• 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 become a member, simply click the Register button at the top right.

Methylation Dosing

Messages
22
How are you supposed to determine the correct dosage of methylation supplements for yourself?

In particular I'm wondering about methylfolate. My understanding is that folate is water soluble, so toxicity probably isn't a big concern, but people have taken anything from mcg's of the stuff to several tens of mg's, so how do you determine the right dose for yourself?

Obviously how you feel will guide things somewhat, but is there a more objective means of judging? I've read that you can over methylate as well, so how do you judge when you are going from under methylating to over methylating.
 

Sushi

Moderation Resource Albuquerque
Messages
19,935
Location
Albuquerque
How are you supposed to determine the correct dosage of methylation supplements for yourself?

In particular I'm wondering about methylfolate. My understanding is that folate is water soluble, so toxicity probably isn't a big concern, but people have taken anything from mcg's of the stuff to several tens of mg's, so how do you determine the right dose for yourself?

Obviously how you feel will guide things somewhat, but is there a more objective means of judging? I've read that you can over methylate as well, so how do you judge when you are going from under methylating to over methylating.

It is a complex study and you will probably need to do a lot of reading. There are two protocols discussed here at length and the doses are given for each supplement--Dr. Rich Van Konynenburg's Simplified protocol and Freddd's active B12 protocol.

I don't know the exact post where Freddd gives his doses (others will probably give a link) but you can find Rich's papers here:

http://phoenixrising.me/treating-cf...e-mecfs-glutathione-and-the-methylation-cycle

Best wishes,
Sushi
 

Lotus97

Senior Member
Messages
2,041
Location
United States
How are you supposed to determine the correct dosage of methylation supplements for yourself?

In particular I'm wondering about methylfolate. My understanding is that folate is water soluble, so toxicity probably isn't a big concern, but people have taken anything from mcg's of the stuff to several tens of mg's, so how do you determine the right dose for yourself?

Obviously how you feel will guide things somewhat, but is there a more objective means of judging? I've read that you can over methylate as well, so how do you judge when you are going from under methylating to over methylating.
The dosage is going to vary a lot from individual to individual. Even though the protocol's by Rich and Fredd work for many people, the two protocols are significantly different although I don't know the specifics. Most of the sticky threads in this forum are about Rich and Fredd's methylation protocols. It might be more helpful to read the comments in the threads rather than the protocol itself so you'll see how experiences can differ a lot for each person. The only advice I'd give is to start slow because there can be risks involved when embarking on any methylation protocol. For myself and many others, overstimulation tends to be a common sign of overmethylating. I'm not sure what other symptoms are. Also, low potassium can be another potentially life threatening symptom of methylation. There a lot of threads devoted to potassium supplementation so read up on that too.
 

Red04

Senior Member
Messages
179
http://forums.phoenixrising.me/inde...tocol-with-micro-titration.17818/#post-273588

Reply #11 in the above thread.

I believe this goes against people talking about detox and overmethylation. You have to embrace the potentially bad symptoms as signs that you induced another deficiency. Then, titrate those symptoms away by correcting them and keeping moving forward until no bad symptoms occur. Then, you can titrate back down to find equilibrium. The slower, more patient you are is probably safest. However, I think there is also a balance in recognizing the induced symptoms and correcting them swiftly by doubling/tripling dosages on the way up in regards to methylfolate and potassium.

I have no medical training and I am an engineer so take my advice for what its worth. I have experienced this by "curing" my wife from life long symptoms of CFS/ME/anxiety depression/weak immune system and pulling my wife out of 6 or so "Crashes" induced by missing several doses of methylation supplements.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
Fredd and Rich both have different approaches, but they both seem to be saying to start slow. Everyone is different so there's no way to create a methylation protocol that works for everyone. They do seem to differ on whether it's possible to overmethylate and overdrive the methylation cycle. As far as toxins released during methylation, that varies a lot from person to person. It's much more than just discomfort that needs to be endured as some people are suggesting. There are very real dangers whether you want to believe that or not is your choice. Maybe this isn't true for most people, but I tend to err on the side of caution and listen to what my body is telling me.
 

Red04

Senior Member
Messages
179
How does a person know if they are having detox symptoms or potassium drop or pradoxical methylfolate symptoms?

I see a lot of people talking about this and that toxin and mobilizing them, but how do you know? I would guess it happens on some level, but just having CFS/ME and all the complexity and crazy symptoms, how can you say definitively that this is mobilizing toxin X and I am overmethylating?

My wife had pretty bad startup symptoms when things kicked off. I don't know what caused all the bad startup symptoms though. Toxins? Maybe? The muscle cramping was definitely potassium as it was reversed immediately. All the neurological stuff? Crazy emotions? Was she healing? Detoxing? Mobilizing? Sulpher? Mercury?
 

Lotus97

Senior Member
Messages
2,041
Location
United States
It is hard to know for sure although for myself I had a lot problems after my tooth with a mercury amalgam cracked. Rich and other people much more knowledgeable than myself agree that overmethylation is possible and perhaps even common among the people here, but I don't know enough to offer my own opinion. This is Rich's answer to someone asking about symptoms during methylation:
I have a fairly short experience of the methylation protocol. I tried it for a few weeks & got pretty ill. I assume it was working & I just got overloaded with stored toxins.
***That is one possibility for causing symptoms on this protocol. The biochemical theory associated with the treatment does support this explanation, some of the symptoms people report do seem to involve mobilization and excretion of stored toxins, and there are measurements that support toxin buildup and excretion on the treatment.
***Other causes of symptoms appear to be excitotoxicity and potassium deficiency. The excitotoxicity-related symptoms are insomnia, anxiety, nervousness, a "wired" feeling, and hypersensitivity of the senses. Low potassium affects the heartbeat as well as causing muscle spasms and other nervous system related effects.
I'd like to continue. I'll probably have to ramp it up slower.
***Quite a few others have taken this approach. It takes longer, but is more tolerable.
I'm just wondering if others have a big release of stored toxins & how to handle it....? Do we work this protocol up very slowly? How long does it take? (I suppose it's an individual thing.)
***Yes, it does seem to be an individual thing. Some people seem to have bigger body burdens of toxins than others. Probably depends on how long a person has been ill, and what they have been exposed to, before and during the illness.
What do you do to absord or excrete the toxins? What are the toxins exactly? Is it heavy metals, pesticides, chemicals? Do we need to find out what is being excreted so we can use the appropriate binder, chelator? Are there tests to find out what the toxins are - exactly?
***There are some tests available. Probably the most commonly used ones are the urine toxic elements test and the red blood cell or whole blood toxic elements tests. There are also the fecal minerals test and the hair minerals test. Doctors Data is one lab that offers these, and they can be obtained through some doctors, or from www.directlabs.com without a doctor's order. In addition, US BioTek offers an environmental pollutants panel. I think that there are toxicology labs that offer pesticide tests. Which toxins a person has again will depend on what they have been exposed to, and it varies a lot. Dr. John McLaren Howard at Acumen Lab in the UK has some very nice tests that look at chemical blockers on the mitochondrial translocator protein, at adducts on the DNA,and at volatile organics in the blood. I don't think these tests are offered now to people in the U.S., because of high demand, but I have seen quite a few reports from people who have had them, and Dr. Howard finds a wide variety of toxins in different people, including chemicals from permanent hair dye, benzene and other organic solvents, perhaps from gasoline fumes, various pesticides, antiseptic agents, cleaning agents, etc.
***All this testing costs money of course, so most of the people I have interacted with have not done much of it, though some have. It would be wonderful if everyone could afford to run all these tests before and after doing the protocol, and then we would have great data! Dream on, Rich! :)-)
***As to what can be done to help get rid of the toxins, there are four approaches that I know of, some easier to do, more available, and less costly than others. They boil down to ways of removing toxins via the urine, the stools, the sweat, and directly from the blood.
***Urine: The idea here is to make the urine more alkaline (higher pH). By doing this, one can cause those toxins that are in the chemical form of weak acids to ionize more, and thus be more likely to go out in the urine, rather than being reabsorbed into the blood by the kidneys. Lemon juice is one way to do that, but it's important to use a drinking straw and to flush the teeth afterward so that the citric acid will not damage the enamel. Paradoxically, lemon juice, which contains citric acid, will actually cause the urine to be more alkaline, because the citrate is metabolized in the body, leaving strong base-formers (sodium, potassium, calcium, magnesium) to go out in the urine.
***Stools: The idea here is to take substances that will bind toxins that are excreted into the gut via the bile from the liver, and make sure that they go on out in the stools, and do not get reabsorbed via the enterohepatic circulation and go back to the liver. In this category are activated charcoal, modified citrus pectin, cholestryramine, zeolites and clays, such as bentonite. Activated charcoal will adsorb a variety of organic substances (including some vitamins, so it's important not to take them together). Modified citrus pectin and other indigestible fibers can bind some toxic elements. Cholestyramine takes out negatively charged toxins, such as biotoxins (as discovered by Dr. Ritchie Shoemaker), zeolites are designed for certain atomic or molecular sized toxins, and clays will take out positively charged toxic elements. Beyond these are the chelators, which are designed to form two bonds to toxic element ions, such as mercury. The excretion can be via either the urine or the stools.
***Sweat: This is the sauna approach, usually the far infrared sauna. It's important to replace the water and minerals that are lost, and to remove sweat promptly, so that the toxins are not reabsorbed through the skin.
***Blood: This is much less commonly used, much more difficult to get access to, and more expensive. It's sort of like the dialysis that the kidney patients get, but the blood is passed over activated charcoal or another substance designed to bind a particular toxin, and then put back into the body. I think this would be lifesaving for more people if it were more widely used. Some people have high body burdens of particular toxins, and their detox system, perhaps for genetic reasons, is not able to take them out.
***Best regards,
***Rich
 

Red04

Senior Member
Messages
179
I understand that you CAN test for detox and toxin loads. And its logical that you might release more toxins when you get your system working. But people talk about detox with a lot of crazy vocabulary that makes it sound like it’s well understood. And then talk about taking milk thistle or cilantro to chelate copper or some other detox method.

Its also logical that a properly working methylation cycle should detox your body.

Has anyone been permanently harmed from detoxing induced by methylation supplements or other methods? What is the real danger there? Potassium deficiency can kill you? Can mobilizing toxins? Does anyone have a research article?

I think if a person "titrates to effect" slowly, and focus more on potassium and methylfolate symptoms, you would be better off than detoxing these metals. The symptoms are confusing and there are so many unknowns, I just don't see how you could wade through it with any reliability. If you go slow, you will eventually trigger healing or detoxing or healing (who knows). It seems to be common thought that your body will either need more potassium, need more methylfolate, be detoxing, or be overmethylated. So, titrate the potassium and methylfolate or chase the toxins. It seems to me there is a lot more evidence to add potassium and methylfolate, instead of chasing toxins.

Again, detox probably happens on some level and probably needs addressed in some cases, I just haven't seen the data or methods to rule out potassium/healing/methylfolate/other b12 reactions over mercury/copper/sulphur/other toxins and it gets mentioned over and over like it’s the absolute truth.
 
Messages
59
Location
New York
I have a similar dosing question:
I have just started Rich's protocol, and I am having large difficulties cutting the pills (even with a pill cutter).
The FolaPro never comes equal and crumbles and the Folinic acid is in a capsule form.
Would upping the dose of the FolaPro & the Folinic acid and to half a pill (400mg) or taking a half pill every other day have adverse or negative reaction?

Thanks,
Lo
 

Lotus97

Senior Member
Messages
2,041
Location
United States
I have a similar dosing question:
I have just started Rich's protocol, and I am having large difficulties cutting the pills (even with a pill cutter).
The FolaPro never comes equal and crumbles and the Folinic acid is in a capsule form.
Would upping the dose of the FolaPro & the Folinic acid and to half a pill (400mg) or taking a half pill every other day have adverse or negative reaction?

Thanks,
Lo
Have you tried using an Exacto knife to cut it? I find that works best with certain tablets, but I haven't tried with the FolaPro. A capsule shouldn't be too hard to divide. The small part of the capsule is 1/3 so a little bit less than that would be 1/4, but dividing it into thirds should be fine. I'm not sure about taking it every other day. As with most things regarding methylation it depends on the individual. If you do that, then maybe take 400 mcg folinic one day and 400 mcg methylfolate on day 2. However, if you would rather just buy something else, Thorne has a lot of B-complexes and multi vitamins in all different doses which would be an easier way to dose it.
 

caledonia

Senior Member
How to test for doses - I use self muscle testing. Usually people use it as a yes/no method for determining if a substance is good or bad for you, but I've developed a method for determining dosage also.

Or you can do trial and error, which is what I used to do before discovering the muscle testing. But the muscle testing is so much faster, that's my primary go-to method.

There are videos on Youtube that show how to get your body to show you the yes/no (strong/weak) response. The most common one seems to the "eye". Once you learn how to tell yes/no with true or false statements, then you progress to testing various known good or bad substances, then when you feel confident, onto unknown substances.

In a similar way, you can hold a good substance and start saying or thinking amounts - 1 pill, 1/2 pill, 1/4 pill. Or even milligrams - 500mg, 250mg, 125mg, etc. Your muscle will test strong on the correct amount and weak on the others. If you're having trouble narrowing it down, you can say, more than 1 pill, less than one pill, less than 1/2 pill etc. to get it rapidly narrowed down.

I retest all my supplements often to make sure the dose doesn't need adjustment or if the substance that was previously ok, is now testing bad or whatever.
 

caledonia

Senior Member
The other thing is to get your methylation SNPs tested. People with certain SNPs will do better or worse with certain substances. For example, someone with COMT mutations will need to be careful about supplementing with too many methyl groups - so a Freddd type protocol is contraindicated.

People with CBS mutations and a high urine sulfate reading will need to address those first before supplementing with methylfolate and methylB12 or it will cause excitotoxicity.

With 23andme at only $99, unless you're really broke, it's a no brainer to get tested. The price will remain that low until they get a million samples.
 

caledonia

Senior Member
I have a similar dosing question:
I have just started Rich's protocol, and I am having large difficulties cutting the pills (even with a pill cutter).
The FolaPro never comes equal and crumbles and the Folinic acid is in a capsule form.
Would upping the dose of the FolaPro & the Folinic acid and to half a pill (400mg) or taking a half pill every other day have adverse or negative reaction?

Crush the pill into powder, then put the powder into empty gel capsules. You can get those at the health food store. Then you can divide the powder into half and half again - 1/2, 1/4, 1/8, 1/16 or even smaller as required. I've been known to divide things as low as 1/256, then gradually be able to build that up to a full dose. But a full dose would have been impossible to start with.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
Crush the pill into powder, then put the powder into empty gel capsules. You can get those at the health food store. Then you can divide the powder into half and half again - 1/2, 1/4, 1/8, 1/16 or even smaller as required. I've been known to divide things as low as 1/256, then gradually be able to build that up to a full dose. But a full dose would have been impossible to start with.
How do you get such a small amount of powder into a capsule? Do you have some sort of device you use?
 

Victronix

Senior Member
Messages
418
Location
California
Crush the pill into powder, then put the powder into empty gel capsules. You can get those at the health food store. Then you can divide the powder into half and half again - 1/2, 1/4, 1/8, 1/16 or even smaller as required. I've been known to divide things as low as 1/256, then gradually be able to build that up to a full dose. But a full dose would have been impossible to start with.

I just started with the Douglas Labs B Complex with Metafolin (which has 400 mcg of Metafolin). The capsule is already in powdered form, so that makes it easier than a solid capsule to cut up.

My husband and I tried one capsule and it was way too much for me, wiped me out for a day, and gave my husband a headache, but nothing else.

So I took a couple of days off, which were not fun either, with muscle problems and emotional ups and downs, and then started at 1/4 of a capsule (I pull the capsule apart and then add the powder to water and drink it) and doubled my potassium intake (foods, coconut water). That was fine for day 1, but with the second day and just one more 1/4 size capsule dose, my mood is starting to roller coaster and the muscle issues are more pronounced, plus I was woken up every 2 hrs at night practically, with a lot of anger at 5 am, then total exhaustion. It seems a lot more of a cumulative effect than B-12 alone was.

So, after a wave of panic this morning, I will take another day or so off from the effort, and then try an even smaller dosage.

Trying to add folate via a B Multi is more complex rather than just methyl folate alone, I suppose, in terms of sorting out what's what, but looking at the 'B2 I love you' thread, the interconnectedness of the B's seems important. I normally take 2 B-Right's per day, so cut that down to 1 per day with the Douglas Labs. B-Right was hugely important to normalizing my B-12 symptoms.

I just sent in my 23andme test -- thanks to the notifications on here about the lowered price.
 

caledonia

Senior Member
How do you get such a small amount of powder into a capsule? Do you have some sort of device you use?

Half of half of half of half the required number of times is 1/256. I use halves because it's easy to eyeball. You don't need a device, just get some empty gel caps (health food store) to put the other half in. You can open up gel caps with your fingers.

I don't actually make up 256 gel caps in one sitting (or I would go mad). What I do is divide one into 1/4 or 1/8 or something. Then take ONE of those and divide it up into the smaller amounts. That way you only have to make 16 or 32 or something. I keep the others and mark what they are in case I have to make up more.
 
Messages
22
Thanks everyone for all the help and info!!!

And I had no idea about the potassium issue. I hadn't heard about that, so thanks for the heads up.

I recently read that you can use niacin to gauge whether you are over or under methylating, although I'm not sure if that's accurate.





When people are referring to methylation based excitotoxicity are they referring to ammonia?
 
Messages
22
People with CBS mutations and a high urine sulfate reading will need to address those first before supplementing with methylfolate and methylB12 or it will cause excitotoxicity.


Interesting. Do you know why that is? I would have thought that the b12 and folate would lower homocysteine, thus lowering cystathione and the resulting ammonia production from the transsulfuration pathway.




And I definitely think there is a detox component to things and it's not just mainly potassium issues because I've gotten liver pains and elevated liver enzymes from methylation supplements, so there's definitely toxin excretion going on - or at least I think there is.
 

caledonia

Senior Member
When people are referring to methylation based excitotoxicity are they referring to ammonia?

There's a thread on here somewhere where we were trying to figure out how the excitotoxicity mechanism works. Yasko is kind of vague about it. Anyway, somewhere between the excess ammonia and sulfur you get both an excitoxicity and a fight or flight rise in cortisol response. The bottom line is you will feel worse.