MTHFR Gene Mutation possibly linked with Endo

Today I have found some unusual information regarding another possible contributory factor in endo. This time a mutated gene is implicated. I tripped over the information by chance when dabbling in xenoestrogens and the anti-oxidant glutathione on the internet. I'll try to explain as best I can but best to check for yourself.

Methyltetrahydrofolate Reductase (MTHFR) is the gene in question. A particular mutation (there are a variety of mutations and you can have more than one) of this gene may cause deficiency in SAMe and glutathione which both help eliminate xenoestrogens. Endometriosis is oestrogen dependant so if our levels of oestrogen are high in relation to progesterone, that can be a contributory factor in the spread of endo. If the gene is faulty then our ability to methylate is poor. Methylation occurs at a cellular level and turns one substance into another so it is detoxified and eliminated from the body.

Some believe that a fault with this gene has something to do with many conditions due to the reduced capability to detoxify the body. There's a very long list that includes conditions that can be concurrent with endo such as IBS, fibromyalgia, chronic fatigue syndrome etc.

I was surprised to discover that attempts to limit the impact of this gene mutation can be made by using supplementation. In particular, methyl folate (an active form of folate) and Methyl B12 and N Acetyl cysteine (which is name checked on another thread I started). However, I don't think getting dosage correct is straightforward and I still need to understand this. It is the sort of thing that needs to be done carefully with a doctor who understands this or is open to learning about it as it is quite complex. Inflammation needs to be reduced first.

I will be raising the whole subject with my doctor in March. I would not recommend treating this gene mutation without a decent doctor. If I manage to decipher anything materially useful I will report back. It would be interesting to know if any of you have heard anything about this.

Here are just some of the sites I came across. If you have a lot of tim! do have a good read and if makes any sort of sense, build your case and badger your doctors.

This whole site is dedicated to this subject

An excellent mindmap

A couple of informative articles

Faulty methylation

Methyl Folate side effects

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27 Replies

  • Thanks for this - you are obviously a scientist ! This is exactly what my medicinal herbalist has been talking about lately.She believes that many with endo have a genetic mutation which means the liver can't detox at stage 2.

    She is currently working on my liver function ,digestion,immune system but has mentioned supplementation with methyl B12.It is available as a supplement for endo,but is very pricey so I have decided to wait see how other approaches help first.

    Very interested to hear how you get on -is you DR on NHS?

  • Hi daffodil,

    No! I'm not a scientist at all! Health is rubbish for 1 week a month and getting worse so can't get a job now. I'm too busy working on Project Me anyway! ha ha!

    It's a long story but by chance I ended up at a private GP 7 years ago. I have stayed with him even though he costs a fair bit. I'm going to email him first and see how knowledgable he is but am thinking of trying to find someone like your medicinal herbalist. I'm with a chinese medicine practitioner for now but feel something additional is required.

    I learnt that inflammation has to be reduced if treatment is to be effective so beware of just taking methyl folate and methyl B12 without addressing this.

    Hope what your trying at the moment yields results.

  • Wow -you are a very educated lady then ! I have also had Meningitis so suffer with memory loss but know we have chatted before here! I find it vey frustrating not to be able to absorb new info,like I used to be able to,but am always researching my conditions and possible cures!I used to be a teacher,pre Meningitis in 2008.

    Make sure you get a herbalist who is member of national institute of Medicinal Herbalists,as they are very highly trained - as long as medics.I have been through an A-Z of complementary therapies for endo,ME,meningitis etc but my herbalist is the best informed and I trust her judgement.My herbalist is actually very reasonablypriced compared to other complementary therapists I have seen,but there is also the additional cost of any supplements.

    I am taking turmeric capsules for inflammation and most interestingly,my inflammatory markers have not been through the roof even though I am in severe pain.On previous endo flares,they have been very raised but my GP is puzzled,but wont believe it can be the turmeric !My gynae,who is one of endo speciaists has shown interest in my herbalist treatments,though still advocating total hysterectomy.I also took a months supply of Serrapeptase,but as endo flared so much and I landed in hospital with kidney infection I got a bit scared and stopped it.

  • Don't know about educated! I know we have chatted before but I couldn't tell you what it was about! My memory has been impaired since 6 months of zoladex a few years ago (prep for op). My memory used to be amazing and I was very thankful for that.

    Have you ever heard of mindmaps? I find they help with ability to absorb and recall info especially when it's all so complex. One of the links above is a mind map and describes everything far better than prose. Search online for Tony Buzan mindmaps.

    Really glad to hear your herbalist is good. I didn't know much about herbalists so thanks for the tip. This might be the way to go with this gene mutation thing.

    Sorry to hear you are in so much pain.

  • Some great information there, thank you.

    I have two daughters (and a son) and worry that they may go on to develop Endo. I wonder if there will ever be gene therapy and screening to predict the chances of developing Endo ?

    Kind regards,

    Barbara x

  • Hi Barbara,

    Reading through the avalanche of info, testing for the gene mutation/s is possible now. I still have to look for somewhere in the UK.

    I have learnt that you can either inherit a gene mutation or develop it in your lifetime due to environmental factors.

    So theoretically you could get your daughters tested for the gene mutation now. If it's ok, then I guess you would attempt to eliminate the endo triggers from their lives and encourage super healthy organic eating to minimise the possibility of the gene mutating....easier said than done!

    I'm not completely clear on how the gene is related to endo but here goes....I think that if there's a specific mutation then certain processes do not function properly, in particular detoxification due in the main to lack of active methyl folate because folate in the diet can't be methylated. (Remember I mentioned your tiredness might be due in part to low folate?!) A battle goes on in the liver trying to process everything and as a result, it is unable to get rid of toxins, heavy metals etc. in an effective manner. Oestrogen doesn't get eliminated effectively either. If endo is laid down when we are embryos then this scenario creates the right environment for it to spring into action and flare up. Either that or the toxic environment causes the endometrium to degrade and bits of it then migrate to the abdominal cavity via retrograde bleeding or to other part of the body by the lymphatic system.

    If that is the case then the next generation will suffer a huge increase in the incidence of endo, not to mention all the other awful diseases and conditions. This is the first thing I have seen that makes the most sense of all the pieces of the jigsaw and I intend to start pursuing it. But I'm aware it could be just one factor in the mad endo nightmare and I might be barking up the wrong tree!

    I understand your worry. I had been thinking of writing about how to protect the next generation of women.

    Hope you're well x

  • That all makes sense,

    I have been researching the real cause of endometriosis. Genes are obviously involved but I'm trying to find out to what extent.

    The environment also plays a key roll,

    We cannot find a cure for endometriosis because we do not know what causes it.

    I would also love to do a straw poll on the link with BMI and Endo. Some studies have found that leaner women are more likely to have Endo. I'm not so sure though. I have a BMI of 30 and have Endo for 20+ years. I have never been classed as LEAN!

    Also fat produces oestrogen which feed Endo..... So surely overweight ladies have more chance of developing endo.?

    Carry on with the great research'

    Barbara xx

  • I am 'lean'. Lean doesn't necessarily mean healthy though. Lean people can have visceral fat around organs which is really bad and can increase inflammation. Someone overweight might have less visceral fat but more subcutaneous fat.

  • Sorry to bore you further..... But I read some research that a new diagnostic test is being researched.

    This involves taking a a small sample of the endometrium and looking at the minute differences in suffers of Endo and non suffers.

    During the research stage the results have been overwhelmingly accurate.

    Fingers crossed it will stop any ladies having to go through a laparoscopy just to diagnose Endo.


  • Not boring at all! A step in the right direction.


  • Wow very good info! I will show my gynae dr too xxx

  • Hi, just had a look at Pubmed (main medical papers online database) and only found one paper searching for MTHFR and endo.

    Szczepańska M, Mostowska A, Wirstlein P, Lianeri M, Marianowski P, Skrzypczak J, Jagodziński PP. (2011) Polymorphic variants of folate and choline metabolism genes and the risk of endometriosis-associated infertility. Eur J Obstet Gynecol Reprod Biol. 157(1):67-72

    The authors state in their conclusions:

    "Our study did not show an association of the 16 studied SNPs in 12 folate and choline metabolism genes, namely BHMT, BHMT2, CBS, CHDH, CHKA, MTHFD1, MTHFR, MTR, MTRR, PCYT1A, PEMT and TCN2, with endometriosis-associated infertility. We observed an interaction, however, between MTHFR Ala222Val and PEMT rs4244593 polymorphic variants in infertile women with endometriosis."

    Translated in to lay terms this means that there is only a small correlation between mutations of genes in this family (MTHFR specifically) and endo-associated infertility. SNPS are small nucleotide polymorphisms, or point mutations in the gene sequence.

    There are more studies listed on Pubmed looking at MTHFR and inflammation-associated pathologies, such as MS, pancreatitis etc, but no endo per se.

    Note of caution: some of the sites you linked to have no proper scientific references, becareful with info in these. As a scientist myself, these worry me a lot.

    Also, there is a wide body of literature on MTHFR which, as for any scientific question, can be contradictory. So again, don't take these sites as gospel.

    Hopefully the discussion with your doctor will clarify things, do keep us posted.

  • Hi bio_is,

    Oh that puts a spanner in the works! Thanks for the info on the paper. Did they test for 1298 also? I still feel that gene mutations (of any gene) could be part of the story but the needle in the haystack has to be found. I know someone currently researching an enzyme in respect of endo which could just be something further along the gene mutation pathway. Even if it isn't this gene, there does perhaps seem to be some link with the body's ability to detoxify and eliminate which of course is related to methylation, folate, glutathione, etc.

    I do completely understand your concern. However, I don't make any firm claims in respect of what I have found and my posts are tempered with the words 'possible', 'if' and the need to check this for yourselves and ask doctors. I have also acknowledged that I may be barking up the wrong tree and that this could be just one factor in the whole story. But I do think that further investigation is warranted. Also, I am aware that some women using this site suffer from additional conditions and diseases that have been linked to mutations of this gene.

    I am also quite willing to explore approaches that have not been underpinned by scientific references. I am using chinese medicine at the moment and it has been helpful. Fortunately I have an open minded doctor.

    I will continue to post info that seems interesting but leave it up to others to decide for themselves. I always caveat the info...people are going to search on the internet anyway whether I post the links or not! I would also add that I have come across the suggestion that only about 50% of scientific research papers are reliable!

  • Hi, I am fine with posting info to expand the knowledge, but a pet peeve is unsubstantiated info on certain websites, especially when "science" is used to peddle a new supplement or another. Not a peeve against your post itself, but some of the info in some of the links.

    Re reliability of scientific papers, well, there are issues with reproducibility at points for specific cases but peer reviewed science is the weapon we have against generalised biased claims.

    As I mentioned on my other answer, there is much we don't know about Endo biology and I am particularly interested in the link with metastasis biology and endo spread. I am not saying that endo leads to metastasis - just that there are parallels that can be explored. I am an endo sufferer myself and would like to further the knowledge in that context.

  • P. S. I have altered the thread title and included the word "possibly"!

  • Hi again bio_is,

    I've had a look at the paper you alerted me to and their quantitative conclusion seems to differ from your translation to lay terms.

    Your reading of the connection is that it is "only a small correlation" which I would read as being 'low' and not worth further research.

    The researchers conclude "Our results showed moderate evidence for the contribution of SNPs located in genes encoding folate and choline metabolism enzymes to infertility in women with endometriosis."

    The word they use is 'moderate'. If we apply the GRADE system of grading then moderate = further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

    They state they they discovered an "epistatic interaction between rs1801133 of MTHFR and rs4244593 of PEMT in endometriosis-associated infertility”. The epistatic interaction is what leads them to conclude the discovery of "moderate evidence".

  • In my field (cancer) a small correlation could be considered a moderate effect - a matter of language, I am sorry if it is confusing.

    I don't know enough about this specific field to comment further at this point, can have a further look if needed.

    There are definitively links between pro-invasion molecules in cancer and endo (i.e., some molecules that modulate invasion in certain cancer types seem to be also important for Endo). One of them is one which a PhD student of mine is working on (on the cancer context). Maybe some of the knowledge might help the Endo cause!


  • Interesting, I'm a negative reuses blood group (not a common one) I also suffer with psoriasis , on my scalp, legs arms and torso. I've had various treatments for it but the latest is that my consultant wants to try tablets that affect the liver, I would have to go for weekly bloods for liver function, I really believe that all this affects each other including my endo x

  • My Mum had endo and also bad psoriasis. I did wonder myself if there was some sort of connection. She's 85 and recently started taking manuka honey 10+ which seems to help.

    If there is trouble in one part of our body then it is bound to impact another aspect of our body. My Chinese medicine treatment focusses on the liver too. It is in fact a gland and is really fascinating. Have a read on Wikipedia. You might think I'm mad but I talk to my liver and sent good healing thoughts to it each day!

    I take a few things which some people think helps the liver but not necessarily proven. I drink hot water and with a few squeezes of lemon on waking. Honey in hot water is supposed to be good too. I juice beetroot and carrots and add other nice fruit and veg to make it taste nice. I drink dandelion or fennel tea, eat black grapes and cook with buckets of garlic.

    Good luck with the tablets. Do you know what they are? Let us know how you get on. x

  • Hi Brownlow - I just wondered if you have progressed any further looking at this possible MTHFR/methylation pathway link to endometriosis. I have done a lot of reading (it is a complicated topic!) and have also had my SNPs tested (via 23andme). Would love to compare notes (via PM) if your thinking and research has moved on (and especially if you have talked to your Dr - I have not gone anywhere near there yet!) x

  • Hi Penguin,

    I have also done a lot of reading on this and you are right, it's not straightforward!! I was going to post something on folic acid, folate, methylfolate etc. but it would probably be so long that nobody would read it! It's a full time job.

    I'm convinced that there are methylation and therefore detoxification issues with endo regardless of whether this gene is implicated. I spoke to my GP about it but we decided to defer doing anything until after my next period as I recently had a polyp removed and I need a bit of a break before I start trying anything new.

  • Hi

    Just stumbled upon this post and thought ... wow what a coincidence! ...

    At present I have asked my hemotologist and my daughters for the blood test for the MTHFR c677t mutation and also for the homocysteine test too. The reason I did this is because my mother has tested positive for the genetic mutation and also v high homocysteine. Her Dr has mentioned that all children should b tested for this too. All 3 od us r already under hemotology as we also r S Protein Defieicent which means we cannot break down blood clots. So far my mother to date has had 22 (many of these as heart attacks, PE's and strokes).

    My mother had major issues with her periods when I was a child, then was diagnosed with cervical cancer. She underwent an oophorectomy and total abdominal hysterectomy age 40. I strongly believe she has severe endo and her diagnosis was missed.

    My reasoning for this is because I too have severe stage 4 endo and I know my symptoms etc were exactly the same as my mothers. I have had 2 major surgeries for my endo and this year underwent a subtotal hysterectomy and oophorectomy for my endo. My daughter (age 17) also has exactly the same symptoms and will undergo her laparoscopy on 28th May for this, although our surgeon says he is fairly sure she also has endo too :-/

    I have requested these blood tests be done for my daughter and me, not because we have endo but because it is genetic and due to my mothers diagnosis we also must b tested. This is the 1st thing I have read that suggests it may b linked to endo .... tho I'm not that surprised. I will however talk to the surgeon when we see him on the 28th about it.

    My daughter is also Chronic Neutropenic which means she has a much lower than average immune system and needs to b very careful. She has spinal fusion surgery 2 years ago for a very severe spinal curvature which I also believe is linked to this mutation.

    I think there could b a link here!! Certainly seems like it to me anyway :-/ Have been awaiting a call from the hemo all week now and he has already recieved the letters confirming these conditions from my mothers Dr's. Can't tell u anymore just now tho until he does the tests and the results r back.... Wish he'd hurry up with it all.

    Thanks for the post too... very good idea

    Cheers Mia x

  • Hi Mia,

    Your family have been through a lot. Hopefully you are now starting to find reasons that will help you find solutions. A total hysterectomy and oopherectomy by laparotomy is also being suggested to me. Hence my need to research everything.

    When it comes to endo, yes I think if that gene is mutated in any way then you will have problems methylating folate and folic acid into a form that is used by the body. This situation eventually leads to the high homocysteine but additionally it has been discovered that high levels of unmetabolised folic acid in the bloodstream is associated with reduced natural killer (NK) cell cytotoxicity (ability to kill cells). And what do women with endo have?.....deficiency in natural killer activity. There could be other links and pathways but this is the main one I've figured out. It's not necessarily causative that I can yet see but possibly contributes to endo's proliferation.

    Therefore the basic key to this is to treat with a form of folate that the body is able to use. It's called methylfolate, metfolin or 5-MTHF. Whatever you do don't take folic acid as this will only make your situation worse and is very dangerous. B12 is also required and dosages of both need to be carefully chosen. Other problems can arise if this is not treated properly.

    Did you know that the UK government is considering adding folic acid to bread? There are people out there with the gene mutation who could end up in serious trouble over this. I'm thinking of starting a petition and lobbying my local MP.

    I have done a great deal of reading on this subject and I know another forum user has also independently come across MTHFR and is researching. I hope to write up something about it to explain a bit more. I feel it is only part of the endo story and prefer to have a multifaceted approach to dealing with endo. If women with endo do not have the gene mutation I still believe there could be problems methylating folate so it can still be a factor.

    Please PM me if you'd like to exchange contact details for a chat. I think it would be useful in putting our minds together on this with a view to sharing our findings with others. Also, it will be helpful to you when you go to your surgeon on the 28th. My bet is that he won't have a clue about this so you will need all the research ready at your fingertips to convince him. xx

  • Of course, I completely forgot, the mutation can ultimately lead to a deficiency in SAMe and glutathione. They both help to eliminate excess oestrogen and we all know that endo is oestrogen driven!

  • Hi Brownlow,

    I have pm'd u about it :-) I'm afraid that I'm still in the early stages about finding out about MTHFR and homocysteine stuff, and I'm REALLY bowled over by how much info there is and exactly how much of that I REALLY dont understand .... yet! ;-) I am sooo confused! I think there is alot of similarities tho and would love to keep in touch. Feel free to email me about it ;-) Did u also know that there is many great pages on fb relating tho this? If not then I could send u the links for them, just let me know. .(maybe u can help me understand it all) Lol!! My daughter and me have many other medical issues and this is just the most recent. To make matters worse we both r S Protein Deficient too which means if we do get a blood clot that our bodies r unable to break them down... not a great thing if we test positive for the MTHFR, so obviously we r worried. I also have psoriasis and major allergies, cellulitus from bites etc, slight scoliosis of my spine and osteo-arthritus there because of that. My daughter also has something called Drusens which is a swelling of her optic nerves and in May 2012 she underwent an enormous surgery to fuse her spine for a very extreme form of Scheurrmanns Disease (she became a hunchback in 11 months) ... which took her a whole year to recover from. Phew! Glad that one's over with!! All of these things I have also found out can b linked to MTHFR too..... I have a very suspicious feeling that we will both test positive as these r very rare problems ;-/ Anyhow, feel free to mail me anytime :-D Take care and speak soon, mia xx

  • I've had endo since menarche at 15, finally diagnosed in 2009, though I had suspected it for years beforehand. My family also has a history of health issues that are commonly seen with the MTHFR defects, but it wasn't until my son was born with a tongue tie that I started to research causes and that led me to MTHFR. When I saw the list of common ailments associated with this defect, I realized I probably had the gene so got tested with 23andme. I'm still wading through a lot of information with the help of 2 family members (both biologists and able to 'translate' the research into layman's terms), but methylation plays a big role in the breakdown and elimination of estrogen. It's an essential part of Phase II detoxification in the liver, so if there is a block anywhere in the methylation process, estrogen will remain in the highly reactive form produced by Phase I detoxification instead of going on to be broken down in Phase II and then eliminated. It remains in the body and does all sorts of damage. Meanwhile, the endometrial implants and healthy endometrial tissue in the uterus go on merrily producing MORE estrogen, further overburdening the detoxification process and having all sorts of other unpleasant side effects. For instance, there is some evidence that women with endometriosis often have insulin resistance later in life to a much greater frequency than in the general population. MTHFR genes are not the only culprits either; there are several other genes that contribute to methylation (as mentioned above) and other associated processes in the body that can directly impact hormonal regulation. If I've learned anything, it's that to look at just one gene or group of genes in isolation is too small a view; as a PP has already mentioned, endo is a multifaceted disease in terms of contributing factors and possible causes. However, from a personal standpoint, for the last 10 months (since September 2013) I have been actively working to address my endo with significant lifestyle changes, and seen some huge results. These changes were: diet - actively avoiding all estrogenic foods for the first few months, and only gradually reintroducing the whole foods. I focus on whole, unprocessed foods, only healthy fats with lots of veggies, especially leafy greens, healthy lean veggies, whole grains (avoiding wheat and other gluten sources), no GMO products. Exercise - I cycle to and from work daily, about 40 minutes in all, 5 days a week. Eating patterns: smaller meals but protein-rich snacks between meals, so I'm eating every 3 hours until about 6.30-7.00pm. No more energy crashes! Acupuncture and Chinese herbs - working with a fantastic Chinese doctor. And finally, supplements. Lots of them. As the OP mentioned, MTHFR is pretty straightforward in that it can be addressed pretty well with a few supplements, but guaging how much and how to take them takes a little homework. In addition, if you have an ongoing condition (like endo) then you may need to look into other supplements. Since I started this program, I've lost a stubborn 25lbs in the first 3 months and kept it off without eating less or going hungry - i'm at my ideal weight and steady. Pain during periods has been majorly reduced, as has duration and intensity of flow, my skin is better, my hair and nails are healthier, I rarely get sick, my IBS has only flared up once in all that time, my concentration and focus is better, my moods are more stable - I could go on, but you get the picture. Endo responds really well to dietary and lifestyle support - I recommend the website - this lady resolved her Stage IV endo entirely naturally and has a lot of great pointers. Just remember she's not a doctor, merely a former sufferer passing along what she has learned. Good luck to all you ladies who've found yourself with endo - it's a sucky club to belong to.

  • Hi Bellenoune,

    You echo just about everything I have discovered. It's so nice to hear from someone who has done their research and implemented changes that have helped. I have also altered my diet to something similar to yours and the results have been very good.

    I agree with you about not focussing on just one gene. What I took from the information was that faulty methylation could be a key culprit.

    Unfortunately 23andme are being reviewed by the FDA and are not permitted to provide the gene profiling service while this is happening. It all seems rather strange.

    I'd be really interested to hear about what Chinese herbs you are taking. I took some for about 3 months and noticed an improvement which has lasted. Also acupuncture and now reflexology. I'd also love to know what supplements you take. I'm always in a quandary about these!

    I hope your little boy is ok now and your health continues to improved.

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