SAN DIEGO, June 29, 2022 — A new study reports significantly reduced mental and physical fatigue in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID patients, with the administration of oral Anhydrous Enol-Oxaloacetate, (AEO), a medical food and nutritional supplement.

The study reports that six weeks of oxaloacetate treatment resulted in,

• Reduction of fatigue in Long COVID patients by up to 46.8%

• Reduction of fatigue in ME/CFS patients by an average of 22.5% to 33%

The controlled clinical trial, using a dose escalating methodology, utilized ME/CFS patients who had been diagnosed for an average of 8.9 years and Long COVID patients with symptoms for at least 6 months.

ME/CFS patients were given oxaloacetate doses of either 500 milligrams twice per day, 1,000 milligrams twice per day or 1,000 milligrams three times per day. Reduction in fatigue was dose dependent, with the smallest dose yielding a 21.7% reduction in fatigue and the largest yielding a 33.3% reduction in six weeks. Long COVID patients were given either 500 milligrams twice per day or 1000 milligrams of oxaloacetate twice per day, with fatigue reduced by up to 46.8% in six weeks.

“This data is showing oral oxaloacetate treatment may play a key role in moving dysfunctional metabolic changes back towards normal functioning,” says David Lyons Kaufman, MD, study coauthor and founder of the Center for Complex Diseases. “We certainly owe it to ME/CFS patients to give this treatment more investigation.”

Oxaloacetate, a human energy metabolite, is present in nearly every cell of the human body. Metabolomic studies in ME/CFS patients vs. normal controls indicate that oxaloacetate levels are significantly reduced in the plasma of ME/CFS patients.

“For the millions of people worldwide struggling to live with chronic fatigue, this is really hopeful news,” says Alan Cash, coauthor of the study published by the Journal of Translational Medicine, a Springer/Nature publication. “Amelioration of fatigue to this degree may be life changing. This could look like the difference between being stuck in bed for months and being able to get back to work, attending a wedding, and enjoying life again.”

The complete peer-reviewed clinical trial results are made available by the Journal of Translational Medicine.

Oxaloacetate Treatment For Mental And Physical Fatigue In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long-COVID fatigue patients: a non-randomized controlled clinical trial

Abstract

Background

There is no approved pharmaceutical intervention for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS). Fatigue in these patients can last for decades. Long COVID may continue to ME/CFS, and currently, it is estimated that up to 20 million Americans have significant symptoms after COVID, and the most common symptom is fatigue. Anhydrous Enol-Oxaloacetate, (AEO) a nutritional supplement, has been anecdotally reported to relieve physical and mental fatigue and is dimished in ME/CFS patients. Here, we examine the use of higher dosage AEO as a medical food to relieve pathological fatigue.

Methods

ME/CFS and Long-COVID patients were enrolled in an open label dose escalating “Proof of Concept” non-randomized controlled clinical trial with 500 mg AEO capsules. Control was provided by a historical ME/CFS fatigue trial and supporting meta-analysis study, which showed average improvement with oral placebo using the Chalder Scale of 5.9% improvement from baseline. At baseline, 73.7% of the ME/CFS patients were women, average age was 47 and length of ME/CFS from diagnosis was 8.9 years. The Long-COVID patients were a random group that responded to social media advertising (Face Book) with symptoms for at least 6 months. ME/CFS patients were given separate doses of 500 mg BID (N = 23), 1,000 mg BID (N = 29) and 1000 mg TID (N = 24) AEO for six weeks. Long COVID patients were given 500 mg AEO BID (N = 22) and 1000 mg AEO (N = 21), again over a six-week period. The main outcome measure was to compare baseline scoring with results at 6 weeks with the Chalder Fatigue Score (Likert Scoring) versus historical placebo. The hypothesis being tested was formulated prior to data collection.

Results

76 ME/CFS patients (73.7% women, median age of 47) showed an average reduction in fatigue at 6 weeks as measured by the “Chalder Fatigue Questionnaire” of 22.5% to 27.9% from baseline (P < 0.005) (Likert scoring). Both physical and mental fatigue were significantly improved over baseline and historical placebo. Fatigue amelioration in ME/CFS patients increased in a dose dependent manner from 21.7% for 500 mg BID to 27.6% for 1000 mg Oxaloacetate BID to 33.3% for 1000 mg TID. Long COVID patients’ fatigue was significantly reduced by up to 46.8% in 6-weeks.

Conclusions

Significant reductions in physical and metal fatigue for ME/CFS and Long-COVID patients were seen after 6 weeks of treatment. As there has been little progress in providing fatigue relief for the millions of ME/CFS and Long COVID patients, anhydrous enol oxaloacetate may bridge this important medical need. Further study of oxaloacetate supplementation for the treatment of ME/CFS and Long COVID is warranted.

Graphical Abstract

1,000 mg BID Normalized Fatigue Data for Baseline, 2-weeks and 6-weeks evaluated by 3 Validated Fatigue Scoring Questionnaires

Key points

Question: Can normalization of metabolism with oxaloacetate help reduce fatigue in ME/CFS and Long COVID?

Findings: Patients with ME/CFS and Long-COVID treated with oral Anhydrous Enol-Oxaloacetate capsules achieved highly significant reductions in physical and mental fatigue within 6 weeks.

Meaning: Pathological Fatigue is an unmet medical problem pervasive in ME/CFS, Long-COVID, and other diseases. Here, treatment to normalize metabolism with Anhydrous Enol-Oxaloacetate has for the first time shown improvements in Pathological Fatigue.

The full study data is made available by the Journal of Translational Medicine.