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Nutrients Nov 2021Trimethylamine -oxide (TMAO) and its precursors, including choline, betaine, and L-carnitine, are gut microbiota-related metabolites associated with the risk of obesity....
Changes in Plasma Choline and the Betaine-to-Choline Ratio in Response to 6-Month Lifestyle Intervention Are Associated with the Changes of Lipid Profiles and Intestinal Microbiota: The ICAAN Study.
Trimethylamine -oxide (TMAO) and its precursors, including choline, betaine, and L-carnitine, are gut microbiota-related metabolites associated with the risk of obesity. We aimed (1) to comprehensively examine whether the changes in plasma TMAO and its precursors induced by lifestyle intervention are associated with the improvements in plasma metabolic parameters; and (2) to identify the fecal microbiome profiles and nutrient intakes associated with these metabolites and metabolic index. Data from 40 participants (obese children and adolescents) having the plasma metabolites data related to the changes in BMI z-scores after 6-month lifestyle intervention were analyzed. In this study, we observed that choline and the betaine-to-choline ratio (B/C) showed different patterns depending on the changes in BMI z-scores by the response to lifestyle intervention. During the 6 months, an increase in choline and a decrease in B/C were observed in non-responders. We also found that changes in choline and B/C were associated with the improvements in plasma lipid levels. Individuals who showed reduced choline or increased B/C from the baseline to 6 months had a significant decrease in LDL-cholesterol over 6 months compared to those with increased choline or decreased B/C, respectively. In addition, the increase in choline or decrease in B/C was associated with the increase in plasma triglycerides. The distribution of gut microbiota belonging to the Firmicutes, such as Clostridia, Clostridiales, Peptostreptococcaceae, , and was altered to be lower during the 6 months both as choline decreased and B/C increased. Moreover, the decrease in choline and the increase in B/C were associated with reduced fat intake and increased fiber intake after the 6-month intervention. Finally, lower abundance of showed the association with lower LDL-cholesterol and higher intake of fiber. In summary, we demonstrated that reduced choline and increased B/C by lifestyle intervention were associated with the improvements of LDL-cholesterol and triglycerides, low-fat and high-fiber intakes, and low abundance of Firmicutes. These indicate that changes to circulating choline and B/C could predict individuals' changes in metabolic compositions in response to the lifestyle intervention.
Topics: Adolescent; Bacteria; Betaine; Carnitine; Child; Choline; Clostridiales; Eating; Feces; Firmicutes; Gastrointestinal Microbiome; Humans; Life Style; Lipid Metabolism; Lipids; Methylamines; Nutrients; Pediatric Obesity; RNA, Ribosomal, 16S
PubMed: 34836260
DOI: 10.3390/nu13114006 -
World Journal of Gastroenterology Oct 2020Nonalcoholic steatohepatitis (NASH) is an important indication for liver transplantation in many Western countries due to the epidemic of obesity and insulin resistance.... (Review)
Review
Nonalcoholic steatohepatitis (NASH) is an important indication for liver transplantation in many Western countries due to the epidemic of obesity and insulin resistance. Unfortunately, no medication is approved for NASH and risk factor modification is often advised. Over the last decade, several clinical trials on NASH have been conducted with several ongoing and the future looks promising. Although betaine (trimethyl glycine) was evaluated for NASH, results were mixed in the clinical trials in large part due to the quality of the studies. It seems reasonable to re-evaluate betaine in clinical trials for NASH and alcoholic liver disease due to its low cost, tolerability and mechanism of action.
Topics: Betaine; Humans; Insulin Resistance; Liver; Liver Cirrhosis; Liver Transplantation; Non-alcoholic Fatty Liver Disease; Obesity
PubMed: 33132631
DOI: 10.3748/wjg.v26.i38.5745 -
Journal of the International Society of... 2022This study examined the effects of short-term betaine supplementation on muscle endurance, plasma lactate, testosterone and cortisol levels, and the testosterone to...
OBJECTIVE
This study examined the effects of short-term betaine supplementation on muscle endurance, plasma lactate, testosterone and cortisol levels, and the testosterone to cortisol (T/C) ratio in response to acute resistance exercise (RE).
METHOD
Using a double-blind, crossover study design, 10 handball players (age ± SD = 16 ± 1 yrs) without prior-structured RE experience performed a high-intensity RE session (leg press followed by bench press; 5 sets to volitional fatigue using 80% baseline 1 repetition maximum (1RM)), before and after 14 days of either placebo (maltodextrin) or betaine (2.5 g·d) supplementation. A 30-day washout period separated each treatment. 48 h prior to testing sessions, participants recorded their food intake and did not perform strenuous exercise. Venous blood was sampled before supplementation, and before and after each RE session.
RESULTS
After betaine supplementation, participants performed more repetitions ( < 0.001) during the leg press (Betaine: 35.8 ± 4.3; Placebo: 24.8 ± 3.6, Cohen's = 2.77) and bench press (Betaine: 36.3 ± 2.6; Placebo: 26.1 ± 3.5, Cohen's = 3.34). Betaine resulted in lower post-exercise cortisol (Betaine: 7.6 ± 1.7; Placebo: 13 ± 3.4 µg.dL, = 0.003, generalized eta squared ( ) = 0.49) and lactate (Betaine: 5.2 ± 0.3; Placebo: 6 ± 0.3 mmol.L, < 0.001, = 0.96) and higher total testosterone (Betaine: 15.2 ± 2.2; Placebo: 8.7 ± 1.7 ng.mL, < 0.001, = 0.87) and T/C ratio (Betaine: 0.21 ± 0.05; Placebo: 0.07 ± 0.02, < 0.001, = 0.82).
CONCLUSIONS
Two weeks of betaine supplementation improved upper- and lower-body muscle endurance and influenced indices of endocrine function following an acute session of high-intensity RE in adolescent handball players.
Topics: Adolescent; Athletes; Betaine; Cross-Over Studies; Dietary Supplements; Double-Blind Method; Humans; Hydrocortisone; Lactic Acid; Muscle Strength; Muscle, Skeletal; Resistance Training; Testosterone
PubMed: 35599921
DOI: 10.1080/15502783.2022.2041988 -
Asia Pacific Journal of Clinical... 2012Choline and betaine are involved in several similar health-relevant metabolic pathways, but the foods sources are different. We have assessed their intakes (individual,...
Choline and betaine are involved in several similar health-relevant metabolic pathways, but the foods sources are different. We have assessed their intakes (individual, sums and ratios) from a dominantly Chinese food cultural point of view. A representative free-living Taiwanese population aged 13-64 years was drawn from the Nutrition and Health Survey in Taiwan (NAHSIT) 1993-1996. Food intake was derived from interviews as 24-hour recalls. The USDA database, with adaptations for Taiwan, provided choline and betaine food compositions. Major food contributors of these nutrients were identified and compared with data from the US Framingham offspring study. Mean and variance reduced median nutrient intakes were calculated. Top ten major food contributors of choline in Taiwan were eggs, pork, chicken, fish, soybean and its products, dark leafy vegetables, dairy, fruit, wheat products and light leafy vegetables in sequence. For betaine, the top ten were dark leafy vegetables, wheat products, fish, pork, bread, chicken, cake/cookies, grain-based alcoholic beverages, rice and its products and sauces. The main contributors of choline in Taiwan and the USA were, respectively, eggs and red meat; and for betaine, greens were similarly best contributor. The rankings of the main food contributors of choline and betaine differed substantially between Taiwan and the USA. The total daily intakes (mean±SE, mg) in Taiwan for choline were 372±19 (median=348) in men and 265±9 (median 261) for women; for betaine, values were 101±3 (median 93) in men and 78±8 (median 76) for women. These allow for health outcome considerations.
Topics: Adolescent; Adult; Age Factors; Betaine; Choline; Cross-Sectional Studies; Databases, Factual; Diet; Eggs; Food Analysis; Humans; Male; Meat; Middle Aged; Nutrition Surveys; Plant Leaves; Sex Characteristics; Taiwan; Vegetables; Young Adult
PubMed: 23017313
DOI: No ID Found -
Nutrients Feb 2022S-adenosylhomocysteine (SAH) is a risk factor of cardiovascular diseases and atherosclerosis. However, the causal association between SAH and atherosclerosis is still...
S-adenosylhomocysteine (SAH) is a risk factor of cardiovascular diseases and atherosclerosis. However, the causal association between SAH and atherosclerosis is still uncertain. In the present study, heterozygous SAH hydrolase (SAHH) knockout mice were bred with apolipoprotein E-deficient mice to produce ApoE/SAHH mice. At 8 weeks of age, these mice were fed on AIN-93G diets added with or without betaine (4 g betaine/100 g diet) for 8 weeks. Compared with ApoE/SAHH mice, SAHH deficiency caused an accumulation of plasma SAH concentration and a decrease in S-adenosylmethionine (SAM)/SAH ratio as well as plasma homocysteine levels. Betaine supplementation lowered SAH levels and increased SAM/SAH ratio and homocysteine levels in ApoE/SAHH mice. Furthermore, SAHH deficiency promoted the development of atherosclerosis, which was reduced by betaine supplementation. The atheroprotective effects of betaine on SAHH-deficiency-promoted atherosclerosis were associated with inhibition of NFκB inflammation signaling pathway and inhibition of proliferation and migration of smooth muscle cells. In conclusion, our results suggest that betaine supplementation lowered plasma SAH levels and protected against SAHH-deficiency-promoted atherosclerosis through repressing inflammation and proliferation and migration of smooth muscle cells.
Topics: Adenosylhomocysteinase; Animals; Apolipoproteins E; Atherosclerosis; Betaine; Dietary Supplements; Mice; Mice, Knockout
PubMed: 35277077
DOI: 10.3390/nu14030718 -
Redox Biology Feb 2024Dementia, with homocysteine (Hcy) as an important risk factor, is a severe public health problem in the aging society. Betaine serves as a methyl donor and plays an...
Dementia, with homocysteine (Hcy) as an important risk factor, is a severe public health problem in the aging society. Betaine serves as a methyl donor and plays an important role in reducing Hcy. However, the effects and mechanisms of betaine on Hcy-induced cognitive impairment remain unclear. Firstly, SD rats were injected with Hcy (400 μg/kg) through vena caudalis, and betaine (2.5 % w/v) was supplemented via drinking water for 14 days. Betaine supplementation could attenuate Hcy-induced cognitive impairment in the Y maze and novel object recognition tests by repairing brain injury. Meanwhile, microglial activation was observed to be inhibited by betaine supplementation using immunofluorescence and sholl analysis. Secondly, HMC3 cells were treated with betaine, which was found to decrease the ROS level, ameliorate cell membrane rupture, reduce the release of LDH, IL-18 and IL-1β, and attenuate the damage of microglia to neurons. Mechanistically, betaine alleviates cognitive impairment by inhibiting microglial pyroptosis via reducing the expressions of NLRP3, ASC, pro-caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-18 and IL-1β. Betaine treatment can increase SAM/SAH ratio, confirming its enhancement on methylation capacity. Furthermore, betaine treatment was found to enhance N-methyladenosine (mA) modification of NLRP3 mRNA, and reduced the NLRP3 mRNA stability through increasing the expression of the mA reader YTH N-methyladenosine RNA binding protein 2 (YTHDF2). Finally, silencing YTHDF2 could reverse the inhibitory effect of betaine on pyroptosis. Our data demonstrated that betaine attenuated Hcy-induced cognitive impairment by suppressing microglia pyroptosis via inhibiting the NLRP3/caspase-1/GSDMD pathway in an mA-YTHDF2-dependent manner.
Topics: Animals; Rats; Rats, Sprague-Dawley; Betaine; Pyroptosis; Interleukin-18; Microglia; NLR Family, Pyrin Domain-Containing 3 Protein; Caspase 1; Cognitive Dysfunction; Homocysteine; Interleukin-1beta; Inflammasomes
PubMed: 38184996
DOI: 10.1016/j.redox.2024.103026 -
Experimental and Molecular Pathology Feb 2012In recent years, methyl one-carbon metabolism has received a great deal of attention because the disruption of methyl balance in a variety of genetically modified mice...
In recent years, methyl one-carbon metabolism has received a great deal of attention because the disruption of methyl balance in a variety of genetically modified mice is associated with the development of various forms of liver injury, namely fatty liver disease and hepatocellular carcinoma (HCC). In addition, patients with liver disease often have an abnormal expression of key genes involved in methionine metabolism as well as elevated serum levels of methionine and homocysteine (Hcy). S-adenosylmethionine (SAMe) has rapidly moved from being a methyl donor to a key metabolite that regulates hepatocyte proliferation, necrosis and differentiation. Biosynthesis of SAMe occurs in all mammalian cells as the first step in methionine catabolism in a reaction catalyzed by methionine adenosyltransferase (MAT). Decreased hepatic SAMe biosynthesis is a consequence of numerous forms of chronic liver injury. In an animal model of chronic liver SAMe deficiency, the liver is predisposed to further injury and develops spontaneous steatohepatitis and HCC. SAMe treatment in experimental animal models of liver injury shows hepatoprotective properties. Meta-analyses also showed that it is effective in the treatment of patients with cholestatic liver diseases. We studied the survival of liver cells treated with SAMe and betaine using Hepa 1-6 and E47/C34 cell lines. We showed that exogenous SAMe decreased the number of Hepa 1-6 and E47/C34 cells, and increased the number of dead cells in vitro. Betaine had no significant effect on the number of surviving cells and the number of dead cells. The combination of both methyl donors significantly increased the survival of liver cells and reduced necrosis, compared to SAMe alone. This study showed the inhibition of the proliferation and increased necrosis in response to SAMe on liver cancer cell lines Hepa 1-6 and C34.
Topics: Animals; Betaine; Cell Death; Cell Line, Tumor; Cell Proliferation; Cell Survival; Hepatocytes; Humans; Mice; S-Adenosylmethionine; Time Factors
PubMed: 22032937
DOI: 10.1016/j.yexmp.2011.10.001 -
The Journal of Nutrition Aug 2015Dietary intakes of betaine and choline may reduce the risk of cardiovascular disease; however, epidemiologic evidence is limited. Seafood is a rich source of betaine and...
BACKGROUND
Dietary intakes of betaine and choline may reduce the risk of cardiovascular disease; however, epidemiologic evidence is limited. Seafood is a rich source of betaine and is a popular traditional food in Japan.
OBJECTIVE
We examined the associations of betaine and choline intakes with cardiovascular disease mortality in a population-based cohort study in Japan.
METHODS
Study subjects were 13,355 male and 15,724 female residents of Takayama City, Japan, who were aged ≥35 y and enrolled in 1992. Their diets were assessed by a validated food frequency questionnaire. Deaths from coronary heart disease and stroke were identified from death certificates over 16 y. Multivariable-adjusted HRs were computed by using Cox regression models.
RESULTS
During follow-up, we documented 308 deaths from coronary heart disease and 676 deaths from stroke (393 from ischemic and 153 from hemorrhagic strokes). Compared with the lowest quartile, the second, third, and highest quartiles of betaine intake were significantly associated with a decreased risk of mortality from coronary heart disease in men after controlling for covariates. The HRs were 0.58 (95% CI: 0.36, 0.93), 0.62 (95% CI: 0.39, 0.998), and 0.60 (95% CI: 0.37, 0.97), respectively. The trend was not statistically significant (P = 0.08). There was no significant association between betaine intake and the risk of mortality from ischemic stroke. In women, betaine intake was unrelated risk of mortality from coronary heart disease and stroke (P = 0.32 and 0.73, respectively, for interaction by sex). There was no significant association between choline intake and cardiovascular disease mortality risk in men or women.
CONCLUSION
Overall, we found no clear evidence of significant associations between choline and betaine intakes and cardiovascular disease mortality risk in Japanese men and women.
Topics: Adult; Animals; Asian People; Betaine; Choline; Coronary Disease; Diet; Female; Humans; Male; Middle Aged; Proportional Hazards Models; Risk Factors; Stroke
PubMed: 26063062
DOI: 10.3945/jn.114.209296 -
Current Vascular Pharmacology 2022Trimethylamine N-oxide (TMAO) is a gut microbiota metabolite derived from trimethylamine- containing nutrient precursors such as choline, L-carnitine, and betaine, which...
Trimethylamine N-oxide (TMAO) is a gut microbiota metabolite derived from trimethylamine- containing nutrient precursors such as choline, L-carnitine, and betaine, which are rich in many vegetables, fruits, nuts, dairy products, and meats. An increasing number of clinical studies have demonstrated a strong relationship between elevated plasma TMAO levels and adverse cardiovascular events. It is commonly agreed that TMAO acts as an independent risk factor and a prognostic index for patients with cardiovascular disease. Although most animal (mainly rodent) data support the clinical findings, the mechanisms by which TMAO modulates the cardiovascular system are still not well understood. In this context, we provide an overview of the potential mechanisms underlying TMAO-induced cardiovascular diseases at the cellular and molecular levels, with a focus on atherosclerosis. We also address the direct effects of TMAO on cardiomyocytes (a new and under-researched area) and finally propose TMAO as a potential biomarker and/or therapeutic target for diagnosis and treatment of patients with cardiovascular disease.
Topics: Animals; Atherosclerosis; Betaine; Cardiomyopathies; Cardiovascular Diseases; Humans; Methylamines
PubMed: 34387163
DOI: 10.2174/1570161119666210812152802 -
Journal of the Science of Food and... Mar 2020Climatic and dietary shifts predispose ruminal microbes to hyperthermal and hyperosmotic stress, leading to poor fermentation and subsequently adverse effects on...
BACKGROUND
Climatic and dietary shifts predispose ruminal microbes to hyperthermal and hyperosmotic stress, leading to poor fermentation and subsequently adverse effects on ruminant productivity. Betaine may function as substrate, osmolyte, antioxidant, and methyl donor for microbes. However, its effect depends on the extent of microbial catabolism. This study revealed the ruminal disappearance kinetics of betaine and its dose effect on ruminal fermentation during thermal and osmotic stress using a rumen simulation technique.
RESULTS
Three different betaine doses were used: 0, 50, and 286 mg L ; each was assigned to two incubation temperatures (39.5 and 42 °C) and two osmotic conditions (295 and 420 mOsmol kg ). Betaine disappeared rapidly within the first 6 h of incubation; however, the rate was lower during hyperosmotic stress (P < 0.05), the stress condition that also suppressed the overall fermentation and degradation of organic nutrients and decreased the bacterial diversity (P < 0.001). During hyperosmotic stress, betaine shifted the fermentation pathway to more propionate (P < 0.05). Betaine counteracted the negative effect of hyperthermal stress on total short-chain fatty acid concentration (P < 0.05) without affecting the composition. Both stress conditions shifted the bacterial composition, but the effect of betaine was minimal.
CONCLUSION
Despite its rapid ruminal disappearance, betaine modulated microbial fermentation in different ways depending on stress conditions, indicating the plasticity of the betaine effect in response to various kinds of physicochemical stress. Although betaine did not affect the abundance of ruminal microbiota, the enhanced fermentation suggests an improved microbial metabolic activity under stress conditions. © 2020 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Topics: Animal Feed; Animals; Bacteria; Betaine; Fatty Acids, Volatile; Fermentation; Gastrointestinal Microbiome; Kinetics; Osmolar Concentration; Osmotic Pressure; RNA, Ribosomal, 16S; Rumen; Temperature
PubMed: 31917480
DOI: 10.1002/jsfa.10255