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Requesting help with treatment for homozygous a1298c

Discussion in 'General Treatment' started by Citizenrain, Jun 6, 2013.

  1. Citizenrain

    Citizenrain

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    Hello,
    I am fairly new to this forum and diagnosis, and quite frankly, I am lost, confused and in need of help with treatment.

    I have found that most research seems to be around the 677 gene, but I am homozygous for the a1298c gene mutation and haven't been able to find definitive answers about this particular defect and there is some debate that a1298c doesn't affect 5-MTHF activity and production but every scientific and academic source I read that describes this genetic mutation says it does. At least what I have come across is that the c677t gene affects enzyme activity to a much greater percentage along with other effects as well. I guess I am suspect about this because my doctor prescribed 15mg Deplin and that is all I took for a month and I had dramatic results then I started getting fatigue and headaches so I started doing some research and found out about MTHFR gene variances and just got tested for the 677 and 1298 only.

    I will provide more info to see if this helps any of you to help provide me and others in the same situation with some answers.

    I have been an fairly healthy and active/athletic person my entire life with some auto-immune issues;flushing and papular rosacea that I have under control from laser treatments, hypothyroid for the past 8 years that is well controlled with levothyroxine and a couple episodes that my doctor described as MS in nature and the possible early signs of MS. I had muscle tremors, decreased vision in one eye, confusion, etc. but they only lasted a couple months and went away and I only had about 3 or 4 episodes of that happening over the past 8-10 years (I am now 36 years old). MRI showed no problems what-so-ever. I had infertility issues, did IVF and now have two beautiful twin girls. I started to develop gestational hypertension towards the end of the pregnancy, but no severe problems. After the delivery I developed post-partum depression that did not respond well to a myriad of medications that my doctors dutifully kept trying to see what would help me. He finally suggested Deplin as he said he just read a study saying that helped some individuals with depression that were not responding to anti-depressants. I started taking 15 mg Deplin fo rthe first 2 weeks then changed to a generic form of l-methylfolate by Virtus pharmacies every evening before bed and within a couple days I felt better, but by about 4 weeks I felt AMAZING!! And I decreased my Pristiq from 100mg to 50mg over that same time.

    All of my smptoms were gone! It seems as though every part of me has become more agile, both my brain and body. My brain fog has lifted, memory and concentration has improved. I had dizzy spells and moments of profound confusion and what I called "brain freeze" where it seemed as though my brain would just stop for several seconds for a time out, that I no longer have. No more extreme fatigue and the heaviness I felt in my muscles and bones is gone. I was almost unable to exercise from the fatigue and muscle and joint pain. My irritability and anxiety have improved and I feel like I can really enjoy life again. The cognitive impairment I experienced bothered me the most because I used to be a very intelligent and highly functioning individual and I suddenly became an idiot after the birth of my twins 3 and a half years ago.

    The issue is I started to get headaches and fatigue and am starting to experience very mild episodes of lack of concentration and cognitive ability to think of the appropriate words and concise logical thoughts and arguments. It seems that I am still having a hard time conveying cogent thoughts to others without at least some extent of stuttering and stammering to get my thoughts across logically. I have improved so much I am reticent to complain, but because I have improved so much I am optimistic that I can find the appropriate treatment regime to really fix this! That is when I really started to research Deplin and l-methylfolate and came across this site and Freddd's recommendations to take active forms of B12 and l-carnitine fumarate and that I might possibly be "overmethyllating"...I have started taking these but I can't seem to get back to that sweet spot I was at and I want that back!! I do also take TMG, DMG, and potassium, but I am confused as to what dosages I should be taking.

    I would love to know what dose of these supplements and what time of day people take these:
    L-methylfolate
    methyl b12
    adenosyl b12
    potassium
    and does it matter if one takes acetyl-L carnitine or L-carnitine fumarate?
    Are amino acid supplements necessary?
    How necessary are the minerals zinc, selenium, manganese, molybdienum, etc as I have read those are beneficial but I feel I probably get enough through my diet...
    I eat a fairly good diet so I feel like I get my other needed vitamins and minerals as much as I have researched.

    Please let me know your thoughts and recommendations as to how to help with the fatigue and mental slowness I am still experiencing. I may be missing some other obvious symptoms as well that I don't even know to observe to give ideas as how to address these issues.

    Thanks so much!
     
  2. xks201

    xks201 Senior Member

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    If you are hypothyroid it is worth testing all of your hormones. I tested each hormone one by one. There seemed to be literally no rhyme or reason as to which ones I was deficient in. Test IGF-1. Refer to usdoctor.com to learn more about hormones. Take DHEA in any event..25mg a day for female, possibly twice a day if no side effects occur.
     
    Citizenrain likes this.
  3. caledonia

    caledonia

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    Hi Citizenrain. My suggestion would be to stop or greatly reduce the amount of methylfolate you're taking. Let the symptoms clear out before restarting at a much lower dose.

    Then I would suggest getting 23andme gene testing done so we can have a look at the other SNPs in your methylation cycle. It's only $99. The other SNPs will impact what supplements to take, and in what order.

    Watch my video series Methylation Made Easy (the first link in my signature). This will give you a good enough overview of the basics, to hopefully understand the more complex stuff.

    In general, Deplin is like using a large sledge hammer, when a small tack hammer will do. In addition, taking such a large amount of methylfolate relative to B12 will cause methyl trapping, which will stop methylation. This is the opposite of what you want to happen.

    Read this link by Ben Lynch about the side effects of methylfolate: http://mthfr.net/methylfolate-side-effects/2012/03/01/

    Watch Ben Lynch's video - he discusses the various prescription forms of folates and his opinion on them (mostly not good). About 1:07 into the video. The link is below in my signature.
     
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  4. Citizenrain

    Citizenrain

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    Thanks for the replies. I am familiar with the methylation pathway and your video didn't answer my question about the affect on the enzyme in both 677 and 1298, it was very basic. I have read a lot of Dr. Ben's site looking for answers and I have found that he does not think a1298c has an issue with the enzyme like c677t but rather biopterin and BH4, but he supplies no information or research to substantiate this and offer any explanation other than 'it is an issue with biopterin.' I am also very suspect about his not liking the prescription forms of methylfolate when he has no research to substantiate that and is only conjecture, when many double blind studies have been conducted showing very effective treatment with 15mg Deplin. Here is a link to two out of many that I have found: http://www.news-medical.net/news/20...ong-term-value-of-Deplin-in-treating-MDD.aspx
    I understand that there is more research around the 677 gene, I was just hoping to find some info or links to more info concerning the 1298 and how it works if it is not the MTHFR enzyme.
    I would also greatly appreciate knowing what dosages others are taking if the only reliable information truly is only conjecture and experience.
    I have stopped and restarted, once again, I just thought I could try to get ahead of the curve a bit if there is any advice others could give.
    I appreciate your time to reply and would appreciate any other replies if anyone has info they think would help me or others in a similar situation. gracias
     
  5. Citizenrain

    Citizenrain

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    xks201,
    thank you for the detailed info. I will ask my doctor to check into these tests and see what we find. I am very optimistic we will get this figured out! I am concerned about the 23andme test though for privacy and legal reasons...I will have to think about it and research it some more.

    caledonia,
    I also wanted to put a link to a study to help explain why I am suspect of DR. Ben's dislike of methylfolate at high doses. Many other Mds and NDs prescribe methylfolate and at even higher doses than 15mg. This study showed methylfolate at 15mg versus even 7.5mg was necessary to see an effect in adjunct therapy with anti-depressants for response and that no patients experienced ill effects that they reported. I understand this is a very small study without genetic info, but it is a study. Here is the abstract:
    Abstract

    OBJECTIVE:​


    The authors conducted two multicenter sequential parallel comparison design trials to investigate the effect of L-methylfolate augmentation in the treatment of major depressive disorder in patients who had a partial response or no response to selective serotonin reuptake inhibitors (SSRIs).
    METHOD:​


    In the first trial, 148 outpatients with SSRI-resistant major depressive disorder were enrolled in a 60-day study divided into two 30-day periods. Patients were randomly assigned, in a 2:3:3 ratio, to receive L-methylfolate for 60 days (7.5 mg/day for 30 days followed by 15 mg/day for 30 days), placebo for 30 days followed by L-methylfolate (7.5 mg/day) for 30 days, or placebo for 60 days. SSRI dosages were kept constant throughout the study. In the second trial, with 75 patients, the design was identical to the first, except that the l-methylfolate dosage was 15 mg/day during both 30-day periods.
    RESULTS:​


    In the first trial, no significant difference was observed in outcomes between the treatment groups. In the second trial, adjunctive L-methylfolate at 15 mg/day showed significantly greater efficacy compared with continued SSRI therapy plus placebo on both primary outcome measures (response rate and degree of change in depression symptom score) and two secondary outcome measures of symptom severity. The number needed to treat for response was approximately six in favor of adjunctive L-methylfolate at 15 mg/day. L-Methylfolate was well tolerated, with rates of adverse events no different from those reported with placebo.
    CONCLUSIONS:​


    Adjunctive L-methylfolate at 15 mg/day may constitute an effective, safe, and relatively well tolerated treatment strategy for patients with major depressive disorder who have a partial response or no response to SSRIs.
    Center for Treatment-Resistant Depression, Depression Clinical and Research Program, the Biostatistics Center, and the Clinical Trials Network and Institute, Massachusetts General Hospital, Boston, MA, USA. gpapakostas@partners.org
    http://www.ncbi.nlm.nih.gov/pubmed/23212058
     
  6. caledonia

    caledonia

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    In 2008, I believe it was, a federal law was passed giving protection against discrimination based on genetics. You can adjust what you want to share (or not) on 23andme.

    Yet you experienced ill effects. So - not a good study.

    Here is what Heartfixer has to say about A1298C (about 1/3 of the way down the page):
    http://www.heartfixer.com/AMRI-Nutrigenomics.htm

    And Yasko (about 2/3 of the way down the page):
    http://www.dramyyasko.com/resources/autism-pathways-to-recovery/chapter-6/

    The methylation cycle is extremely complex. You have to consider the methylation cycle as a whole, not just MTHFR. Treatment has to be individualized for each person. Everything has to be in balance, and things have to be done in a certain order.

    In general, if you just start taking supplements willy nilly without doing some kind of testing (preferably both genetic and functional), the chances are high you're going to run into roadblocks that you won't be able to solve. In fact, it's already happened.

    You can look for a physician at the MTHFRsupport.com practitioner page. If there isn't anyone in your area, there are several you can do phone consultations with. http://www.mthfrsupport.com/practitioner-2/
     
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  7. Citizenrain

    Citizenrain

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    Caledonia,

    Thank you for the information, I appreciate it.

    Federal law ensuring privacy only applies if you are an American and 23andme provides the best information if you are white. What if I am neither? There have been instances of individuals' identity being found out and this may not be an issue, but if I am the relative of a high profile public figure this could be an issue and the impact of me knowing genetic information,well, that could cause tensions. I may be a public figure myself, who knows? There is also an issue with certain types of insurance once you know certain medical information. As I said, I just need to do more research to find the best answer for me.

    And as far as experiencing ill effects, there is no reason to automatically assume my ill effects of headache and fatigue are caused by the dose of methylfolate I am taking. It could be caused by any number of issues ranging from serious to as simple as I was dehydrated and simply needed to drink more water. I feel much better now that I have worked my way back up to 15mg, I just take it twice a day rather than once.
    I am sorry that you feel all those studies were not good based on my saying I have experienced some headaches and fatigue. If the protocol of starting so low and not going that high in dosage had been implemented those people would never have achieved therapeutic levels of methylfolate to relieve their depression. No scientist or doctor would consider starting patients at 15mg of methylfolate to treat depression willy nilly after reading these studies. That is called evidence based medicine and generally highly respected.

    I am sorry if I have angered you or made you upset and defensive for any reason. We are obviously approaching this very differently and if you are happy with your sources and methodology and you are well and healthy or on your way there, then, that is all that matters. I greatly appreciate that you have taken the time to try to help me, the links you have provided are going to be of great help in my search for information.
    Thanks
     
  8. Valentijn

    Valentijn Activity Level: 3

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    No, HIPAA applies to every patient/client of an american doctor/clinic/whatever. Some doctors who should know better have said otherwise, but they are wrong.

    Also, genetic info is relevant to all races. Prevalence of some alleles may vary between those races, but risks of disease and malfunctioning genes based on SNPs are pretty much the same.
     
  9. NilaJones

    NilaJones Senior Member

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    Citizenrain:

    I appreciate your respect for the scientific method. I often get frustrated with people who are not empirical enough for my taste :).

    One thing to consider is that scientific publication is slow. Acquiring funding, selecting subjects, doing a study, writing it up, publishing it -- this can take years or decades. Folks of this forum are on the cutting edge of methylation research. Some are published scientists. And some are more new-agey.

    There is an enormous amount of experimental data here. People with the same SNPs and/or side effects connect with each other, experiment on themselves, and note which treatments work for them and which don't. Research scientists weigh in with theoretical explanations for the observed results. Slowly, people are building up a picture of the many, many places things can go wrong in the methylation cycle and how to treat the problems that occur.

    Eventually the results of this collaboration between researchers and patients will make it into the scientific literature. And it's ok if you want to wait until then before trying the treatments people here are using. But I don't think it's accurate to frame the work being done here as unscientific.

    I am relatively new to the forum, these are simply my own observations and impressions, and I trust that where I am wrong other posters will correct me.
     
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  10. roxie60

    roxie60 Senior Member

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    With A1298C you may have issues with B12 absorption (I also have A1298C and I was B12 deficient based on blood test). I had taken two shots a month of cobolamin and some B vitamins. My B12 blood levels increased significantly but I had no improvement in symps. Then Dr found I had MTHFR mutation (polymorphism) and speculated even though B12 numbers were now high I was not absorbing or getting benefit from them. She stopped the cobolamin shots and put me on Mentanx.

    In recent research I found that those with B12 deficiency can make SSRIs/SNRIs ineffective (an SNRI means that it not only blocks serotonin reuptake but also norepinepherine(adrenaline). http://www.livestrong.com/article/528436-vitamin-b12-ssris/ . Additionally this week I found out that estrogens can actually deplete B12 (depression had come back with a vengence the last few weeks and I was puzzled as why so asked Dr), Dr had just put me on estrodiol in March and increased the dose in May. Guess w should have increased my B's with the introduction of estrogen, so now taking more metylfolate and B complex to see if depression lifts. It has only been a couple days and I think I sense a difference (maybe wishfull thinking) .

    Anyway my point is if you are MTHFR, have B12 absorption issues and are taking an SSRI/SNRI you may want to discuss the impact of B12 on your depression, the reason I mention is you indicated you had an amazing response to Deplin initially (I believe it was helping with your B12, to get around or support the MTHFR, sadly if it stopped working might be due to other polymorphism which is wy many have suggested you try 23andME and find out what other methylation genes might be affecting you so you can put a long term plan together. I also was very concerned about the privacy regarding 23andMe but eventually feeling sick, wanting a solution won out over my concern for privacy. You will know when you reach that point in your walk with these health issues ......
     
  11. Citizenrain

    Citizenrain

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    Roxie60, thanks for the input, I will definitely evaluate that. What were the doses? As I said I take 7.5mg twice a day and take 500mg of acetyl-L carnitine, about 2mg of dibencozide and 1250mcg of methylcobalamin.

    Valentijn,

    Genetic info is relevant to all races but risks are not the same for all races and HIPAA only applies to covered entities. https://en.wikipedia.org/wiki/Race_and_health

    " HIPAA’s Privacy Rule currently applies only to “covered entities” and business associates of covered entities. A covered entity is a health plan, health care clearinghouse, or a health care provider. Since a company providing genomic sequencing services is not a health plan or a health care clearinghouse, HIPAA will apply only if such a company is determined to be a health care provider or a business associate of a covered entity.
    Direct-to-consumer (DTC) genomics companies are not likely to be considered business associates of HIPAA covered entities. HIPAA defines a business associate as a person or organization that, on behalf of a covered entity, performs an activity involving the use or disclosure of individually identifiable health information, or otherwise performs services for a covered entity where the covered entity provides such health information to the business associate."

    This article is a couple years old, but I haven't been able to find anything more recent to contradict it. It is rather interesting and educational, it can be found here:
    http://www.genomicslawreport.com/in...he-financially-troubled-dtc-genomics-company/

    NilaJones,
    I am very aware that there is not a lot of published work, that is why I am on here asking for links and more info! :) and if I wanted to only wait for peer reviewed studies I wouldn't be on here either! I posted asking for advice and one of the only pieces of advice I initially received happened to be something I don't agree with and I supplied what I view to be very strong evidence to support my point.
    I never said everything on here was not scientific, but some of it obviously is not and that is ok. Some of it is blatantly wrong and that could be detrimental to others that don't have the ability to research its veracity. The studies I posted links to might just change some peoples' views of treatment and they will be able to weigh two different options and help themselves.
    Every theory starts out as conjecture, but that idea becomes even better when it moves to a hypothesis and gets tested. I strongly believe that there needs to be a balance between both logic and intuition. I did not intend to come across as only wanting evidence based treatments. I am on here asking for help because I have seen people post some very good information and I am looking for that.
    I find it very amusing that the one theory of treatment I have read and don't agree with is Dr. Ben's idea that a1298c should be treated with b12 and not methylfolate and that he doesn't agree with the prescription meds at high doses, but that is the one piece of advice I received. C'est la vie.
    There is a lot of good information contained here and I was hoping to hear some of it.
     
  12. caledonia

    caledonia

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    I can see where your privacy concerns are more than the average person. Another option is to do the genetics with Dr. Amy Yasko. Most of us here do 23andme due to financial hardship. Yasko's panel would actually be the preferred thing to do if you can afford it ($499).

    Like Valentijn is saying, race is not an issue. Genetics are genetics are genetics. However, I can see where 23andme's medical and ancestry interpretations might be less accurate for non-white races who have less representation. This should improve over time as more and more people join and add to the database.

    However, for methylation purposes, you're actually not using any of 23andme's interpretations. What you do is pull out the SNPs used by Amy Yasko and use her interpretations. There are also a few SNPs that Yasko has, that 23andme doesn't have. So if you can afford Yasko's panel, that's the way to go.

    Yeah, I was feeling kind of grumpy and irritable last night, and I probably shouldn't have been posting. Sorry about that. I'm tapering from Zoloft and that can cause that from time to time.

    But in general, I'm confused by your posts. It's almost like two different people are posting. First you say you're confused and need help. Then when we give you information you say you know that already. Then you want to take random supplements based on Freddd's program with no testing, but then you want to have everything backed up with scientific evidence. ?????:confused:
     
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  13. caledonia

    caledonia

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    Can you post a link of where Dr. Ben says not to use methylfolate for A1298C? I've never heard of this.
     
  14. roxie60

    roxie60 Senior Member

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    Hang in there citizen. There can be miscommunication when dealing with one dimensional internet. PR has great value to many but I also think the more substantiated info is the best. Problem seems to be replicating the studies and the results. I also have a scientific bent but until a theory is proven right or wrong with replication I try to look at everything I can and draw my conclusions and plan as best possible, we are only as good as the info we get. That said, take what you find of value, share what you have found (I appreciate being able to look at multiple views and drawing my own conclusions since I'm the one that has to live with the results of any actions I take). Steel sharpens steel, just not always feel very good when when our education is being sharpened, I leanr something new everyday.

    As far as what I take to help support methylation (BTW I have not taken and SSRI or SNRIs since 2006, early 2007):

    MethylB12 (methylcobalamin) sublingual 5000 mcg (3-4 x's / wk)
    Folate (as Metafolin, L-5-MTHF) 1000 mcg (4x's / wk)
    MentanX (see ingredients below) 3x's / wk
    (L-Methyfolate Calcium (as Metafolin) 3mg)
    (P5P 35 mg)
    (Methylcobalamin 2mg)
    Ultra Bcomplex w/ PQQ (some ingredients below) 4x's /wk w/ the Folate above
    (P5P 10 mg)
    (Folate as Metafolin 400 mcg (not much)
    (Methylcobalamin B12 1000 mcg - pill - probably less effective)
    Daxitrol (taking primarily for the NAC, pheylananine and LDopa to support neurotransmitters even tho also has P5P, folic acid and cyanocobalamin which I doubt is of any use to my system)
    MegaFoods Daily Vit - 1x daily (has many ingredients but related to my B12 probs it has B1, B2, B6, B12 (2 mg) and Folate 80 mg (fr broccoli).
    Also take D3 5000 daily for VDR issue and D defficiency (have been able to bring D3 number to bottom of range)

    I think taking these supps plus reducing my activities has reduced fatigue slightly, having less tingling. Still having probs with memory but if memory serves :) it took longer for that to recover. Eliminating certain foods has helped IBS. Depression kicked in recently but know informed that was probably due to addition of estrogen (estridiol) which can deplete B12 which can then result in depression (this was someting I learned this week). That is why more B's are being added. Hope this helps give you an idea. I'm not the person I was 6-7 years ago but I'm trying to just feel a bit better, restore some hope. Still looking for that elusive energy however. Taking all this has not given me energy.
     
  15. Crux

    Crux Senior Member

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    roxie60;
    If DHEA is low, there can be fatigue and depression.
     
  16. roxie60

    roxie60 Senior Member

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    True, there are many things that can contribute. I did not mean to imply low B12 was the only thing. I appreciate the reminder.
     
  17. Citizenrain

    Citizenrain

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    Thanks for the replies,
    trying to find the right balance of b vitamins seems tricky for me. I seem to have a narrow window between fatigue and feeling too wired, and at least I thought it was the b vitamins but thyroid and dhea are great points to look into.

    And you are right, Dr. Ben never said to not take methylfolate, but from what I have read so far, my interpretation is that he seems to think b12 is more important for a1298c than methylfolate. And I am finding the contradictory studies and his recommendations are making this very confusing for me.
    I can see how I might be coming across as so conflicted, roxie60 said it very well and I too would prefer some great scientific studies, but in their absence I will take everything I can get to help me along the way and i know there are people on here that have some great ideas and info that could help me and others. I really appreciate your links to Dr. Yasko and the heartfixer page, that was exactly what I was looking for. I didn't mean to say that I completely understand the methylation cycle but that I already knew as much as your video explained, I want more in-depth and technical info. Although, to be honest, I don't know what to do with that information...it still doesn't answer all my questions! I never realized how type-A I was until now!;)

    In searching I did just find the answer to one of my questions on Dr. Ben's site:
    I believe that no one truly knows the distinctions between 1298 and 677. We are talking about 1 base change in a gene that is 20,000 bases long. This single base change does affect the shape of the MTHFR enzyme and thus its function.
    Research is needed to suss out the little differentiators between 1298 and 677 and other SNPs.
    I appreciate all the help!

     
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  18. Valentijn

    Valentijn Activity Level: 3

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    MTHFR is a folate gene, not a B12 gene. It doesn't make much sense to take methylB12 for a problem with producing methylfolate. Does he have an explanation for taking methylB12 instead of methylfolate?
     
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  19. Artful

    Artful

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    I'm a new member of PhoenixRising having only the other day discovered that I am homozygous for A1298C (that's one copy, right?). Discovered on the same test that I also have high lactate.

    35 yrs. ago I began to find solutions to my at that time not fully recognized problems. I was searching for a cure for my then 8 1/2 yo, I believe autistic, maybe PDD, learning disabled and emotionally disturbed son. An allergy Rotation Diet unearthed food allergies which were causing his worst symptoms and getting those foods out of his diet precipitated a miraculous normalizing of his brain function.

    Shortly thereafter we were able to get into the studies which developed basic Spectracell.com testing. Eavesdropping here leads me to believe that y'all are not aware of spectracell or I don't think you'd be so confused about your individual nutritional deficiencies.

    My children were in the study for 3 yrs. I was in for 25 years. Taking the supplements indicated by his Spectracell tests permanently healed in those 3 yrs. my son's gut - so that to this day, over 30 yrs. later, he can eat anything to no ill avail. The researchers told me that this was a common story for them. That the younger they could get a kid, the more-likely they could cause apparently permanent changes in the child's biochemistry.

    My own symptoms were DRAMATICALLY helped by my supplements but I wasn't totally healed as he was. I still need to take megadoses of Bs and other nutrients, including a large amount of magnesium glycenate to stave off what I call "twitchies" which, if not addressed early, become full-blown very painful muscle cramps. I discovered way back then that an extremely low-carb - no dairy, no grains - diet dramatically helped my former chronic fatigue, fungal/yeast problems, brain fag, etc.. My doctors and I believe that as a consequence of all this is the fact that I'm the healthiest 67 yo we know. Reading here leads me to believe that I'm blessed to be ahead of the scientific papers? I'm prowling around here to try to find out WHY.
     
    Last edited: Nov 2, 2013

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