Kynurenine

Kynurenine is an amino acid that is produced in the body by the metabolism of the essential amino acid tryptophan.

ME/CFS

The Open Medicine Foundation's ME/CFS Severely Ill, Big Data Study found that patients in the study group with severe ME had one of several defects involving the IDO2 gene, which affected tryptophan - kynurenine metabolism. This lead to the Metabolic Trap theory.

Kynurenine is a neuroprotectant and a potential treatment. A clinical trial has been announced to investigate the effects of kynurenine, Robert Phair has stated the potential benefits of kynurenine in people with ME/CFS that may be:

• reduced brain fog
• reduced memory impairment, and
• improvements in headache symptoms

Uppsala trial, Sweden

In April 2020, the Open Medicine Foundation announced a pilot treatment trial of kynurenine for ME/CFS. Dr Jonas Bergquist will be running the trial.

Trial type

Pilot trial, with cross-over at 3 months. Patients receiving the kynurenine will change to the placebo after 3 months, and patients receiving the placebo will switch to the kynurenine. No control group.

Aims

To see whether kynurenine improves cognitive impairment (brain fog), headaches and memory in ME/CFS patients.

Patients

Only 20 out of a group of 100 ME/CFS patients. Patients will be those identified as having a low level of kynurenine in blood serum and ME/CFS.

Outcomes

Measurements will be taken from wearable sensors.

Potential benefits

Kynurenine might be beneficial to ME/CFS patients; the Open Medicine Foundation's kynurenine trial aims to investigate this.

Suppose that some brain cells in a particular brain nucleus are in the IDO metabolic trap. This means that in those cells the concentration of tryptophan is too high, and the concentration of kynurenine is too low.

Supplying an outside source of kynurenine, as Dr. Bergquist proposes, could conceivably solve part of the problem by allowing those brain cells to make the neuroactive metabolites of kynurenine that they cannot make if the metabolic trap has been sprung. So, the clinical trial might improve symptoms caused by too little kynurenine or too little kynurenic acid, a known neuroprotectant.

Dr. Bergquist's expertly designed clinical trial of kynurenine in ME/CFS to improve brain fog, memory, and headache is both important and timely.

— Robert Phair, Kynurenine and the Metabolic Trap Hypothesis

Learn more

• Kynurenine - PubChem
• L-Kynurenine - PubChem
• Kynurenine clinical trial - Open Medicine Foundation

See also

• Kynurenine pathway
• Metabolic trap
• Open Medicine Foundation
• IDO
• IDO2
• Tryptophan

serum The clear yellowish fluid that remains from blood plasma after clotting factors have been removed by clot formation. (Blood plasma is simply blood that has had its blood cells removed.)

indoleamine (IDO) - any derivatives of an indole (e.g., serotonin, tryptophan) that contain an amine group

indole (IDO) - a signalling molecule produced by bacteria as a result of metabolising tryptophan, found in the intestines

metabolic trap hypothesis An hypothesis which proposes that the normal metabolic functioning of the cell has become "trapped" in an abnormal state, which may lead to body-wide symptoms.

metabolite A chemical compound produced by, or involved in, metabolism. The term is often used to refer to the degradation products of drugs in the body.

metabolic trap hypothesis An hypothesis which proposes that the normal metabolic functioning of the cell has become "trapped" in an abnormal state, which may lead to body-wide symptoms.