Cipro: A Mitochondrial Killing Machine

I hope that the title of this article drew you in.  Seriously, if I put up the title that I was thinking about, “Current Research:  Ciprofloxacin Has Dramatic Effect on Mitochondrial DNA Topology,” how many of you would have passed this article by?   But seriously, the research paper that is the core of this article, published in August of 2018, reiterates again that the health of all those who take Ciprofloxacin (Cipro), or any fluoroquinolone (FQ) antibiotic, is at risk.  Serious Risk.

In this article I refute the smoking gun scenario regarding FQ damage, discuss why some people seemingly do not have adverse events, reveal why Cipro damages the brain, why they are still on the market, and reiterate just how horribly damaging the FQ’s are to mitochondria.

Recently, another excellent research paper hit academia on the negative effects of FQ antibiotics.  Published by Oxford Academic in its Nucleic Acids Research, the paper entitled “Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2” the paper damningly discusses how Ciprofloxacin impairs mitochondrial DNA replication.

No Smoking Gun, Instead More Insidious

Years ago, I used to look for a single cause of FQAD.  Something that would be irrefutable or at least pretty hard to deny.  I knew both alternative and academic researchers that were looking also and to this day some are still fixated on the premise that there is ‘one cause’ of FQAD.

What this paper reiterates, and what I have for known for quite some time now, there is no smoking gun.  

The phrase that toxicity comes through a “broad range of mechanisms” is clear enough.

Many years ago, before I understood the complexities of the FQ’s, I spent an inordinate amount of time researching a single cause, a genetic predisposition, etc.…  Then one day, looking at the totality of the evidence, I personally came to the determination that there is no single way that the FQ’s do their insidious damage. When you look at a class of drug that can hit a million points at once, interact with so many variables combined with the fact that many different modes of damage have already been documented by academic researchers, you come to the conclusion there are many ways that Cipro, and the whole family of quinolones, cause damage and all of them are, putting it mildly, terrible.

You might be asking yourself “Yes Dave, but what about all those people who take FQ’s and don’t have a reaction?

My answer “How do you know that they didn’t?” followed by, “What does a FQ reaction look like?” followed by “How many sicknesses and disease processes in the world today are actually caused by FQ’s but have missed by doctor’s and patient?” followed by “How do you know that the FQ’s didn’t start something that will become pathogenic later in life?” (Read Twist of Fate)

That is why it is important for us to warn, inform, and get the word out.  If everyone would do this in their little circle of life, we would make difference.  

These drugs set the stage for long term disease.  

Now back to the research paper. In this paper, researchers from Finland and Estonia determined that “Ciprofloxacin caused a dramatic effect on mtDNA topology, blocking replication initiation, reducing copy number and inhibiting mitochondrial transcription.”(1)

Cipro’s toxicity to mitochondria has been reported in various studies, suggesting a broad range of mechanisms including topoisomerase inhibition, oxidative stress, altered calcium handling and photosensitization, just to name a few (2,3,4)

So, to reiterate one more time before I move on, please hear me again, there is no single smoking gun, period, nada.  We, as a community, could do so much more if we would stop spending money on looking for a smoking gun and move on to researching how to quantify the level of mitochondrial damage and how to repair the broken machinery?  The latter is easier as the technology to quantify the level of damage is being developed.  Anyway, I sure hope the community can come together someday and get behind technology that can help us.

Topoisomerase

Beatrice Golomb at the University of California, San Diego, a FQ researcher whom I have had the privilege of working with in the past as a participant Dr. Beatrice Golomband case study subject, believes that FQ’a are damaging mitochondria, cellular power plants because they retain some similarities to their bacterial ancestors.  This idea is not new, and several prominent mitochondrial researchers have noticed the uncanny similarity between mitochondria and bacteria. Because of this, FQ antibiotics pose a threat to mitochondria and the result is that every cell in the body can be affected. Dr. Golomb says this explains why a wide range of symptoms can appear and get worse over time.

For those of you who do not know about Topoisomerases here is a brief overview of these complex enzymes. There are a number of different types of topoisomerases, each specializing in a different aspect of DNA manipulation which ranges from accessing DNA, removing DNA supercoils, strand breakage during recombination, chromosome condensation, and disentangling intertwined DNA.  To make it simple, topoisomerases are like the tools kids need for school. If you look in their desk you will see ruler, scissors, glue and erasers.  Topoisomerases perform all these functions with your nDNA and mtDNA plus much more. 

Because of this, topoisomerases have been the focus of pharmaceuticals used to kill cells, such as anti-cancer drugs, and of course the FQ’s.

The article’s researchers have found that mitochondria contain two forms of Topoisomerase 2. The isoforms of Topoisomerase 2 are Top2α and β. These isoforms have specialized roles in the maintenance of the nuclear genome and mitochondrial genome.

It is imperative that Top2α and β function correctly to maintain mitochondrial homeostasis which allows for damage to be repaired to a certain degree. This paper documents that Ciprofloxacin caused a dramatic effect on mtDNA topology, blocking replication initiation, reducing copy number and inhibiting mitochondrial transcription.  It also stops the cleavage/re-ligation reaction of type II topoisomerases midway, generates double-strand breaks, creates persistent protein–DNA adducts, and reduces also the overall enzyme activity (5).

FQ’s bind to the topoisomerases that perform the gluing action. As part of normal cell division, topoisomerase act like scissors and cut a DNA strand, untwists it, then try to glue the strans back together. The FQ’s block the gluing action forcing the cell to literally cut up its own DNA.

The effects of this type of damage need not be readily apparent.  Especially by those individuals who vehemently argue that they ‘feel fine’ after taking an FQ.  Nay, it sets the stage for many as disease that happens down the road.   

Sinister, isn’t it?

Yet, Cipro is the third most commonly used antibacterial antibiotic.

 It is so terribly toxic to mitochondria.

Adducts

Let me take a quick moment and talk about adducts that I just mentioned in the previous section. DNA adducts are aDr. Mark Nobleform of DNA damage caused by covalent attachment of a chemical moiety to DNA. Adducts that are not removed by the cell can cause mutations that may give rise to cancer and other dysfunctions. They are frequently used as biomarkers for chemical hazard exposure or cancer therapy efficacy.  Often, adducts will show when damage is being done to the DNA.

In the past I asked Dr. Noble if DNA adducts were the cause of FQAD. To reiterate Dr. Mark D Noble is a professor in the Dept of Neuroscience and Biomedical Genetics at the University of Rochester. He is a pioneering researcher in the fields of stem cell biology and stem cell medicine. 

On a side note speaking of stem cell medicine, I will be writing an article on the current stem cell treatment fad for FQ damage, very soon. 

Anyway, Dr. Noble is one of the smartest men I know.  He told me that the symptoms we see in FQAD could not be wholly explained by adducts alone.  He said there are other avenues at work, of which I agree.   Dr. Noble’s information concurs with what this research paper clearly states. FQ’s have already been found in various studies to damage via a broad range of mechanisms, one of these is topoisomerase inhibition which by adductions would not be repaired, if they form.   

Could adducts be causing some of the problems we see in FQAD? Yes, but not exclusively.  If adducts are occurring, they will not be consistent across the population.  There will be other types of damage occurring as well. Secondly, if the do exist, they will primarily exist because the repair mechanisms are being altered by the FQ’s.  If topo 2 could do its job properly things like adducts, crosslinking and other DNA insults, for the most part, would not occur

It is my opinion that wasting time or money looking for adducts is not productive.  That is like pursuing the rabbit down the proverbial rabbitRabbit Hole hole.  There are many substances in our world today from hair color to fried fats that can form DNA adducts.  It is virtually impossible to quantify if the adduct is causing the metabolic problem or not.  What concerns me even more is the epigenetic capabilities of the FQ’s which can turn on ‘bad genes’ to start a disease process.   

When academic researchers, who have access to the latest technology, including being able to detect and quantify adducts, tell us that the FQ’s damage via a “broad range of mechanisms” we should accept this, consolidate our efforts and stop pursuing just one avenue.

Mitochondria Take A Beating

The severe side effects of ciprofloxacin and other FQ’s include tendinopathies such as tendon rupture, joint inflammation, muscle weakness, central and peripheral neuropathies, epilepsy and psychological symptoms such as depression. Much of the damage in these systems have been connected to enhanced oxidative stress (6). The reduction of mtDNA copy number and mitochondrial transcription caused by the altered topology of mtDNA might result in severe dysregulation of the electron transport chain complexes, as known to occur under ciprofloxacin treatment (7), lead to respiratory chain dysfunction and cause the observed enhanced oxidative stress.

Ciprofloxacin has also been reported to interfere with physiologically significant cell differentiation processes, such as spermatogenesis (8), brain development (9), bone mineralization (10), as well as to induce renal toxicity and heart arrhythmia (11).  What do these systems have in common? Mitochondria play a central role in all of them, making mitochondrial impairment a likely culprit for the disturbed cellular physiology.

Researchers found the inhibition of mtDNA maintenance in ciprofloxacin concentrations that could well be exceeded in patients with altered pharmacokinetics.  This could be due to obesity, age, renal impairment or simultaneous corticosteroid use as these groups more often experience the immediate adverse side effects of fluoroquinolones (12,13).

My take on this is that those with altered pharmacokinetics experience the ‘shotgun’ or immediate reaction more than those who have normal pharmacokinetics. This does not mean however that those with normal pharmacokinetics escape harm.  Mitochondrial damage can set the stage for late effects or delayed adverse events and other types of disease pathology not readily connected back to the FQ.

Neuropsychiatric Issues

The fact that Top2β, affected by ciprofloxacin, exists in brain mitochondria at far higher levels compared to other tissues, suggests a specific demand for mtDNA topology regulation in neural cells.  This could indicate that the brain could have higher sensitivity against TOPO 2inhibition. This could explain the neuropsychiatric effects of cipro seen by many folks in the FQ community and recently researched and documented by Dr. Bennett (Bennett 1, Bennet 2).

The FQ’s are insidious in their ability to damage.  Anytime you damage mitochondria the way the FQ’s do, you set the stage for disease pathology to take hold.  This could be immediate or later on down the road.   The researchers of this paper concluded that Fluoroquinolone clinical use should be considered with great care.

What Could We Do As a Community?

It is my opinion that as a community we could pool our resources and invest time and money is solutions as opposed to chasing rabbits.  It is already been established that the FQ’s can damage mitochondria via several mechanisms or avenues.  There is no smoking gun, no single point of damage. Instead we should be working alongside with researchers in the mitochondrial and chronic fatigue communities who are blazing new paths into research that will find novel ways to identify disease/dysfunction and develop treatments.  

We need to work with these groups and invest our time and money in to metabolomics research which will allows us to identify what is breaking in each person.  It is truly individualized medicine. We need to abandon a ‘one size fits all’ causation which wastes time and money.

Why Aren’t These Drugs Off The Market?

FQ’s were released on the public in the 1970s.  It wasn’t until 2013 that the FDA started sounding the warning, and even then, it was a lukewarm one. The adverse events of FQ’s are disparate and by all definitions, outrageous.  They range from permanent nerve damage, tendons spontaneously rupturing, organ failure, psychosis, and literally dozens more. Most doctors consider this preposterous as they simply can’t wrap their heads around a differential diagnosis to include the FQ’s.  Hell, most of them don’t know what to look for or how to connect the symptoms.  Because of this, they don’t get documented.

The FQ’s kill and damage through so many mechanisms that it is not usually connected by doctors.

Also, when nalidixic acid, a non-fluorinated quinolone antibiotic, was first invented and thereafter for some time, researchers did not know about mitochondrial DNA.Snowball Effect  So how the first quinolones and the subsequent fluoroquinolones affected the mitochondria was not on the researcher’s radar scope.  The ignorance continued on while the snowball was rolling downhill ever faster and getting much larger.

Remember, there were other FQ’s, such as trovafloxacin or temifloxacin, that had “good” safety profiles, that passed all medical standards, and then removed when they started killing patients.  The damage these two FQ’s inflicted was immediate, in your face, thus they had to be dealt with.  But what about when the FQ’s start the machinery in motion that kills slowly over time?  There really is no measure for this type of insidious damage.  This style of damage is ‘off the radar scope’ of most doctors who are taught outdated paradigms in medical school.

Many of you reading this article will know of individuals who have taken FQ’s or are faced with taking FQ’s.  Many of you will encounter folks who will staunchly defend the FQ’s stating they took them with no problem whatsoever.   Many times there are safer alternatives available. These drugs set the stage for long term damage. This damage may not be readily apparent for weeks, months or years.   Just because the damage is not readily apparent does not mean it does not exist.

Fluoroquinolones are used for chemotherapy.

Fluoroquinolones kill human mitochondria.

Fluoroquinolones kill human eukaryotic cells (14, 15)

Fluoroquinolones kill! Period.

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Admin

...damaged by fluoroquinolones in 2007 at age 46. Prior to, a healthy law enforcement official. Now an amateur FQ researcher, author, and blogger.

27 Responses

  1. Stephen Yount Ascher says:

    As a lay person I don’t understand much of what you write about but accept it as to a factual description of the damage levaquin did to me, an 82 year old. (Took four pills of the eight prescribed at which point I associated the pain with the pills and stopped taking them.) What really piqued my interest was the one word you used “cure”. Is it possible that if your work is continued and substantiated that a cure could follow? Seems to me such a cure would be complex and years to decades away? Your thoughts. Thanks.

    • Admin says:

      Stephen, Thank you for your response. I don’t understand much of what I write about as well 🙂 Seriously, “Cure” NO, The possibility of treatment “Yes”. FQ’s can hit us in a million points at once. There is only one technology today that can quantify and identify the individual damage, that is metabolomics. It is currently being researched/developed to identify what is breaking in those with Chronic Fatigue/Mito issues. Once the broken systems are identified (individually) then treatments can be explored. I can see the path out, getting there is entirely another story. We have some willing academic researchers, but lack of money, lack of adequate community leaders, and competing agendas will cause the inevitable delays. Over 30 years in law enforcement taught me the paramilitary hierarchical system is the only way to get it done right. In a perfect world if I had an unlimited budget and the right leaders it could happen. Until then the only option we have is to piggyback on the strides of others. I tried the bureaucratic leadership role in the FQ community once, it was like “herding cats.”

  2. Kate King says:

    Excellent article! Can you help me understand what “metabolomics” is? Is anyone practicing this yet? Also, I was so pleased to see that you plan on writing about the stem cell treatment fad. I was floxed 9 months ago, my life turned upside down, my husband had to retire five years earlier than planned, never in a million years could I have expected to potentially spend the rest of my life in bed, and can’t understand why doctors are so ill informed. I’m over 60 and was prescribed Cipro for uncomplicated diverticulitis, even though the American Gastroenterological Association no longer recommends antibiotics for the uncomplicated type. And then to have the prescribing physician, who I had considered a friend, not believe me and treat me as a nut case. Thank you for all you are doing to raise awareness. Seems like it should be a slam dunk …. but too many other factors are at play.

    • Admin says:

      Thank you. Metabolomics is a comprehensive profiling of small molecule metabolites in cells, tissues, or whole organisms. It takes a look at what is malfunctioning in small detail. Currently it is only available at the University level, for the most part (there are a few private labs that are using it). It looks at biomarkers to identify dysfunction. Right now as we speak, the Chronic Fatigue community, through grants, have a few larger universities developing metabolomic standards for testing. It has undergone a rapid technological evolution just within the last year. For example, one of the leading researchers has a son that is plagued by Chronic Fatigue. He is bedridden and tests ‘normal’ on all standard testing. When they subjected him to detailed metabolomics analysis, I believe his father said “he lit up like a Christmas tree.” Researchers could see what was malfunctioning in his body and they hoped to develop an individualized treatment regime within a year’s time. We have one academic researcher that has the metabolomics equipment, another academic researcher that wants to develop a cheap test to properly gauge the level of mitochondrial functioning on an individual level using novel cutting edge technology. We just need money and, like I mentioned in the above comment reply, adequate leaders, both of which we don’t have. Then and only then can the universities develop biomarkers for floxed folks and then hopefully treatments.

      • JR Wright says:

        What do you mean “we” have one with equipment and one to make a cheap test? Meaning they are on board to help FQ victims if we can come up with the money or do you mean the reasearchers are in separate areas and thoughts and we need them to be together? If they are ready to go, how much money are we talking about? I’ve never raised money but there must be a way. But then, I always come up with the grand ideas and end up sleeping instead. Trying to recharge my mitochondrial batteries.

        • Admin says:

          Yes and Yes. Both are at separate universities and both have and are willing to work with FQ victims. I hesitate to place a dollar amount but it would need to be fairly substantial. Money talks, and whoever controlled the purse strings could make things happen fairly quick. Alas, it is just the way things work. Also, by fairly quick I mean much faster than the snails pace that research has moved through the FQ community in the last two decades. Since we do not suffer from a true organic process that is universally recognized we have been treated like stepchildren and had to grovel for handouts in the research world. In the past, I have both tried to raise money and to lead, both were abject failures, like I said in a comment above. It was like herding cats. We need a very wealthy benefactor.

      • jill says:

        big Pharma needs to pay for this research!! PERIOD

  3. WayneD says:

    You knocked it out of the park with this one David. Thanks for making hard subjects easy to understand. I wish the FQ community had more money and adequate leaders to get the job done.

  4. Andrea says:

    I have been given Cipro over a 11 year period , the last time I had it was back in November 2015 after I had a womb biopsie & suffered infection afterwards , in the jan of 2016, I was descending down the stairs to take my son to the airport & I felt as though summit popped in the back of my heel, I could not put my foot down & ended up at my gps later that day , who sent me for a X-ray , which confirmed that I had ruptured my tendon , I was given an appointment to see a specialist who did a mri scan & I now have to wear like a front & back shin guard to support it , I’ve been left with a bump on my heel , so I’m thinking did this do that !! , I no the mitochondria is the power house of all cells but what does it do to the dna ?

  5. Robin says:

    This article from 2015 confirms your theory that it’s multi-factors & damage(including the MtDNA).
    Horrifying especially to this 30 year multi-Floxed “victim”!
    How they can release a study like this & not do anything about these poisons is mind blowing!
    Thanks for doing your part to advocate & for another informative article!
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600819/#!po=29.1209

  6. Neal says:

    Do you think that persistent adducts from FQ’s are that significant? From my understanding many, I mean many, things in life can form adductions, so if we prove them what does it really matter?

    • Admin says:

      I have seen repeat mass spec data that shows changes in supposed permanent adducts, making them not so permanent, or at the very least fluid. That is not to say that people do not develop permanent adducts but I cannot see the fallacy of pursuing them at this time. It is not going to prove anything to researchers as they will acknowledge that FQ’s can cause adducts, among a gazillion other things as well. It probably is not going to win any big lawsuits as big pharma will come with their own scientists as say “so what if they cause adducts, prove to us that it causes a disease process.” This is just one research avenue that I think is foolish to pursue. We have the ability within our grasp to help floxed folks by being able to identify what is breaking in each person (again it is primarily different for each person) using existing technology and then, based on the findings, look at various treatment options based on the malfunctioning pathways. It is not a slam dunk by any means but it offers real time avenues that we can explore today, especially if we work with the CFS/ME/Mito communities.

  7. Katie says:

    Excellent article

  8. Katie says:

    Excellent article.

  9. Michael Blackwood says:

    Great article David. Depressing but good… My mitochondria are most likely shot given the downward spiral for years and latent onset of issues after Cipro.

  10. Preston says:

    The question is how to reverse or at least slow the deterioration of our mitochondria? What gives us the best chance of preventing or reversing the multitude of issues? Thank you for this article. I am split between trying to understand what is happening to me and wanting to just never think of it again. Pretend I will one day be well. I would say in the 4 months since I was floxed I am improving. I no longer have chest pains and irregular heart beats frequently. They happen infrequently. My muscle twitching still happens every day, but it is not constant. My tendons still hurt every day, but they do seem to be very slowly improving. Thank you for the important work you are doing.

    • Admin says:

      Preston, Thank you for your comment. At four months, despite looking bleak, you have a lot of reasons for hope. I do want to come off as presumptuous, but you are still in a stage where your case could turn around my friend. I have seen this happen time and time again. There are ways to slow down mitochondrial deterioration and that involves getting the ROS under control. However, this is not a one size fits all proposition and has to be developed by trial and error. I pray that you see increased healing.

  11. Kim Daniels says:

    My daughter forwarded this report to me. She my biggest advocate. I was forced by my Infection control Dr to take Cipro for 6months straight 500mg daily. It was prescribed correctly. As I had Pseudomonas from contaminated hardware in my neck. I was told I could become a quadriplegic or death with in days/weeks.
    After Months of complaining to my Dr of horrible horrible side effects …. he finally said to me “ the benefits outweighed the damages”. I begged to differ…. This is a whole other death sentence!!!
    I’m almost 2 years into this… I feel like death.. completely robbed of my life.. with no hope in sight
    They should’ve let me die. 😫

    • Admin says:

      Kim, I know that life is a living hell for you. Please do know this, you are not alone. There is not a day goes by that I don’t get contacted by someone in your (our) shoes who have been chronically and devastatingly impacted by this drugs. I will pray for comfort for you. ~David

  12. Darlene Donalddson says:

    Well written David

  13. Cindy B says:

    I was floxed four times in a 6 year period, only to get worse every time. The fourth time on the third pill I literally could feel the damage happening, I felt as if tendons in my back, going up to my neck were tearing, I could hardly lift my head off the pillow, the pain was excruciating. Since then I’ve had just about every symptom on the black box warning over the years, including two torn meniscus, torn rotator cuff, chronic fatigue, brain fog, SVT 240bpm of my heart, weak spot in my retina,
    And many other things . I would always use all my sick days for work and more, but I was still able to work. When I was given the Cipro, it came along with Flagyl another horrible antibiotic and of course I was taking Alieve with it because of the excruciating headaches, which is a big no no, but I didn’t know that. My question to you is, 22 months ago, again I came down with diverticulitis, I was given Metronizidole/ Flagyl, I really didn’t want to take it and asked for a different antibiotic, but she insisted on Metronizidole, my question is why did this antibiotic make all my Cipro symptoms come back worse with a vengeance? I feel like I’m 5 times worse than I was, on top of it, the Metronizidole gave me the worst anxiety, depression and the chronic fatigue so much worse! Not only did Cipro steal my strong healthy body, Metronizidole stole my mind, these two drugs are like a nuclear bomb going off in your body and mind. People need to know not to take these. Why did the Metronizidole make my Cipro symptoms so, so much worse? I haven’t been able to work since this.

    • Madge Hirsch says:

      Flagyl is a neurotoxin. There are people online who have been poisoned by this drug without being floxed. The poisoning seems to be shorter in duration than for floxing. I was given a Cipro / Flagyl iv combo for diverticulitis. The next time I got it I refused both and was given Augmentin which worked perfectly well though maybe a little slower. I then had a colectomy. I was given Flagyl as prophylactic during the op but do not seem to have had much of a reaction to it this time. I would recommend the op if you get repeated attacks of diverticulitis. The floxing has left me with widespread tendonitis .

      • Admin says:

        Yes, for some, Flagyl can be very damaging. It’s toxicity however has to do with a complex disruption of the thiamine metabolism. Although I am no expert, I have had contact over the years with those who have recovered from Flagyl problems by using thiamine. Again, one would have to consult with someone who is more knowledgeable on the issue. Depending on the ‘state’ of the floxed person’s nervous system, Flagyl can be very aggravating to symptoms.

  14. Angela B. says:

    I just discovered your site and can say I’m super excited! I think FQ may finally be the diagnosis I’ve been looking for over the past 3 years. In the summer of 2015 I had cancer. I completed 7 rounds of cisplatin chemo along with other meds and 28 sessions for radiation. Towards the end I developed severe bladder issues. In the possibility it was a UTI I was given Cipro. Life has not been the same since. I’ve had type 1 diabetes for 33 years with no complications. But developed neuropathy in my legs. After nearly two years on tramadol the neuropathy seemed to subside. I weaned myself off and have spent the last year drug free. However over the last 3 months I’ve had significant muscle pain/weakness in my legs. Sadly I’ve started leaning on tramadol again. Apologies for rambling, I’m curious if you’ve come across anything relating chemo/radation/diabetes/cipro interactions. When I was nearly finished with the dose I found out it should not be given with cisplatin. I was so sick at that point all I could think was, what’s done is done. I was fit, healthy and active my whole life, the last 3 years have been a struggle. I’ve had all the vitamin deficiencies you’ve mentioned and so many other symptoms make sense now. I’ll be following up with my dr in a week and will share this possibility. Thank you for listening! Thank you for sharing!!

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