Phoenix Rising tells QMUL: release the PACE trial data
Mark Berry, Acting CEO of Phoenix Rising, presents the Board of Directors’ open letter to Queen Mary University of London (QMUL) urging them to release the PACE trial data, and hopes that other non-UK organisations will join British charities in the same request...
Discuss the article on the Forums.

Folic Acid: Bad Idea or VERY Bad Idea and how much is too much?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Lotus97, Mar 21, 2013.

  1. Lotus97

    Lotus97 Senior Member

    Messages:
    2,035
    Likes:
    522
    United States
    There seems to be a consensus that there aren't any good reasons to take folic acid, but I'd like to hear more about why we shouldn't take it. I've heard that it causes problems for some people, but the only thing I've heard so far that applies to everyone is that it uses up NADPH. I assume it competes with methylfolate for absorption to a certain extent, but as far as blocking methylfolate I'm not sure this happens with everyone. A certain percentage of the population can convert folic acid into folinic acid and methylfolate otherwise this supplement wouldn't exist. I'm trying to decide whether to stop folic acid entirely or just limit it. I'd also like to know what advice to give to others.
     
  2. Freddd

    Freddd Senior Member

    Messages:
    4,940
    Likes:
    1,475
    Salt Lake City
    Hi Lotus,

    Actually nobody knows, What you can know, and ONLY by doing about 3 cycles of A-B comparison. you will absolutely know. If you are uncertain you don't have a problem. The difference is very obvious generally. I've given you a summary of what is known and may be so and what is pragmatically determined and may be so. I'd take the bet on the pragmatic over the hypothetical. Good luck Maybe you will find what helps us all figure this folate puzzle out. I'm not sure if it affects everybody or if it affects everybody at high enough dosage or what. It didn't seem to affect a good friend of mine but neither did l-methylfolate until very recently, at the same time as my deep CNS healing got going.


    One other thing that I would bet on for everybody is that folic acid decreases the serum halflife of b12s following a dose as compared to l-methylfolate. If you are willing to do a series of large enough injections on folic acid and then the same series with l-methylfolate the amount of b12 in the 3 hour urine collection will be very obviously different, between 50% and 100% more most likely with the folic acid.
     
  3. Plum

    Plum Senior Member

    Messages:
    446
    Likes:
    308
    UK
    I am just checking I understand that you are talking about folic acid and not folinic acid? Is there an issue with folinic as part of methylation protocol? Thanks and sorry for being a dweeb!
     
  4. Freddd

    Freddd Senior Member

    Messages:
    4,940
    Likes:
    1,475
    Salt Lake City
    Hi Plum,

    I the folic acid problem is at least recognized as genetically limited. Some unknown percentage of population has a folinic acid problem. The only way to know is to try a pure l-methylfolate trial and switch back and forth a few times or try adding the folinic acid back in and see what happens. I don't know of any way to predict who would have folinic acid problems.

    Those that had certain typical symptoms patterns as children probably have a similar conversion problems with folinic acid. However, that doesn't address a different mechanism, the donut hole folate insufficiency. When healing turns on it may just be that folinic acid simply can't supply the l-methylfolate quickly enough or maybe past the biological limit and then somehow appears to compete making it more difficult for the methylfolate.
     
  5. Plum

    Plum Senior Member

    Messages:
    446
    Likes:
    308
    UK
    Thanks Freddd. Can I ask what would be happening to signify a problem? Or point me in the direction of where I can learn about this.
    Also, is there a post on doing a L-methylfolate trial? I need to learn more about this as it's new to me.

    I am following Rich's protocol and am up to 500mcg methylB12 and 100 folinic acid. So far I've had tiredness, sleeping more, a little nausea and some disorientation. I take a day or two off when I feel a bit weird. The B12 seems to be causing the tiredness and the folinic the others.
     
  6. Freddd

    Freddd Senior Member

    Messages:
    4,940
    Likes:
    1,475
    Salt Lake City
    Hi Plum,

    The lists below can help make clear the distinctions amongst several different common response patterns. Both things can be happening at the same time. More than 2 things can be happening.

    Can you be more specific about the sleep changes and sleepiness. Different pattern? More of the same? Normal dreaming? There can be a number of different things.

    A couple of the common things that happen are when cell formation increases are lower potassium that causes one set of symptoms and another major response is needing more l-methylfolate. Tiredness and sleepiness can sometimes be caused by a lack of AdoCbl and/or l-carnitine fumarate. Sleeping more can be any number of things including ending a sleep disorder with melatonin increasing.

    I'll be posting soon a possible tie to childhood symptoms for paradoxical folate insufficiency.


    Group 1 – Hypokalemia onset. Symptoms may appear with serum potassium as high as 4.3. May become dangerous if ignored. Considered “rare” with cyanocobalamin it is very common with methylb12 and adensosylb12 and less so with hydroxycobalamin..

    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

    IBS – Steady diarrhea, IBS – Diarrhea alternating with normal, Stomach ache, Uneasy digestive tract, increased hypersensitive responses , Skin rashes, Increased acne, Skin peeling around fingernails, Skin cracking and peeling at fingertips, Angular Cheilitis, Canker sores, Coated tongue, 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, Depression, Less sociable, Impaired planning and logic, Brain fog, Low energy, Light headedness, Sluggishness, Forgetfulness, Confusion, Difficulty walking, Behavioral disorders, Dementia, Reduced sense of taste, Increase irritability, Loss of reflexes, Fevers, Old symptoms returning, Heart palpitations, Bleeding easily.
     
  7. Linda

    Linda

    Messages:
    29
    Likes:
    3
    Hi, Lotus

    2 years ago I was almost better from CFS. Still had some cognitive difficulties so decided to try Methylation sups. Added in half a country life AD-B12, which contains Folic Acid. The next day had intolerable nerve pain in my face and scalp muscles which I still have.

    The only thing that keeps this pain at a manageable level is 100mc Folate and 2000mc HB-12. If I increase the Folate or try Methyl-B12 the nerve pain becomes worse along with depression.

    So I would tell people to NEVER take Folic Acid, or to be extremely careful with it.

    I feel I would have now been almost recovered if I hadn't taken it.

    Linda
     
  8. Freddd

    Freddd Senior Member

    Messages:
    4,940
    Likes:
    1,475
    Salt Lake City
    Hi Linda,

    That sounds like a brutal reaction to folic acid. Have you considered trying microtitrating AdoCbl for it's possible affect on inflammation and nerve repair? Good luck.
     
  9. Plum

    Plum Senior Member

    Messages:
    446
    Likes:
    308
    UK
    Thanks for the info Freddd. Where is a link to your methylation protocol? I keep trying to find it but am clearly going wrong somewhere!

    In the morning I take my methylB12. 2 days ago I tried your suggestion of sticking it under my top lip - good tip! It was 500mcg. After about 15mins I was pretty wired. Kind of like a couple of coffees wired but with the fatigue still there. It took an hour to dissolve and I felt like my eyelids were super glued open! Then later on the folinic acid which seems to amplify the methylB12 feelings. Didn't feel sleepy until the evening. Woke up with a sore throat!

    As I had felt too wired, yesterday I did 1/4 methylB12, so 250mcg. Same feeling of wiredness but not quite so strong! Folinic amplified this again. Felt sleepy in the afternoon so slept and then went to bed early as still really tired. I am also suffering some leg cramp pains but not quite cramping like I'm used to. Legs feel very achy like someone is squeezing them every few seconds. This leg ache is also something that happens when I have a heavy Perrin therapy session but goes away after 24 hours. I've had it now for 3 days - I am assuming it's a potassium problem? I am also having bad dizziness problems when I bend over and nearly black out. Am tired walking up the steps and have to rest for 5 mins. The blacking out/dizziness and tired walking up steps is how I feel when I'm not in a good ME way. So it's like I've gone backwards.

    The description of the group 1 onset is actually symptoms I've experienced most of my life with muscle cramps!

    You asked:
    Can you be more specific about the sleep changes and sleepiness. Different pattern? More of the same? Normal dreaming? There can be a number of different things.

    I have been sleeping more soundly and having less nightmares. I have been getting up fewer times to go to the bathroom in the night. I am tired (not just fatigued), most of the day UNLESS I am wired! I will sleep for 1 to 2 hours in the afternoon if not too wired, which I wasn't doing before. Night time sleep - will sleep 6 to 7 hours then be awake for about 1 hour trying to get back to sleep, and then will sleep for 3 to 4 hours more. Used to get 8 to 9 hours total sleep - now am able to get 10-12 hours total sleep at night. Was having bad nightmares - now these are reduced. The sleep feels good actually. It feels like my body is finally get the rest it needs - but this just might be my excuse for it!

    It looks like my symptoms are from group 1 and group 3. Definitely agree with group 3 the most. And I guess 2b minus the headache.

    Symptoms from group 1 for me: Tightening muscles, nausea, muscle weakness, emotional changes

    Symtoms from 2b for me: increased malaise, fatigue

    From group 3 for me: Coated tongue, Runny nose, Increased Multiple Chemical Sensitivities, rapidly increasing Generalized inflammation in body, Increased Inflammation pain in muscles, Achy muscles, Flu like symptoms, Less sociable, Impaired planning and logic, Brain fog, Low energy, Light headedness, Sluggishness, Forgetfulness, Confusion, Reduced sense of taste, Increase irritability, Loss of reflexes, Fevers, Old symptoms returning

    I am yet to start the last of Rich's supplements.
     
  10. Linda

    Linda

    Messages:
    29
    Likes:
    3
    Freddd

    I'm pretty sure this is nerve damage as at the beginning of CFS I had similar nerve pain in all the same places except it felt more like shooting nerve pain and as if things were actually crawling along the nerves.

    I can tolerate AD-B12 quite well. I'm not sure the dose to go up to though?

    At the moment I'm taking 2.5mg of source naturals. I've tried Dibencoplex but it does not seem to dissolve for me.

    As I can tolerate the AD-B12 I'm sure it was the Folic acid that had this effect.

    Linda
     
  11. Branston

    Branston

    Messages:
    54
    Likes:
    4
    Montreal, Canada
    Bit of a simplified explanation that I found....... but it helps me understand. There is now way I would take Folic Acid now.....

    What’s the difference between folate and folic acid?

    Folate is a general term for a group of water soluble b-vitamins, and is also known as B9. Folic acid refers to the oxidized synthetic compound used in dietary supplements and food fortification, whereas folate refers to the various tetrahydrofolate derivatives naturally found in food. (1)
    The form of folate that can enter the main folate metabolic cycle is tetrahydrofolate (THF). (2) Unlike natural folates, which are metabolized to THF in the mucosa of the small intestine, folic acid undergoes initial reduction and methylation in the liver, where conversion to the THF form requires dihydrofolate reductase. The low activity of this enzyme in the human liver, combined with a high intake of folic acid, may result in unnatural levels of unmetabolized folic acid entering the systemic circulation.
    Several studies have reported the presence of unmetabolized folic acid in the blood following the consumption of folic acid supplements or fortified foods. (3) Human exposure to folic acid was non-existent until its chemical synthesis in 1943, and was introduced as a mandatory food fortification in 1998. (4) Food fortification was deemed mandatory due to overwhelming evidence for the protective effect of folic acid supplementation before conception and during early pregnancy on the development of neural tube defects (NTD) in newborns.
    Risks associated with excessive folic acid intake

    While the incidence of NTDs in the United States been significantly reduced since folic acid fortification began, there has been concern about the safety of chronic intake of high levels of folic acid from fortified foods, beverages and dietary supplements. (5) One of the major risks associated with excessive intake of folic acid is the development of cancer. (6) In patients with ischemic heart disease in Norway, where there is no folic acid fortification of foods, treatment with folic acid plus vitamin B12 was associated with increased cancer outcomes and all-cause mortality. In the United States, Canada, and Chile, the institution of a folic acid supplementation program was associated with an increased prevalence of colon cancer. (7, 8) A randomized control trial found that that daily supplementation with 1 mg of folic acid was associated with an increased risk of prostate cancer. (9)
    Researchers have hypothesized that the excessive consumption of folic acid in fortified foods may be directly related to the increase in cancer rates. Excess folic acid may stimulate the growth of established neoplasms, which can eventually lead to cancer. The presence of unmetabolized folic acid in the blood is associated with decreased natural killer cytotoxicity. (10) Since natural killer cells play a role in tumor cell destruction, this would suggest another way in which excess folic acid might promote existing premalignant and malignant lesions.
    A high intake of folic acid might mask detection of vitamin B12 deficiency and lead to a deterioration of central nervous system function in the elderly. In one study, consumption of folic acid in excess of 400 micrograms per day among older adults resulted in significantly faster rate of cognitive decline than supplement nonusers. (11) Another study found a higher prevalence of both anemia and cognitive impairment in association with high folic acid intake in older adults with a low vitamin B12 status. (12) As vitamin B12 deficiency is a common problem for many older adults, these studies suggest that high folic acid intake could cause serious cognitive consequences in the elderly.
     
    Asklipia and Little Bluestem like this.
  12. Lotus97

    Lotus97 Senior Member

    Messages:
    2,035
    Likes:
    522
    United States
    I'd recommend slowing down. Since you switched to using the sublingual to your upper lip you're probably absorbing more which is why the effects are magnified. I think you're on the right track by lowering your dose of mb12. Most people can convert folinic acid to methylfolate which would then increase methylation. I see you're interested in checking out Freddd's protocol and he might give you a different answer, but as far as what Rich would say Rich felt that overdriving the methylation cycle should be avoided which is why he recommends low starting doses and also starting with hydroxocobalamin:
    As you know, I have suggested a somewhat different approach to treating the methylation cycle partial block than Freddd has suggested.

    When high dosages of methylfolate and methyl B12 are taken together, the cells are no longer able to control the rate of the methylation cycle, and it becomes overdriven.

    One result of this is a rapid buildup of folates in the cells, because of the rapid production of tetrahydrofolate by the methionine synthase reaction.

    Tetrahydrofolate is readily converted to the forms of folate needed to support DNA and RNA synthesis, and this releases cells from a block at the S phase of the cell cycle.

    They rapidly start dividing, and this produces a strong demand for potassium.

    As Alex has noted, it has been shown that the intracellular potassium levels are low in CFS (likely because of an ATP deficit at the membrane ion pumps, due to mito dysfunction, in turn due to primarily to glutathione depletion), so there is no reserve there.

    The result is that the plasma level of potassium drops, and that accounts for the tachycardia.
    That's because the cells have control of the rate of conversion of hydroxo to methyl B12, and thus have more control of the rate of the methylation cycle.

    Note that another effect of overdriving the methylation cycle is a further drop in glutathione, as less homocysteine is available to go toward cysteine synthesis.

    There seem to be more and more people who are exhibiting effects of overdriving the methylation cycle from taking high dosages of methylfolate and methyl B12 together. I do not recommend this approach.

    I had also considered changing the form of B12 to methylcobalamin. Some PWMEs do need to use this form, particularly if their glutathione and/or S-adenosylmethionine are very low. However, use of hydroxocobalamin is a “gentler” approach to lifting the partial methylation cycle block, and many PWMEs need such an approach. Use of hydroxocobalamin also keeps the cells in control of the rate of the methylation cycle, preventing it from being overdriven, which slows the rise of glutathione. So I have decided to stay with hydroxocobalamin as the first form of B12 to try. For people who do not get a response from the SMP within a couple of months, switching to methylcobalamin would be an option to try. Another option would be to try adding some adenosylcobalamin (dibencozide). However, I do not favor raising the overall dosage of B12 very much above 2,000 micrograms per day, and especially not when it is combined with dosages of methyfolate that are much above the RDA range of 400 to 800 micrograms per day. This combination can overdrive the methylation cycle and hinder the rise of glutathione.
    As always, I recommend working with a physician while on this type of protocol.

    Best regards,

    Rich
     
    Plum likes this.
  13. Plum

    Plum Senior Member

    Messages:
    446
    Likes:
    308
    UK
    So it brings me to a question - why is folinic acid included in Rich's protocol? Is it best to leave it out BUT take the rest of his suggested supplements in the simplified protocol?
     
  14. Lotus97

    Lotus97 Senior Member

    Messages:
    2,035
    Likes:
    522
    United States
    As I said above, most people can convert folinic acid into methylfolate, but there are people with certain MTHFS and MTHFR polymorphisms that have trouble making the conversion which is why Rich has both folinic acid and methylfolate in his methylation protocol.
    I actually prefer including both folinic acid and 5-MTHF. 5-MTHF is the form needed by methionine synthase, which is the enzyme with the partial block. Many people's cells are able to convert folinic acid to 5-MTHF well, but many others have inherited genetic polymorphisms that slow this conversion down considerably. The polymorphisms in the MTHFR enzyme are a good example, and these are very prevalent in the population.

    Folinic acid is helpful for a couple of reasons. One is that it is very versatile, in that it can be converted to other forms of folate, which are needed to make DNA, RNA, and purines in general. Another factor is that folinic acid is polyglutamated when it is inside the cells, and this can help to lower the amount of free glutamate, which is an excitotoxin. Excitotoxicity is a problem in CFS, and it is often exacerbated when methylation cycle treatment is entered upon.
    I think Rich might have been referring only to the MTHFR C677T SNP (and not all MTHFR polymorphisms) in the quote above. Also, Rich believed that the MTHFS polymorphism is rare, but Freddd and at least one or two other people here do have it. If you do have an MTHFS polymorphism then folinic acid should be avoided, but with MTHFR I don't think low doses will cause problems, but I'm not positive.

    As Rich mentioned above, folinic acid has many other uses besides just converting to methylfolate for methylation. There was a study on CFS patients using folinic acid (not methylation, just folinic acid)
    http://www.natural-holistic-health.com/cd19-blood-test-and-chronic-fatigue-syndrome/
    They found that 81% of the patients reported improvement within two months. Unfortunately, at the conclusion of the study the researchers didn’t perform a cytometry measurement that would have given insight into the clinical efficacy of the drug leaving them only with the functional reports of improvement.

    Folinic acid co-enzymes are responsible for several important metabolic functions. These include the formation of DNA and RNA, the formation of heme protein in hemoglobin, formation of amino acids and the formation of glutathione.
    Folic acid on the other hand should be avoided if possible and Rich lists some reasons why
    In people in general, folic acid competes with the active, chemically reduced forms of folate for absorption by the gut and for transport into the cells.

    In people who have ME/CFS, lab testing has shown that NADPH is low. A folic acid molecule requires two NADPH molecules for its conversion to tetrahydrofolate, which is chemically reduced, is the "hub" of the folate metabolism and can be converted to other useful, chemically reduced forms of folate. NADPH is also needed for other important reactions, including MTHFR (which is used to make methylfolate) and glutathione reductase. So taking folic acid will use a substrate that is already low and is needed elsewhere in the biochemistry.

    Some people are genetically not able to convert folic acid very rapidly. Then it builds up in the blood, and there is some evidence that it inhibits the action of natural killer cells and can increase cancer risk, though there is not a consensus on this.

    Since the natural forms of folate (methylfolate and folinic acid) are now available over-the-counter as supplements, it is best to use them. Some people do not tolerate folinic acid well, and in that case, methylfolate is the one to use. Most do tolerate folinic acid, and it offers benefit in supplying other forms of folate in the early part of treatment, when methylfolate is not being converted to tetrahydrofolate very rapidly.

    Best regards,

    Rich
     
    Plum likes this.
  15. Plum

    Plum Senior Member

    Messages:
    446
    Likes:
    308
    UK
    Thanks Lotus97 - My question actually got posted in the wrong place. Thx for coping in Rich's comments. Despite having gone through Rich's lectures myself and making notes I still have questions now that I'm actually doing the protocol. I really appreciate such detailed comments as it helps me learn what's really going on :)
     
  16. Lotus97

    Lotus97 Senior Member

    Messages:
    2,035
    Likes:
    522
    United States
    I'm glad to help. I've learned so much from him in the past few months. I don't think I would have continued with methylation if it weren't for him. Since Rich only recommended hydroxocobalamin until his recent revision last year, it seems you'll be the guinea pig for trying his protocol with methylcobalamin. I hope you can post your progress in the thread for his revised protocol. Both the thread with Rich's Revised Simplified Methylation Protocol and Freddd's Active B12 Protocol are stickied at the top of this forum. Freddd also has a micro titration thread that isn't sticky. I'd like it if both people from Rich's protocol and Freddd's protocol posted in those stickied threads so I can see how everyone is doing. Even though my methylation dosages are closer to Rich's, I'm still curious how people on Freddd's protocol fare.

    Once I get up to 2000 mcg of hydroxocobalamin I think I might try methylcobalamin. I still have a nearly full bottle of Enzymatic Therapy's methylcobalamin that I tried before switching to hb12. Based on your comments it seems that Solgar is effective for you so far, but when you switch to Enzymatic Therapy's methylcobalamin you might have to lower your dosage since it's supposed to be the best quality. I actually bought Solgar methylcobalamin for my parents since they keep strict kosher (including supplements) so I might try a few of those first before going to Enzymatic's. Swanson actually had a sale on Swanson's brand 5 mg methylcobalamin that was half the price as Enzymatic's 1 mg. I know people are probably thinking that Enzymatic's is still more potent even though it's only 1 mg, but I'm actually hoping that it is less potent so I can start slow. Just to be on the safe side I am going to do Solgar and then Enzymatic first just on the off chance that Swanson's is more potent than expected.
     
  17. Freddd

    Freddd Senior Member

    Messages:
    4,940
    Likes:
    1,475
    Salt Lake City
    Hi Linda,

    Sounds like you were feeling a new demyelination with the nerve essentially shorting out. These can be repaired, the sooner treated the greater the chance for healing this fully.

    This kind of nerve pain is not characteristic of CFS that I am aware of. It is a pain of one neuropathy or another most likely.
     
  18. Freddd

    Freddd Senior Member

    Messages:
    4,940
    Likes:
    1,475
    Salt Lake City
    Hi Plum,

    Hi Plum,

    Titrating potassium, trying 300mg or so with a glass of water and see if that reduces the set. If so every few hours you could try some potassium and see how you feel in a day. That can give you an estimate of what to take as a total the next day plus any more doses needed to bring those symptoms down. Then work on the possible methylfolate insufficiency symptoms. At low doses 200mg 4 times a day added to the present. To just plain test the idea and know quickly, one could try 800 or 1600mcg which are more likely to stop the symptoms decisively. A person sometimes has to go back and forth a few times to get it all adjusted. AdoCbl and LCF can often decrease that sleepiness. I slept several 16 hr decreasing to 12 hours after a few days when I first had my pain reduced enough to let me sleep. And sometimes feeling convalescent is just that, your body is doing some healing and draining your resources. However, getting the potassium and folate adjusted comes first, then go for the next layer. The sleepiness may resolve by itself before you make the next set of additions. Sleep quality appears to be improving. All of the Deadlock Quartet are involved in sleep. However, sleep isn't an aiming point in all this so much as a result of a lot of things coming together and it has to make several different sets of adjustments as a person starts each of many supps.
     
    Plum likes this.
  19. Branston

    Branston

    Messages:
    54
    Likes:
    4
    Montreal, Canada
    Does the MTHFS polymorphism show up on the 23andme testing?
     
  20. Plum

    Plum Senior Member

    Messages:
    446
    Likes:
    308
    UK
    Thank you Freddd for all the great info. I shall try working on all of this slowly. I had a hospital appointment for an un ME related issue today which has left me rather drained. So I shall have to wait til the end of the week before I can start considering all this and getting my head around it. It is great to be able to get such great advice so thank you :)
     

See more popular forum discussions.

Share This Page