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.


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.


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.