I have been taking my DNA analyses further and getting some real insights into my body make up.
Laymans explanation to give you a heads up:
I have reduced ability to methylate folate and folic acid to make methylfolate required by B12. Since have replaced folic acid with methylfolate I have needed less B12 each day.
I have several genes that inhibit absorption including B12, vitamin D, vitamin A and copper.
I have slow transportation of B12 from blood to cells which explains why I benefit from more frequent injections.
I am currently doing some research of what my next improvement plan will look like whilst enjoying a plateau of symptom free being. In the New Year I will have a plan.
🤗🤗🤗
Written by
Wwwdot
To view profiles and participate in discussions please or .
I had 4 different tests done and then a 3 hour meeting to go through it all! I am still going through the video of the meeting and reading up the detail and when I have the details I will post further details. My heads still reeling!
Well congradulations on your being symptom free, wow I'm so happy for you. yes please let us know more of your research. I tried the methfolate and it's way to much for my brain, I could not handle it. I wish I could take it. the folate I take is all natural plant based vitamin folate throughout the day. for now thats all I can tolerate. maybe later when I'm stronger. I have two mutated genes so one of them does not use the folate as well. mthfr
ok good to know they have a rub I'm going to try and find some too. I may get a suppliment to take orally just a low dose, I eat bananas and avocado during the day but I think I may need more, my legs calfs have been getting little cramps. I just started to up my vit D3. 5000 IU a day I'm not sure how many MG that is. but thank you that helps.
Good luck with it. I had genetic testing done via a nutritionist and it had enabled me to understand the various issues I have and tailor my supplementation accordingly with a huge positive impact on my recovery.
JesusMercy60 have you looked into folinic acid? I can’t tolerate methylfolate and cannot take folic acid due to folate trap. I’ve found folinic acid a game changer.
Thank you that’s great to know as that is what I am attempting to do. So far so good and it is making so much sense of why I do well with somethings and not with others. Methylfolate was a game changer for me as I had very high folate blood levels but poor methylation. It’s fascinating but I also find it very complicated!
Good suggestion to JM to consider folinic acid as it’s short cutting the folic acid/folate pathway to covert to methylfolate as folinic acid is made from folic acid/folate into methylfolate- this is my layman explanation I know it’s far more complicated!
Both my folate and folic acid pathways are blocked and my folinic acid part of the cycle is compromised too which is why methylfolate works for me.
So as Malderum has experienced it may be that for you too folinic acid is a better short cut.
Well I may try the folinic acid again, I tried it too after I tried the methyl folate, I read that folinic acid is more mild, maybe I should give it another try. I had really bad head racing and loose bowels and anxiety, I did not even take the entire dose. let's see how I do on a day with another small dose.
Hi - can I ask where/how you got this testing done? I think I have PA, transport problems and methylation problems. I would love to be able to “prove” it particularly as I think my daughter is also affected. I worry about the number of possibly less reliable places that offer DNA testing. Would appreciate a recommendation as you seem to have found a very helpful setup.
That is very good news. I would be very interested in which test they did to find the show absorption issue. I look forward to updates. So many on here do folate, but mine is high already so i don't take it. Is yours low? Do some take it even if they're not deficient? If so why?
Even if you have an MTHFR variant , whether you take folic acid or methylfolate doesn't make much of a difference to folate cycle metabolism.
"this isn’t how folates are processed; rather than an assembly line, it is a cycle, so even if MTHFR is skipped once, it will be involved as the folates get cycled through the pathway again and again. Because this cycling occurs hundreds or thousands of times a day, Shane explained that the advantage of giving L-methylfolate, compared to folic acid, is “absolutely minimal.” "
^ Quote from Barry Shane, a nutrition researcher and professor emeritus at the University of California, Berkeley, who has been studying folate metabolism for over 45 years.
Interesting, thank you. This research could be useful.
I would expect that the quote is made within the context of researching the operation and performance of a healthy, correctly functioning folate cycle rather than within a person suffering B12D or Pernicious Anaemia. In the circumstance of a healthy body it would be entirely reasonable that the addition of L-methylfolate compared to folic acid would be "absolutley minimal".
However, the folate cycle is made up of a series of cycles or conveyors which effectively act as nested cycles or conveyors, some in series and some in parallel and is governed by several genes, not just MTHFR although that is the gene most often associated with the folate cycle. To operate correctly the inputs (supply) to a cycle or conveyor need to match the output (demand).
My DNA analysis showed that some parts of my cycle which process folate (from foods) and synthetic folic acid were compromised and worked very slowly so I ended up with a high blood folate level, yet I was still short of methylfolate which effectively meant that although the cycle was operating, it was not working correctly or efficiently with the consequence that the output of methyfolate (supply) could not keep up with my body's demand for methylfolate.
So my experience of the advantage of taking L-methylfolate directly contradicts the opinion that "the addition of L-methylfolate compared to folic acid would be "absolutley minimal".
Of more significance, is that I had expressed the inconvenience of needing 4-5 injections of B12 a day to the Functional Nutritionist and it was she who suggested that I stop taking folic acid as prescribed, but to take L-methylfolate instead. She gave her advice BEFORE the DNA test results were available. I did not ask why she gave the advice and had no expectation other than to hopefully start feeling better.
It was a complete surprise to me that after a couple of weeks of taking L-methylfolate, I started to have a reduced need for B12 and I was able to settle at 3 injections a day. It was a revelation to then have the results of the DNA analysis which showed that I had compromised function in the FOLH1, MTHFD1, MTHFR and RFC1 genes, the latter gives me reduced ability to take up, retain, and metalbolise folate.
I think most of us on this forum are trying to identify what aspects of our body cycles are not working and how to fix them. Therefore the observation by Professor Barry Shane would be useful for us to eliminate any issues with our folate cycle, because if no advantage is gained by taking L-methylfolate instead of folic acid , it would suggest that our folate cycle was working correctly.
Wwwdot I think it's important to understand the folate cycle.
Even if the folate cycle is not functioning as well as it should be due to to the presence of the gene variants you mention, the nature of the folate cycle itself does not change.
I mean in the sense that folates are cycled through the folate cycle hundreds or thousands of times per day. At each stage of the folate cycle, a different form of folate is involved. These are:
Dihydrofolate (DHF)
Tetrahydrofolate (THF)
5-formimino THF
10-formyl THF
5,10 methylene THF
5,10 methenyl THF
5-methyl THF (methylfolate)
Notice that methylfolate is just one of the folate forms involved in the cycle. The point that Barry Shane is making is that, because this cycle happens hundreds or thousands of times per day, supplying just one of these forms, even if that form is methylfolate, does not have any real advantage since folate needs to cycle through all these forms hundreds or thousands of times a day.
If there is some inefficiency at some point in the folate cycle (such as with MTHFR), methylfolate only bypasses it once out of hundreds or thousands of cycles. The benefit is basically negligible and this is just as valid if you have many genes causing poor folate metabolism than if you have none.
Taking methylfolate doesn't fix whatever genetic folate metabolism inefficiencies may exist, nor does it bypass them to any significant degree.
In terms of B12 injections, to be honest I find the idea that anyone would need 4-5 B12 injections per day to be highly implausible. Even in the context of PA and broken entero-hepatic recirculation, this makes little sense. At this frequency you would be at least 4 injections past continuously saturating every single TC2 active B12 transporter in the blood every second of the day.
The body does not have an infinite demand for B12, not even if you have PA. At this injection frequency your body will just be expending effort getting rid of thousands of mcg of B12 it doesn't need and keeping it out cells which already have more than enough. It seems pointless, wasteful, expensive and inconvenient.
There's no clear reason that I can see why supplementing folate would affect how much B12 is needed. Nor vice-versa.
I understand that you maintain that your experience of methylfolate contradicts the explanation provided of how the folate cycle works.
I would say you should consider more seriously the possibility of placebo effects in your chosen treatment protocols, especially when the available scientific research and understanding of biology and metabolism flatly contradicts the conclusions you are drawing.
I would like to share the written words of the late, great Dr Chandy who devoted his life to the treatment of patients with B12D and Pernicious Anaemia, who when referencing Shane’s 2008 research wrote “The metabolism of vitamin B12 in the human body is complex and not fully understood.”
Chandry suggests that where the entero -hepatic circulation is not operating efficiently, B12 levels fall rapidly resulting in a need for more frequent injections and he refers to daily injections needed by some patients. It is noteworthy that despite his wealth of research, knowledge and experience, Dr Chandry still only suggests a reason, conceding it is not known why some patients need more frequent injections.
Thankfully, this modest, knowledgeable and exceptionally experienced GP did not share the view that a need for frequent injections is “highly implausible”.
Whilst I acknowledge your best wishes, I sense your representation of Shane’s work, although well intentioned, is somewhat oversimplified and that Shane’s research is more appropriately represented by Dr Chandry.
(Chandy) "did not share the view that a need for frequent injections is “highly implausible”.
This is a strawman, I never claimed that a need for frequent injections due to PA was "highly implausible". I specifically said that needing 4-5 daily injections was biologically implausible.
If you think that I have oversimplified Shane's research, I would happy to learn what I have oversimplified. I think his statement which I quoted was clear, understandable and eminently applicable to this situation. I already explained why his argument holds just as well for someone with genetic defects in folate metabolism. If you have a specific criticism of this logic, I'd like to hear it but simply stating that I'm oversimplifying his research is not an argument unless you support that claim as to what I have oversimplified and how that affects the validity of the argument.
Chandy is of course correct that B12 levels fall more quickly when the enterohepatic recirculation is not functional and thus more frequent injections are needed, But what you were implying was that as much as 5,000mcg needs to replaced every day in someone with PA. The problem for this argument is that only 5/6 mcg is lost through bile when enterohepatic recirculation is broken.
I only share my experiences of recovery and I certainly did not imply that “5,000mcg needs to be replaced every day in someone with PA” - those are your words not mine. I was sharing my experience of needing 4-5 injections a day at one stage during my recovery. I apologise to everyone on this forum if I implied otherwise.
I responded to your original comment about my personal need for frequent B12 when you said “In terms of B12 injections, to be honest I find the idea that anyone would need 4-5 B12 injections per day to be highly implausible.”
I hope you can see you are mistaken when you now say that you “never claimed that a need for frequent injections due to PA was "highly implausible"”and that you “specifically said that needing 4-5 daily injections was biologically implausible.”
I do not profess to be a medic or anything more than a sufferer of PA who is trying to find ways to recover. I do not make an “argument” for anything in my posts but simply share my experiences, which in this case is that I felt better and had been able to increase the time between injections after switching from folic acid to methylfolate on the advice of a Functional Nutritionist.
I do not believe that I mischaracterised what you were saying but nonetheless if you believe I did then I am sorry - I don’t want anyone to feel offended or upset when contributing to discussions. Life’s too short.
I am not drawing conclusions but simply sharing how my quality of life is improving by listening to my body.
Interestingly, I have seen a dentist and dental hygienist recently both of whom appeared very knowledgeable about B12D and Pernicious Anaemia. I was able to discuss my self treatment with them and I explained my achy teeth when I missed injections which I sometimes do when I am busy or something happens and they said that in practical terms my B12 intake and the effect when I don’t was logical. If you work it out the amount of B12 I am taking approximates what a healthy body wound be circulating and RECYCLING except with PA we don’t recycle … that’s a key problem.
The placebo effect is interesting and I have considered this myself frequently which is why I reduce my injections. However, I do not believe placebo effect is a key player in my treatment. When I have tried to reduce injections I do this quietly without letting my family know and yet it is them who individually notice that after a few days I am “not myself” and I begin to have subtle physical symptoms which they pick up.
My self- treatment could be placebo but if it is that’s great as the placebo effect has cleared all the inflammation in my knuckles and wrists, I have strength in my hands again and I can do a days work and pursue hobbies and enjoy a full life without being so exhausted I need to recover by going to bed for a few days! Also I have not had a headache in 18 months and I have not taken paracetamol in over 18 months - I cannot remember the last time I felt as well as I do now.
I am sharing my experience to help others who want to try to explore if a better quality of life can be achieved despite having this insidious illness. The truth is the amount of research into how the body works has only scratched the surface and there is even less quality research into how our bodies compensate when a part of the body malfunctions.
We will have to agree to disagree on this subject because I know for certain my quality of life has improved beyond recognition by increasing my B12 frequency and taking methylfolate and ensuring all cofactors are optimal. It is for others to decide their own self-treatment.
"If you work it out the amount of B12 I am taking approximates what a healthy body wound be circulating and RECYCLING except with PA we don’t recycle … that’s a key problem. "
It doesn't though. No healthy person has 5,000 mcg of new (or recycled) B12 entering their bloodstream every day. Saturation of every TC2 receptor in the blood only happens in the context of a B12 injection.
Just because you have PA does not mean that your body has no ability to store B12 anywhere in the body and thus needs thousands of micrograms of B12 to be replaced every day. B12 is not stored only in the liver.
The amount of B12 entering the bile every day is estimated at around 5mcg. Normally most of this is recovered, save 1mcg, but as you point out, this does not happen in PA. But we're talking about an additional daily loss of 5mcg (so 6mcg total), not 5,000 mcg. So the presence of broken enterohepatic recirculation can't explain a supposed requirement that you suggest of 5,000 mcg of B12 a day.
I'm not disputing your recovery or your improvement in quality in life. I'm not claiming that the "placebo effect" was what cleared all the inflammation in your knuckles and wrists. What I doubt is your claim that 4-5 injections per day was necessary for that to happen and that methylfolate is more effective than folic acid in the presence of genetic issues with metabolism of folate.
The first is implausible and the second contradicts what is understood about the folate cycle by those who have researched folate for decades.
I'm not sure why you would tell me "it's for others to decide their own self-treatment"? I don't see how me or anyone here can make treatment decisions for anyone else?
I can only share what I understand of how B12 and folate metabolism works. In some instances that may contradict an interpretation someone has made of their personal experience. That is what it is. Folks can draw their own conclusions. No is deciding anything for anyone else.
I understand you are sharing with the intention of helping others - that is also my intention, I want to help with an understanding of what might or might not be effective and why, so that people do not spend time or money on things which are not effective or cause unnecessary inconvenience or disruption to quality of life.
I do wish you well and am happy for your recovery.
This is all fascinating. I've started twitching again recently and am wondering if folic acid isn't being properly absorbed despite blood levels of 17. In the summer I dropped from 5mg folic acid ×3 per week that I'd been taking since February to methylfolate drops at a lower dose of 400micrograms daily, then ran out in September and was without for a couple of weeks and had a massive slump... think I'll try folinic acid to see if there's any difference. Would I still need the 5mg levels? By the way, I 💚 the placebo effect and wish I could harness it at every possible opportunity! Safe, painless, no side effects... 😂
My GP put me on 5mg of folic acid and my levels quickly reached 24 (can’t recall the units) which is top of the range. So I reduced to pregnancy level which is 400 mg a day.
The B12 consultant I saw said keeping cofactors optimal is important and folate is a cofactor. I stopped flic acid and gradually introduced methylfolate at 1 mg a day then increased to 2mg a day which is what I take now.
I would consider starting with a low dose and increase if needs be as no point taking more than is needed. It will be interesting to see if your twitches go 🤞🤞and that you recover out of your slump. It’s a horrible feeling.
I've just seen a liquid version so will try that. Folic acid even in liquid form and with food gives me dreadful stomach pain, so maybe folinic won't. Thanks for dosage advice. Placebo here I come! 😄
I think 5mg folic acid gave me stomach cramps too but to be honest my gut issues were so bad then it is hard to be sure. I do know that when I was taking the folic acid I felt nausea and the only other time I took folic acid was when I was pregnant so no real benchmark.
I just try things and make notes and sometimes I can see a pattern and sometimes not.
I find it interesting that so few people can fathom injections closer together to have a different efficacy than once every 24 or 48 hours with the same amount.
Maybe it is a medication and not supplementation mindset. Made worse by the supplement being more effective as an injection.
Could be not working with logarithmic principles or differential equations in a practice way. Some people seem to only be able to add and subtract or divide.
Yes, I agree. It’s a different mindset. The logic would be questioned if it was suggested we eat a weeks worth of food in one sitting yet we are expected to manage a weeks worth of B12 in one injection! My body certainly does not appreciate being over faced with high amounts of anything - including food!
I suspect that if injectable B12 came in 0.1mg doses, I may still be needing 3 injections a day because as you suggest it’s the frequency of supply that’s most influential. But the B12 vials are offered in1mg or 1.5mg doses and currently I can only obtain 1.5mg and I don’t like the idea of keeping the B12 once opened.
To be clear I have not concluded that the frequency is more important than the amount only the same amount more frequently is more effective and that a higher concentration at the same amount is more effective. For me.
That would mean that if you were to switch from 1.5 mg to 1 mg you would need more injections to achieve the same efficacy if you kept the daily amount the same.
Yes agree. There are so many factors, dose, concentration, frequency, form and of course parallel supplementation.
Combine that with our use of physical, emotional and mental energy and the permutations of factors affecting our well-being becomes more complex.
However, for me frequency is a key factor and it’s a shame I don’t have access to smaller injectable doses - who knows perhaps one day things will be different?
I really wish frequency was less of a factor in my well-being as I really do not like self injecting and some days I have to be very strong minded not to skip an injection.
But I am only two years into treatment from severe B12 deficiency so time will tell.
I have just done a DNA test which I am sending off today. So I am looking forward to seeing if this shows any anomalies. Saw my nutritionist yesterday and we think I may have various issues going on with imbalances in my body, including methylation. One of the things we think may be affecting me is Histamine intolerance, so that is something we are looking into.
It will be interesting to see what you learn. I must confess my results are overwhelming in that there is so much to understand of the cycles the results relate to and then to try to understand what it means and how that translates into self treatment.
I have had 6 hours of meetings on the results and took notes but I need to sit down over Christmas and go through it all again more slowly. I am so busy at work at the moment which in some ways is good as I couldn’t have worked like I am now a year ago but equally I would like a little less pressure! I am never happy am I!
I found that using a methylated form of folic acid helped with stabbing pains in my ankles when I started walking.
Please note that genetics is, strictly speaking, off topic for this forum - its a hugely complex area and I doubt that we will ever get to a point, given interactions between different processes, that we will ever get to a point of being able to predict how one person is going to respond to B12 treatments when it is used by so many processes that go on in cells - coded by dozens and more of genes.
I have edited some replies that breached the conduct code for the forum.
I am closing this post to further responses.
The ability to reply to this post has been turned off.
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
Treated for low B12 and now low folic acid
Confusion over conflicting information regarding low b12 
B12 injection and neck rash
B12 and folic acid
Folic acid and b12
