascular disease. We presented a method for targeted profiling of TMAO and betaine in serum and food samples based on a combination of one-step sample pretreatment and proton nuclear magnetic resonance spectroscopy. The key step included a processing of sample preparation using a selective solid-phase extraction column for retention of basic metabolites. Proton signals at 3.29 and 3.28 were employed to quantify TMAO and betaine, respectively. The developed method was examined with acceptable linear relationship, precision, stability, repeatability, and accuracy. It was successfully applied to detect serum levels of TMAO and betaine in TMAO-fed mice and high-fructose-fed rats and also used to determine the contents of TMAO and betaine in several kinds of food, such as fish, pork, milk, and egg yolk.
Topics: Animals; Betaine; Female; Food Analysis; Male; Metabolomics; Methylamines; Mice; Mice, Inbred C57BL; Oxides; Rats; Rats, Wistar
PubMed: 33801417
DOI: 10.3390/molecules26051334