• 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, 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.

.:: Sustained-release Methylation Protocol (SRMP) ::.

Sherpa

Ex-workaholic adrenaline junkie
Messages
699
Location
USA
.:: Sustained-release Methylation Protocol ::. -- Version 1.0 --
This protocol uses sustained-release formulas of B12 and methylfolate to provide steady support for the methylation cycle and neurotransmitter production. It does not require taking dozens of pills or sucking on sublingual B12 lozenges all day. These supplements help my body produce more glutathione with less chance of over-stimulation, confusing "paradoxical" reactions or electrolyte imbalance problems.

qCCER62.jpg

These supplements support my MAO A R297R +/+ (requires B2), MTRR A66G (requires a steady supply of B12 & some B2), and MTHFR (requires B2 and folate) mutations... as well as my basic nutritional needs. I am sharing my personal protocol to inspire you to find supplements that work for your own unique SNPs and sensitivities. Working with a qualified, nutritionally informed practitioner is strongly recommended. The following is for informational purposes only, it is not medical advice.

The Supplements (which I added, slowly, in numerical order):
  1. Nature Made B-complex with C - 1 tablet / A.M.
  2. All in One Multi-vitamin (Holistic Health / Dr. Yasko) - 1 capsule per day, or more
  3. Pic-Mins Multimineral (Thorne) - 1 capsule / P.M.
  4. NT Factor EnergyLipids powder - 1 scoop A.M. / 1 scoop P.M. (start with 1/4 scoop and increase gradually as tolerated)
  5. B12 Oils transdermal B12 spray sustained-release - 1 to 2 squirts per day
  6. Jigsaw Magnesium with sustained-release methylfolate & P5P - 2 tablets A.M, 2 tablets P.M. or more
Support for my MAO A R297R +/+ mutation:
In addition to the Nature Made B-complex (with 10.2mg of B2) listed above, I took 1/4 of a Solgar B2 50mg tablet (12.5mg) before lunch and 1/4 tablet before dinner for about one month before starting the B12 Oil and Jigsaw Magnesium w/ methylfolate. Here's why:
  • The most common reason for people to respond poorly to methylfolate is vitamin B2 deficiency.
  • Lack of B2 in combination with MAO +/+ means that your ability to turn off your neuronal stimulus is greatly reduced, thus leading to 'apparent' over-stimulation of nerves
  • MAO requires a metabolite of B2 called FAD to be present when the enzyme is synthesized.
  • It normally takes 2-4 weeks of regular B2 supplementation (e.g. 5mg or more, 3x daily) to normalize activity of MAO. This is provided that you have normal thyroid function.
Be aware that starting up methylation when MAO A is still not functioning well can cause reactions that are quite similar to the side effects of MAO inhibitor drugs, and that are also confusingly similar to the symptoms of low potassium and/ or B12 deficiency. I experienced dry mouth, sudden awakening at night (insomnia), muscle jerking, tingling in arms and legs. I found these symptoms resolved with continued B2 supplementation.

Nutrient Dosages for the basic package -- 1 All in One + 1 B-Complex + 1 PIC-MINS + 4 Jigsaw magnesium tabs + 1 B12 Oils spray:
  • B1 - 15mg
  • B2 - 13mg
  • B3 - 60mg
  • B5 - 23mg
  • B6 - 13mg
  • Folate - 226mcg
  • B12 - 2.5mg
  • Biotin - 38mcg
  • A - 1250 I.U.
  • C - 370mg
  • D - 100 I.U.
  • K - 10mcg
  • Zinc - 18.75mg
  • Copper - 0mg
  • Selenium - 125mcg
  • Maganese - 2.75mg
  • Chromium - 125mcg
  • Magnesium - 500mg
(*Note: some values were rounded to the nearest milligram)

Rationale for the supplements:
  • Nutrient levels can easily be titrated by splitting tablets or adding additional capsules - as low or high as you want! Lower dose B-vitamin support may prevent electrolyte imbalance and over-driving the methylation cycle. I want enough minerals (Zinc, manganese, etc.) to prevent insufficiency without going too high & triggering metal detox.

  • Lower dose, time-release methylfolate reduces the likelihood of electrolyte (potassium) imbalances and overcomes the short serum half-life of standard methylfolate - which caused me to experience mood swings & extremely confusing "paradoxical reactions." The Jigsaw Magnesium seems to provide a steady trickle of methylfolate that lasts for about 8 hours, keeping the folate cycle steadily humming along.

  • Sustained-release transdermal B12 Oils are highly preferred due to the low absorption & very short (1 to 2 hour) effect of B12 sublinguals and the corrosive effects of sugar and acids on tooth enamel. The spray seems to provide full B12 coverage at least 6 to 8 hours, or more. I like Adenosylcobalmin/Methylcobalmin mix or the B12 Ice (AdCbl + MeCbl with Vitamin D3 and THC, a curcumin derivative).

  • Lipid replacement therapy (NT Factor EnergyLipids) is used to help repair cellular membranes from the oxidative stress that very often occurs with CFS/ME. I believe NT Factor helped me heal and tolerate methylation supplements better after a couple months. It was very stimulating at first, so I started with small amount and gradually increased to the recommended dose. Ignore what the product label says about a double "loading dose" if you are at all sensitive to supplements.

  • I use some "proprietary supplements" that are only available from one source or are more expensive than common brands or generics - Jigsaw Magnesium w/ Methylfolate, All in One Multivitamin/Mineral, NT Factor EnergyLipids, and B12 Oils - but I believe that the quality and delivery technology of these products justify the cost.

  • I use some low cost supplements like Nature Made B-complex and Pic-Mins to boost the overall dose of vitamins and minerals in order to reduce the number of capsules of the All in One Multivitamin (w/ methylation cofactors). 1 or 2 caps per day is more affordable than taking the full dose of 4 per day ($33/month).

Additional Co-factors - as required: Riboflavin (B2), regular B6 or coenzymated B6 (sublingual P5P), Vitamin C, Vitamin D3, curcumin, Doctor's Best L-carnitine Fumarate, Extramel SOD extract, D-ribose, NADH, thyroid glandular, and additional Metafolin (methylfolate).

Potassium: There is a lot of online discussion about low potassium on methylation protocols. In my opinion, low potassium (hypokalemia) is sometimes over-diagnosed by sick people on web forums... who assume any unusual symptom or reaction must be low potassium. I misdiagnosed other symptoms as "low potassium" and ended up taking too much potassium (when I didn't need any at all) and messed up my electrolyte balance and caused myself discomfort and setback. On the other hand, ignoring actual low potassium levels can be dangerous. It's tricky to figure out! Therefore, I believe that its better for me not to take supplements at doses that commonly disrupt electrolyte balance... unless I was under expert medical care and monitoring.

I supplement magnesium & try to eat a higher potassium diet to support the increased cell division & growth that occurs with increased methylation. So far, I only seem to need extra potassium when I do strenuous exercise that makes me lose electrolytes through sweat. After serious exertion I may go for some potato chips, coconut water or Optimal Electrolyte drink. The lower doses of methylfolate (less than RDA of 400 - 800mcg) I'm using have not caused me any low potassium issues in my normal, day-to-day life.
 
Last edited:

MAF14

Senior Member
Messages
195
Thank you for sharing.

"Support for my MAO A R297R +/+ mutation:
In addition to the Nature Made B-complex (with 10.2mg of B2) listed above, I took 1/4 of a Solgar B2 50mg tablet (12.5mg) before lunch and 1/4 tablet before dinner for about one month before starting the B12 Oil and Jigsaw methylfolate. And I continue to take B2.
  • The most common reason for people to respond poorly to methylfolate is vitamin B2 deficiency.
  • Lack of B2 in combination with MAO +/+ means that your ability to turn off your neuronal stimulus is greatly reduced, thus leading to 'apparent' over-stimulation of nerves
  • MAO needs FAD -- a metabolite of B2 -- to be present when the enzyme is synthesized.
  • It normally takes 2-4 weeks of high dose B2 (e.g. 3x daily) supplementation to normalize activity of MAO. This is provided that you have normal thyroid function."
I have the same MAO Homozygous defect. For the 2-4 week high dose B2 period, what dose would you recommend?

I wouldn't say I have experienced much negative side effects since starting methylation (3-4 weeks) except waking up thirsty during the night. Overall I feel better with high doses of methylfolate.

I ask because Freddd warns that high doses may cause methylfolate to drop....
 

Sherpa

Ex-workaholic adrenaline junkie
Messages
699
Location
USA
Thank you for sharing.

"Support for my MAO A R297R +/+ mutation:
In addition to the Nature Made B-complex (with 10.2mg of B2) listed above, I took 1/4 of a Solgar B2 50mg tablet (12.5mg) before lunch and 1/4 tablet before dinner for about one month before starting the B12 Oil and Jigsaw methylfolate. And I continue to take B2.

I have the same MAO Homozygous defect. For the 2-4 week high dose B2 period, what dose would you recommend?
.

I have read that taking at least 5mg of riboflavin 3x a day might be enough to normalize B2 levels. The dose regime that I personally took is spelled out above. ^^^^^^^^

Not everyone who is MAO A +/+ is also B2 deficient, but I was... and treating the deficiency was critical to be able to being able to methylate properly. Before adding B2 I got uncomfortably overstimulated by large doses of B12 and even small doses of methylfolate.
 
Last edited:

Kathevans

Senior Member
Messages
689
Location
Boston, Massachusetts
Thank you Sherpa.

Your posts have helped me clarify my thinking enormously. I realized today that I’d missed one of my snps on my signature, the MAO +/+, and realizing as per your previous post how important the B2 is, and just how low in it I am, I’m going to start there with the addition of B6. I had the awful experience of starting with methylfolate last year before I knew much of anything. Taking very tiny doses for about four days left me on a rollercoaster for a couple of weeks. It was nightmarish. Needless to say, once bitten…
 

PeterPositive

Senior Member
Messages
1,426
Version 1.0 --

The Supplements (which I added on in numerical order):
  1. Nature Made B-complex with C - 1 tablet / A.M.
  2. All in One Multi-vitamin/Mineral (Holistic Health / Yasko) - 1 capsule per day, or more
  3. Pic-Mins Multimineral (Thorne) - 1 capsule / P.M.
  4. NT Factor EnergyLipids powder - 1 scoop A.M. / 1 scoop P.M. (start with 1/4 scoop and increase gradually)
  5. B12 Oils transdermal B12 spray sustained-release - 1 to 2 squirts per day
  6. Jigsaw Magnesium with sustained-release methylfolate & P5P - 2 tablets A.M, 2 tablets P.M. or more
About the All-in-One Multi, as regards folate it says:
Folate (as Folic Acid, calcium folinate, and Methyltretrahydrofolic Acid, Glucosamine Salt as Quadrefolate™)
Does it contain synthetic folic acid too? Sounds weird, although the dosage is very low. Just wondering... :)
 

Sherpa

Ex-workaholic adrenaline junkie
Messages
699
Location
USA
@PeterPositive Yes, Dr. Yasko's formulation contains a tiny, microgram sized amount of folic acid. It's a very gentle formula with an especially good proprietary cofactor blend to support methylation. "It just works" says my body, regardless of what I read online about the Evils of Folic Acid. ;)
 
Last edited:

PeterPositive

Senior Member
Messages
1,426
@PeterPositive Yes, Dr. Yasko's formulation contains a tiny, microgram sized amount of folic acid. It's a very gentle formula with an especially good proprietary cofactor blend to support methylation. "It just works" says my body, regardless of what I read online about the Evils of Folic Acid. ;)
:D
 

Sherpa

Ex-workaholic adrenaline junkie
Messages
699
Location
USA
I had the awful experience of starting with methylfolate last year before I knew much of anything. Taking very tiny doses for about four days left me on a rollercoaster for a couple of weeks. It was nightmarish. Needless to say, once bitten…

@Kathevans
I too, was terrified of methylfolate after having unbearable inflammation and insomnia reactions to it when I tried it alongside high-dose vitamin formulas in my earlier methylation attempts.

I found that too high Bs drove some sort of cycle too fast, and I feel mellower on lower dose vitamin blends. I also think that a few months on the NT Factor may have healed my mitochondria enough to allow me to "drive faster" more comfortably. The biggest shift was after supplementing B2 and getting my levels up.

Now, when I take too much methylfolate it just feels like I drank a little too much coffee... then it mellows out after a couple hours, like coffee... rather than an uncomfortable nightmare scenario. It's almost enjoyable.

I also had a major problem with B6 deficiency. My OAT tests shows levels of 0.0 despite making a conscious effort to eat foods high in B6 the day before. For some reason I am not absorbing it and need supplemental doses. I am not sure if its an oxalate issue or ???
 
Last edited:

Sherpa

Ex-workaholic adrenaline junkie
Messages
699
Location
USA
@Gondwanaland I eat a higher potassium diet - my main carb is boiled green bananas. Main fat is coconut oil, olive oil & some grass fed butter. No sugar, no gluten, no artifical junk. I eat some white rice, steamed green beans and carrots, leafy greens like romaine letuce & lactiano kale, grass fed beef and sardines. I eat a low-moderate amount of fresh fruit - average 1 piece per day. I also like lentils (very high in folate) sometimes, and I make a point to eat sea vegetables (nori) for iodine. My typical breakfast is 3 boiled green bananas sliced and seasoned with coconut oil and Coconut Aminos + 2 eggs and 1 sardine.

I have tried paleo-primal (low carb, medium protein, high fat) diets and they work well for my digestion, thyroid & satiety but I had concerns about eating so much fat when my homocysteine level was high. I also think I need carbs and calories at this point in my journey to support healing, exercise and growth. This protocol is improving my methylation status (based on feelings and symptoms) and I need to retest homocysteine soon.

My avatar is an old picture of me tracking a snow leopard, high in the Himalayas. I figured it represents the username "sherpa" which, to me, means someone willing to navigate a long, hard path to get where we want to be: healthy and capable again!
 
Last edited:

Kathevans

Senior Member
Messages
689
Location
Boston, Massachusetts
I’m impressed by your diet. And love the metaphor you’ve chosen for your healing.

As to supps, you’re further along with your experimenting. I’ve been wondering myself if the B-Complex I’ve taken for years is actually too much for me. The doses on your B-Complex are much lower, and as you say, you feel much more mellow on the lower doses. I see on another thread that Freddd recommends a ‘low strength B-complex’ with ‘no folic acid’ among other low doses. So that may be a place for me to start.

I see my newest alternative doc in two weeks and he may be able to help me sort through some of this. The thing is, the doses in the Country Life Coenzyme B-Complex I take are huge and while I’m inclined to go ahead with the activated B6 (P-5-P), I’m wondering about more B2 when the Country Life already has 50 mg of it.

Yikes. I may be talking myself into stopping this particular supp. In any case, I’m going to go slow till I have my own OAT test in a couple of weeks.

Lastly, I’ve never heard of NT Factor, but you say it greatly helped in your moving forward...
 

jason30

Senior Member
Messages
516
Location
Europe
@Gondwanaland I eat a higher potassium diet - my main carb is boiled green bananas. Main fat is coconut oil, olive oil & some grass fed butter. No sugar, no gluten, no artifical junk. I eat some white rice, steamed green beans and carrots, leafy greens like romaine letuce & lactiano kale, grass fed beef and sardines. I eat a low-moderate amount of fresh fruit - average 1 piece per day. I also like lentils (very high in folate) sometimes, and I make a point to eat sea vegetables (nori) for iodine. My typical breakfast is 3 boiled green bananas sliced and seasoned with coconut oil and Coconut Aminos + 2 eggs and 1 sardine.

I have tried paleo-primal (low carb, medium protein, high fat) diets and they work well for my digestion, thyroid & satiety but I had concerns about eating so much fat when my homocysteine level was high. I also think I need carbs and calories at this point in my journey to support healing, exercise and growth. This protocol is improving my methylation status (based on feelings and symptoms) and I need to retest homocysteine soon.

My avatar is an old picture of me tracking a snow leopard, high in the Himalayas. I figured it represents the username "sherpa" which, to me, means someone willing to navigate a long, hard path to get where we want to be: healthy and capable again!

Hi Sherpa, interesting diet! Are there any benefits of boiling the bananas or is it just a taste thing? And how long do you boil the bananas and do you put those eggs in it as well?
 

Sherpa

Ex-workaholic adrenaline junkie
Messages
699
Location
USA
@jason30 Boiled green bananas are a great carb that supports methylation. It has all the potassium and B6 of bananas but little of the sugar, tastes like a white potato. Raw, or cooked and then cooled .. It contains less-digestable, resistant starch. More filling w/ less blood sugar swing.




I get them very green and hard at a Caribbean grocery. I boil them using this method for about 18 minutes. Can store in fridge for about 3 days. I mash up one boneless & skinless sardine into flakes, stir into two eggs with a pinch of salt to make an omelette. I slice the 3 boiled green bananas and stir fry 'em with 1 tbsp of Coconut Aminos and 1 tbsp coconut oil. (Or if I want resistant starch for fat burning & gut flora feeding properties... I eat them cold... And drizzle the coconut oil and Aminos on.) I sprinkle the stir fried banana slices with kosher salt and nori flakes and then eat. Yum and filling, gives energy for hours.
 
Last edited:

Gondwanaland

Senior Member
Messages
5,094
I mash up one boneless & skinless sardine, stir into two eggs with a pinch of salt to make an omelette.
Hey, that is my recipe to loose hair. What is in it that makes my hair fall? I guess it is the avidin in the egg whites :grumpy:
 

Sherpa

Ex-workaholic adrenaline junkie
Messages
699
Location
USA
Hey, that is my recipe to loose hair. What is in it that makes my hair fall? I guess it is the avidin in the egg whites :grumpy:

Eggs (especially pastured eggs) + sardine contains plenty of B12, folate, omega 3s, protein, choline and natural lechitin that helps rebuilds cell membranes just like NT Factor...
 
Last edited:

MAF14

Senior Member
Messages
195
I have read that taking at least 5mg of riboflavin 3x a day might be enough to normalize B2 levels. The dose regime that I personally took is spelled out above. ^^^^^^^^

Not everyone who is MAO A +/+ is also B2 deficient, but I was... and treating the deficiency was critical to be able to being able to methylate properly. Before adding B2 I got uncomfortably overstimulated by large doses of B12 and even small doses of methylfolate.

Thanks, I see.

I would assume I'm not deficient as I can handle multiple mg of methylfolate and methylcobalamin at a time.
 

Sherpa

Ex-workaholic adrenaline junkie
Messages
699
Location
USA
@Sherpa: What's your opinion of the Jigsaw product so far compared to other forms of magnesium?

Jigsaw is expensive but worth it for the time release and methylfolate, B6 and tiny bit of B12. So for me its the all-around best. I have tried a few forms of oral magnesium...oxide, citrate, glycinate,..chloride in oil... and I find they affect me roughly the same. My gut is not as sensitive as some to the Mg.
 

MAF14

Senior Member
Messages
195
Jigsaw is expensive but worth it for the time release and methylfolate, B6 and tiny bit of B12. So for me its the all-around best. I have tried a few forms of oral magnesium...oxide, citrate, glycinate,..chloride in oil... and I find they affect me roughly the same. My gut is not as sensitive as some to the Mg.

Is it dimagnesium malate itself that is slow release or do they add something to it to slow the release? Looked but couldn't find much on my phone...