L.M. Forsyth, M.D.; A.L. MacDowell-Carnciro, M.D.; G.D. Birkmayer, M.D.; Ph.D.; H.G. Preuss, M.D.; and J.A. Bellanti, M.D.; Departments of Pediatrics and Microbiology-Immunology and the Immunology Center, Georgetown University Medical Center, Washington, D.C.

Background:
Chronic fatigue syndrome (CFS) is a disorder of unknown etiology, consisting of prolonged, debilitating fatigue, and a multitude of symptoms including neurocognitive dysfunction, flu-like symptoms, myalgia, muscle weakness, arthralgia, low-grade fever, sore throat, headache, sleep disturbances, and swelling and tenderness of lymph nodes. No effective treatment for CFS is known.

Objective:
The purpose of the study was to evaluate the efficacy of the reduced form of nicotinamide adenine dinucleotide (NADH) administered orally in a randomized, double-blind, placebo-control, crossover study in patients with CFS. NADH is known to trigger energy production through ATP generation, which may form the basis of its potential effects. The study drug is ENADA® NADH the only stabilized absorbable oral form of NADH a nutritional supplement product.

Methods:
Twenty-six evaluatable patients who fulfilled the CDC criteria for CFS completed the study. Medical history, physical examination, laboratory studies and questionnaire were obtained at baseline, 4, 8, and 12 weeks. Subjects were randomly assigned to receive either 10 mg of NADH (ENADA®) or placebo at week 0 for a four-week period, followed by a four-week wash-out period, followed by a final four-week period in which subjects were crossed to an alternative regimen.

Results:
No adverse effects were observed related to the study drug. Within this cohort of twenty-six patients, four times more patients responded to NADH (ENADA®) compared to placebo.

Conclusion:
Collectively, the results of this preliminary study indicate that NADH (ENADA®) may be an effective therapy in the management of Chronic Fatigue Syndrome and suggests that further clinical trials be performed to establish its efficacy in this clinically perplexing disorder.
The full scientific study is submitted for peer-review publication in the Annals of Allergy, Asthma and Immunology.

Open-Label Study:
During a follow-up, open label, pilot study, it was observed that 73% of the subjects achieved marked improvement over time. Therefore, based upon these encouraging results, we have decided to continue the open-label study in a larger cohort of participants.