X-Message-Number: 31794 Date: Sat, 4 Jul 2009 22:27:52 -0700 (PDT) From: Subject: betaine is a probable lifespan extender in humans [Mortality in aged humans is associated with reduced muscle strength, and increased nfkappab expression. Betaine has been proven to increase muscle endurance in young humans, and to decrease nfkappab in aged rats. It would be interesting to see the results of an intervention study of these parameters in aged humans. It has also been proposed that the relative longevity of bats is due to their proteins being less vulnerable to urea induced denaturation than those of mice. Betaine just happens to directly inhibit urea induced denaturation.] [Dosage of betaine used below was 2.5 gm/day.] J Int Soc Sports Nutr. 2009 Feb 27;6:7. Effect of betaine supplementation on power performance and fatigue. Hoffman JR, Ratamess NA, Kang J, Rashti SL, Faigenbaum AD. Department of Health and Exercise Science, The College of New Jersey, PO Box 7718, Ewing, New Jersey 08628, USA. ABSTRACT: BACKGROUND: The purpose of this study was to examine the efficacy of 15 days of betaine supplementation on muscle endurance, power performance and rate of fatigue in active college-aged men. METHODS: Twenty-four male subjects were randomly assigned to one of two groups. The first group (BET; 20.4 +/- 1.3 years; height: 176.8 +/- 6.6 cm; body mass: 77.8 +/- 13.4 kg) consumed the supplement daily, and the second group (PL; 21.4 +/- 4.7 years; height: 181.3 +/- 5.9 cm; body mass: 83.3 +/- 5.2 kg) consumed a placebo. Subjects were tested prior to the onset of supplementation (T1) and 7 (T2) and 14 days (T3) following supplementation. Each testing period occurred over a 2-day period. During day one of testing subjects performed a vertical jump power (VJP) and a bench press throw (BPT) power test. In addition, subjects were required to perform as many repetitions as possible with 75% of their 1-RM in both the squat and bench press exercises. Both peak and mean power was assessed on each repetition. On day two of testing subjects performed two 30-sec Wingate anaerobic power tests (WAnT), each test separated by a 5-min active rest. RESULTS: No differences were seen at T2 or T3 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. 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. No differences in any power assessment (VJP, BPT, WAnT) was seen between the groups CONCLUSION: Two-weeks of betaine supplementation in active, college males appeared to improve muscle endurance of the squat exercise, and increase the quality of repetitions performed. PMID: 19250531 Free text: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19250531 [High doses of betaine returned nfkappab to youthful levels.] Biol Pharm Bull. 2007 Dec;30(12):2244-9. Betaine modulates age-related NF-kappaB by thiol-enhancing action. Go EK, Jung KJ, Kim JM, Lim H, Lim HK, Yu BP, Chung HY. Department of Pharmacy, College of Pharmacy, Pusan National University, Gumjung-ku, Busan 609-735, Korea. Depletion of glutathione levels and perturbations in redox status are considered to play a crucial role in aging and chronic inflammatory processes through the activation of redox sensitive transcription factors, including nuclear factor-kappaB (NF-kappaB). In the current study, we assessed the regulatory action of dietary betaine in the suppression of NF-kappaB by comparing kidney tissue from old, betaine-supplemented rats or non-betaine-supplemented rats (age 21 months) and 7 month-old rats. In addition, cultured HEK 293T cells were utilized for the molecular assessment of betaine's restorative ability of redox status when treating cells with potent glutathione (GSH)-depleting agents. Results showed that in old rats a short-term feeding (10 d) with betaine attenuated the age-related decrease in thiol levels, increase in reactive species and TNFalpha expression via NF-kappaB activation, compared to the young controls. These findings were verified in the cell-cultured system. Further investigations found that redox imbalance due to thiol depletion caused increased NF-kappaB activation, and cyclooxygenase (COX)-2 and TNFalpha levels, both of which were suppressed by betaine treatment. Based on both in vivo and in vitro data, we concluded that betaine exerts its efficacy by maintaining thiol status in the regulation of COX-2 and TNFalpha via NF-kappaB activation during aging. PMID: 18057706 Free text: http://www.jstage.jst.go.jp/article/bpb/30/12/30_2244/_article [If protein denaturation is a major driving force behind aging, then betaine could be expected to slow this process.] [Also note: If denaturation accounts for much of the toxicity of vitrificaion solutions, then betaine could be expected to reduce solution toxicity.] J Phys Chem B. 2009 Apr 16;113(15):5327-38. Osmolyte counteracts urea-induced denaturation of alpha-chymotrypsin. Venkatesu P, Lee MJ, Lin HM. Department of Chemical Engineering, National Taiwan University of Science and Technology, 43 Keelung Road, Section 4, Taipei 106-07, Taiwan. The stability of proteins is reduced by urea, which is methylamine and nonprotecting osmolyte; eventually urea destabilizes the activity and function and alters the structure of proteins, whereas the stability of proteins is raised by the osmolytes, which are not interfering with the functional activity of proteins. The deleterious effect of urea on proteins has been counteracted by methylamines (osmolytes), such as trimethylamine N-oxide (TMAO), betaine, and sarcosine. To distinctly enunciate the comparison of the counteracting effects between these methylamines on urea-induced denaturation of alpha-chymotrypsin (CT), we measured the hydrodynamic diameter (d(H)) and the thermodynamic properties (T(m), DeltaH, DeltaG(U), and DeltaC(p)) with dynamic light scattering (DLS) and differential scanning calorimeter (DSC), respectively. The present investigation compares the compatibility and counteracting hypothesis by determining the effects of methylamines and urea, as individual components and in combination at a concentration ratio of 1:2 (methylamine:urea) as well as various urea concentrations (0.5-5 M) in the presence of 1 M methylamine. The experimental results revealed that the naturally occurring osmolytes TMAO, betaine, and sarcosine strongly counteracted the urea actions on alpha-chymotrypsin. The results also indicated that TMAO counteracting the urea effects on CT was much stronger than betaine or sarcosine. PMID: 19354310 Am J Clin Nutr. 2008 Feb;87(2):424-30. Comment in: Am J Clin Nutr. 2008 Feb;87(2):277-8. Am J Clin Nutr. 2008 Jul;88(1):247-8; author reply 248. Dietary choline and betaine intakes in relation to concentrations of inflammatory markers in healthy adults: the ATTICA study. Detopoulou P, Panagiotakos DB, Antonopoulou S, Pitsavos C, Stefanadis C. Department of Nutrition Science-Dietetics, Harokopio University, Athens, Greece. BACKGROUND: Choline and betaine are found in a variety of plant and animal foods and were recently shown to be associated with decreased homocysteine concentrations. OBJECTIVE: The scope of this work was to investigate the associations between dietary choline and betaine consumption and various markers of low-grade systemic inflammation. DESIGN: Under the context of a cross-sectional survey that enrolled 1514 men (18-87 y of age) and 1528 women (18-89 y of age) with no history of cardiovascular disease (the ATTICA Study), fasting blood samples were collected and inflammatory markers were measured. Dietary habits were evaluated with a validated food-frequency questionnaire, and the intakes of choline and betaine were calculated from food-composition tables. RESULTS: Compared with the lowest tertile of choline intake (<250 mg/d), participants who consumed >310 mg/d had, on average, 22% lower concentrations of C-reactive protein (P < 0.05), 26% lower concentrations of interleukin-6 (P < 0.05), and 6% lower concentrations of tumor necrosis factor-alpha (P < 0.01). Similarly, participants who consumed >360 mg/d of betaine had, on average, 10% lower concentrations of homocysteine (P < 0.01), 19% lower concentrations of C-reactive protein (P < 0.1), and 12% lower concentrations of tumor necrosis factor-alpha (P < 0.05) than did those who consumed <260 mg/d. These findings were independent of various sociodemographic, lifestyle, and clinical characteristics of the participants. CONCLUSIONS: Our results support an association between choline and betaine intakes and the inflammation process in free-eating and apparently healthy adults. However, further studies are needed to confirm or refute our findings. PMID: 18258634 [PubMed Free text: http://www.ajcn.org/cgi/content/full/87/2/424 Br J Nutr. 2007 Nov;98(5):960-8. Epub 2007 May 31. The association of betaine, homocysteine and related metabolites with cognitive function in Dutch elderly people. Eussen SJ, Ueland PM, Clarke R, Blom HJ, Hoefnagels WH, van Staveren WA, de Groot LC. Division of Human Nutrition, Wageningen University, P.O. Box 8129 6700 EV Wageningen, The Netherlands. The importance of the one-carbon metabolites, choline and homocysteine, to brain function is well known. However, the associations between the one-carbon metabolites choline, betaine, methionine and dimethylglycine with cognition in elderly are unclear. We therefore examined the associations of these metabolites with cognition in a double-blind, placebo-controlled trial. Individuals (n 195) were randomized to receive daily oral capsules with either 1000 microg cobalamin (vitamin B12), or 1000 microg cobalamin plus 400 microg folic acid, or placebo for 24 weeks. Concentrations of homocysteine, methionine, choline, betaine and dimethylglycine were assessed before and after 12 and 24 weeks of treatment. Cognitive function, including domains of attention, construction, sensomotor speed, memory and executive function, was assessed before and after 24 weeks of treatment. At baseline, elevated plasma homocysteine was associated with lower performance of attention, construction, sensomotor speed and executive function. In addition, betaine was positively associated with better performance of construction, sensomotor speed and executive function, whereas elevated concentrations of methionine were positively associated with sensomotor speed. Daily combined supplementation with cobalamin plus folic acid decreased total homocysteine concentrations by 36%, and increased betaine concentrations by 38%. Participants with the largest increases in betaine concentrations showed a borderline significant (P = 0.07) higher memory performance compared to those without it. Although this trial observed associations of homocysteine and betaine with cognitive domains prior to supplementation, decreased concentrations of homocysteine were not related to improved cognitive performance. There was a tendency of participants with the largest increases in betaine concentrations to show the greatest improvement in memory function. PMID: 17537289 Free text: http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=1376800 J Radiat Res (Tokyo). 2005 Mar;46(1):117-21. Glycine betaine, a beer component, protects radiation-induced injury. Monobe M, Uzawa A, Hino M, Ando K, Kojima S. Department of Radiation Biosciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda-shi, Chiba, Japan. Human whole-blood was exposed to 137Cs gamma-rays or 50 keV/microm carbon ions in the presence or absence of glycine betaine, a beer component in vitro. The dicentrics of chromosome aberrations in human lymphocytes were significantly (p < 0.05) reduced by glycine betaine after irradiation with 4 Gy of either gamma-rays or carbon ions. The maximum protection by glycine betaine for gamma-rays or carbon ions was 37% and 20%, respectively. C3H/He female mice, aged 14 weeks, received an i.p. injection of glycine betaine 15 min before whole-body irradiation with gamma-rays or 50 keV/microm carbon ions. Glycine betaine significantly (p < 0.05) increased the percent survival of irradiated mice with either gamma-rays or carbon ions. In conclusion, glycine betaine is a potent protector against damages caused by low- and high-LET radiation. PMID: 15802867 Free text: http://www.jstage.jst.go.jp/article/jrr/46/1/46_117/_article Br J Nutr. 2004 Oct;92(4):665-9. The effect of low doses of betaine on plasma homocysteine in healthy volunteers. Alfthan G, Tapani K, Nissinen K, Saarela J, Aro A. Department of Health and Functional Capacity, National Public Health Institute (KTL), Helsinki, Finland. Homocysteine is a risk factor for vascular diseases, and lowering of plasma total homocysteine (tHcy) may be beneficial for health. Homocysteine can be remethylated to methionine by betaine-homocysteine methyltransferase using betaine (2(N,N,N-trimethyl)glycine) as methyl donor. A dose of 6 g betaine/d has been used in the treatment of homocystinuria, but data on the dose-response are scarce. Thirty-four healthy men and women were supplied with doses of 1, 3 and 6 g betaine and then with 6 g betaine+1 mg folic acid for four consecutive 1-week periods. The mean plasma tHcy concentration decreased by 1.1 (NS), 10.0 and 14.0 % (P<0.001) after supplementation with 1, 3 and 6 g betaine respectively. A further decrease in plasma tHcy by 5 % (P<0.01) was achieved by combining 1 mg folic acid with the 6 g betaine dose. Plasma betaine increased from 31 (sd 13) to 255 (sd 136) mumol/l in a dose-dependent manner (R(2) 0.97). We conclude that plasma tHcy is lowered rapidly and significantly by 3 or 6 g betaine/d in healthy men and women. PMID: 15522136 Free text: http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=915632 Am J Gastroenterol. 2001 Sep;96(9):2711-7. Comment in: Am J Gastroenterol. 2001 Sep;96(9):2534-6. Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot study. Abdelmalek MF, Angulo P, Jorgensen RA, Sylvestre PB, Lindor KD. Divisions of Gastroenterology and Hepatology and Surgical Pathology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. OBJECTIVES: No effective therapy currently exists for patients with nonalcoholic steatohepatitis (NASH). Betaine, a naturally occurring metabolite of choline, has been shown to raise S-adenosylmethionine (SAM) levels that may in turn play a role in decreasing hepatic steatosis. Our aim was to determine the safety and effects of betaine on liver biochemistries and histological markers of disease activity in patients with NASH. METHODS: Ten adult patients with NASH were enrolled. Patients received betaine anhydrous for oral solution (Cystadane) in two divided doses daily for 12 months. Seven out of 10 patients completed 1 yr of treatment with betaine. RESULTS: A significant improvement in serum levels of aspartate aminotransferase (p = 0.02) and ALAT (p = 0.007) occurred during treatment. Aminotransferases normalized in three of seven patients, decreased by >50% in three of seven patients, and remained unchanged in one patient when compared to baseline values. A marked improvement in serum levels of aminotransferases (ALT -39%; AST -38%) also occurred during treatment in those patients who did not complete 1 yr of treatment. Similarly, a marked improvement in the degree of steatosis, necroinflammatory grade, and stage of fibrosis was noted at 1 yr of treatment with betaine. Transitory GI adverse events that did not require any dose reduction or discontinuation of betaine occurred in four patients. CONCLUSIONS: Betaine is a safe and well tolerated drug that leads to a significant biochemical and histological improvement in patients with NASH. This novel agent deserves further evaluation in a randomized, placebo-controlled trial. PMID: 11569700 Acta Odontol Scand. 1998 Apr;56(2):65-9. Betaine-containing toothpaste relieves subjective symptoms of dry mouth. Soderling E, Le Bell A, Kirstila V, Tenovuo J. Institute of Dentistry, University of Turku, Finland. Subjects with dry mouth often experience irritation of the oral mucosa when using sodium lauryl sulfate containing products for oral hygiene. Betaine, or trimethylglycine, reduces skin-irritating effects of ingredients of cosmetics such as sodium lauryl sulfate. The aim of the present study was to compare the effects of a betaine-containing toothpaste with a regular toothpaste on the oral microbial flora, the condition of the oral mucosa, and subjective symptoms of dry mouth in subjects with chronic dry mouth symptoms. Thirteen subjects with chronic dry mouth symptoms and with a paraffin-stimulated salivary flow rate < or = 1 mL/min participated in the double-blind crossover study. Ten subjects had a very low salivary flow rate (< or = 0.6 mL/min). The subjects used both experimental toothpastes (with or without 4% betaine) twice a day for 2 weeks. Oral examinations and microbiologic sample collections were made at the base lines preceding the two experimental periods and at the end. Standardized questions on subjective symptoms of dry mouth were used when the subjects were interviewed at the end of the two experimental periods. No study-induced significant changes were observed in the microbiologic variables (plaque index, mutans streptococci, lactobacilli, Candida species) or in the appearance of the oral mucosa. The use of the betaine-containing toothpaste was, however, associated with a significant relief of several subjective symptoms of dry mouth. Betaine appears thus to be a promising ingredient of toothpastes in general and especially of toothpastes designed for patients with dry mouth. PMID: 9669455 Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=31794