Serum 5-Methyltetrahydrofolate Status Is Associated with One-Carbon Metabolism-Related Metabolite Concentrations and Enzyme Activity Indicators in Young Women.

Maintaining optimal one-carbon metabolism (OCM) is essential for health and pregnancy. In this cross-sectional study, folate status was assessed based on 5-methyltetrahydrofolate (5-MTHF) levels, and the association between 5-MTHF and OCM-related metabolites was investigated in 227 female Japanese university students aged 18-25 years. The participants were divided into high and low 5-MTHF groups based on their folate status. Serum samples of the participants were collected while they were fasting, and 18 OCM-related metabolites were measured using stable-isotope dilution liquid chromatography-electrospray tandem mass spectrometry. The association between serum 5-MTHF and OCM-related metabolite concentrations was assessed using Spearman's rank correlation coefficient. Serum 5-MTHF concentrations were negatively correlated with total homocysteine (tHcy) concentrations and positively correlated with S-adenosylmethionine (SAM) and total cysteine (tCys) concentrations. Serum 5-MTHF concentrations demonstrated a stronger negative correlation with tHcy/tCys than with tHcy alone. The negative correlation between betaine and tHcy concentrations was stronger in the low 5-MTHF group than in the high 5-MTHF group. The 5-MTHF status could be linked to Hcy flux into the transsulfuration pathway via SAM. Therefore, the tHcy/tCys ratio may be a more sensitive indicator of the 5-MTHF status than tHcy alone. Furthermore, a low 5-MTHF status can enhance Hcy metabolism via betaine.

Association of maternal blood and umbilical cord blood plasma fatty acid levels with the body size at birth of Japanese infants.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mainly obtained from fish, have been implicated in fetal development. Because few studies have examined maternal and umbilical cord blood fatty acid levels and infant body size in Japan with a fish-eating culture, we examined differences in plasma fatty acid levels in pregnant women and infant size at birth. This study is a large birth cohort study of 1476 pairs of Japanese pregnant women and their infants. Maternal blood DHA levels and infant birth weight showed a positive relationship. However, analysis adjusted for gestational age did not reveal correlations. Negative relationships were found between cord blood DHA levels and infant body size, and between the difference in mother-to-child DHA levels and infant body size. Thus, the smaller the birth size, the higher the differences in umbilical cord blood DHA levels and mother-to-child DHA levels when considering gestational age.

Longitudinal Analysis of One-Carbon Metabolism-Related Metabolites in Maternal and Cord Blood of Japanese Pregnant Women.

One-carbon metabolism (OCM) is a complex and interconnected network that undergoes drastic changes during pregnancy. In this study, we investigated the longitudinal distribution of OCM-related metabolites in maternal and cord blood and explored their relationships. Additionally, we conducted cross-sectional analyses to examine the interrelationships among these metabolites. This study included 146 healthy pregnant women who participated in the Chiba Study of Mother and Child Health. Maternal blood samples were collected during early pregnancy, late pregnancy, and delivery, along with cord blood samples. We analyzed 18 OCM-related metabolites in serum using stable isotope dilution liquid chromatography/tandem mass spectrometry. We found that serum S-adenosylmethionine (SAM) concentrations in maternal blood remained stable throughout pregnancy. Conversely, S-adenosylhomocysteine (SAH) concentrations increased, and the total homocysteine/total cysteine ratio significantly increased with advancing gestational age. The betaine/dimethylglycine ratio was negatively correlated with total homocysteine in maternal blood for all sampling periods, and this correlation strengthened with advances in gestational age. Most OCM-related metabolites measured in this study showed significant positive correlations between maternal blood at delivery and cord blood. These findings suggest that maternal OCM status may impact fetal development and indicate the need for comprehensive and longitudinal evaluations of OCM during pregnancy.

Relationship between Serum Homocysteine Concentration and Dietary Factors in Young Japanese Women.

Homocysteine is a methionine metabolism intermediate and its increased blood levels are associated with a higher risk of noncommunicable diseases. Reportedly, blood homocysteine levels increase with inadequate folate, vitamin B6, and vitamin B12 intake; however, its relationship with dietary factors other than these three vitamins remains unknown. Thus, we investigated the relationship of homocysteine with other nutrient intake. We performed a dietary survey on 227 young women using a food record with approximate amounts for 7 consecutive days in conjunction with digital imaging. We collected early morning fasting blood samples the day after the dietary survey was completed and analyzed the serum homocysteine levels. We observed that the serum homocysteine concentrations were significantly negatively associated with soluble, insoluble, and total fiber intake. In addition, participants with high fruit and mushroom intake displayed lower serum homocysteine concentrations, suggesting dietary fiber involvement from these foods. However, we observed no serum homocysteine concentration-related association with cereals and vegetables (well-documented dietary fiber sources) or with fruits and mushrooms. In conclusion, fiber quality-related differences could thus be caused by different sources, including antioxidant components such as fruit polyphenols and mushroom antioxidant and anti-inflammatory factors.

Postprandial fatty acid metabolism with coconut oil in young females: a randomized, single-blind, crossover trial.

BACKGROUND: Approximately 84% of the fatty acids contained in coconut oil (CO) are saturated fatty acids (SFAs), and approximately 47% of the SFA are lauric acid with 12 carbon atoms. Lauric acid carbon chain length is intermediate between medium and long-chain fatty acids (LCFAs). We examined how CO acts on lipid-related substances in the blood to determine whether its properties were similar to medium-chain fatty acids (MCFAs) or LCFAs. METHODS: This is a randomized controlled, single-blind, crossover study. Fifteen females were enrolled, using 3 test meals containing 30 g each of 3 different oils: CO (CO-meal), medium-chain triacylglycerol oil (MCT-meal), and long-chain triacylglycerol oil (LCT-meal). Blood samples were collected at fasted baseline and every 2 h for 8 h after the intake of each test meal. RESULTS: Repeated measures ANOVA of the ketone bodies and triglyceride (TG) showed an interaction between time and the test meal (P < 0.01 and P < 0.001, respectively). In subsequent Tukey's honestly significant difference (HSD) test of the ketone bodies, statistically significant differences were observed between the CO-meal and the LCT-meal (P < 0.05) 83.8 (95% CI, 14.7, 153.0) and between the MCT-meal and the LCT-meal (P < 0.05) 79.2 (95% CI, 10.0, 148.4). The incremental area under the curve (iAUC) and maximum increase in very low-density lipoprotein cholesterol (VLDL-C) and intermediate-density lipoprotein cholesterol (IDL-C) were the lowest for CO-meal intake. CONCLUSIONS: The characteristics of lauric acid contained in CO, including the kinetics of ß-oxidation and effects on blood TG, were very similar to those of MCFA. Moreover, regarding the iAUC and peak increment, VLDL-C and IDL-C were the lowest with the CO-meal. These results suggest that the intake of CO after fasting does not increase the TG, VLDL-C, and IDL-C, and may help prevent dyslipidemia. This trial was registered at UMIN (URL of registration: https://www.umin.ac.jp) as UMIN000019959.

Association of Fatty Acid Desaturase 1 rs174547 Polymorphism with the Composition of Long-Chain Polyunsaturated Fatty Acids in Serum Glycerophospholipids during Pregnancy.

The increase in fetal requirements of long-chain polyunsaturated fatty acids (LCPUFAs) during pregnancy alters maternal fatty acid metabolism, and therefore, fatty acid desaturase (FADS) gene polymorphisms may change blood fatty acid composition or concentration differently during pregnancy. We investigated the relationship between a FADS1 single-nucleotide polymorphism (SNP) and maternal serum LCPUFA levels in Japanese pregnant women during the first and third trimesters and at delivery. Two hundred and fifty-three pregnant women were included, and fatty acid compositions of glycerophospholipids in serum (weight %) and the FADS1 SNP rs174547 (T/C) were analyzed. LCPUFAs, including arachidonic acid (ARA) and docosahexaenoic acid (DHA), significantly decreased from the first to the third trimester of pregnancy. Furthermore, DHA significantly decreased from the third trimester of pregnancy to delivery. At all gestational stages, linoleic acid (LA) and α-linolenic acid were significantly higher with the number of minor FADS1 SNP alleles, whereas γ-linolenic acid and ARA and the ARA/LA ratio were significantly lower. DHA was significantly lower with the number of minor FADS1 SNP alleles only in the third trimester and at delivery, suggesting that genotype effects become more obvious as pregnancy progresses.

Non-target GC-MS analyses of fecal VOCs in NASH-hepatocellular carcinoma model STAM mice.

The increased incidence of obesity in the global population has increased the risk of several chronic inflammation-related diseases, including non-alcoholic steatohepatitis (NASH)-hepatocellular carcinoma (HCC). The progression from NASH to HCC involves a virus-independent liver carcinogenic mechanism; however, we currently lack effective treatment and prevention strategies. Several reports have suggested that fecal volatile organic compounds (VOCs) are strongly associated with NASH-HCC; therefore, we explored the biomarkers involved in its pathogenesis and progression. Fecal samples collected from control and NASH-HCC model STAM mice were subjected to headspace autosampler gas chromatography-electron ionization-mass spectrometry. Non-target profiling analysis identified diacetyl (2,3-butandione) as a fecal VOC that characterizes STAM mice. Although fecal diacetyl levels were correlated with the HCC in STAM mice, diacetyl is known as a cytotoxic/tissue-damaging compound rather than genotoxic or mutagenic; therefore, we examined the effect of bioactivity associated with NASH progression. We observed that diacetyl induced several pro-inflammatory molecules, including tumor necrosis factor-α, cyclooxygenase-2, monocyte chemoattractant protein-1, and transforming growth factor-ß, in mouse macrophage RAW264.7 and Kupffer KPU5 cells. Additionally, we observed that diacetyl induced α-smooth muscle actin, one of the hallmarks of fibrosis, in an ex vivo cultured hepatic section, but not in in vitro hepatic stellate TWNT-1 cells. These results suggest that diacetyl would be a potential biomarker of fecal VOC in STAM mice, and its ability to trigger the macrophage-derived inflammation and fibrosis may partly contribute to NASH-HCC carcinogenesis.

Investigation of Maternal Diet and FADS1 Polymorphism Associated with Long-Chain Polyunsaturated Fatty Acid Compositions in Human Milk.

Increasing the amount of long-chain polyunsaturated fatty acids (LCPUFA) in human milk is an important strategy for infant growth and development. We investigated the associations of LCPUFA compositions in human milk with maternal diet (especially fish and shellfish intake), with fatty acid Δ5 desaturase gene (FADS1) polymorphisms, and with gene-diet interactions. The present study was performed as part of an adjunct study of the Japan Environment and Children's Study. The participants were 304 lactating females, who provided human milk 6−7 months after delivery. Fatty acids in human milk were analyzed by gas chromatography, and dietary surveys were conducted using a brief self-administered diet history questionnaire. We also analyzed a single nucleotide polymorphism of FADS1 (rs174547, T/C). There was a significant difference in arachidonic acid (ARA) composition in human milk among the genotype groups, and the values were decreasing in the order of TT > TC > CC. The concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were also different between TT and CC genotype, indicating a tendency for decreasing values in the same order. The composition of ARA showed significant gene−dietary interactions in multiple regression analysis, and the positive correlation between fish and shellfish intake and ARA composition in human milk was significant only in the CC genotype. Moreover, the factor most strongly associated with EPA and DHA composition in human milk was fish and shellfish intake. Therefore, it was suggested that increasing fish and shellfish intake in mothers may increase EPA and DHA composition in human milk, while increasing fish and shellfish intake in CC genotype mothers may lead to increased ARA composition in human milk.

The Body Fat Percentage Rather Than the BMI Is Associated with the CD4 Count among HIV Positive Japanese Individuals.

Maintenance of the cluster of differentiation 4 (CD4) positive lymphocyte count (CD4 count) is important for human immunodeficiency virus (HIV) positive individuals. Although a higher body mass index (BMI) is shown to be associated with a higher CD4 count, BMI itself does not reflect body composition. Therefore, we examined the association of body weight, body composition and the CD4 count, and determined the optimal ranges of CD4 count associated factors in Japanese HIV positive individuals. This cross-sectional study included 338 male patients treated with antiretroviral therapy for ≥12 months. Multiple logistic regression analysis was used to identify factors significantly associated with a CD4 count of ≥500 cells (mm3)-1. The cutoff values of factors for a CD4 ≥ 500 cells (mm3)-1 and cardiovascular disease risk were obtained by receiver operating characteristic curves. Age, body fat percentage (BF%), nadir CD4 count, duration of antiretroviral therapy (ART), years since the HIV-positive diagnosis and cholesterol intake showed significant associations with the CD4 count. The cutoff value of BF% for a CD4 ≥ 500 cells (mm3)-1 and lower cardiovascular disease risk were ≥25.1% and ≤25.5%, respectively. The BF%, but not the BMI, was associated with CD4 count. For the management of HIV positive individuals, 25% appears to be the optimal BF% when considering the balance between CD4 count management and cardiovascular disease risk.

Associations of umbilical cord fatty acid profiles and desaturase enzyme indices with birth weight for gestational age in Japanese infants.

Long-chain polyunsaturated fatty acids (LCPUFAs) required for infant development are produced by Δ6 desaturase (D6D) and Δ5 desaturase (D5D). The D6D index and D5D index are calculated based on their respective precursor/product ratios. The D5D and D6D indices are related to obesity and lifestyle-related diseases. The aim of the present study was to examine the associations of umbilical cord fatty acid profiles, D6D index, and D5D index in appropriate for gestational age (AGA), small for gestational age (SGA), and large for gestational age (LGA) infants. This was a nested case-control study, and the relationship between case and control maternal blood and umbilical cord blood fatty acid compositions was examined. Cases were small for gestational age (SGA; n = 55) and large for gestational age (LGA; n = 149) infants, whereas controls were appropriate for gestational age (AGA; n = 204) infants. Fatty acid profiles in maternal blood and umbilical cord plasma were analyzed by gas-liquid chromatography. The D6D index was calculated as dihomo-γ-linolenic acid (DGLA 20: 3 n-6) / linoleic acid (18: 2 n - 6), and the D5D index was calculated as arachidonic acid (20: 4 n - 6) / DGLA (20: 3 n - 6). Statistical analysis of umbilical cord blood fatty acids was performed with multiple comparisons. SGA infants showed high umbilical cord values for α-linolenic acid and DHA and lower values for DGLA compared to AGA infants. SGA infants showed a higher D5D index but a lower D6D index than AGA infants. LGA infants showed high values for α-linolenic acid and DGLA and lower values for arachidonic acid than AGA infants. LGA infants showed a high D6D index and a low D5D index relative to AGA infants. No significant differences in maternal blood fatty acid profiles, the D6D index, and D5D index desaturase activities were found among the three groups. There were differences in umbilical cord fatty acid profiles and D6D and D5D indices among AGA, SGA, and LGA infants, but further study is needed.

Distribution of 5-Methyltetrahydrofolate and Folic Acid Levels in Maternal and Cord Blood Serum: Longitudinal Evaluation of Japanese Pregnant Women.

"Total" folate in blood has usually been measured to evaluate the folate status of pregnant women. However, folate is composed of many metabolites. The main substrate is 5-methyltetrahydrofolate (5-MTHF), with folic acid (FA) representing a very small component as an unmetabolized species in blood. We longitudinally evaluated 5-MTHF, FA and total homocysteine in maternal and cord blood from Japanese pregnant women. Subjects were 146 pregnant women who participated in the Chiba study of Mother and Child Health (C-MACH) prospective cohort study. Sera were obtained in early and late pregnancy, at delivery, and from cord blood. Species levels were measured by isotope-dilution mass spectrometry. Both 5-MTHF and FA levels were lower than reported levels from pregnant women in populations from countries with mandatory FA fortification. As gestational age progressed, serum 5-MTHF levels decreased, whereas serum FA levels were slightly reduced only at delivery compared to early pregnancy. A significant negative association between serum 5-MTHF and total homocysteine was shown at all examined times, but no associations with FA were evident. At delivery, cord 5-MTHF was significantly higher than maternal levels, while FA again showed no significant correlation. These results suggest that 5-MTHF is actively transported to the fetus through placental transporters and may reflect folate status during pregnancy as a physiologically important species.

Association Between Risk Factors and Intensive Nutritional Intervention Outcomes in Elderly Individuals.

BACKGROUND: The purpose of this study was to identify risk factors for intensive nutritional intervention outcomes in elderly undernourished patients to help reduce the number of patients with prolonged hospital stay or without recuperation of previous activities of daily living and quality of life. METHODS: In total, 230 patients who received interventions from a nutrition support team (NST) between January 2016 and July 2018 were included. Patients were classified into two groups based on NST intervention outcomes: patients with improved nutritional status were included in the successful group, whereas those whose nutritional status did not improve, as defined by progressive illness or death, were classified into the non-successful group. We assessed patient characteristics, laboratory data, and nutrition support methods. RESULTS: Our multivariate Cox proportional hazard analysis showed that: 1) The presence of peripheral parenteral nutrition (hazard ratio (HR): 1.80; 95% confidence interval (CI): 1.13 - 2.88) was identified as an independent risk factor for NST intervention outcomes; 2) The energy fill rate to total energy expenditure was < 66.0% (HR: 1.61; 95% CI: 0.98 - 2.66); and 3) A geriatric nutritional risk index score < 70.0 (HR: 1.54; 95% CI: 0.92 - 2.56) tended to be negatively associated with NST intervention outcomes. CONCLUSIONS: In addition to the nutrition therapy provided by a traditional NST, patients with the risk factors require nutritional intervention. Elderly individuals should also receive nutrition care because they have been recuperating at their home or in long-term care facilities, to prevent experiencing adverse conditions.