Methylfolate -> joint pain

Hey guys, so looking for someone who knows a bit of Biochem.

So here’s the story. I’m double MTHFR 677 and I also have a double COMT mutation. I’ve read a lot about methylation and I believe it plays a big part in epigenetics, detox, dna regeneration and energy production. I think this could be PART of the reason I’m vulnerable to chronic sickness.

Anyway, the way I understand it, SAMe has two jobs. It hands off a methyl group that eventually turns into homocysteine (which is then used to either create glutathione, or be remethylated by methylfolate into methionine and keep the cycle going), and its second job is to hand off a methyl group to norepinephrine so that it can be discarded.

Since I’m double COMT it makes sense that I’m super anxious and agitated my whole life (low COMT activity = low norepinephrine methylation = epinephrine hangs around a long time = anxiety). It also makes sense that I would need more SAMe so I can methylate more neurotransmitters. Therfore methylfolate should help me.

Since I’m double MTHFR it makes sense that I would need methyfolate.

Here’s the rub. When is started taking methylfolate a few days ago I started to feel worse almost immediately. Joint pain in my knees, hips bicepts and neck. And I didn’t take a lot, just 100 MICRO grams. Some people do up to 10 milligrams. So I stopped, thinking I had some detox issue or a blocked methylation pathway for some other reason. I then took some Liposomal glutathione, and boom the joint pain exploded. I feel like I’m 100 years old.


My question is, biochemically what can cause this? Why would I feel worse? The only think I can think is that the glutathione, and the methylfolate to the extent that it creates glutathione, is causing my body to move metals. That’s the only explanation I can think of. The book says I should feel better, particularly on such low doses. Instead I feel worse. This seems to be a common story in mercury toxic people, they do IV glutathione and permanently damage themselves.

Do people think this confirms a metals issue, or is there something else going on?

I considered the methylfolate creates a sulfite issue through the transulfation pathway, maybe that’s the issue? But when I pee on the sulfite stick it doesn’t show as elevated.

Post Edited (dcd2103) : 2/22/2020 8:34:58 PM (GMT-7)

Hey Georgia.

Thank you for the info! I don’t have an active case of lyme tho. Mine is post infection autoimmune, so I’m not sure there’s a ton to kill. Also, the immune system theory would be a third order process (open up detox pathways -> boosted immune -> herxing from killing pathogens). I took so little methylfolate, 100 micrograms for 4 days, that it couldn’t have boosted my immune system so much that suddenly im killing things in that short a span. Has to be a more direct biochemical explanation.

Your idea in eating the methylfolate is a good one. I had been considering the Wahls protocol diet which includes enormous amounts of leafy vegetables, and this is another reason to do that.

Where might I have a BH4 issue? Is it an SNP that causes it, or just a nutrional deficiency? Any tips for fixing?

So you’re saying I was “herxing” from 100 micrograms of methylfolate? Yet I’ve yet to herx from antibiotics or herbs.

The *simplest* definition for a detox way? I dont know the answer to that, what is it?

I had extreme anxiety, a temp and extreme pain that got me to urgent care on my 4th day of liposomal glutathione.

I was taking it for mold detox but in retrospect I think it was from mercury in system.

Could mold be an issue for you?

To answer one question above, detoxing is simply a chemical reaction that nullifies a charged particle. There are many ways to do this as there are many chemical reactions that can occur. Without detoxing, charged particles floating around can cause all kinds of havoc. An example of a simple form of detox would be for potassium to bind a compound to negate its charge. What would happen if no potassium was available? That compound would either "cause havoc" or be bound by something else with the same valance as potassium. One common alternate to potassium is rubidium. If rubidium is not available, then cesium may take its place. Potassium is usually available for such a reaction and a quick bond nullifies oxidative stress relatively quickly. Having to find a rubidium or cesium for such a reaction takes longer and allows more oxidative stress. That compound may not be as stable with rubidium or cesium which may allow for increase problems in the future.

Borrelia and other pathogens in our blood stream go where ever they can to survive. Our immune response is so focused that very little can live in our blood very long. Some pathogens have found ingenious ways to stay a live like borrelia binding to plasminogen and pathogens binding fibroblasts. They can use various methods for doing this like using a metallothionein copper binding site or binding the proteoglycan decorin. Why is this important?

I'll try to explain it like this, one drop of cyanide will kill you but 1000 drops of Kool-Aide won't. One causes a very different reaction than the other. Your immune response used to be like cyanide to pathogens and now it's Kool-Aide. This happens to all of us over time as we age. The sicker we are or the more pathogens we are exposed to, the faster it happens. With a lot of pathogens, a cyanide equivalent immune system kills everything it comes in contact with and that causes a lot of oxidative stress. Oxidative stress is harmful and if it happens for a long period of time, the body must make a business decision. Keep doing what it's doing (and have problems) or down regulate to lower the oxidative stress. It down regulates. So now you have a Kool-Aide equivalent immune response but lower oxidative stress. You down regulate your immune response through epigenetic shifts and substrate availability. Add some methylfolate, manganese, copper, or anything else that can increase immune response and you give your immune response the ability to find those pathogens that have found safe harbor on your extracellular matrix or other hard places that are difficult for your immune system to access. Each item affects our pathways differently so the amount you need to do this varies.

I'm not taking about the major pathogens we all think about, I'm referring to everyday bacteria that we all harbor. Staph, Strep, Bilophila, Klebsiella, Candida, etc, one or some of these are the ones that can be causing you issues. Some strains are more virulent than others, some make biofilms and some bind with metals. You could have EBV, West Nile, Adeno, Mono, Coxsackievirus, Cowpox, Hepatitis, or any other of the long list of human viruses. IMO, I would say you do because it is much easier to get a herx from a virus when using methylfolate than it is a bacteria. That is just my opinion.

How and what you eat dictates how many pathogens translocate from your GI tract to your periphery. That is another topic.

Post Edited (Georgia Hunter) : 2/25/2020 3:24:45 AM (GMT-7)

Methylation is so darn difficult. I gave up on it after a solid 2 years

Genetics probably affects our health about 10% of the time. Environment affects our health about 90% of the time.

The inflammatory process causes polyamines to bind polyvalent cations extracellularly and the acidic environment causes them to be lost. Chronic inflammation over time leads to decreases in most predominantly intracellular polyvalent cations over time. Dietary intake plays a role in determining if these cations get replaced. In a high percentage of cases, these cations are not adequately replaced.

Copper is needed to bind the enzyme that breaks down serotonin and dopamine. If you have problems with these neurotransmitters, it can help you determine if you are high or low on copper.

Manganese levels would show up as low cholesterol and low BH4. It helps make dopamine, helps detoxify ammonia, and is required for insulin production. If manganese is supplemented, it must be done in very low doses because it can lower BH4 levels which may already be low.