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

[Sherpa]

@jason30

I currently take 1/2 of a "Methyl B Compete" capsule per day, orally, swallowed. The taste is terrible astringent, I do not recommend putting the powder in your mouth.

I am slowly working up to a full capsule. My homocysteine level dropped from 13.8 to 10 after starting the Methyl B Protect (TMG & folinic + methylfolate)

I weighed out the contents of one full cap (608mg) to find the full amount for reference - and wrote the dose on top of the bottle in black permanent marker for reference. . Then on future days I pour out half (304mg) onto a digital milligram scale and into another empty gelcap, keep the half full original... and I get two half capsules. This quickly and evenly divides them.

I personally use B12 Ice... which is half methylcobalmin , half adenosylcobalmin... with Vitamin D and anti-inflammatory tumeric derivative tetrohydrocurcumin (THC).

 

[jjxx]

@Sherpa I studied your regimen and the entire thread as best I could, thank you and many others!
Your regime is significantly gentle due to much smaller amount of other B1, 2, 3...etc, small dose/slow-release methylfolate. In my father's case, potassium is a big concern. Therefore, your regime makes more sense for him.
In my own case, I am roughly following a stronger regiment from Freddd's, with Solgar 800mcg metafolin, 2000mcg methylb as one single dosage two hours after other essential nutrients as he recommends. It has been almost two weeks, I do feel energy lift without any major side effect except a very slight headache and a faster heart beat. I guess my body handles folate/b12 better?

 

[Sherpa]

@Sherpa I am roughly following a stronger regiment from Freddd's, with Solgar 800mcg metafolin, 2000mcg methylb as one single dosage two hours after other essential nutrients as he recommends. It has been almost two weeks, I do feel energy lift without any major side effect except a very slight headache and a faster heart beat. I guess my body handles folate/b12 better?

Yeah I had a MAO A related hypersensitivity to methyl donors. I had to get methylation started extremely gently. It sounds like you are "normal" and have an expected response

 

[Athene*]

.:: 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.

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.

Above protocol is very clearly laid out and hopefully will help someone. A lot of it is very similar to what Greg of B12oils has been recommending to some of us who have consulted with him by email (see thread on B12 oils), with the addition of some co-factors you've included which he didn't mention (Doctor's Best L-carnitine Fumarate, Extramel SOD extract, D-ribose, NADH, thyroid glandular and NT Factor). Have you consulted him too?

Interestingly I had exactly the same advice as you have above, on 'MAO' in one email, and on potassium too, but unfortunately B2 didn't work for me in the end, though I still take it at low dose, similar to above, and I need high dose potassium (going to food only sources nearly killed me even on the oils (not injections) and I ended up in ER with potassium of 3.0 instead of my usual 4.5).

Some of those who weren't bed/house bound did ok (see thread I mentioned). Unfortunately it didn't work for others. It made me a lot worse. In particular I regret dropping my B12 high dose injections. I gradually failed when I switched to the oils - without realising it, the benefit of the injections was gradually running out. I'm back on high dose b12 injections now with 4 doses of methylfolate spaced out during the day (similar to 'sustained release' I guess) and feeling much better. This requires high dose potassium too. Happily, I just got some blood tests and my kidney function is still >90 as always even after a year of high dose potassium (except for a very brief period of low dose potassium). According to my doc you can take a lot of potassium for a very long time if you have normal kidney function. I take the same mineral complex as above and magnesium too and the nature made b complex.

Btw, for anybody thinking of trying the B12 Ice, the D made me very ill (currently being tested for high vitamin D 1.25 OH which any form of D supplements will make worse). The BGroup Oil made me ill too - perhaps the high niacinamide (niacin? - whichever one is in it - it was a while ago).

The methyl oil was fine, though didn't help my B12 levels.

Having said all that - my cousin who has a straightforward B12 deficiency, caught early, finds the plain methylb12 oil works very well for her at two doses per day. The one with Adenosylcobalamin made her feel lousy - perhaps she doesn't need it for now.

I might go back to using the Ado oil with my injections. For now sublingual Ado.

Perhaps our individual responses to differing protocols depends on how much damage has been done/how long one is B12 deficient. It's hard to know for many of us, how long we've been deficient because of how some of us have elevated serum b12, even when it's not reaching our cells.

 

[bigmillz]

To those who have gotten this to work for them, what B2 doses were you taking? On day 3 of 50mg (25 and 25 split) and so far so good. I've got the 50mg Solgar B2 on the way so that I can split it up more if needed - 100mg NOW capsules are tricky for this.

 

[Kathevans]

@bigmillz I'm still working on this and have to say none of it has been easy. I've stopped and started B2 on several occasions, currently use that tiny Solgar 100mg Riboflavin tablet, which believe it or not, I open and divide into four separate doses. In two of them, which I take morning and night, I add 1/2 150- Molybdenum tablet and 1/2 22mg Zinc Pincolinate tablet, so that I get my daily doses of these. I also get another 20mg of B2 in my daily B-Complex by Seeking Health, B-Minus.

Yet at 120mg--and brielfy more--B2/day seems to be more than I need, or at least, I haven't noticed when I lower the dose to the Solgar B2 3x/day, or about 75mg and then the addition 20mg in the complex.

All said, I'm still trying to figure out Folate, and stayed off it for so long that I seem to have quite a deficiency. I'm up to about 7-8,000mcg/day and unclear where I am and whether I need more Adeno (probably) or or even more Folate (probably this, too)

All this is on a base of a Squirt of Methyl B12 Oil and other minerals. I think someone else has pointed out that the fix may not be instantaneous. For me, at any rate, things seem to have shifted over time...new needs have appeared and so forth.

Good luck!

 

[bigmillz]

@bigmillz I'm still working on this and have to say none of it has been easy. I've stopped and started B2 on several occasions, currently use that tiny Solgar 100mg Riboflavin tablet, which believe it or not, I open and divide into four separate doses. In two of them, which I take morning and night, I add 1/2 150- Molybdenum tablet and 1/2 22mg Zinc Pincolinate tablet, so that I get my daily doses of these. I also get another 20mg of B2 in my daily B-Complex by Seeking Health, B-Minus.

Yet at 120mg--and brielfy more--B2/day seems to be more than I need, or at least, I haven't noticed when I lower the dose to the Solgar B2 3x/day, or about 75mg and then the addition 20mg in the complex.

All said, I'm still trying to figure out Folate, and stayed off it for so long that I seem to have quite a deficiency. I'm up to about 7-8,000mcg/day and unclear where I am and whether I need more Adeno (probably) or or even more Folate (probably this, too)

All this is on a base of a Squirt of Methyl B12 Oil and other minerals. I think someone else has pointed out that the fix may not be instantaneous. For me, at any rate, things seem to have shifted over time...new needs have appeared and so forth.

Good luck!

That doesn't sound so bad. Were you unable to tolerate folate before the B2? I'd say if you're up to 7-8mg you're doing alright! I can't even get 100mcg down for more than a few days without starting to get all overstimulated.

 

[Kathevans]

I could never tolerate more than abut 1600-1800, and not very well. I felt over-hyped, as you say. I began to add B2 back in last September after working on molybdenum and selenium levels over the summer. I began with small amounts in my B-complex 20mg/day, then began to add FMN, 1/4 of a 25mg tablet 4x/day and had little or NO folate for some months, feeling unable to tolerate it. All along I was taking 1 squirt of the B12 Oil/day. In December I raised the amount of B2 I was taking to about 135-145/day and also added a bit of Lithium Orotate - 5mg/day. Slowly, I began to push up the folate, following symptoms--runny nose, headaches, insomnia--and was able to titrate up 400-800-2000 by the end of January. And so on. It was definitely a process; and I'm still engaged in it. I'll have to have another NutrEval Test or some such in another month or two to see where I'm at. I'm also still playing with B2 levels, trying to ascertain whether I need as much as I'm taking. I've lowered it to about 95mg/day and seem to be doing ok.

I suspect staying away from folate for so long made my deficiency worse and it may be a while before I 'refeed' it sufficiently. Meanwhile, I feel out of balance still, now with not only the folate, but also Adenosyl B12.

It looks to me that B2 could help you.

 

[niki]

It is impossible for me to say anything without seeing all of his epigenetic (methylation) SNPs.

Stay away from calcium is all I really can say.

I just realized this is an old post, but I had an ND that initially said to avoid Calcium and then after 6 mo of testing said I fell into a small group of 12% that actually do need Ca...prob because I've never consumed dairy or much high Ca foods. So there are exceptions... I hope as I started taking ionic Ca with my ionic Mg.

I'm interested in your taking of FMN, I feel like I've read it's not good to take this form, do you still? I'm trying to up my B2 so I can handle methyls better.

Thanks

 

[Kathevans]

@ppodhajski was a wonderfully brilliant guy who spent a lot of time here a while ago. Many of us learned a lot from him and miss him. He was very knowledgeable about genetics, particularly epigenetics or discovering how to use diet and supps to respond to our genetic polymorhisms. I'm not sure if you can go back and look at his posts, but anyway. ..

I have no idea about calcium levels as it hasn't been an issue of mine, though my own PCP said not to take it now as mainstream medicine says it can cause heart issues.

As to FMN, many here take it, I suspect as much because it's one way to get a lower dose of B2 than 100mg. I'm not sure. I do know that Greg Russell-Jones is against it because something is done to make it the 'active' form, which he (PhD in biochemistry) says the liver has to undo to utilize anyway--so don't waste your money! I believe what some have found, myself certainly, is that this active form made a real difference when we couldn't ascertain any difference with regular riboflavin. Once I'd worked with B2 for over a year, ramped up as high as about 150mg and then back down again, I seem to utilize both, and at this point work with a 100mg capsule (divided by 4, then each of these in half to get very roughly about 12mg/cap) and ingest about 25mg in this form, another 18 mg of FMN (or 25 riboflavin) with my daily divided dose of B-Complex (B-Minus), which has another 20mg of 'active' B2, or FMN. This totals around 65-70 mg of B2/day, and it's entirely possible I may need less still, but I don't know yet and haven't tested it!

One thing I know for sure is that it has taken my body a good long while to get used to varying supps, and for their effects to 'kick in'. I've tried some things and then tried them again. And again. In all of this don't be discouraged early on. That's why reading the major methylation threads is important. There's just so much advice given in these, especially by Fred, that we can learn from, and continue to climb back up on that horse each time it feels as if we've been thrown off.

 

[niki]

Thank you! I think I replied in my head but I have lots of reading to do! This is perfect because I was looking for Fred's protocol (it was mentioned all over) but I couldn't find it!
I was hoping it wouldn't take a year to sort out one aspect of methylation, as I've ben at this for so long and getting too old for my "family planning", but that's life.
Many thanks for sharing links and your experience as it's a big help!

 

[bigmillz]

Question for @Sherpa and anyone else who's had success with B2 here...did you guys lower the amount of B2 you've been taking after it allowed you to successfully take methylfolate? I'm wondering this so as to not overdrive MAOA, as I've read there can be issues with it being too effective. A lot about that in the "no love for B2" thread.

 

[Sherpa]

I took a conservative amount of B2 close enough to what was recommended in studies (e.g. 5mg three times per day) or close enough. I did that for a few weeks and then I could handle methylfolate. (I am not able to scientifically for sure that is what allowed me to tolerate it, as other varaibles in my diet or supplements could change... even placebo effect could played a part... but I *think* it was the B2)

After I fixed my insufficiency I just went to a standard B-complex for maintenance. I had since had no problems with methylfolate up to around 1000mcg per day, but too much TMG still makes me overmethylate.

 

[bigmillz]

I took a conservative amount of B2 close enough to what was recommended in studies (e.g. 5mg three times per day) or close enough. I did that for a few weeks and then I could handle methylfolate. (I am not able to scientifically for sure that is what allowed me to tolerate it, as other varaibles in my diet or supplements could change... even placebo effect could played a part... but I *think* it was the B2)

After I fixed my insufficiency I just went to a standard B-complex for maintenance. I had since had no problems with methylfolate up to around 1000mcg per day, but too much TMG still makes me overmethylate.

Thanks man. I was taking 25mg but I'm trying to drop down to half that now that things are going more smoothly.

Same thing here with TMG, which I oddly used to do just fine with. Or maybe it wasn't actually fine, and now I realize I feel better without the TMG lol.

 

[bjl218]

Great thread. I hope it's not too old for me to comment. I didn't really have anything to add other than the following: A few years ago, I saw a functional medicine MD for various issues (don't need to go into them here) and learned that my homocysteine was high. I am MTHFR C667T +/- and MTRR A66G +/+. I started on various methylation supplements and didn't seem to have any issues. Fast forward to now where I'm having some additional issues (probably mostly mold-related) including even higher homocysteine and I find that this time around I seem to be sensitive to methylation supplements. I've read this and some of the other B2-related threads, recently did a NutrEval, and saw that I'm low in most of the B vitamins (including B12 and folate). But of all the B's B2 seems to be the most deficient. And that seems to fit in with the "low-B2 causing methylation supp sensitivity" theories. So I'm going to start on a B2-only regimen then add back in the other B's after a while. I plan to use Seeking Health's Optimal Start when I start adding back other B's since 1 capsule contains very low dosages of the various B's. It excludes B12 and folate so I'll use something else (probably what @Sherpa has recommended) for that

 

[Kathevans]

@bjl218 This is a sound approach, I think. At any rate, over time it worked for me. Just be sure you have the B2 supports in place—according to Greg Russel Jones, the B12 Oil Biochemist. You need to have sufficient iodine for thyroid, selenium and molybdenum to have the B2 work properly. I had to titrate with the molybdenum for a couple of months, starting with 1drop in a quarter cup of waterr and using a teaspoon, then a tablespoon and so on.

B2 did help me to increase other things, though. It was a necessary starting place. And I still use the the Seeking Health B Minus, just for the reason you mention. It has no B12 or Folate and you get to see how each of those works on its own.

 

[bjl218]

Thanks for the support @Kathevans !

 

[bjl218]

For those of you using FMN (a/k/a R5P, a/k/a co-enzymated B2) to build up your B2 prior to starting other B's and methylation support, how much FMN are you taking per day? I'm taking one Source Naturals Co-enzymated B-2 sub-lingual alone right now which is 25mg FMN (18mg riboflavin). My urine turns greenish/yellow pretty quickly after I take it.

Also, I'm a bit confused about the relationship between riboflavin, FMN, and FAD. Does riboflavin convert to FMN and FAD. If so, then it seems like I should be including riboflavin (not co-enzymated) in addition to the FMN. Or does riboflavin convert to FMN which then is converted to FAD. I've done some Googling on this and have come up with conflicting information. Or maybe I'm not understanding the information I've read. Not as smart as I used to be...

 

[bjl218]

Status report. I've had a very enlightening email discussion with Greg (from b12oils.com) who again stressed the importance of B2 in supporting methylation and avoiding side-effects from methylation supplements. I've been loading up on B2 primarily using Source Naturals Co-enzymated B2 (FMN) 1x or 2x/day. I can feel that the B2 is doing something. I'm pretty sure I feel a bit calmer although I might also be having the low-serotonin crash in the early evening someone in this thread mentioned a while back. So I think I'm going to switch to 1x/day in the evening on the B2.

At Greg's suggestion, I've also started taking the Life Extension Mix Powder which is a multi-vitamin (and then some) that contains all of the B2 support Greg suggests (molybdenum, selenium, iodine). I chose the powder because I can easily adjust the dosage. The full dosage (3 scoops) is pretty strong so I've been taking only 1 scoop/day for now.

I've received my B12 oils and plan to start with 1 squirt of the adenosyl/methyl in a few days. I'll report back again in a few weeks.

Summary of current protocol:
- Source Naturals Co-enzymated B2, 1x/day
- Life Extension Mix Powder, 1 scoop/day
- Lithium Orotate, 5mg/day
- Magnesium Glycinate (various brands), 400-800mg/day

 

[Eastman]

- Life Extension Mix Powder, 1 scoop/day

Important question: How does that taste?