Serotonin in Chronic Fatigue Syndrome & Fibromyalgia

Townsend Letter for Doctors and Patients, Nov, 2001 by Melvyn R. Werbach

While the picture is far from clear, serotonin metabolism appears to play a role in both chronic fatigue syndrome (CFS) and fibromyalgia -- although the nature of that role appears to differ.

Tryptophan is the dietary precursor to serotonin and, for fibromyalgia, there is some evidence that tryptophan levels are depressed. For example, in a study of fibromyalgia patients suffering from severe pain, plasma free tryptophan levels were inversely related to the severity of their pain. [1] Moreover, when fibromyalgia patients were compared to normals, plasma tryptophan levels tended to be lower in the patient group, and their transport ratio of tryptophan to the other competing amino acids was significantly decreased, suggesting that brain serotonin levels may also be depressed. [2]

Does the administration of a serotonin precursor help patients with fibromyalgia? In the general population, tryptophan supplementation usually provides a mild degree of analgesia. Moreover, it may be especially effective for the subset of chronic pain patients with a disorder of serotonergic transmission. [3]

As to fibromyalgia, a group of 50 patients received 100 mg 3 times daily of 5-hydroxytryptophan, the metabolite of tryptophan and immediate precursor of serotonin, in an open trial. After 3 months, nearly half of the group had a fair to good degree of overall improvement. There were highly significant improvements in fatigue, the number of tender points, pain intensity, anxiety and sleep quality. [4] These results were similar to those of an earlier double-blind study by the same group of investigators, [5] and suggest that fibromyalgia patients may respond to L-tryptophan supplementation similarly to other patients suffering from anxiety, depression, insomnia and pain.

Turning to CFS, at least 3 studies have found L-tryptophan to be depressed in the plasma of CFS patients [6-8] -- a finding already noted in fibromyalgia patients. However, in contrast to fibromyalgia, there is evidence that OFS is marked by serotonergic hyperactivity. One study found not only that CFS patients had higher baseline plasma tryptophan levels, but also that these levels failed to rise and fall normally during exercise, causing the researchers to speculate that an abnormally high level of brain serotonin may cause the persistent central fatigue. [9] (In healthy subjects, L-tryptophan administration can cause central fatigue. [10]) Moreover, several other studies have also found evidence of increased serotonergic activity in CFS patients." [11-14]

If CFS is marked by serotonergic hyperactivity, then medications that block serotonin receptors may be beneficial. Indeed, a small pilot study found that the use of serotonin (5-HT3) receptor antagonists was followed by at least a 35% improvement in about one-third of patients. [15]

Would nutritional supplements be equally effective while having less danger of adverse side effects? The efficacy of nicotinamide adenine dinucleotide (NADH), the reduced coenzyme form of niacin, has been investigated in a double-blind crossover study. At baseline, CFS patients were found to have elevated urinary concentrations of 5-hydroxyindoleacetic acid, the major metabolite of the neurotransmitter serotonin. They received 10 mg daily of NADH or placebo. Not only was NADH significantly more effective in reducing CFS symptoms than placebo, but the elevated 5-HIAA levels dropped to normal -- suggesting that the efficacy of NADH could well be due to an ability to normalize serotonergic hyperactivity. [16]

Perhaps other nutritional approaches that reduce brain serotonin levels would also be effective. For example, CFS patients could be placed on a low-tryptophan diet, or they could be supplemented with the essential amino acids that compete with tryptophan for brain uptake (phenylalanine, tyrosine, leucine, isoleucine, and valine). Hopefully, researchers will eventually pursue these lines of investigation.

Doctor Werbach cautions that the nutritional treatment of illness should be supervised by physicians or practitioners whose training prepares them to recognize serious illness and to integrate nutritional interventions safely into the treatment plan.

References

(1.) Moldofsky H, warsh JJ. Plasma tryptophan and musculoskeletal pain in non-articular rheumatism ('fibrositis syndrome'). Pain 5(1):65-71, 1978

(2.) Yunus MB et al. Plasma tryptophan and other amino acids in primary fibromyalgia: a controlled study. J Rheumatol 19(1):90-4, 1992

(3.) Liberman HR et al. Mood, performance and pain sensitivity: Changes induced by food constituents. J Psychiatr Res 17(2):135-45, 1982-3

(4.) Puttini PS, Caruso I. Primary fibromyalgia syndrome and 5-hydroxy.L-tryptophan: a 90-day open study. J Int Med Res 20(2):182-9, 1992

(5.) Caruso I et al. Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome. J Int Med Res 18(3):201-9, 1990

(6.) Bralley JA, Lord RS. Treatment of chronic fatigue syndrome with specific amino acid supplementation. J Appl Nutr 46(3):74-8, 1994