I have been asked to write about how MTHFR (Methylene tetrahydrofolate reductase) genetic mutations relate to fluoroquinolone toxicity. The question is – Are people with MTHFR and other methylation-related genetic mutations more likely to get “floxed?” And, can addressing methylation issues help “floxies” to heal?
I think that the answers to both are yes. However, that’s about as far as my insight into the matter goes. For some reason, I have been reluctant to study genetic mutations and how they relate to FQ toxicity. It has been too daunting for me, thus far. So, I’m going to post some information that I found interesting about MTHFR mutations / methylation. For more thorough information about genetic variations/SNPs/mutations, I suggest that you look through the following sites:
All of the people who run those sites are familiar with fluoroquinolone toxicity, so please reach out to them if you have any questions. Dr. Amy Yasko also has a lot of great information about methylation, but I’m not sure whether or not she’s familiar with FQ toxicity – http://www.dramyyasko.com/our-unique-approach/methylation-cycle/.
Here are a few things about MTHFR mutations that I found to be interesting, so I’m sharing them with you. Please note that these are interesting observations from other floxies, not peer-reviewed journal articles.
From fellow floxie Ken J:
If memory serves many people get some help from fish. Many types of fish are high in b12. in fact things like beans, fish, leafy greens they each contain parts of the b12 folate and b6 cycles.
Funny thing about the B12 is it’s not naturally occurring in plants… or animals for that matter. Only certain types of bacteria can create it and those bacteria can accumulate in animal meats like liver, beef, fish, eggs ect.
Deficiency in B12 has symptoms like:
Weakness, tiredness, or lightheadedness
Heart palpitations and shortness of breath
A smooth tongue
Constipation, diarrhea, a loss of appetite, or gas
Nerve problems like numbness or tingling, muscle weakness, and problems walking
Mental problems like depression, memory loss, or behavioral changes
It can also result in high homocysteine which carries increased risk of heart attack, embolisms, stroke and bone breaks, as well as neuropathy, twitches, tinitis, nerve damage, and dementia like issues.
I’ve been shown in tests to have low folate and b12, and high homocysteine. Recently my homocysteine levels were 35mcmol/L where the standard should be 5-10. this is after the prescription of a z-pak antibiotic (post-flox).
The catch for me, and I find myself wondering if it may be the case for others, is I have a gene variant known as MTHFR that effects part of my bodies handling of b vitamins, and some variants in MTRR genes, which also relate to b vitamin cycles, predominantly in relation to neuro transmitters.
Where this becomes a problem is that the common vitamin supplements and “enriched” foods that use folic acid, b12 and other b vitamins, not only can’t be used by my body, but actually clog up things so they can actually behave like blockers for the natural FOLATE and methylcobalamin (b12). Making symptoms worse. and these fortified ingredients are everywhere.
So what does that have to do with the price of rice? or floxing? Turns out the cycles these vitamins regulate (and thus deficiencies or genetic variants that can cause deficiencies) are the methylization processes the body uses to get rid of toxins including the effects of some antibiotics. So an antibiotic may very well be the thing that sets things off balance and crash the whole house of cards.
I can’t say one way or the other if that is the case for other people, but I would definitely suggest anybody dealing with the effects of a floxing, get their folate, b6, b12, and homocysteine levels checked (and Vit D check wouldn’t hurt either). That will tell you some very important things to know.
I know about my gene variants because I’ve done genetic testing through 23and me and had my raw data checked against key genes in the methylization cycles through another site online. Some doctors can do a check for MTHFR these days as it’s starting to get attention. if you know or think this is an issue for yourself or a loved one, please use food sources of these vitamins rather than enriched, fortified or supplements until you can work with a nutritionist/holostic practitioner to get the right kinds of supplements that won’t actually make things worse. (Salmon, beef, liver, shrimp, clams, makerel, cod – for b12; beans, lentils, spinach, for folate; spinach, potato (including sweet potatos), and poultry for b6).
I think that getting B vitamins from foods that naturally contain them, and avoiding fortified foods, are excellent recommendations. Just a little personal note – I drank tons of kombucha post-flox. It is a good natural source of folate, B12, and other vitamins. Maybe it helped me to heal. I’m not sure, but I really do love the stuff.
Ken’s note also got me wondering if all antibiotics, not just fluoroquinolones, are killing our B-vitamin synthesizing bacteria and leading to high levels of homocysteine which leads to all sorts of ailments. Maybe… to be explored.
I also found the following information, posted by Carol on FB, to be interesting:
HISTAMINE REACTION… After taking NIACIN
If you took NIACIN and flushed and developed terrible itching that was not an allergy.
Flushing and itching is what would be expected to happened to a person who is an under-methylator. An under-methylator is someone who doesn’t have much SAMe to work with because their “Methylation Cycle” is not working very well due to any of the following genetic enzymatic variances.
MTHFR C677T…poor production of L-Methyl Folate
MTRR [slow]…trouble making Methyl-B12
MTR [slow]…trouble transferring a methyl group onto HOMOCYSTEINE
MAT [slow]…trouble turning Methionine into SAMe
CBS [slow]…a backup of the “Transsulfuration Pathway”
BHMT [slow]…poor conversion of Homocysteine into methionine in the LIVER and KIDNEY
When a person already has few available SAMe molecules and then they take Niacin they will develop this expected reaction of flushing and itching, but it is NOT an allergy.
………………..THE BIOCHEMISTRY….for those who are interested in details…….
The enzyme that inactivates Histamine inside cells is called Histamine-N-MethylTransferase [HNMT].
The HNMT enzyme requires SAMe [S-AdenosylMethionone] in order to do its job of inactivating histamine.
When such a person who doesn’t make enough SAMe takes Niacin their SAMe gets totally all used up.
Now, because there is insufficient SAMe the histamine doesn’t get inactivated as it should and the person will flush and get itchy because of the excess histamine that cannot be inactivated because of the lack of SAMe.
HISTAMINE Metabolism…HNMT enzyme uses SAMe to inactivate Histamine
Well, that struck a chord, because about 6-months post-flox I took a niacin supplement and proceeded to break out in hives all over my body and I turned a lovely shade of reddish purple. I went to the doctor and she said, “yup, it’s the niacin.” I haven’t gotten my genes analyzed by an expert yet, but I certainly understand that I had a massive histamine release upon taking niacin, and that that’s an indication that I’m an under-methylator. Noted.
The tie-in of methylation and histamine is interesting too. Most floxies have symptoms of histamine intolerance. More information about that can be found in this post – https://floxiehope.com/2015/10/01/can-fluoroquinolones-activate-mast-cells/
Before you do anything to address your methylation issues, I encourage you to speak with an expert about it. The people who run the above-referenced sites can help you to analyze your genetic profile, and with that information it is best to consult with a doctor or naturopath.
Fellow-floxie Jason asked me to share this write-up:
Hello all. I’ve been researching Genetics and Methylation quite a bit in the last half a year, and I think of the few possibilities of why some people take a long time to heal, and why some never appear to heal at all, this has been one very very important reason that has been significantly overlooked and underestimated by the entire Floxie Community for a long time (of course in the Medical World this is all ‘relatively new’ though). I would like to discuss some aspects of this potential reason, and why I think they are important, in hopes that some struggling Floxies and anyone else out there suffering ‘might’ just find some healing.
Methylation is behind MANY important process’s in the body (DNA activities and detoxing 2 big ones for Floxies IMO), and many experts like Dr. Amy Yasko and many more are finding that by testing and then treating people accordingly, many find relief from serious multi-year Malaises. Here are some reasons why (this is not a full list) Methylation can be very important to finding good health for many people:
– Repairing and Building DNA & RNA
– Glutathione synthesis and Detoxification
– Controlling Inflammation
– Myelination (very important in nerve health)
– Metal Detoxification
– DNA Silencing
– Energy Production
– Immune function
– Digestive issues
– Membrane fluidity
– Homocysteine metabolism
– Gene expression
– Cardiovascular health
– Protein Activity
– Cancer prevention
– Neurotransmitter balance
All of these are incredibly important to Health, many are affected by Floxing some of which I’ll discuss, and then if Methylation is also impaired, healing will be that much more challenging IMO. It has long been thought by many experts that Autism and similar Mental Ailments, Dementia, Alzheimer’s, and then even things like Chronic Fatigue, etc can all be caused by Metal toxicity, and they now think these accumulate more in these people than the average person due to under-Methylation and impairment of the above body functions.
Okay so here is one small example on how it could apply to Floxies on only one aspect from above, where many are very important. Take someone with Peripheral Neuropathy for example, some quick searching reveals several sites noting chemo drugs (of which FQ’s are a “failed” one) can damage the Myelin Sheath. (There is one rat study that says 2 of the drugs don’t, so it might not be conclusive). Several sites also come up saying damaged Myelin Sheath can be the “cause” of PN.
Now take someone with an impaired Methylation cycle. You can take supplements til the cows come home, 25 different ones, but if they don’t address your impaired Methylation Cycle, Myelination is likely also impaired and the Sheath will still have trouble healing.
Another example with Tendons. Both Fluoride/Fluorine, and FQ’s, are widely known to disrupt collagen synthesis/metabolism, and can result in calcification of ligaments tendons muscle and thyroid cartilage and thus break down of the collagen, bone, tendons, skin, cartilage, lungs, trachea, and kidney etc. Many Floxies have reported loose joints and ligaments, tendon issues etc, almost like it melted away.
Here is what one website says about this: Quote “When collagen breaks down, tissues simply lose their substance, their framework. Fluoride dissolves the body’s glue simply by preventing new collagen from being formed. DR Y gives a masterful explanation of fluoride’s disruption of collagen, not only is the collagen incorrectly formed, it is wrongly mineralized. Some things in the body like bones and teeth, should be mineralized in order to give it hardness. Other collagen structures, like ligaments, tendons and, and muscles, should not be mineralized, in order to keep them flexible and resilient. Fluoride mineralizes the tendons, and muscles and ligaments, making them crackly and painful and inflexible. At the same time fluoride interferes with mineralization of bones and teeth, causing osteoporosis and mottling or dental fluorosis.”
Here are a few other websites discussing the Fluoride aspect of this, there are many studies out there on this and then also on how the FQ’s do tendon damage as well:
Here are a couple more good links on Tendinitis, Tendonosis, Tendinopathy:
Why this is all important I think, is related to a couple quotes from the last website linked, noting “the Tendonosis cycle begins when breakdown exceeds repair,” and “Tendinosis (including Achilles, rotator cuff, lateral and medial elbow, posterior tibial, digital flexor, and patellar), as well as carpal tunnel syndrome and even TMJ disorders are associated with a failed healing response in which the body’s fibroblasts produce abnormal tendon and ligament collagen”.
Now I would like to take those statements and relate them to Floxies, DNA and Methylation. DNA damage, can cause “abnormal DNA” to be formed when DNA is getting rebuilt for some time, until the body slowly corrects this through its DNA repair process, if the process is working and if it is not being overwhelmed by continual damage from more toxins being released or reintroduced. IF DNA is the core of the problem for any injury (not saying it is for Floxie tendons etc, but the FQ’s DO damage DNA), and in the case of tendons not from other things like overuse, inflammation etc, its easy to see why NO supplements and/or therapies etc once again would seem to help someone who’s DNA repair process is hindered (unless they are addressing Methylation). However having said that, if there are many factors involved in the damage and not just the DNA, like inflammation adding to the problem etc, IMO this is where some things even other than Methylation supplements could likely help (In the case of my own Floxing where joints were falling apart for example, it was VERY noticeable the days I was away from home and not taking my usual supplements as things would always be worse, I was trying to at least ‘keep up with the damage’)
So another potential reason Methylation can be critical to healing here, because when it is inefficient/impaired, so is the DNA repair process. The more damage someone has, the more bad DNA gets churned out each time instead of good DNA, slowing and even preventing healing in some cases if the body is overwhelmed and not able to keep up.
Then there is the entire Detoxification aspect of FQ Toxicity and Methylation, which detox alone in my opinion is extremely important and again deserves its own article. I will keep this section relatively short though, bottom line the body stores toxins, Cipro is a very nasty toxin, it does a lot of oxidative and other damage like DNA damage. Fluorine is attached to the rest of the Cipro drug and has been cited to “mobilize” from body stores through exercise and other detoxification stimulating methods. If someone’s Methylation is impaired, their Glutathione synthesis and Detoxification ability can be impaired too, so instead of purging these toxins in an efficient manner probably like those that do not end up “Floxed”, much of it can stay stored and can occasionally circulate and do more damage, and then can be redistributed (reabsorbed) again instead of being excreted by the body, keeping someone sick for a long time or possibly even indefinitely. (stresses the importance of avoiding as many other toxins as possible as well)
This is a good little article with some great links in it and talks about the importance of Glutathoine, disease, the Genetic tie-in, and more. Here’s just one quote, “As Dr. Jacob Teitelbaum explains, your body needs ATP and NADPH (which requires TPP) to make glutathione. These building blocks may be low in people who have illnesses like chronic fatigue and immune dysfunction. It becomes a vicious cycle as excessive glutathione depletion causes mitochondrial dysfunction, low triphosphate and ATP which leads to chemical toxicity and medication sensitivity.”
http://phoenixrising.me/treating-cfs-chronic-fatigue-syndrome-me/treating-chronic-fatigue-syndrome-mecfs-glutathione-and-the-methylation-cycle/a-simplified-treatment-approach-based-on-the-glutathione-depletion-methylation-cycle-block-pathogenesis-hypothesis-for-chronic-fatigue-syndrome-cfs-by-rich-van-konynenburg-ph-d One more (long) link here from the late Dr. Konynenburg, talking about Glutathione, Methylation and more, how “his theory” started on why CFS is tied to Methylation issues, and about how he developed his own protocol for people, one that is still being used today by people in this forum linked. One quote, “Two of the most significant effects of a methylation cycle block are that neither the immune system nor the detox system can operate properly. If the methylation cycle remains blocked for an extended period of time, infections and toxins can be expected to build up in the body.”
So I talked about DNA repair before, now let’s look a little closer at actual DNA replication, and how it relates to repair, and to FQ Toxicity.
One of the most important aspects of the Quins, and why they are so effective against bad bacteria, is that they are designed to inhibit the DNA replication process of the bacterial cells, thus damaging the bacterial cells’ ability to reproduce. Here is just one study on this, I can’t remember how many others there are but I imagine there are a decent amount on this and recall reading at least a few in the past: http://jac.oxfordjournals.org/content/51/suppl_1/29.full.pdf
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1762815/ This is not about Floxing, but an interesting study on how quote “unequivocally, mtDNA mutations are an important cause of genetic disease”
The problem with this mechanism as we know, is this doesn’t just happen with the “bad” cells/bacteria, in typical Chemo-like fashion it ends up damaging the good cells/bacteria too. So that is the bad news.
The potential good news again, is Methylation can possibly come to the rescue, IF that is one big factor holding someone back. Here is one good excerpt from a paper on this, one why that can happen:
“The Importance of the Methylation Pathway – New cell synthesis and repair
Mutations in the methylation pathway can cripple the ability of the body to make the building blocks (purines and pyrimidines) needed for new DNA and RNA synthesis. A reduced capacity for new DNA and RNA synthesis means that any new cell synthesis is impaired. For an organism to live, it must create new cells as fast as cells die. This requires that the body make millions of cells every minute, relying on DNA and RNA synthesis. A reduced synthesis capacity due to methylation cycle mutations is a particular issue for cells that already have difficulties meeting their needs for DNA and RNA synthesis under normal conditions.
Adding a significant methylation issue to the cell synthesis makes it nearly impossible to recover from damage or stress on these tissues. Stress increases the need for nucleotides to overcome negative effects of hormones released during stressful conditions. Cell repair after injury increases the need for nucleotides. In particular, the nervous system has the highest concentration of RNA in the body, and therefore has the highest requirement of methylation need.”
So my summary to this and apply it to a Floxie:
FQ’s damage a cell’s ability to reproduce. Genetic Mutations in the Methylation Pathway can cripple the cell’s ability to reproduce. What do you get when you add these things together? A DISASTER.
Now add up all the above, and then start considering some of the other aspects I never even went into like Gut Health, Inflammation, Energy Production and more, and hopefully you see why I think this is so critical.
So in having said all this, what can someone do about it? Someone can have their Genetics tested, like through a service called 23andme (note there are 11 Methylation SNP’s missing from the test Amy Yasko does, and a bunch included she does not test the better value by far is the 23andme test, it is a shame those 11 are missing but 23andme does included the majority of the most important ones currently). With this test, someone can then do some of the reports linked below (I think the MTHFRsupport one is said to be the best by most people, they all have their advantages though, like free in some cases etc) which help take the raw Genetic Data from 23andme and group things together on a report (like for Methylation). Here are some of the most popular options:
I believe this one is considered of the best, I think it is currently $30
This one is Amy Yasko’s own website, and I think is free, I would also recommend this one:
Here is a link to another one “Live Wello” and some ideas on what else to do with it, it is $20, and is similar to the mthfrsupport one, both are good I think mthfr one is a touch better:
Here is one more thread I have saved with many people discussing options/ideas:
There is also Genetic Genie, it might be free or cheap not sure, I don’t think considered one of the better ones but might still be worth doing, not sure
Once someone has these reports, they can then consult a Doctor who has studied the Methylation Cycle and determine if they are having problems, and what they can do about it.
*** IMPORTANT NOTE *** – There are a couple dangers here, especially for someone already damaged like a Floxie. If someone has a “stalled” Methylation Cycle, and they jump start it too fast the body can dump a bunch of stored toxins all at once and overwhelm the system in a big way. There are sadly MANY reports of this happening out there, in the Autism forums, CFS forums and other places, it even happened here in this forum, and these reports are only the people that actually realized what happened too, I reckon many many instances go unreported. One way this happens is when someone has significant hindrances due to MTHFR SNP’s they have, which are fairly common. What happens here is the body now has trouble processing Folic Acid into an “active” (usable) form of Folate, which is greatly needed for the Methylation Cycle to fully function, and in some people this can be a huge factor that impairs the whole cycle. So why not just take active Folate then? Ah yes, this is exactly where people get into trouble, either through self diagnosis and treatment or worse they trusted a Doctor or Advisor who told them, “just take 400mcg of active Folate and you’ll be feeling better in no time” (more than one ‘prominent’ Doctor even recommends a dose that high to start). Oh they feel good alright, sometimes for a day, maybe even a week, then many get hit by a freight train, and it can take a VERY long time to recover from, Rene from this website took a full year to recover from this.
So anyone who suggests to “just take active Folate”, is someone to avoid, and even more so if the dose is above 200mcg to start IMO. Moreover though, there is MUCH more to consider here before ever taking Folate. Vitamin B12 is another very important nutrient needed in Methylation, and some people find they are too low in this Vitamin also, some are even too high, and some people have bad reactions to some types of B12 as well like Methylcobalamin for example. The reasons here lead into the next important point, there is MUCH more to Methylation than MTHFR, Dr. Amy Yasko has outlined roughly 25 other important Genetic SNP’s that all play a part in the Cycle. Her focus is somewhat on Autism and thus her approach to treatment is on the cautious side IMO , however to me it does not undermine the importance she stresses on why some other important things in the body and Meth Cycle need to be addressed before someone ever adds active Folate, and to me they definitely apply to a Floxie here. This is a whole other in-depth topic beyond the scope of this article, however I will give one or two small examples. The Gaba/Glutamate balance is very important in Autism, Dr. Amy warns that this needs to be addressed early on in treatment or issues can be exasperated, many Floxies also have this balance disturbed due to Gaba receptor damage, so to me this is big one. For another, “CBS” is an important Methylation Genetic SNP discussed by Dr. Amy, it is an “upregulation” in the Methylation Cycle, that causes some undesired effects, if you start kick-starting the cycle more before addressing CBS you once again exasperate this issue. This all starts to get very complicated, for people that want to learn more I highly recommend downloading Dr. Amy’s 247 page book here (remarkably free!) and note the title is very misleading, this is mostly about the Methylation Cycle: http://www.dramyyasko.com/wp-content/files_flutter/1327512160_9_1_1_8_pdf_02_file.pdf
One more note here, as you can start to see from this section, much like Floxing itself, there is no “One size fits all”. Everyone has different Genetic variations, and only through testing and proper educated analysis can someone come up with a meaningful treatment plan to address their own personal shortcomings taking all the important SNP’s, and then their other many important personal factors into account.
In closing, I just want to say that though many suffering people out there are finding levels of success through Methylation supplementation, and to me it looks promising for some Floxies which I hope I outlined why; it takes a good amount of dedication and time, and right now there seems to be very limited reports out there on Floxies getting treated for this. So I’m not making any promises with all this info, its not a quick fix, and I’m not suggesting everyone run out and get their Genetics tested necessarily (even though I generally think it is awesome important info to have on yourself). However, I do hope the many points made throughout the article do get some of you thinking about the real possibility here, that Methylation could be a key factor behind why some Floxies are having trouble healing.
Good luck Floxie Friends. I really do hope, that this gives some hope to some of you out there, especially those Severely Floxed people who I think this is going to apply to even more so, and who really need that hope, and potential help, more than ever. My heart goes out to each and every Floxie out there. God Bless you all.
Thank you, as always, Jason! Those of you who follow the comments on this site know how much time, effort, dedication, and insight Jason puts into his posts. He does it all to help us – what a rockstar! 🙂
Last, but not least, Nancy wrote this in a comment:
I suspect some of you know of or have heard of Shawn Bean and Jess Armine over at Bio-Individualized Medicine since they tend to treat a lot of folks who have been floxed and/or who have chronic disease. I believe that the folks at the MTHFR team looked at the genetic tests (23 & Me) of 38 different floxies using Sterling Hill’s interpretative software and discovered that almost every floxie (in the group of 38 they examined) has one out of these three SOD mutations:
rs2855262 and/or rs4880
I thought this information would be of interest, particularly since the topic of SOD came up during this podcast.
I don’t know about you, but I find all of this to be quite daunting. I have no doubt that genetics and methylation are big parts of the FQ toxicity puzzle, but it’s still, well, daunting. At the same time though, it’s interesting and figuring the floxing puzzle out is exciting and valuable. I hope that those of you who are interested in this path find some answers either through this post or through the links in the post! Whether you find it interesting or not, I hope that it leads you toward a path of healing.
Please be cautious when trying to treat methylation problems. Again, it is something that should be done under the supervision of a professional (a doctor or naturopath or other expert).
Please also remember that your genes are not your destiny, and that people with all sorts of genetic mutations have thrived for all of human history. Lifestyle and epigenetics matter, and you are not, by any means, doomed.