Driving research of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS),
Post Treatment Lyme Disease Syndrome (PTLDS), Fibromyalgia and Long Covid

Nitrogen Metabolism and
Testing Nitrogen Hypothesis in ME/CFS

This project aims to test the nitrogen hypothesis, which is that damaging, nitrogen-containing by-products of energy metabolism accumulate more readily in the cells of ME/CFS patients.

  • Christopher Armstrong, PhD
  • Ronald Davis, PhD
  • Paul Gooley, PhD
  • Neil McGregor, PhD

Of particular interest are the mitochondria and their role in energy production and resolution of the inflammation that is generated by muscular stress and exercise. It is both possible and even likely that clues for potential biomarkers for PEM will be revealed in these highly detailed studies. 


We hypothesize that toxic nitrogen-containing by-products of energy metabolism accumulate more readily in the cells of ME/CFS patients. This accumulation, in turn, creates a cycle of energy generation to overcome a stressed state while generating more toxic nitrogen by-products in the process. We will also identify the compounds that can circumvent the production of toxic nitrogen by-products and release patients from this cycle.


To test this hypothesis, we will culture white blood cells in growth media with added nitrogen-labelled amino acids and measure the nitrogen-labelled by-products of energy metabolism. Cells from 30 ME/CFS patients and 20 age and sex-matched controls will be collected and processed at the Stanford Genome Technology Center and cultured for our nitrogen tracking experiment. These experiments will be conducted on blood cells directly from ME/CFS patients and cells cultured from ME/CFS patients.

To capture whether there is an ammonia accumulation in vivo, our best available option is observing the urine concentration of nitrogen-containing metabolites over a short time-course in which varying levels of physical/mental activity have occurred. The 30 ME/CFS patients and 20 sex-match control subjects from the above experiment will be required to provide all urine samples over 4 consecutive days (~20 samples per individual) while their exertion and heartbeat data is collected using wearable technology. Normally, most nitrogen by-products are converted to primary urea along with amino acids, peptides, creatine, creatinine, and polyamines.

In a pathological state, highly reactive, toxic nitrogen by-products are excreted in the urine as nitrate, nitrite, and ammonia. We will measure the ratios of healthy to pathological nitrogen metabolites in the urine and correlate this with the metadata activity.

Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS) Post Treatment Lyme Disease Syndrome (PTLDS), Fibromyalgia Leading Research. Delivering Hope.Open Medicine Foundation®

What are the advantages of giving from your Donor Advised Fund (DAF)?

  • Your gifts to your donor advised fund entitle you to an immediate income tax deduction at the time of contribution.
  • You avoid capital gains tax on appreciated assets you place in your donor advised fund.
  • Your fund’s investment gains accumulate tax free.
  • Funds are distributed to Open Medicine Foundation in your name and immediately put to use to support our worldwide research efforts.

How do I make a donation through my DAF?

Just click on the DAF widget below. It is simple and convenient to find your fund among the over 900 funds in our system.

Still can’t find your fund? 

  • Request a grant distribution through your Donor Advised Fund sponsor
  • Be sure to use OMF’s EIN #26-4712664
  • You can also designate OMF as a beneficiary for your Donor Advised Fund
  • Questions? Give us a call at 650-242-8669