Starting the Protocol, Have questions

[Arius]

Hello!

I've started the best approximation I could get of Rich Van Konynenberg's methylation protocol. (The multivitamin/mineral mix was impossible to source. I also had a heck of a time finding folinic acid and had to hire a naturopath to play detective and track some down for me; it needed to be imported from America.)

I'm taking the following supplements:


1, One Pure Encapsulations "UltraNutrient" multivitamin.
2. 2000 mcg hydroxycobalamin (under the tongue)
3. 200 mcg folinic acid (under the tongue)
4. 200 mcg Folapro (L-5-Methyltetrahydrofolate)
5. Sunflower Lecithin (from Helianthus annuus seed oil) 1/4 tsp, which I believe amounts to about 1200mg.


The dosages have been somewhat approximate. I don't have a pill splitter so I've done my best to quarter the 800mcg Folapro and folinic acid pills. In particular I have to sort of guess at what a 1/4 tsp of the liquid lecithin is, because I don't own any measuring spoons presently. (Ha ha I am ALL out of spoons over here.)

(Is it important to be precise? If so, why? It's challenging shopping during COVID when I am barely able to leave the house, but I could probably get a pill splitter and measuring spoons if it'll make a difference.)

I'm also taking RelaxMax (Inisitol, Taurine, GABA, magnesium, L-Theanine), Ashwagandha Matrix (Ashwagandha root extract, L-theanine), and Holy Basil tea for anxiety, plus glycine (3 grams before bed) for deeper sleep.


I've been taking the methylation protocol supplements for about 10 days and so far haven't noticed any change. I do get a subtle but consistent "high" feeling in my chest about an hour after I take the supplements, but it only lasts maybe half an hour or so. So far that's the only reaction. The questions I have are:

Should I have noticed something by now?
How long can it take to kick in?
At what point should I up the dosages, and if so, by how much?

I'm afraid my brain fog is bad enough that doing my own research on this has been nearly impossible, so it would be wonderful to have input from some folks who know what you're talking about. Please break your responses up into small paragraphs.

Thank you!
Arius


P.S. Edited this to add a question I forgot to ask initially.... how long do folks find they need to stay on the protocol for? We talking weeks, months, years, for life? I'm living on an inadequate disability income and kinda started this thing on some gift money, so I don't know how long I'll be able to keep it up for before I'm broke again.

 

[gbells]

Hello!

I've started the best approximation I could get of Rich Van Konynenberg's methylation protocol. (The multivitamin/mineral mix was impossible to source. I also had a heck of a time finding folinic acid and had to hire a naturopath to play detective and track some down for me; it needed to be imported from America.)

I'm taking the following supplements:


1, One Pure Encapsulations "UltraNutrient" multivitamin.
2. 2000 mcg hydroxycobalamin (under the tongue)
3. 200 mcg folinic acid (under the tongue)
4. 200 mcg Folapro (L-5-Methyltetrahydrofolate)
5. Sunflower Lecithin (from Helianthus annuus seed oil) 1/4 tsp, which I believe amounts to about 1200mg.


The dosages have been somewhat approximate. I don't have a pill splitter so I've done my best to quarter the 800mcg Folapro and folinic acid pills. In particular I have to sort of guess at what a 1/4 tsp of the liquid lecithin is, because I don't own any measuring spoons presently. (Ha ha I am ALL out of spoons over here.)

(Is it important to be precise? If so, why? It's challenging shopping during COVID when I am barely able to leave the house, but I could probably get a pill splitter and measuring spoons if it'll make a difference.)

I'm also taking RelaxMax (Inisitol, Taurine, GABA, magnesium, L-Theanine), Ashwagandha Matrix (Ashwagandha root extract, L-theanine), and Holy Basil tea for anxiety, plus glycine (3 grams before bed) for deeper sleep.


I've been taking the methylation protocol supplements for about 10 days and so far haven't noticed any change. I do get a subtle but consistent "high" feeling in my chest about an hour after I take the supplements, but it only lasts maybe half an hour or so. So far that's the only reaction. The questions I have are:

Should I have noticed something by now?
How long can it take to kick in?
At what point should I up the dosages, and if so, by how much?

I'm afraid my brain fog is bad enough that doing my own research on this has been nearly impossible, so it would be wonderful to have input from some folks who know what you're talking about. Please break your responses up into small paragraphs.

Thank you!
Arius

I just reviewed the methylation protocol. Basically it is a deficiency of usable folate that results in SAM-e deficiency (depression) and homocysteinuria. Depression is common in ME patients but that could be HHV-6. Are you positive for homocysteinuria on blood tests? If not there doesn't seem to be an indication for the treatment.

 

[Mary]

Basically it is a deficiency of usable folate that results in SAM-e deficiency (depression) and homocysteinuria.

A folate deficiency can cause macrocytic anemia, which can cause fatigue. A B12 deficiency can also cause macrocytic anemia. These have nothing to do with homocystinuria. When I started taking methylfolate in 2010, my energy noticeably increased within a day or 2. I didn't have homocystinuria, which WebMD defines as

Homocystinuria

(HCY) is a rare condition that interferes with your body’s ability to break down a protein from the food you eat.

A specific enzyme in your body breaks down methionine. If you have HCY, either you don’t make this enzyme or it’s not working right.

A pair of genes tells your body how to make this enzyme correctly. If both don’t work, you’ll get homocystinuria.

This is an inherited illness. The gene must be passed down from both of your parents.

What Is Homocystinuria? (webmd.com)

One thing I did have was borderline high MCV (mean corpuscular volume) on blood work, near the top of the range, though still "normal". But when I started taking methylfolate I had an almost immediate increase in energy. A high MCV often indicates macrocytic anemia - low B12 or folate, or both.

@Arius - I don't know of any way to determine exactly how much of what supplements to take. I think most of us had to experiment to find the right doses. I tried Rich Van Konynenberg's protocol back in 2007 I think and tried it off and on for some 3 years but I didn't do well on it. Each time I tried I felt a bit sick and more tired. In 2010 I came across member Freddd here's protocol, and stopped Rich's supplements, and went to straight methylfolate (Solgar brand worked well for me) and through experiment worked up to I think 1600 mcg. a day. I felt results almost immediately, within a day or 2. I'd already been taking a high dose of methylcobalamin, though eventually worked up to two 5,000 mcg. doses of sublingual liquid methylcobalamin before I felt results.

In retrospect, all I can figure is that there was something contained in one of the particular products that Richvank recommended which I reacted badly to.

So you may have to experiment, and increase your doses, before you see results. And I can't advise you here.
One other thing you should be aware of is that starting methylation can cause your potassium levels to tank, possibly quite badly and quickly. This is because if one is deficient in B12 or folate, and starts to remedy that deficiency, their cells will start dividing more rapidly and doing what they are supposed to, which uses potassium, and thus it may cause a functional potassium deficiency. My potassium tanked 2 or 3 days after starting the methylfolate - my chief symptom was severe fatigue after an initial boost in energy. Fortunately I'd read about this potential happening in Freddd's posts so was able to start taking potassium and titrated up until the severe fatigue abated, and was thus able to keep taking methylfolate. Richvank explains why and how this happens here: Why is potassium supplementation needed in methylation treatmt? | Phoenix Rising ME/CFS Forums

 

[Arius]

A folate deficiency can cause macrocytic anemia, which can cause fatigue...

Mary, thank you so much for your post, and for setting the record straight about homocysteinuria. I was pretty thrown off by gbells authoritatively-worded comment, although I wasn't about to quit the protocol based on one person's opinion either. It was particularly helpful to hear that you noticed results in 1-2 days. I kinda assumed that the response would be pretty immediate if it was going to come, but I had no idea... so that gives me a good sense of what to expect and how long to wait (maybe 3-4 days?) before upping my doses.

I will start experimenting with different dosages and also look into Freddd's protocol. I had heard the warning about potassium deficiency before, so I'll definitely be keeping an eye out for that.

 

[drmullin30]

@Arius, have you had your genetics profiled? I have been doing methylation protocols for over ten years and they didn't work until I tailored them to my specific genetics. There can be dozens of treatment conflicts between supplements etc. that unless you know your specific SNPs (single nucleotide polymorphisms) can create more problems if not addressed.

I'm now on a genetically tailored version of Freddd's protocol and I am in the best health of my life but if I had followed anyone's program to the letter (RichV, Fredd, Ben Lynch or Amy Yasko) I wouldn't be here so it has to be VERY individual. Go slow and pay attention to symptoms of deficiency like potassium, iron, calcium, magnesium, copper, zinc molybdenum, boron, manganese etc. At one time or another due to methylation or oxalates I have been deficient in all of these.

This website is very useful for determining deficiency and overdose symptoms of minerals and b-vitamins:
https://acu-cell.com/index.html

My health has also dramatically improved by eliminating oxalates from my diet which were a huge driver of physical and mental health problems for me and many other PWCs.

Oxalates interfere with methylation, thyroid function and were a direct driver of depression and anxiety for me. I recommend to anyone here now to get their genetics profiled and get checked for hyperoxaluria.

 

[Arius]

@Arius, have you had your genetics profiled? I have been doing methylation protocols for over ten years and they didn't work until I tailored them to my specific genetics. There can be dozens of treatment conflicts between supplements etc. that unless you know your specific SNPs (single nucleotide polymorphisms) can create more problems if not addressed.

I'm now on a genetically tailored version of Freddd's protocol and I am in the best health of my life but if I had followed anyone's program to the letter (RichV, Fredd, Ben Lynch or Amy Yasko) I wouldn't be here so it has to be VERY individual. Go slow and pay attention to symptoms of deficiency like potassium, iron, calcium, magnesium, copper, zinc molybdenum, boron, manganese etc. At one time or another due to methylation or oxalates I have been deficient in all of these.

This website is very useful for determining deficiency and overdose symptoms of minerals and b-vitamins:
https://acu-cell.com/index.html

My health has also dramatically improved by eliminating oxalates from my diet which were a huge driver of physical and mental health problems for me and many other PWCs.

Oxalates interfere with methylation, thyroid function and were a direct driver of depression and anxiety for me. I recommend to anyone here now to get their genetics profiled and get checked for hyperoxaluria.

There's a lot of good suggestions here - thank you!

I actually talked with my naturopath about getting genetic testing recently and we were thinking that might be a good next move for me. So far I've held off because I have extremely limited financial resources and it is quite pricey. (I'm aware that there are corporations who will do it for "free," but I am not okay having my extremely private biological information sold.) But I think it's time.

As far as I'm aware, the only high-oxalate food I consume is spinach. But I'll look into that more!

 

[Arius]

Okay so I'm about 6 weeks into the methylation protocol. I've increased my doses every 2 weeks. So far no noticeable effects. Nothing.

These were my starting doses:

1, One Pure Encapsulations "UltraNutrient" multivitamin.
2. 2000 mcg hydroxycobalamin (under the tongue)
3. 200 mcg folinic acid (under the tongue)
4. 200 mcg Folapro (L-5-Methyltetrahydrofolate)
5. Sunflower Lecithin (from Helianthus annuus seed oil) 1/4 tsp, which I believe amounts to about 1200mg.

Note: the lecithin dosage has been guesswork every time because I have no way of measuring it accurately, especially since it sticks to the measuring spoon. Could this be the reason I'm not seeing any results?

This had no effect, so I doubled my dosages. (I've mostly been taking just one multivitamin though, although sometimes I'll take two. Makes no difference anyway.)

I did that for another two weeks with no discernable effect, so I tripled the original doses, again with no effect at all. That's where I'm at now. Today I didn't bother taking them.

I've sent my saliva to 23andMe for analysis and am expecting results mid-April. In the meantime, I'm not sure if I should just stop the protocol, as so far it's been an expensive waste of supplements, and wait for my results, or if there's something else I can try in terms of tweaking it. Suggestions?

I might try going up to 4x the original dose (ie 8000mcg hydroxycobalamin, 800 mcg folinic acid, etc) but I'm confident the result will be the same.

 

[xinamatusx]

A folate deficiency can cause macrocytic anemia, which can cause fatigue. A B12 deficiency can also cause macrocytic anemia. These have nothing to do with homocystinuria. When I started taking methylfolate in 2010, my energy noticeably increased within a day or 2. I didn't have homocystinuria, which WebMD defines as What Is Homocystinuria? (webmd.com)

One thing I did have was borderline high MCV (mean corpuscular volume) on blood work, near the top of the range, though still "normal". But when I started taking methylfolate I had an almost immediate increase in energy. A high MCV often indicates macrocytic anemia - low B12 or folate, or both.

@Arius - I don't know of any way to determine exactly how much of what supplements to take. I think most of us had to experiment to find the right doses. I tried Rich Van Konynenberg's protocol back in 2007 I think and tried it off and on for some 3 years but I didn't do well on it. Each time I tried I felt a bit sick and more tired. In 2010 I came across member Freddd here's protocol, and stopped Rich's supplements, and went to straight methylfolate (Solgar brand worked well for me) and through experiment worked up to I think 1600 mcg. a day. I felt results almost immediately, within a day or 2. I'd already been taking a high dose of methylcobalamin, though eventually worked up to two 5,000 mcg. doses of sublingual liquid methylcobalamin before I felt results.

In retrospect, all I can figure is that there was something contained in one of the particular products that Richvank recommended which I reacted badly to.

So you may have to experiment, and increase your doses, before you see results. And I can't advise you here.
One other thing you should be aware of is that starting methylation can cause your potassium levels to tank, possibly quite badly and quickly. This is because if one is deficient in B12 or folate, and starts to remedy that deficiency, their cells will start dividing more rapidly and doing what they are supposed to, which uses potassium, and thus it may cause a functional potassium deficiency. My potassium tanked 2 or 3 days after starting the methylfolate - my chief symptom was severe fatigue after an initial boost in energy. Fortunately I'd read about this potential happening in Freddd's posts so was able to start taking potassium and titrated up until the severe fatigue abated, and was thus able to keep taking methylfolate. Richvank explains why and how this happens here: Why is potassium supplementation needed in methylation treatmt? | Phoenix Rising ME/CFS Forums

@Mary Is it safe to take that much folate and b12 indefinitely?

 

[Mary]

@Mary Is it safe to take that much folate and b12 indefinitely?

Hi @xinamatusx - sorry, but I can't answer your question. We're all different and our needs can change over time. All I can say is what has worked for me - I now take about 5000 mcg. liquid methylcobalamin (in two 2500 mcg. doses) a day, and 3200 mg. (in divided doses) metafolin (from Solgar) a day and do well with it.

But many couldn't tolerate those doses and some need more.

 

[Arius]

I got my genetic testing results and plugged them into Genetic Genie!

Looks like I may have a Caspase-8 deficiency (which maybe explains my abnormal blood tests / low WBC and platelet counts / lack of immune function?) and (quelle surprise) an MTHFR deficiency (thermolabile variant). (Called it!)

I gather that my EPHX1 variant leaves me more vulnerable to oxidative stress, and my MBL2 variant leaves me more vulnerable to mannose-rich pathogens.

My FAH gene may also be worth looking at. It said something about tyrosinemia (type 1).

Not sure if this is relevant or even what exactly this means, but my NAT2 gene variant could be causing slow acetylation.

That was all the stuff I could find that seemed relevant.



Anybody have any clue how all of this would affect my protocol / treatment approach?

 

[Learner1]

2000 mcg hydroxycobalamin (under the tongue)
3. 200 mcg folinic acid (under the tongue)
4. 200 mcg Folapro (L-5-Methyltetrahydrofolate)

Many of us take much higher doses of 5-MTHF, like 10-15mg. I wouldn't necessarily recommend your going out and taking that much without testing first or adjusting other supplements, but could be why you feel nothing.

Additionally, many of us take methyl B12, not hydroxoB12. There are reasons to take one or the other, and various doses, and might be wise to discuss with your doctor.

One other thing you should be aware of is that starting methylation can cause your potassium levels to tank, possibly quite badly and quickly. This is because if one is deficient in B12 or folate, and starts to remedy that deficiency, their cells will start dividing more rapidly and doing what they are supposed to, which uses potassium, and thus it may cause a functional potassium deficiency. My potassium tanked 2 or 3 days after starting the methylfolate - my chief symptom was severe fatigue after an initial boost in energy. Fortunately I'd read about this potential happening in Freddd's posts so was able to start taking potassium and titrated up until the severe fatigue abated, and was thus able to keep taking methylfolate. Richvank explains why and how this happens here: Why is potassium supplementation needed in methylation treatmt? | Phoenix Rising ME/CFS Forums

@Mary While this is important to know, as too much or too little potassium can affect heart rhythm, I've never found this to be a problem, no matter how much folate of B12 I take, nor am I aware of this issue in dozens of other patients. Not that it doesn't affect a few, with serious effect.

It strikes me that there's some sort of genetic situation that might cause this rare potassium depletion problem. Have you ever figured out what it is? It might be worth figuring out as it might lead to other helpful clues.

 

[Arius]

Thank you, Learner!

What sort of testing would you recommend before taking a high dose of 5-MTHF?

 

[Mary]

While this is important to know, as too much or too little potassium can affect heart rhythm, I've never found this to be a problem, no matter how much folate of B12 I take, nor am I aware of this issue in dozens of other patients. Not that it doesn't affect a few, with serious effect.

It strikes me that there's some sort of genetic situation that might cause this rare potassium depletion problem. Have you ever figured out what it is? It might be worth figuring out as it might lead to other helpful clues.

@Learner1 - I've never read about this being a genetic issue. It is well documented that when treating megaloblastic anemia, potassium levels may drop suddenly. I've seen many people here who had symptoms of low potassium after starting folate and/or B12 and whose symptoms improved rather quickly with something like low-sodium V-8 (high in potassium) or just a potassium supplement. It's really not uncommon.

Here are a couple of links with more info:

Megaloblastic Anemia | IntechOpen

"The response to therapy should be closely monitored using complete blood count (CBC), reticulocyte count, lactate dehydrogenase (LDH) levels, indirect bilirubin, hemoglobin level, serum potassium and serum ferritin.

"It is very important to closely monitor the serum potassium which falls with treatment and may result to death. Potassium supplementation should be given in case of hypokalemia using oral potassium supplement ."

How is response to therapy for megaloblastic anemia monitored? (medscape.com)

Although patients may feel better as soon as therapy is started, improvements must be monitored with. Laboratory tests to order include the following:

. . . .
Serum potassium level

Serum potassium levels can fall during therapy for severe cobalamin or folate deficiency and can lead to sudden death. Therefore, potassium should be monitored and supplements may be indicated.

 

[Mary]

too much or too little potassium can affect heart rhythm,

You're right about this of course. But I believe it's very hard to get too much potassium in food, unless one has kidney problems. I usually suggest people try drinking a couple of glasses of low-sodium V-8 which is high in potassium to see if if makes them feel better, and very often it does. Then they can decide if they want to take a potassium supplement.

The RDA for potassium is 4700 mg. I've found that I need to take 1000 mg a day of potassium gluconate to keep my levels up. So I'm taking less than 25% of the RDA in the form of a potassium supplement.

Did you look at richvank's post about why people with ME/CFS very well may need extra potassium during methylation treatment? Why is potassium supplementation needed in methylation treatmt? | Phoenix Rising ME/CFS Forums

It explains how we can have normal blood levels of potassium but intracellularly can be a very different matter, so we can't go by what's on our blood work. Actually I had symptoms of low potassium off and on for some years before I discovered what those symptoms meant. My potassium on blood work had always been fine, albeit on the low side of normal. Chief symptoms were severe fatigue and just feeling awful which were unrelated to exertion. And when I started taking methylfolate in 2010 (after reading about potential low potassium problems), I was very surprised when the symptoms of low potassium hit because they were identical to what I had been experiencing off and on for some years. It was such a relief when the symptoms subsided when I added in potassium, and I haven't had those symptoms since I've been supplementing with potassium.