Betaine is atheroprotective

Paraoxonase (PON1) is an antioxidant enzyme that prevents LDL oxidation as well as detoxifies homocysteine thiolactone (HCTL), both of which can cause atherosclerosis. Chronic alcohol (ETOH) and high ω-3 polyunsaturated fatty acids (ω-3 PUFA) consumption may affect PON1 status presumably via reactive oxygen species by depleting liver glutathione (GSH), whereas betaine may counter their effects.

Experimental rats belonging to various dietary groups were pair-fed with Lieber-DeCarli low (2.8% the dietary calories as ω3-fatty acids) and high (13.8% the dietary calories as ω3-fatty acids) menhaden fish alcohol-liquid diets with and without betaine (10 g/l diet) for 8 weeks after which liver PON1 mRNA, GSH, lipid score, and serum PON1, HCTLase, and ALT activities were measured.

Betaine restored liver PON1 mRNA expressions in low and high ω-3 PUFA ETOH groups with parallel restorations of PON1 activity and liver GSH. Concomitantly, betaine reduced hepatosteatosis accompanied by alleviation of liver injury caused by chronic alcohol and high ω-3 PUFA.

Dietary betaine was atheroprotective by restoring liver glutathione (GSH) that quenches free radicals, but also may alleviate liver injury by reducing hepatosteatosis.

Varatharajalu et al (2009). "Betaine Protects Chronic Alcohol and Omega-3 PUFA-Mediated Down-Regulations of PON1 Gene, Serum PON1 and Homocysteine Thiolactonase Activities With Restoration of Liver GSH." Alcoholism: Clinical and Experimental Research. Epub Dec 17.

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.

Betaine treatment of NAFLD

This was a randomized placebo-control study of 55 patients with biopsy-proven NASH who received either oral betaine (20 g daily) or placebo for 12 months. Treatment groups were comparable at baseline. Of the 35 patients (17 betaine, 18 placebo) who completed the study, 34 patients (16 betaine, 18 placebo) underwent posttreatment liver biopsy.

Compared to placebo, betaine improved hepatic steatosis and may protect against worsening steatosis. High-dose betaine supplementation failed to reduce S-adenosylhomocysteine and did not positively affect any of the second hit mechanisms postulated to contribute to NASH.

Abdelmalek et al (2009). "Betaine for nonalcoholic fatty liver disease: Results of a randomized placebo-controlled trial." Hepatology 50(6): 1818-26.

Amniotic fluid metabolites

This study aimed to establish and compare normative metabolite concentrations in 2nd and 3rd trimester human amniotic fluid samples in an effort to reveal metabolic biomarkers of fetal health and development.

21 metabolite concentrations were compared between 2nd and 3rd trimester amniotic fluid samples using (1)H high resolution magic angle spinning (HR-MAS) spectroscopy. 16 of 21 metabolite concentrations differed significantly between 2nd and 3rd trimester groups. Betaine and creatinine concentrations increased significantly, while glucose, citrate, pyruvate, and numerous amino acid concentrations decreased significantly with advancing gestation.

These results provide key normative data for 2nd and 3rd trimester amniotic fluid metabolite concentrations and provide the foundation for future development of magnetic resonance spectroscopy (MRS) biomarkers to evaluate fetal health and development.

Cohn et al (2009). "Quantitative metabolic profiles of 2nd and 3rd trimester human amniotic fluid using (1)H HR-MAS spectroscopy." Magma. Epub Sept.

Obesity, high fat diet, and urine metabolites

To investigate metabolic changes in the urine of a rat model of obesity induced by a high-fat diet (HFD), rats were divided into the following four groups based on the diet type and degree of weight gain: normal-diet (ND) low gainers, ND high gainers, HFD low gainers, and HFD high gainers. Biochemical analyses of visceral fat-pad weight, plasma, and liver tissues were performed.

It was observed that the metabolic profile of urine obtained by 1H-NMR-spectroscopy-based metabolomic analysis differed between ND low gainers and ND high gainers even though these animals consumed the same normal diet. Several key metabolites in urine, such as betaine, taurine, acetone/acetoacetate, phenylacetylglycine, pyruvate, lactate, and citrate contributed to the classification of these two groups. The metabolic profile of urine also differed between ND low gainers and HFD high gainers, which consumed the different diet and showed a different weight gain.

In short, these key metabolites, including betaine, were at higher concentrations in urine for high gainers vs low gainers.

This study has identified features of urine metabolites in various groups and demonstrated the reliability of an NMR-based metabolomics approach to investigate the effects of the diet and the physical constitution on obesity.

Kim et al (2009). "(1)H-nuclear magnetic resonance spectroscopy-based metabolic assessment in a rat model of obesity induced by a high-fat diet." Anal Bioanal Chem. Epub August

Ovarian cancer risk

The authors prospectively examined the relationship between the intake of choline/betaine and ovarian cancer risk among participants from the Nurses' Health Study (NHS) and NHSII. There were no associations between total choline, betaine, as well as choline plus betaine intake and ovarian cancer risk. Results did not vary by alcohol consumption, folate intake or after the exclusion of cases diagnosed during the 4-year period after dietary assessment.

Kotsopoulos et al (2010). "Dietary betaine and choline intake are not associated with risk of epithelial ovarian cancer." Eur J Clin Nutr 64(1): 111-114.

Fibrates may cause abnormal urinary betaine loss

Abnormal urinary loss of betaine is common in patients with the metabolic syndrome or diabetes mellitus. These patients are often treated with fibrates which alter renal function and raise plasma homocysteine concentrations.

- patients taking bezafibrate had higher betaine excretion than patients not taking fibrates
- of 32 patients taking bezafibrate, 20 had abnormal (>97.5 %-ile) betaine excretion
- plasma homocysteine correlated positively with betaine excretion in male patients with lipid disorders who were not taking fibrate, but the relationship was stronger if patients taking bezafibrate were included
- in elderly (>65 years) subjects with hypertension there was a similar correlation, which was stronger when a subject taking bezafibrate was included

Abnormal betaine excretion is common in patients treated with bezafibrate. Bezafibrate appears to exacerbate betaine loss, which will cause a rise in plasma homocysteine. Betaine supplementation could be considered in conjunction with fibrate therapy.

Lever et al (2009). "Fibrates may Cause an Abnormal Urinary Betaine Loss Which is Associated with Elevations in Plasma Homocysteine." Cardiovasc Drugs Ther. Epub Aug 4