Many of my readers know I am particularly concerned with chronic fluoroquinolone (FQ) reactions; those long term reactions that separate cause and effect and are denied by most medical practitioners and confound many more. There is a vast array of symptoms that plague these long term chronic FQ sufferers. I suspect we will eventually see confirmation that points the finger squarely at mitochondrial dysfunction as the driving factor of chronicity. That is why it is so important to support awareness like the citizen’s petition.
Backing up for a moment and taking a look at the initial ‘why’ a person has a reaction to the FQ’s in the first place is truly a study in chaos. There is no simple answer. I also imagine that someday we will probably have a good idea for the set of conditions that are required to precipitate an initial serious adverse event. Given that, I also believe that there are multiple paths from the initial reaction to the unfortunate result of chronicity. FQ’s can affect a person’s body in different and catastrophic ways. They can exert great pressure on underlying latent genetic tendencies, exacerbate dormant conditions, or as some believe, become the outright cause of some neurodegenerative diseases.
Going forward and attempting to look at the cellular cause in cases of chronicity where FQ’s are the precipitating factor is truly another mind boggling effort that can be just as chaotic. However, I do love a mystery, albeit I would prefer to tackle something less persona,l such as a good Agatha Christie book. I have been thinking about chronic FQ reactions a lot lately, mainly because I have been spending a lot of time in my genetics, looking at the genetics of others, and reading about our nuclear gene’s influence on mitochondrial function and for that matter, dysfunction. Recently, I put pen to paper to see if I could come up with a good ‘guesstimation’ that could explain the vast array of symptoms that we see in chronicity.
So what does happens when someone crosses over into the long term chronic reaction? As science into FQ reactions moves at a snail’s pace, it falls upon those of us in the community, who are able to pursue these questions, to speculate, ponder and debate these issues in hopes of stumbling across something that explains sheds light on our symptoms. Recently, I had one of those thought processes, where, for a brief moment things seem to make a little sense.
From my humble anecdotal observations over many years, the floxing community does not appear to have a higher cancer rate than the general population. Technically, if egregious mutagenesis is occurring at the hands of the FQ’s, we should at least, statistically speaking, have a slight to moderate increase in cancer. I would be the first to admit that, at this juncture, it would be very difficult, given the variables involved, to determine if FQ’s are causing cancer themselves. However based on their method of action, I suspect not. I did have a fellow floxed person tell me that we may have a mutagenic process taking place however it is not what we think of, when we normally think of cancer, an interesting thought and quite intuitive.
There are some in the community that believe that decomposed compounds are cleaving/adducting to DNA. If this was so, and it is entirely possible in some cases, then we would have to naturally assume that the FQ’s are not interfering with cellular mutagenic protections. In other words if the FQ’s stopped cell protection then we should see more cancer. I have no doubt that FQ’s are damaging our DNA but I believe the methods for that damage are many.
Still there are others who believe the main method of action is interference in the orderly death of a cell, called apoptosis (12). I too believe this is also a valid method of damage. FQ’s interfere, as we know, with cell signaling proteins (1) (2), as well as many aspects of the apoptotic process (3).
Also, as we know, the FQ’s cause oxidative stress (4) and it appears in many cases, runaway oxidative stress. The FQ’s deplete anti-oxidant levels (11) and can set the stage for chronic runaway oxidative stress. This too is a very valid method of FQ damage.
I have a theory; it is possible that the FQ’s via three avenues, #1 apoptotic interference, #2 elevated reactive oxygen species, or #3 DNA damage (but not a true Hayflick limit (5)), or a combination of all three, drive cells into an early senescence.
For those of you who do not know, the Hayflick limit is the number of times a normal human cell population will divide until cell division stops. Empirical evidence shows that the telomeres (which are structures akin to the plastic tips on shoelaces, because they keep chromosome ends from fraying and sticking to each other) associated with each cell’s DNA will get slightly shorter with each new cell division until they shorten to a critical length. One a cell reaches the limit of division in the classic sense it enters a state of senescence or dormancy.
Please note, I have found that there is a great misconception by many, including doctors, about the concept of senescence. Most believe it is just simply ‘old age’. For those who do not know, senescent cells, simply put, just ‘exist’ (6). Unfortunately, viewing senescent cells as just ‘old’ cells, or ones that just ‘sit’ around, is a very narrow focus of the concept. We need to view the cell as not getting old but changing its cell state. For the floxed person its meaning is far more serious.
In our case these senescent cells, simply put, experience a false “aging” (6). They sit around, do not replicate and interfere with some metabolic process (6). In addition they use up resources. Technically, in our case, they do not contribute to positive functions of our body even though they remain metabolically active. The implications of this are vast, especially when the numbers of senescent cells grow. Depending on the amount and location in the body, senescent cells can cause: the morphological changes of skeletal muscle and tendon we see (7), vast neurological problems (8), ocular problems, and any other problems that you would see with rapid aging (9).
In addition, and a very critical point, some senescent cells adopt certain phenotypes as they enter into senescence (10). These phenotypes such as flattened cell morphology can interfere with tendon repair, or they can adopt pro-inflammatory secretory response could explain why some floxies have inflammatory or auto-immune issues and others do not.
Senescence in the body can serve a positive function. For example, if cellular changes activate the ‘oncogene’, this genetic change triggers cell senescence as a mechanism to protect against unregulated cell proliferation and the creation of tumors (14). Is it possible that widespread, above named influences, trigger a systemic cellular senescence response in the body of the floxed person? And that, depending on factors such as cell location and cell phenotype, the cell takes on a derogatory activity that interferes with tendon repair, causes inflammation, consumes resources and contributes to premature aging? I think this is entirely possible.
My article is not designed to provide definitive answers, nor can it. It is designed to present a theory that could hopefully now, or in the future, spur further investigation into how cellular senescence could play a role in the mechanism that creates long term chronic floxing. For some, there is a possibility that the factors that create this cellular condition, such as oxidative stress, could be tamed using novel agents, in the hope that the floxed person could get back on the front of the healing curve instead of behind it. Do not give up hope, someday we will find answers to our questions.