Methylphenidate ameliorates the homeostatic balance between levels of kynurenines in ADHD children

Molina-Carballo, Antonio; Cubero-Millán, Isabel; Fernández-López, Luisa; Checa-Ros, Ana; Machado-Casas, Irene; Jeréz-Calero, Antonio; Blanca-Jover, Enrique; Cantarero-Malagón, Antonio-Manuel; Uberos, J.; Muñóz-Hoyos, Antonio

doi:10.1016/j.psychres.2021.114060

Cited by 11 publications

(20 citation statements)

References 38 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%

“…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: 88%

“…According to Uberos et al (2010), in children, the urinary excretion of KYNA is even higher, ranging from 14.0–17.6 mg/day/person [ 59 ]. In another study performed by Molina-Carballo et al (2021) on children aged 5–14 years, KYNA was found to be 5–7 μg per mg creatinine [ 60 ]. After mathematical conversion, the amount of the excreted KYNA can be estimated at the level of 2.64–3.30 mg/day/child.…”

Section: Excretion Of Kynurenic Acidmentioning

confidence: 99%

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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%

Section: Excretion Of Kynurenic Acidmentioning

confidence: 88%

Section: Excretion Of Kynurenic Acidmentioning

confidence: 99%

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

et al. 2022

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“…Irrespective of the link between serotonin and aggression, the assumption that tryptophan exerts its effects via serotonin has also been questioned, with more recent studies offering alternative mechanisms of action of tryptophan including alternations to the brainderived neurotrophic factor (BDNF), nitric oxide synthase, kynurenine metabolites, which can then impact on NMDA receptor function, cerebral blood flow, and microtubules (van Donkelaar et al 2011;Yousefzadeh et al 2020). Furthermore, research already implicates BDNF (Guyon et al 2021) and NMDA receptors (Zhang et al 2021) in aggression and BDNF, nitric oxide and kynurenine are all linked to ADHD (Molina-Carballo et al 2021;Sharma et al 2021;Sari et al 2020), suggesting these mechanisms may be particularly relevant to the studies reviewed here.…”

Section: Discussionmentioning

confidence: 83%

Tryptophan modulation in individuals with attention deficit hyperactivity disorder: a systematic review

2022

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The serotonergic system is implicated in ADHD, but the impact of serotonin’s precursor molecule, tryptophan, on ADHD symptomology remains unclear. Systematic searches of randomised controlled trials with an experimental tryptophan intervention in children and adults with ADHD identified 14 studies measuring core and related symptoms of the condition. Risk of bias was assessed using the Cochrane Risk of Bias tool. The 14 studies all used acute tryptophan depletion procedures, and most did not investigate core ADHD symptoms (inattention, impulsivity, hyperactivity) as primary outcome measures. Only two studies examined attention and revealed mixed effects of tryptophan. Similar effects were found for impulsivity in a small number of studies. No studies investigated hyperactivity. Most studies focused on reactive aggression, but samples were heterogenous and small, rendering potential meta-analyses inconclusive or misleading. However, the narrative analysis indicates tryptophan interventions may impact reactive aggression. More research is needed on the effect of tryptophan modulation on core ADHD symptoms, especially in adults, using more diverse samples to determine potential as an intervention. From current data, tryptophan modulation appears to alter aggressive behaviour in ADHD; however, the available studies were insufficient for the planned meta-analysis.

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“…It is worth pointing out that with the existence of comorbidities such as suicidal behavior, depressed patients illustrate higher decrement in circulating TRP compared to those without these comorbidities [ 61 , 62 , 63 , 64 ]. Surprisingly, the simultaneous presence of two diseases such as obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) symptoms may increase the amount of TRP [ 65 , 66 , 67 , 68 , 69 ]. Ramos-Cha’vez et al illustrated that anxiety positively correlates with depression scores and negatively correlates with TRP in a cohort study including 77 women over 50 [ 70 ].…”

Section: The Role Of Trp In Psychiatric Disordersmentioning

confidence: 99%

The Role of Tryptophan Metabolites in Neuropsychiatric Disorders

Davidson

Rashidi

Nurgali

et al. 2022

IJMS

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In recent decades, neuropsychiatric disorders such as major depressive disorder, schizophrenia, bipolar, etc., have become a global health concern, causing various detrimental influences on patients. Tryptophan is an important amino acid that plays an indisputable role in several physiological processes, including neuronal function and immunity. Tryptophan’s metabolism process in the human body occurs using different pathways, including the kynurenine and serotonin pathways. Furthermore, other biologically active components, such as serotonin, melatonin, and niacin, are by-products of Tryptophan pathways. Current evidence suggests that a functional imbalance in the synthesis of Tryptophan metabolites causes the appearance of pathophysiologic mechanisms that leads to various neuropsychiatric diseases. This review summarizes the pharmacological influences of tryptophan and its metabolites on the development of neuropsychiatric disorders. In addition, tryptophan and its metabolites quantification following the neurotransmitters precursor are highlighted. Eventually, the efficiency of various biomarkers such as inflammatory, protein, electrophysiological, genetic, and proteomic biomarkers in the diagnosis/treatment of neuropsychiatric disorders was discussed to understand the biomarker application in the detection/treatment of various diseases.

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Methylphenidate ameliorates the homeostatic balance between levels of kynurenines in ADHD children

Cited by 11 publications

References 38 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

Tryptophan modulation in individuals with attention deficit hyperactivity disorder: a systematic review

The Role of Tryptophan Metabolites in Neuropsychiatric Disorders

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