The Efficacy of L-cysteine in Prevention of Headache Attacks in Migraine Patients. Randomized Intervention Trial With a Medical Device (Acetium®Capsules)

Background: Globally, 15% of the population is affected by migraines at some point in their life-time. Pprophylactic treatment of migraines is an important part of the total management of migraine patients, having twofold goals: i) to reduce the frequency, painfulness, and/or duration of migraines, and ii) to increase the effectiveness of abortive therapy. During the past several decades, a large number of optional modalities have been tested as preventive measures of migraine attacks. Not unexpectedly, the effects of any such preventive therapies are highly variable, and in many patients, the attack frequency is not under satisfactory control. Many of these drugs also have untoward side effects that offset their potential benefits.

Recently, spontaneous case testimonials were received by Biohit Oyj from migraine patients, reporting that our new medical device, Acetium™ capsule (containing 100mg L-cysteine, developed for inactivation of acetaldehyde in the stomach contents after alcohol intake), proved to be highly effective against migraine attacks. Their headache attacks disappeared almost immediately after onset of L-cysteine administration, all of them remaining in complete remission for several months up to several years by now.

These spontaneous testimonials prompted us to formulate a novel study hypothesis that could possibly explain these dramatic effects of L-cysteine in migraine prevention, to be tested in this RCT. This novel hypothesis is starting from the fact that, swelling and dilatation of cerebral blood vessels is necessary to provoke the attack in this vascular-type of headache.

It is known that Nitric Oxide (NO) is the final trigger of migraine attack, operating through phosphorylated protein kinase G (PKG) and Ca2+ channels, slowing the influx of calcium into the cell, which leads to smooth muscle relaxation and vasodilation. Histamine is a potent inducer of NO Synthase, making NO available locally on the vasculature, acting through endothelial H1-receptors. Histamine is synthesized from histidine in tissue mast cells, which are ubiquitous cells and their activation e.g. in the meninges has long been suspected to be involved in generating migraine headaches. Finally, one of the potent liberators of histamine from the mast cells is acetaldehyde, which, in turn, is effectively inactivated by L-cysteine (Acetium capsule). This led us to rational that by eliminating acetaldehyde in the stomach, L-cysteine could block (or reduce below the threshold levels) histamine liberation from the tissue mast cells and ECL cells in the stomach, thus arresting its multitude of functions, of which vasodilatation is critically involved in the migraine attack.

Objective: To validate the novel hypothesis that daily use of L-cysteine is an effective means to decrease the frequency of (or completely abort) the headache attacks in migraine patients.