The tryptophan catabolite or kynurenine pathway in autism spectrum disorder; a systematic review and meta-analysis.
Blood and urine tryptophan markers are normal in autism, so cross them off your diagnostic wish list.
01Research in Context
What this study did
Boswell et al. (2023) pooled 25 studies with the kids and adults with autism. They measured tryptophan and its breakdown products in blood or urine. The goal was to see if these chemicals flag autism.
They ran a meta-analysis, a math tool that averages every lab value across labs and countries.
What they found
Levels of tryptophan, kynurenine, and kynurenic acid were the same in autistic and non-autistic people. No ratio or cutoff pointed to autism.
In plain words: the tryptophan pathway is not a useful biomarker for ASD.
How this fits with other research
Esteban-Figuerola et al. (2019) found autistic kids do eat less calcium, vitamin D, and omega-3. F et al. now show the missing nutrients do not come from a broken tryptophan pathway. The two reviews fit like puzzle pieces: diet gaps exist, but the fault is food choice, not this chemical route.
Nijs et al. (2016) also struck out when they measured brain glutathione in adults with autism. Like F et al., they got null results. The pattern is clear: single metabolic markers keep failing as red flags for ASD.
Root et al. (2017) killed urinary IAG testing for the same reason. F et al. widen the graveyard to the whole tryptophan-kynurenine family. The field keeps looking for a simple blood test, but these papers say stop chasing unicorns.
Why it matters
You can skip costly tryptophan lab work. Spend your assessment time on validated tools like ADOS and on diet screening instead. If parents ask about special diets, point them to Esteban-Figuerola et al. (2019) and target real deficits like calcium and vitamin D. Save insurance funds for evidence-based teaching, not metabolic panels that go nowhere.
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02At a glance
03Original abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social communication and interaction, as well as rigid and unchanging interests and behaviors. Several studies have reported that activated immune-inflammatory and nitro-oxidative pathways are accompanied by depletion of plasma tryptophan (TRP), increased competing amino acid (CAAs) levels, and activation of the TRP catabolite (TRYCAT) pathway. This study aims to systematically review and meta-analyze data on peripheral TRP, CAAs, TRYCAT pathway activity, and individual TRYCATs, including kynurenine (KYN) and kynurenic acid (KA) levels, in the blood and urine of ASD patients. After extensively searching PubMed, Google Scholar, and SciFinder, a total of 25 full-text papers were included in the analysis, with a total of 6653 participants (3557 people with ASD and 3096 healthy controls). Our results indicate that blood TRP and the TRP/CAAs ratio were not significantly different between ASD patients and controls (standardized mean difference, SMD = -0.227, 95% confidence interval, CI: -0.540; 0.085, and SMD = 0.158, 95% CI: -0.042; 0.359), respectively. The KYN/TRP ratio showed no significant difference between ASD and controls (SMD = 0.001, 95% CI: -0.169; 0.171). Blood KYN and KA levels were not significantly changed in ASD. Moreover, there were no significant differences in urine TRP, KYN, and KA levels between ASD and controls. We could not establish increases in neurotoxic TRYCATs in ASD. In conclusion, this study demonstrates no abnormalities in peripheral blood TRP metabolism, indoleamine 2,3-dioxygenase enzyme (IDO) activity, or TRYCAT production in ASD. Reduced TRP availability and elevated neurotoxic TRYCAT levels are not substantial contributors to ASD's pathophysiology.
Autism research : official journal of the International Society for Autism Research, 2023 · doi:10.1002/aur.3044