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

Nutrients related to one-carbon metabolism and risk of renal cell cancer

Purpose - Folate, vitamins B6 and B12, methionine, choline, and betaine are nutrients related to one-carbon metabolism and have been hypothesized to decrease cancer risk. Few studies have evaluated dietary intakes of these nutrients in relation to renal cell cancer (RCC).

Methods - We conducted prospective follow-up studies of women in the Nurses’ Health Study and men in the Health Professionals Follow-up Study. Diet was assessed repeatedly using a validated semi-quantitative food-frequency questionnaire in both studies.

Results - During follow-up of 24 years among 77,208 women (918,891 person-years) and 22 years among 47,886 men (1,731,752 person-years), we accrued 436 cases of RCC (225 women and 211 men). Intakes of folate, vitamins B6 and B12, methionine, and betaine were not found to be related to RCC risk. Higher intake of free choline, but not other forms of choline, was associated with reduced RCC risk. The results were similar in men and women.

Conclusions - We found little evidence that higher intakes of nutrients related to one-carbon metabolism lower RCC risk. One-carbon metabolism may have little influence on renal carcinogenesis.

Cho, E., E. Giovannucci, and H.-K. Joh, Nutrients related to one-carbon metabolism and risk of renal cell cancer. Cancer Causes & Control 2012: p. 1-10

Betaine stabilizes cell volume and protects against apoptosis in human corneal epithelial cells under hyperosmotic stress

Elevated tear osmolarity is one of the key pathological factors in dry eye leading to ocular discomfort associated with damage to the ocular surface and inflammation. The aim of this study was to determine the capacity of the organic osmolyte, betaine, to act as an osmoprotectant against hypertonic stress-induced human corneal epithelial cell shrinkage and apoptosis using in vitro cell culture models. Human corneal limbal epithelial (HCLE) cells exposed to culture medium for 16 h at 300 mOsm (isotonic) or 500 mOsm (hyperosmotic) in the presence or absence of betaine (5 or 10 mM) were evaluated for cell volume changes; cell viability; and apoptosis. Betaine (10 mM) ameliorated hyperosmotically induced reduction of cell volume (from 27% reduction to 11%) and resulted in increased mitochondrial activity (by 17%) and an increase in viable cell numbers (by 12%) compared to controls (exposure to hyperosmotic medium without betaine). Hyperosmotically shocked HCLE cells in the presence of betaine (10 mM) halved the number of damaged cells (apoptotic/necrotic) compared to cells in the absence of betaine. The presence of betaine (at 5 or 10 mM) significantly reduced the activity of caspase-8, -9 and -3/7 and release of TNF-α was also reduced by 34% or 55% after exposure of HCLE to 500 mOsm in the presence of 5 or 10 mM betaine, respectively. Using polyclonal antibody against Betaine/GABA transporter 1 (BGT-1), we detected the presence of BGT-1 in HCLE. We demonstrated that the transport of betaine was facilitated by increased osmolarity. In conclusion, betaine stabilized corneal epithelial cell volume under hyperosmotic stress and limited hyperosmotic stress-induced HCLE apoptosis.

Garrett, Q., et al., Betaine stabilizes cell volume and protects against apoptosis in human corneal epithelial cells under hyperosmotic stress. Experimental Eye Research, 2013

The nutritional burden of methylation reactions

Purpose of review: Methyl group metabolism is a metabolically demanding process that has significant nutritional implications. Methionine is required not only for protein synthesis but also as the primary source of methyl groups. However, demethylated methionine can be remethylated by methyl groups from methylneogenesis (via folate) and betaine (synthesized from choline). This review discusses the impact of methylation precursors and products on the methionine requirement. Recent findings: Recent evidence has clearly demonstrated that transmethylation reactions can consume a significant proportion of the flux of methionine. In particular, synthesis of creatine and phosphatidylcholine consume most methyl groups and their dietary provision could spare methionine. Importantly, methionine can become limiting for protein and phosphatidylcholine synthesis when creatine synthesis is upregulated. Other research has shown that betaine and choline seem to be more effective than folate at reducing hyperhomocysteinemia and impacting cardiovascular outcomes suggesting they may be limiting. Summary: It appears that methyl groups can become limiting when dietary supply is inadequate or if transmethylation reactions are upregulated. These situations can impact methionine availability for protein synthesis, which can reduce growth. The methionine requirement can likely be spared by methyl donor and methylated product supplementation.

Bertolo, R.F. and L.E. McBreairty, The nutritional burden of methylation reactions. Current Opinion in Clinical Nutrition & Metabolic Care, 2013. 16(1): p. 102-8.

Betaine attenuates Alzheimer-like pathological changes and memory deficits induced by homocysteine

Hyperhomocysteinemia (Hhcy) may induce memory deficits with β-amyloid (Aβ) accumulation and tau hyperphosphorylation. Simultaneous supplement of folate and vitamin B12 partially restored the plasma homocysteine level and attenuated tau hyperphosphorylation, Aβ accumulation and memory impairments induced by Hhcy. However, folate and vitamin B12 treatment have no effects on Hhcy which has the methylenetetrahydrofolate reductase genotype mutation. In the present study, we investigated the effects of simultaneous supplement of betaine on Alzheimer-like pathological changes and memory deficits in hyperhomocysteinemic rats after a 2-week induction by vena caudalis injection of homocysteine (Hcy). We found that supplementation of betaine could ameliorate the Hcy-induced memory deficits, enhance LTP and increase dendritic branches numbers and the density of the dendritic spines, with upregulation of NR1, NR2A, synaptotagmin, synaptophysin and phosphorylated synapsin I protein levels. Supplementation of betaine also attenuated the Hcy-induced tau hyperphosphorylation at multiple AD-related sites through activation PP2A with decreased inhibitory demethylated PP2A(C) at Leu309 and phosphorylated PP2A(C) at Tyr307. In addition, supplementation of betaine also decreased Aβ production with decreased presenilin-1 protein levels. Our data suggest that betaine could be a promising candidate for arresting Hcy-induced AD-like pathological changes and memory deficits.

Chai, G.-S., et al., Betaine attenuates Alzheimer-like pathological changes and memory deficits induced by homocysteine. Journal of Neurochemistry, 2012 (10.1111/jnc.12094).

Choline and betaine intake is inversely associated with breast cancer risk: A two-stage case-control study in China

Few epidemiological studies have evaluated the association of choline and betaine intake with breast cancer risk and the results remain inconsistent. This study aimed to assess the relationship between dietary intake of choline and betaine and the risk of breast cancer among Chinese women. A two-stage case-control study was conducted, with 807 cases and 807 age (5-year interval) and residence (rural/urban)-matched controls. A validated food frequency questionnaire was used to assess dietary intake by face-to-face interview. Unconditional logistic regression model was used to calculate multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). A significant inverse association was found between dietary choline and betaine consumption and breast cancer risk. The adjusted ORs for the highest quartile of intake compared to the lowest were 0.40 (95%CI=0.28-0.57) for total choline intake, 0.58 (95%CI=0.42-0.80) for betaine intake, and 0.38 (0.27-0.53) for choline plus betaine intake, respectively. Intakes of individual choline compouds, choline from glycerophosphocholine, phosphocholine, phosphatidylcholine, sphingomyelin, and free choline were also negatively associated with breast cancer risk. The inverse association between choline intake and breast cancer risk was primarily confined to participants with low folate level with an OR (95% CI) of 0.46 (0.23-0.91) comparing the fourth quartile with the first quartile of choline intake. This study suggested that consumption of choline and betaine was inversely associated with the risk of breast cancer. The association of choline intake with breast cancer risk was probably modified by folate intake.

Zhang, C.-X., et al., Choline and betaine intake is inversely associated with breast cancer risk: A two-stage case-control study in China. Cancer Science, 2012 (Dec 26).

Metabolomics reveals the metabolic shifts following an intervention with rye bread in postmenopausal women- a randomized control trial

BACKGROUND: Epidemiological studies have consistently shown that whole grain (WG) cereals can protect against the development of chronic diseases, but the underlying mechanism is not fully understood. Among WG products, WG rye is considered even more potent because of its unique discrepancy in postprandial insulin and glucose responses known as the rye factor. In this study, an NMR-based metabolomics approach was applied to study the metabolic effects of WG rye as a tool to determine the beneficial effects of WG rye on human health. METHODS: Thirty-three postmenopausal Finnish women with elevated serum total cholesterol (5.0-8.5 mmol/L) and BMI of 20-33 kg/m2 consumed a minimum of 20% of their daily energy intake as high fiber WG rye bread (RB) or refined wheat bread (WB) in a randomized, controlled, crossover design with two 8-wk intervention periods separated by an 8-wk washout period. At the end of each intervention period, fasting serum was collected for NMR-based metabolomics and the analysis of cholesterol fractions. Multilevel partial least squares discriminant analysis was used for paired comparisons of multivariate data. RESULTS: The metabolomics analysis of serum showed lower leucine and isoleucine and higher betaine and N,N-dimethylglycine levels after RB than WB intake. To further investigate the metabolic effects of RB, the serum cholesterol fractions were measured. Total- and LDL-cholesterol levels were higher after RB intake than after WB. CONCLUSIONS: This study revealed favorable shifts in branched amino acid and single carbon metabolism and an unfavorable shift in serum cholesterol levels after RB intake in postmenopausal women, which should be considered for evaluating health beneficial effects of rye products.

Moazzami, A.A., et al., Metabolomics reveals the metabolic shifts following an intervention with rye bread in postmenopausal women- a randomized control trial. Nutr J, 2012. 11: p. 88