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Background Alcoholic steatohepatitis (ASH) is caused in part by the effects of ethanol (EtOH) on hepatic methionine metabolism. Methods To investigate the phenotypic and epigenetic consequences of altered methionine metabolism in this disease, we studied the effects of 4-week intragastric EtOH feeding with and without the methyl donor betaine in cystathionine beta synthase (CβS) heterozygous C57BL/6J mice. Results The histopathology of early ASH was induced by EtOH feeding and prevented by betaine supplementation, while EtOH feeding reduced and betaine supplementation maintained the hepatic methylation ratio of the universal methyl donor S-adenosylmethionine (SAM) to the methyltransferase inhibitor S-adenosylhomocysteine (SAH). MethylC-seq genomic sequencing of heterozygous liver samples from each diet group found 2 to 4% reduced methylation in gene bodies, but not promoter regions of all autosomes of EtOH-fed mice, each of which were normalized in samples from mice fed the betaine-supplemented diet. The transcript levels of nitric oxide synthase ( Nos2) and DNA methyltransferase 1 ( Dnmt1) were increased, while those of peroxisome proliferator receptor- α ( Pparα) were reduced in EtOH-fed mice, and each was normalized in mice fed the betaine-supplemented diet. DNA pyrosequencing of CβS heterozygous samples found reduced methylation in a gene body of Nos2 by EtOH feeding that was restored by betaine supplementation and was correlated inversely with its expression and positively with SAM/SAH ratios. Conclusions The present study has demonstrated relationships among EtOH induction of ASH with aberrant methionine metabolism that was associated with gene body DNA hypomethylation in all autosomes and was prevented by betaine supplementation. The data imply that EtOH-induced changes in selected gene transcript levels and hypomethylation in gene bodies during the induction of ASH are a result of altered methionine metabolism that can be reversed through dietary supplementation of methyl donors. [ABSTRACT FROM AUTHOR]

Background: S-adenosyl-L-methionine (SAM) is the methyl donor for all methylation reactions and regulates the synthesis of glutathione, the main cellular antioxidant. Previous experimental studies suggested that SAM may benefit patients with established alcoholic liver diseases (ALDs). The aim of this study was to determine the efficacy of SAM in treatment for ALD in a 24-week trial. The primary endpoints were changes in serum aminotransferase levels and liver histopathology scores, and the secondary endpoints were changes in serum levels of methionine metabolites. Methods: We randomized 37 patients with ALD to receive 1.2 g of SAM by mouth or placebo daily. Subjects were required to remain abstinent from alcohol drinking. A baseline liver biopsy was performed in 24 subjects, and a posttreatment liver biopsy was performed in 14 subjects. Results: Fasting serum SAM levels were increased over timed intervals in the SAM treatment group. The entire cohort showed an overall improvement of AST, ALT, and bilirubin levels after 24 weeks of treatment, but there were no differences between the treatment groups in any clinical or biochemical parameters nor any intra- or intergroup differences or changes in liver histopathology scores for steatosis, inflammation, fibrosis, and Mallory-Denk hyaline bodies. Conclusions: Whereas abstinence improved liver function, 24 weeks of therapy with SAM was no more effective than placebo in the treatment for ALD. [ABSTRACT FROM AUTHOR]

Several studies have documented that length gain often lags behind weight gain during infancy and early childhood, suggesting that linear growth is partly regulated by initial body mass or fatness. To investigate this hypothesis, we analysed data from four longitudinal studies on growth of infants in the first 12 months: (1) U.S. breast-fed and formula-fed infants (n = 89); (2) breast-fed infants in Ghana (n = 190); (3) normal birthweight, breast-fed infants in Honduras (n = 108); and (4) term, low-birthweight breast-fed infants in Honduras (n = 119). The dependent variable was length gain during each 3-month interval (1– 4, 2–5, 3–6, 4–7, 5–8, 6–9, 7–10, 8–11 and 9–12 months). Three main independent variables were examined: initial weight-for-length z-score (W/L), weight change during the prior 3 months, and initial skinfold thickness. Controlling for maternal height, infant sex, and initial length-for-age z-score, length gain was positively correlated with initial W/L and prior weight change during all age intervals and with initial skinfold thickness at 3 and 4 months (r = 0.15–0.36;P < 0.01). There was no evidence of a threshold effect. These associations were evident in all four populations, in both boys and girls, and in breast-fed and formula-fed infants. The consistency of this relationship across studies supports the hypothesis that linear growth is partly regulated by initial body mass or fatness in infants. [ABSTRACT FROM AUTHOR]

To determine the effects of energy density and feeding frequency of complementary foods (CFs) on total daily energy intake and breast milk consumption, we measured intakes of semisolid cereal porridges and breast milk by 18 healthy, breastfed infants 8-11 mo of age. During 9 separate, randomly ordered dietary periods lasting 3-6 days each, children received coded porridges with energy densities 0.5, 1.0 or 1.5 kcal/g, either 3, 4, or 5 times/d. Ad libitum intakes of porridges and breast milk were measured during the last two days of each period. The mean amounts of CFs consumed were inversely related to their energy density and positively related to the number of meals/d (P <0.0001 for both), whereas energy intakes from CFs were positively related to both factors (see Table). Despite ∼8-12% decreases in breast milk intake when CFs with energy density 1.5 kcal/g were served (P <0.0001), and when meal frequency increased from 3 to 5 meals/d (P=0.01), total energy intakes (kcal/d) increased in relation to both energy density and feeding frequency of CFs (P < 0.0001 for both). Longer term effects of complementary feeding practices on breast milk intake should be explored. [ABSTRACT FROM AUTHOR]

The deuterated retinol dilution (DRD) technique provides a quantitative estimate of total body vitamin A (TBVA) pool size. The paired-DRD technique permits calculation of the change (+ or -) in TBVA pool size that occurs in response to consumption of different amounts of vitamin A (mean change in pool size = final pool size minus initial pool size). We used the paired-DRD technique to estimate the level of daily vitamin A intake that is required to maintain a constant TBVA pool size, i.e. the level of daily intake at which TBVA pool size is maintained, in two groups of adult males (n=32/group) with initial mean (± SD) TBVA pool sizes of either 0.059 ± 0.032 mmol or 0.181 ± 0.062 mmol. TBVA pool size was estimated before and 60 d after consumption of a low vitamin A diet, that was supplemented daily with one of 16 levels of vitamin A (100-2300 µg/d). Change in TBVA pool size was plotted against level of daily vitamin A intake, and the point where the regression line crosses the x-axis was used as an estimate of the level of daily vitamin A intake required to maintain a constant vitamin A pool size. Preliminary data indicate that an intake of 368 µg/d (95% CI: 274, 527; n=16) maintained a constant pool size among individuals with lower initial TBVA; and an intake of 763 µg/d (95% CI: not yet defined; n=16) maintained a constant pool size among individuals with larger initial TBVA. [ABSTRACT FROM AUTHOR]