1. Patients launch $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
Give ME the Money
Graham McPhee spells out some of the cold, hard facts about the dismal state of ME research and politics, and has some suggestions as to what we can do about it ...
Discuss the article on the Forums.

Advice needed to help decide whether to start methylation

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by topaz, Jun 3, 2011.

  1. topaz

    topaz Senior Member

    Messages:
    148
    Likes:
    3
    I am a newbie to this site and am very impressed with the support and information provided here and desperately seek some advice as I am at a crossroad.

    Just when it all seemed crystal clear, it's now clear as mud....

    Research of my symptoms led me to believe that I would be an ideal candidate to benefit from the B12/methylation protocol . While continuing my research, I asked my doctor for a B12 test (already having had folate, B6 and full blood tested). I realised immediately after the B12 test that the test ordered was Serum B12 and not Active B12 and would be useless. So, back I went for Active B12 and homocysteine to be tested. In the meantime my own research continued and I was just about to order the critical and essential basics per Freddds protocol when my Active B12 results came in.

    In short, my Serum B12 was high (this was not unexpected as I was taking a B-complex 4x/week and the serum result would likely be mirroring the B12 (cyanocobalamin) in my blood but not providing Active B12 levels.

    A few days ago the Active B12 (HoloTC) result came in high at 128 (reference range 23-100 pmol/L).

    tHcy (homocysteine) = 9 umol/L (referance range 5-12 umol/L)
    RBC Folate = 2093 nmol/L (reference range 800 3000 nmol/L)
    Serum B12 = 740 pmol/L (reference range 200 700 pmol/L)

    I have not yet gone down the more extensive diagnostic testing route and have only had the standard blood tests above (plus full blood) through my GP.


    Q: Should I start on the methylation protocol anyway (based on a comment by Freddd Treating to specific test results appears to produce unreliable and poor results in the realm of b12 and folate testing including the indirct Hcy and MMA tests. Only trying both active b12s plus methylfolate can tell you if you will respond to one, two or three of them

    Or should I undergo further testing before starting methylation/B12?

    Advice desperately sought.

    Big thanks in advance.
     
  2. determined

    determined Senior Member

    Messages:
    295
    Likes:
    59
    USA: Deep South
    Hi Topaz,
    While you are waiting for some more knowledable people to weigh in here, I just wanted to say hi and let you know that I understand how difficult these decisions can be. I would think that there would be no problem in trying the methylation supplements in very very small doses and see if you get an obvious effect. Perhaps you are taking forms that are not helping you, and may even be hindering the effective use of the small amount of active forms that you do have.....I will follow this thread and see how you do!
     
  3. Sushi

    Sushi Moderator and Senior Member Albuquerque

    Messages:
    7,291
    Likes:
    6,361
    Albuquerque
    Hi Topaz,

    Welcome to the forum!

    One suggestion--if you can edit the title of your thread, you might get responses from the most knowledgeable people on methylation. As it displays now, the word methylation is not visible until you click on the thread and since most people don't read every thread, your question could be missed.

    Best wishes,
    Sushi
     
  4. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    758
    Hi, Topaz.

    Based on our history here, I'm pretty sure that Freddd's advice will be different from mine :rolleyes:, but I'll share some thoughts, for what they are worth.

    I don't know what your symptoms are, or whether it is likely that you have ME/CFS or not. I also don't know whether you have had symptoms all your life, or whether you have an acquired disorder, such as ME/CFS is defined to be.

    Your test results so far indicate that your intake of B12 and folate have been adequate for a normal, healthy person. Your gut has been able to absorb them and convey them to the blood. You have adequate transcobalamin to carry B12 to your cells. It isn't clear from the test results you have whether or not you have a functional B12 deficiency or a partial methylation cycle block.

    You could certainly decide to go ahead and try a methylation-type treatment, such as the one Freddd recommends. You could proceed right away, without having to wait for more testing, and you wouldn't have the additional expense of more testing. If it helped from a symptoms point of view, that would be great, but I don't think you would know exactly why it was helping, in the sense that you wouldn't know whether you had the type of vicious circle mechanism involving glutathione depletion and a partial methylation cycle block, or whether you had an inborn error of metabolism involving the intracellular B12 processing enzymes. But maybe you wouldn't care to know that, anyway, and would just be happy that you had found something that helped. It's often difficult to tell how the treatment is going from symptoms alone, which may not change right away, or may fluctuate, even getting worse before better. But if you were willing to hang in there for a while, you would probably be able to tell if it was helping or not.

    Alternatively, you could decide to do some more testing to try to understand what is going on in your case. I realize that Freddd does not recommend testing, and does not have much confidence in it. My experience (but note that I focus on ME/CFS, not the broad range of B12-related issues that Freddd's treatment can be used for) is that a couple of panels are very useful. The first is the methylation pathways panel that is offered by the Health Diagnostics and Research Institute in New Jersey, USA, and the European Laboratory of Nutrients in the Netherlands. This panel gives direct information about the status of the methylation cycle, glutathione, and the folate metabolism. The other panel I find useful is the Genova Diagnostics Metabolic Analysis Profile. It gives indirect information about the glutathione status, the methylation cycle, the folate status and whether there is a deficiency in adenosylcobalamin, which is a good indicator of the type of B12 functional deficiency that occurs in ME/CFS. It is especially helpful to have an amino acids panel run in conjunction with this latter panel, to help in interpreting it.

    Why do such testing? The methylation pathways panel will nail down whether or not there is a partial block in the methylation cycle and glutathione depletion. This will tell you whether you have the vicious circle mechanism that appears to be characteristic of ME/CFS. Therefore, it helps with diagnosis, so that you will know what you are actually dealing with.

    Some people try the treatment and get no response initially. Is that because they don't have a partial methylation cycle block? You can know this if you have run this panel and have found that you do have such a block, and will then know that you need to look for something in addition that is blocking the cycle, such as a heavy metal toxin or lack of a cofactor.

    The other advantage of running this panel is that you will have baseline data for comparison later, after doing the treatment for a while. Some people who have just gone ahead and tried the treatment have said later that they wish they had run this panel first, so they could see how far they had come in comparison to how far they still needed to go. Symptoms alone can be fickle, and people get used to the state they are in to a certain degree, so that they are not always able to judge how well they are in comparison to what would be normal.

    We do have a body of data from this panel that can be used for comparison to one's own case, which gives some perspective that can be helpful.

    The Metabolic Analysis Profile (MAP) does include MMA and Figlu, and in my experience, if both are elevated, it's a pretty good indication of a partial methylation and folate block. Pyroglutamate on this panel gives a pretty good indication of the glutathione status, and often the Krebs cycle metabolite pattern does, also. There are also a number of other markers on this panel that can give information about other aspects of the metabolism, especially if there are data on amino acids and toxic and essential elements available from other panels.

    It does take some experience and some understanding of biochemistry in order to evaluate the results of the MAP panel, unlike simply noting whether a particular marker is in or out of the lab reference range. The methylation pathways panel is more straightforward.

    Whatever you decide to do, I will be interested in how it goes for you.

    Best regards,

    Rich
     
  5. illsince1977

    illsince1977 A shadow of my former self

    Messages:
    356
    Likes:
    22
    Welcome, Topaz. You sound like a cautious person who really investigates alternatives thoroughly. I will be interested to see how you progress and wishing you well.
    I wish I had something to contribute in answer to your question, but I'm mostly a listener who really values the knowledgeable perspectives and experiences I hear on the forum. I will listen with you.
    Thank you, once again Rich for taking the time to share your knowledge here.
     
  6. topaz

    topaz Senior Member

    Messages:
    148
    Likes:
    3
    Thank you very much Rich for your very generous and considered response. I have a couple of questions on your comment:

    I don't know what your symptoms are, or whether it is likely that you have ME/CFS or not. I also don't know whether you have had symptoms all your life, or whether you have an acquired disorder, such as ME/CFS is defined to be.

    I dont know whether I have CFS or not as I have not yet had the symptoms for 6 months yet. I believe that CFS is the most likely diagnosis. I have suffered from depression on and off for about a decade but in the 10 weeks I have experienced debilitating brain fog and complete physical exhaustion (which I refer to as flat-lining) to an extent never experienced before in my life! The end of a day of cycling up the Andes is nothing compared to what has come upon me now. Just over two months ago I organised a function (which was not taxing at all) and now that appears like an unattainable task. I would be unable to do that today. In fact I have beeen unable to do much beyond basic looking after self since this condition arose 10 weeks ago.

    In the last 10 days, I have had about 5 good days when I have been about 30% better. These are the first 5 days in over 10 weeks of consistent , relentless and debilitating fatigue and brain fog. However the days have not been in a row but 5 over about 10 days.

    The only thing that I have changed (after dropping the commercial Vitamin B supplement) is addition of magnesium (via powder in bio-active form which also contains, among other things, 550mg glutamine - I discovered this after purchase and before I read Freddd's findings re glutathiione and will be discontinued once finished) and increasing vitamin C (again bio available form).

    Overall, my diet is good (imo). I suffer from IBS and have overcome these symptoms by eating a carb-free diet. Only carbs are vegetables and nuts and dairy. Otherwise, high protein, moderate fats and vegetables. Generally speaking, no processed foods, only grass fed beef/protein and mix of organic and conventionally grown produce.

    I plan to continue with the above however the problem is still far from solved.

    It isn't clear from the test results you have whether or not you have a functional B12 deficiency or a partial methylation cycle block.


    Q: Does the Active B12 (HoloTC) not measure active B12 and hence the methylation cycle? Or is it only a partial result ie is it possible to have a partial methylation cycle block with my Active B12 figures?

    [Im suspecting/hoping that a folate supplement (l-methylfolate) taken with B12s methylcobalmin and adenosylcobalamin may assist.?]

    From my initial (minimal) testing via conventional medicine routes, my homosycteine result that appears elevated. Although in the normal range, I am led to believe from my research that anything over 6.3/7 indicates a problem and needs to be addressed???

    I have yet to have full panel testing, including MMA and methionine etc.
    Thank you for your test suggestions. As I am in Australia I will not be able to use the US labs suggested, however I can request the same tests from labs here in Australia so the advice was not wasted!

    It remains difficult to decide whether just to jump in with supplements addressing the methylation cycle or to undergo testing first (with its additional cost)? I feel anxious to resolve this.

    Ofcourse, there is always the possibility that I have some heavy metal toxicity (sudden exposure or cumulative) as I have had recent hair loss also (predominantly in the front hairline extending about 1.5 inches back at the temples where there is now a mass of baby hairs growing (to full length and normal thickness eventually hopefully)! I have not mentioned the hair loss to doctors yet as compared to the debilitating fatigue and brain fog, it appeared minor however it is now giving me concern and is likely one of the symptoms (although may or may not be related to the CFS symptoms).

    Again, thanks in advance
     
  7. topaz

    topaz Senior Member

    Messages:
    148
    Likes:
    3
    Thank you sushi, determined and illsince1977 for your welcome.

    I think this forum is just terrific and the perfect balance of information and support!

    Im looking forward to more exchanges!
     
  8. determined

    determined Senior Member

    Messages:
    295
    Likes:
    59
    USA: Deep South
    Topaz, I do hope that you can turn this around. It does seem that the longer a person has been ill, the more fragile we become in terms of trying things. I hope the methylation supplements can work for you, and quickly!
     
  9. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    758
    Hi, Topaz.

    It sounds as though there's a good chance that you have ME/CFS and that you have caught it early, which is a good thing. The six months is sort of an artificial interval in a definition developed by a committee (In engineering, we used to have a saying, "A camel is a horse designed by a committee." :)-))

    I think that adding magnesium and vitamin C was a good move.

    Yes, it's still possible to have a functional B12 deficiency with your test results. Your results indicate that B12 is being delivered to your cells well, but they don't tell us whether the cells are able to use it properly, or whether they are just sending it back to the blood bound to haptocorrin. An MMA measurement or a methylation pathways panel would tell you about that.
    People in Australia get the methylation pathways panel from the European Laboratory of Nutrients in the Netherlands. The lab sends out a blood collection kit with vials that contain special preservatives. The kit is FedExed back to the Netherlands with an ordinary ice pack. I don't know if Genova Diagnostics serves Australia, but I know that Metametrix does, and they offer an Organix panel that includes MMA and Figlu.

    If you do have a partial methylation cycle block, I think it's likely that the combination of supplements you mentioned will lift it, though you may need some other cofactor vitamins and minerals, depending on your nutritional status.

    Your homocysteine level is not too bad, but with a partial methylation cycle block, it isn't a very helpful indicator. It can be high, low or normal. If it's normal, as yours is, it doesn't mean much, because you could still have a partially blocked methylation cycle. The homocysteine level in that case depends on the methionine level and on whether you have a polymorphism in the cystathionine beta synthase enzyme. If homocysteineis either high or low, that does suggest a problem with the methylation cycle or the transsulfuration pathway, or both.

    Heavy metal toxicity is very common in ME/CFS. I think the reason is that glutathione is depleted, and it is normally responsible for taking out heavy metals. If you think you might have a high mercury body burden, I would suggest coming up slowly with the methylcobalamin, since it is chemically capable of methylating mercury and moving it into the brain. Whether or not this is an actual issue under conditions in the body, I don't know. It's one of the reasons I suggest that people start with hydroxocobalamin, rather than methylcobalamin. This is one of the points on which Freddd and I differ, and I know that he has his reasons.

    Best regards,

    Rich
     
  10. topaz

    topaz Senior Member

    Messages:
    148
    Likes:
    3
    Thank you Rich

    I too hate committees for that very reason they nearly always result in sub-optimal outcomes (lowest common denominator always wins!).

    I added the magnesium and Vitamin C to the (basic) cocktail of (Fishoil, Vitamins A, D, E (having dropped the B about 3 weeks ago) and (flushing) Niacin introduced as of a few days ago (starting at 100mg and plan to build up). Plus one for adrenal function (called Adaptan here in Australia) I figure it cant harm me and was given to me by my integrative practitioner. I started this basic regime a couple of weeks after first developing symptoms however have not seen any benefit other than Mg and Vitamin C.

    Which brings me to my next point nicely. This is my first foray into orthomolecular/integrative medicine and it has been a little difficult selecting a practitioner here. Not that there is a shortage, but in finding a good one. Since I am transitioning from traditional medicine (and wow! what a glorious learning curve that has been/is) I decided to find an orthomolecular practitioner who is/was a GP and transitioned into this area. I have the support of my traditional medicine GP but she has been limited in her ability to recommend (not being very conversant in this area). I managed to find several via reliable references and finally settled on one (the one recommended by my GPs practice partner).

    Today I took the plunge and decided to go for the full gamut of tests and not start self medicating until after the tests. However, as I cannot get an appointment before 25 August (yes! 3 months but I am on a wait list in the (I believe likely) event of a cancellation) I am reconsidering what to do about testing. On one hand - as it is expensive it is best ordered after a consultation (here $399 for Metametrix Organix Comprehensive profile, $465 for stool analysis, $225 for Baseline+Adrenal Hormone Profile plus the hair tissue test around $150-200?). On the other as I have my suspicions as to what may be causing my conditions I should just start as the methylation treatment is very unlikely to do any harm (and I remain ever optimistic that itll be the right path).

    Thank you for the caution about coming up slowly with methylcobalamin in the event that heavy metal toxicity (mercury) is present. I had read about this (here on this site from memory) but it was not in the front of my mind until thinking about this possibility again.

    Active B12 test: thank you for explaining how the active B12 test results do not indicate whether the cells are utilising it properly.

    I will sooner or later be tested for MMA, methionine and figlu etc (methylation pathways panel). It may make sense to wait until after my consultation with the practitioner who will likely be treating me and if Im unfortunate not to see him (Dr Robert (Bob) Allen) within 3 months, I may very well be self cured by then!

    When I mentioned that I would commence on the B12, B6 and folate, it was my intention to include the co-factors as well (per Freddds protocol).

    I will now go back and read your protocol (again) now that I have more knowledge, heed your preference for hydroxycobalamin, re-consider which methylation protocol to follow and order in the morning.

    Again, big thanks! Your advice and comments have been both reassuring and very informative - a leg-up on the learning curve!

    Best regards

    ps If I understand correctly, you advocate hydroxycobalamin as this allows the cells to convert as much to methylcobalamin and adenosylcobalamin as they need and prevents over stimulation of the methylation cycle. In my case it appears from holoTC test that I have adequate active B12 being delivered to the cells but we dont know what happens after that. If using hydroxycolbalamin does not produce the desired results, we could then consider the possibility that the intracellular B12 processing metabolism is not operating normally and then I would switch to methylcolbalamin??

    pps Can you explain why you use both folinic acid and methylmate in your protocol? Do you have a strong preference for Methylmate over Metafolin or can they be substituted (I am influenced by Freddd's strong preference for Metafolin and not generic methylfolate)? I apologise if this has been addressed by you elsewhere and I have not yet found that post.

    ppps What is your view of taking 5-htp? It has been on my radar but from what I have read of late, I am led to understand that if the methylation cycle is properly resumed, then this should increase serotonin levels and perhaps the 5-htp is not required??

    pppps given that my cortisol levels are unknown (state of adrenals unknown but could be fatigued (hypoadrenia)- I believe that adrenal fatigue is common in CFS however addressing methylation assists adrenals and afterall, you can only start at one point.. ), should I embark on Phosphatidyl Serine Complex or lecithin?

    ppppps Reviewing the contents of the Neurological Health Formula:
    - It contains cyanocobalamin and folic. You have addressed the issue of the folic acid amount (200mg) not being too high in another post. At post #267 of your main thread you say that the level of cyanobalmin (at 500mg) is acceptable as you add back 2,000 mcg of hydroxocobalamin. Its just a shame that there isn't another beneficial forumula available that does not contain these two.
    - I note that it has magnesium and Vit C (in acceptable forms) so presumably I would decrease my current supplementation of those two by the amount in the NHF?
    - Its not ultimate that NHF includes synthetic Vit A (palmitate), niacanimide instead of nicotinic acid (although many do like to avoid the beneficial flushing) as these are not my preferred forms but I guess I'll have to live with that .
    - Is the level of potassium adequate - I have been heavily influenced by Freddd's warnings to supplement with potassium while on the methylation protocol so I want to ensure I have enough (while cognisant of the dangers of too much).
    - You say that you like this product despite that it contains folic acid and cyancobalamin as it has a lot of other cofactors and I would have to agree as it appears to contain a lot of other cofactors that I have come across in my recent research which I put on my radar (inositol being one of several).

    I am so very sorry for all these questions (I am an analyst by profession, and by nature it seems!) but I'm on the starting line waiting for the gun to start!
     
  11. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    758
    That's O.K. I do recommend that you discuss my suggestions with your physician and be monitored by your physician while on this type of treatment, because a small number of people have reported experiencing serious adverse effects while on it, even though it consists only of nutritional supplements. I am not a licensed physician.

    Best regards,

    Rich
     
  12. illsince1977

    illsince1977 A shadow of my former self

    Messages:
    356
    Likes:
    22
    Oh, really, Topaz, I couldn't tell! ;);)

    I used to be one myself, but can't keep the various methylation recommendations straight for the life of me at this point. I couldn't be one anymore for the life of me, either. I can't believe how well you seem to have grasped it all. Of course there's an obvious logical fallacy in that statement, since I'm not competent to judge someone else's grasp of the material, having not grasped it myself!
     
  13. topaz

    topaz Senior Member

    Messages:
    148
    Likes:
    3
    Thanks Rich

    I hope it didnt appear that I was using you as a substitute physician - its just that I cannot get in to see one until 25/08 and want to start.

    Big thanks
     

See more popular forum discussions.

Share This Page