Tryptophan availability and the susceptibility to stress in multiple sclerosis: a hypothesis.

In his seminal description of the clinical manifestations of multiple sclerosis (MS) in 1868 Charcot suggested that psychological stress is an important factor in the pathogenesis of the disease. MS patients often relate that mental stress exacerbates their symptoms and even provokes attacks of their disease. Moreover, a subgroup of MS patients experiences exacerbation of symptoms following a period of mental stress rather than occurring at times when stress is maximal, i.e., attacks are reported to occur on the rebound from stress. Psychological stress may also contribute to the onset and long term clinical deterioration of the disease. Mental stress is associated with activation of the hypothalamic-pituitary adrenal (HPA) axis resulting in increased release of ACTH and cortisol secretion. Stress-induced activation of the HPA axis is associated with an increased metabolism of cerebral serotonin (5-HT) the synthesis of which is dependent upon the availability of its precursor tryptophan. Thus, increased tryptophan availability may partly underlie the general response to stress. Plasma and CSF tryptophan levels are diminished in chronic MS patients and it is suggested that plasma tryptophan levels are even lower in patients who are stressed. Attenuated increase in the availability of systemic tryptophan in response to stress is thought to underlie the susceptibility of MS patients to stress. This hypothesis is supported by the findings in chronic MS patients of a significantly diminished adrenal cortisol reactivity to insulin-induced hypoglycemia which is considered a stress response mediated through the 5-HT system. Consequently, since patients with MS exhibit an abnormal response to stress it follows that increased tryptophan availability through dietary supplementation would diminish their vulnerability to psychological stress. Additionally, if sustained or repeated stress contributes to progression and clinical deterioration of the disease then chronic tryptophan supplementation also may halt its progression.