THE MEASUREMENT OF 5-HIAA URINARY CONCENTRATION AS A POSSIBLE PREDICTIVE MARKER OF DISEASE ACTIVITY AND THERAPEUTIC EFFICACY OF NADH IN THE CHRONIC FATIGUE SYNDROME

Joseph A Bellanti MD'; Linda M Forsyth MD'; Ana Luiza MacDowell-Carneiro MD'; Dawn B. Wallerstedt, MSN, FNP'; Harry G Preuss MD2 and Georg D Birkmayer MD. PhD3

From the Departments of Pediatrics and Microbiology-Immunology and the International Center for Interdisciplinary Studies of Immunology1 and the Department of Medicine, Division of Nephrology2, Georgetown University Medical Center, Washington, DC; and Birkmayer Pharmaceuticals3, Vienna, Austria

Background: Chronic fatigue syndrome (CFS) is a disorder of unknown etiology characterized by prolonged, severe fatigue that persists six months or greater in duration and by a multitude of symptoms including neurocognitive dysfunction, flu-like symptoms, myalgia, muscle weakness, arthralgia, low-grade fever, sore throat, headaches sleep disturbances and swelling and tenderness of the lymph nodes. We have recently demonstrated the clinical effectiveness of reduced nicotinamide adenine dinucleotide (NADH) in a group of 26 patients with CFS in a double-blinded, placebo-controlled, crossover study .

Objective: The overall goal of the present study was to extend our initial observations of the clinical efficacy of NADH in CFS to the measurement of a spectrum of biochemical neurotransmitter metabolites which might serve as predictive marker(s) of disease activity. Plasma concentrations of norepinephrine, dopamine and serotonin as well as urinary metabolites, 5-hydroxyindole acetic acid (5-HIAA) and homovanillic acid (HVA) were measured.

Methods: Ten of the originally reported patients with CFS were evaluated. Plasma concentrations of the norepinephrine metabolite MHPG and urinary concentrations of the serotonin and dopamine metabolites, 5-HIAA and HVA, respectively, were measured and the results were analyzed and correlated with treatment of subjects with NADH or placebo.

Results: No significant changes in plasma metabolites were observed. In contrast, baseline values of urinary concentrations of 5-HIAA were elevated (>2mgfL) prior to NADH or placebo in 15/20 (75%) of patient-paired-sample measurements. Following NADH treatment these elevated 5-HIAA concentrations returned to the normal range (<2mg/L) in 7/10(70%) of subjects receiving NADH and in 3/10 (30%) of subjects receiving placebo. The mean negative change in urinary 5-HIAA concentration over the 4 week treatment period was -3.41 in NADH-treated subjects vs. -1.92 in placebo-treated subjects; the mean positive change in urinary 5-HIAA concentration over the 4 week period was +0.17 in the NADH-treated subjects vs. +4.73 in the placebo-treated group (p<0.05).

Conclusions: The results of these preliminary studies not only suggest that NADH is a safe naturally occurring biological substance which may be a useful therapeutic adjunct in the management of the chronic fatigue syndrome, but also that the measurement of urinary 5-HIAA may serve both as an important predictive marker of disease activity as well as an objective marker of improvement following NADH therapy.