Tag Archives: magnesium

Floatation Therapy for Fluoroquinolone Toxicity

From the ages of 12 through 18 (1992-1998) I lived in a big, somewhat ridiculous, but interesting, house. One of the ridiculous but interesting things about it was that there was a sensory deprivation tank in the attic above the master bedroom. We never used the sensory deprivation tank, which we referred to as “the floatarium,” because we had no idea how to hook it up or work it, and because it required that we haul 1,000+ pounds of epsom salt up several flights of stairs and a ladder to the attic where it was stored. To give you an idea of how out-of-the-way the floatarium was within the house, we surmised that either the house was built around it or that a crane was used to put it in through the roof–there was no way anyone could have gotten it through the front door. Anyhow, it was a novelty that I haven’t thought about much since the 1990’s.

I bring up the floatarium because I just got done with a session in a sensory deprivation tank, and I wonder if it would be good for my floxie friends. There are a few components of floatation therapy (apparently “sensory deprivation tank” sounded too severe, so most floatation spas call it floatation therapy or REST–Restricted Environmental Stimulation Therapy) that I think can be beneficial to floxies.

First, it’s a way to deeply meditate, and meditation has many demonstrated health benefits. I found meditation to be immensely helpful in my journey through fluroquinolone toxicity (you can read more about my thoughts on meditation for floxies here, here, and here). As a facilitator for meditation, floatation therapy is wonderful.

Second, floatation tanks are filled with 1,000+ pounds of epsom salt, which is magnesium sulfate. Magnesium has helped to alleviate many symptoms of fluoroquinolone toxicity for many people. Floatation may be a good way for floxies to soak up a lot of magnesium. It’s significantly more concentrated than any epsom salt bath you’re likely to take at home. It feels like soaking in magnesium “oil” (many floxies have found topical application of magnesium oil to be helpful), and I emerged from the tank with my skin feeling silky, smooth, and as if it was covered in magnesium oil. Magnesium also has many health benefits, and I wonder if many of the health benefits that are attributed to the meditation and sensory deprivation aspects of floating are actually from soaking up a large amount of magnesium. I think that both are generally good. (However, if you have any sort of kidney issues, or sulfur metabolism issues, magnesium sulfate can be harmful, so please be cautious and talk to your doctor about these issues.)

Third, floating is relaxing. When you don’t have any visual, auditory, or tactile sensory input, you are able to rest, relax, and just be. A lot of floxies suffer from anxiety, and floating may be a good way to relax.

Personally, I felt pretty good going into the floatation tank, and I felt even better–with a nice sense of peace and wellbeing–after I emerged from it. I think it was good for me, and it may be good for many of my floxie friends.

Some of the studied benefits of floatation therapy are noted in Discovery Magazine’s article, “Floating Away: The Science of Sensory Deprivation Therapy.

“In the early 1980s, a group of psychologists at the Medical College of Ohio initiated a series of experiments that looked at the physiological responses to REST. Both within and across flotation sessions, blood pressure and levels of stress-related hormones dropped – effects that persisted long after the cessation of the last flotation experience. In 2005, a meta-analysis further confirmed that flotation was more effective at reducing stress than other popular methods such as relaxation exercises, biofeedback or relaxing on the couch.

These results prompted researchers to investigate whether flotation could help patients with stress-related disorders. The treatment was used as a primary intervention for disorders as diverse as hypertension, headaches,insomnia and rheumatoid arthritis; all of these studies showed positive effects in small sample sizes. Those suffering from intractable chronic pain particularly benefited from weekly REST sessions: their level of perceived pain dropped, their sleep improved and they reported feeling happier and less anxious. An ongoing project is investigating the use of flotation for fibromyalgia pain management with positive preliminary results.”

As the author of “Floating Away: The Science of Sensory Deprivation Therapy” notes, the sample sizes for these studies were small, but still, it’s interesting, promising, and worth a try for many people.

It should be noted that if your kidneys aren’t functioning well, or if you don’t respond well to epsom salt baths at home, floatation therapy probably isn’t for you. However, for many floxies, I think that floatation therapy has some interesting benefits that may be helpful.

For floxies and non-floxies alike, rest, relaxation, and even sensory deprivation are healthy and helpful. For those who have access to a floatation spa (they can be found in most big cities), it’s something to look into.

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Mitigating Fluoroquinolone Damage

What if a loved one must take a fluoroquinolone because it is the only option available to save their life? How do they avoid getting “floxed” and experiencing the devastation that fluoroquinolones have brought to too many lives?

Undeniably, there is a range of reactions to fluoroquinolones – from people not reacting badly at all, to people being permanently disabled and in excruciating pain, and everything in between. If a loved one must take a fluoroquinolone because it is the only viable option, is there any way to push them toward the “not hurt” end of the spectrum?

Who Gets Floxed?

At this time, no one knows what makes someone susceptible to getting “floxed.” No one knows why some people tolerate fluoroquionlones well but other people don’t. No one knows why an individual can tolerate fluoroquinolones fine at one time, but have a horrible reaction another time. No one knows what genetic predispositions contribute to some people getting hurt by fluoroquionlones.

The epidemiologists say that the risk of fluoroquinolone-induced tendon ruptures is higher in those over the age of 60. However, there are many “floxies” under the age of 60, and many of them suffer from tendon ruptures and other musculoskeletal problems.

It is hypothesized in, “Fluoroquinolone Antibiotics and Thyroid Problems: Is there a Connection?” that, “anyone with any underlying genetic predisposition, or possibly harboring a subclinical, latent, or silent endocrinopathy might be ‘pushed over the edge’ into full blown clinical pathology” by fluoroquinolones. But I have a friend who is over the age of 60 and who has thyroid problems, as well as osteoporosis, who recently took a course of Cipro and was fine afterward. I saw her yesterday and she is doing well. I would have thought that she would have been predisposed toward an adverse reaction… but she wasn’t.

As a strong and athletic 32 year old who had no history of illness, I certainly didn’t think that I was predisposed to having an adverse reaction to Cipro, but it happened. Cipro made me sick for a while.

There seems to be a certain amount of “Russian Roulette” going on when one takes a fluoroquinolone. There aren’t any tests to determine who will react poorly to fluoroquinolones, and even known risk factors only sometimes make a difference. Some people seem to get lucky, while others get very, very unlucky. I realize that attributing adverse reactions to bad luck and “Russian Roulette” is a frustrating non-answer, but, unfortunately, that’s where we’re at right now – the land of frustrating non-answers. Welcome to being a floxie.

Despite the seeming randomness of adverse reactions, there is sufficient evidence that people who are over the age of 60, athletes, those who have a history of psychiatric illness, those with a history of benzodiazepine withdrawal, people who regularly use NSAIDs, people using corticosteroids, people who have an existing autoimmune or endocrine disorders, those who are immunocompromised, and people who have a mitochondrial disorder (in any of its manifestations, including ME/CFS and fibromyalgia) should avoid fluoroquinolones if at all possible. (More about this can be found in the post, “Don’t Take Cipro, Levaquin or Avelox If….” on Hormones Matter.)

When it’s the Only Option

Given that few people think that an adverse drug reaction will happen to them, and that antibiotic resistance is reducing the number of safe antibiotics available to treat many infections, many people are stuck with fluoroquinolones being the only option available to them.

If this is the situation for you (yes, I do realize that many/most floxies would rather die than take a fluoroquinolone again, but that’s not the case for everyone) or a loved one, is there anything that can be done to mitigate the damage done by the drug?

Maybe.

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Mitigating Fluoroquinolone Damage

Studies have noted that magnesium and vitamin E can mitigate some of the damage done by fluoroquinolones. In, Musculoskeletal Complications of Fluoroquinolones: Guidelines and Precautions for Usage in the Athletic Population, it is noted that:

“Pfister et al [25] studied the effects of oral vitamin E (tocopherol) and magnesium supplementation on ciprofloxacin-associated chondrotoxicity. Juvenile rats were divided into 4 groups: those fed a normal diet, a vitamin E– enriched diet, a magnesium-enriched diet, or a diet enriched with both vitamin E and magnesium. These diets were initiated 10 days before the rats were given ciprofloxacin. Two days after fluoroquinolone exposure, cartilage samples from the knee joints were histologically examined, and cartilage and plasma concentrations of magnesium, calcium, and vitamin E were measured. Fluoroquinolone-associated cartilage changes were observed in all groups, but the supplemented groups showed significantly less change, with the magnesium and vitamin E combination group demonstrating the least change. Both plasma and cartilage concentrations of magnesium and tocopherol were significantly higher in the supplemented groups than in the animals that received the normal diet, which supports the potential role of magnesium deficiency in the pathogenesis of fluoroquinolone-associated chondrotoxicity.”

Does that mean that magnesium and vitamin E should be taken along with fluoroquinolones to mitigate damage? Maybe. It should be noted that magnesium inhibits fluoroquinolones both for better and for worse, and that the magnesium may decrease the ability of the FQ to fight the bacterial infection.

Additionally, it is noted in “Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells,” that:

“Mice treated with clinically relevant doses of bactericidal antibiotics similarly showed signs of oxidative damage in blood tests, tissue analysis, and gene expression studies. This ROS-mediated damage could be reversed by the powerful antioxidant N-acetyl-l-cysteine (NAC) without disrupting the bacteria-killing properties of the antibiotics.”

Since NAC doesn’t disrupt the bacteria-killing properties of the antibiotics, it’s a better bet (IMO).

It is also noted in Musculoskeletal Complications of Fluoroquinolones: Guidelines and Precautions for Usage in the Athletic Population, that:

“A mitochondrial-targeted form of ubiquinone (MitoQ) demonstrated a larger protective effect than did untargeted ubiquinone. Oxidative stress frequently occurs in the mitochondria [22], and fluoroquinolone-induced oxidative damage to mitochondria in tenocytes and chondrocytes has been reported [26].”

Some “floxies” have found MitoQ to be helpful in healing fluoroquinolone-induced damage. Perhaps it can also prevent the damage from occurring.

If a loved one of mine had to take a fluoroquinolone, I would try to get him or her to load up on magnesium before-hand, and I would try to get vitamin E, NAC, and MitoQ into him/her while the FQ was being administered.

I certainly wouldn’t claim to know for sure that they would be safer while taking those antioxidants, but it’s worth a try.

Russian Roulette

People should be aware of the dangers of fluoroquinolones, and they should know that there is a certain amount of Russian Roulette that is being played with every pill administered. For better or for worse, I don’t think that people really understand fluoroquinolone toxicity until it happens to them. As scary as it is for those of us who have been hurt by fluoroquinolones to stand by and watch while our loved ones take these pills, some of us will have to do just that at some point. Maybe some of the fluoroquinolone-induced damage can be mitigated by the supplements mentioned above. I hope so.

 

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Fluoroquinolones and Mercury Poisoning

I recently received a message from a floxie friend that raised an interesting question. My friend asked:

Have you ever heard that FQ antibiotics can release stored toxins like mercury into the body? It has been two years since Cipro for me, and one month ago they found out I am highly mercury poisoned. But before I took Cipro, I was okay. The doctors are guessing that I have been mercury poisoned for a long time but somehow it is showing up in my blood now. Since the symptoms of Cipro toxicity and mercury poisoning are about the same, I’m wondering if they’re related.”

Over the years, several people have raised the question of whether or not fluoroquinolone toxicity is related to mercury poisoning, but I hadn’t heard of test-documented increases in mercury levels after taking fluoroquinolones until my friend sent me the message above.

The symptoms of mercury poisoning are similar to those of fluoroquinolone toxicity. The symptoms of mercury poisoning are:

skin rashes and dermatitis; mood swings; memory loss; mental disturbances; muscle weakness; nervousness, irritability, and other emotional changes; insomnia; headache; abnormal sensations; muscle twitching; tremors; decreased cognitive functions; peripheral neuropathy and more.

According to Dr. Thomas Nissen, “ Symptoms of mercury toxicity are many and varied, since mercury can both reach and affect nearly every cell in the body! Systemic (overall) effects can occur for this reason. The particular symptoms you experience first depend on your own genetic weakest links and on other toxic suppressors.”

Similarity of symptoms does not necessarily mean that two disorders are one in the same. For example, Chronic Lyme Disease and AIDS have similar symptoms, but that doesn’t mean they’re the same diseases. But it’s still interesting to explore the possibility of fluoroquinolone toxicity being related to mercury poisoning.

I searched for journal articles about the effects of quinolones on mercury. Unfortunately, I didn’t find much information. Most of the information I have is anecdotal and stems from me attempting to understand fluoroquinolone toxicity (with zero background in biochemistry), so please take this information for what it’s worth.

Fluoroquinolones have been documented to chelate magnesium and iron from cells. I wonder if mercury in the body is bound by these minerals, and then gets released into the body when the fluoroquinolone chelates the necessary mineral from the body (or when the quinolone binds to the mineral, stealing it from whatever it’s currently bound to).

Dr. Nissen points out that mercury can displace other minerals in the body, and that mineral displacement can cause serious health problems:

Replacement reactions, also called fight for site, occur when mercury (usually with a +2 charge) grabs the biological spaces which should be filled by necessary minerals. Symptoms that can be caused by a deficiency of minerals displaced by mercury include:

  • Magnesium: irregular heartbeat, receding gums
  • Iron: anemia
  • Copper: anemia, thyroid dysfunction, impaired digestion
  • Zinc: anorexia nervosa, loss of taste and smell, loss of appetite, low libido, PMS
  • Iodine: thyroid dysfunction”

For floxies, I wonder if the fluoroquinolone begins the cycle of mineral replacement. Fluoroquinolones chelate minerals, then mercury binds to the site that was vacated by the mineral, then mercury toxicity leads to chronic health conditions.

There are many “drug muggers” out there – drugs that deplete vital minerals and nutrients from the body. I wonder if all the drugs that deplete necessary minerals from the body are opening people up to mercury poisoning.

There are a variety of factors that determine how well one’s body can deal with mercury. Genetic factors such as MTHFR mutations (which play a role in determining how well a person deals with toxins) certainly play a role, as do an individual’s antioxidant levels. Many floxies have MTHFR mutations, and fluoroquinolones have also been shown to deplete glutathione and other antioxidants. Some floxies, including Richard and the author of Say Friend and Enter, have dealt with mercury poisoning issues as well as fluoroquinolone toxicity issues. Obviously, people who suffer from fluoroquinolone toxicity are less adept at metabolizing and clearing fluoroquinolones than those who take Cipro, Levaquin and Avelox without ill effects. Perhaps floxies are less able to handle other toxins, including heavy metals, as well.

There are a variety of mercury detoxification protocols that you can find online. Dr. Mercola’s protocol seems like a good place to start – http://www.mercola.com/article/mercury/detox_protocol.htm. He suggests:

  1. Avoid sugar, milk, grains and processed foods
  2. Eat foods that increase glutathione
  3. Take probiotics and eat probiotic rich foods
  4. Supplement magnesium
  5. Supplement chlorella
  6. Supplement MSM
  7. Eat garlic and cilantro
  8. Supplement minerals
  9. Make sure that you have sufficient hydrochloric acid levels to absorb minerals from your food
  10. Supplement vitamins C and E
  11. DMPS therapy

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Please note that chelation therapies (DMPS) can be dangerous and they should not be done without the direct supervision of a doctor. They can be hard on the kidneys, so they should also not be done unless absolutely necessary. Be careful, please!

As I noted earlier, this post is about possible connections, not established facts. Fluoroquinolones are not documented to have anything to do with mercury toxicity according to the journals I could find. The symptoms of fluoroquinolone toxicity and mercury poisoning are similar though, and given that fluoroquinolones have been documented to have profound effects on cellular mineral homeostasis, I think that it’s a hypothesis that’s worth exploring.

Post-script – If anyone reading this gets their mercury levels tested, please let me know what the tests say – I’m quite curious. Thank you!

Post-post-script – I wanted to point out some comments that Jason recently made on the floxie hope home-page about mercury. He has done extensive research on the topic and what he has to say is certainly valuable:

Toxic Metals and other Toxic substances (like Cipro…) are a HUGE issue, and as I guess you have gathered a mouth full of Mercury is bad situation to be in, and a major potential cause of Brain Fog and many many more issues for someone. This can be grossly exaggerated with someone with a MTHFR Gene issue, since they will NOT be able to detox Metals, Fluorides, Chlorine’s, and all the other Toxic Waste/Toxic Metals/Chemicals that we are subjected to on a daily basis properly, thus they will build up in the body and make the person more and more unwell. Since you are in the USA, for $99 the 23andme test is definitely a “no-brainer” in my opinion if you have not done it already, to find out if you do have these issues or not, on top of potentially being toxic in Mercury and other Metals.

Pretty much every living person has a toxic burden, Metals, Halides, and more; many people are able to keep it low enough to be healthy because their Methylation pathway works properly, actively detox, etc but others are not so lucky, and are even more unlucky if they do not realize this is the cause of most/all their issues. There was a whole bunch of discussion on Genes and the 23andme test last page starting from post 2 if you are interested in finding out more about this important part of someone’s health.

I would suggest to find a good ND, but be very careful with “Challenge Tests”. Many of them will want to give you a dose of DMSA or something else like DMPS, EDTA, etc and often the doses are VERY big, and quite dangerous (a big dose will ensure high levels show up on test, ensuring more money for them since you will “need” treatment = dangerous greed tactic). DMSA will mobilize several toxins in the body all at once, and if a person’s toxic load is large enough the body will not be able to handle all the poison being in the system at one time, and terrible damage can result. If you google Andy Cutler you will see he recommends not doing a challenge test at all, many people are following his advice and his Protocol for detoxing the body of Metals, he believes it needs to be done is slow safe fashion, which makes sense to me.

I myself am a little torn on the “testing issue”. I had a hair test done for Metals and Minerals which is what many people recommend you do to find out your toxic load. The things is it does NOT give you the whole picture, it is really telling you what the body is “expelling”, it is NOT telling you what your body is potentially harboring, since many of the Metals are hidden/stored in the body in Fat Cells, like the Brain, and if not mobilized they just sit there and screw you over, and will not come out in the hair, thus your hair test could say you are “low” in Uranium, or Nickel, but in fact you are not low, you are just not efficiently expelling/detoxing it at the time of the test. However, if the test shows you are high in something, there is a good chance you are actually too high and your body is trying to detox the excess of which some of it ends up in the hair. So these levels that show up, are somewhat dependent on if someone has a Methylation issue also, since poor Methylators are poor detoxer’s potentially skewing the results.

Having said all that, it is one of the best tests to do for this, and highly recommended to do regardless to find out what your Mineral profile looks like, though I still think there might be some viability of a “safe challenge test”, which would be as described above only with a smaller safer amount of a Chelator given right before a Urine test. Yet the reliability of the Hair test for Minerals is too somewhat questionable, out of the 100 or so labs around the USA that do these tests, 98 of them WASH the hair before doing the test. The trouble with this is many of the Minerals are water soluble, so washing the hair with a mild detergent and acetate like most do can skew the results of many of the Minerals. Google “Dr. Wilson Hair Test” and you will see more of what I am talking about. You will also find recommended ND’s on his site that use the one good lab in the USA that do not wash the hair.

This is all my opinion, one that is shared but none-the-less where I stand on the whole thing. I apologize for not giving a “Clear” solution, but this is frankly because in my opinion there isn’t one. As a result, for many years I did “nothing”, I now regret this and don’t recommend that course of action either. For yourself, my unprofessional recommendation is to “not” have a challenge test done, especially with Mercury still in your mouth, also do NOT take any chelators, and avoid Cilantro too, as this crosses the Blood Brain Barrier and taking this can bring Metal from the Mouth/Body right into the Brain. Doing the Hair test is a good idea, it will give you at least some idea on what is going on in your body, and if we are to believe Dr. Wilson, a VERY good idea, he has written a very long book on Hair Tests (his Mentor invented the idea) and how to interpret them, one I wish I had, but there is a lot of info on his website and ARL Labs website (the one he recommends) about how to interpret the results, and a good ND will hopefully be educated on these methodologies. Regardless of the results, if you can afford it if I was you I would find a good Huggins Dentist (trained in removing Mercury fillings safely) asap and start getting those removed. I had one that was “cracked”, and have no doubt it has caused me issues. Good luck, if you do have a heavy toxic load please be patient in its removal.

AND

I think the most popular is the Andy Cutler Protocol, which is a very slow/safe but PITA method, and uses synthetic Amino Acid Chelators DMSA, DMPS and also ALA all in small doses on a very strict time schedule due to their half lives. Lots of info on net about this you will see, chelators are bought from company out of Africa IIRC, there is a good Yahoo support group/forum where people answer questions etc (poorly organized unfortunately)

There are some others of note, and some are opposed to Cutler method such as Dr. Lawrence Wilson http://drlwilson.com/articles/chelation.htm (very good website with a TON of info on everything health). EDTA can be used, Dr. Mercola has made some suggestions like using Cilantro and others, funny enough Cutler warns against using EDTA and Cilantro, for potentially valid reasons, confusing the issue further. 😦

I think the best course of action for someone depends on many things. Do they still have Mercury fillings? Do they have the MTHFR & other mutations in their Genes? (found out with 23andme test) How big is their toxic load?

The first course of action is always to get fillings removed safely, and then getting a Hair metal/mineral test done. To me getting the 23andme test for $99 should be done too, for reasons I noted on FH. Then with that done, and with that information a suitable course of action can be recommended (I sound like a bluddy Naturopath here….) If someone has a huge toxin burden, I think the Cutler method makes sense, but the MTHFR could complicate this. If someone is moderately toxic, Cutler method might still be good, or a combination of ideas might be good enough, again depending on the MTHFR issue. If someone is only mildly toxic, they should for sure address the MTHFR issues first and foremost, which would help the body alleviate the burden on it’s own (of course with a MTHFR issue someone is likely NOT going to have small burden, depending on their age and exposures of course). Also with smaller toxic burden, things like Cilantro, Wheat Grass and regular exercise and Saunas should be enough to bring the burden down, assuming they limit their future exposures.

I hope that helps, unfortunately the waters are a little muddy on this, not unlike Cipro poisoning.

Just a final note that these are only my “untrained” opinions. Toxic load is a serious wide-spread issue, causes very serious health issues, and removal has to be taken very seriously and not “toyed” with, someone needs to put their trust in a professional or do a whole lot of research. There are many complicating factors, such as Candida overgrowth (something DMSA potentially stimulates), MTHFR & other Genes, current past/health problems of the person and things like condition of Liver/Kidney’s, Cancer, FQ toxicity, etc. (Emphasis added by Lisa.)

I also forgot to mention Spirulina & Chlorella, although I did mention Dr. Mercola, and this is 2 things he advocates. They are also something Dr. Sircus recommends (along with a few others, see link), here is a good article on the whole topic here: http://drsircus.com/medicine/essentials-natural-chelation

He actually gives a LOT of accurate advice in this article in my opinion, like his notes on ALA which are important, and note what he says about Magnesium too, which applies 10 fold to a Floxie with Heavy Metals. He notes that some studies found Chlorella on its own, did not seem to chelate anything effectively. However when used with Cilantro, it does, and this makes perfect sense to me because Cilantro is a “mobilizer”, it irritates the Metals stored and Chlorella is a “binder”, it is extremely absorbent and will bind to Metals to help them exit the body and not be “re-absorbed” once they are mobile, which is critical. Done wrong, the Metals from one area can mobilize and then be re-absorbed in other areas causing great oxidative damage like to the Brain.

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Fluoroquinolones Deplete Iron and Lead to Epigenetic Changes

In my ciprofloxacin toxicity recovery story I note that:

I take a low dose iron supplement – only 5 mg. – daily. The brand of iron supplement that I use is Pur Absorb, but I’m guessing that other low-dose iron supplements will work equally well. Within just a couple days of starting taking the iron supplement, my energy levels increased dramatically. I could walk a mile without being exhausted afterward. In addition to improving my energy level, the iron supplement seems to make my muscles and tendons more supple and malleable. When my tendons are feeling tight, a dose of iron helps to loosen them up – within just a couple hours. Too much iron is really bad for you, so please be careful with supplementing it (ask your doctor, yada yada), but it helps me immensely.”

I’ve always wondered why iron helped me to recover from fluoroquinolone toxicity. In some ways, it didn’t make sense – iron is an oxidant (according to a doctor friend, it’s a bit more complicated than that, and in some situations iron can be an antioxidant and in others it can be an oxidant), and antioxidant supplements are what help most floxies. Also, iron is a component of the Fenton Reaction, and the Fenton Reaction is where, “Iron(II) is oxidized by hydrogen peroxide to iron(III), forming a hydroxyl radical and a hydroxide ion in the process. Iron(III) is then reduced back to iron(II) by another molecule of hydrogen peroxide, forming a hydroperoxyl radical and a proton. The net effect is a disproportionation of hydrogen peroxide to create two different oxygen-radical species, with water (H+ + OH–) as a byproduct.” Basically, iron can “donate or accept free electrons via intracellular reactions and help in creating free radicals.” Free radicals are ROS. Some of the nastiest ROS are created in the Fenton Reaction – hydroxyl radicals and hydroperoxyl radicals. According to “Oxidative Stress Induced by Fluoroquinolones on Treatment for Complicated Urinary Tract Infections in Indian Patients,” fluoroqinolones increase the production of ROS, and it has been postulated (by myself and others) that the mechanism for fluoroquinolone toxicity is an excess of ROS wreaking havoc on all systems of the body.

So, why did iron make me feel so much better?

It’s a question that has perplexed me for years.

Answers to that question can be found in the article, “Non-antibiotic effects of fluoroquinolones in mammalian cells” which was published in the July, 2015 issue of The Journal of Biological Chemistry. In this post I will highlight some of the more interesting findings from “Non-antibiotic effects of fluoroquinolones in mammalian cells.” All excerpts from the article are quoted and italicized.

Here we show that the FQ drugs Norfloxacin, Ciprofloxacin, and Enrofloxacin are powerful iron chelators comparable to Deferoxamine, a clinically-useful iron chelating agent.”

Fluoroquinolones suck iron out of (chelate) cells just as well as drugs that are meant to suck the iron out of cells (Deferoxamine). Iron is an essential mineral that is critical for transporting oxygen throughout the body. Chelation of iron from cells can be detrimental to health in multiple ways including, “delayed cognitive function, poor exercise performance and lowered immune function. In children, iron deficiency anemia can cause psychomotor and cognitive abnormalities resulting in future learning difficulties.

We show that iron chelation by FQ leads to epigenetic effects through inhibition of α-ketoglutarate-dependent dioxygenases that require iron as a co-factor.”

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Iron depletion leads to adverse epigenetic effects through inhibition of iron-dependent enzymes. This is a very big deal – Fluoroquinolones can change genetic expression (epigenetics) in human cells. Later in the article it is noted that, “This is the first study to show global epigenetic changes induced by FQ antibiotics.” It had been previously postulated in “Epigenetic side-effects of common pharmaceuticals: A potential new field in medicine and pharmacology” (2009) that all fluoroquinolone adverse effects were the result of epigenetic changes, but “Non-antibiotic effects of fluoroquinolones in mammalian cells” describes the first study of human cells that shows epigenetic changes caused by fluoroquinolones. Epigenetics wasn’t even a notion, much less a field of study, when the FDA approved fluoroquinolones, drugs whose mechanism of action is, “inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA replication, transcription, repair, and recombination.” Think about that next time you pick up a drug from the pharmacy and assume that it’s safe because the FDA approved it.

Dioxygenases are enzymes that are necessary for aerobic life. Fluoroquinolones inhibit α-ketoglutarate-dependent dioxygenases, which require iron as a co-factor.  Depletion of α-ketoglutarate-dependent dioxygenases leads to changes in how genes are expressed.

Fluoroquinolones were also found to inhibit several demethylases, “enzymes that remove methyl (CH3-) groups from nucleic acids, proteins (in particular histones), and other molecules. Demethylase enzymes are important in epigenetic modification mechanisms. The demethylase proteins alter transcriptional regulation of the genome by controlling the methylation levels that occur on DNA and histones and, in turn, regulate the chromatin state at specific gene loci within organisms.” FQs were found to inhibit “Jumonji domain histone demethylases, TET DNA demethylases, and collagen prolyl 4-hydroxylases, leading to accumulation of methylated histones and DNA, and inhibition of proline hydroxylation in collagen, respectively. These effects may explain FQ-induced nephrotoxicity and tendinopathy.” (emphasis added).

Many possible mechanisms for the tendinopathy and compromised collagen integrity caused by fluoroquinolones have been proposed. It has been suggested that fluoroquinolone caused destruction of connective tissues are due to metalloprotease (MMP) malfunctions, magnesium depletion, and the NO/ONOO cycle. In “Non-antibiotic effects of fluoroquinolones in mammalian cells” it is asserted that iron chelation, and the inhibition of enzymes that utilize iron, are behind the fluoroquinolone-caused musculoskeletal adverse effects:

These results suggest, for the first time, that FQ treatment can cause unanticipated epigenetic effects. Moreover, we suggest that the well-established linkage between FQ treatment and tendinopathy reflects impairment of collagen maturation by FQ. We suggest that it is the inhibition of collagen 4 prolylhydroxylases by FQ mediated iron chelation, and repression of collagen P4H1 and LH1 transcription that underlies the peculiar tendinopathy side effects of FQ antibiotics.”

And:

FQ are potent iron chelators capable of inhibiting 2-KG dependent dioxygenases because of the crucial role of iron in the active site. We show that FQ treatment inhibits collagen maturation. Prolyl 4- hydroxylase and lysyl hydroxylase are iron dependent enzymes essential for the post-translational modification of collagen. Both play central roles in collagen maturation through hydroxylation of proline and lysine residues to mediate collagen cross-linking. Covalent crosslinks are required for the tensile strength of collagen fibers (64). We suggest that it is iron chelation by FQ that accounts for suppressed collagen hydroxylation, giving rise to tendinopathies.”

And:

Additionally, suppression of HIF-1α can have drastic effects on vascularization and energy metabolism in connective tissues, contributing to decreased blood flow in an already hypoxic and avascular tissue. We suggest that these three insults – inhibition of prolyl and lysyl dioxygenases, reduction of P4HA1 and LH1 mRNA levels, and reduced tendon vascularization upon HIF-1α depletion – together account for FQ induced tendinopathies.”

To sum up the excerpts, fluoroquinolones chelate iron from cells, this leads to inhibition of iron-dependent enzymes, which lead to epigenetic changes that result in collagen malformation and tendinopathies. It should also be noted that fluoroquinolones chelate other minerals, including magnesium, from cells, and magnesium-dependent enzymes are inhibited by fluoroquinolones as well.

All doctors and researchers, and the FDA, should note that in chelating necessary minerals from the body, fluoroquinolones are not only inhibiting necessary enzymatic reactions, they’re also changing genetic expression, and that the long list of severe adverse effects of fluoroquinolones may be due to adverse expression of genes. Neither long-term, nor intergenerational effects of fluoroquinolones are currently known.

So… what should floxies do with this information? Personally, I supplement iron and I find that it helps me immensely. Not everyone can, or should, supplement iron though. Too little iron is bad, but too much is also harmful. The prudent thing to do is to get your iron levels tested and to supplement if necessary under the care of your doctor.

When I corresponded with Dr. Maher, one of the authors of “Non-antibiotic effects of fluoroquinolones in mammalian cells,” he noted that, “I would simply emphasize that what we demonstrate in this work involves human cells grown in culture, and lab conditions, and we want to make it clear that these are findings of potential mechanisms of fluoroquinolone antibiotics that could be relevant for patients, but we provide no direct data related to human patients or treatments. Further studies will be required to understand if these or related effects actually occur in people.”

I am thankful to Doctors Badal, Her and Maher for their work on “Non-antibiotic effects of fluoroquinolones in mammalian cells!” Of course, caution should be used when drawing conclusions from their results. Though I shouldn’t draw conclusions about how FQs react in a complex human body from how human kidney cells react in a petri dish, I don’t think that it’s completely out of line to say that the potential implications of this research are huge. The chelation of minerals from cells by fluoroquinolones may be leading to epigenetic changes in the people who take fluoroquinolones. What this means for their health is not currently known.

The epigenetic adverse effects of fluoroquinolones were found to be reversible by exposing the floxed cells to iron, and studies have shown that magnesium, vitamin E, MitoQ and NAC can reverse some of the effects of fluoroquinolones, so please have hope, hang in there, and take your mineral supplements (under the supervision of your doctor, yada, yada).

 

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Fluoroquinolones Linked to Type 2 Diabetes

Diabetes Article Graph Pic

Fluoroquinolone antibiotics and type 2 diabetes mellitus Telfer, Stephen J. Medical Hypotheses , Volume 83 , Issue 3 , 263 – 269

Please read Fluoroquinolone Antibiotics Linked to Diabetes on Hormones Matter.

http://www.hormonesmatter.com/fluoroquinolone-antibiotics-diabetes-risk/

And here is the source article, “Fluoroquinolone antibiotics and type 2 diabetes mellitus” – http://www.medical-hypotheses.com/article/S0306-9877(14)00217-5/fulltext

The thought that fluoroquinolones cause cellular damage and magnesium depletion to the point that they increase the risk of type 2 diabetes is frightening, for sure.  There is quite a bit of evidence that dietary adjustments can influence type 2 diabetes significantly though.  So, that’s a reason for some hope.

The role of magnesium depletion in FQ toxicity described in “Fluoroquinolone antibiotics and type 2 diabetes mellitus” helps to explain why magnesium is the supplement that seems to help floxies almost across the board.  Magnesium is necessary for hundreds of enzymatic reactions.

A hopeful thing about the article, “Fluoroquinolone antibiotics and type 2 diabetes mellitus” is that it is a huge help in building a case against the makers of fluoroquinolones.

Smart, resourceful, intelligent people are working on this.  Change will happen.  It will.  It must.

 

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