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Tryptophan Metabolism

Tryptophan is an essential amino acid that serves as a biochemical precursor for multiple neuroactive and immunomodulatory compounds. Dr. G. Bjørklund offers comprehensive assessments of tryptophan metabolism, with a focus on its critical role in mood regulation, sleep quality, immune function, and energy production. By identifying imbalances in this pathway, it is possible to target underlying contributors to both physical and mental health conditions.

How Tryptophan Metabolism Works

Tryptophan is converted into several bioactive metabolites, primarily through two distinct pathways:

  • Serotonin: Regulates mood, appetite, sleep, and pain perception.
  • Melatonin: Controls circadian rhythms and supports immune defense.
  • Kynurenine pathway: Involved in immune regulation and mitochondrial energy production.

Up to 95% of dietary tryptophan is metabolized via the kynurenine pathway, while only a small fraction contributes to serotonin and melatonin synthesis. Inflammatory processes often drive this imbalance further toward kynurenine production, potentially leading to reduced serotonin levels and increased generation of neurotoxic metabolites such as quinolinic acid.

Health Implications of Tryptophan Imbalance

Disruptions in tryptophan metabolism may contribute to a wide range of disorders:

  • Mental health conditions: Depression, anxiety, and chronic stress are associated with decreased serotonin and increased production of quinolinic acid.
  • Sleep disorders: Reduced melatonin levels can impair circadian rhythm regulation.
  • Autoimmune diseases: Overactivation of the kynurenine pathway may modulate immune tolerance and promote autoimmunity.
  • Neurodegenerative disorders: Elevated quinolinic acid is linked to Alzheimer’s, Parkinson’s, and multiple sclerosis.
  • Gastrointestinal disorders: Tryptophan supports gut barrier integrity and microbiome homeostasis.

Diagnostic Evaluation at Orion Biomedica

A precise assessment of tryptophan metabolism is used to uncover root causes of unexplained symptoms. The diagnostic approach includes:

  • Fecal tryptophan analysis: Evaluates intestinal availability and absorption.
  • Serotonin and melatonin levels: Measured in blood or saliva to assess neurotransmitter status.
  • Kynurenine-to-tryptophan ratio (KTR): Indicates degree of immune-driven tryptophan catabolism.
  • Quantification of quinolinic acid and kynurenic acid: Reveals neuroinflammatory burden.
  • IDO and KMO enzyme activity: Identifies which enzymatic routes dominate and their impact on immune regulation.

Personalized Therapeutic Strategies

Treatment plans are tailored based on laboratory findings, targeting restoration of metabolic balance:

  • Dietary support: Increased intake of tryptophan-rich foods (e.g., eggs, fish, nuts) and anti-inflammatory nutritional strategies.
  • Nutrient repletion: Supplementation with cofactors critical for tryptophan metabolism such as vitamin B6, B2, magnesium, and SAMe.
  • Microbiome optimization: Use of probiotics and prebiotics to improve intestinal health and tryptophan absorption.
  • Inflammation control: Natural IDO inhibitors such as curcumin, quercetin, and resveratrol may help normalize kynurenine metabolism.
  • Neurotransmitter support: For serotonin and melatonin deficiency, tryptophan or 5-HTP supplementation may be considered (with caution in patients using psychotropic medications).
  • Neuroprotection: In the presence of high quinolinic acid, antioxidants such as vitamins C and E and N-acetylcysteine (NAC) may help mitigate oxidative damage to neurons.

When Should Tryptophan Metabolism Be Assessed?

Testing is recommended in the following situations:

  • Mood disorders: depression, anxiety, irritability
  • Insomnia and circadian rhythm disruption
  • Chronic fatigue syndrome (CFS/ME)
  • Autoimmune diseases (e.g., Crohn’s, ulcerative colitis, MS)
  • Neurodegenerative conditions (e.g., Alzheimer’s, Parkinson’s)
  • Gastrointestinal inflammation or dysbiosis
  • Psychiatric conditions such as autism and ADHD

Safety Considerations

Important: Tryptophan or 5-HTP supplements should be avoided in patients taking SSRIs, SNRIs, MAO inhibitors, or triptans due to the risk of serotonin syndrome.

📌 Learn more about gut microbiota analysis and its influence on tryptophan metabolism.

Selected Literature

Kałużna-Czaplińska J, Gątarek P, Chirumbolo S, Chartrand MS, Bjørklund G. How important is tryptophan in human health? Crit Rev Food Sci Nutr. 2019;59(1):72–88. doi: 10.1080/10408398.2017.1357534.

Kałużna-Czaplińska J, Jóźwik-Pruska J, Chirumbolo S, Bjørklund G. Tryptophan status in autism spectrum disorder and the influence of supplementation on its level. Metab Brain Dis. 2017;32(5):1585–1593. doi: 10.1007/s11011-017-0045-x.

📞 For more information or to schedule an appointment, contact Dr. G. Bjørklund at Orion Biomedica.

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