Betaine improves performance under heat stress in rabbit model

The objective of this study was to determine the effects of dietary betaine supplementation on growth performance, carcass characteristics, rectal temperature, respiration rate and immune response of growing rabbits under high ambient temperature.

A total of 120 weaned New Zealand White male rabbits, 6 weeks old, were randomly divided into five experimental treatments (24 each). Animals were fed ad libitum the basal diet supplemented with 0 (control), 250, 500, 750 and 1000 mg betaine/kg diet from 6 to 12 weeks of age. Animals were provided with water freely. The average daily temperature and relative humidity inside the rabbitry were 30.3 ± 0.9 °C and 76.2 ± 2.5%, respectively. Under heat stress conditions, diet significantly increased the body weight and hot carcass weight and significantly reduced the feed conversion. Dietary 1000 and 750 mg betaine/kg increased (P < 0.05) final body weights (2529.1 and 2418.5 g, respectively) compared with the control (2110.3 g). Betaine supplementation ameliorated some of the adverse effects of heat stress on immune responsiveness, rectal temperature and respiration rate. Dietary 250, 500, 750 and 1000 mg betaine/kg led to a decrease in rectal temperature (40.03, 39.85, 39.63 and 39.53 °C, respectively) compared with the control (40.20 °C). The inclusion of 1000 mg betaine/kg in the growing rabbits' diets nearly doubled the humoral and immune responses compared to the controls (P < 0.05) and significantly reduced rectal temperature and respiration rate. Serum T3, T4, total protein, globulin and total lipids were significantly increased while serum glucose concentration was significantly decreased due to dietary betaine.

In conclusion, supplemental dietary betaine enhanced growth performance and humoral and cell-mediated immunity as well as reduced rectal temperature and respiration rate in growing rabbits subjected to heat stress. From an economic point of view, high levels of betaine are not recommended because betaine is reasonably effective at lower, less expensive, doses.

Hassan et al (2011). "Effect of dietary betaine supplementation on growth, carcass and immunity of New Zealand White rabbits under high ambient temperature." Livestock Science 135(2-3): 103-109.

Betaine alleviates heat stress in chickens

Exposing broilers to a high temperature increases water and electrolyte K(+) and Na(+) excretion, which negatively affects the heat dissipation capacity and acid-base homeostasis, resulting in losses in growth performance.

In this experiment, the efficacy of providing oral rehydration therapy and betaine on growth performance, acid-base balance, and water and electrolyte retention was evaluated. A total of 432 one-day-old broiler chicks (Cobb) were allocated to 72 metabolic cages and reared to 31 d of age under standard conditions. From 32 to 41 d of age, chicks were exposed to heat stress (ambient temperature, 32 degrees C) and high RH (80 to 100% RH) for 9 h daily. The ameliorative effects of a 3 x 3 factorial array of treatments administered via drinking water were evaluated in 8 replicates of 6 chicks per cage for each treatment. Two oral rehydration therapy (ORT) fluids, based on either citrate or bicarbonate salts, were added to tap water. In addition, betaine was added to tap water at an inclusion rate of 0, 500, or 1,000 mg/L to complete the array of 9 liquid-based treatments. Growth performance was assessed at 32, 35, and 41 d of age. From 32 to 35 d of age, chicks receiving ORT fluids exhibited improved growth performance, water balance, and electrolyte (K(+), Na(+)) retention. In addition, the physiological response to stress was attenuated, as indicated by lower heterophil-to-lymphocyte ratios and blood glucose concentrations relative to the negative controls. The addition of betaine at an inclusion rate of 500 mg/L improved BW gain. From d 36 to 41, treatments did not significantly influence growth performance, which suggests that chicks receiving tap water were able to compensate and adapt to the heat-stress conditions.

The results demonstrate that the beneficial effects of providing ORT fluids and 500 mg of betaine/L were observed only during the first 4 d of heat exposure. After this period, adaptation to the heat appears to occur, and none of the treatments was successful in improving growth performance.

Sayed and Downing (2011). "The effects of water replacement by oral rehydration fluids with or without betaine supplementation on performance, acid-base balance, and water retention of heat-stressed broiler chickens." Poult Sci 90(1): 157-67.

High dietary betaine reduces risk of Barrett's esophagus

Folate plays a key role in DNA synthesis and methylation. Limited evidence suggests high intake may reduce risks of esophageal cancer overall; however, associations with esophageal cancer subtypes and Barrett's esophagus (BE), a precancerous lesion, remain unexplored.

We evaluated the relation between intake of folate, B vitamins, and methyl-group donors (methionine, choline, betaine) from foods and supplements, polymorphisms in key folate-metabolizing genes, and risk of BE, esophageal adenocarcinoma (EAC), and esophageal squamous cell carcinoma (ESCC) in 2 population-based case-control studies in Australia. BE patients without (n = 266) or with (n = 101) dysplasia were compared with population controls (n = 577); similarly, EAC (n = 636) or ESCC (n = 245) patients were compared with population controls (n = 1507) using multivariable adjusted logistic regression. Increasing intake of folate from foods was associated with reduced EAC risk (P-trend = 0.01) and mitigated the increased risks of ESCC associated with smoking and alcohol consumption. In contrast, high intake of folic acid from supplements was associated with a significantly elevated risk of BE with dysplasia. High intakes of riboflavin and methionine from food were associated with increased EAC risk, whereas increasing betaine intake was associated with reduced risks of BE without (P-trend = 0.004) or with dysplasia (P-trend = 0.02). Supplemental thiamin, riboflavin, niacin, and vitamin B-12 were associated with increased EAC risk. There were no consistent associations between genetic polymorphisms studied and BE or EAC risk. High intake of folate-containing foods may reduce risk of EAC, but our data raise the possibility that folic acid supplementation may increase risks of BE with dysplasia and EAC.

Ibiebele, T.I., et al., High intake of folate from food sources is associated with reduced risk of esophageal cancer in an Australian population. J Nutr, 2011. 141(2): p. 274-83.

Consumption of wheat aleurone-rich foods increases fasting plasma betaine and modestly decreases fasting homocysteine and LDL-cholesterol

There is strong evidence that whole-grain foods protect against heart disease. Although underlying mechanisms and components are unclear, betaine, found at high levels in wheat aleurone, may play a role. We evaluated the effects of a diet high in wheat aleurone on plasma betaine and related measures.

In a parallel, single-blinded intervention study, 79 healthy participants (aged 45–65 y, BMI ≥ 25 kg/m2) incorporated either aleurone-rich cereal products (27 g/d aleurone) or control products balanced for fiber and macronutrients into their habitual diets for 4 wk. Fasting blood samples were taken at baseline and postintervention (4 wk) from participants. Compared with the control, the aleurone products provided an additional 279 mg/d betaine and resulted in higher plasma betaine (P < 0.001; intervention effect size: 5.2 μmol/L) and lower plasma total homocysteine (tHcy) (P = 0.010; −0.7 μmol/L). Plasma dimethylglycine and methionine, which are products of betaine-mediated homocysteine remethylation, were also higher (P < 0.001; P = 0.027) relative to control. There were no significant effects on plasma choline or B vitamins (folate, riboflavin, and vitamin B-6). However, LDL cholesterol was lower than in the control group (P = 0.037).

We conclude that incorporating aleurone-rich products into the habitual diet for 4 wk significantly increases plasma betaine concentrations and lowers tHcy, which is attributable to enhanced betaine-homocysteine methyltransferase-mediated remethylation of homocysteine. Although this supports a role for betaine in the protective effects of whole grains, concomitant decreases in LDL suggest more than one component or mechanism may be responsible.

Price et al (2010). "Consumption of Wheat Aleurone-Rich Foods Increases Fasting Plasma Betaine and Modestly Decreases Fasting Homocysteine and LDL-Cholesterol in Adults." The Journal of Nutrition 140(12): 2153-2157.

Betaine prevents ethanol induced oxidative stress through regulation of gene expression

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.