Method for Evaluation of the Requirements of B-group Vitamins Using Tryptophan Metabolites in Human Urine

Shibata, Katsumi; Hirose, Junko; Fukuwatari, Tsutomu

doi:10.4137/ijtr.s24412

Cited by 5 publications

(5 citation statements)

References 37 publications

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“…The presence of KYNA in human urine obtained from adults and children has been repeatedly reported [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ] ( Figure 2 b) ( Table S3 ). The urine concentration of KYNA ranges between 4.04 and 22.18 μM in adults.…”

Section: Distribution Of Kynurenic Acidsupporting

confidence: 54%

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A Review of the Health Benefits of Food Enriched with Kynurenic Acid

et al. 2022

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Kynurenic acid (KYNA), a metabolite of tryptophan, is an endogenous substance produced intracellularly by various human cells. In addition, KYNA can be synthesized by the gut microbiome and delivered in food. However, its content in food is very low and the total alimentary supply with food accounts for only 1–3% of daily KYNA excretion. The only known exception is chestnut honey, which has a higher KYNA content than other foods by at least two orders of magnitude. KYNA is readily absorbed from the gastrointestinal tract; it is not metabolized and is excreted mainly in urine. It possesses well-defined molecular targets, which allows the study and elucidation of KYNA’s role in various pathological conditions. Following a period of fascination with KYNA’s importance for the central nervous system, research into its role in the peripheral system has been expanding rapidly in recent years, bringing some exciting discoveries. KYNA does not penetrate from the peripheral circulation into the brain; hence, the following review summarizes knowledge on the peripheral consequences of KYNA administration, presents data on KYNA content in food products, in the context of its daily supply in diets, and systematizes the available pharmacokinetic data. Finally, it provides an analysis of the rationale behind enriching foods with KYNA for health-promoting effects.

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Section: Distribution Of Kynurenic Acidsupporting

confidence: 54%

“…The excretion of KYNA in human urine has been repeatedly reported [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ] ( Table S3 ). It can be concluded that the excretion of KYNA in urine ranges from 1.14 to 6.29 mg/day/adult person.…”

Section: Excretion Of Kynurenic Acidmentioning

confidence: 87%

A Review of the Health Benefits of Food Enriched with Kynurenic Acid

et al. 2022

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“…Disruption of the one-carbon metabolism could also underlie the inverse association between first trimester maternal 5-HTP and embryonic and fetal growth. TRP metabolism provides one-carbon units for the folate cycle and shares cofactors with one-carbon metabolism, which is crucial for epigenetic programming of cells and tissues ( Steegers-Theunissen et al , 2013 ; Shibata et al , 2015 ). A deficiency of a shared cofactor, for example vitamin B6, can lead to increased 5-HTP and homocysteine concentrations ( Shabbir et al , 2013 ; Steegers-Theunissen et al , 2013 ).…”

Section: Discussionmentioning

confidence: 99%

First trimester maternal tryptophan metabolism and embryonic and fetal growth: the Rotterdam Periconceptional Cohort (Predict Study)

van Zundert,

van Egmond,

van Rossem

et al. 2024

Human Reproduction

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STUDY QUESTION What is the association between first trimester maternal tryptophan (TRP) metabolites and embryonic and fetal growth? SUMMARY ANSWER Higher 5-hydroxytryptophan (5-HTP) concentrations are associated with reduced embryonic growth and fetal growth and with an increased risk of small-for-gestational age (SGA), while higher kynurenine (KYN) concentrations are associated with a reduced risk of SGA. WHAT IS KNOWN ALREADY The maternal TRP metabolism is involved in many critical processes for embryonic and fetal growth, including immune modulation and regulation of vascular tone. Disturbances in TRP metabolism are associated with adverse maternal and fetal outcomes. STUDY DESIGN, SIZE, DURATION This study was embedded within the Rotterdam Periconceptional Cohort (Predict Study), an ongoing prospective observational cohort conducted at a tertiary hospital from November 2010 onwards. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 1115 women were included before 11 weeks of gestation between November 2010 and December 2020. Maternal serum samples were collected between 7 and 11 weeks of gestation, and TRP metabolites (TRP, KYN, 5-HTP, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid) were determined using a validated liquid chromatography (tandem) mass spectrometry method. Serial 3D ultrasound scans were performed at 7, 9, and 11 weeks of gestation to accurately assess features of embryonic growth, including crown–rump length (CRL) and embryonic volume (EV) offline using virtual reality systems. Fetal growth parameters were retrieved from medical records and standardized according to Dutch reference curves. Mixed models were used to assess associations between maternal TRP metabolites and CRL and EV trajectories. Linear and logistic regression models were utilized to investigate associations with estimated fetal weight (EFW) and birthweight, and with SGA, respectively. All analyses were adjusted for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE Maternal 5-HTP concentrations and the maternal 5-HTP/TRP ratio were inversely associated with embryonic growth (5-HTP, √CRL: β = –0.015, 95% CI = –0.028 to –0.001; 5-HTP 3√EV: β = –0.009, 95% CI = –0.016 to –0.003). An increased maternal 5-HTP/TRP ratio was also associated with lower EFW and birthweight, and with an increased risk of SGA (odds ratio (OR) = 1.006, 95% CI = 1.00–1.013). In contrast, higher maternal KYN concentrations were associated with a reduced risk of SGA in the unadjusted models (OR = 0.548, 95% CI = 0.320–0.921). LIMITATIONS, REASONS FOR CAUTION Residual confounding cannot be ruled out because of the observational design of this study. Moreover, this study was conducted in a single tertiary hospital, which assures high internal validity but may limit external validity. WIDER IMPLICATIONS OF THE FINDINGS The novel finding that maternal 5-HTP concentrations are associated with a smaller embryo and fetus implies that disturbances of the maternal serotonin pathway in the first trimester of pregnancy are potentially involved in the pathophysiology of fetal growth restriction. The association between higher maternal KYN concentrations and a reduced risk of SGA substantiate the evidence that the KYN pathway has an important role in fetal growth. More research is needed to delve deeper into the potential role of the maternal TRP metabolism during the periconception period and pregnancy outcome for mother and offspring. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Department of Obstetrics and Gynecology and the Department of Clinical Chemistry of the Erasmus MC, University Medical Center, Rotterdam, the Netherlands. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER N/A.

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“…Vitamin B6 serves as an illustrative example as it is crucial not only for converting total homocysteine into cystathionine, but also for the conversion of KYN into downstream metabolites and for the conversion of 5-HTP to 5-HT. 10 , 19 , 59 , 60 However, future research is warranted to elucidate the exact mechanism underlying the observed associations, and explore the role of various cofactors in this complex interplay between the tryptophan metabolism and one-carbon metabolism.…”

Section: Discussionmentioning

confidence: 99%

“… 10 , 13 - 18 Derangement of the one-carbon metabolism often coincides with disruption of the tryptophan metabolism, as the tryptophan metabolism provides once-carbon units for the folate cycle and shares cofactors with the one-carbon metabolism. 10 , 19 Tryptophan metabolites are involved in redox reactions, and can have pro- and anti-oxidative properties. Disruption of the tryptophan metabolism can induce excessive oxidative stress and subsequent inflammation, which are involved in adverse pregnancy outcomes.…”

Section: Introductionmentioning

confidence: 99%

Periconceptional Non-medical Maternal Determinants Influence the Tryptophan Metabolism: The Rotterdam Periconceptional Cohort (Predict Study)

van Zundert,

van Rossem,

Mirzaian

et al. 2024

Int J�Tryptophan�Res

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Background: The vital role of the maternal tryptophan (TRP) metabolism in maternal health and pregnancy is well established. However, non-medical maternal determinants influencing the TRP metabolism have been poorly investigated. We hypothesise that periconceptional maternal non-medical determinants alter the TRP metabolism, affecting both kynurenine (KP) and serotonin pathway (SP) metabolite concentrations. Therefore, we investigated the influence of non-medical maternal determinants on the TRP metabolism during the periconception period. Methods: About 1916 pregnancies were included from the Rotterdam Periconceptional Cohort between November 2010 and December 2020. Data on periconceptional non-medical maternal determinants were collected through questionnaires. Serum samples were collected at 8.5 (SD = 1.6) weeks of gestation and TRP, kynurenine (KYN), 5-hydroxytryptophan (5-HTP), 5-HT (5-hydroxytryptamine) and 5-hydroxyindole acetic acid (5-HIAA) were determined using validated liquid chromatography (tandem) mass spectrometry. Mixed models were used to determine associations between periconceptional non-medical maternal determinants and these metabolites. Results: In total 11 periconceptional non-medical maternal determinants were identified. Protein intake was positively associated with TRP ( β = .12, 95% CI = 0.07-0.17), while age, energy intake and body mass index (BMI) ( β = −.24, 95% CI = −0.37 to −0.10) were negatively associated with TRP. Age, BMI and total homocysteine were associated with higher KYN, whereas non-western geographical origin was associated with lower KYN ( β = −.09, 95% CI = −0.16 to −0.03). Protein intake and total homocysteine ( β = .07, 95% CI = 0.03-0.11) had a positive association with 5-HTP, while a negative association was found for energy intake. A non-western geographical origin and drug use were associated with higher 5-HT, and BMI with lower 5-HT ( β = −6.32, 95% CI = −10.26 to −2.38). Age was positively associated with 5-HIAA ( β = .92, 95% CI = 0.29-1.56), and BMI negatively. Conclusions: Periconceptional non-medical maternal determinants, including age, geographical origin, drug use, energy and protein intake, BMI and total homocysteine, influence KP and SP metabolite concentrations.

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Method for Evaluation of the Requirements of B-group Vitamins Using Tryptophan Metabolites in Human Urine

Cited by 5 publications

References 37 publications

A Review of the Health Benefits of Food Enriched with Kynurenic Acid

A Review of the Health Benefits of Food Enriched with Kynurenic Acid

First trimester maternal tryptophan metabolism and embryonic and fetal growth: the Rotterdam Periconceptional Cohort (Predict Study)

Periconceptional Non-medical Maternal Determinants Influence the Tryptophan Metabolism: The Rotterdam Periconceptional Cohort (Predict Study)

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