Alterations in one-carbon metabolism in metabolic dysfunction associated steatotic liver disease may be modified by semaglutide.

Introduction And Objectives: Disruptions in one-carbon metabolism (OCM) have been linked to cardiometabolic diseases. We evaluated alterations in OCM metabolites and enzymes and the impact of semaglutide in MASLD.

Materials And Methods: Using targeted metabolomics and bulk-transcriptomics, we analyzed components of OCM in plasma samples and liver biopsies from MASLD patients (n=100 with F0-F4 fibrosis, 51% type 2 diabetes) and healthy controls (n=50).

Infant vitamin B12 status and its predictors - cross-sectional baseline results from an ongoing randomized controlled trial.

Background: Vitamin B12 is a crucial micronutrient for infant growth and development.

Objective: The objective of this study was to describe vitamin B12 status in Norwegian infants aged 6-15 wk using multiple biomarkers and cut-off approaches, and to identify its predictors.

Methods: From November 2021 through August 2024, infants aged 6-15 wk and their mothers were recruited from public health clinics in Innlandet County, Norway, as part of an ongoing randomized controlled trial.

Association Between Dietary Intake and Blood Concentrations of One-Carbon-Metabolism-Related Nutrients in European Prospective Investigation into Cancer and Nutrition.

We examined the association between dietary intake and blood concentrations of one-carbon metabolism (OCM)-related nutrients in the European Prospective Investigation into Cancer and Nutrition (EPIC). Blood concentrations and dietary intake of the vitamins riboflavin (B2), Pyridoxal 5'-phosphate (PLP and B6), folate (B9), B12, and methionine, concentrations of homocysteine, and dietary intake of betaine, choline, and cysteine were pooled from 16,267 participants in nine EPIC nested case-control studies. Correlation analyses between dietary intakes and blood concentrations were carried out.

Tryptophan-kynurenine metabolites associate with inflammation and immunologic phenotypes in common variable immunodeficiency.

Background: A large proportion of patients with common variable immunodeficiency (CVID) have autoimmune and inflammatory manifestations characterized by chronic T-cell- and monocyte/macrophage activation of unknown etiology. The tryptophan-kynurenine pathway has previously been linked to immune activation involving T cells and monocytes/macrophages, as well as with gut microbial dysbiosis in some inflammatory diseases.

Objective: We aimed to characterize the tryptophan-kynurenine pathway in CVID and its potential association with clinical/immunologic phenotype and gut microbial dysbiosis.

The kynurenine pathway and markers of neurodegeneration and cerebral small vessel disease: The Maastricht Study.

Background: The kynurenine pathway, the main metabolic pathway of tryptophan degradation, has been mostly studied in neurodegenerative disorders, while its role in cerebrovascular pathology is less clear. We investigated whether kynurenines are associated with markers of neurodegeneration and cerebrovascular pathology in the general population.

Methods: Cross-sectional data was used from 1589 individuals (60.

Parkinson's disease is characterized by vitamin B6-dependent inflammatory kynurenine pathway dysfunction.

Recent studies demonstrate that Parkinson's disease (PD) is associated with dysregulated metabolic flux through the kynurenine pathway (KP), in which tryptophan is converted to kynurenine (KYN), and KYN is subsequently metabolized to neuroactive compounds quinolinic acid (QA) and kynurenic acid (KA). Here, we used mass-spectrometry to compare blood and cerebral spinal fluid (CSF) KP metabolites between 158 unimpaired older adults and 177 participants with PD. We found increased neuroexcitatory QA/KA ratio in both plasma and CSF of PD participants associated with peripheral and cerebral inflammation and vitamin B deficiency.

Kynurenines and neopterin are interferon-gamma-inducible biomarkers for Sjögren's disease.

Objectives: The aim was to investigate whether kynurenine pathway metabolites and neopterin increase probability for Sjögren's disease (SjD) and their associations with clinical parameters and inflammatory biomarkers.

Methods: In this case-control study, 97 SjD patients and 63 age- and sex-matched healthy volunteers were enrolled. Clinical and immunological characteristics, EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and the EULAR Sjögren's Syndrome Patient-Report Index (ESSPRI) were evaluated.

Vitamin B status is related to disease severity and modulated by endurance exercise in individuals with multiple sclerosis: a secondary analysis of a randomized controlled trial.

Background: Low circulating concentrations of B vitamins are linked to various chronic and neurodegenerative diseases. Notably, pyridoxal 5'-phosphate (vitamin B) deficiency is linked to altered inflammatory responses and cellular immune function, both critical in multiple sclerosis (MS). Nevertheless, most MS research has focused on folate (vitamin B) and vitamin B, leaving other B vitamins understudied.

Exercise training restores longevity-associated tryptophan metabolite 3-hydroxyanthranilic acid levels in middle-aged adults.

Aim: Recent pre-clinical evidence suggests that the tryptophan metabolite 3-hydroxyanthranilic acid (3-HAA) and the related enzyme activity along the kynurenine metabolic pathway (KP) are associated with lifespan extension. We aimed to translate these findings into humans and expose exercise training as a potential non-pharmacological intervention to modulate this metabolic hub.

Methods: To explore whether recent pre-clinical findings might also be of relevance for humans, we analyzed the evolutionary conservation of KYNU and HAAO, the two core KP enzymes associated with 3-HAA.

Modeling how iso-caloric macronutrient substitutions are longitudinally associated with plasma kynurenines in colorectal cancer survivors up to 12 months post-treatment.

Dietary intake of several macronutrients is associated with plasma kynurenines after colorectal cancer (CRC), and kynurenines have been linked to health-related outcomes. It is unknown how macronutrient substitution affects plasma kynurenines, which may be relevant for developing guidelines to improve post-CRC quality of life through dietary changes. Using iso-caloric substitution models, we investigated how substituting one macronutrient with another is longitudinally associated with plasma tryptophan, kynurenines, and kynurenine ratios in CRC survivors.

Longitudinal associations of dietary intake with fatigue in colorectal cancer survivors up to 1 year post-treatment, and the potential mediating role of the kynurenine pathway.

Introduction: A healthy diet may help to reduce cancer-related fatigue, but evidence is limited and mechanisms remain unclear. Both diet and fatigue following colorectal cancer (CRC) have been linked to metabolites (kynurenines) of the kynurenine pathway (KP). We investigated longitudinal associations between dietary intake and fatigue, and the potential mediating role of the KP, in CRC survivors up to 1 year post-treatment.

Elevated plasma trimethyllysine is associated with incident atrial fibrillation.

Background/aim: Trimethyllysine (TML) is a methylated amino acid, which is linked to epigenetic regulation and can serve as a precursor of trimethylamine-N-oxide (TMAO). TMAO is a microbiota-derived metabolite and a potential risk factor of cardiovascular disease. TML has recently been linked to atherosclerosis, acute myocardial infarction and prevalent atrial fibrillation (AF).

Vitamin B6 status and chronic chemotherapy-induced peripheral neuropathy: a prospective cohort study among patients with non-metastatic colorectal cancer receiving oxaliplatin-based chemotherapy.

Objective: Chronic chemotherapy-induced peripheral neuropathy (CIPN) is a long-lasting side-effect of oxaliplatin. Vitamin B6 might play a role in the pathogenesis of CIPN. Therefore, we investigated associations between plasma vitamin B6 markers and the occurrence and severity of chronic CIPN in patients with non-metastatic colorectal cancer (CRC).

Mitochondrial dysfunction and lipid alterations in primary sclerosing cholangitis.

Objectives: Indications of mitochondrial dysfunction are commonly seen in liver diseases, but data are scarce in primary sclerosing cholangitis (PSC). Analyzing circulating and liver-resident molecules indirectly reflecting mitochondrial dysfunction, we aimed to comprehensively characterize this deficit in PSC, and whether this was PSC specific or associated with cholestasis.

Materials And Methods: We retrospectively included plasma from 191 non-transplant patients with large-duct PSC and 100 healthy controls and explanted liver tissue extracts from 24 PSC patients and 18 non-cholestatic liver disease controls.

Baseline Inflammation but not Exercise Modality Impacts Exercise-induced Kynurenine Pathway Modulation in Persons With Multiple Sclerosis: Secondary Results From a Randomized Controlled Trial.

Background: The kynurenine pathway (KP) is an important hub in neuroimmune crosstalk that is dysregulated in persons with multiple sclerosis (pwMS) and modulated by exercise in a modality-specific manner.

Objectives: To compare changes in the KP metabolite profile of pwMS (1) following combined treatments including either high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) during a 3-week multimodal rehabilitation, (2) to evaluate exercise response in relation to baseline systemic inflammation, and (3) to investigate associations of kynurenines with physical capacity and clinical outcomes.

Methods: For this secondary analysis of a randomized controlled trial, serum concentrations of kynurenines at baseline and after 3 weeks were determined using targeted metabolomics (LC-MS/MS).

Acute exercise boosts NAD metabolism of human peripheral blood mononuclear cells.

Nicotinamide adenine dinucleotide (NAD) coenzymes are the central electron carriers in biological energy metabolism. Low NAD levels are proposed as a hallmark of ageing and several diseases, which has given rise to therapeutic strategies that aim to tackle these conditions by boosting NAD levels. As a lifestyle factor with preventive and therapeutic effects, exercise increases NAD levels across various tissues, but so far human trials are mostly focused on skeletal muscle.

Breastfeeding and biomarkers of folate and cobalamin status in Norwegian infants: a cross-sectional study.

Folate and vitamin B (cobalamin) are essential for growth and development. This cross-sectional study aims to describe folate and vitamin B status according to infant age and breastfeeding practices in Norwegian infants. Infants aged 0-12 months ( = 125) were recruited through public health clinics.

Folate and cobalamin status, indicators, modulators, interactions, and reference ranges from early pregnancy until birth: the Reus-Tarragona birth cohort study.

Background: Folate and cobalamin status, although essential for pregnancy, are not routinely monitored in prenatal care.

Objectives: To investigate folate and cobalamin status and determinants throughout pregnancy, in the absence of mandatory folic acid (FA) fortification.

Methods: In a cohort study of 831 mothers recruited at <12 gestational weeks (GW), plasma folate, total homocysteine (tHcy), cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), red blood cell folate (RBCF), and the combined cobalamin status indicator (cB12) were determined at ≤12, 15, 24-27, 34 GW, labor and in the cord.

Circulating tryptophan-kynurenine pathway metabolites are associated with all-cause mortality among patients with stage I-III colorectal cancer.

Alterations within the tryptophan-kynurenine metabolic pathway have been linked to the etiology of colorectal cancer (CRC), but the relevance of this pathway for prognostic outcomes in CRC patients needs further elucidation. Therefore, we investigated associations between circulating concentrations of tryptophan-kynurenine pathway metabolites and all-cause mortality among CRC patients. This study utilizes data from 2102 stage I-III CRC patients participating in six prospective cohorts involved in the international FOCUS Consortium.

Sex-specific associations of kynurenic acid with neopterin in Alzheimer's disease.

Background: Sex differences in neuroinflammation could contribute to women's increased risk of Alzheimer's disease (AD), providing rationale for exploring sex-specific AD biomarkers. In AD, dysregulation of the kynurenine pathway (KP) contributes to neuroinflammation and there is some evidence of sex differences in KP metabolism. However, the sex-specific associations between KP metabolism and biomarkers of AD and neuroinflammation need to be explored further.

Longitudinal associations of plasma kynurenines and ratios with fatigue and quality of life in colorectal cancer survivors up to 12 months post-treatment.

Fatigue is prevalent in colorectal cancer (CRC) survivors, impacting their health-related quality of life (HRQoL). Inflammation-induced activation of the kynurenine pathway may play a role in cancer-related fatigue and HRQoL, but evidence is scarce. Therefore, we aimed to investigate longitudinal associations of plasma tryptophan, kynurenines, and ratios with fatigue and HRQoL in CRC survivors up to 12 months post-treatment.

Maternal serum unmetabolized folic acid concentration following multivitamin and mineral supplementation with or without folic acid after 12 weeks gestation: A randomized controlled trial.

Pregnant women are advised to take folic acid (FA) supplements before conception and during the first trimester of pregnancy. Many women continue FA supplementation throughout pregnancy, and concerns have been raised about associations between excessive FA intake and adverse maternal and child health outcomes. Unmetabolized folic acid (UMFA) is found in serum after high FA intakes and is proposed as a biomarker for excessive FA intake.