Moderate-to-Heavy Alcohol Consumption May Cause a Significant Decrease in Serum High-Density Lipoprotein Cholesterol in Middle-Aged Women: A Cohort Study of the National Database Study in the Kanto 7 Prefectures-4.

Aims Little is known about the association between habitual alcohol consumption and serum high-density lipoprotein cholesterol (HDL-C) in women. We aimed to investigate this association in middle-aged Japanese women in a community-based cohort study using conventional statistical analyses and explainable artificial intelligence (AI) analysis. Methods We retrospectively investigated the association between alcohol consumption and HDL-C after 10 years in 90,053 women aged 40-64 years whose drinking habits were generally consistent for 10 years. Results After 10 years, 11.3% and 17.9% of subjects had serum HDL-C decreased by ≥10 mg/dL and ≥10%, respectively. In unadjusted analysis, moderate-to-heavy alcohol consumption may both increase and decrease serum HDL-C levels after 10 years. After adjustment for potential confounding factors, moderate (23-45 g/day) and heavy (≥46 g/day) alcohol consumption were each significantly associated with decreases in HDL-C (OR (95% CI): 1.18 and 1.36 (1.11-1.26 and 1.21-1.53) for ≥10 mg/dL, 1.11 and 1.29 (1.05-1.17 and 1.17-1.43) for ≥10%), but not associated with an increase in HDL-C (0.96 and 0.98 (0.91-1.01 and 0.89-1.08) for ≥10 mg/dL, 0.97 and 0.96 (0.93-1.01 and 0.88-1.05) for ≥10%). Further analysis after adjustment for baseline serum HDL-C showed the same results. AI analysis showed that alcohol consumption was the 8th positive contributor to the decrease in HDL-C, following baseline high HDL-C (≥77 mg/dL), high low-density lipoprotein cholesterol (≥133 mg/dL), high body mass index (≥23.1 kg/m2), pharmacotherapy for dyslipidemia, high triglycerides (≥70 mg/dL), age 44-64 years, and smoking. Heavy alcohol consumption was a more positive contributor to decreased HDL-C than were other alcohol consumption levels. Conclusions Habitual moderate-to-heavy alcohol consumption may cause a significant decrease in serum HDL-C in middle-aged women, which may be modified by concomitant factors.

Agreement in All-in-One Dataset between Diagnosis and Prescribed Medication for Common Cardiometabolic Diseases in the NDB-K7Ps.

The Japanese National Database (NDB), a useful data source for epidemiological studies, contains information on health checkups, disease diagnoses, and medications, which can be used when investigating common cardiometabolic diseases. However, before the initiation of an integrated analysis, we need to combine several pieces of information prepared separately into an all-in-one dataset (AIOD) and confirm the validation of the dataset for the study. In this study, we aimed to confirm the degree of agreement in data entries between diagnoses and prescribed medications and self-reported pharmacotherapy for common cardiometabolic diseases in newly assembled AIODs. The present study included 10,183,619 people who underwent health checkups from April 2018 to March 2019. Over 95% of patients prescribed antihypertensive and antidiabetic medications were diagnosed with each disease. For dyslipidemia, over 95% of patients prescribed medications were diagnosed with at least one of the following: dyslipidemia, hypercholesterolemia, or hyperlipidemia. Similarly, over 95% of patients prescribed medications for hyperuricemia were diagnosed with either hyperuricemia or gout. Additionally, over 90% of patients with self-reported medications for hypertension, diabetes, and dyslipidemia were diagnosed with each disease, although the proportions differed among age groups. Our study demonstrated high levels of agreement between diagnoses and prescribed medications for common cardiometabolic diseases and self-reported pharmacotherapy in our AIOD.

Eating behaviour characteristics and dietary intake among Japanese junior high school students: A cross-sectional study.

BACKGROUND: Psychological characteristics of eating behaviour may be related to dietary habits. AIM: We investigated the association between eating behaviour characteristics and nutrition and food intake adequacy in Japanese adolescents. METHODS: This cross-sectional survey was conducted among 136 junior high school students (boys: 90, girls: 46) at a junior high school in Tokyo, Japan. Eating behaviour was categorised into three types (emotional, external, and restrained) using scores on the Japanese version of the Dutch Eating Behaviour Questionnaire. Dietary intake was assessed using a validated, brief self-administered diet history questionnaire. Inadequate nutrient intake was determined by counting the number of nutrients not meeting the dietary reference intake (DRI) for the Japanese population. The statistical analyses included Wilcoxon signed-rank tests, Spearman's rank correlation coefficient, and multiple regression analysis using JMP ver.14 (SAS Institute Inc., Cary, NC, USA). All reported p values are two-tailed, and p < 0.05 was regarded as statistically significant. RESULTS: Multiple regression analysis showed that restrained eating score was inversely associated with the number of nutrients not meeting the DRI (ß = - 0.28; p = 0.0027) and with total weight of snack intake (ß = - 0.30; p = 0.0010). Neither emotional nor external eating was significantly associated with the number of nutrients not meeting the DRI and with total weight of snack intake. CONCLUSIONS: These results suggest that adolescents with low restrained eating scores may have less self-control over their eating behaviour and may therefore have inadequate dietary intake.

Acute liver failure increases kynurenic acid production in rat brain via changes in tryptophan metabolism in the periphery.

The tryptophan metabolite, kynurenic acid (KYNA), is a preferential antagonist of the α7 nicotinic acetylcholine receptor and N-methyl-d-aspartic acid receptor at endogenous brain concentrations. Recent studies have suggested that increased brain KYNA levels are involved in psychiatric disorders such as schizophrenia and depression. Most of the brain kynurenine (KYN), the KYNA precursor, comes from the periphery, and the liver has a central role in the peripheral tryptophan metabolism. In this study, the effect of acute liver failure (ALF) on brain KYNA production and on the peripheral tryptophan metabolism was investigated in rats. ALF was induced by administration of the hepatotoxin, thioacetamide (TAA). Brain KYNA levels were increased by TAA-induced ALF, and these increases were consistent with KYN levels in the brain, serum and liver. These results suggest that the ALF-induced increase in serum KYN contributes to the increase in brain KYNA via elevated KYN uptake within the brain. This increase in serum KYN level can be caused by the changes in tryptophan-2,3-dioxygenase activity in the liver and the immune-related activation of indoleamine-2,3-dioxygenase in extrahepatic tissues. These findings suggest that hepatic dysfunction may contribute to neurological and psychiatric diseases associated with increased KYNA levels.

Inhibition of Large Neutral Amino Acid Transporters Suppresses Kynurenic Acid Production Via Inhibition of Kynurenine Uptake in Rodent Brain.

The tryptophan metabolite, kynurenic acid (KYNA), is a preferential antagonist of the α7 nicotinic acetylcholine receptor and N-methyl-D-aspartic acid receptor at endogenous brain concentrations. Recent studies have suggested that increases of brain KYNA levels are involved in psychiatric disorders such as schizophrenia and depression, and regulation of KYNA production has become a new target for treatment of these diseases. Kynurenine (KYN), the immediate precursor of KYNA, is transported into astrocytes via large neutral amino acid transporters (LATs). In the present study, the effect of LATs regulation on KYN uptake and KYNA production was investigated in vitro and in vivo using an LATs inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). In the in vitro study, cortical slices of rat brain were incubated with a physiological concentration of KYN and 3 µmol/L-3 mmol/L BCH. BCH inhibited KYNA production and KYN uptake in a dose-dependent manner, and their IC50 values were 90.7 and 97.4 µmol/L, respectively. In the in vivo study, mice were administered KYN (50 mg/kg BW) orally and BCH (200 mg/kg BW) intravenously. Administration of KYN increased brain KYN and KYNA levels compared with the mice treated with vehicle, whereas additional administration of BCH suppressed KYN-induced elevations in KYN and KYNA levels to 50 and 70 % in the brain. These results suggest that inhibition of LATs prevented the increase of KYNA production via blockade of KYN uptake in the brain in vitro and in vivo. LATs can be a target to modulate brain function by regulation of KYNA production in the brain.

Amino acids inhibit kynurenic acid formation via suppression of kynurenine uptake or kynurenic acid synthesis in rat brain in vitro.

The tryptophan metabolite, kynurenic acid (KYNA), is a preferential antagonist of the α7 nicotinic acetylcholine receptor at endogenous brain concentrations. Recent studies have suggested that increase of brain KYNA levels is involved in psychiatric disorders such as schizophrenia and depression. KYNA-producing enzymes have broad substrate specificity for amino acids, and brain uptake of kynurenine (KYN), the immediate precursor of KYNA, is via large neutral amino acid transporters (LAT). In the present study, to find out amino acids with the potential to suppress KYNA production, we comprehensively investigated the effects of proteinogenic amino acids on KYNA formation and KYN uptake in rat brain in vitro. Cortical slices of rat brain were incubated for 2 h in Krebs-Ringer buffer containing a physiological concentration of KYN with individual amino acids. Ten out of 19 amino acids (specifically, leucine, isoleucine, phenylalanine, methionine, tyrosine, alanine, cysteine, glutamine, glutamate, and aspartate) significantly reduced KYNA formation at 1 mmol/L. These amino acids showed inhibitory effects in a dose-dependent manner, and partially inhibited KYNA production at physiological concentrations. Leucine, isoleucine, methionine, phenylalanine, and tyrosine, all LAT substrates, also reduced tissue KYN concentrations in a dose-dependent manner, with their inhibitory rates for KYN uptake significantly correlated with KYNA formation. These results suggest that five LAT substrates inhibit KYNA formation via blockade of KYN transport, while the other amino acids act via blockade of the KYNA synthesis reaction in brain. Amino acids can be a good tool to modulate brain function by manipulation of KYNA formation in the brain. This approach may be useful in the treatment and prevention of neurological and psychiatric diseases associated with increased KYNA levels.