Choline suppresses hepatocellular carcinoma progression by attenuating AMPK/mTOR-mediated autophagy via choline transporter SLC5A7 activation.

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated death. Emerging evidence suggests that autophagy plays a critical role in HCC tumorigenesis, metastasis, and prognosis. Choline is an essential nutrient related to prolonged survival and reduced risk of HCC. However, it remains unclear whether this phenomenon is mediated by autophagy. Methods: Two HCC cell lines (HUH-7 and Hep3B) were used in the present study. Cell growth was evaluated by cell counting kit 8 (CCK-8), colony formation, and in vivo mouse xenografts assays. Cell motility was calculated by wound healing and transwell assays. Autophagosomes were measured by transmission electron microscope (TEM), and autophagy flux was detected by mRFP-GFP-labeled LC3 protein. The mRNA level of genes was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels were detected by Western blotting (WB). Results: We found that choline inhibited the proliferation, migration, and invasion of HCC cells by downregulating autophagy in vitro and in vivo. Upregulated expression of the solute carrier family 5 member 7 (SLC5A7), a specific choline transporter, correlated with better HCC prognosis. We further discovered that choline could promote SLC5A7 expression, upregulate cytoplasm p53 expression to impair the AMPK/mTOR pathway, and attenuate autophagy. Finally, we found that choline acted synergistically with sorafenib to attenuate HCC development in vitro and in vivo. Conclusions: Our findings provide novel insights into choline-mediated autophagy in HCC, providing the foothold for its future application in HCC treatment.

Mitigating the impact of bisphenol A exposure on mortality: Is diet the key? A cohort study based on NHANES.

Bisphenol A (BPA) is a widespread environmental pollutant linked to detrimental effects on human health and reduced life expectancy following chronic exposure. This prospective cohort study aimed to examine the association between BPA exposure and mortality in American adults and to explore the potential mitigating effects of dietary quality on BPA-related mortality. This study utilized data from 8761 American adults in the 2003-2016 National Health and Nutrition Examination Survey (NHANES). Urinary BPA levels were employed to assess BPA exposure, and dietary quality was evaluated using the Healthy Eating Index-2015 (HEI-2015). All-cause, cardiovascular disease (CVD), and cancer mortality statuses were determined until December 31, 2019, resulting in a cumulative follow-up of 80,564 person-years. The results showed that the highest tertile of urinary BPA levels corresponded to a 36% increase in all-cause mortality and a 62% increase in CVD mortality compared to the lowest tertile. In contrast, the highest tertile of HEI-2015 scores was associated with a 29% reduction in all-cause mortality relative to the lowest tertile. Although no significant interaction was found between HEI-2015 scores and urinary BPA levels concerning mortality, the association between HEI-2015 scores and both all-cause and CVD mortality was statistically significant at low urinary BPA levels. Continuous monitoring of BPA exposure is crucial for evaluating its long-term adverse health effects. Improving dietary quality can lower all-cause mortality and decrease the risk of all-cause and CVD mortality at low BPA exposure levels. However, due to the limited protective effect of dietary quality against BPA exposure, minimizing BPA exposure remains a vital goal.

Infant feeding practices and autism spectrum disorder in US children aged 2-5 years: the national survey of children's health (NSCH) 2016-2020.

OBJECTIVE: To investigate the relationship between infant feeding practices and autism spectrum disorder (ASD) among children aged 2-5 years in the United States (US). METHODS: Data from the 2016-2020 National Survey of Children's Health, a nationally representative cross-sectional survey, were utilized for this study. Questionnaires were administered to parents of children aged 2-5 years to gather information on ASD diagnosis, infant feeding practices, and demographic factors (e.g., child sex, ethnic group, and maternal age at birth). Logistic regression with sample weights was employed to assess the association between infant feeding practices and ASD, while controlling for demographic variables. Polynomial regression models were used to examine trends in exclusive breastfeeding and ever breastfeeding rates among children with and without ASD. RESULTS: A total of 35,050 children aged 2-5 years were analyzed, including 616 diagnosed with ASD, after excluding participants with missing information on breastfeeding and ASD diagnosis. Of these children with ASD, 76.6% (n = 472) had a breastfeeding history, with 67.5% (n = 416) engaged in partial breastfeeding and 9.1% (n = 56) exclusively breastfed. Adjusted odds ratios for each additional month of breastfeeding compared to never being breastfed were 0.98 (95% CI, 0.96-1.01). The adjusted odds ratios for breastfeeding durations of > 0-6 months, > 6-12 months, > 12-24 months, and > 24 months were 0.81 (95% CI, 0.50-1.31), 0.65 (95% CI, 0.36-1.18), 0.81 (95% CI, 0.44-1.49), and 0.48 (95% CI, 0.23-1.01), respectively. Compared to children who were never breastfed, the adjusted odds ratio for children who were ever breastfed was 0.74 (95% CI, 0.47-1.18). Among children with ASD, the proportion of ever breastfeeding declined from 82.0% in 2017 to 64.3% in 2020, while exclusive breastfeeding decreased from 12.0% in 2016 to 4.2% in 2020. CONCLUSIONS AND RELEVANCE: Although no significant association was found between infant feeding practices and ASD among US children aged 2-5 years, the rates of breastfeeding, particularly exclusive breastfeeding, were suboptimal among children with ASD. This highlights the need for specific policies and practices to promote and support breastfeeding among parents of children with ASD or those at high risk of having a child with ASD.

Association between maternal gestational diabetes and allergic diseases in offspring: a birth cohort study.

BACKGROUND: Previous studies have linked gestational diabetes (GDM) with allergies in offspring. However, the effect of specific glucose metabolism metrics was not well characterized, and the role of polyunsaturated fatty acids (PUFAs), a modifier of metabolism and the immune system, was understudied. We aimed to investigate the association between maternal GDM and allergic diseases in children and the interaction between glucose metabolism and PUFAs on allergic outcomes. METHODS: This prospective cohort study included 706 mother-child dyads from Guangzhou, China. Maternal GDM was diagnosed via a 75-g oral glucose tolerance test (OGTT), and dietary PUFAs were assessed using a validated food frequency questionnaire. Allergic disease diagnoses and the age of onset were obtained from medical records of children within three years old. RESULTS: Approximately 19.4% of women had GDM, and 51.3% of children had any allergic diseases. GDM was positively associated with any allergic diseases (hazard ratio [HR] 1.40; 95% confidence interval (CI) 1.05-1.88) and eczema (HR 1.44; 95% CI 1.02-1.97). A unit increase in OGTT after two hours (OGTT-2 h) glucose was associated with an 11% (95% CI 2%-21%) higher risk of any allergic diseases and a 17% (95% CI 1-36%) higher risk of food allergy. The positive associations between OGTT-2 h glucose and any allergic diseases were strengthened with decreased dietary a-linolenic acid (ALA) and increased n-6 PUFAs, linoleic acid (LA), LA/ALA ratio, and n-6/n-3 PUFA ratio. CONCLUSIONS: Maternal GDM was adversely associated with early-life allergic diseases, especially eczema. We were the first to identify OGTT-2 h glucose to be more sensitive in inducing allergy risk and that dietary PUFAs might modify the associations.

Effects of low-dose B vitamins plus betaine supplementation on lowering homocysteine concentrations among Chinese adults with hyperhomocysteinemia: a randomized, double-blind, controlled preliminary clinical trial.

PURPOSE: To test the hypothesis that daily supplementation with low-dose B vitamins plus betaine could significantly reduce plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia and free from background mandatory folic acid fortification. METHODS: One hundred apparently healthy adults aged 18-65 years with hyperhomocysteinemia were recruited in South China from July 2019 to June 2021. They were randomly assigned to either the supplement group (daily supplementation: 400 µg folic acid, 8 mg vitamin B6, 6.4 µg vitamin B12 and 1 g betaine) or the placebo group for 12 weeks. Fasting venous blood was collected at baseline, week 4 and week 12 to determine the concentrations of homocysteine, folate, vitamin B12 and betaine. Generalized estimation equations were used for statistical analysis. RESULTS: Statistically significant increments in blood concentrations of folate, vitamin B12 and betaine after the intervention in the supplement group indicated good participant compliance. At baseline, there were no significant differences in plasma homocysteine concentration between the two groups (P = 0.265). After 12-week supplementation, compared with the placebo group, there was a significant reduction in plasma homocysteine concentrations in the supplement group (mean group difference - 3.87; covariate-adjusted P = 0.012; reduction rate 10.1%; covariate-adjusted P < 0.001). In the supplement group, the decreased concentration of plasma homocysteine was associated with increments of blood concentrations of both folate (ß = -1.680, P = 0.004) and betaine (ß = -1.421, P = 0.020) after 12 weeks of supplementation. CONCLUSIONS: Daily supplementation with low-dose B vitamins plus betaine for 12 weeks effectively decreased plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov as NCT03720249 on October 25, 2018. Website: https://clinicaltrials.gov/ct2/show/NCT03720249 .

Dietary fatty acids and risk of non-alcoholic steatohepatitis: A national study in the United States.

Background: Non-alcoholic steatohepatitis (NASH), the early invertible stage of non-alcoholic fatty liver disease, has become a public health challenge due to the great burden and lack of effective treatment. Dietary nutrients are one of the modifiable factors to prevent and slow down disease progression. However, evidence linking dietary fatty acids intake and risk of NASH is lacking. Objectives: This study aimed to examine the association between dietary total saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), their subtypes, the ratio of unsaturated (UFAs) to SFAs, and the risk of NASH among a nationwide population in the United States. Methods: This cross-sectional study was conducted among 4,161 adults in the national health and nutrition examination survey in 2017-2018 cycle. Moreover, NASH was defined by transient elastography. Dietary fatty acids were assessed using a validated 24-h food recall method. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: A total of 2,089 (50.2%) participants with NASH were identified. Compared with participants in the bottom tercile of dietary intakes of total PUFAs, those in the highest tercile had lower risk of NASH, with an adjusted OR of 0.67 (95% CI: 0.46-0.97). Similar associations were found between the subtype of PUFA 18:3 and NASH, while the fully adjusted OR in the highest tercile was 0.67 (95% CI: 0.47-0.96). Interactions of dietary PUFAs and body mass index (BMI) could be found influencing NASH risk. Stronger associations of dietary total PUFAs intakes with NASH risk were found in obese participants (OR, 95% CI: 0.41, 0.22-0.75) than in the non-obese participants (OR, 95% CI: 1.00, 0.70-1.43; p-interaction = 0.006). Similar effects on risk of NASH were also observed between BMI and dietary intakes of PUFA 18:3. However, no significant associations were observed between NASH risk and dietary total SFAs, MUFAs, their subtypes as well as the ratio of UFAs to SFAs. Conclusion: Dietary intakes of total PUFAs, as well as its subtype of PUFA 18:3, were inversely associated with risk of NASH. The further large prospective studies need to be conducted to confirm the findings of this study.

Dietary linoleic acid and the ratio of unsaturated to saturated fatty acids are inversely associated with significant liver fibrosis risk: A nationwide survey.

Since no pharmaceuticals have been proven to effectively reduce liver fibrosis, dietary fatty acids may be beneficial as one of the non-pharmaceutical interventions due to their important roles in liver metabolism. In this cross-sectional study, we analyzed the data from the 2017-2018 cycle of National Health and Nutrition Examination Survey to examine the associations between the proportion and composition of dietary fatty acid intakes with significant liver fibrosis among US population. The dietary fatty acid consumptions were calculated based on two 24-h dietary recalls. Significant liver fibrosis was diagnosed based on liver stiffness measurement value derived from the vibration controlled transient elastography. Multivariate logistic regression analysis and sensitivity analysis were performed to assess the association between dietary fatty acid consumption and significant liver fibrosis risk. Finally, restricted cubic spline analysis was carried out to explore the dose-response between polyunsaturated fatty acids (PUFA) or linoleic acid intakes and the risk of significant liver fibrosis. The results showed that the multivariate adjusted odds ratios (95% confidence intervals) of significant liver fibrosis were 0.34 (0.14-0.84), 0.68 (0.50-0.91), and 0.64 (0.47-0.87) for the highest level of unsaturated to saturated fatty acid ratio, dietary PUFA, and linoleic acid intakes compared to the lowest reference, respectively. The sensitivity analysis and restricted cubic spline analysis produced similar results, reinforcing the inverse association of unsaturated to saturated fatty acid ratio, PUFA, and linoleic acid consumptions with significant liver fibrosis risk. However, other dietary fatty acids did not show the statistically significant association with significant liver fibrosis. In conclusion, dietary linoleic acid may play a key role in the inverse association between the unsaturated to saturated fatty acid ratio and the risk of significant liver fibrosis. Further studies are needed to confirm these findings.

Combined lifestyle, mental health, and mortality in US cancer survivors: a national cohort study.

BACKGROUND: Adopting healthy lifestyles and staying mentally health are two cost-effective modifiable strategies that cancer survivors can implement in self-management. We aimed to evaluate the independent, mediation, interaction, and joint associations of combined lifestyle and mental health with mortality in cancer survivors. METHODS: We performed a cohort study including 3145 cancer survivors from National Health and Nutrition Examination Survey (2005-2018). A healthy lifestyle score was constructed based on post-diagnosis body mass index, physical activity, diet, smoking, and drinking. Post-diagnosis mental health was assessed by Patient Health Questionnaire (PHQ-9). Hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cancer, and non-cancer mortality were computed using Cox proportional hazards regression models. RESULTS: After 20,900 person-years of follow-up (median, 6.3 years), cancer survivors with higher lifestyle score had decreased mortality, independent of mental health. Compared to participants with lower lifestyle score (0-1), HRs (95% CIs) for all-cause and non-cancer mortality among those with higher lifestyle score (3-5) were 0.68 (0.52-0.89) and 0.69 (0.56-0.85), respectively. 6.2-10.3% of the associations were mediated by mental health. Similar trends were observed among participants categorized by mental health, those with better mental health had lower mortality, independent of lifestyle. Participants with better mental health benefited more from adopting healthy lifestyles, and vice versa. Combinations of higher healthy lifestyle score and better mental health were associated with significant decreased mortality, the lowest mortality was seen in participants with highest healthy lifestyle score and concurrently with best mental health. CONCLUSIONS: For the first time, in this cohort study with a nationally representative sample of US cancer survivors, we comprehensively explored the complex associations of lifestyle, mental health, and mortality. Evidence derived from this study may give much confidence to cancer survivors and healthcare providers that, changing one's lifestyle and/or staying mentally healthy after cancer diagnosis can improve survival.

Profiling of triacylglycerol composition in the breast milk of Chinese mothers at different lactation stages.

Triacylglycerol (TAG) is the primary constituent of human milk fat and plays a vital role in the healthy development of infants. But few studies reported the sophisticated profile of TAG molecular species in human breast milk and its temporal changes during a prolonged lactation period. An efficient ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) method was adopted to examine TAGs. A total of 128 TAGs in 296 human breast milk samples collected during postnatal 0 to 400 days were identified. The changes in the human milk TAG profile mainly took place in the early stages of lactation (postnatal 0-45 days), and the TAG profile became stable in mature milk after 200 days of lactation. Odd chain fatty acids (OC-FAs) may be important markers for identifying human breast milk of different lactation stages. This study could provide evidence for developing safe and efficacious human-milk substitutes for children without access to human breast milk.

Dietary intake of one-carbon metabolism-related nutrients and hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort.

Dietary intake of one-carbon metabolism-related nutrients has been linked to cancer-related outcomes, but their effects on hepatocellular carcinoma (HCC) mortality are still unknown. The objective was to assess whether pre-diagnostic dietary intakes of methionine, folate, Vitamin B6, Vitamin B12, riboflavin and niacin are associated with HCC survival in this prospective cohort study. In total, 905 newly diagnosed HCC patients were recruited in the Guangdong Liver Cancer Cohort study between September 2013 and April 2017. Dietary intake was assessed using a validated 79-item food frequency questionnaire. Cox proportional hazard regression models were utilized to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the overall and HCC-specific mortality. During a median of 791 days of follow-up, we documented 395 deaths, 353 (89%) of which resulted from HCC. The multivariate-adjusted HRs in the highest vs. the lowest quartile of methionine intake were 0.59 (95% CI: 0.42-0.80; P for trend = 0.001) for overall mortality and 0.68 (95% CI: 0.49-0.93; P for trend = 0.027) for HCC-specific mortality. However, no significant association of other micronutrients involved in one-carbon metabolism with HCC survival was observed. Our research suggests that a high level of methionine intake, but no other one-carbon metabolism-related nutrients, may improve survival in patients with newly diagnosed HCC.

Lactational Changes of Phospholipids Content and Composition in Chinese Breast Milk.

Phospholipids are pivotal polar lipids in human milk and essential for infants' growth and development, especially in the brain and cognitive development. Its content and composition are affected by multiple factors and there exist discrepancies in different studies. In this study, we determined five major phospholipids classes (phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidylcholine, and sphingomyelin) in 2270 human milk samples collected from 0 to 400 days postpartum in six regions of China. The high-performance liquid chromatography coupled with an evaporative light scattering detector (HPLC-ELSD) was performed to quantify the phospholipids. Total phospholipid median (IQR) content was in a range between 170.38 ± 96.52 mg/L to 195.69 ± 81.80 mg/L during lactation and was higher concentrated in colostrum milk and later stage of lactation (after 200 days postpartum) compared with that in the samples collected between 10 to 45 days postpartum. Variations in five major sub-class phospholipids content were also observed across lactation stages (phosphatidylethanolamine: 52.61 ± 29.05 to 59.95 ± 41.74 mg/L; phosphatidylinositol: 17.65 ± 10.68 to 20.38 ± 8.55 mg/L; phosphatidylserine: 15.98 ± 9.02 to 22.77 ± 11.17 mg/L; phosphatidylcholine: 34.13 ± 25.33 to 48.64 ± 19.73 mg/L; sphingomyelin: 41.35 ± 20.31 to 54.79 ± 35.26 mg/L). Phosphatidylethanolamine (29.18-32.52%), phosphatidylcholine (19.90-25.04%) and sphingomyelin (22.39-29.17%) were the dominant sub-class phospholipids in Chinese breast milk during the whole lactation period. These results updated phospholipids data in Chinese human milk and could provide evidence for better development of secure and effective human milk surrogates for infants without access to breast milk.

High serum fibroblast growth factor 21 is associated with inferior hepatocellular carcinoma survival: A prospective cohort study.

BACKGROUND & AIMS: Epidemiological evidence linking fibroblast growth factor 21 (FGF21) with hepatocellular carcinoma (HCC) prognosis lacked. We aimed to evaluate the associations between serum FGF21 levels and HCC survival in a large prospective cohort. METHODS: 825 newly diagnosed, previously untreated HCC patients from the Guangdong Liver Cancer Cohort were enrolled between September 2013 and April 2017. Serum FGF21 levels were measured by ELISA. Liver cancer-specific survival (LCSS) and overall survival (OS) were calculated. Multivariable Cox proportional hazards models were performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Compared with patients in the lowest tertile of serum FGF21 levels, patients in the highest tertile had inferior survival outcomes. HRs in the fully adjusted models were 1.44 (95% CI: 1.07, 1.94; P-trend  = .014) and 1.48 (95% CI: 1.12, 1.97; P-trend  = .002) for LCSS and OS, respectively. The associations were not significantly modified by selected metabolic disorder diseases or state such as arterial hypertension, diabetes, dyslipidemia, fatty liver, cirrhosis, and body mass index ≥25.0 kg/m2 , except for that stronger associations were observed in patients co-occurred more than three metabolic disorder diseases (P-interaction  = .046 for OS and .151 for LCSS), with an HR of 2.01 (95% CI: 1.04, 3.85; P-trend  = .009) for OS and 1.51 (95% CI: 0.73, 3.10; P-trend  = .195) for LCSS. CONCLUSIONS: Higher serum FGF21 levels were associated with worse survival in HCC patients, suggesting that serum FGF21 may be used as a novel metabolism-related prognostic biomarker for HCC.

Dietary protein and prognosis of hepatocellular carcinoma: a prospective cohort study.

Dietary protein has been linked with all-cause and cancer mortality. However, the relationship between dietary protein and the prognosis of hepatocellular carcinoma (HCC) is still unknown. The purpose of this study was to investigate whether dietary protein intake was related to HCC mortality using data from the Guangdong Liver Cancer Cohort (GLCC), a prospective cohort study of HCC survivors established at the Sun Yat-sen University Cancer Center. Dietary information one year before the diagnosis of HCC was obtained through a 79-item semi-quantitative food frequency questionnaire (FFQ). A total of 883 patients with newly diagnosed HCC who were recruited between September 2013 and April 2017 were included in this study. The hazard ratio (HR) and 95% confidence intervals (95% CIs) were estimated by Cox proportional hazard models. The multivariate-adjusted HRs in the highest vs. the lowest tertile of total protein intake were 0.68 (95% CI: 0.52-0.91, P-trend = 0.007) for all-cause mortality and 0.74 (95% CI: 0.55-0.99, P-trend = 0.040) for HCC-specific mortality. However, the associations of animal protein intake, plant protein intake, and animal-to-plant protein ratio with all-cause and HCC-specific mortality were not significant (all P-trend >0.05). Our research suggests that higher prediagnostic dietary intake of total protein was associated with reduced all-cause and HCC-specific mortality.

Profiling of phospholipid molecular species in human breast milk of Chinese mothers and comprehensive analysis of phospholipidomic characteristics at different lactation stages.

Phospholipids are critical for milk digestion and infant development. But the profile of phospholipid molecular species in human milk and its dynamic changes during the lactation period have never been reported. The present study elucidated precise qualitative and quantitative analysis of 258 phospholipid molecular species in 486 human milk samples. Phosphatidylcholine is the most abundant class, followed by phosphatidylserine, phosphatidylethanolamine and sphingomyelin as the second abundant class in different lactation period. The plasmalogens declined along the lactation period, and the polyunsaturated-phospholipids decreased after 10-15 days. The decrease of phosphatidylcholines and phosphatidylglycerols, and the increase of lysophosphatidylethanolamines and lysophosphatidylcholines are critical changes from 0 to 5 days to 10-15 days; increase of phosphatidylinositols, phosphatidylserines, lysophosphatidylethanolamines and lysophosphatidylcholines is the key changes from 10-15 days to 40-45 days; the decrease of most phospholipid molecular species is the characteristic change from 40-45 days to 200-240 days; and the phospholipid profile achieved stability after 200 days.

Effects of probiotic supplementation on serum trimethylamine-N-oxide level and gut microbiota composition in young males: a double-blinded randomized controlled trial.

PURPOSE: To explore whether probiotic supplementation could attenuate serum trimethylamine-N-oxide (TMAO) level and impact the intestinal microbiome composition. DESIGN: Forty healthy males (20-25 years old) were randomized into the probiotic group (1.32 × 1011 CFU live bacteria including strains of Lactobacillus acidophilus, Lactobacillus rhamnosus GG, Bifidobacterium animalis, and Bifidobacterium longum daily) or the control group for 4 weeks. All participants underwent a phosphatidylcholine challenge test (PCCT) before and after the intervention. Serum TMAO and its precursors (TMA, choline and betaine) were measured by UPLC-MS/MS. The faecal microbiome was analyzed by 16S rRNA sequencing. RESULTS: Serum TMAO and its precursors were markedly increased after the PCCT. No statistical differences were observed in the probiotic and the control group in area under the curve (AUC) (14.79 ± 0.97 µmol/L 8 h vs. 19.17 ± 2.55 µmol/L 8 h, P = 0.106) and the pre- to post-intervention AUC alterations (∆AUC) (- 6.33 ± 2.00 µmol/L 8 h vs. - 0.73 ± 3.04 µmol/L 8 h, P = 0.131) of TMAO; however, higher proportion of participants in probiotic group showed their TMAO decrease after the intervention (78.9% vs. 45.0%, P = 0.029). The abundance of Faecalibacterium prausnitzii (P = 0.043) and Prevotella (P = 0.001) in the probiotic group was significantly increased after the intervention but without obvious differences in α- and ß-diversity. CONCLUSIONS: The current probiotic supplementation resulted in detectable change of intestinal microbiome composition but failed to attenuate the serum TMAO elevation after PCCT. CLINICALTRIALS. GOV IDENTIFIER: NCT03292978. CLINICALTRIALS.GOV WEBSITE: https://clinicaltrials.gov/ct2/show/NCT03292978 .

Dietary choline, rather than betaine intake, is associated with hepatocellular carcinoma mortality.

The dietary intakes of choline and betaine have been related to the mortality of some neoplasms, but their effects on hepatocellular carcinoma (HCC) mortality are still unknown. We examined the associations between dietary choline, five choline-containing compounds, different choline forms, betaine intake and HCC mortality. In total, 905 newly diagnosed HCC patients were enrolled in the Guangdong Liver Cancer Cohort study. Dietary intake was assessed by a valid food frequency questionnaire. Liver cancer-specific mortality (LCSM) and all-cause mortality (ACM) were calculated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed by Cox proportional hazards models. It was found that a higher total choline intake was associated with lower ACM, Q4 vs. Q1: HR = 0.72, 95% CI: 0.53-0.97, Ptrend = 0.012 in the fully adjusted model. The associations between total choline intake and LCSM were not significant. Similar associations were found between water-soluble choline intake and HCC mortality, where the fully adjusted HR for ACM was 0.72, 95% CI: 0.53-0.98, Ptrend = 0.017. However, null associations were found between neither phosphatidylcholine (the most abundant lipid-soluble choline) nor total lipid-soluble choline intake and HCC mortality. These results implied that the favorable associations between the total choline intake and ACM were more attributed to water-soluble choline. Furthermore, no significant associations were observed between betaine intake and HCC mortality. Future human intervention trials regarding choline supplementation and liver disease recovery should take the forms into consideration rather than just the total amount alone.

Association between dietary patterns and prognosis of hepatocellular carcinoma in the Guangdong liver cancer cohort study.

AIM: Adherence to dietary recommendations has been linked to a reduced risk of developing hepatocellular carcinoma (HCC) and dying of chronic liver disease. However, its role in the prognosis of HCC is still unclear. We prospectively investigated the association of two dietary quality indices, the Chinese Healthy Eating Index (CHEI) and the Healthy Eating Index-2015 (HEI-2015), with all-cause and HCC-specific mortality in a large prospective cohort of HCC survivors. METHODS: We included 887 patients with newly diagnosed, previously untreated HCC enrolled in the Guangdong Liver Cancer Cohort (GLCC) between September 2013 and April 2017 in the analysis. CHEI and HEI-2015 scores were calculated based on the dietary intake in the year before diagnosis of HCC. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for each index. RESULTS: During a median follow-up of 797 days, 389 deaths were identified, including 347 from HCC. Higher CHEI scores, reflecting favorable adherence to the 2016 Dietary Guidelines for Chinese, were associated with a lower risk of all-cause mortality (T3 vs. T1 : HR = 0.75, 95% CI: 0.58-0.98) and HCC-specific mortality (T3 vs. T1 : HR = 0.74, 95% CI: 0.56-0.98). Non-significant, inverse associations of HEI-2015 score with all-cause mortality (T3 vs. T1 : HR = 0.86, 95% CI: 0.67-1.11) and HCC-specific mortality (T3 vs. T1 : HR = 0.93, 95% CI: 0.71-1.21) were suggested. CONCLUSIONS: Our findings suggest that better adherence to the 2016 Dietary Guidelines for Chinese may reduce the risk of all-cause and HCC-specific mortality in patients with HCC.

Serum choline is associated with hepatocellular carcinoma survival: a prospective cohort study.

BACKGROUND: Higher choline and betaine levels have been linked to lower risk of liver cancer, whereas existing data in relation to hepatocellular carcinoma (HCC) prognosis are scarce. Our objective was to examine the associations of the serum choline and betaine with HCC survival. METHODS: 866 newly diagnosed HCC patients were enrolled in the Guangdong Liver Cancer Cohort. Serum choline and betaine were assessed using high-performance liquid chromatography with online electro-spray ionization tandem mass spectrometry. Liver cancer-specific survival (LCSS) and overall survival (OS) were calculated. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Serum choline levels were associated with better LCSS (T3 vs. T1: HR = 0.69, 95% CI: 0.51-0.94; P -trend < 0.05) and OS (T3 vs. T1: HR = 0.73, 95% CI: 0.54-0.99; P -trend < 0.05). The associations were significantly modified by C-reactive protein (CRP) levels but not by other selected prognostic factors including sex, age, etc. The favorable associations between serum choline and LCSS and OS were only existed among patients with CRP ≥3.0 mg/L. No significant associations were found between serum betaine levels and either LCSS or OS. CONCLUSIONS: This study revealed that higher serum choline levels were associated with better HCC survival, especially in HCC patients with systemic inflammation status. No significant associations were found between serum betaine and HCC survival. Our findings suggest the benefits of choline on HCC survival. TRIAL REGISTRATION: The Guangdong Liver Cancer Cohort was registered at clinicaltrials.gov as NCT03297255.

Prediagnostic dietary intakes of vitamin A and ß-carotene are associated with hepatocellular-carcinoma survival.

Vitamin A and its precursor (ß-carotene) have been linked with cancer incidence and mortality. However, the relationship between vitamin A and the prognosis of hepatocellular-carcinoma (HCC) is still unknown. Therefore, we investigated whether dietary intakes of vitamin A, retinol, and ß-carotene were associated with survival in patients with HCC who participated in the Guangdong Liver Cancer Cohort (GLCC) study. Patients aged 18-80 years with a diagnosis of incident Primary Liver Cancer (PLC) were enrolled within one month of diagnosis prior to cancer treatment at the Sun Yat-sen University Cancer Center. Dietary information one year before diagnosis of HCC was obtained using a 79-item, validated semiquantitative food frequency questionnaire (FFQ). We restricted the present analysis to 877 HCC patients enrolled in the GLCC between September, 2013 and April, 2017 who had completed FFQ. Cox proportional hazard regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for overall and HCC-specific survival. After a median follow-up of 797 days, 384 deaths were documented, 343 of which died from HCC. The multivariable-adjusted HRs (95% CI) of overall and HCC-specific survival for the highest versus the lowest quartile were 0.70 (0.53-0.94) and 0.68 (0.50-0.92) for vitamin A, and 0.72 (0.54-0.96) and 0.69 (0.51-0.94) for ß-carotene, respectively. However, no significant association of dietary retinol intakes with survival outcomes was observed. Our observations suggest that higher prediagnostic dietary intakes of vitamin A and ß-carotene were associated with improved overall and HCC-specific survival.