Betaine attenuated the toxicity and oxidative stress from excess selenium intake

The present study was undertaken on male rats to elucidate the selenosis induced by sodium selenite and the role played by betaine in alleviating selenium toxicity. Rats were treated with sodium selenite (6 mg/kg body weight/day) with or without betaine (240 mg/kg body weight/day). Selenotoxicosis was evident from the elevated plasma levels of total bilirubin, transaminases, and alkaline phosphatase activities. Moreover, the total protein levels decreased, and this decrease associated with a decreased albumin level, whereas the globulin level increased in selenium-intoxicated rats. The development of selenosis corresponded well with the induction of oxidative stress evident from decrease of total thiol level and glutathione content. Furthermore, activities of glutathione reductase, glucose-6-phosphate dehydrogenase, catalase, and paraoxonase-1 were decreased in selenium-treated rats. In contrast, superoxide dismutase and glutathione peroxidase activities were increased by excess selenium administration compared with control animals. As well, malondialdehyde and protein carbonyl were elevated in rats treated with selenium. Supplementation of betaine simultaneously with selenium caused less marked alteration in the investigated parameters. Betaine attenuated the selenotoxicosis by restoring thiol levels that preserve enzymatic antioxidants activity and attenuate the oxidation of lipids and proteins.

Harisa, G.I., Oxidative Stress and Paraoxonase Activity in Experimental Selenosis: Effects of Betaine Administration. Biol Trace Elem Res, 2013

Co-administration of methyl donors (including betaine) with GAA increases serum creatine without development of hyperhomocysteinaemia

Guanidinoacetic acid (GAA) is the natural biosynthetic precursor of creatine, in a metabolic reaction that requires only a methyl group transfer. The use of GAA as a food additive for restoring creatine load in human tissues is rather unexplored and data on efficacy and safety are limited. In particular, an increase in serum homocysteine after GAA administration can be regarded as critical and should be prevented. The present study evaluated the effects of orally administered GAA with and without methyl group donors on serum and urine creatine concentrations, and the occurrence of adverse events during an intervention in healthy human subjects. A total of twenty male and female volunteers were randomised in a double-blind design to receive either GAA (2.4 g/d) or GAA with methyl donors (2.4 g/d of GAA and 1.6 g/d of betaine HCl, 5 mug/d of vitamin B12, 10 mg/d of vitamin B6 and 600 mug/d of folic acid) by oral administration for 8 weeks. Serum and urine creatine increased significantly from before to after administration in both groups (P< 0.001). The proportion of participants who reported minor adverse events was 33.3 % in the GAA group, and 10.0 % in the GAA with methyl donors group (P= 0.30). Hyperhomocysteinaemia was found in 55.6 % of participants supplemented with GAA, while no participant experienced hyperhomocysteinaemia in the group supplemented with GAA and methyl donors (P= 0.01). In summary, both interventions strongly influenced creatine metabolism, resulting in a significant increase in fasting serum creatine. The concomitant supplementation of methyl donors along with GAA largely precluded the elevation of serum homocysteine caused by GAA administration alone.

Ostojic, S.M., et al., Co-administration of methyl donors along with guanidinoacetic acid reduces the incidence of hyperhomocysteinaemia compared with guanidinoacetic acid administration alone. Br J Nutr, 2013: p. 1-6.

Betaine intake may be protective against lung cancer for certain genetic phenotypes

PURPOSE: Folate metabolism, with its importance to DNA repair, provides a promising region for genetic investigation of lung cancer risk. This project investigates genes (MTHFR, MTR, MTRR, CBS, SHMT1, TYMS), folate metabolism related nutrients (B vitamins, methionine, choline, and betaine) and their gene-nutrient interactions. METHODS: We analyzed 115 tag single nucleotide polymorphisms (SNPs) and 15 nutrients from 1239 and 1692 non-Hispanic white, histologically-confirmed lung cancer cases and controls, respectively, using stochastic search variable selection (a Bayesian model averaging approach). Analyses were stratified by current, former, and never smoking status. RESULTS: Rs6893114 in MTRR (odds ratio [OR] = 2.10; 95% credible interval [CI]: 1.20-3.48) and alcohol (drinkers vs. non-drinkers, OR = 0.48; 95% CI: 0.26-0.84) were associated with lung cancer risk in current smokers. Rs13170530 in MTRR (OR = 1.70; 95% CI: 1.10-2.87) and two SNP*nutrient interactions [betaine*rs2658161 (OR = 0.42; 95% CI: 0.19-0.88) and betaine*rs16948305 (OR = 0.54; 95% CI: 0.30-0.91)] were associated with lung cancer risk in former smokers. SNPs in MTRR (rs13162612; OR = 0.25; 95% CI: 0.11-0.58; rs10512948; OR = 0.61; 95% CI: 0.41-0.90; rs2924471; OR = 3.31; 95% CI: 1.66-6.59), and MTHFR (rs9651118; OR = 0.63; 95% CI: 0.43-0.95) and three SNP*nutrient interactions (choline*rs10475407; OR = 1.62; 95% CI: 1.11-2.42; choline*rs11134290; OR = 0.51; 95% CI: 0.27-0.92; and riboflavin*rs8767412; OR = 0.40; 95% CI: 0.15-0.95) were associated with lung cancer risk in never smokers. CONCLUSIONS: This study identified possible nutrient and genetic factors related to folate metabolism associated with lung cancer risk, which could potentially lead to nutritional interventions tailored by smoking status to reduce lung cancer risk.

Swartz, M.D., et al., Investigating multiple candidate genes and nutrients in the folate metabolism pathway to detect genetic and nutritional risk factors for lung cancer. PLoS One, 2013. 8(1): p. e53475.

Maternal Diet Supplementation with Methyl Donors and Increased Parity Affect the Incidence of Craniofacial Defects in the Offspring of Twisted gastrulation Mutant Mice

Diets rich in methyl-donating compounds, including folate, can provide protection against neural tube defects, but their role in preventing craniofacial defects is less clear. Mice deficient in Twisted gastrulation (TWSG1), an extracellular modulator of bone morphogenetic protein signaling, manifest both midline facial defects and jaw defects, allowing study of the effects of methyl donors on various craniofacial defects in an experimentally tractable animal model. The goal of this study was to examine the effects of maternal dietary supplementation with methyl donors on the incidence and type of craniofacial defects among Twsg1(-/-) offspring. Nulliparous and primiparous female mice were fed an NIH31 standard diet (control) or a methyl donor supplemented (MDS) diet (folate, vitamin B-12, betaine, and choline). Observed defects in the pups were divided into those derived mostly from the first branchial arch (BA1) (micrognathia, agnathia, cleft palate) and midline facial defects in the holoprosencephaly spectrum (cyclopia, proboscis, and anterior truncation). In the first pregnancy, offspring of mice fed the MDS diet had lower incidence of BA1-derived defects (12.8% in MDS vs. 32.5% in control; P = 0.02) but similar incidence of midline facial defects (6.4% in MDS vs. 5.2% in control; P = 1.0). Increased maternal parity was independently associated with increased incidence of craniofacial defects after adjusting for diet (from 37.7 to 59.5% in control, P = 0.04 and from 19.1 to 45.3% in MDS, P = 0.045). In conclusion, methyl donor supplementation shows protective effects against jaw defects, but not midline facial defects, and increased parity can be a risk factor for some craniofacial defects.

Billington, C.J., Jr., et al., Maternal Diet Supplementation with Methyl Donors and Increased Parity Affect the Incidence of Craniofacial Defects in the Offspring of Twisted gastrulation Mutant Mice. J Nutr, 2013

Effects of dietary supplementation with betaine on a nonalcoholic steatohepatitis (NASH) mouse model.

The effects of betaine supplementation on non-alcoholic steatohepatitis (NASH) model mice were examined by measuring the accumulation of fat in the livers of NASH model mice compared to a control. Betaine from sugar beets was provided to the model mice as a dietary supplement. After 3 wk of dietary supplementation. there were no significant differences in body weight or liver weight between the groups. However, the liver to body weight ratio in the high-fat diet with betaine (HM) group was significantly higher than that in the high-fat diet (HF) group. There were no differences in scrum triglyceride (TG) concentrations. AST and ALT activities, or hepatic glutathione concentrations between the groups. Hepatic TG level in the Ha group was significantly lower than that in the HF group. Hepatic cells obtained from the HF group showed increased occurrence of explosive puff and necrosis as compared with those in the HFB group. Betaine supplementation had an inhibitory effect on fat accumulation in the liver: the Oil red-positive area in the Ha group (0.82 +/- 0.85%) was significantly smaller than that in the HF group (9.06 +/- 2.24%). These results indicate the potential of betaine to serve as an agent for amelioration of hepatic steatosis in NASH model mice.

Kawakami, S., et al., Effects of dietary supplementation with betaine on a nonalcoholic steatohepatitis (NASH) mouse model. Journal of Nutritional Science and Vitaminology, 2012. 58(5): p. 371-5

Higher plasma betaine in children is associated with better language score

Choline is an essential nutrient that is found in many food sources and plays a critical role in the development of the central nervous system. Animal studies have shown that choline status pre- and postnatally can have long-lasting effects on attention and memory; however, effects in human subjects have not been well studied. The aim of the present study was to examine the association between plasma concentrations of free choline and its related metabolites in children and their neurodevelopment in the Seychelles Child Development Nutrition Study, an ongoing longitudinal study assessing the development of children born to mothers with high fish consumption during pregnancy. Plasma concentrations of free choline, betaine, dimethylglycine (DMG), methionine and homocysteine and specific measures of neurodevelopment were measured in 210 children aged 5 years. The children's plasma free choline concentration (9.17 (sd 2.09) mumol/l) was moderately, but significantly, correlated with betaine (r 0.24; P= 0.0006), DMG (r 0.15; P= 0.03), methionine (r 0.24; P= 0.0005) and homocysteine (r 0.19; P= 0.006) concentrations. Adjusted multiple linear regression revealed that betaine concentrations were positively associated with Preschool Language Scale - total language scores (beta = 0.066; P= 0.04), but no other associations were evident. We found no indication that free choline concentration or its metabolites, within the normal physiological range, are associated with neurodevelopmental outcomes in children at 5 years of age. As there is considerable animal evidence suggesting that choline status during development is associated with cognitive outcome, the issue deserves further study in other cohorts.

Strain, J.J., et al., Choline status and neurodevelopmental outcomes at 5 years of age in the Seychelles Child Development Nutrition Study. Br J Nutr, 2013: p. 1-7.

Betaine: a promising antioxidant agent for enhancement of broiler meat quality

1. Antioxidant and methyl donor effects of betaine in experimental animal models have recently been demonstrated. The present study was therefore designed to examine the antioxidant effects of betaine on the antioxidant status and meat quality of breast muscles in broilers.
2. Cobb broilers were randomly divided into Control, Methionine low, Methionine low plus betaine, and Betaine groups.
3. The activity of the main antioxidant enzyme (glutathione peroxidase) in the Betaine and the Methionine low plus betaine groups significantly increased compared to the Methionine low and Control groups. Catalase and superoxide dismutase activities were significantly higher in the Betaine group compared to the Methionine low group, and lipid peroxidation was significantly higher in the Control and the Methionine low groups.
4. The present study indicates that adding betaine (1 g/kg) to a diet deficient in methionine can significantly improve antioxidant defences and meat quality, decreasing lipid peroxidation in the breast muscles of broiler chickens.
Alirezaei, M., et al., Betaine: a promising antioxidant agent for enhancement of broiler meat quality. British Poultry Science, 2012. 53(5): p. 699-707