Background: Depression is a prevalent mental disorder with high morbidity and mortality globally. Methylmalonic acid (MMA) is involved in the pathogenesis of numerous diseases. However, it is unclear whether there is an association between MMA and the prevalence of depression.Methods: This study enrolled 7866 US adults from the 2011-2014 survey of the National Health and Nutrition Examination Survey (NHANES). Individuals were categorized into depression group and non-depression group based on Patient's Health Questionnaire-9 (PHQ-9) score. The association between MMA concentrations and prevalence of depression was analysed by multivariate logistic and linear regression, restricted cubic spline regression, and subgroup analysis. Mediation analysis was used to explore the role of inflammation in the relationship between MMA and depression.Results: MMA concentrations were higher in participants with depression than those without depression. There was a positive and linear relationship of MMA concentrations with PHQ-9 score and depression risk, respectively. Moreover, the association was stable in most subgroups. Furthermore, inflammatory factors were positively correlated to MMA concentrations and prevalence of depression. In addition, white blood cell, neutrophil and alkaline phosphatase (ALP) mediated the relationship between MMA and depression.Conclusion: Our findings revealed that there was a linear and positive correlation between MMA and the prevalence of depression in US adults, which might be mediated by inflammation.

Vitamin B12 (B12) plays a critical role in fatty- and amino-acid metabolism and nucleotide synthesis. While the association between B12 deficiency and neurological dysfunction is well-known, the exact threshold for adequacy remains undefined in terms of functional impairment and evidence of injury. The objective was to assess whether B12 levels within the current normal range in a cohort of healthy older adults may be associated with measurable evidence of neurological injury or dysfunction.

We enrolled 231 healthy elderly volunteers (median age 71.2 years old) with a median B12 blood concentration of 414.8 pmol/L (as measured by automated chemiluminescence assay). We performed multifocal visual evoked potential testing, processing speed testing, and magnetic resonance imaging to assess neurological status. Moreover, we measured serum biomarkers of neuroaxonal injury, astrocyte involvement, and amyloid pathology.

Low (log-transformed) B12, especially decreased holo-transcobalamin, was associated with visual evoked potential latency delay (estimate = -0.04; p = 0.023), processing speed impairment (in an age-dependent manner; standardized β = -2.39; p = 0.006), and larger volumes of white matter hyperintensities on MRI (β = -0.21; p = 0.039). Remarkably, high levels of holo-haptocorrin (biologically inactive fraction of B12) correlated with serum levels of Tau, a biomarker of neurodegeneration (β = 0.22, p = 0.015).

Healthy older subjects exhibit neurological changes at both ends of the measurable "normal" B12 spectrum. These findings challenge our current understanding of optimal serum B12 levels and suggest revisiting how we establish appropriate nutritional recommendations. ANN NEUROL 2025;97:1190-1204.

The association between dietary indices and metabolic dysfunction-associated steatotic liver disease (MASLD) has shown inconsistent results in previous studies. Additionally, the potential mediating variables linking dietary quality to MASLD have not been adequately explored.

We analyzed data from 6,369 participants in the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Three dietary indices-Healthy Eating Index (HEI), Energy-adjusted Dietary Inflammatory Index (EDII), and Composite Dietary Antioxidant Index (CDAI)-were evaluated for their associations with MASLD using logistic regression models adjusted for a comprehensive range of covariates. Mediation analysis was performed to evaluate the roles of potential mediators from four domains: insulin resistance (homeostatic model assessment of insulin resistance, HOMA-IR; metabolic score for insulin resistance, METS-IR), systemic inflammation (systemic inflammatory response index, SIRI; systemic immune-inflammation index, SII), obesity or visceral fat distribution (a body shape index, ABSI; body roundness index, BRI), and oxidative stress (Gamma-Glutamyltransferase, GGT; Bilirubin; Uric Acid).

After adjusting for all covariates, only HEI showed a consistent inverse association with MASLD, while EDII and CDAI showed no significant associations. Mediation analysis identified METS-IR, HOMA-IR, BRI, and ABSI as significant mediators in the relationship between HEI and MASLD, with mediation proportion accounting for 47.16%, 48.84%, 52.69%, and 13.84%, respectively.

Higher HEI is associated with a reduced risk of MASLD. The findings suggest that insulin resistance and visceral fat distribution partially mediate the relationship between HEI and MASLD, providing insights into potential mechanisms linking diet and liver health.

diabesity (coexistence of diabetes and obesity) and metabolic associated steatotic liver disease (MASLD) are two very frequent pathologies whose prevalence is increasing every day.

to find out how these two pathological entities are associated in a group of Spanish workers.

a descriptive, cross-sectional study was carried out in 219477 workers to assess the association between diabesity (applying a double criterion, the body mass index BMI and the Clínica Universitaria de Navarra body adiposity estimator CUN BAE) and different risk scales for MASLD and liver fibrosis.

all MASH and liver fibrosis risk scales show higher values in people with diabesity applying the two criteria compared to people without diabesity.

diabesity and MASLD and liver fibrosis risk scales show a significant association in our study.

Liver metabolism is closely linked to glucose levels. Studies have shown that the aspartate aminotransferase to platelet ratio index (APRI), as a marker of liver fibrosis, is associated with type 2 diabetes mellitus (T2DM). However, the existing evidence remains insufficient to establish this association definitively. Furthermore, no prior studies have investigated the potential relationship between APRI and diabetic retinopathy (DR). This study aimed to investigate the association of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to platelet ratio index (APRI) scores with dysglycemia and DR.

This cross-sectional study analyzed data from 5828 participants aged 50 and older. All participants underwent laboratory blood tests, ophthalmological examinations, and interviews using questionnaires. Multiple linear regression models and receiver operating characteristic (ROC) curves explored the association between ALT and AST APRI scores and dysglycemia. Binary logistic regression was used to analyze the association between ALT and AST APRI scores and DR. Analyses were conducted for males and females separately to examine sex-specific effects.

In the multiple linear regression models, ALT and AST APRI scores were associated with fasting blood glucose after adjusting various potential confounders in the whole population or subgroup analysis (all P <0.05). ALT APRI score was superior to AST APRI score in the discrimination of hyperglycemic participants. In the univariate analysis, the ALT and AST APRI scores were associated with DR in the female participants with diabetes (P = 0.043, P=0.022). However, binary logistic regression models found no evident significant association between the ALT and AST APRI scores and DR in the female participants with diabetes (all P>0.05).

ALT and AST APRI scores are potential markers for the diagnosis of hyperglycemia, and ALT APRI score is superior to AST APRI score. ALT and AST APRI scores are not independent risk factors for DR.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide. However, the role of folate in MASLD remains controversial. This study aimed to investigate the association between two folate indicators [serum folate and red blood cell (RBC) folate] and MASLD prevalence using data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES).

A total of 3,879 participants without liver disease or significant alcohol consumption were included in the final analysis. Hepatic steatosis was assessed via transient elastography, with MASLD defined as a controlled attenuation parameter (CAP) ≥285 dB/m and the presence of at least one cardiometabolic risk factor. Logistic regression and generalized additive models (GAMs) were used to evaluate associations between folate levels and MASLD, with subgroup analyses stratified by age, gender, and body mass index (BMI).

After full adjustment for confounders, RBC folate exhibited a significant positive association with MASLD (OR = 1.111 and 95% CI: 1.015-1.216 per 1-unit increase). In contrast, serum folate showed a transient negative association in minimally adjusted models (OR = 0.869 and 95% CI: 0.802-0.941), which disappeared after further adjustments. Subgroup analyses confirmed that age, gender, and BMI did not modify the RBC folate-MASLD relationship.

These findings suggest that elevated RBC folate levels are independently associated with MASLD prevalence, whereas serum folate may lack clinical relevance due to susceptibility to confounding factors. RBC folate, as a stable biomarker of long-term folate status, may serve as a superior indicator for investigating folate-MASLD associations.

Excessive alcohol consumption is a major contributor to illness and mortality on a global scale. Per-capita alcohol consumption rose from 5.5 litres in 2005 to 6.4 litres in 2016 and is projected to reach 7.6 litres by 2030. In 2019, alcohol was associated with roughly a quarter of all cirrhosis-related deaths worldwide. The aim of this study is to assess the economic impact of premature mortality due to cirrhosis in Spain.

To estimate the economic impact of premature mortality due to cirrhosis, we utilized the human capital method. This method involved collecting data on mortality rates, average salaries, and unemployment rates. Our objective was to quantify the financial implications of cirrhosis-related deaths, offering valuable insights for policymakers and healthcare professionals.

In 2022, 45% of cirrhosis deaths occurred among individuals of working age. This resulted in the loss of 20,190 years of potential life lost (YPLL), contributing to productivity losses totalling €20.4 billion over a decade. These statistics highlight the significant economic and societal burdens associated with cirrhosis mortality.

Over the past two decades, there has been a global increase in alcohol consumption, a trend expected to persist and possibly escalate through 2030. As a direct consequence, projections indicate a corresponding increase in cirrhosis-related deaths over the coming decade. This anticipated rise underscores the ongoing public health challenge posed by alcohol-related liver diseases worldwide.

Limited and inconclusive evidence exists regarding the correlation between serum zinc levels and non-alcoholic fatty liver disease (NAFLD) and advanced fibrosis. The objective of this cross-sectional study was to investigate the association between serum zinc concentration and both NAFLD and advanced liver fibrosis among the United States (US) adults. 3398 subjects from National Health and Nutrition Examination Survey (NHANES) 2011-2016 were included. Serum zinc concentration was measured by inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS). NAFLD was diagnosed with Hepatic Steatosis Index (HSI), and advanced fibrosis risk was assessed by NAFLD Fibrosis Score (NFS). Weighted logistic regression and restricted cubic splines (RCS) were used to examine the association between serum zinc concentration and NAFLD and advanced fibrosis. Linear trend tests were conducted by incorporating the median of serum zinc quartiles as a continuous variable in the models. We employed sensitivity analysis and subgroup analysis to enhance the robustness of our results. The results from the RCS regression revealed no evident nonlinear relationship between serum zinc concentration and the presence of NAFLD and advanced fibrosis (p-nonlinear > 0.05). Compared with those in the lowest quartile (Q1) of serum zinc concentrations, the odds ratios (95% confidence intervals) of NAFLD were 1.49 (0.89,2.49) in Q2, 0.99 (0.68,1.45) in Q3, and 2.00 (1.40,2.86) in Q4 (p-trend = 0.002). Similarly, the odds ratios (95% confidence intervals) for advanced fibrosis in Q2-4 compared to Q1 were 0.86 (0.50,1.47), 0.60 (0.26,1.39), and 0.41 (0.21,0.77), respectively (p-trend = 0.006). Subgroup analyses and sensitivity analyses reinforce the same conclusion. The investigation revealed a positive linear relationship between serum zinc concentrations and the probability of developing NAFLD. Conversely, an inverse correlation was observed between serum zinc concentrations and the incidence of advanced liver fibrosis among individuals diagnosed with NAFLD.

Aims/Background Kawasaki disease (KD) is the common acute, self-limiting vasculitis in children, often affecting coronary arteries, which may lead to coronary artery dilation, stenosis, or in severe cases, myocardial infarction. This study aimed to identify new approaches for reducing or preventing coronary artery lesions (CAL) in KD patients by analyzing specific serological markers across various paediatric groups. Methods Clinical data were collected from 100 children diagnosed with Kawasaki disease (KD) admitted at First Affiliated Hospital of Hebei North University between May 2023 and June 2024. These children were divided into two groups based on coronary artery injury status: Occurrence group (n = 31) and Non-occurrence group (n = 69). Additionally, data from 100 children with acute upper respiratory tract infections (URTI) and 100 healthy children who underwent routine physical examination during the same period (Healthy group) were included for comparison. Serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), D-dimer (D-D), albumin (ALB), and T-cell subsets were measured and compared across groups to evaluate their clinical utility in diagnosing coronary artery damage in KD. Results NT-proBNP and D-D levels were highest in KD children with coronary artery injury and lowest in the healthy group, while ALB levels were lowest in KD children with coronary artery injury and highest in the healthy group, with statistically significant differences (p < 0.001). Analysis of T-cell subsets revealed that cluster of differentiation (CD)3+, CD4+, and CD4+/CD8+ levels were highest in the Healthy group, while CD8+ levels were highest in the Occurrence group, with statistically significant differences (p < 0.001). The combined diagnostic model demonstrated an area under the curve (AUC) value of 0.885 (95% CI: 0.829-0.941), showing higher specificity and AUC value compared to each marker individually. Conclusion The combination of serum NT-proBNP, D-D, ALB, and T-cell subsets offers valuable predictive insights for coronary artery damage in KD children and may serve as an auxiliary diagnostic tool.

Nonalcoholic fatty liver disease (NAFLD) has emerged as a significant global health concern, with advanced fibrosis increasing mortality risks. Despite the abundance of dietary guidelines for managing NAFLD, the precise impact of diet quality on mortality among individuals with advanced fibrosis remains elusive. This study aims to explore the influence of five dietary quality indexes on mortality among NAFLD patients and advanced fibrosis patients.

This study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2005 to 2018 to assess dietary quality based on the Alternate Mediterranean Diet (aMED), Healthy Eating Index-2020 (HEI-2020), Dietary Approach to Stop Hypertension (DASH), Alternate Healthy Eating Index (AHEI), and Dietary Inflammatory Index (DII). Weighted Cox proportional hazard regression models along with restricted cubic splines and subgroup analyses were employed in this study.

The analysis encompassed 3,634 NAFLD patients. After a median follow-up of 89 months, it was found that higher scores on the aMED (HR 0.814, 95% CI 0.681-0.972), HEI-2020 (HR 0.984, 95% CI 0.972-0.997), DASH (HR 0.930, 95% CI 0.883-0.979), and AHEI (HR 0.980, 95% CI 0.966-0.995) were associated with lower mortality risks, while DII scores (HR 1.280, 95% CI 1.098-1.493) indicated an increased risk of mortality. Additionally, a nonlinear relationship was identified solely between AHEI scores and all-cause mortality in NAFLD patients. Notably, among patients with advanced fibrosis, HEI-2020 as a categorical variable (T3: HR 0.519, 95% CI 0.280-0.964), DASH as a continuous variable (continuous: HR 0.921, 95% CI 0.849-0.999), AHEI (continuous: HR 0.971, 95% CI 0.945-0.997; T2: HR 0.545, 95% CI 0.310-0.960; T3: HR 0.444, 95% CI 0.245-0.804), and DII (continuous: HR 1.311, 95% CI 1.121-1.534; T3: HR 2.772, 95% CI 1.477-5.202) exhibited significant associations with all-cause mortality. Subgroup analyses revealed an interaction between AHEI scores and sex among NAFLD patients, where higher AHEI scores correlated with lower all-cause mortality in females, but no such association was observed in males. For other dietary quality, subgroup analyses indicated that their relationships with mortality were robust.

Our study suggests that a high-quality diet could potentially mitigate mortality risk in both NAFLD and advanced fibrosis patients.

This study aimed to examine the association between the triglyceride-glucose (TyG) index and liver fibrosis (LF) in U.S. adults with Metabolic Dysfunction-Associated Steatotic Liver Disease (MAFLD).

Using data from the 2017 to 2020 National Health and Nutrition Examination Survey (NHANES) database, we conducted a population-based cross-sectional study with 1,324 participants. MAFLD was defined as a controlled attenuation parameter (CAP) score ≥ 248 dB/m accompanied by metabolic dysfunction. A median liver stiffness measurement ≥ 8.2 kPa was used to identify significant fibrosis (≥ F2). Multivariable logistic regression was employed to assess the impact of the TyG index on LF outcomes. A restricted cubic spline (RCS) model was used to explore nonlinear effects, and receiver operating characteristic (ROC) curves were applied to evaluate the effectiveness in predicting.

Among the participants, 716 were men and 608 were women, aged 20 to 80 years, representing various racial groups. Significant fibrosis was observed in 137 out of 1,324 participants. After adjusting for confounding factors, a higher TyG index was significantly associated with an increased incidence of MAFLD-related LF (OR = 2.18, 95% CI, 1.14-4.18; p < 0.05). Elevated TyG levels showed a positive correlation with significant fibrosis, with an odds ratio (OR) exceeding 1 when the TyG index was above 8.054. Subgroup analyses stratified by sex, age, and body mass index (BMI) revealed differences after adjusting for confounders. The association was stronger in women (OR = 2.53, 95% CI, 1.16-5.53) than in men (OR = 1.95, 95% CI, 0.81-4.72). A significant correlation was also found between TyG levels and obesity status (overweight: OR = 4.80, 95% CI, 1.27-18.2; obese: OR = 2.26, 95% CI, 1.20-5.53). In MAFLD patients aged 40-59, TyG was strongly associated with LF (OR = 2.85, 95% CI, 1.16-6.79). Furthermore, the area under the ROC curve (AUC) for the TyG index in predicting significant fibrosis in MAFLD patients was 0.73 (95% CI, 0.68-0.78), indicating moderate predictive ability.

In the general U.S. population, elevated TyG index levels were positively associated with an increased risk of LF in MAFLD patients.

The relationship between dietary folate intake and prior mortality in adult patients with Non-alcoholic Fatty Liver Disease (NAFLD) has not been clearly studied. We aimed to examine the relationship between dietary folate intake and all-cause and cardiovascular (CVD) mortality in adult NAFLD patients in the US.

Using data from National Health and Nutrition Examination Survey (NHANES) 2003-2018 and associated mortality data we conducted a cohort study of US adult NAFLD subjects. Multivariable Cox proportional hazards regression models were used to evaluate the relationship between dietary folate intake and both all-cause mortality and CVD mortality, accounting for potential confounders. The study employed restricted cubic spline analysis to investigate the non-linear association between dietary folate levels and mortality from all causes and cardiovascular disease.

Our final cohort consisted of 3,266 NAFLD patients, with a median follow-up of 10.3 years, 691 deaths were observed, including 221 cardiovascular deaths. Compared to participants with a folate intake in Quartile 1 (≤250 μg/d), those in Quartile 4 (≥467.5 μg/d) had multivariable-adjusted hazard ratios of 0.69 (95% CI, 0.51-0.94) for all-cause mortality (p for trend = 0.028) and 0.55 (95% CI, 0.29-1.04) for CVD mortality (p for trend = 0.107). A non-linear relationship between dietary intake and risk of death was not observed.

Greater dietary folate intake is associated with a reduced risk of all-cause in American adults with NAFLD. Higher dietary folate intake not found to be associated with lower CVD mortality. These findings suggest that dietary folate may improve the prognosis of adult NAFLD patients. The measured-response relationship between dietary folate intake and mortality in patients with NAFLD requires further investigation.

There are conflicting studies reporting both an increase and a decrease in vitamin B12 (VB12) levels in non-alcoholic fatty liver disease (NAFLD). In this study, we aimed to dissect the effects of steatosis and fibrosis on VB12.

This is a cross-sectional study including all patients with a vibration-controlled transient elastography (VCTE) performed at the Hospital Miguel Servet (Zaragoza, Spain) between 2019 and 2022 for a chronic liver disease and having a recent blood test for VB12 levels. Liver fibrosis was assessed by VCTE and hepatic steatosis by ultrasonography and/or through controlled attenuation parameter (CAP).

1195 patients (NAFLD n = 441, other chronic liver disease n = 754) were included. Median age was 57 years, 53% female. Patients with NAFLD had lower levels of VB12 compared to the rest of chronic liver diseases (289 vs. 313 pg/mL, p < 0.001). A significant negative correlation was observed between VB12 levels and hepatic steatosis measured by CAP (r = -0.13, p < 0.001). A significant positive correlation was observed between VB12 levels and liver stiffness in patients with NAFLD in both sexes (men r = 0.31, p < 0.001 and women r = 0.15, p = 0.016). A significant association between VB12 levels and liver fibrosis in cirrhosis stage was observed in patients with NAFLD (OR 1.06, 95% CI, 1.025-1.098, p = 0.001).

VB12 levels were lower with greater hepatic steatosis. In NAFLD, VB12 levels were lower compared to other chronic liver diseases but their levels increased with higher liver stiffness and in cirrhosis stage.

To explore the association between oxidative balance score (OBS) and cardiovascular diseases (CVD) in patients with hypertension, and further clarify the mediating role of methylmalonic acid (MMA) in the relationship between OBS and CVD risk.

We included 4,137 participants with hypertension from the 2011-2014 National Health and Nutrition Examination Survey cohort. The study endpoint was the incidence of CVD in patients with hypertension. OBS was calculated based on 16 dietary and 4 lifestyle components. Weighted multivariable logistic regression models were adopted to assess the associations between OBS and CVD risk, OBS and MMA levels, and MMA levels and CVD risk. Odds ratios (OR) and 95% confidence interval (CI) were estimated. We used distribution-of-product method to test for mediation effect, with a presence of mediation indicated by 95% CI that does not include 0 for the distribution-of-product method and 95% CI that does not include 1 for the indirect effect.

Totally 812 developed CVD. In weighted multivariable logistic regression models, lower OBS category (OBS < 15.72) was associated with increased odds of CVD (OR = 1.53, 95%CI: 1.17-2.01) and MMA levels (OR = 1.32, 95%CI: 1.06-1.65), respectively, compared with higher OBS category as reference. A positive relationship between higher MMA levels (≥154.90 nmol/L) and CVD risk was observed (OR = 1.34, 95%CI: 1.07-1.68). Importantly, according to the distribution-of-product test, a potential mediating effect of MMA on the relationship between OBS and CVD was found (OR = 1.08, 95%CI: 1.01-1.19), with a 95% CI for distribution-of-product of 0.08 (95% CI: 0.01-0.17). The mediated proportion was 17.8%. Subgroup analysis revealed a mediating effect of MMA in individuals with dyslipidemia, with a mediated proportion of 14.9%.

MMA plays a critical mediating role in the pathway between OBS and CVD risk.

The relationship between dietary antioxidants and fatty liver disease remains a topic of debate. This study aimed to examine the association between the Composite Dietary Antioxidant Index (CDAI) and nonalcoholic fatty liver disease (NAFLD)/metabolic-associated fatty liver disease (MAFLD).

The study analyzed data from the 2003-2018 cycles of the National Health and Nutrition Examination Survey. The study included 16,321 individuals aged 20-85 years. Food and nutrient intake data were based on the 24-h recall method. Multivariate logistic regression models were employed to examine the relationship between CDAI and NAFLD/MAFLD.

In the fully adjusted multivariate logistic regression model, CDAI demonstrated a significant negative correlation with NAFLD and MAFLD. Mediation analysis showed that inflammatory factors partially mediated the relationship between CDAI and NAFLD/MAFLD prevalence. The combination of high CDAI levels with effective physical activity was associated with a greater reduction in NAFLD/MAFLD prevalence than high CDAI levels alone.

Our study highlighted a negative association between CDAI and NAFLD/MAFLD, mediated by inflammatory factors. Additionally, participants with characteristics of active physical activity and high levels of CDAI were more strongly correlated with the reduced prevalence of NAFLD/MAFLD. Further research in clinical cohorts should be conducted to comprehensively investigate the impact of CDAI on NAFLD/MAFLD prevalence.

The fibrosis-4 index (FIB-4) is a noninvasive fibrosis test that is recommended for patients who are at risk of developing hepatic fibrosis. The aim of the study was to explore the correlation between FIB-4 index and the decline of cognitive function among older patients with hypertension. The study used a cross-sectional design to analyze data obtained from the NHANES 2011-2014. The significance of the FIB-4 index correlation with cognitive function in individuals over the age of 60 was evaluated via multivariate regression models. The nonlinear link was described and fitted smoothed curves. There were a total of 2039 participants in the study, and those with a higher FIB-4 index were more susceptible to developing cognitive decline. In the completely adjusted model, the association remained statistically significant between the FIB-4 index and poor cognitive function as measured by CERAD: Total Score (OR = 0.72, 0.57-0.91), Animal Fluency Score (OR = 0.66, 0.48-0.91), and Digit Symbol Score (OR = 0.36, 0.17-0.77). A nonlinear association was found between the FIB-4 and poor cognitive ability: Total Score, CERAD: Score Delayed Recall, Digit Symbol Score, and Animal Fluency Score. In elderly patients with hypertension, a high FIB-4 index is correlated with an increased prevalence of cognitive decline. Hence, the FIB-4 index could potentially serve as a valuable tool for determining individuals with hypertension who are susceptible to both liver-related complications and cognitive impairment.

The systemic immune-inflammation index (SII) and trouble sleeping are independent risk factors for nonalcoholic fatty liver disease (NAFLD). Nevertheless, studies investigating the combined effects of the SII and troubled sleeping on NAFLD are lacking. In this study, we investigated the independent relationships and interactions between trouble sleeping and the SII among patients with NAFLD.

Data from seven survey cycles of the National Health and Nutrition Examination Survey (NHANES) (2005-2018) were analyzed. The SII was obtained by counting platelets, neutrophils, and lymphocytes. NAFLD was diagnosed using the US fatty liver index. Trouble sleeping was diagnosed using a sleep disorder questionnaire. The correlation between trouble sleeping and the SII in NAFLD was investigated using multiple regression analysis, subgroup stratification, interaction tests, and restricted cubic spline, and the presence or absence of additive or multiplicative interactions was determined. Additionally, mediation analyses were performed to explore the role of the SII in mediating the effects of trouble sleeping on NAFLD.

The survey included 10 963 participants. Multivariate logistic regression revealed that SII (OR: 1.21, 95% CI 1.08-1.35) and trouble sleeping (OR: 1.24, 95% CI 1.05-1.47) were positively correlated with NAFLD. For NAFLD, an additive but not multiplicative interaction was noted between the SII and trouble sleeping. The SII partially mediated the association between trouble sleeping and NAFLD, accounting for approximately 3.11% of the total effect (95% CI 0.01-0.05).

The SII and trouble sleeping were independently correlated with NAFLD risk. Furthermore, a combined effect may exist between SII and trouble sleeping, which increases the risk of NAFLD.

Polychlorinated Biphenyls (PCBs) persist in the environment and accumulate in humans. Currently, there is a lack of understanding about the overall impact of PCBs on human health, and effective interventions for exposed populations are insufficient.

Our study aimed to assess the impact of PCBs on various diseases and mortality risks using data from the National Health and Nutrition Examination Survey, while proposing lifestyle adjustments, particularly dietary modifications, to mitigate mortality risk. Statistical analyses employed principal component analysis, multifactorial logistic regression, multifactorial Cox regression, comorbidity network analysis, and machine learning prediction models.

Results indicated significant associations between 7 types of PCBs and 12 diseases (p < 0.05), with 6 diseases showing significant positive correlations (OR > 1, p < 0.05), along with listing the 25 most relevant diseases, such as asthma and chronic bronchitis (OR [95% CI] = 5.85 [4.37, 7.83], p < 0.0001), arthritis and osteoporosis (OR [95% CI] = 6.27 [5.23, 7.55], p < 0.0001). This suggested that PCBs may be intimately involved in the development and progression of multiple diseases. By constructing multidimensional machine learning models and conducting multiple iterations for precision and error measurement, PCBs may have the potential to become specific biomarkers for certain diseases in the future. Building upon this, we further suggested that controlling dietary intake to reduce dietary inflammatory index (DII) could lower mortality and disease risks.

While PCBs were independent risk factors for mortality, substantial evidence suggested that adjusting DII might mitigate the adverse effects of PCBs to some extent. Further physiological mechanisms require deeper exploration through additional research.

The purpose of this study was to explore the correlation between Hashimoto's thyroiditis and Metabolic dysfunction-associated fatty liver disease (MAFLD), and at the same time to screen high-risk groups for liver fibrosis in MAFLD, find out the high-risk related indicators. The physical examination population was included as the study subjects and was grouped according to the diagnostic criteria for MAFLD. APRI > 1 or NFS > 0.676 or FIB-4 > 2.67were used to assess people at high risk of liver fibrosis, and logistic regression analysis was used to identify risk factors associated with high risk of liver fibrosis in MAFLD. ROC curves are used to look for indicators of diagnostic value. The proportion of people with Hashimoto's thyroiditis was lower in the MAFLD group. The MAFLD high-risk group for liver fibrosis had higher TSH levels, lower FT3 and FT4 levels, higher TGAB levels, and differences in biochemical markers. Age, BMI, FBG, and AST are risk factors for the high risk of liver fibrosis in MAFLD patients. ROC curve analysis showed that the AUC of age was 0.741 (0.721-0.761), and the optimal stage value was 57.5 years, while the AUC of AST was 0.729 (0.707-0.751), and the optimal cut-off value was 39.5 U/L. Age, BMI, FBG, and AST are risk factors for the high risk of liver fibrosis in MAFLD patients.The age is greater than or equal to 57.5 years, or the AST is greater than or equal to 39.5 U/L, indicating that the MAFLD patients are at high risk of liver fibrosis.

To investigate the independent and joint associations of vitamin B12 and methylmalonic acid (MMA) with all-cause, cardiovascular disease (CVD), and cancer mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

We included 6797 individuals with MASLD from the U.S. National Health and Nutrition Examination Survey. Serum MMA was measured using gas/liquid chromatography-mass spectrometry. Serum vitamin B12 was measured using commercial kits. The separate and joint associations of dietary intake and serum vitamin B12 (cutoff: 400 pg/mL) and MMA (cutoff: 250 nmol/L) levels with mortality were assessed by Cox proportional hazards regression.

During a median follow-up of 9.3 years, 1604 deaths were documented, including 438 from CVD and 365 from cancer. In MASLD patients, dietary intake and serum vitamin B12 did not associate with mortality, while MMA was associated with a 1.35-fold increased risk of all-cause mortality (P-trend < 0.001). The adjusted hazard ratios for the joint association of vitamin B12 and MMA with all-cause and CVD mortality were 1 in the B12lowMMAlow group (reference), 1.02 (0.87-1.20) and 1.15 (0.90-1.47) in the B12highMMAlow group, 1.55 (1.29-1.86) and 1.84 (1.28-2.65) in the B12lowMMAhigh group, and 1.82 (1.49-2.21) and 2.28 (1.40-3.71) in the B12highMMAhigh group, respectively. The joint association was modified by serum folate (P-interaction = 0.001).

In MASLD patients, MMA rather than dietary and serum vitamin B12 was positively associated with all-cause mortality. The joint effect of high levels of MMA and vitamin B12 showed the strongest associations with all-cause and CVD mortality, with a significant interaction with serum folate.

Approximately 10-20% of individuals with non-alcoholic fatty liver disease (NAFLD) are lean, and the underlying pathophysiology is not yet understood. This study aims to explore the characteristics and the diagnostic value of triglyceride-glucose index (TyG) in early diagnosis of lean NAFLD.

99 patients with lean NAFLD and 1891 healthy controls were included in the health examination. The characteristics were compared between groups. Restricted cubic spline was utilized to analyze the relationship between TyG index and the risk of lean NAFLD. Logistic regression and receiver operating curve (ROC) were applied to explore the diagnostic value of TyG index for lean NAFLD.

Overall, 99 (4.97%) patients had lean NAFLD. Patients with lean NAFLD have significant abnormal glycolipid metabolism and higher TyG index. Restriction cube spline analysis showed a significant dose-response relationship between the TyG index and risk of lean NAFLD. After adjusting for confounders, the relationship remained and the risk of developing lean NAFLD increased 2.99 times for per unit increase of TyG index (95% CI: 1.94, 4.67, P<0.001). The areas under the ROC of the TyG index for lean NAFLD detection were 0.851 (0.815 to 0.886).

The TyG index is positively associated with the risk of developing lean NAFLD and could be a useful marker for early diagnosis of lean NAFLD.

Numerous studies emphasize the pivotal role of inflammation in metabolic dysfunction-associated steatotic liver disease (MASLD) development. Some link specific systemic immune biomarkers (e.g., systemic immuno-inflammatory index [SII], neutrophil-to-albumin ratio [NPAR] and neutrophil-to-lymphocyte ratio [NLR]) to hepatic steatosis risk. However, the relevance of other markers like systemic immune-inflammation index [SIRI], platelet-to-lymphocyte ratio [PLR] and lymphocyte/monocyte ratio [LMR] in MASLD remains unclear. Limited literature covers all six markers together. This study aims to investigate the association between SII, SIRI, LMR, NLR, PLR, and NPAR and MASLD, assessing their predictive value.

In this cross-sectional analysis of adults from NHANES (2007-2018), we investigated the relationship between six systemic immune biomarkers, stratified by quartiles: quartile1 (Q1), quartile2 (Q2), quartile3 (Q3) and quartile4 (Q4), and the outcome of MASLD assessed by Fatty Liver Index (FLI) and United States Fatty Liver Index (USFLI). Logistic regression and restricted cubic splines (RCS) were employed to assess the association between systemic immune biomarkers and MASLD risks. Propensity score matching controlled for potential confounders, and receiver operating characteristic (ROC) curve analysis evaluated the biomarkers' predictive performances for MASLD. Subgroup and interaction analysis were conducted to explore the effects of systemic immune biomarkers on MASLD risks. Multicollinearity was quantified using the variance inflation factor.

In total, 14,413 participants were included and 6,518 had MASLD. Compared with non-MASLD, participants with MASLD had higher SII, SIRI, NLR, PLR, and NPAR (p < 0.001). SII, SIRI, NLR, and NPAR were further validated in the restricted cubic splines (RCS) regression model and identified as positive linear relationships (p for nonlinear >0.05). The prevalence of MASLD increased with the Q4 of SII [OR = 1.47, 95%CI (1.24, 1.74)], SIRI [OR = 1.30, 95%CI (1.09, 1.54)], NLR [OR = 1.25, 95%CI (1.04, 1.49)], PLR [OR = 1.29, 95%CI (1.09, 1.53)] and NPAR [OR = 1.29, 95%CI (1.09, 1.54)] compared to the Q1 after adjusting for the bias caused by potential confounders. However, the propensity score matching analysis only supported an association between the highest SII, SIRI, NLR NPAR and the risk of MASLD. The results of the subgroup analysis showed considerable robustness in the relationship.

Higher SII, SIRI, NLR and NPAR were positively associated with a heightened risk of MASLD. NPAR showed the superior predictive value, followed by SII, SIRI and NLR. This needs to be validated in additional longitudinal studies and clinical trials.

Evidence from observational studies on the association between folate and metabolic dysfunction-associated steatotic liver disease (MASLD) is conflicting.

This study aimed to investigate the association between serum folate concentration and MASLD and further assess the causal relationship using Mendelian randomization (MR) analysis.

To investigate the causal relationship between serum folate and MASLD, we conducted a cross-sectional study that selected 1,117 participants from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). The association between serum folate level and the risk of MASLD was evaluated under a multivariate logistic regression model. In addition, we conducted a two-sample MR study using genetic data from a large genome-wide association study (GWAS) to compare serum folate level (37,465 individuals) and MASLD (primary analysis: 8,434 cases/770,180 controls; Secondary analysis:1,483 cases/17,781 controls) were performed to infer causal relationships between them. Inverse variance weighted (IVW) was used as the primary method of MR Analysis.

The results from the NHANES database showed that Tertile 3 group (Tertile 3: ≥ 48.6 nmol/L) had a significantly lower risk (OR = 0.58, 95% CI: 0.38-0.88, p = 0.010) of MASLD than Tertile 1 group (Tertile 1: < 22.3 nmol/L) after complete adjustments. However, in the IVW of MR analysis, there was no causal relationship between serum folate level and MASLD risk in the primary analysis (OR = 0.75, 95% CI: 0.55-1.02, p = 0.065) and secondary analysis (OR = 0.83, 95% CI: 0.39-1.74, p = 0.618).

In observational analyses, we observed an inverse association between higher serum folate concentrations and a reduced risk of MASLD. Our MR study generated similar results, but the association failed to reach the significance threshold of p < 0.05, suggesting that our MR study does not support a causal relationship between serum folate levels and MASLD risk. Additional research involving a larger number of cases would contribute to enhancing the confirmation of our preliminary findings.

Background and Objectives: The goal of this study was to assess the impact of supplementation with a combination of nutrients on metabolic-dysfunction-associated steatotic liver disease (MASLD)-related liver parameters, and other parameters related to metabolic syndrome in adults with obesity. These measurements included anthropometric and lipid profiling, and FibroScan technology (controlled attenuation parameter (CAP) and transient elastography (TE) values). Materials and Methods: A double-blind, placebo-controlled pilot clinical trial was conducted over a three-month treatment period. Adults with metabolic syndrome and obesity were allocated to receive either a cocktail of nutrients with defined daily dosages (5-MTHF, betaine, alpha-linolenic acid, eicosapentaenoic acid, choline bitartrate, docosahexaenoic acid, and vitamin B12) or a placebo. The participants were evaluated at the start and the end of the three-month treatment period. Results: A total of 155 participants entered the study, comprising 84 in the treatment group and 71 in the placebo group. The administration of the nutritional supplement resulted in a notable reduction in both CAP and TE scores when compared to the placebo group. The treatment group exhibited a mean reduction in CAP of 4% (p < 0.05) and a mean reduction in TE of 7.8% (p < 0.05), indicative of a decline in liver fat content and fibrosis. Conclusions: The supplementation over a period of three months led to a significant amelioration of liver fibrosis and steatosis parameters in adults with metabolic syndrome and obesity. These findings suggest that this supplementation regimen could be a beneficial adjunct therapy for improving liver health in adults with obesity-induced MASLD.

and design: Considering the clinical link between non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (AS), we performed bioinformatics analysis to uncover their pathogenic interrelationship.

Data from the U.S. National Health and Nutritional Examination Survey (NHANES) 1999-2018 were included. Among 4851 participants in NHANES, NAFLD was significantly associated with atherosclerotic cardiovascular disease risk (ASCVD risk) (OR = 2.32, 95%CI: 2.04-2.65, P < 0.0001). We conducted WGCNA analysis for NAFLD (GSE130970) and AS (GSE28829) and identified three modules positively related to NAFLD severity and two modules accelerating atherosclerosis plaque progression. 198 key-modules genes were obtained via overlapping these modules. Next, we mined the disease-controlled differentially expressed genes (DEGs) from NAFLD (GSE89632) and AS (GSE100927), respectively. The final common risk genes (ACP5, TP53I3, RPS6KA1, TYMS, TREM2, CA12, and IFI27) were defined by intersecting the upregulated DEGs with 198 genes and validated in new datasets (GSE48452 and GSE43292). Importantly, they showed good diagnostic ability for NAFLD and AS. Immune infiltration analysis showed both illnesses have dysregulated immunity. Analysis of single-cell sequencing datasets NAFLD (GSE179886) and AS (GSE159677) uncovered different abnormal expressions of seven common genes in different immune cells while highlighting metabolic disturbances including upregulation of fatty acid biosynthesis, downregulation of fatty acid degradation and elongation.

We found 7 shared hub genes with good diagnostic ability and depicted the landscapes of immune and metabolism involved in NAFLD and AS. Our results provided a comprehensive association between them and may contribute to developing potential intervention strategies for targeting both disorders based on these risk factors.

Though years of education have been connected to nonalcoholic fatty liver disease (NAFLD), the exact mechanism underlying this linkage is still unknown. To investigate the causal association between years of education and NAFLD, we will use a 2-sample Mendelian randomization (MR) technique. : Genome-wide association studies data on years of education (n = 766,345) and genome-wide association studies data on nonaffiliated mental illness (n = 778,614) were screened for genetic variations as instrumental variables in the Mr-Base database. MR-Egger regression, weighted median, and inverse variance weighted were used in the MR analysis. Years of education (odds ratio = 0.63; 95% confidence interval: 0.47-0.79; P = 1.28 × 10-8) might be protective against the development of NAFLD. Among the sensitivity analyses were the following: the MR-Egger intercept test revealed P > .05, suggesting that there was no horizontal pleiotropy in the MR analysis and that the inverse variance weighted results were trustworthy; the Cochran Q test revealed P > .05, suggesting that there was no heterogeneity between the 2 samples; Funnel plot results demonstrated that there was no bias in the link between the measure of variability and the impact size. Leave-1-out analysis results demonstrated that no 1 single nucleotide polymorphism had a significant effect on the study's results, showing that the MR results were stable. This study has investigated the connection between years of education and NAFLD, offering novel suggestions for NAFLD treatment and prevention.

We aim to explore the relationship between the newly introduced CVH indicator "Life's Essential 8 (LE8)" and cirrhosis.

The global burden of cirrhosis is increasing, with a rising number of deaths, leading to significant societal and economic challenges. Cardiovascular health (CVH) has been found to have potential associations with liver diseases.

All participants aged 20 and older from National Health and Nutrition Examination Survey 2005 to 2018 were included. CVH was accessed by LE8, consisting of 4 health behaviors (diet, physical activity, nicotine exposure, and sleep health) and 4 health factors (body mass index, lipid levels, blood sugar, and blood pressure). Cirrhosis was determined based on abnormal liver function test results, with an aspartate aminotransferase to platelet ratio index >2. Participants' mortality status was obtained by matching with the National Death Index and all-cause mortality served as the follow-up endpoint.

This extensive cross-sectional study reveals that LE8 was not associated with cirrhosis. A higher health behaviors score was associated with lower cirrhosis. Moreover, there is an inverse U-shaped relationship between the LE8 score and all-cause mortality in participants with cirrhosis, signifying a decrease in all-cause mortality when LE8 surpasses 60. A greater health behaviors score is linked to a decreased proportion of all-cause mortality in cirrhosis patients.

Maintaining better health behaviors may be beneficial for cirrhosis, especially through a balanced diet, regular exercise, smoking cessation, and quality sleep.

Folate is a water-soluble B vitamin involved in the synthesis of purines and pyrimidines and is one of the essential vitamins for human growth and reproduction. Folate deficiency due to low dietary intake, poor absorption of folate, and alterations in folate metabolism due to genetic defects or drug interactions significantly increases the risk of diseases such as neural tube defects, cardiovascular disease, cancer, and cognitive dysfunction. Recent studies have shown that folate deficiency can cause hyperhomocysteinemia, which increases the risk of hypertension and cardiovascular disease, and that high homocysteine levels are an independent risk factor for liver fibrosis and cirrhosis. In addition, folate deficiency results in increased secretion of pro-inflammatory factors and impaired lipid metabolism in the liver, leading to lipid accumulation in hepatocytes and fibrosis. There is substantial evidence that folate deficiency contributes to the development and progression of a variety of liver diseases, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), viral hepatitis, hepatic fibrosis, and liver cancer. Here we review key studies on the role of folate in the pathophysiology of liver diseases, summarize the current status of studies on folate in the treatment of liver diseases, and speculate that folate may be a potential therapeutic target for liver diseases.

Obesity, whose prevalence is increasing globally, is malnutrition that causes micro/macronutrients and vitamin deficiencies in adolescents. Vitamin B12 plays a prominent role in the body systems such as remethylation, deoxidation, and DNA synthesis. We aimed to examine the relationship between severe obese/obese adolescents and vitamin B12 levels in this study. This study was conducted as a case-control study consisting of 44 obese and 40 healthy control adolescents aged 11-17 years. Obesity was diagnosed using body mass index (BMI) charts defined by the World Health Organization according to age and gender. Vitamin B12 deficiency was found to be 34.1% in the patient obesity group, while it was 12.5% in the control group (p = 0.02). Homeostatic Model Assessment for Insulin Resistance levels were found to be 3.09 (1.9-5.29) higher in the severely obese group (p < 0.001). The median level of vitamin B12 in the obese group was 173 (122.5-220.7) in the severe obese group, 197 (146.5-302.7) in the obese group, and 252.5 (192.8-302) in the control group (p = 0.021). We found that obesity has a 1.6-fold decreasing effect on vitamin B12 levels. This study shows the clinician the importance of monitoring BMI and vitamin B12 levels in obese adolescents, given the effects of vitamin B12 on neuronal migration, metabolic reactions, and many systems in the body. Further researches are needed to investigate the pathophysiology and effect of low vitamin B12 levels in obese adolescents.

Metabolic-associated fatty liver disease (MAFLD) is a chronic liver disease characterized by the excessive accumulation of fat in hepatocytes. However, due to the complex pathogenesis of MAFLD, there are no officially approved drugs for treatment. Therefore, there is an urgent need to find safe and effective anti-MAFLD drugs. Recently, the relationship between the gut microbiota and MAFLD has been widely recognized, and treating MAFLD by regulating the gut microbiota may be a new therapeutic strategy. Natural products, especially plant natural products, have attracted much attention in the treatment of MAFLD due to their multiple targets and pathways and few side effects. Moreover, the structure and function of the gut microbiota can be influenced by exposure to plant natural products. However, the effects of plant natural products on MAFLD through targeting of the gut microbiota and the underlying mechanisms are poorly understood. Based on the above information and to address the potential therapeutic role of plant natural products in MAFLD, we systematically summarize the effects and mechanisms of action of plant natural products in the prevention and treatment of MAFLD through targeting of the gut microbiota. This narrative review provides feasible ideas for further exploration of safer and more effective natural drugs for the prevention and treatment of MAFLD.

Aim: This study used urinary caffeine and its metabolites to evaluate their relationships with liver steatosis and advanced liver fibrosis. Methods: A total of 2068 adult participants with required data were filtered from the 2009-2014 National Health and Nutrition Examination Survey (NHANES) cycles. Non-invasive scores were applied to define liver steatosis and advanced liver fibrosis. Logistic regression models, weighted quantile sum (WQS) regression models, quantile-based g-computation (QG-Comp) models, and restricted cubic spline (RCS) regression models were used to assess the associations of urinary caffeine and its metabolites with liver steatosis and advanced liver fibrosis. A series of additional analyses were conducted to examine the subgroup-specific differences and test the robustness of the observed results. Results: The major caffeine metabolite mixture and most individual caffeine metabolites were found to be negatively associated with the risk of advanced liver fibrosis with subgroup-specific variations. Only 7-MX consistently showed a negative association with liver steatosis in all analyses, while no association was observed between the major caffeine metabolite mixture and liver steatosis. Conclusion: The major caffeine metabolite mixture and most individual urinary caffeine metabolites exhibited inverse associations with advanced liver fibrosis with subgroup differences. Further prospective and experimental studies are urgently needed to verify our results and further identify the possible mechanisms.

Evidence from epidemiological literature on the association of circulating micronutrients with risk of nonalcoholic fatty liver disease (NAFLD) is inconsistent. We aimed to elucidate the causal relationships using Mendelian randomization (MR). Single-nucleotide polymorphisms associated with 14 circulating micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B6, B12, C, D, K1 and zinc) were employed as instrumental variables. Summary level data for NAFLD were obtained from a genome-wide association study (GWAS) meta-analysis of 8434 cases and 770,180 controls (discovery stage) and another two datasets including 1483 NAFLD cases and 17,781 controls (replication stage 1) and 2134 NAFLD cases and 33,433 controls (replication stage 2). Inverse variance-weighted method (IVW) was used as primary analysis, supplemented with a series of sensitivity analysis. Genetically predicted higher β‑carotene levels were suggestively associated with reduced NAFLD risk [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.66-0.99; P = 0.047], whereas the association did not survive the false discovery rates (FDR) correction (PFDR = 0.164). Genetically predicted circulating iron (OR 1.16, 95% CI 1.05-1.29; P = 0.006, PFDR = 0.028), selenium (OR 1.11, 95% CI 1.03-1.20; P = 0.005, PFDR = 0.028) and vitamin B12 (OR 1.08, 95% CI 1.03-1.13; P = 0.002, PFDR = 0.028) were significantly associated with increased risk of NAFLD. Moreover, the findings were consistent in individual datasets (Pheterogeneity > 0.05) and confirmed in sensitivity analysis. Our study provided evidence that circulating iron, selenium and vitamin B12 might be causally linked to the risk of NAFLD, which deserves further exploration of the potential biological mechanism.

To analyze the relationship between leg skeletal muscle mass index (LSMI) and non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM) and the ability of LSMI to predict NAFLD.

Two hundred patients with T2DM and NAFLD treated at Changzhou Second People's Hospital Affiliated with Nanjing Medical University and the National Metabolic Management Center from June 2022 to June 2023 were divided into four LSMI quartiles. The clinical information from the four patient groups was compared, and the relationship between type 2 diabetes and LSMI and NAFLD was examined. We used receiver operating characteristic curves to determine how well the LSMI predicts NAFLD in T2DM.

The lowest quartile (Q1) had a higher prevalence of NAFLD than group Q4 (P < 0.05). LSMI was negatively associated with body mass index, LS, CAP, and other markers (P < 0.05). Receiver operating characteristic curve analysis LSMI predicted NAFLD with an ideal critical value of 0.64 and an area under the curve of 70.9%. The combined predictive value of the LSMI and the appendicular skeletal muscle mass index was more significant.

Reduced LSMI is associated with NAFLD.

Most studies have explored the relationship between serum total folate and nonalcoholic fatty liver disease (NAFLD) in adults, but there has been no study on the relationship between different folate forms and hepatic steatosis or liver stiffness in adolescents.

To investigate the association of different folate forms with hepatic steatosis or liver stiffness in adolescents, and further explore the intermediary role of BMI in this relationship.

The cross-sectional study included 549 participants from the 2017-2018 National Health and Nutrition Inspection Survey (NHANES) survey cycle who had complete data. Four folate data (red blood cell folate, serum total folate, 5-methyl-tetrahydrofolate and folic acid) were included in our study. Controlled attenuation parameters (CAP) and liver stiffness came from the results of liver ultrasound transient elastography. We used linear regression to analyze the relationship between different forms of folate and CAP or liver stiffness, and logistic regression to analyze the relationship between different forms of folate and NAFLD or significant fibrosis. We also used restricted cubic splines to analyze the nonlinear relationship between different forms of folate and NAFLD or significant fibrosis. Finally, we used regression-based intermediary analysis to distinguish the direct and BMI-mediated effects of folate on CAP or liver stiffness. All the analyses adjusted the relevant covariates.

The means of CAP and liver hardness in this study were 223.02dB/m and 5.03kPa, respectively. We found that in model 2, there was a negative correlation between serum total folate (β: -18.53; 95%CI: -29.32 to -7.73) or 5-methyltetrahydrofolate (β: -14.13; 95%CI: -28.98 to -7.86) and CAP. However, when the BMI was further adjusted in model 3, this negative correlation no longer existed (serum total folate: β: -8.36; 95%CI: -17.69 to 0.97; 5-methyltetrahydrofolate: β: -8.05; 95%CI: -17.19 to 1.09). Similarly, we found a negative correlation between serum total folate or 5-Methyl-tetrahydrofolate and liver stiffness in model 2. There was no significant correlation between red blood cell folate or folic acid and CAP or liver stiffness in either model 2 or model 3. The nonlinear relationship between different folate forms and NAFLD or significant fibrosis was not significant. It is estimated that 76% of the total association between serum total folate and CAP is mediated by BMI. The mediating proportion of BMI in the total correlation between serum total folate and liver stiffness was 50%. Similarly, we found that BMI significantly mediated the relationship between 5-Methyl-tetrahydrofolate and CAP or liver stiffness, with a mediating ratio of 77% and 49%, respectively.

Our results show that serum total folate or 5-Methyl-tetrahydrofolate are negatively correlated with hepatic steatosis or liver stiffness in adolescents, and BMI plays major mediating role in this relationship. Our findings emphasize the importance of monitoring the concentration of serum folate, not just the serum total folate concentration.

Vitamin B12 (or cobalamin) is an essential vitamin for DNA synthesis, fatty acid and protein metabolism as well as other metabolic pathways fundamental to the integrity of cells and tissues in humans. It is derived from the diet and mostly stored in the liver. Its deficiency has been associated with metabolic derangements, i.e., obesity, glucose intolerance, increased lipogenesis and metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH). However, data with regard to body weight across the whole spectrum (from underweight to severe obesity) in children and young individuals are scarce. The present study aims to describe the association between serum total vitamin B12 and body mass index (BMI) ranging from underweight to severe obesity in a large population of children, adolescents and young adults. This study also investigates associations with visceral adiposity, glucose and lipid metabolism and liver dysfunction. A cross-sectional, single-centre study was conducted at the Paediatrics and Endocrinology units of the "Bambino Gesù Children Hospital", a tertiary referral institution for eating disorders. Clinical charts were reviewed and 601 patients aged from 5 to 25 years were enrolled in order to analyse anthropometric, auxological, clinical, biochemical and liver ultrasound data using robust statistical approaches. Analyses were adjusted for potential confounders. A reduction in serum total B12 levels was associated with a linear increase in body weight, as expressed by WHO BMI SDS (r = -0.31, p < 0.001, BCa 95% -0.38, -0.24). Lower B12 levels were associated with higher waist circumference but only in pubertal girls (r = -0.33, p = 0.008, BCa 95% -0.53, -0.11). Hepatic insulin resistance was higher in males with lower B12 levels (B = -0.003 (-0.007, -0.0001), p = 0.039), but not in females, whereas whole-body insulin resistance was unaffected. Serum lipid profiles (total, HDL and LDL cholesterol and triglycerides) were not influenced by serum cobalamin levels. However, lower cobalamin levels were associated with higher grading of ultrasound-scored hepatic steatosis (ptrend = 0.035). Lastly, both AST and ALT showed a significant and direct correlation with total B12 levels in underweight (r = 0.22 and 0.24, p = 0.002 and <0.001, respectively) and severely obese subjects (r = 0.24 and 0.32, p = 0.002 and <0.001). In conclusion lower vitamin B12 levels are associated with higher body weight, adiposity and with worse metabolic health in a large population of children, adolescents and young adults.

Non-alcoholic fatty liver disease (NAFLD) is increasingly common globally, particularly among postmenopausal women. Diet plays a fundamental role in the treatment of NAFLD. However, clinical research on the dietary intakes of B vitamins, specifically in postmenopausal women, is scant. Hence, it is imperative to study the impact of B vitamin dietary intake in postmenopausal women.

This study utilized National Health and Nutrition Examination Survey (NHANES) data for 668 postmenopausal women. Logistic regression analysis was conducted to investigate the association of the intakes of B vitamins with hepatic steatosis and liver fibrosis prevalence. The analysis accounted for various covariates and employed restricted cubic spline analysis to examine potential nonlinear relationships. Additionally, interactions among age, diabetes, and B-vitamin intakes, as well as the interaction between folate and vitamin B12 intake, were explored.

Higher intakes of folate [0.30 (0.10-0.88)], choline [0.26 (0.07-0.95)], vitamin B1, and vitamin B2 were associated with a reduced risk of hepatic steatosis in postmenopausal women. The associations of niacin (P-nonlinear = 0.0003), vitamin B1 (P-nonlinear = 0.036), and vitamin B2 (P-nonlinear<0.0001) intakes with hepatic steatosis showed a nonlinear pattern. However, no significant associations were observed between the intakes of niacin, vitamin B6 and vitamin B12 and hepatic steatosis. Furthermore, there were no significant associations between B-vitamin intakes and liver fibrosis. No interaction effects were observed.

Dietary intakes of folate, choline, vitamin B1, and vitamin B2 may be associated with liver steatosis in postmenopausal women, these results suggest that optimizing the intake of these specific B vitamins may have a protective effect against liver steatosis in postmenopausal women, offering valuable insights into potential dietary strategies to promote their well-being.

Oxidative stress is an important contributor to the progression of nonalcoholic fatty liver disease (NAFLD), but whether dietary and lifestyle pro- and antioxidants may have combined or independent effects on NAFLD, and advanced liver fibrosis (AHF) remains unclear. We aimed to elucidate the relationship between a well-established oxidative balance score (OBS) and NAFLD/AHF.

This was a cross-sectional study. We included adult participants with complete data from the National Health and Nutrition Examination Survey 1999-2018. Survey-weighted adjusted multivariate regression analyses were used to examine the association of all OBS with NAFLD/AHF. A combination of restricted cubic splines, mediation analysis, stratified analysis, and sensitivity analysis were used to further elucidate these associations.

We included 6,341 eligible adult participants with prevalence of NAFLD and AHF of 30.2 and 13.9%, respectively. In the fully adjusted model, the highest quartile of OBS, dietary OBS, and lifestyle OBS were associated with 65, 55, and 77% reduced risk of NAFLD, respectively, compared with the reference population, respectively. However, all OBS were not associated with the risk of AHF. All OBS were nonlinearly associated with risk of NAFLD and had a more pronounced reduced risk for OBS, dietary OBS, and lifestyle OBS after exceeding 26, 21, and 5 points, respectively. OBS may exert a protective effect indirectly through inflammation, oxidative stress, and glycolipid metabolism markers. Stratification and sensitivity analyses demonstrate the robustness of our findings.

All OBS were nonlinearly and negatively associated with NAFLD risk. These effects may exert indirectly through inflammation, oxidative stress, and glycolipid metabolism markers.