tryptophan, serotonin and epilespy. A new approch to control seizures

Hello, I’m Paolo Mainardi, I’m a chemistry and I work on epilepsy in the Neurological Clinic of University of Genoa since 1982. I had a lot of experience on amino acids and peptides in plasma and CSF in different neurological diseases. In ’90 I found decreased plasma levels of Tryptophan and the other Large Neutral Amino Acids (LNAAs) in epileptics respect controls (Lunardi G, Mainardi P, Albano C in Allegri Flippini G et al eds, Tryptophan and Epilepsy in Recent advances in tryptophan research Plenum Press, New York). Tryptophan (trp) is the only brain precursor of serotonin and by our results I can estimate a 30% reduction of trp brain uptake in epileptics respect controls. In the same years we started clinical studies on Selective Serotonin Reuptake Inhibitor drugs, largely used as anti depressant. These drugs was wrongly believed to be pro-convulsants, but our results shown their able to help the seizure control (Favale E, Mainardi P, Albano C. Neurology 45: 1926. 1995; Favale E, Albano C. Seizures 12: 316. 2003). In agreement with our results Jobe and Browing (Jobe PC, Browining RA. Epilepsy Behav 7: 602. 2005) put forward a theory ) about the presence in the brain of exterior defensive shields. In their view, both epilepsy and affective disorders have different intrinsic fabricators, i.e. neuronal circuits which actually initiate and sustain dysfunctional episodes. However, they share common exterior defensive shields which are made up of circuits using noradrenaline and serotonin and protect the system from a deranged function of the intrinsic fabricators. This may lead to either the epileptic pathology or affective disorders, such as depression, according to the particular fabricator involved. Therefore an increase in brain serotonin level has both anticonvulsive and antidepressant effects. The decrease in the amount of tryptophan which arrives to the brain is likely to result in a corresponding decrease of brain serotonin synthesis and in a diminished serotonin control. A des-metabolic gastro-intestinal absorption of LNAAs could be a concomitant cause of epileptic pathogenesis. Because in the gastrointestinal system LNAAs (trp included) compete to the same carrier, like to BBB, I thought that a protein rich in trp and poor in the other LNAAs is able to increase trp/LNAAs plasma ratio I think better than only trp. Unfortunaly Tryptophan is the limiting amino acid in most sources of proteins, then these cause a decrease in plasma Trp-LNAAs ratio and are therefore not suitable for supplementation of tryptophan. Finally I found alpha-lactalbumin (ALAC), a whey protein, naturally occurring in human milk, with the highest Trp-LNAAs ratio of all quantitatively relevant, food-derived proteins. It is shown that ALAC can increase plasma Trp-LNAAs ratio of up to 48% compared to casein. By ALAC I developed Serplus (Giofarma Srl, info@giofarma.it) a serotoninergic food supplement. In a pilot trial on 18 drug resistant epileptic patients we had a good clinical outcome in 10 out 18 (Albano C, Leonardi A, Mainardi P. 7th European congress on epilottology, Helsinki 2006). The mean percent seizures decrease was 48% ± 36% min= 0%, max= 100%. After Serplus in 13 patients, the seizures were milder; 5 pts referred a marked amelioration of mood. In 1 pt body weight was reduced; in 1 pt turned up a sleep improvement. In these days a local multicenter trial is starting. The patients who have had a good clinical outcome (10 out 18) still now, after a year, have a good control of the seizures.