The role of kynurenine pathway and NAD+ metabolism in myalgic encephalomyelitis/chronic fatigue syndrome

Mona Dehhaghi, Hamed Kazemi Shariat Panahi, Bahar Kavyani, Benjamin Heng, Vanessa Tan, Nady Braidy, Gilles J. Guillemin*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

14 Citations (Scopus)
319 Downloads (Pure)


Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious, complex, and highly debilitating long-term illness. People with ME/CFS are typically unable to carry out their routine activities. Key hallmarks of the disease are neurological and gastrointestinal impairments accompanied by pervasive malaise that is exacerbated after physical and/or mental activity. Currently, there is no validated cure of biomarker signature for this illness. Impaired tryptophan (TRYP) metabolism is thought to play significant role in the pathobiology of ME/CFS. TRYP is an important precursor for serotonin and the essential pyridine nucleotide nicotinamide adenine dinucleotide (NAD+). TRYP has been associated with the development of some parts of the brain responsible for behavioural functions. The main catabolic route for TRYP is the kynurenine pathway (KP). The KP produces NAD+ and several neuroactive metabolites with neuroprotective (i.e., kynurenic acid (KYNA)) and neurotoxic (i.e., quinolinic acid (QUIN)) activities. Hyperactivation of the KP, whether compensatory or a driving mechanism of degeneration can limit the availability of NAD+ and exacerbate the symptoms of ME/CFS. This review discusses the potential association of altered KP metabolism in ME/CFS. The review also evaluates the role of the patient's gut microbiota on TRYP availability and KP activation. We propose that strategies aimed at raising the levels of NAD+ (e.g., using nicotinamide mononucleotide and nicotinamide riboside) may be a promising intervention to overcome symptoms of fatigue and to improve the quality of life in patients with ME/CFS. Future clinical trials should further assess the potential benefits of NAD+ supplements for reducing some of the clinical features of ME/CFS.

Original languageEnglish
Pages (from-to)698-711
Number of pages14
JournalAging and Disease
Issue number3
Publication statusPublished - 18 May 2022

Bibliographical note

Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


  • gut microbiota
  • Kynurenine pathway
  • myalgic encephalomyelitis/chronic fatigue syndrome
  • NAD+
  • tryptophan


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