Welcome to Phoenix Rising!
Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.
To register, simply click the Register button at the top right.
Rich based his protocol mainly on the study he conducted with Dr. Nathan. I assume undermethylators would need extra methyl donors such as SAMe and/or TMG, but I don't know much about SNPs. They might also need methylcobalamin and higher doses of methylfolate. Before Rich's most recent protocol, he would just tell people who didn't have success with his protocol to try Freddd's protocol which seems to be more geared towards undermethylators. In this protocol (his most recent one), Rich does say to switch to methylcobalamin and adenosylcobalamin if you aren't improving and also suggests increasing methylfolate. This is what Rich has said in the past about this subjectI'm wondering why there is no mention of supplemental SAMe in this protocol? I'd read elsewhere that this was recommended for undermethylators.
A little TMG is often helpful when methylfolate and B12 supplementation are started, because it can help to raise SAMe, needed for recycling methyl B12. After these supplements are well underway and methionine synthase is coming up in activity, the TMG can be stopped, or DMG can be added to counter the BHMT pathway, so as to route more of the homocysteine to the methionine synthase pathway and the transsulfuration pathway.
Some people have had good experience with methylcobalamin. It can be especially helpful if a person has a shortage of methyl groups, though that can also be helped by taking some additional trimethylglycine (some of which is in the multi that is part of the simplified treatment). or some SAMe. It's used a lot subcutaneously by the DAN! doctors in autism treatment, and as you probably know, freddd on this forum advocates its use as well. In his case, because of a mutation in the intracellular B12 processing enzymes, his body is not able to utilized hydroxocobalamin readily. But I believe that this is a rare situation, based on the published literature. freddd does not agree that it is rare, based on his experience.
TMG stimulates the BHMT (betaine homocysteine methyltransferase) reaction, as it is a reactant for it. This reaction takes place in the liver and kidneys. It is an alternative pathway for converting homocysteine into methionine, and it will help to produce SAMe in those organs.
There are a couple of ways that it might produce symptoms. One is that it will initially lower the flow of homocysteine into the transsulfuration pathway, so the rate of production of glutathione may drop lower initially. So symptoms could be caused by initially making the glutathione depletion somewhat more severe.
Another possible mechanism is that it can also take homocysteine away from the main methionine synthase pathway initially, and that will impact the folate metabolism, since the conversion of methylfolate to tetrahydrofolate will decrease in the liver and kidneys.
Betaine and TMG are the same substance. Betaine HCl has a hydrochloric acid molecule bound to it. Yes, if you take betaine HCl, you will also have the benefit of TMG. However, note that TMG stimulates the alternative BHMT pathway from homocysteine to methionine in the liver and kidneys. TMG will promote production of SAMe, but it can shunt flow away from the methionine synthase enzyme, which is partially blocked in ME/CFS. It's important to get this enzyme going, because it is linked to the folate metabolism, which is needed to make new DNA and RNA, and also because it regulates the entire sulfur metabolism. In Amy Yasko's protocol, she recommends starting with some TMG, and then after the B12 and folate have been built up some, to add DMG, which will inhibit the BHMT reaction by product inhibition, and that will push more of the homocysteine through the methionine synthase reaction. The benefit of doing TMG first is that it can increase the level of SAMe, and that is needed by the methionine synthase reductase reaction, which rescues the cobalamin coenzyme of methionine synthase when it becomes oxidized, thus restoring it to the +1 oxidation state and giving it a methyl group, so that it is a functional methylcobalamin molecule again. I don't know what dosage of betaine HCl will interfere with the methionine synthase reaction. Some people use the Allergy Research Group's dilute HCl solution to augment their stomach acid, and then there is no TMG (betaine) involved. Others use lemon juice (note that it is important to use a drinking straw and to flush the teeth with water afterward, because the citric acid in lemon juice chelates calcium and can damage the enamel on the teeth over time).
I'm wondering why there is no mention of supplemental SAMe in this protocol? I'd read elsewhere that this was recommended for undermethylators.
Rich doesn't recommend a specific brand for folinic acid. The reason Rich doesn't recommend intriniB12 is because the formula changed so it no longer has folinic acid. Source Naturals sells Megafolinic which seems to be reasonably priced.Can someone clarify the brand or name of folinic acid that Rich is recommending here other than the one available from Yasko's site.
At one time Metagenics 'Intrinsi B12/Folate' was being used but I see it's been discontinued at iherb which is where I normally shop.
Are there others or can you tell me the specific term of the ingredient I look for on the label?
No problem. What happened with your earlier attempt(s)?Hi Lotus,
Thanks so much for clarifying this and also for the providing the links. Much appreciated. I'm getting ready to retry the protocol and of course, have to relearn all of the pertinent information again.
It's always good to start with low doses and also make sure you don't have low potassium. I'm not sure if the passing out is from low potassium or not, but you might want to look into that.When trying it years ago, I can't remember all the reasons for setting it aside. Probably have notes on it somewhere. But I do remember there were major problems with passing out. Was always running for the closest couch or bed.
B12 taken orally (such as that in the B Right) isn't very effective for the people here because the absorption rate in the gut is very low compared to B12 taken sublingually. The B Right b complex isn't recommended though because it has folic acid and folic acid can cause problems for some people. I don't know if it's absolutely necessary for you to stop folic acid immediately, but it would be good to transition towards using supplements without folic acid. In post #67 of this thread, I recommended a b complex and multi dose multivitamins that can be used as b complexes. If you do try one of these b complexes, make sure you adjust your methylation dose accordingly since they either have folinic acid (as calcium folinate) or folinic acid and methylfolate. It would be good to stick to the recommended doses when starting the protocol. If you're taking the Neurological Health Formula you might not want to also take the one with a lot of P5P since the NHF also has P5P. There's also a supplement on sale (buy one get one free) at Swanson's that has B1, B2, B3, B5, and choline (no B6/P5P or biotin) which could be used as a b complex.I'm sorry I can't read very much right now, but can someone help me by letting me know how a B complex like Jarrow B Right fits into this? If it has Methyl B12 can I also take Hydroxy B12?
I hoped I could ask a further few questions about treatment (apologies for cross posting):
1. Is it acceptable to post up the Methylation Pathway Panel analysis here? I don't have a doctor to do this for me.
2. What does "rebalancing" mean in terms of doses of mythylfolate and Metafolin? I only see, for example, 200mcg of methylfolate as the dose to use.
3. I'm having real difficulty establishing the vitamins/mineral base - 100mg of Vit C (powder) seemed to give me a sore throat; 100mg of magnesium oxide seems to make my heart beat hard for about 10-15 mins (and epsom salt baths wipe me out for days) . I'm now getting a bit gun shy. Are these normal? I've a very leaky gut due to candida and seem to be reacting to many foods. I'm also willing to accept that some symptoms could be psychosomatic!
The ingredients of the magnesium tablets are as followed:
Magnesium Oxide, Bulking Agent (Microcrystalline Cellulose), Sodium Carboxymethylcellulose, Anti- Caking Agents (Magnesium Stearate, Magnesium Silicate), Glazing Agents (Hydroxypropyl Methylcellulose, Glycerine, Carnauba Wax), Colour (Titanium Dioxide).
Has anyone tried magnesium oil?
4. I know magnesium and potassium are both electrolytes, so I wondered if titrating the dose of one could intensify the deficiency in the other?
Thanks very much.
I think this is only the second report I've seen, the other one being from a person in Germany, who also had good results. I think the cost has prevented some people from trying it. I started suggesting it, as well as liposomal glutathione, some time back, as two possibilities for actually getting glutathione into the cells to help raise it faster on the methylation protocol. Most IV glutathione is taken out of the blood by the kidneys, which probably do benefit, but it isn't a very effective way to raise glutathione in other organs, tissues and cells, and especially not for the longer term. I'm glad to hear that Dr. Klinghardt is encouraging the use of S-acetyl glutathione, too.