Allergies and MCS and the methylation protocol
QUESTION FOR RICH--
Will the protocol help with MCS and with histamine reactions to pollen and other allergens?
You haven't talked much about MCS, and I'm curiouswhat your experinece has been with that...?
Hi, Dreambirdie.
With regard to lowering histamine and thus helping to decrease allergic symptoms, I think it probably will. In the early days of CFS research, there was work done on allergies, because PWCs reported that they had a big problem with them. I think the late Stephen Straus of the NIH (not a very popular figure among the PWCs of the day because of his emphasis on depression in CFS) was involved in this work, as I recall, and the result was that PWCs were not found to have more Type 1 (IgG-histamine) allergies than the normals, and this has always been a puzzle. It may be that because of the methylation deficit, the histamine level rises higher and stays up longer when there is an allergic reaction in a PWC, and maybe that accounts for the reports that allergies are worse in CFS.
With regard to MCS, maybe.
I think there is more than one subset within MCS. Some people with MCS can trace the onset of it to a big exposure to some volatile chemical that they had at a certain time in the past. This apparently damaged the olfactory epithelium in their nasal cavity so that there is no longer a good barrier to prevent entry of chemicals and their transport to the brain via the olfactory bulb, and they develop sensitivity to a whole range of different chemicals after that.
Other people with MCS report that their cases of it came on more gradually, so an acute damage event involving the olfactory epithelium would probably not be involved in those cases.
Marty Pall (who has studied MCS a lot more than I have) has told me that some cases of MCS clearly do not involve entry into the brain via the olfactory epithelium, so perhaps in those cases the chemicals enter the blood via the lungs and are transported across the blood-brain barrier from the blood to the brain. This would be a slower process than direct entry via the olfactory epithelium, I think. Marty also told me that several of the chemicals to which people with MCS are sensitive are known to excite the NMDA receptor, and that would produce excitotoxicity.
I do know that Dr. Grace Ziem has had some success in treating MCS using glutathione and B12 mixed together in a nebulizer, so that suggests that glutathione depletion might be involved in at least some cases of MCS.
A few years ago I cooked up a hypothesis that might explain at least a subset of MCS. It's pasted below. I don't know if it's valid or not, but it might be. If it is, then I think the answer to your question would be yes, at least for a subset of MCS. I would be interested in hearing from people who have MCS whether they found any benefit from this protocol.
So as I wrote, maybe.
Best regards,
Rich
February 15, 2008
Hypothesis for the Pathogenesis of Multiple Chemical Sensitivity
Rich Van Konynenburg, Ph.D.
The olfactory epithelium in the ceiling of the nasal cavities is a small patch of tissue that is made up of two major types of cells, the olfactory neurons and the supporting or sustentacular cells, which are interspersed with the neurons. The olfactory neurons have axons that are connected into the olfactory nerve, which is the shortest pathway to the brain from the outside.
The olfactory neurons have cilia on their surfaces facing the nasal cavities, and these incorporate receptors that are specific for the various substances that can be smelled.
In addition to the olfactory neurons and the supporting cells, the olfactory epithelium also contains cells that secrete mucus, which covers the cilia.
The supporting cells contain cytochrome P450 enzymes at concentrations higher than are found in the liver. It seems clear that their role is to break down (perform Phase I detoxication on) substances that are inhaled.
In normal operation, inhaled substances are dissolved in the mucus, and those for which there are sensitive neurons elicit nerve impulses that travel to the brain and give the sensation of particular smells. The supporting cells apparently then break down and dispose of these substances, maintaining the sensitivity of the olfactory neurons to substances that are newly arrived, and protecting them from the entry of toxic substances.
It is known that glutathione plays a major role in detoxication. Not only does it conjugate certain toxic substances in one of the major Phase II pathways, but it also serves to quench hydrogen peroxide that results from the action of superoxide dismutase on the superoxide free radicals that are generated by the action of the cytochrome P450 enzymes in Phase I detoxication.
If the supporting cells are deficient in the reduced form of glutathione, I suggest that two adverse effects would occur. First, a state of oxidative stress would arise, because of the buildup of reactive oxygen species. These species would be likely to damage the membranes of both the supporting cells and the olfactory neurons. Second, toxic substances would not be broken down, but instead, in the presence of the damaged cell membranes, would likely enter the neurons, and from there would have a short path to travel into the brain, thus producing symptoms such as headache. Neurons are known to have transport mechanisms involving molecular motors that move substances along microtubules.
It would seem that this model for multiple chemical sensitivity would explain several of the observed features of this disorder. One is that people with MCS are sensitive to a range of volatile substances. Another is that symptoms appear very rapidly upon exposure to inhalation of these substances. Another is that temporary relief can often be obtained by using a glutathione nasal spray.
If this model is correct, then it would seem that a cure for MCS might be brought about by restoring the levels of reduced glutathione in the sustentacular cells on a longer term basis. In autism and in chronic fatigue syndrome, it appears that glutathione levels are held down by a vicious circle mechanism that involves a partial block in the methylation cycle, at methionine synthase. Since MCS often occurs together with chronic fatigue syndrome, perhaps this same biochemical mechanism is responsible for MCS. If this is true, the same treatments that are being found helpful in autism and CFS may be helpful for MCS.