BH4 supplement for a1298c?

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  • #1192 Reply

    Dea McKenzie

    My 7 yr old daughter (compound hetero) and I (homozygous for a1298c) take a supplement called BH4 at the advice of our nutritionist. It seems to help me with mood and generally feeling better, and sometimes I think it’s helping my daughter in the same way and sometimes I’m not sure. Also I’m not confident that we have enough information on how much to take. It’s a supplement that is very hard to find and there is little information on it. Can anyone offer insight into using the supplement BH4 — it’s from Ecological Formulas BH4 Homeopathic 2.5 mg Capsules. The ingredients list only BH4 (2x) but the bottle also says “BH4 contains Biopterin, a cofactor to critical enzyme pathways in human physiology.” Thank you in advance to anyone who can assist me.

    #1280 Reply

    Lisa Stroyan

    My 15 year old son takes this same brand and it helps him a lot with fatigue and a little with emotional fragility. However, one thing to know is that it requires a lot of vitamin C. When I inadvertently switched from 1000mg pills of Vit C to 500, it stopped working, and I emailed our doctor and he figured it out.

    So far we have been unsuccessful at adding a second BH4 without him falling apart. I’ve read on the Yasko boards that BH4 can cause strong detox, so that’s something to watch out for.

    However, our biggest effect for regulating his mood has been to take him completely off of all glutamates. The truthinlabeling site has a list of hidden sources, or I write about it on my blog as well, .

    #1363 Reply

    Debbie McQueen

    I am a compound heterozygote, 1298 and 677, and have BH4 Deficiency which was confirmed via urine Neopterin/Biopterin testing. I tried self-treating w/pure BH4 powder from Schircks in Switzerland. It seemed to help but I discontinued taking it due to side-effects including eye hemorrhages.

    #1448 Reply

    Dr Lynch

    Debbie, Lisa and others –

    There are ways to increase BH4 safely – without supplementing directly with biopterin.

    The biggest gains in increasing biopterin are:
    – decreasing inflammation
    – decreasing infections
    – – – both of these decrease neopterin which in turn increases biopterin formation
    When neopterin is elevated, biopterin typically is decreased.

    – decreasing ammonia levels
    – adding methylfolate, iron, vitamin C, magnesium, b6 and others.

    It is always best to support a cycle with the necessary precursors rather than supplementing directly with the end product.

    #2080 Reply

    Monica Brown

    Dear Dr Ben, My son is 6 years old (48 lbs) has autism and is heterozygous for A1298 in his MTHFR test. Is there a supplement that you can recommend for this issue?

    #2282 Reply


    Does anyone know a safe way to bring ammonia levels down rather quickly? maybe not even that but effectively and safely? I want to try to get my biopterine levels under control. I want to try to get my Vitamin C intake lowered as it is pretty expensive the amount I am taking.

    Thank You for any reply,

    #2301 Reply


    CBS mutations can increase ammonia, and people with those mutations are advised to lower the amount of meat they eat. Maybe that would work for you. I don’t think it means a person has to go vegetarian. Mmeat is the best food source of Vitamin B12, which you need for your MTHFR mutation, so that puts you in a bit of a quandry.

    #3230 Reply


    I am heterozygous for all three SNPs in genoset 223 (rs10483639, rs3783641, and rs8007267) which indicate mildly lower levels of tetrahydrobiopterin (BH4). I’ve started taking royal jelly in honey, but I haven’t noticed a difference. I’m considering taking a BH4 supplement. If I do, I’ll post back here with my results.

    #3396 Reply

    Ricardo Garza

    Could somebody please give me a link to this “Ecological Formulas” BH4 Supplement? Cant find it anywhere.

    #5669 Reply


    Not sure about the Ecological Formula one, but this link sends you to something that looks exactly the same:

    #222977 Reply


    Dr Ben, In the light of work by james Clelland (, I am wondering if the BH4 deficiency could be genetic in addition to problems with inflammation and infection. As you probably know, Dr Amy yasko is finding many of the chronically ill adults on her forum have issues with low lithium. I am wondering if there are dots to be connected here.. Does lithium run low because the body is struggling to maintain/regulate BH4?

    I do ok on BH4, but only if I am taking lithium with it *I think.*

    Also in terms of supporting that pathway.. don’t many of us (CFS patients/kids on the spectrum) have low magnesium because there is not sufficient B6 to transport it into the cell …and aren’t we low in B6 because there’s no B2 to activate it?

    thanks for your thoughts on these points.

    #378795 Reply


    Dr Ben,
    In addition to an A1298C mutation, I also have GenoSet GS224 (mild GTPCH1-deficient-HPA equivalent?). Unfortunately, the combination of my MTHFR A1298C mutation and my GS224 GenoSet apparently doubly impacts my ability to generate BH4. I believe this explains many of the mental/emotional and physical symptoms that I’ve been experiencing for decades now. Especially some symptoms similar to those of MS, Parkinson’s and PKU. Along with kidney issues, insomnia, tremors, muscle spasms, numbness & tingling, headaches, slurred speech, wild swings in blood pressure (hyperphenylalaninemia), (etc.). My father has lots of Parkinsonian-type symptoms that may from from a BH4-related issue too, so I’m going to test for his gene mutations next. My deceased paternal grandfather likely had it too, with all of his similar symptoms.

    Instead of a BH4 suppliment, I see you have mentioned the following for possibly helping with the support of a BH4-deficiency:
    methylfolate, iron, vitamin C, magnesium, b6

    I also just read that 5-hydroxytryptophan (5-HTP) and even L-DOPA might help with my BH4-deficiency.

    Honestly, I don’t even know where to start. Are there therapeutic entry points, reasonable ranges, targets, and maximum limits for all these supplements? Side effect and/or any gotchas?

    Also, since a GP doesn’t know anything about any of this, would it be a neurologist that would know how to assess, treat and monitor this?


    #379184 Reply


    I am seconding Scott_C’s post. I have virtually the same issues, and my case is further compounded by other SNPs.

    What can be done if you are either homozygous or heterozygous for all MTHFR A1298c, MTHFR C677T, CBS, COMT, NOS and SUOX, though, in which methylfolate is contraindicated? Can BH4 be produced and utilized without methylfolate?

    Furthermore, does anyone know of a reputable source of BH4 in the UK without prescription? I do in fact have hyperphenylalaninemia but my GP will not treat it because it is apparently not high enough yet.

    #381359 Reply


    Hi, I just found out through 23andme that my daughter is only heterozygous for A1298C (I am homozygous), but she is unfortunately homozygous for VDRTaq, MAO A r297R, and CBS A360A along with 7 other heterozygous mutations on the methylation profile (but not C677T). I have suffered terribly nonstop since childhood up to 42 years from depression, memory loss, word loss and so on with only disastrous effects from all the antidepressants my doctors have had me try (repeatedly, at that, because they feel the need to try something). I am at a point where even though I know the horror it will cause, I still try the SSRI’s they want me to because I do it for their sake. Isn’t that crazy in and of itself? But if I refuse and tell them I’ve tried and it was bad, they take me as being defiant to treatment and then I worry that the anxiolytic they do allow, they will deny me. I am terrified my daughter will have the same issues. With the genetics listed, her BH4 is supposedly very low. I cannot find any doctors in a 60mile radius that even know the slightest about this stuff. My own GP said she cannot help me whatsoever with my homozygous status because she has never heard of it. I work for a hospital system and emailed the main genetics dept asking if they could help and they know nothing either. I am so feeling defeated now with knowing my daughters status. I am maybe going to try BH4 myself and see what happens. OF NOTE: I noticed a dramatic decline in my daughters cognitive functioning after she, at the age of 5, first went to the dentist and got 5 amalgam fillings. (it was probably the mercury in them that caused it) For any of you out there reading this, if your child needs fillings, maybe the ceramic ones would be safer. The danger is in the dust created and inhaled/ingested (from which the mercury is absorbed into your system) while the dentist is filing the filling to fit your bite. …..ANYWAYS, as always, I am sooo thankful to Dr Ben and his creation of this website because it pretty much literally saved my life. I always knew there was a reason for the way I felt. I searched for years and years for an explanation. And now I understand it–even if my doctors don’t and refuse to even educate themselves on these genetics. At least I no longer have to live with the horrible guilt I used to feel for feeling the way I did and how I couldn’t ‘be normal and happy’ like everyone else. I no longer beat myself up every second of every day for it. When I have bad days, I tell myself the tide will turn if I just be patient and wait. And eventually it does, though it may take a few days. But before it was those days when it was very bad that the added self-guilt and self-hatred for not being able to ‘snap out of it’ like everyone would tell me, that made it ten times harder. Thanks to Dr Ben, and his information, I do not have to feel that bad anymore.

    #381360 Reply


    For Scott C above –I once was tried on a drug in patch form that kind of works like L-Dopa. It is called Emsam patch and is marketed for depression but the drug that it is –Selegilene is also available in oral tablet form for the treatment of Parkinson’s disease. It is an MAO inhibitor and stops the metabolism/breakdown of Dopamine in the brain and so keeps the Dopamine available (increases Dopamine levels). But because it is an MAO inhibitor, there is high risk of hypertensive crisis when you eat foods which contain Tyramine (which is pretty much in a lot of processed food these days.) Because it is an MAO inhibitor, they Tyramine is also not being metabolized and the effect of tyramine is acute hypertension. Like I said, I used the patch form because the tablet form has higher risk of the tyramine interaction. The patch is extremely expensive depending on dose it can range from $400 to $600 for a month supply. My Dr would not let me take the oral form for depression because they were worried of the risks. Even on the patch, there were times I got worried that I had eaten too much of something containing tyramine and I would get worried. But I never did have anything major happen. And of all the antidepressants I have tried (ALOT) the Emsam patch was the only one that actually helped me the most and without all the horrible side effects the others gave me. I stopped though because after about 6 months, the effect wore off (this does happen with most all antidepressants) and the adhesive on the patch itself -I was allergic to and so I had continuously healing squares all over my body and I was too vain for that. Of note: my daughter is VDRTaq +/+ and COMT -/- and it says that combination has the lowest levels of dopamine. QUESTION FOR DR BEN, FOR VDRTAQ +/+, SHOULD I GIVE MY DAUGHTER EXTRA VIT D?

    #381433 Reply

    Angeline Pacy

    I found the cure for this illness before I knew the name of the disease. Today, I am a survivor. What is more, I am getting my life back! I have been struggling with a mild PKU since childhood from this very same gene mutation. It cycled with infections which were always chronic. It also came with mast cell disease, previously diagnosed as chronic idiopathic anaphylaxis and MCS, which I recently learned goes hand-in-hand with this specific mutation. Protein starving exacerbated a chronic and reactive hypoglycemia and my central nervous system was a mess. On top if it, the infections triggered auto-antibodies against my nervous system. Through a partnership with integrative clinicians who worked their butts off to help me AND an amazing research organization called GeroNova research (who make amazing products) and a lot of research, I have gone from terminal to independent. It also takes constant PT. I also loved the MTHFR support boards. They were a lifesaver. My BH4 went up because I can even eat some meat now (small amounts). But I do stay away from meat and cows milk casein during infections. I developed a cocktail of pharmaceutical and nutriceutical medications that changed my world! I have so much to be thankful for. Contact me if you would like to learn more about how to manage this horrible mutation! You can be a victor!!

    #381434 Reply

    Angeline Pacy

    Ooops. I forgot to leave my information.

    #381639 Reply

    Alba Vaz

    Angeline Pacy….what are your actual mutations? I just found out I’m compound heterozygous c677T and A1298C, plus I have have many hetero comt, mao, vdr; and to top it off homozygous BHMT 02 and 08. I’ve tried many supplementation protocols to improve methylation, yet find that I re-act adversely and appears that I overmethylate easily. Even my well meaning osteopath knows little of this from what I gather, and follows Yaskos protocol which has not been successful for me; plus he’s not into testing, or recommends tests that are beyond my financial capabilities, so I’m pretty much left to self navigate treatment. Like many, I ended up at 23andme for affordability and to get some basic data. Any insight appreciated. Thanks everyone for sharing so openly. ps: I also have spina bifida occulta (one rare at c1) and bi lateral pars defect. Wondered if anyone out also has congenital spinal defects.

    #381705 Reply


    @Alba Vaz: You are probably not overmethylating, you probably need to detox from heavy metals, ammonia, sulfates and other issues first. Try a hair heavy metal test.

    #382326 Reply

    Alba Vaz

    Terri….thank-you for your comment. I’ve been putting off the hair analysis but will do soon; any particular labs you recommend? I’m considering ARL or Trace Elements. Your opinion appreciated. Heavy metals is definitely something that I must address more aggressively due to my higher than most exposure, plus I suspect I am a non-secretor which would make me more susceptible to accumulating toxins. I’ve just ordered sulfate test strips. Cheers!

    #382990 Reply

    Angeline Pacy

    Alba, I am so sorry to hear that you were struggling to develop an effective therapeutic cocktail. I have 2 copies of the A1298C. In my experience, which is limited to patient mentoring and self-experimentation, several complex factors could be impacting your ability to have a positive experience with the methylation therapy that is critical for your condition.

    I will agree with our other writer above. One component of what you are experiencing with methylation could be related to a rebound reaction. When beginning methylation therapy, it is important to remember that this is a detoxification process. You could be experiencing side effects from moving out several types of toxins in your body.

    But in my experience, detoxification through methylation should soon be a very helpful and pleasant experience (not painful). If you are experiencing very unpleasant symptoms when methylating, it is very important to start looking at other impaired detoxification pathways. Likely, you are carrying other mutations in pathways like glutathione and acetylation. When you carry other mutations for these impaired pathways, it’s time to get creative.

    But when I say that it’s time to get creative, I don’t mean it’s time to get freaky. I am going to give you some very sound, well-studied advice that you can take to the bank. Antioxidant therapy is critical to aid in the removal of toxins that you can otherwise not do on your own. Research shows that lipid-soluble antioxidants will help you detoxify your central nervous system. R-lipoic acid, the active form of lipoic acid in the body, stimulates the production of glutathione (both intracellularly and extracellularly). Glutathione will help you finish the detoxification process where your methylation cycle is impaired. It is also water-soluble, in addition to lipid-soluble, which allows it to work all over your body. Three research studies also show that astaxanthin, a lipid-soluble antioxidant carotenoid derived from algae, is an excellent central nervous system detoxifier. I have had tremendous success with both of those therapies. They should be a part of any MTHFR protocol, especially for anyone who wants to live into their 40s.

    And finally, I am convinced that what you choose to methylate with really does matter. As for the nitty-gritty with methylation options, the Merk Manual calls for daily methylcobalamin injections (some versions recommend the hydro). It is a central nervous system detoxifier (in addition to a methyl donor). It is critical to make this your primary methyl donor. Everything else is built upon that therapy. Many of the methyl donors do not reach the central nervous system. It is critical that you get all types of methyl donors.

    Trimethylglycine is perfect for a standard MTHFR gene mutation because it is a precursor to several major neurotransmitters that are difficult to manufacture for this population. Unfortunately, there is another SNP that impairs the ability to breakdown dopamine. You may or may not have that mutation. But typically I tell patients to use trimethylglycine cautiously in the beginning in case they are struggling to break down dopamine.

    Other types of methyl donors may be disagreeable to you for the same reasons. Personally, I found great success with a supplement called MSM. However, those with an SNP for the impaired ability to breakdown sulfur compounds may find MSM to be inert or even unhelpful. You must find what works for you specifically.

    #382994 Reply

    Dave B

    Angeline, I couldn’t agree with you more about the positive effects of Astaxanthin, the powerful antioxidant that you mentioned. It virtually single-highhandedly turned my life /severe health problems around! It is a carotenoid pigment found in algae, which stops oxidatinve damage in algae cells caused by photosynthetically generated free radicals. It is the red colouring found in lobster, salmon, fish roe etc. It crosses the blood brain barrier (the only one that I know which does ) and has many health benefits. See below

    I am compound heterozygous C677T and A1298C and it wasn’t until I learned that MTHFR causes low glutathione/antioxidant levels levels, that I realised why I got so much benefit from taking Astaxanthin. I have spend hundred of hours researching it’s properties, and it’s almost completely free from side effects (can interact with blood pressure reduction medication so one needs to be careful of that) SO far it is the most powerful antioxidant that I have found. It is not expensive (50c /day ) and I buy the 400mcg capsules fro iHerb (brand Bioastin) Dr Ben Lynch mentioned its great properties in a recent podcast of his I listened to.

    There is not enough time for me to go through all the life changing health effects I have experienced, but in a nutshell, I swear by it. If your immune/antioxidant systems are not coping, why not help yourself by supplementing with antioxidants, while you are rebuilding your own glutathione/antioxidant levels naturally through active MTHF supplementation (assuming you do not have any other SNP’s that make this difficult)

    I take 400mcg /day, which equates to one meal of oily salmon/day. Always remember …less is often more.

    Please note that my success is anecdotal evidence only, and as such, does not constitute scientific proof.

    Here are a couple of links if you are interested.

    Good luck

    #383019 Reply

    Angeline Pacy

    Dave B.,

    Aren’t the lipid-sluble antioxidants powerful??? I have to tell you, I am not sure that I would even be alive without using them at a therapeutic level. I don’t dabble in supplements. I am a hard-core advocate for understanding the chemical structure, form, properties, and therapeutic dose of everything that I buy. I don’t just need research though. I need it to work for me! My lipid-soluable antioxidants not only work for me, I thrive with them. For all the others suffering with neuro-inflammation, allergies/anaphylaxis, and MTHFR, if you haven’t tried astaxanthin at a therapeutic dose (email me for details), you owe it to yourself.

    All that aside, Dave, you have to try my favorite R-Lipoic Acid. GeroNova Research makes several terrific products. But, I find that the liquid potassium r-lipoate is awesome. You have to take it a couple times a day but honestly, its pretty fast-acting. Thats it’s plus side. It literally takes glucose and converts it into ATP, something that anyone struggling with mitochondrial disease (in all its many forms, from ALS, PD, and Alzheimer’s to Chronic Fatigue Syndrome and Auto-immune attack on mitochondria) needs desperately. There is a definitive break in the Kreb’s cycle for these patients (in several areas) that prevents the formation of ATP from glucose. Anyway, GeroNova has a host of terrific products, but I cry when I run out of this particular one! Their R-lipoic acid products absorb and metabolize better than intravenous alpha lipoic acid and you can find the PK studies on their website that prove it. They have altered their molecules just a little (to add sodium and potassium) for better absorption. That is why I have become the lipoic acid and astaxanthin guru and the GNR stalker . . .

    Anyway, since we have so much in common, please tell us what else you love and what else can radically change the quality of life for this population dealing with a host of disease related to MTHFR!!

    #383042 Reply



    i was prescribed BH4 (Kuvan) 25 mg daily
    anybody know where can i get the BH4


    #383046 Reply

    Dave B

    HI Angeline,

    Sorry to take so long to respond, but I have had one hell of a week and are only just coming up for air now!

    I love reading posts like yours, because you are testament to the fact that with consistent, persistent, unrelenting effort, using the intelligence/courage/strengths we have been given, we can overcome the most difficult of obstacles (and MTHFR certainly falls into that category) Finding the exact combination of supplements/food and lifestyle changes is difficult, make no mistake about that, particularly when we are currently swimming against the tide of medical knowledge/opinion…. but the tide is turning. People like you show that!

    After reading your post I can see that you have taken research / analysis on supplements/MTHFR to another level than I have, which leads me to suspect that you must be either a doctor/medical research worker, etc This area is not easy for any of us. I have a biology degree majoring in biochem/cell biology, and is has taken me a good 6 months of solid reading to get me head around a basic understanding of all the interrelated pathways, although I did start from a pretty rusty base.

    I only found out that I had MTHFR in 2011, so for the 30 years before that, I was really stumbling around in the dark when trying to solve my debilitating health problems. I was trying to join up the dots, when the most critical piece of the jigsaw puzzle was missing:) As it turned out, everything that I discovered that worked during those years, fitted into my diagnosis of compound heterozygous (C677T & A1298C) MTHFR. I was on the right track, and I thank my intuition for guiding me along the path……

    Like you I do my research, and at the end of the day, like you, I only use supplements that work. I problem solve scientifically/methodically, always testing/checking one compound at a time, before moving onto the next. In the end after all these years, the only things that I can say have definitely worked for me are:
    1) Astaxanthin (4mg/day….not 400mcg as I previously stated),
    2) Active Methylfolate (400 mcg/day; Thorn Methyl Guard)
    3) Vit D (2000iu/day)

    Angeline I couldn’t agree more with you that anyone with neuro-inflammation, allergies/anaphylaxis, and MTHFR, couldn’t help themselves any more, than by taking Astaxanthin. I owe getting my life back to a combination of it and active methylfolate. When you research the benefits of Astaxanthin why wouldn’t you take it?

    In the end I feel that a reasoned, informed approach to the whole MTHFR is an absolute must…..get rid of everything from your diet/environment that contributes to your toxic burden ….be consistent and persistent….start with small doses of whatever the supplements you are taking…..look for a medical professional who is knowledgeable in this area and encourages your active participation in solving the problems…….. don’t get discouraged if you run into medical dead ends (including doctors and specialists), but keep the faith……address any fears /psychological issues that may be contributing to your stress levels, and which ultimately exacerbate methylation problems… alert for help from unexpected sources…show your subconscious mind that you are serious in healing your health issues, by taking /making the hard calls in diet/lifestyle consistently… kind do in yourself when you regress/fall off the wagon, because we all do…. believe that you deserve wonderful health… keep your fingers crossed :)

    I don’t have use any other supplements that I can credit with saving my health…just the above. I think I may have got lucky, because many folks have other SNP’s which confuse the whole issue. (I am almost sure that I have only C677T and A1298C) This is where finding a knowledgeable medial professional to help is vital.

    Thanks, I Will look into R-Lipoic Acid. GeroNova Research. Good health to you

    #383128 Reply

    Angeline Pacy

    Dave, thanks for the uplifting and thoughtful post for us all. Like you, my gut told me that you had a biology background. I have been able to consult in my field (clinical research), but that is all. Hopefully, that will change in the future!!! I am optimistic. I was fortunate to not start off with a blank slate in terms if insight into the human body and for that I give thanks.

    My parents were hippies and nutrition-based folks, so much so that my father consulted in that area. I “unplugged” for that reason and as I grew, I learned essential things from him and his friends/business partners. That set us up for success. It wasn’t a hard fall down before I “unplugged” and went a fully integrative path that saved my life. I do not lie. My diagnosis and prognosis are horrible. Everyday, I defy the odds and I rejoice at how far I have come in just a couple years. Not that long ago, the only thing I was able to do was to raise my heart to heaven.

    Today, I am a very different women (healthy on the inside). But there was a time when grief from the health barriers and suffering from genetic illness in my family (there is more than one if us) drove my unconscious. As you have wisely said, dealing with the unconscious must be top priority on the path to life and wellness. I am grateful to have learned those lessons early on in my path, but I am on a faster time-table. . . My life is unordinary. Love has guided my path and I am truly thankful because it hasn’t been just bitter, the opportunity was there to turn it into something sweet.

    MTHFR is really complicated because it can come with so many other things. Your particular combination can present it’s self differently from my own, which often presents it’s self in an extremely neuro-metabolic way, to the point of where the cascade that spins down from the chaos can look like any of the major three neurodegenerative diseases. That’s why I need much higher doses of astaxanthin (more in line with the positive ALS studies starting at 80mg/day) and other antioxidants like the r-lipoic acid. But to fight back and say “this is beatable” and then to win the fight has been more rewarding than I can say.

    I still have my glitches and limitations like everyone. But, I have hope where there was none. . . I have more to be thankful for than you can imagine!

    I recently began mentoring a young woman with your particular combination of mutations. She presents with a variety of complaints, few taken seriously. She appears to be degenerating into a dysautomie with some quirks. Giving her medical advice is more challenging than anything I have ever done. She, like many others facing prolonged toxicity, has developed intolerances to a variety of therapeutic solutions and environmental illness. I pray for her and patients like her everywhere. Her illness is complicated by a true Lyme disease, like many others I have met over the years. She is a winner, though, and I know she can beat this thing!

    That’s one thing that is so great. I am on my own time-table and so is she! The only person I race against is me; I strive to be the best version of me that is possible and nothing more. It helps to wash away fear and disappointment and vicious self-comparisons that are only destructive. I cannot say enough about self-pacing. :-)

    I look forward to connecting one day in real time. Until then, much thanks for the input!!

    #383146 Reply

    Dave B

    Hi Angeline

    Looks like we are both on the intuitive side :) Biology is fascinating, and I think we all owe it to ourselves to become as knowledgeable about MTHFR we possibly can. What do they say….knowledge is power!

    Seems like you are a battler like me, who doesn’t take no for an answer when it comes to rising above difficulties

    My health issues were pretty bad/untenable for 35 years, but early on I made a promise to myself to ‘play the hand I was given, to the end of the game’ even though for most of the time I felt like packing it in. What I found, was that ‘life’ seemed to step in to give me a hand, after I had exhausted all my own resources in trying to solve the issues. I am a great believer in help from unexpected sources.

    Sounds like you have had a very difficult hand to play, but though sheer persistence and using whatever innate skills/ strengths you have, you have risen above adversity. What a truly wonderful effort…and you are a poet !

    Yes the ‘ol unconscious…imo it drives probably 90% of our behaviour. If we can’t get our unconscious to cooperate with us to help heal ourselves, then the road is pretty tough. It seemed that deep fears kept fueling my MTHFR driven ‘episodes/depression’, so decided to public speak for a living to openly challenge those fears. My confidence and enjoyment as a presenter … methylfolate/astaxanthin supplementation, has gone hand in hand with reducing my episodes down to know only 1 x episode in the last 4 years (touch wood) I don’t profess to understand how it all works, but it seems that the expression of our MTHFR mutations/defects are in part dependant on our mental and emotional states. I think that this is where stress and anxiety come in to exacerbate the problem. (see Bruce Lipton/biologist) ‘Don’t worry’ is easy to say, but can be very hard to do.

    You have many wonderful sayings and attitudes Angeline. Seems like in challenging our difficulties, we have both become ‘friends of life’ and do our best to support others in rising above their health difficulties. I dream of a happy ending for all, including our animal, bird and plant friends. Yes … we are all both teachers and students in this great game of life.

    Please feel free to contact me whenever you want on email below …and yes perhaps one day we may meet and say hi :)

    Cheers Dave

    #383182 Reply



    Have you ever compared R-Lipoic Acid to Liposomal Glutathione? I’m curious if it is more economical to stimulate your body to make glutathione, or to take it directly.

    #383192 Reply

    Angeline Pacy

    Heather, that is the million dollar question and I will speak straight from the heart. Fortunately, I have experience to back it up . . . I have taken the following therapeutics for extended periods: intravenous glutathione, oral / liposomal glutathione, r-lipoid acid (non-GeroNova Research), and every R-lipoid acid formulation that GeroNova Research makes.

    After combating a quickly moving neurodegenerative disease and now winning the fight, I can tell you several things: no MTHFR patient with complications (autoimmune, infectious, other SNPs, all of the above) can place a rapidly neurodegenerative disease into remission with any one of these therapies. It takes a cocktail of therapies and diet. Two, I have found the leading commercial brands of R-lipoic Acid (and alpha) to be marginally effective, if not inert for any one of my conditions described in the paragraphs above. In contrast, I experience almost immediate relief (depending on what is already in my stomach) in various symptoms from the liquid-potassium-sodium-r-lipoic acid that GeroNova Research makes. I can make the comparison to various delivery systems of glutathione for you: one, intravenous glutathione is most unimpressive if you are dying. If you are dying, it’s not even going to put a dent in it. Two, I don’t spend the money anymore because I can’t justify the expense when this liquid r-lipoic acid product works better than both intravenous glutathione and intravenous alpha lipoic acid. Three, To glutathione’s credit, I have experienced an increase in energy (ATP) with the liposomal glutathione products. They were not inert. But, glutathione did not supply the anti-inflammatory, anti-histamine, pain -relief, increased concentration, or as quick delivery as the liquid r-lipoic acid from GeroNova Research does. They have PK studies to back the superiority over intravenous alpha lipoic acid too! But, I didn’t need the studies to know because I’ve tried it all.

    Now that all being said, I take both the GeroNova Research liquid r-lipoic acid product AND their “Curcumin plus lipoic acid” product daily (in incremental doses). It has managed mast cell degranulation symptoms so well that I no longer take Claritin D (my former nick-name) and I have not needed to detonate an epinephrine auto-injector. All that being said, I do have a comprehensive protocol in addition to these therapies that includes a rigid diet. But, I have experienced remarkable symptom management. I hope to get my dancing shoes on soon! We’ll dance together!!

    #383291 Reply


    I take a number of supplements for my A1298 mutations. A lot of this comes from this page:

    I take L-Ornithinine, Yucca Root for ammonia control as well as a weekly charcoal flush with magnesium citrate/charcoal. I take NADH and Royal Jelly as well for BH4 support. There are a number of supplements recommended for A1298 in the note I have linked above. I take a few other supplements they recommend for Ammonia and BH4 support as well as for other reasons. The other supplements I have that may help as well are b vitamins (specifically methylfolate, P5P, B3, and B12), lithium, 5-HTP and GABA.

    #383322 Reply


    I’m heterozygous for MTHFR A1298C and MTHFR C677T and looks like I probably have at least one of the downstream (in the methylation cycle) gene complexes as well.

    Yeah, the litany of health challenges is pretty familiar to others here and I won’t go into any detail about that, but I’m doing a whole lot better since I worked out my protocol over the past 12 years (it is almost identical to Dr. Lynch’s recommendations for heterozygous people, so he gets a big gold star from me for independent verification!) I’m not a practitioner, just bright with a wild gift for biology (and slightly autistic, which really helps with tracking details and sticking to logical debugging behavior.)

    BH4 is hard to get hold of, but four years ago I managed to get my former naturopath (no longer practicing) to get me one bottle of the Ecological Formulas capsules, from a source which promptly quit carrying it. BH4 helped me get focused in the mornings. I ended up saving it for monumental brain fog days, due to not being able to find a way to order more BH4. I would break open the capsule and take the contents under the tongue. This provided good clarity starting about a minute later and lasting for 20-30 mins., long enough for me to put together and start eating my usual raw-greens breakfast and get body and brain activity ramped up, which would launch me on a more-functional track for the day. I’m so much better now that I almost never get that level of brain fog any more.

    Pleased to note that R-Lipoic Acid has come up on this forum. I use it almost daily; discovered it on my own ten years ago and am never without it since. Typically I need more of it in the winter and less in the summer.

    #383588 Reply


    (Hoping you read this.)
    Hi, this thread has inspired me to start astaxanthin. Upon searching online, I’ve only found 4 mg. doses and am curious about how you take your therapeutic doses of 80 mg. Thank you for any suggestions!

    #383612 Reply


    Has anyone had any side effects to taking BH4. With a dose do 1 pill at 2.5 or 2 pills at 2.5 one am and one pm

    #383670 Reply


    Just found this site when researching BH4. First I want to comment on the BH4 mentioned at the begining of this thread –
    “Can anyone offer insight into using the supplement BH4 — it’s from Ecological Formulas BH4 Homeopathic 2.5 mg Capsules. The ingredients list only BH4 (2x) but the bottle also says “BH4 contains Biopterin, a cofactor to critical enzyme pathways in human physiology.”
    So, any time you see an ingredient followed by a (2x) or (3x) or (10x) you are looking at a homeopathic remedy. What the (2x) tells you is that 1 drop of BH4 (BH4 is Biopterin) was added to 100 drops of water and then shaken AND then 1 drop from that is added to another 100 drops of water and then shaken. It is a dilution formula and the idea behind it is that you are receiving the ENERGY of the substance (in this case BH4) but it is not like taking true, undiluted BH4.
    I am heterozygous for both A1298C and C677T and I too have been ill from birth. I was called pouty-puss because I was often unhappy and didn’t feel well. I am so grateful to finally know that everything I have expeienced over the 5 decades since then WAS REAL!!!!!! AND, real can be dealt with. I also have another SNP (genetic defect) that is associated with lower levels of BH4. Thank you to all of you who have shared such wonderful information – that I am now going to try for myself, a little at a time. I have taken small doses of astaxanthin before, but never realized that I could safely go much higher and that it could penetrate my blood brain barrier! I have had a number of hair analysis over the last 5 – 6 years and I have a fairly large quantity of Mercury, Lead, Aluminum and possibly Arsenic in my body (I believe the lion’s share is in my poor brain). I am looking forward to being Clean & Pristine again in the near future by cleaning this crap OUT.
    I wanted to add one of my “secret weapons” to this space – SAM-e! SAM-e is a fabulous, powerful methyl donor and I and my son have been amazed at how much it helped to decrease our Inatentive ADD symptoms. There are tons of reviews about it on Amazon (at least for the Nature Made brand). The tablets come in 200mg or 400mg doses and I started low and worked up slowly to the 400mg. Many reviewers reported happily taking up to 1,600mg daily with no negative side effects! Remember, though – ALWAYS start slow. I recently switched to the Jarrow brand because it has no Talc in it. I buy that on-line at iherb (they have the best price). The Nature Made brand I bought at Costco whenever it went on sale. Anyway, for people who can’t methylate properly a powerful methyl donor is like a dream come true! FYI — SAM-e is supposed to be fabulous for joint pain too.
    I am in the processs of working with my naturopath to possibly start taking very small, daily doses of prescription BH4. If that works out I’ll be sure to share all of the info. with all of you. Best wishes…

    #383744 Reply


    Chrissalissa- I agree with your comment clarifying the BH4 supplement as being homeopathic in nature, and not nutritional. The “X” dilution is one in ten, and a “C” designation is one in one hundred, based on Roman numerals. This is such a great topic! I so appreciate all the comments I’ve read.

    #475316 Reply

    Tammy V

    Question: how are you supposed to first decrease inflammation when every single thing (including water), causes severe inflammation? How/when am I supposed to start supplementing when I’ve been so sick and inflamed for decades? I’m so confused, and getting a little frustrated at this point…. Thanks!

    #475954 Reply

    Dave B

    HI Tammy

    I read your personal story, but there were just too many complications for me to add anything meaningful. Seems like you have everything but the kitchen sink. :( I feel for your situation.

    My guess is that your gut issues are at the root of everything. If your gut is not working properly then all manner of nasty things/complications show up. Because the gut lining cells are replaced every 3 drys, if you have methylation issues/imbalances/build up of toxic biproducts etc, then this cell replication process is just not going to be working properly… and then all manner of hell can break loose!

    If I was in your situation, 1) I would have the 23and me genetic test done. 2) I would then find out whether I had raised sulphur levels in my urine and depending on these results, 3) I would then start a strict diet eating mostly fresh natural foods (low sulphur depending on your urine test?), with lots of green leafy veg. 4) I would also take an antioxidant to help with any inflammation (eg Astaxanthin), 5) get rid of any personal care products that had preservaties/additives in them, 6) replace aluminum cookware with stainless steel/cast iron, 7) get any mercury fillings removed, etc. IMO you need to reduce the amount of toxins going into your body asap. You need to be kind to your body.

    Once my 23andme results came back, I would then look for a functional medical doctor (or and open minded orthodox one) and go through the results and make the appropriate changes to diet, lifestyle, supplements etc. There is no easy fix. Slow and steady usually wins the race here. Unfortunately your body doesn’t seem to be able to deal with the food/chemicals you have put into it over a lifetime, so it’s limping along really badly. I have no idea why your body cannot tolerate water.

    Your neuro-psychiatric issues may certainly be related to your methylation issues, as A298C appears to be partic troublesome when it comes to neurotransmitter production … and I know that because I am compound heterozygous A1298C (+/-) and C677T(+/-)

    good luck

    #485466 Reply


    Hello everyone,

    I read this post en was interesting in the materie.
    I just found out ( 23andme ) that im homozygoot for A1298C.
    I got 10mutations in the methylation cycle. 8 of them are homozygoot en 2 are heteozygoot. So ik screwed!

    I got much of neurological problems. Tingling crap muscles twiching pain etc etc. My symptoms lookslike muliple sclerose.
    And im really often depressed. I think because of los dopamine serotonine etc.

    How can i boost my bh4? And my depression?
    I thougt or i use sam-e to boost serotonin levels or with sint johns wort ( that will boost depamin en serotonin also right?).
    I use also astaxanthin 4mg and 1000mcg metafolin ( thorne multi) and use methyl b12 and inject myself with one time a week methyl b12 and hydroxocobalamin.

    Is there somsone with the same mutation dat also got CVS? And fructose intoleranz?

    I cant eat anything, because i react on so much things. Its such a difficult materie!

    I hooe someone could help me !
    Im sorry for my englisch but i come from holland and there are here no doctors who know something about methylation :(


    #488073 Reply

    Dave B

    HI Kelly,

    Your English is good enough I can understand what you are saying perfectly well.

    Yes homozygous for A1298C can be quite difficult. You make some 70% less BH4, which impacts on many things, including your capacity to make neurotransmitters, including serotonin, dopamine, adrenalin and noradrenalin. The end results can be very severe neuro-psychiatric issues.

    I am compound heterozygous (C677T and A1298C) so according to my research, like you, I also make some 70% less neurotransmitter substances. I have had many years of severe migraines/depression/anxiety …and I also have two neural tube defects. The evidence seems to point to the fact that all these problems are the result of faulty folate metabolism/methylation (ie MTHFR, etc) My mother also had Multiple Sclerosis

    The BH4 cycle is very complicated and is often not an easy fix. I can only tell you what I did which has resolved my problems … and hopefully this might be helpful to your situation. I have other polymorphisms as well, which feed into my MTHFR mutations, which make my neurotransmitter production/storage and release even more problematic

    These are my polymorphisms that relate to serotonin, dopamine etc, production. MTHFR C677T(+/-), MTHFR A1298C(+/-), COMT V158M(+/+), COMT H62H(+/+), VDRTaq(+/+), and MAO-A R297R(+/+), MTRR A66G(+/-)

    These are the supplements that I take. They seem to have resolved a lifetime of problems. (touch wood)
    1 Change of diet to include lots of fresh green leafy veg/fresh food
    2 400mcg active methylfolate/day (Vit B9)
    3 400mcg methylcobalamin/day (Vit B12)
    4 4000IU Vit D/day
    5 5mg Astaxanthin/day (Bioastin)
    6 Dealt with most of my life stressors and reduced my overall anxiety

    The fix in my situation was rather simple and straightforward (thank god). I hope your fix is equally as straightforward. I believe if you are persistent you will find the keys to your own problems. Because we all have unique combinations of polymorphisms/mutations, we generally all have problems unique to each of us alone. The one size fits all paradigm does not apply here!

    Good luck

    #489032 Reply


    Hi dave!!

    Thanks for youre message.
    THE productschap that you take do i also take. So astaxanthine, 10.000mcg methyl b12, and i inject methyl 10mg b12 once a week, and hydro 10mg injecties once a week. Methylfolate i took 1mg a dat but that ist enough in my case :(

    IVe got vers much mutations also…


    VDR Taq
    MTRR A66G
    CBS A360A

    And Hetro:
    MTHFR 03 P39P
    MTRR A664A

    So you see a difficult combination.
    You are not in a anti depressant or something?
    And you do not use Some supplementshoek for neurotransmitters?

    I Will Search for a BH4 supplement and i think i Will try SAM-E or Sint John worth… Do you think thats a good combination?

    My brother has got diabetici type 1, i read that hè is also low in BH4, but he’s not depressed or something.. Weird right?

    And my BH4 does stand “no call” at 23andme, is that also at youre test?

    Thanks a lot for helping me i appreciate iT.

    #489038 Reply


    And what terrible to haar from youre Mother that she had to deal with MS. In youre familly you also have to deal with auto immuun disease?
    I think iTS al because of this mutations…
    I also have SPNs that have a higer risk of ALS and Parkinson i saw … My symptoms looks like MS and Parkinson …

    What are youre symptoms?

    Have a nice weekend.

    #489099 Reply

    Susan Shears

    Hi Debbie,
    I read that you had an issue with very low BH4 and that it caused a myriad of issues as well as a swallowing problem. I have been supplementing with homeopathic BH4 for the last month or so – and yet my symptoms of difficulty with swallowing have increased not decreased. Could I be going thru major detox? Dr. Amy Yasko told me that I was very low in BH4 for the following reasons: High Aluminum on my HMT, the MTHFR/A1298C mutation, and a CBS/699 mutations. She said the bacteria in my gut is holding onto aluminum and consequently my BH4 levels are quite low now. Do you have any suggestions as to how I can slowly (thru supplementation etc.) go about regaining my swallowing ability? Dr Amy said to work with my doctor and add in the homeopathic BH4 but I am on a long waiting list to see the doctor here in Denver and in the mean time I need some direction now. Any thoughts would be appreciated? Thanks, Susan

    #494271 Reply

    Dave B

    Hi Kelly

    No I do not take any antidepressants… never have. I always wanted to work out why I wasn’t producing enough neurotransmitters myself, and then fix the problem at the source. In the end I discovered the reason (methylation cycle polymorphisms) and supplemented accordingly.

    You share many polymorphisms with me. I can see from your list that you would really struggle to make enough serotonin / dopamine …hence your depression/anxiety/neuropsychiatric issues etc

    I used the following supplements to resolve my depression /neuropsychiatric issues. I take these supplements every day and will continue to do so for the rest of my life unless things change.

    Methylfolate (B9)… because I don’t make enough active methylfolate, myself due to MTHFR C677T(+/-) / MTHFR(A1298C (+/-) (-70%), this helps me to make sufficient BH4 a required co-factor in dopamine/serotonin production. I have not looked at my BH4 results on 23andme results yet, but I will get back to you on this. If your brother is low in BH4, I would expect him to have neuropsychiatric issues ….perhaps depression , perhaps something else.

    VitD … because of my VDR Taq (+/+) I make very little Dopamine (-70%), because Vit D is a required co-factor in dopamine production

    Methylcobalamin (B12) … because I don’t make enough due to MTRR A66G(+/-)

    Mum had MS but somehow she ended up in remission after having B12 /folic acid injections. Bit of a mystery really. No other auto-immune diseases in the family except for some Rheumatoid arthritis. I agree … I also think it is because of methyl cycle polymorphisms

    I had severe migraines/depressive episodes regularly for 35years which were debilitating. I have no symptoms now, and have not had an ‘episode for 3.5 years (touch wood/thank god!). The supplements seem to have fixed the problem. A rather simple fix I know, but a fix none-the-less :-)

    SAM-e and St johns wort sound helpful but I cant tell you a lot about either

    Good luck

    #513602 Reply


    Hi Dave,

    I had the 23andme testing done and have been having a tough time putting the puzzle pieces together, so after reading all of these helpful posts, I thought I would share my mutations and ask for any feedback/advice.

    I have a history of cancer and was just diagnosed with MS a little over a year ago. I have also suffered from bouts of anxiety (which is better after eliminating gluten), irritability, depression, brain fog, and fatigue. I follow an autoimmune paleo style diet, have taken several measures to reduce stress, detox my system and boost my mood. I am doing much better overall, but I am still struggling and think it is due to some of my mutations. The good news is that I don’t have the MTHFR mutations, but I do have several other mutations in the methylation genes, including the following homozygous mutations:

    CBS A13637G rs2851391
    DAO rs3741775
    GAD1 rs12185692 and rs3828275
    MAO A R297R
    MTHFD1L rs6922269
    NOS2 rs2274894 and rs2248814
    NOS3 rs1800783 and rs1800779

    I am also VDRtaq +/+, and I have several heterozygous mutations in the MTR, MTRR, COMT, BHMT and ACE genes.

    The challenge I am having is addressing the methylation issues and the CBS mutation, which I think complicates things a bit. Any thoughts, suggestions or advice, as far as which supplements I could try would be greatly appreciated.

    Thank you!

    #516823 Reply

    Dave B

    HI Cherie.

    You are no orphan there. It is not easy for any of us to put the jigsaw pieces together. It took me quite a while, and without some ‘dumb luck ‘ along the way … well …..

    Unfortunately we are all so unique and different with our specific polymorphisms and health issues, that I cant tell you a lot with limited time and info. So many variables. What I can tell you is that you share several homozygous polymorphisms with me … VDR Taq (+/+) , Mao R297R (+/+)

    Having no MTHFR polymorphisms, should mean that you produce sufficient active methylfolate, hence enough B4(co-factor in neurotransmitter production), hence sufficient neurotransmitters. However because you are VDR Taq (+/+) then this means that you may not still may not be producing sufficient dopamine/nor-epinephrine/epinephrine. As a consequence of my VDR Taq homozygous mutation, I take 4000IU Vit D daily and will do so for the the foreseeable future.

    Your MAO polymorphism means that you break down neurotransmitters (serotonin in partic, slowly ) This means that you would be prone to changing neurotransmitter levels (cycling) leading to neuro-psychiatric issues. (this is where my problems lie) In a sense the effects of these two polymorphisms tend to cancel each other out.

    I can only tell you that to increase my dopamine /serotonin levels (and to reduce my homocysteine level), I needed to take active methylfolate (low dose because of COMT(+/+)/MAO (+/+)… Vit D, active Vit B12 (because I am hetero MTRR A66G) and Astaxanthin (an anti-oxidant) to assist free radical destruction /lowered Glutathione levels. I also changed diet, reduced environmental toxin intake and reduced stress levels

    The CBS mutations are not all that well understood, and recent research does not find sufficient evidence to support Amy Yasko’s model of high up-regulation, said to generate excess ammonia, sulphur /sulphites/ H2S etc. There may be a significant effect, but at the moment the jury is out. I don’t have any CBS polymorphisms, so I haven’t had to navigate my way through this one.

    I am sorry that I cannot be more helpful that this.

    Do you have anyone who could assist you with a strategy? cheers

    #518745 Reply


    Hi Dave,

    Thank you for the thoughtful response. It is quite a puzzle and fascinating at the same time. At any rate, I have been taking vitamin d3 and will continue to do so. I will also look into your other suggestions. I am in the process of setting up an appointment (currently on a waiting list) with a functional medicine practitioner and hope to get more insight. I will share anything I find out, especially about CBS.


    #552434 Reply


    Hi. Through 23andme and found I have a similar profile to you. Heterozygous (C677T and A1298C). And have 5 homozygous GAD genes – difficulty synthesizing GABA —My dr said he had never seen this before!! This means I burn Serotonin too fast. So really do not have any.
    MAO – told me to take 5HTP 100 mg up to 8 a day! I have only been take 1 a day
    MTRR – antioxidants
    SOD SNP’s – eat berries, vitamin C, CoQ10
    GST SNP’s (single nucleotide polymorphisms) – take epson salt baths.

    I have been taking Thorne MethyGaurd Plus (see ingredients below)and after only 3 days of starting was doing AMAZING. But then after about 1 1/2 mnths I started feel bad again. Anxiety, depression has come back. Soo tired, hard to get out of bed. Sleep over 12 hrs a night and still tired etc. I’m so frustrated. Not sure what to do. Also, I have horrible nerve pain in my arm. tingly fingers.

    Should I try Niacin? Wonder if I do need more 5HTP? Someone wrote about SamE – wonder if that would work for me. Any suggestion would be appreciated.
    Thanks SO much

    Methyl-Guard Plus ingredients:
    Riboflavin (as Riboflavin 5′-Phosphate Sodium) 90 mg
    Vitamin B6 (as Pyridoxal 5′-Phosphate) 45 mg
    Folate (as L-5-Methyltetrahydrofolate from L-5-Methyltetrahydrofolic Acid, Glucosamine Salt) 3 mg
    Vitamin B12 (as Methylcobalamin) 3 mg
    Betaine Anhydrous (Trimethylglycine) 1,800 mg

    #554251 Reply

    Dave B

    HI Janie

    Yes indeed we seem to share many risk alleles. These are my most problematic ones (according to current knowledge)

    MTHFR C677T (+/-)
    MTHFR A1298C (+/-)
    COMT V158M (+/+)
    COMT H62H (+/+)
    MAO-A R297R (+/+)
    VDR Taq (+/+)
    MTRR A66G (+/-)
    MTR A2756G (+/-)

    hahaha! …beat you ….I have 7 x homozygous GAD genes :)

    GAD1 C10180T (+/+)
    GAD1 C14541T (+/+)
    GAD1 C2627A (+/+)
    GAD1 G39901 (+/+)
    GAD1 G3992 (+/+)
    GAD1 G5276A (+/+)
    GAD1 T21922C (+/+)

    Welcome to the world of endless anxiety in all its forms. We have a real problem at calming ourselves down, due to our difficulty in converting glutamate to GABA. But then I wouldn’t have to tell you that!

    The issue you most probably have with Thorne Methyl Guard plus is that you are taking all the supplements together so that you never really know what is doing what. On top of that, if you have MAO-A (+/+) and/or any COMT (+/+) then you would probably not be able to tolerate high levels of methyl groups … and MethylGuardPlus has high levels of methyl groups in it.

    Have you ever thought about micro-managing your symptoms/problems by taking the supplements you need individually, one ingredient at a time, in a slow but systematic fashion, starting off with low doses of the the required supplement. For example, I can only tolerate low doses of supplemented methyl groups due to my MAO and COMT polymorphisms, so I take 400mcg of methyl B12/day.. yet you take 3000mcg of methyl B12! No wonder you have had ongoing problems. (If you suspect you have OD’d on methyl groups, you can mop them up with Niacin and then start again). Note, I have never had to do this.

    Why don’t you start again …change your diet to include all the good vitamins/foods …reduce your exposure to environmental toxins …take an anti oxidant (I use Astaxanthin 400mcg/day) to support your ability to detox/get rid of damaging antioxidants ….then if you don’t have any major CBS (+/+) mutations (according to Amy Yasko) start supplementing with very low dose of active Methylfolate (5-MTHF), raising the level every few weeks until you feel comfortable …then you could add in some methylB12 again at low dosage and gradually increase. This way you can monitor what you are taking. Then do the same for all the other supplements. This is what I did. I knew that I was on the right track, when my homocysteine levels dropped from 13 (very high) to 7.8 (good) after 2 months of 5-MTHF supplementation

    If you eat foods high in the vitamins/minerals that you may be lacking, then at least you will supplying your body minimal Vit requirements, while you are working out the rest.

    My motto is gently gently, with a careful reasoned approach with very small initial doses of anything

    There is one other thing that I think you might look into.

    You say “So tired, hard to get out of bed. Sleep over 12 hrs a night and still tired etc. I’m so frustrated. Not sure what to do.”

    Well that sounds suspiciously like you may have a thyroid problem (I am sub-clinical hypothyroid), and if you do, then that needs to be addressed Thyroxine, (the thyroid hormone )is implicated in the production of 5-MTHF because it helps produce one of the required co-factors (FAD) in methylfolate synthesis. Low thyroxine levels point to low MTHF, and remember you may already have a problem because you are compound heterozygous MTHFR

    Please realise that I am not medically trained, so you need to consult a health professional before taking any partic. course of action (However I do have a BSc. in biology and genetics, so I do have a solid basic understanding of cell biology…. and … I have resolved many severe health problems over a lifetime using the above approach (plus a bit of creative problem solving). It is my opinion that taking full responsibility for our own health is the best thing that we can do.

    *Just letting you know that my healing was fast tracked big time when I started taking the powerful anti-oxidant Astaxanthin. It was a life changer for me

    Good luck

    #560913 Reply

    David Reed, RPh

    After reading multiple posts, I felt compelled to let all of you know about Enlyte. It is the first folate source that addresses the various polymorphisms involved in the one-carbon or methylation cycle. The ability of a person to methylate properly is paramount for production of monamines. Enlyte contains folic acid, folinic acid, and l-methylfolate magnesium. The key is that it also provides all of the cofactors,
    B1, B2, B3, B6, B12, required in the cycle. It also contains DHA, EPA,
    Magnesium, reduced iron, vitamin C. All of these cofactors are in a reduced form, bypassing the various polymorphisms that cause incomplete methylation and hyperhomocysteinemia. Homocysteine itself is toxic to neural tissue, and is the easiest level to identify. Enlyte lowers homocysteine levels, indicating that methylation is occurring properly.
    It is a prescription only product. See for more information.
    It is natural, safe, and effective. The American Psychiatric Association recommends folates as first-line and adjunctive treatment for depression.

    #561415 Reply


    David Reed – your post looks like a sneaky add for a pharmaceutical company. While the individual ingredients in Enlyte may be helpful, a one-size-fits-all approach simply does not work for those of us with these mutations. After 5 years of dealing with tweaking these and other supplements for the variety of mutations mentioned in this thread for multiple family members, I can tell you that your Enlyte product could a) be harmful for some in my family, or b) be ineffective.

    Other posters have called out for a reasoned approach of working with the supplements individually to come up with a customized cocktail. Not a bad approach, but we’ve also found that the cocktail changes over time as pathways open up and detoxification happens. And there’s no substitute for working with an expert doctor who can prioritize what supps to use when for the smoothest recovery over time.

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