Many studies suggest that trimethylamine-N-oxide (TMAO), a gut-flora-dependent metabolite of choline, contributes to the risk of cardiovascular diseases, but little is known for non-alcoholic fatty liver disease (NAFLD). We examined the association of circulating TMAO, choline and betaine with the presence and severity of NAFLD in Chinese adults. We performed a hospital-based case-control study (CCS) and a cross-sectional study (CSS). In the CCS, we recruited 60 biopsy-proven NAFLD cases and 35 controls (18–60 years) and determined serum concentrations of TMAO, choline and betaine by HPLC-MS/MS. For the CSS, 1,628 community-based adults (40-75 years) completed the blood tests and ultrasonographic NAFLD evaluation. In the CCS, analyses of covariance showed adverse associations of ln-transformed serum levels of TMAO, choline and betaine/choline ratio with the scores of steatosis and total NAFLD activity (NAS) (all P-trend <0.05). The CSS revealed that a greater severity of NAFLD was independently correlated with higher TMAO but lower betaine and betaine/choline ratio (all P-trend <0.05). No significant choline-NAFLD association was observed. Our findings showed adverse associations between the circulating TMAO level and the presence and severity of NAFLD in hospital- and community-based Chinese adults, and a favorable betaine-NAFLD relationship in the community-based participants.

Background and AimPrevious studies have indicated that neck circumference is a valuable predictor for obesity and metabolic syndrome, but little evidence is available for fatty liver disease. We examined the association of neck circumference with fatty liver disease and evaluated its predictive value in Chinese adults.MethodsThis cross-sectional study comprised 4053 participants (1617 women and 2436 men, aged 20-88) recruited from the Health Examination Center in Guangzhou, China between May 2009 and April 2010. Anthropometric measurements were taken, abdominal ultrasonography was conducted and blood biochemical parameters were measured. Covariance, logistic regression and receiver operating characteristic curve analyses were employed.ResultsThe mean neck circumference was greater in subjects with fatty liver disease than those without the disease in both women and men after adjusting for age (P<0.001). Logistic regression analysis showed that the age-adjusted ORs (95% CI) of fatty liver disease for quartile 4 (vs. quartile 1) of neck circumference were 7.70 (4.95-11.99) for women and 12.42 (9.22-16.74) for men. After further adjusting for other anthropometric indices, both individually and combined, the corresponding ORs remained significant (all P-trends<0.05) but were attenuated to 1.94-2.53 for women and 1.45-2.08 for men. An additive interaction existed between neck circumference and the other anthropometric measures (all P<0.05). A high neck circumference value was associated with a much greater prevalence of fatty liver disease in participants with both high and normal BMI, waist circumference and waist-to-hip ratio values.ConclusionsNeck circumference was an independent predictor for fatty liver disease and provided an additional contribution when applied with other anthropometric measures.

The dietary intake of methyl donors is favorably associated with many diseases, but the findings regarding primary liver cancer (PLC) risk are limited. This study investigated the association between the intake of choline, betaine and methionine and PLC risk in adults. This 1:1 matched case-control study enrolled 644 hospital-based PLC patients and 644 community-based controls who were matched by sex and age, in Guangzhou, China. An interviewer-administered questionnaire and a food-frequency questionnaire were used to collect general information and dietary intake information. Conditional logistic regression showed a significantly inverse association between total choline and betaine intakes and PLC risk. The multivariable-adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) for PLC for the top (vs. bottom) tertile were 0.34 (0.24–0.49; P -trend < 0.001) for total choline and 0.67 (0.48–0.93; P -trend = 0.011) for betaine. No significant association was observed between the intake of methionine and PLC risk (P > 0.05). For individual choline compounds, higher consumptions of free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine and sphingomyelin were associated with a lower PLC risk (all P-trend < 0.05). The studied associations were not significantly modified by the folate intake (P-interactions: 0.488–0.890). Our findings suggest that higher choline and betaine intakes may be associated with a lower risk of PLC.

Dietary intake of vitamin A (VA) and carotenes has shown beneficial effects for decreasing the risk of some types of cancer, but findings on the risk of primary liver cancer (PLC) are inconsistent. This case–control study explored the associations between the dietary intake of VA and carotenes and the risk of PLC. We recruited 644 incident PLC patients (diagnosed within one month of each other) and 644 age- and gender-matched controls in Guangzhou, China. A food frequency questionnaire was used to assess habitual dietary intake. Logistic regression analyses found that higher intakes of VA and carotenes were independently associated with decreased PLC risk (all P-trend < 0.001). The multivariable-adjusted ORs (95% CI) of PLC for the highest (vs. lowest) quartile were 0.34 (0.24–0.48) for vitamin A and 0.35 (0.25–0.49) for carotenes. The associations were not significantly modified by smoking, alcohol, or tea drinking (P-interactions: 0.062–0.912). Dose–response analysis showed a U-shaped VA–PLC relationship, with sharply decreased risks at the intakes of about 1000 μg retinol equivalent (RE)/day, and then slowly went down toward the flat-bottomed risks with the lowest risk at 2300 μg RE/day. Our findings suggest that greater intake of retinol, carotenes, and total VA may decrease PLC risk among the Chinese population at an intake of 1000 μg RE/day or greater from food sources.

Prenatal intake of choline has been reported to lead to enhanced cognitive function in offspring, but little is known about the effects on spatial learning deficits. The present study examined the effects of prenatal choline supplementation on developmental low-protein exposure and its potential mechanisms. Pregnant female rats were fed either a normal or low-protein diet containing sufficient choline (1.1g/kg choline chloride) or supplemented choline (5.0g/kg choline chloride) until delivery. The Barnes maze test was performed at postnatal days 31-37. Choline and its metabolites, the synaptic structural parameters of the CA1 region in the brain of the newborn rat, were measured. The Barnes maze test demonstrated that prenatal low-protein pups had significantly greater error scale values, hole deviation scores, strategy scores and spatial search strategy and had lesser random search strategy values than normal protein pups (all P<.05). These alterations were significantly reversed by choline supplementation. Choline supplementation increased the brain levels of choline, betaine, phosphatidylethanolamine and phosphatidylcholine of newborns by 51.35% (P<.05), 33.33% (P<.001), 28.68% (P<.01) and 23.58% (P<.05), respectively, compared with the LPD group. Prenatal choline supplementation reversed the increased width of the synaptic cleft (P<.05) and decreased the curvature of the synaptic interface (P<.05) induced by a low-protein diet. Prenatal choline supplementation could attenuate the spatial learning deficits caused by prenatal protein malnutrition by increasing brain choline, betaine and phospholipids and by influencing the hippocampus structure.