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Methylation protocol issues, only three months in


I started Fredd's MP a couple of years ago and had to abort around the three month mark....and it's happening again, although for different reasons, at pretty much the same three month point :-(

I purposefully took it easy this time with a view to building up, and this was my daily regime for two months:

Breakfast followed by one general RDA multivit that I've been taking for years (Carlson Mini Multi)
One 100mcg NOW Selenium tablet mid-morning (taken for years)
Half a Thorne Basic B capsule (split into another veggie cap) late afternoon
One magnesium malate tablet at bedtime (again, I've been taking these for years)

So basically all I added to my daily regime as a gentle starting off point was the half a Thorne Basic B Complex, which is a co-enzyme formula.
As a backgound, I have CFS/ME and have been getting slowly worse over these past four years after a pretty sustained and nasty period of personal stress.

Anyway, just like the last time I tried coenzyme B Complex, I experienced noticeable improvements in my mood, energy and post-exertional malaise. Nothing like a cure or a quick fix of course but improvements nonetheless and I'm loathe to pack this in. HOWEVER, around the two month mark I started to notice slight swelling in my lower legs, the first few inches above my ankle. This got steadily worse and apart from being uncomfortable and my socks leaving deep, bruised indentations, I became worried that I had some major issue like heart failure or something! Only the fact this came on whilst taking active Bs has reassured me (*a little) that this is a coincidence and is related to my methylation, or a possible intolerance to something.

SO, reading up on the web as to what might be causing this I came up with nothing except the usual suspects of heart failure and furred-up arteries etc. Not pleasant reading! On here though, Phoenix Rising, after reading for hours & hours, I did see some slight mention of edema and I also noticed that low potassium can cause it. Therefore I started munching bananas, I ate approx four per day whilst continuing to take all my supplements. The leg swelling improved a little but is still hanging around and on some days it is quite bad. SO, alongside the bananas I started to add 1/4 of a Solgar metafolin tablet to my daily regime thinking that I was under/over methylating but I haven't got a clue. This seemed to have no positive effect other than making me feel more fatigued, so I added half a Solgar sublingual MB12 lozenge (half of 1000mcg). Again this has had no positive effect on my lower leg swelling.

So I'm lost now. I haven't a clue on which supplement to cut back, which to increase the dose, or indeed what to add next. I'm loathe to quit taking the active Bs as they are definitely helping, but I can't stand this lower leg swelling/edema. It will end up making me stop (which I indeed did for a few days with no real improvement).

Any ideas? I'm fairly sure that if I stop all the Bs and folate that eventually everything will return to normal but I'm looking for some advice on how to keep the wheels turning.


Senior Member
Salt Lake City
Hi Sunking101,

Edema is, for me, a L-methylfolate deficiency symptom. Here are groups of symptoms that come up after starting well caused by induced deficiency. I'm up to 24mg daily of Metafolin in 3 doses of 8mg. For the first time I no longer have edema and other methylfolate deficiency symptoms that occurred every two weeks for much of my life and made identifieable by watching the effects of l-methylfolate. I have titrated there over several years and have charted how the symp[toms changed. Edema is the first to occur and the last to stop occurring. I don't knopw if anybody else has such a periodic effect but when I got up to about 12 mg daily I had to quit my diuretic as it was no longer needed and doing damage. I dropped a total of 85 pounds net of water as two 45 pound loses after two rounds of healing. Even after that for 6 or 7 more years I had edema come on each 2 weeks with the induced (paradoxical) folate deficiency. Good luck.

Version 1.3 01/27/2015

Group 1 – Hypokalemia onset. Symptoms may appear with serum potassium as high as 4.3. May become dangerous if ignored. Considered “rare” with CyCbl (Cyanocobalamin) it is very common with MeCbl (methylcobalamin) and AdoCbl (adenosylcobalamin) and less so with HyCbl (Hydroxycobalamin).

There does not appear to be a clear order of onset. The order of onset varies widely from person to person but many appear consistent for each episode for any given person. There tend to be more and more intense symptoms as it gets worse. Some people have ended up in the ER because of not recognizing the symptoms.

IBS – Steady constipation, Nausea, Vomiting, Paralyzed Ileum,

Hard knots of muscle, Sudden muscle spasms when relaxed, Sudden muscle spasms when stretching , Sudden muscle spasms when kneeling, Sudden muscle spasms when reaching , Sudden muscle spasms when turning upper body to side, Tightening of muscles, spasms and excruciating pain in neck muscles, waking up screaming in pain from muscle spasms in legs. Muscle weakness

Abnormal heart rhythms (dysrhythmias), increased pulse rate, increased blood pressure

Emotional changes and/or instability, dermal or sub-dermal Itching, and if not treated potentially paralysis and death.

Group 2a - Both

IBS – Diarrhea alternating with constipation, IBS – Normal alternating with constipation

Group 2b – Either or both

Headache, Increased malaise, Fatigue

Group 3 - Induced and/or Paradoxical Folate deficiency or insufficiency

These symptoms appear in 2 forms generally, the milder symptoms that start with partial methylation block and the more severe symptoms that come on as partial methylation block gets worse or very quickly with methyltrap onset.

Edema - An additional thing I would like to mention. I would never have found it without 5 years of watching the onset of paradoxical folate insufficiency and trying to catch it earlier and earlier and to figure out what was causing it and to reverse it. For me the onset order goes back to the day of onset now with edema and a sudden increase of weight. I noticed that within 2 hours of taking sufficient Metafolin I would have an increase in urine output.

Old symptoms returning


Angular Cheilitis, Canker sores,

Skin rashes, increased acne, Increased itchy acne on scalp and face, Skin peeling around fingernails, Skin cracking and peeling at fingertips,

Increased hypersensitive responses, Runny nose, Increased allergies, Increased Multiple Chemical Sensitivities, Increased asthma, rapidly increasing Generalized inflammation in body, Increased Inflammation pain in muscles, Increased Inflammation pain in joints, Achy muscles, Flu like symptoms

IBS – Steady diarrhea, IBS – Diarrhea alternating with normal, Stomach ache, Uneasy digestive tract,

Coated tongue, Depression, Less sociable, Impaired planning and logic, Brain fog, Low energy, Light headedness, Sluggishness, Increase irritability, Heart palpitations,

Longer term, very serious

Loss of reflexes, Fevers, Forgetfulness, Confusion, Difficulty walking, Behavioral disorders, Dementia, Reduced sense of taste, bleeding easily

Group 4 - HyCbl onset, degraded MeCbl onset, MeCbl after photolytic breakdown onset.

Itchy bumps generally on scalp or face that develops to acne like lesions in a few days from start.
Thanks for your reply Fredd.
I've never had edema before though, or certainly not so that I would notice. It seems to get a little better if I take a lot of potassium but the effects are shortlived and not entirely satisfactory. I tried upping my methylfolate today and felt instantly shattered. I've also had diarrohea. :(

Would you say that these symptoms are (still) pointing towards a folate deficiency?


Senior Member
Salt Lake City
Angular Cheilitis, - Canker sores, increased acne, Increased itchy acne on scalp and face,
IBS – Steady diarrhea, IBS – Diarrhea alternating with normal,
Skin rashes,
Skin cracking and peeling at fingertips
Skin peeling around fingernails,

These can be the first ones for some people to notice. People vary.
Coated tongue, Less sociable, Impaired planning and logic, Brain fog, Low energy, Light headedness, Sluggishness, Increase irritability, Heart palpitations,

For me each time it came on when I let it go long enough this is the order of onset pretty much with the first two on day one and angular cheilitis etc day 2-3 and IBS by day 3, but this was after I was healing for a while. In the beginning I had most of them for decades and they got worse from time to time. I found that what it too was to take the dose 3 times a day and increase all doses by 50%-100% or so each day until the symptoms start to go away. The edema wasn't affected however until I had healed considerably. That was the last one to become intermittent. and then be mostly eliminated. The cheilitis was the first to notice with the "fire" going out of it the first day and the sores healing quickly, the acne fading fast but that can also be HyCbl. It got worse hard when I started Metafolin.

The potassium needs to be taken in at least 4 doses a day for best effects.

200mcg increase just tortures the person indefinitely. Once Metafolion became easily avaialble I learned that incrteasing by 800cmg at each of 3 or 4 doses a day worked well without taking too long. From 2400mcg x3 to 3200mcg 3x per day I went to 4800mcg to 6400mcg to 8000mcg 3 times a day, where I presently am. . Smaller increases were not effective. With each increase one or more of the symptoms stayed gone from 3200 mcg x3 per day. This is what worked for me and similar for others. Good luck. The IBS is gone now unless I drink milk or eat cheese.


Senior Member
@sunking101 I looked at the multi vitamin you posted, and if it is the correct one, it has 400mcg of folic acid. It also has some cyanocobalamin. Many of us around here avoid folic acid as much as possible. There are studies that indicate folic acid can block folate receptors. I know that if I get even small amounts of folic acid I start getting @Freddd 's paradoxical folate deficiency symptoms.

You might want to look at a new multi vitamin that doesn't have folic acid and cyanocobalamin. Just a thought.


Senior Member
Hi sunking,

You're running into a lot of roadblocks.

Like Phred, I suggest discontinuing the Carlson multivitamin as it contains the wrong forms of folate and B12.

The B12 in both the Carlson multi and the Thorne Basic B are both oral, and therefore will absorb very little. I don't even bother to count oral B12.

So unless you're taking an absorbable sublingual B12 along with these vitamins, you're getting folate without B12 causing methyl trapping, which can make you worse.

Also I'm not sure how well the Solgar B12 absorbs. Some brands are better than others.

Freddd suggests :
Enzymatic Therapy B12 infusion 1 mg sublingual
Country Life Methyl B12 5mg sublingual

I suggest Douglas Labs methylcobalamin liquid used sublingually.

Also some people such as myself have trouble deriving potassium from food. I suggest using NOW potassium gluconate powder.

In addition, there may be some missing co-factors which will cause roadblocks, especially if you discontinue the multi.

If you wish to follow Freddd's protocol, there is a good synopsis here: http://forums.phoenixrising.me/index.php?entries/a-guide-to-freddds-protocol.1618/

I have also a document called Roadblocks to Successful Methylation which may be helpful. It's based on several methylation protocols not just Freddd's. See my signature link.
Thanks guys, I'll have a look into all of that. I am aware that the multivit has folic acid but I've been taking it for years and this lower leg swelling has only started in the last 4-6 weeks since taking the methyl B's. I didn't think that small RDA levels of folic acid and cyanocobalomin would mess things up unduly?
Most multivits I look at have something in them I'm either intolerant to, or is the incorrect form. It is rather a nightmare! Can anyone recommend a good multivit?

Also, will there come a time where I don't have to load up on potassium? I've noticed that my leg swelling goes down a fair bit a couple of hours after taking potassium. I find it the hardest supplement to take because it isn't just like popping a pill once or twice a day, my mind needs to be thinking about taking on potassium pretty much all the time and it's both laborious & scary. I eat potatoes, bananas and potassium pills by the sackload but still don't feel adequately on top of it.
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Senior Member
Seattle, WA

I've been on Freddd's protocol for not quite 11 months.

I understand the frustration -- I went through it -- a lot of us did. For me it came down to a question of how badly I needed to get better. I ended up clearing the metaphorical table completely of all vitamins and starting over. I don't take a multi vitamin at all now -- I take each thing I need individually. Yes, it's a LOT more work, but after having read now hundreds of labels to understand exactly what's going into combination tablets, I wouldn't go back. So many multi-vitimins or b-complexes are using forms of supplements that are simply not bioavailable, from folic acid to the non-active B12s to zinc oxide and on and on. These things make a huge difference in their effects on my body and to say they are not interchangeable is putting it lightly. :) I have been stunned, over and over, to find that different forms of supplements are not the same at all. (Most recently zinc. Wow.)

I take potassium to symptoms of deficit, so my needs can go up and down depending -- usually up when I made some change that is effective then down again when my body starts finding a steady state. I probably take 3-5 grams a day, but I don't keep track any more. Just take it when I need it, and before sleep. Potassium is great stuff, and I have no expectation that some day I'll stop taking it. Or L-MTHF, which my body can't make itself in sufficient quantities. Or MeCbl, or any of a number of other supplements I take.


Senior Member
I'm in a similar predicament. After maybe 3 months of the Fred Protocol the effects wore off. Nothing bad happened - but all the good stuff (there was a long list) just kinda faded away. Doubling the doses for 10 days did nothing. So I stopped (which didn't seem to change anything).

Since then I've found I have pyroluria, & pyroluria supps (mainly zinc & B6 in high-ish doses) have made a huge difference. They may even be cranking up methylation for all I know, as the effects are similar.

I've also found I'm low on adrenal hormones hydrocortisone & DHEA, & T3, so take all of those. So energy is back. And life isn't bad.

But I am still intrigued by those huge initial gains from the FP, and where they went.