QUESTION: I am following up on our discussion about your treatment protocol for patients that have severe methylation issues, and your slow titrations/nutritional protocols. I discussed with you a patient with COMT homozygous, MTHFR heterozygous, and GST allele absent, who has numerous multi-system complaints and has a pacemaker. He tried only 2 grams of MSM orally and claims that he is ‘allergic to it’, and that he feels this lead to some PVCs. Keep in mind that he claims he is allergic to everything, and besides genuine upregulation of methylation problems (COMT) converting to epinephrine… anxiety about a potential reaction can induce the HPA axis further leading to increased problems. Thank you for your willingness to share your protocols for these types of patients. This patient has methylation (COMT ++, MTHFR +-), acetylation (NAT++) and glucorination reactions (GST allele absent) as well as oxidative stress problems (SOD ++).
ANSWER: This is what I think and do with this sort of patient:
Methyl defect + COMT defects = tricky… SNP at COMT = 1/2 less catecholamine removal at least when you methylate them they form Epi and can’t get it out fast enough – since the only back up to MAO is COMT- AND- they generally are poor sulfation people too. And if poor glucuronidation you have more back up and “allergy” really detox inadequacy to a lot of things.
You have to saturate the co factors for the back up detox pathways first so they tolerate the methyl support.
- Sulfation is Molybdenum dependent
- MAO is B2 and B6 dependent
- Glucuronidation needs L-glutamine, aspartic acid, iron, magnesium, B3 and B6
I typically stop all methyl donors for a time to up-regulate the Catecholamine and SO4 back ups THEN add in methyl support slowly.
Methyl support looks like:
- 200-400mcg molybdenum QD to BID
- Riboflavin 5-phosphate 65-100mg BID
- P5P 100 mg bid
- Consider 500 mg Niacinamide BID,
- Mg
- 1 -3 grams glutamine BID
Most do very well with titrated doses of IV glutathione (500 mg IVP then 1-2 grams 1-2X a week). Then start the Methyl support with a balanced formula at LOW dose (like Methyl Guard Plus etc) Never give a COMT injured person 5MTHF (or most of the time any single methylator) alone.