Cho‐il Kim

Chronic ethanol consumption by baboons (50% of energy from a liquid diet) for 18 to 36 mo resulted in significant depletion of hepatic S –adenosyl–L–methionine concentration: 74.6 ± 2.4 nmol/gm vs. 108.9 ± 8.2 nmol/gm liver in controls (p < 0.005). The depletion was corrected with S –adenosyl–L–methionine (0.4 mg/kcal) administration (102.1 ± 15.4 nmol/gm after S –adenosyl–L–methionine-ethanol, with 121.4 ± 11.9 nmol/gm in controls). Ethanol also induced a depletion of glutathione (2.63 ± 0.13 μmol/gm after ethanol vs. 4.87 ± 0.36 μmol/gm in controls) that was attenuated by S –adenosyl–L–methionine (3.89 ± 0.51 μmol/gm in S –adenosyl–L–methionine–methanol vs. 5.22 ± 0.53 μmol/gm in S –adenosyl–L–methionine controls). There was a significant correlation between hepatic S –adenosyl–L–methionine and glutathione level (r = 0.497; p < 0.01). After the baboons received ethanol, we observed the expected increase in circulating levels of the mitochondrial enzyme glutamic dehydrogenase: 95.1 ± 21.4 IU/L vs. 13.4 ± 1.8 IU/L; p < 0.001, whereas in a corresponding group of animals given S –adenosyl–L–methionine with ethanol, the values were only 30.3 ± 7.1 IU/L (vs. 9.6 ± 0.7 IU/L in the S –adenosyl–L–methionine controls). This attenuation by S –adenosyl–L–methionine of the ethanol–induced increase in plasma glutamic dehydrogenase (p < 0.005) was associated with a decrease in the number of giant mitochondria (assessed in percutaneous liver biopsy specimens), with a corresponding change in the activity of succinate dehydrogenase, a mitochondrial marker enzyme. Succinate dehydrogenase activity was increased in liver homogenates of animals fed ethanol (81.4 ± 4.0 mU/mg protein vs. 55.4 ± 2.1 mU/mg in controls; p < 0.001), probably reflecting the increased mitochondrial mass. S –adenosyl–L–methionine decreased succinate dehydrogenase levels (66.7 ± 3.6 mU/mg protein in S –adenosyl–L–methionine–ethanol group vs. 45.5 ± 2.2 mU/mg in S –adenosyl–L–methionine controls; p < 0.001). S –adenosyl–L–methionine supplementation also significantly lessened the ethanol–induced increase of plasma AST. Thus long–term ethanol intake is associated with hepatic S –adenosyl–L–methionine depletion, which can be corrected at least in part by S –adenosyl–L–methionine administration, resulting in an attenuation of some alcohol–induced liver injury.

BACKGROUND: Saturated fat (SFA), ω-6 (n-6) polyunsaturated fat (PUFA), and trans fat (TFA) influence risk of coronary heart disease (CHD), but attributable CHD mortalities by country, age, sex, and time are unclear. METHODS AND RESULTS: National intakes of SFA, n-6 PUFA, and TFA were estimated using a Bayesian hierarchical model based on country-specific dietary surveys; food availability data; and, for TFA, industry reports on fats/oils and packaged foods. Etiologic effects of dietary fats on CHD mortality were derived from meta-analyses of prospective cohorts and CHD mortality rates from the 2010 Global Burden of Diseases study. Absolute and proportional attributable CHD mortality were computed using a comparative risk assessment framework. In 2010, nonoptimal intakes of n-6 PUFA, SFA, and TFA were estimated to result in 711 800 (95% uncertainty interval [UI] 680 700-745 000), 250 900 (95% UI 236 900-265 800), and 537 200 (95% UI 517 600-557 000) CHD deaths per year worldwide, accounting for 10.3% (95% UI 9.9%-10.6%), 3.6%, (95% UI 3.5%-3.6%) and 7.7% (95% UI 7.6%-7.9%) of global CHD mortality. Tropical oil-consuming countries were estimated to have the highest proportional n-6 PUFA- and SFA-attributable CHD mortality, whereas Egypt, Pakistan, and Canada were estimated to have the highest proportional TFA-attributable CHD mortality. From 1990 to 2010 globally, the estimated proportional CHD mortality decreased by 9% for insufficient n-6 PUFA and by 21% for higher SFA, whereas it increased by 4% for higher TFA, with the latter driven by increases in low- and middle-income countries. CONCLUSIONS: Nonoptimal intakes of n-6 PUFA, TFA, and SFA each contribute to significant estimated CHD mortality, with important heterogeneity across countries that informs nation-specific clinical, public health, and policy priorities.

Characteristic features of alcoholic liver injury include fibrosis and striking membrane alterations, with associated phospholipid changes. To offset some of these abnormalities, a 10-yr study was conducted in baboons: 12 animals (eight females, four males) were fed a liquid diet supplemented with polyunsaturated lecithin (4.1 mg/kcal) for up to 8 yr, with either ethanol (50% of total energy) or isocaloric carbohydrate. They were compared with another group of 18 baboons fed an equivalent amount of the same diet (with or without ethanol), but devoid of lecithin. In the two groups, comparable increases in lipids developed in the ethanol-fed animals, but striking differences in the degree of fibrosis were seen. Whereas at least septal fibrosis (with cirrhosis in two) and transformation of their lipocytes into transitional cells developed in seven of the nine baboons fed the regular diet with ethanol, septal fibrosis did not develop in any animals fed lecithin (p less than 0.005). They did not progress beyond the stage of perivenular fibrosis (sometimes associated with pericellular and perisinusoidal fibrosis) and had a significantly lesser activation of lipocytes to transitional cells. Furthermore, when three of these animals were taken off lecithin, but continued on the same amount of the ethanol-containing diet, they rapidly (within 18 to 21 mo) progressed to cirrhosis, accompanied by an increased transformation of their lipocytes to transitional cells. These results indicate that some component of lecithin exerts a protective action against the fibrogenic effects of ethanol. Because we had previously found that choline, in amounts present in lecithin, has no comparable action, the polyunsaturated phospholipids themselves might be responsible for the protective effect.