Decades ago, women who had bravely fought breast cancer and survived, started describing various adverse symptoms long after completing their course of chemotherapy. One of the most predominant adverse symptoms was cognitive impairment or “brain fog.” For a long time, most women who brought up these symptoms found their concerns dismissed by doctors (1). Brain fog wasn’t considered a valid medical condition and a narrow way of thinking prevented doctors from connecting disparate symptoms and for a long time prevented doctors from recognizing it. This is despite the fact that ALL the women had chemotherapy as the common factor.
The medical community has a long-standing reputation for dismissing patient complaints that fall outside standard paradigms. It is the old adage, “can’t see the forest through the trees.” This behavior isn’t unique to just a certain select group of chemotherapy patients, this dismissal of patient complaints is fairly universal phenomenon.
Despite the fact that common sense should have prevailed, Julia Rowland, Ph.D., director of NCI’s Office of Cancer Survivorship said that doctors are starting to realize that “you have to understand what the consequences of therapy are and that very few if any of our treatments are entirely benign,” something that patients have known for a very long time.
Chemotherapy Brain or “Chemobrain”
Like previously mentioned, one of the major phenomenon that these aforementioned cancer survivors were describing was cognitive impairment or colloquially coined as “brain fog.” Since they were all chemotherapy recipients the moniker “chemobrain” was coined. One of the predominant symptoms they experienced was cognitive impairment, but researchers fully admit that the patients experienced varied impairments, with cognitive impairments, fairly universal.
Because of the sheer number of chemotherapy-induced cognitive impairment reports or complaints, the phenomena is now becoming increasingly recognized as a significant complication of cancer chemotherapy (2).
Despite the increased attention this issue has garnered from the clinical and research communities, the mechanisms of the resulting cognitive impairment are not fully understood but are thought to be caused by the peripheral toxic effects of chemotherapy drugs that lead to downstream structural and functional changes in the brain.
It is determined that chemotherapy exposure causes changes in global genome DNA methylation and hydroxymethylation. These changes directly exert epigenetic pressures and change gene expression in areas that are important in health and disease. Of these areas affected are cognitive regulation, memory and aging (3). These Central Nervous System (CNS) adverse events effects “aka Chemobrain” have been reported in several forms of chemotherapy, but interestingly enough one of these is topoisomerase inhibitors (3).
Now let’s make some logical connections:
Fluoroquinolones are topoisomerase inhibitors (4).
Fluoroquinolones affect methylation and epigenetics in “mammalian” eukaryotic cells (6).
Fluoroquinolones cause CNS adverse events, so much so that the FDA required a class wide labeling change to list CNS adverse events in their own ‘mental health” label classification (7).
Of these FQ CNS adverse events “brain Fog” is a commonly reported adverse event, whose duration can vary from short to long term, and in some cases be quite debilitating (8).
It is my contention that FQ induced “brain fog” is, at its very essence, Chemobrain.
Let’s look at some compelling causes…
How FQ’s Could Cause Chemobrain
In October of 2018 an 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 (9).
Researchers found that mitochondria contain two forms of Topoisomerase 2. The isoforms of Topoisomerase 2 are Top2α and Top2β. These isoforms have specialized roles in the maintenance of the nuclear genome and mitochondrial genome. For our discussion we will focus on Top2β.
It is imperative that Top2α and Top2β function correctly to maintain mitochondrial homeostasis which allows for damage to be repaired to a certain degree. Their research documented that Ciprofloxacin caused a dramatic effect on mtDNA topology, causing various insults to the DNA such as blocking replication initiation, reducing copy number and inhibiting mitochondrial transcription. Additionally, 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 (10).
Interestingly, their researchers found that Top2β, affected by the FQ’s, exists in brain mitochondria at far higher levels compared to other tissues. Let me repeat that, Top2β, affected by the FQ’s, exists in brain mitochondria at far higher levels compared to other tissues. This suggests a specific demand for mtDNA topology regulation in the delicate neural cells. This would logically explain why we see a whole host of neuropsychiatric effects of FQ’s, including brain fog or or FQ chemobrain. These adverse events are commonly seen and reported by many individuals in the FQ community, acknowledged in case reports (8) and recently researched and documented by Dr. Bennett (11).
Dr. Noble’s Research
In 2006, research from a team led by Dr. Mark Noble, professor at the University of Rochester Medical Center, revealed the shocking extent of the chemobrain problem: common chemotherapy drugs used to treat breast, ovarian, and colon and rectal cancer, as well as non-Hodgkin’s lymphoma, were more toxic to multiple kinds of brain cells than the cancer cells themselves.
Dr. Noble has worked with the FQ community in the past at our behest. Our team initially contacted Dr. Noble in 2010 due to his research with chemotherapeutic pharmaceuticals such as 5FU, chemo brain, and the capabilities of his lab. We noticed strong similarities in the adverse events of fluorouracil (5FU) and that of FQ’s. This information can be read here and here.
A later study by Noble’s team done in mice showed that another commonly used chemotherapeutic drug caused damage to oligodendrocytes, the cells that cover axons with myelin. Myelin helps expedite messaging among nerve cells, or neurons. When oligodendrocytes are damaged, myelin breaks down, disrupting communication among the nerve cells vital to brain functioning.
From Dr. Noble to our FQ team in 2010…. To put our findings on Levaquin in the context of our previous work on chemotherapeutic agents, the outcomes of the Levaquin experiments are disturbingly similar to the kinds and levels of toxicity that we initially found in our work on 5-fluorouracil. When clinically relevant drug concentrations exhibit such toxicities in vitro, this is very troublesome.”
Dr. Noble found the same disturbing toxicities to the myelin–forming oligodendrocytes of the CNS when exposing them to Levaquin (FQ’s), just as if they were negatively affected by commonly used chemotherapeutic drugs such as 5-fluorouracil.
Other researchers at the University of Rochester Medical Center hypothesized the drugs that cause chemo brain are those best able to cross the blood-brain barrier. Which as most people know, is no problem for the FQ’s (18).
How Common is FQ Chemobrain?
Very common. I would call it a class effect. Almost all floxies suffer from it to one degree or another in their timeline. Anecdotally the data on brain fog is all over the place in terms of onset, duration, and severity with some individuals barely bothered by it, while others are incapacitated by its brain numbing effects. The one thing that is true is that it happens very frequently.
For me I suffered from FQ Chemobrain starting about two years post floxing and it lasted moderately for about a year. I still occasionally get bouts of it when my CFS symptoms are bad. I was blessed that I maintained my IQ although I have had reports of individuals who felt they were ‘dumbed down’ by the horrible affects of the FQ’s.
For the majority, especially those experiencing an immediate adverse event, FQ Chemobrain shows up quite soon after the adverse event ensues, but we have had reports of cases showing up as long two years or longer post floxing. Then there are the others who have reported cyclical FQ Chemobrain manifestations.
Common Cause, Uncommon Trajectory
Despite the fact that brain fog could, at its core, be easily caused by Top2β inhibition or Dr. Noble’s nerve damage findings, what follows after FQ exposure is a study in chaos theory. Like branches in a tree, the tentacles of FQ pathology could encompass a vasts array of options. In floxies we have found mast cell activation, alterations in neurotransmitters, dysregulation of blood pressure and/or blood sugar, poor quality sleep, toxin overload from SIBO or Candida, and much more which can all contribute to brain fog.
Because of this brain fog, especially in floxies, is very hard to universally dissect. Although each floxed person could have similar brain fog symptoms, the underlying pathology, despite being initiated by the FQ’s, can be wildly variable.
The good news is that, in time, the symptoms of FQ Chemobrain, for many, seem to lesson. Because the symptoms and severity differ from person to person, treatment for brain fog tends to be quite personal. For some, finding a professional that could work with them to develop an individualized approach was one of the best options, but also one of the hardest to do. These professionals ranged from neuropsychologists to Naturopaths, but according to the opinion of many, finding care is easier said than done. Unfortunately it has left a majority of floxies to experiment on their own to find out what works and what doesn’t work for them.
To reiterate, since there is no one-size-fits all solution, finding substances to help with brain fog is very individual. In the next section I will list a few supplements that came in as being higher rated as help some individuals.
Please Note: this brain fog help list is not all inclusive nor is it listed in order of effectiveness or importance. It was compiled by information supplied by floxed individuals.
Clinical trials involving Rhodiola rosea show that it fights brain fog by energizing the central nervous system. Animal studies involving Rhodiola indicate it also repairs damaged neurons and stimulates brain cell growth in the hippocampus. (12)
In a randomized, double-blind, placebo-controlled study involving 60 adult men and women who reported symptoms of mental fatigue, Rhodiola rosea increased attention, reduced fatigue, and improved cognitive function. Researchers concluded that, “Rhodiola, acting as an adaptogen, increases attention and endurance in situations of decreased performance cause by fatigue. (13)
Rhodiola is best known for its mood-boosting, stress-busting properties. For mental fatigue and brain fog caused by burnout, Rhodiola’s mechanisms work to protect the brain from the effects of stress and repair damaged cells.
Citicoline is considered a powerful all-around brain boosters. There are several clinical studies that show that citicoline boosts mental energy by improving cerebral blood flow and protecting brain cells from free radical damage. This nootropic is so powerful that it’s used to enhance cognitive function damaged by neurological disorders or brain trauma.
Citicoline boosts acetylcholine levels, a neurotransmitter closely involved in learning and memory. Citicoline contains CDP choline, an active component of phosphatidylcholine, a phospholipid that preserves brain cell membranes, protects memory, and facilitates neural communication.
A study investigating a certain form of Citicoline, called Cognizin® found that citicoline can mitigate the effects of mental fatigue by increasing frontal lobe activity brain energy reserves.(14)
There are some cautions that need to pointed out. The FQ’s interfere with acetylcholine levels. For instance, the FQ’s are contraindicated in those with Myasthenia Gravis because they exhibit a peculiar nerve blocking capability. The exact mechanism by which FQ’s affect neuromuscular transmission is not entirely understood; however, a main theories are that they inhibit acetylcholine release presynaptically and/or they have a direct toxic effect on the acetylcholine channel. I lean towards the latter.
Another caution is that some floxes have reported that too much CDP choline can actually worsen brain fog. Even the study mentioned above showed that research participants benefited more from a lower dose. More is not better with this nootropic.
It is theorized that brain fog can appear in floxies after the depletion of catecholamines like dopamine and norepinephrine that your brain needs to stay sharp and quick. Again, another effect of the FQ’s.
A lot of floxed individuals report that after floxing when the put some stress on their brains, a downward cognitive spiral results in crippling brain fog.
N-Acetyl L-Tyrosine (NALT) combats brain fog by boosting catecholamine levels. It can help some meet the demands of stress and protecting cognitive functions.
Animal studies show that tyrosine supplementation lowers stress levels, enhances catecholamine synthesis, and protects the brain from neurochemical depletion. This multi-faceted approach staves off brain fog by preserving cognitive functions like learning and working memory.(15)
Phosphatidylserine a phospholipid and is a component of the cell membrane, seems to have a positive affect on short-term and long-term memory functions like learning, recall, and attention.
It works by protecting the myelin sheath that surrounds nerve pathways and cell membranes. Studies show that its protective mechanisms can safely slow, stop, and even reverse nerve cell deterioration. Better nerve cell integrity and communication improves concentration, problem-solving, communication, and language skills.(16)
Human studies show that phosphatidylserine is effective for preserving cognitive activity, protecting against cognitive aging, and retaining optimal cognitive functioning abilities. This was personal favorite of mine years ago when I suffered from brain fog. It also had the added benefit of helping me to have less disturbed sleep by cortisol spikes. There is also a soy free variety, for those sensitive to soy.
Magnesium has mixed reviews among floxies where some have touted it as a miracle cure to others who feel much worse after they take it. There is a lot of questionable information floating around about magnesium and floxing in general and the theory that magnesium, or the lack thereof, plays a role in floxing is still controversial. Some misinformation about Mag is pushed by those selling ebooks. The problem is that different forms of magnesium do different things in the body. For instance magnesium glycinate is the best form to help with sleep. Magnesium plays a very important role in the many metabolic reactions but that is not our focus right now. Anyway, Magnesium l-threonate is not your run of the mill magnesium either. Many individuals are very surprised by this supplement after given it a try, even by those cynical individuals who have tried other forms of magnesium in the past with little to no effect.
According to an MIT, this form of magnesium, albeit rather expensive, was shown to be effective at loading magnesium into the brain and at enhancing brain function. Their results were that As a result, studies show that magnesium-L-threonate improves brain plasticity, leading to direct and significant improvements in memory, learning, and cognition (17). Some floxies have reported this form of magnesium has help their brain fog considerably.
On average it takes while for Magnesium l-threonate to build up enough to start working but again this varies greatly from person to person.
Lipids are a key cellular component in our body. Phospholipids, a class of lipids, or fats, are especially crucial to the health of both cell membranes and neurotransmitters. Brain cell membranes are rich in two phospholipids in particular: phosphatidylserine (mentioned above) and phosphatidylcholine (also, mentioned above as well in the form of Citicoline), with PC accounting for the larger percentage.
There is something called the gut-brain axis in our body where the brain and GI tract constantly communicate with each other by sending signals. Many of these signals involve both initiation and halting of inflammation. With excessive inflammation initiated in the brain, it can lead to a “leaky brain”, which mostly translates to slowed mental ability and brain fog.
Some individuals have found success in using standard lecithin to help combat brain fog. It is usually much less expensive than some of the more ‘tailored’ supplements and contains necessary phospholipids for brain health. Regardless of whether it helps with the brain fog or not, I believe lecithin is a good foundational supplement for overall cellular health.
Obviously this list is not all inclusive. I am sure that there are many other individuals that have found supplements or treatments to help their brain fog. If you have used something that has helped, please be sure to share it with me so I can supply that data to others.
Until the medical community understands that FQ’s are, in essence, chemotherapy (and that is not too likely anytime soon) we will see these adverse events treated as disparate pieces of information and not connected to one another.
Do you know of a loved one, a friend, a co-worker, or someone else who suffers from brain fog of unknown origin? If so ask them to do some detective work and search their medical history, and not necessarily their immediate past. Tell them that FQ’s are often given during surgery, often without the patient’s knowledge.
If you are faced with potential antibiotic use, for yourself or a loved one, please become informed as to the choices that you have available. If antibiotic use is necessary, there are generally safer alternatives than the Fluoroquinolones. Discuss all concerns with your doctor about treatment to help you choose the safest possible method.