Moderate changes in dietary choline/betaine intake and blood indicators of status

Healthy premenopausal women (n=45, 18–46 years) with the MTHFR 677CC (n=28) or TT (n=17) genotype consumed a folate-restricted diet for 2 weeks followed by randomization to one of four dietary treatments (n=6–9/group) differing in total choline (344–486 mg/day), betaine (122–349 mg/day) and/or folate (400–800 μg dietary folate equivalents/day) content for 12 weeks.

No significant changes were detected in the measured variables (plasma levels of choline moieties (i.e., betaine, choline, phosphatidylcholine and sphingomyelin) and/or leukocyte global DNA methylation) in response to dietary increases in choline (i.e., 41% increase) or betaine (i.e., 286% increase) intake between pretreatment (Week 2) and posttreatment (Week 14) values. However, the MTHFR C677T genotype, alone or together with a diet, influenced betaine (P=.03) and phosphatidylcholine (P=.03).

These data suggest that choline/betaine status is not a reliable indicator of moderate changes in dietary choline/betaine intake possibly due to the engagement of compensatory mechanisms. In addition, the MTHFR C677T genotype appears to influence the direction and use of choline moieties in this group of women.

Abratte et al (2009). "Choline status is not a reliable indicator of moderate changes in dietary choline consumption in premenopausal women." J Nutr Biochem 20(1): 62-9.

Protection against myocardial infarction

This study investigated the protective effect of betaine on changes in the levels of lysosomal enzymes and lipid peroxidation in isoprenaline-induced myocardial infarction in Wistar rats, an animal model of myocardial infarction in man. Male albino Wistar rats were pretreated with betaine (250 mg/kg body weight) daily for a period of 30 days. After the treatment period, isoprenaline (11 mg/100 g body weight) was intraperitoneally administered to rats at intervals of 24 h for 2 days.

In isoprenaline-injected rats, the activities of plasma lysosomal enzymes (beta-glucuronidase, beta-galactosidase, beta-glucosidase, and acid phosphatase) increased significantly (p < 0.05), but activities decreased in heart tissue. Also, the level of lipid peroxidation was higher in heart lysosomes of isoprenaline-injected rats. Pretreatment with betaine prevented the changes in the activities of these lysosomal enzymes. Thus, the results show that betaine protects the lysosomal membrane against isoprenaline-induced myocardial infarction. The observed effects might be due to the free radical-scavenging and membrane-stabilizing properties of betaine.

Ganesan and Anandan (2009). "Protective effect of betaine on changes in the levels of lysosomal enzyme activities in heart tissue in isoprenaline-induced myocardial infarction in Wistar rats." Cell Stress Chaperones. March 18 Epub.

Greater daily gain and lean deposition in pigs

This study investigated the interactions between dietary ractopamine and betaine on growth and carcass characteristics in restrictively fed pigs. Pigs fed betaine had:

- greater daily gain (+8%)
- greater lean deposition (+5%)
- no effect on fat deposition

Dunshea et al (2009). "Dietary betaine and ractopamine combine to increase lean tissue deposition in finisher pigs, particularly gilts." Animal Production Science 49(1): 65-70.

Effect of pH on protein stabilizing property of betaine

This study investigated the pH dependence of the stabilizing effect of betaine on three different proteins - α-lactalbumin (α-LA), lysozyme and ribonuclease-A (RNase-A). They measured Tm (midpoint of denaturation), ΔHm (denaturational enthalpy change at Tm), ΔCp (constant-pressure heat capacity change) and ΔGDo (denaturational Gibbs energy change at 25 °C) of proteins in the presence of different betaine concentrations.

They found that betaine:

- stabilizes RNase-A at all pH values
- has opposite effects on α-LA and lysozyme at high pH and low pH values
- did not significantly change ΔHm and ΔCp

Singh et al (2009). "Glycine betaine may have opposite effects on protein stability at high and low pH values." Biochim Biophys Acta. Epub

Betaine reduces athersclerosis and inflammatory response

This study investigated the effect of betaine supplementation on atherosclerotic lesion in apolipoprotein (apo) E-deficient mice. Four groups of these mice were fed AIN-93G diets supplemented with 0, 1, 2, or 4 g betaine/100 g diet (no, 1, 2, and 4% betaine, respectively). Wild-type C57BL/6 J mice were fed AIN-93G diet (wild-type). Mice were sacrificed after 0, 7, or 14 weeks of the experimental diets. Atherosclerotic lesion area in the aortic sinus, levels of tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 in aorta and serum, serum lipids, and methylation status of TNF-α promoter in aorta were determined.

The results showed:

- compared with no-betaine mice after 14 weeks, mice receiving 1%, 2%, or 4% betaine had 10.8, 41, and 37% smaller lesion area, respectively.
- betaine supplementation reduced aortic expression of TNF-α in a dose-dependent way.
- betaine supplementation for 14 weeks led to higher concentrations of serum total cholesterol (P < 0.01), LDL cholesterol (P < 0.05), and lower body weight (P < 0.05).

The authors concluded that despite exacerbating hyperlipidemia in apoE-deficient mice, betaine may exert its anti-atherogenic effect by inhibiting aortic inflammatory response mediated by TNF-α.

Lv et al (2009). "Betaine supplementation attenuates atherosclerotic lesion in apolipoprotein E-deficient mice." Eur J Nutr 48(4): 205-12.

Muscle endurance and quality of repetitions

This study examined the efficacy of 15 days of betaine supplementation on muscle endurance, power performance and rate of fatigue in active college-aged men. Male subjects (24) were randomly assigned to one of two groups; the first consumed betaine daily (2.5 g/d), and the second consumed a placebo. Subjects were tested prior to the onset of supplementation (T1) and 7 (T2) and 14 days (T3) following supplementation. Subjects were tested over a 2-day period for:

- vertical jump power (VJP)
- bench press throw (BPT) power
- number of squat repetitions at 75% 1-RM (peak and mean power)
- number of bench press repetitions at 75% 1-RM (peak and mean power)
- two 30-sec Wingate anaerobic power tests (WAnT) (Day 2)

There were no differences in power assessment (VJP, BPT, WAnT) between the groups, or in the repetitions performed to exhaustion or in the number of repetitions performed at 90% of both peak and mean power between the groups in the bench press exercise.

However, the number of repetitions performed in the squat exercise for BET was significantly greater (p < 0.05) than that seen for PL at T2. The number of repetitions performed at 90% or greater of peak power in the squat exercise was significantly greater for BET at both T2 and T3 than PL. It was concluded that either 1 or 2 weeks of betaine supplementation in active, college males improved muscle endurance of the squat exercise, and increased the quality of repetitions performed.

Hoffman et al (2009). "Effect of Betaine Supplementation on Power Performance and Fatigue." Journal of the International Society of Sports Nutrition 6(1): 7.

Liver proteomics

A proteomic profiling strategy examined the effects of ethanol and betaine diet supplementation on major liver protein level changes. Male Wistar rats were fed control, ethanol or betaine supplemented diets for 4 weeks. Livers were removed and liver cytosolic proteins resolved by one-dimensional and two-dimensional separation techniques.

In rats fed the betaine supplemented ethanol diet, there was significant upregulation of:

- betaine homocysteine methyltransferase-1
- methionine adenosyl transferase-1
- glycine N-methyltransferase

The authors hypothesise that this concerted upregulation of these methionine metabolic pathway enzymes is the protective mechanism by which betaine restores a normal metabolic ratio of liver S-adenosylmethionine to S-adenosylhomocysteine. Ethanol also induced significant downregulation of carbonic anhydrase-III protein levels which was not restored by betaine supplementation. Carbonic anhydrase-III can function to resist oxidative stress, and the authors hypothesise that carbonic anhydrase-III protein levels compromised by ethanol consumption, contribute to ethanol-induced redox stress.

Kharbanda et al (2009). "Proteomics reveal a concerted upregulation of methionine metabolic pathway enzymes, and downregulation of carbonic anhydrase-III, in betaine supplemented ethanol-fed rats." Biochem Biophys Res Commun 381(4): 523-7.

Betaine intake measurement

The three-year reliability of reported dietary intake was similar for betaine and related nutrients, in the range as that published in the literature for other micronutrients. The mean intake of betaine was estimated at 106 mg/d.

Bidulescu et al (2009). "Repeatability and measurement error in the assessment of choline and betaine dietary intake: the Atherosclerosis Risk in Communities (ARIC) Study." Nutrition Journal 8(1): 14.