There is a need for a nontoxic antioxidant agent to be identified which will prevent alcoholic liver disease (ALD) in alcoholic patients. We tested 4 candidate agents: quercetin, EGCG, catechin and betaine, all of which occur naturally in food. HepG2 cells overexpressing CYP2E1 were subjected to arachidonic acid, iron and 100 mM ethanol with or without the antioxidant agent. All the agents prevented oxidative stress and MDA/4HNE formation induced by ethanol, except for EGCG. Catechin prevented CYP2E1 induction by ethanol. All the agents tended to down-regulate the ethanol-induced increased expression of glutathionine peroxidase 4 (GPX4). All the agents, except catechin, tended to reduce the expression of SOD2 induced by ethanol. Heat shock protein 70 was up-regulated by ethanol alone and betaine tended to prevent this. All 4 agents down-regulated the expression of Gadd45b in the presence of ethanol, which could explain the mechanism of DNA demethylation associated with the up-regulation of the gene expression observed in experimental ALD.
In conclusion, the in vitro model of oxidative stress induced by ethanol provided evidence that all 4 agents tested prevented some aspect of liver cell injury caused by ethanol.
Oliva, J., et al., Protective effect of quercetin, EGCG, catechin and betaine against oxidative stress induced by ethanol in vitro. Exp Mol Pathol, 2011. 90(3): p. 295-9.
Wednesday, March 9, 2011
Wednesday, February 23, 2011
Plasma betaine is lower in children with cystic fibrosis
Choline is an important constituent of acetylcholine. Choline is needed for acetylcholine in the nonneuronal acetylcholine system that includes epithelial cells of the lung and intestine, endothelial cells, and immune cells. Plasma free choline concentrations are low in children with cystic fibrosis (CF), but the implications for acetylcholine are unknown.
We determined the relation between plasma free choline and related metabolites and leukocyte acetylcholine in children with CF and in a control group of healthy children without CF. This was a cross-sectional study in 34 children with CF who were pancreatic insufficient and taking pancreatic enzyme-replacement therapy and in 16 healthy children. Plasma free choline, betaine, dimethylglycine, methionine, homocysteine, and leukocyte acetylcholine concentrations were quantified by using isotope-dilution HPLC–tandem mass spectrometry. Mean (±SE) plasma free choline was 9.30 ± 0.37 and 6.54 ± 0.38 μmol/L (P < 0.05) and leukocyte acetylcholine was 1.21 ± 0.016 and 0.077 ± 0.011 pmol leukocyte acetylcholine/106 cells (P < 0.05) in control children and children with CF, respectively. Leukocyte acetylcholine was positively correlated with plasma free choline concentration in children with CF (r = 0.412, P < 0.05) but not in control children. Plasma betaine, dimethylglycine, and methionine concentrations were also lower in children with CF than in control children (P < 0.05).
A low free choline and methyl status in children with CF is associated with reduced acetylcholine in leukocytes. Whether these changes are explained by a mutation in the CF transmembrane conductance regulator or disturbances in choline metabolism and the implications for immune cell dysfunction in CF are unknown.
Innis et al (2011). "Plasma choline depletion is associated with decreased peripheral blood leukocyte acetylcholine in children with cystic fibrosis." The American Journal of Clinical Nutrition 93(3): 564-568
We determined the relation between plasma free choline and related metabolites and leukocyte acetylcholine in children with CF and in a control group of healthy children without CF. This was a cross-sectional study in 34 children with CF who were pancreatic insufficient and taking pancreatic enzyme-replacement therapy and in 16 healthy children. Plasma free choline, betaine, dimethylglycine, methionine, homocysteine, and leukocyte acetylcholine concentrations were quantified by using isotope-dilution HPLC–tandem mass spectrometry. Mean (±SE) plasma free choline was 9.30 ± 0.37 and 6.54 ± 0.38 μmol/L (P < 0.05) and leukocyte acetylcholine was 1.21 ± 0.016 and 0.077 ± 0.011 pmol leukocyte acetylcholine/106 cells (P < 0.05) in control children and children with CF, respectively. Leukocyte acetylcholine was positively correlated with plasma free choline concentration in children with CF (r = 0.412, P < 0.05) but not in control children. Plasma betaine, dimethylglycine, and methionine concentrations were also lower in children with CF than in control children (P < 0.05).
A low free choline and methyl status in children with CF is associated with reduced acetylcholine in leukocytes. Whether these changes are explained by a mutation in the CF transmembrane conductance regulator or disturbances in choline metabolism and the implications for immune cell dysfunction in CF are unknown.
Innis et al (2011). "Plasma choline depletion is associated with decreased peripheral blood leukocyte acetylcholine in children with cystic fibrosis." The American Journal of Clinical Nutrition 93(3): 564-568
Monday, January 31, 2011
A whole-grain diet increases plasma betaine, and decreases total and LDL-cholesterol compared with a refined-grain diet
Epidemiological studies have repeatedly found that whole-grain (WG) cereal foods reduce the risk of several lifestyle-related diseases, though consistent clinical outcomes and mechanisms are elusive.
To compare the effects of a WG-rich diet with a matched refined-grain (RG) diet on plasma biomarkers and bowel health parameters, seventeen healthy subjects (eleven females and six males) completed an exploratory cross-over study with a 2-week intervention diet based on either WG- or RG-based foods, separated by a washout of at least 5 weeks. Both diets were the same except for the use of WG (150 g/d) or RG foods. Subjects undertook a 4 h postprandial challenge on day 8 of each intervention diet. After 2 weeks, the WG diet tended to decrease plasma total and LDL-cholesterol (both P = 0.09), but did not change plasma HDL-cholesterol, fasting glucose, C-reactive protein or homocysteine compared with the RG diet. Plasma betaine and alkylresorcinol concentrations were elevated after 1 week of the WG diet (P = 0.01 and P < 0.0001, respectively). Clostridium leptum populations in faeces were increased after the WG diet, along with a trend for decreased faecal water pH (P = 0.096) and increased stool frequency (P < 0.0001) compared with the RG diet. A short controlled intervention trial with a variety of commercially available WG-based products tended to improve biomarkers of CVD compared with a RG diet.
Changes in faecal microbiota related to increased fibre fermentation and increased plasma betaine concentrations point to both fibre and phytochemical components of WG being important in mediating any potential health effects.
Ross et al (2011). "A whole-grain cereal-rich diet increases plasma betaine, and tends to decrease total and LDL-cholesterol compared with a refined-grain diet in healthy subjects." Br J Nutr: 1-12.
To compare the effects of a WG-rich diet with a matched refined-grain (RG) diet on plasma biomarkers and bowel health parameters, seventeen healthy subjects (eleven females and six males) completed an exploratory cross-over study with a 2-week intervention diet based on either WG- or RG-based foods, separated by a washout of at least 5 weeks. Both diets were the same except for the use of WG (150 g/d) or RG foods. Subjects undertook a 4 h postprandial challenge on day 8 of each intervention diet. After 2 weeks, the WG diet tended to decrease plasma total and LDL-cholesterol (both P = 0.09), but did not change plasma HDL-cholesterol, fasting glucose, C-reactive protein or homocysteine compared with the RG diet. Plasma betaine and alkylresorcinol concentrations were elevated after 1 week of the WG diet (P = 0.01 and P < 0.0001, respectively). Clostridium leptum populations in faeces were increased after the WG diet, along with a trend for decreased faecal water pH (P = 0.096) and increased stool frequency (P < 0.0001) compared with the RG diet. A short controlled intervention trial with a variety of commercially available WG-based products tended to improve biomarkers of CVD compared with a RG diet.
Changes in faecal microbiota related to increased fibre fermentation and increased plasma betaine concentrations point to both fibre and phytochemical components of WG being important in mediating any potential health effects.
Ross et al (2011). "A whole-grain cereal-rich diet increases plasma betaine, and tends to decrease total and LDL-cholesterol compared with a refined-grain diet in healthy subjects." Br J Nutr: 1-12.
Monday, November 8, 2010
Cytosol betaine decreases with a high fat diet
Liver and serum metabolites of obese and lean mice fed on high fat or normal diets were analyzed using ultraperformance liquid chromatography-quadrupole-time-of-flight mass spectrometry, gas chromatography-mass spectrometry, and partial least-squares-discriminant analysis (PLS-DA).
Obese and lean groups were clearly discriminated from each other on PLS-DA score plot and major metabolites contributing to the discrimination were assigned as lipid metabolites (fatty acids, phosphatidylcholines (PCs), and lysophosphatidylcholines (lysoPCs)), lipid metabolism intermediates (betaine, carnitine, and acylcarnitines), amino acids, acidic compounds, monosaccharides, and serotonin. A high-fat diet increased lipid metabolites but decreased lipid metabolism intermediates and the NAD/NADH ratio, indicating that abnormal lipid and energy metabolism induced by a high-fat diet resulted in fat accumulation via decreased beta-oxidation. In addition, this study revealed that the levels of many metabolites, including serotonin, betaine, pipecolic acid, and uric acid, were positively or negatively related to obesity-associated diseases.
On the basis of these metabolites, we proposed a metabolic pathway related to high-fat diet-induced obesity. These metabolites can be used to better understand obesity and related diseases induced by a hyperlipidic diet. Furthermore, the level changes of these metabolites can be used to assess the risk of obesity and the therapeutic effect of obesity management.
Kim et al (2010). "Metabolomic analysis of livers and serum from high-fat diet induced obese mice." J Proteome Res 10(2): 722-31.
Obese and lean groups were clearly discriminated from each other on PLS-DA score plot and major metabolites contributing to the discrimination were assigned as lipid metabolites (fatty acids, phosphatidylcholines (PCs), and lysophosphatidylcholines (lysoPCs)), lipid metabolism intermediates (betaine, carnitine, and acylcarnitines), amino acids, acidic compounds, monosaccharides, and serotonin. A high-fat diet increased lipid metabolites but decreased lipid metabolism intermediates and the NAD/NADH ratio, indicating that abnormal lipid and energy metabolism induced by a high-fat diet resulted in fat accumulation via decreased beta-oxidation. In addition, this study revealed that the levels of many metabolites, including serotonin, betaine, pipecolic acid, and uric acid, were positively or negatively related to obesity-associated diseases.
On the basis of these metabolites, we proposed a metabolic pathway related to high-fat diet-induced obesity. These metabolites can be used to better understand obesity and related diseases induced by a hyperlipidic diet. Furthermore, the level changes of these metabolites can be used to assess the risk of obesity and the therapeutic effect of obesity management.
Kim et al (2010). "Metabolomic analysis of livers and serum from high-fat diet induced obese mice." J Proteome Res 10(2): 722-31.
Monday, October 25, 2010
Betaine should be combined fibrates for hyperlipidemia
Because most of the cardiac risk remains despite successful statin therapy there has been renewed interest in fibrate therapy for persisting hyperlipidaemia. Fibrate therapy lowers triglycerides but causes the urinary loss of betaine, which is an essential metabolite that is involved in osmoregulation, in methyl group metabolism, and which also affects lipid partitioning in the body. Loss of betaine is associated with an elevation of homocysteine and may compromise the potential benefits of fibrate therapy. However, betaine deficiency could be easily and inexpensively corrected by concurrent betaine supplementation. Clinical trials of combinations of betaine and fibrate, to complement statin therapy, are needed to determine the value of these agents in reducing the residual cardiovascular disease risk
Lever et al (2010). "Fibrates plus betaine: a winning combination?" N Z Med J 123(1324): 74-8.
Lever et al (2010). "Fibrates plus betaine: a winning combination?" N Z Med J 123(1324): 74-8.
Betaine protects the brain against alcohol and aspirin
Physicians recommend aspirin for prevention of heart attacks and stroke in people above the age of 40 years. In some cases, alcohol consumption accompanies aspirin intake. In this study, the in vitro effects of different doses of ethanol (50, 100, and 200 mM) and 100 μg/mL of aspirin and the possible protective role of betaine (0.5 and 1 mM) were investigated on rat cerebral synaptosomes.
Synaptosomally enriched fractions, derived from Sprague Dawley rat brains, were incubated with ethanol and aspirin so as to measure sialic acid (SA), nitric oxide levels, and adenosine deaminase (ADA) activities, which are known to be the markers of alcohol damage. When combined with aspirin, ethanol increased SA levels compared with the control group at all doses, resulting in loss of SA residue from synaptosomal membrane. Betaine (0.5 mM) decreased SA levels with respect to the ethanol (200 mM) plus aspirin group (p < .05), thereby preventing SA loss. Moreover, betaine reversed the destructive effects of ethanol by elevating reduced nitric oxide levels. Aspirin, when combined with all doses of ethanol, increased ADA activity, which is crucial for purine metabolism. ADA activities were also elevated in betaine-administered groups.
We propose that betaine is an effective compound in protecting the rat brain synaptosomes against ethanol and aspirin together.
Sogut and Kanbak (2010). "In vitro effects of ethanol with aspirin on rat brain synaptosomes: the potential protective role of betaine." Int J Neurosci 120(12): 774-83.
Synaptosomally enriched fractions, derived from Sprague Dawley rat brains, were incubated with ethanol and aspirin so as to measure sialic acid (SA), nitric oxide levels, and adenosine deaminase (ADA) activities, which are known to be the markers of alcohol damage. When combined with aspirin, ethanol increased SA levels compared with the control group at all doses, resulting in loss of SA residue from synaptosomal membrane. Betaine (0.5 mM) decreased SA levels with respect to the ethanol (200 mM) plus aspirin group (p < .05), thereby preventing SA loss. Moreover, betaine reversed the destructive effects of ethanol by elevating reduced nitric oxide levels. Aspirin, when combined with all doses of ethanol, increased ADA activity, which is crucial for purine metabolism. ADA activities were also elevated in betaine-administered groups.
We propose that betaine is an effective compound in protecting the rat brain synaptosomes against ethanol and aspirin together.
Sogut and Kanbak (2010). "In vitro effects of ethanol with aspirin on rat brain synaptosomes: the potential protective role of betaine." Int J Neurosci 120(12): 774-83.
Friday, October 1, 2010
Betaine is an important component of whole grain health benefits
Epidemiological studies have clearly shown that whole-grain cereals can protect against obesity, diabetes, CVD and cancers. The specific effects of food structure (increased satiety, reduced transit time and glycaemic response), fibre (improved faecal bulking and satiety, viscosity and SCFA production, and/or reduced glycaemic response) and Mg (better glycaemic homeostasis through increased insulin secretion), together with the antioxidant and anti-carcinogenic properties of numerous bioactive compounds, especially those in the bran and germ (minerals, trace elements, vitamins, carotenoids, polyphenols and alkylresorcinols), are today well-recognised mechanisms in this protection.
Recent findings, the exhaustive listing of bioactive compounds found in whole-grain wheat, their content in whole-grain, bran and germ fractions and their estimated bioavailability, have led to new hypotheses. The involvement of polyphenols in cell signalling and gene regulation, and of sulfur compounds, lignin and phytic acid should be considered in antioxidant protection. Whole-grain wheat is also a rich source of methyl donors and lipotropes (methionine, betaine, choline, inositol and folates) that may be involved in cardiovascular and/or hepatic protection, lipid metabolism and DNA methylation. Potential protective effects of bound phenolic acids within the colon, of the B-complex vitamins on the nervous system and mental health, of oligosaccharides as prebiotics, of compounds associated with skeleton health, and of other compounds such as α-linolenic acid, policosanol, melatonin, phytosterols and para-aminobenzoic acid also deserve to be studied in more depth. Finally, benefits of nutrigenomics to study complex physiological effects of the ‘whole-grain package’, and the most promising ways for improving the nutritional quality of cereal products are discussed.
Fardet A. New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre? Nutrition Research Reviews. 2010;23(01):65-134.
Recent findings, the exhaustive listing of bioactive compounds found in whole-grain wheat, their content in whole-grain, bran and germ fractions and their estimated bioavailability, have led to new hypotheses. The involvement of polyphenols in cell signalling and gene regulation, and of sulfur compounds, lignin and phytic acid should be considered in antioxidant protection. Whole-grain wheat is also a rich source of methyl donors and lipotropes (methionine, betaine, choline, inositol and folates) that may be involved in cardiovascular and/or hepatic protection, lipid metabolism and DNA methylation. Potential protective effects of bound phenolic acids within the colon, of the B-complex vitamins on the nervous system and mental health, of oligosaccharides as prebiotics, of compounds associated with skeleton health, and of other compounds such as α-linolenic acid, policosanol, melatonin, phytosterols and para-aminobenzoic acid also deserve to be studied in more depth. Finally, benefits of nutrigenomics to study complex physiological effects of the ‘whole-grain package’, and the most promising ways for improving the nutritional quality of cereal products are discussed.
Fardet A. New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre? Nutrition Research Reviews. 2010;23(01):65-134.
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