X-Message-Number: 31794
Date: Sat, 4 Jul 2009 22:27:52 -0700 (PDT)
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 

[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

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[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

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[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 
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, 

    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

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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

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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

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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, 

    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

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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

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