Plasma betaine was inversely associated with colorectal cancer risk

Few studies have examined associations between plasma choline metabolites and risk of colorectal cancer (CRC). Therefore, we investigated associations between plasma biomarkers of choline metabolism [choline, betaine, dimethylglycine and trimethylamine N-oxide (TMAO)] and CRC risk among postmenopausal women in a case-control study nested within the Women's Health Initiative Observational Study. We selected 835 matched case-control pairs, and cases were further stratified by tumor site (proximal, distal, or rectal) and stage (local/regional or metastatic). CRC was assessed by self-report and confirmed by medical records over the mean 5.2y of follow-up. Baseline plasma choline metabolites were measured by liquid chromatography-tandem mass spectrometry. In multivariable-adjusted conditional logistic regression models, plasma choline tended to be positively associated with rectal cancer risk [OR (95% CI)highest vs. lowest quartile=2.44 (0.93-6.40);P-trend=0.08], while plasma betaine was inversely associated with CRC overall [0.68 (0.47-0.99);P-trend=0.01] and with local/regional tumors [0.64 (0.42-0.99);P-trend=0.009]. Notably, the plasma betaine:choline ratio was inversely associated with CRC overall [0.56 (0.39-0.82);P-trend=0.004] as well as with proximal [0.66 (0.41-1.06);P-trend=0.049], rectal [0.27 (0.10-0.78);P-trend=0.02] and local/regional [0.50 (0.33-0.76);P-trend=0.001] tumors. Finally, plasma TMAO, an oxidative derivative of choline produced by intestinal bacteria, was positively associated with rectal cancer [3.38 (1.25-9.16);P-trend=0.02] and with overall CRC risk among women with lower (vs. higher) plasma vitamin B12 levels (P-interaction=0.003). Collectively, these data suggest that alterations in choline metabolism, which may arise early in disease development, may be associated with higher risk of CRC. The positive association between plasma TMAO and CRC risk is consistent with an involvement of the gut microbiome in CRC pathogenesis.

Bae, S., et al., Plasma choline metabolites and colorectal cancer risk in the Women's Health Initiative Observational Study. Cancer Res, 2014

Effects of Betaine on Energy Utilization in Growing Pigs - A Review

One of the well known biological functions of betaine is that of a methyl donor. Therefore, betaine may partly replace choline and methionine in the diet. Another widely documented role of betaine is to restore and maintain the osmotic balance. As an organic osmotic compound, betaine regulates the water balance, thus exerting a stabilizing influence on tissue metabolism, particularly within the digestive tract. As a donor of methyl groups necessary for various reactions in the body, betaine is indirectly involved in lipid metabolism. Due to its metabolic functions, betaine is also believed to play a significant role in energy metabolism in pigs. Of particular note are the results of experiments in which a positive effect of betaine supplementation was observed as the energy content of the diet was decreased.

Lipinski, K., et al., Effects of Betaine on Energy Utilization in Growing Pigs - A Review. Annals of Animal Science, 2012. 12(3): p. 291-300

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.

Betaine improves nutrient digestion

The study was conducted to investigate the effects of graded dietary inclusion levels of betaine on ileal and total tract nutrient digestibilities and intestinal bacterial metabolites in piglets.

A total of eight barrows with an average initial body weight of 7.9 kg were randomly allocated to one of the four assay diets with two pigs per treatment in four repeated measurement periods. The assay diets included a basal diet based on wheat, barley and soybean meal alone, or supplemented with a liquid betaine product at dietary levels of 1.5, 3.0, or 6.0 g betaine per kilogram diet (as-fed). Ileal digestibilities of dry matter and neutral detergent fibre increased both quadratically and linearly, and ileal digestibility of glycine increased linearly as dietary betaine level increased (p < 0.05). Furthermore, total tract digestibility of crude protein increased quadratically (p < 0.05) and total tract digestibilities of most amino acids tended to increase quadratically (p = 0.06 to p = 0.11) with increasing dietary betaine level. Moreover, there were linear increases in the concentrations of most bacterial metabolites which were significant p < 0.05 for ileal d-lactic acid and for faecal diaminopimelic acid.

The results demonstrate that dietary betaine supplementation stimulates bacterial fermentation of fibre in the small intestine and bacterial degradation of crude protein in the large intestine.

Ratriyanto et al (2010). "Effect of graded levels of dietary betaine on ileal and total tract nutrient digestibilities and intestinal bacterial metabolites in piglets." J Anim Physiol Anim Nutr (Berl) 94(6): 788-96.

Metabonomics in ulcerative colitis

Nuclear magnetic resonance (NMR) spectroscopy and appropriate multivariate statistical analyses have been employed on mucosal colonic biopsies, colonocytes, lymphocytes, and urine from patients with ulcerative colitis (UC) and controls in order to explore the diagnostic possibilities, define new potential biomarkers, and generate a better understanding of the pathophysiology.

Samples were collected from patients with active UC, quiescent UC, and from controls and analyzed by NMR spectroscopy. Significant differences between controls and active UC were discovered in the metabolic profiles of biopsies and colonocytes. In the biopsies from patients with active UC higher levels of antioxidants and of a range of amino acids, but lower levels of lipid, glycerophosphocholine (GPC), myo-inositol, and betaine were found, whereas the colonocytes only displayed low levels of GPC, myo-inositol and choline. Interestingly, 20% of inactive UC patients had similar profiles to those who were in an active state.

This study demonstrates the possibilities of metabonomics as a diagnostic tool in active and quiescent UC and provides new insight into pathophysiologic mechanisms.

Bjerrum et al (2009). "Metabonomics in ulcerative colitis: diagnostics, biomarker identification, and insight into the pathophysiology." J Proteome Res: Epub Oct.