Monthly Archives: November 2017

Fluoroquinolones Increase Risk of Aortic Aneurysm

 

Evidence is mounting that fluoroquinolone antibiotics (Cipro, Levaquin, Avelox, Floxin, and their generic equivalents) increase the risk of aortic aneurysm and dissection, yet the FDA is denying the connection between fluoroquinolone use and the potentially deadly vascular conditions.

In a May, 2017 notice on fda.gov, the FDA stated:

“As part of our ongoing review of fluoroquinolone antibiotics, FDA is informing the public that patient cases identified by the FDA and findings from published studies currently do not support reports that these medicines may result in detachment of the retina in the eyes, or bulges or tears in the aorta blood vessel called aortic aneurysm and aortic dissection. We will continue to assess safety issues with fluoroquinolones and will update the public if additional actions are needed.”

This statement was made after two major studies were released, showing the statistically significant increase in risk of aortic dissection and aneurysm with fluoroquinolone use. “Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone” (JAMA Internal Medicine, 2015), and “Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study” (BMJ Open, 2015) both found that fluoroquinolone use is associated with an increased risk of aortic aneurysm and dissection, with “Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone” concluding that:

“Use of fluoroquinolones was associated with an increased risk of aortic aneurysm and dissection. While these were rare events, physicians should be aware of this possible drug safety risk associated with fluoroquinolone therapy.”

Both “Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone” and “Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study” are major studies, with “analysis of 1477 case patients and 147 700 matched control cases from Taiwan’s National Health Insurance Research Database (NHIRD) from among 1 million individuals longitudinally observed from January 2000 through December 2011” for the former, and 1.7 million older adults in Ontario, Canada, for the later. They are robust studies that show a statistically significant association between fluoroquinolone-use and aortic aneurysm and dissection.

Still, the FDA doesn’t acknowledge that there is a connection between fluoroquinolone-use and these potentially deadly disorders.

Before you defend the FDA by saying something like, “correlation doesn’t mean causation,” or, “an association doesn’t prove anything,” think about what it would take to do a study that would actually show a causal link between fluoroquinolones and aortic dissection and aneurysm–researchers would have to intentionally expose a group of people who they knew were at-risk for aortic dissection and/or aneurysm to Cipro, and another group of people who presumably had an infection to a placebo, then see whether or not they were hurt or died from the exposure. You can’t do this experiment on humans for fairly obvious reasons.

However, you can do the experiment with mice, and a team of researchers from Baylor College of Medicine, the Texas Heart Institute, and Baylor College of Medicine’s Cardiovascular Research Institute, “found that ciprofloxacin, a widely prescribed antibiotic, increases the risk of tears and rupture on the main artery of the body, the aorta, in a mouse model of human aortic aneurysms and dissections (AAD), a disease that carries high risk of death from aortic rupture.” (source) The study showed that:

“normal, unstressed mice treated with ciprofloxacin did not show significant negative effects on the aorta. In mice with moderately stressed aortas that had received the placebo, 45 percent developed AAD, 24 percent developed aortic dissection and none had rupture. On the other hand, 79 percent of the mice with moderately stressed aortas that received antibiotic developed AAD, 67 percent had aortic dissection, and 15 percent had fatal rupture. These results were similar in males and females.” (source)

Though mice with normal aortas weren’t negatively affected by the Cipro exposure, those with stressed aortas were harmed–some fatally. These results, combined with the human population-based longitudinal cohort studies noted above, show, as strongly as we can without subjecting humans to unethical experiments, that fluoroquinoloes (or at least Cipro), increase the risk of aortic aneurysm and dissection in those with previously stressed aortas.

To further their case that fluoroquinolone-use led to aortic aneurysm and dissection, the Baylor researchers also explored the mechanism(s) through which Cipro/ciprofloxacin damages the extracellular matrix, and contributes to the weakening of aortic tissues:

“The researchers then looked deeper into the effects of ciprofloxacin on mouse aortas searching for insights into the antibiotic’s mechanism of action. Compared with the aortas from stressed mice treated with the placebo, the aortic tissue of stressed mice treated with the antibiotic showed more destruction and fragmentation of elastic fibers; decreased activity of LOX, a key enzyme involved in stabilizing the extracellular matrix; increased activity of MMP enzymes involved in extracellular matrix degradation; and enhanced activation of cellular pathways that lead to cell death. Separate laboratory experiments on human aortic smooth muscle cells revealed that sustained ciprofloxacin exposure reduced the expression of LOX while enhancing the expression of MMP and inducing cell death. In these experimental settings, the antibiotic is disrupting the natural processes that maintain the integrity of the extracellular matrix that is essential for normal aortic function.” (source)

Links to studies that show that fluoroquinolones increase expression of damaging MMP enzymes, as well as oxidative stress, can be found in the posts, “Fluoroquinolones Increase Expression of MMPs” and “Antioxidant Depletion by Fluoroquinolones.

The evidence that fluoroquinolones increase the chance of aortic aneurysm and dissection in succeptible individuals is significant. The large population-based studies are compelling, the mouse study establishes a stronger causal link, and many studies that show the damaging effects of fluoroquinolones on cell, collagen, and extracellular matrix, health, each add weight to the argument that fluoroquinolones are contributing to potentially deadly aortic aneurysm and dissections. Yet, the FDA is still claiming that studies don’t support a connection. I’m not sure what else they need in order to convince them that aortic aneurysm and dissection are, indeed, linked to fluoroquinolones. The evidence seems strong and compelling to me, and I suspect that they are just wrong.

Additionally supporting the link between fluoroquinolones and aortic aneurysm and dissection are personal testimonials of connections and damage done. In comments on the post, “Hurt by a Generic Drug? Victims have no Recourse unless the FDA Changes Rules,” published on hormonesmatter.com, one person noted that:

“I took a generic levaquin, a week or so later I had an aortic dissection. It was descending so it was not fixed by surgery. I now have an aortic aneurysm. The tear is pasted together with blood clots. A CT scan every 6 mos to check the size of the aneurysm. Keep my bp below 120.”

Another responded that:

“Took generic Leviquin 7 weeks later aortic dissection. Tore 2 layers of muscle from over my aortic valve down thru and ended in my thighs. Doctor said I would not survive operation. Tear was so big over the valve had to put in synthetic patch.”

In testimony to the FDA, Sherry Reiver stated:

“Four years ago today, my 93 year old dad died. He FELL at home and was taken to the hospital by a neighbor. By the time my husband and I arrived in Florida, my dad had no idea who we were. They THOUGHT he had pneumonia so they IV’d him with Levaquin. It turned out that he did NOT have pneumonia but he continued to hallucinate for 6 weeks and then died. He was sharp as a tack before Levaquin dripped into his body. He did have an aortic aneurysm for many years which was being watched but it ruptured on November 4th. I would have never connected the AA with FQs until I read this research paper dated October 5th 2015. So here is another RARE side effect that can occur, which it did in my dad’s case. How many others have died from AAs and had taken a FQ drug?”

There is significant evidence that fluoroquinolones contributed to these aortic aneurysms and dissections, as well as those of thousands of other patients. These patients weren’t warned that fluoroquinolones could increase their chances of aortic aneurysm or dissection, and they haven’t had the opportunity to gain retribution or justice, in part because the FDA has failed to acknowledge the connection between fluoroquinolones and aortic aneurysm and dissection.

With the publishing of the Baylor mouse study, I hope that the FDA will acknowledge the connection between fluoroquinolone use and aortic aneurysm and dissection. I also hope that acknowledgement from the FDA will lead to justice for victims, and pain for the pharmaceutical company perpetrators who produce and market these dangerous drugs.

Also, all of the studies that connect fluoroquinolones to aortic aneurysm and dissection are greatly appreciated, and I want to thank all of the researchers and scientists who conducted the studies, as well as those who fund them. Research into adverse drug reactions, and patient safety, are important. All of the researchers and scientists who look into adverse drug reactions, especially fluoroquinolone reactions, are appreciated, and I thank them sincerely.

 

 

 

 

Is Big-Pharma Silencing You?

Every once in a while someone asks me if I’m afraid that Bayer or Johnson & Johnson will retaliate against me for speaking out about the dangers of fluoroquinolones, and specifically the fluoroquinolones they manufacture, market, and distribute–Cipro and Avelox by Bayer, and Levaquin by Johnson & Johnson.

The answer is no.

No, they haven’t done anything bad to me, and no, I don’t think or fear that they will.

Not that corporate pharmaceutical companies like Bayer and J&J haven’t been evil before–they have, and I’m sure they are currently being evil, and will continue to be evil into the future–I just don’t think that they’ll be evil or vindictive toward me.

As a patient, patient advocate, and blogger, I don’t think I’m on their radar. Perhaps I’m naive for thinking that–I just have a hard time believing that big bad Bayer actually cares what little me (Lisa) has to say. In some ways, I wish they did. If they cared, it would be because they felt threatened, and to be capable of threatening big-pharma would be pretty amazing. I don’t think I’m on that level though–for better or for worse.

When I first started this site I asked an attorney how I should protect myself. She said, “always tell the truth,” and “they can’t argue with your story – it’s yours.” Just like my story and truth are valid, your story and truth are valid too. This site has my story, and the stories of others like me who have been hurt by fluoroquinolones. Our stories are true. They are our testimonials. They are what happened to us. No one can take away our experiences, our truths, or our stories. Our stories are valuable beyond measure, and they are making a difference in how people think about fluoroquinolones specifically, antibiotics generally, and even about how pharmaceutical reactions are connected to various illnesses and symptoms.

I want everyone to be empowered to share their story. Stories of pain and injury caused by fluoroquinolones are important and they matter. So, it bothers me when people refrain from telling their stories/truths out of fear that Bayer or J&J will retaliate against them. I can’t know what will happen to anyone in the future, but I can tell you that over the past 4+ years of running this site, having my story of fluoroquinolone toxicity available, and writing about the dangers of fluoroquinolones, neither Bayer nor J&J have done anything bad to me. (And while this means that I’m not as threatening to them as I want to be, it also means that I’m not having my life ruined, and, well, that’s a good thing IMO.)

What bothers me even more than fear-based self-censorship of patients is fear-based self-censorship of scientists, researchers, and doctors. A floxed friend approached a research scientist she knew personally and professionally to ask if he would do some research into fluoroquinolone toxicity, and he declined while flippantly saying something about not wanting to jeopardize his future funding prospects. I have no idea whether or not researching fluoroquinolone toxicity would affect this research scientist’s future funding prospects, but the fact that he fears pharma reprisal, and is willing to overlook horrifying fluoroquinolone reactions in his friend and colleague just to avoid the possibility of big-pharma’s reprisal, is bothersome. Unfortunately, reluctance to take on and question pharma seems common among researchers. As the saying goes, “don’t bite the hand that feeds you,” and so much research (even academic research) is funded, at least in part, by pharmacuetical companies.

Pharma money controls the conversation. They don’t have to make overt threats. They don’t have to ruin the lives of scientists (though they do, as seen in the story of the battle between researcher Tyrone Hayes and big-ag chemical giant Syngenta or the destruction of Andrew Wakefield’s career over his questioning of the effects of the MMR vaccine on the gut biome). They just have to control the purse-strings, and many people will fall in-line.

When research scientists limit the questions that they are willing to ask in order to avoid rocking the pharma boat, they are doing us all a dis-service. There is nothing thoughtful, curious, righteous, or even scientific about failing to research adverse drug reactions out of fear of reprisal from pharma, and drugs will continue to be more and more dangerous if all incentives are for research scientists to look away. I hope that my friend’s friend is unusually timid, and that most research scientists are willing to challenge big-pharma. Though I hope that, I don’t believe it. I believe that most research scientists are falling in-line with what their funders want, either consciously or unconsciously, and that because of biases toward their funders, we, as patients and consumers, are less safe.

I have hope that individuals will get over their fear of big-pharma, and speak out about the harm that they have experienced as a result of fluoroquinolone toxicity or other adverse drug reactions. (Shout your truth – tell your story – it’s empowering – trust me, it really is!) I even have some hope that individual scientists will face their fears and confront their big-pharma funders. But I have less hope that the system of corporate, academic, and even government “science” will go against the big-pharma, big-ag, and big-chemical giants that fund and feed them. It’s too scary. Even if the fear is largely self-inflicted, it’s still too scary for most people to question and challenge paradigms.

When I got floxed, I couldn’t help but question my existing paradigms. A pharmaceutical, an ANTIBIOTIC no less, hurt me. It made me ill for a long time, and there was nothing that doctors could do to help me. I didn’t gain any acknowledgement, support, or solutions from traditional doctors (some people do though, everyone’s experience is different). It made me realize that when the medical system hurts people, they don’t know how to put them back together, and all my assumptions about the ability of the medical system to solve human health mysteries went out the window. I realized that the doctors in the Western medical system have no idea how to treat complex illnesses like fluoroquinolone toxicity (or other multi-symptom, chronic illnesses), and that the patients dealing with mysterious illnesses are largely on their own. When I realized that pharmaceuticals are hurting people and leading to chronic illness, I started to question whether or not the good done by pharmaceuticals is worth the harm. I started to see that many of the illnesses of modernity can be linked to pharmaceuticals (and antibiotics specifically, and fluoronated drugs specifically), as well as the endocrine-disrupting chemicals of big-ag and other corporate chemical companies. My paradigm shifted when I got hurt by ciprofloxacin, so it wasn’t a risk to my world-view to actively criticize Bayer, J&J, or the other pharmaceutical companies after-the-fact. There are many obvious disadvantages of getting hurt by ciprofloxacin and other pharmaceuticals, but a silver lining was that my world-view shifted, and my fear dissipated.

I’m not afraid of big-pharma. Maybe it’s because I’m naive about their power, influence, and ability to ruin my life. Maybe it’s because I’m not a threat to them, and neither of us have any reason to fear the other. But I like to think that I don’t fear them because my world-view doesn’t give them power any more. Of course they have actual power–they have money, influence, and the ability to poison and hurt me, every other human, and the earth–but they no longer have the power of me believing that they are the answer. I don’t believe that they are the answer. I believe that they are the problem. And I believe that challenging them is the right thing to do. I also believe that answers to the problems caused by pharmaceuticals are in the stories of patients who are willing to speak out about what happened to them, and in the willingness of researchers and scientists who are willing to buck-the-system and question the pharma paradigm. Some bravery is required on behalf of both patients and scientists who question and challenge big-pharma. The bravery is worth it though, and others may find, like I did, that there is nothing to fear but fear itself.

 

 

 

Fluoroquinolones Increase Expression of MMPs

Fluoroquinolones degrade both the cellular matrix and collagen, and degradation of both are related to all the symptoms of fluoroquinolone toxicity. Torn tendons, nerve damage, and even memory loss and aging can be linked to cellular matrix and collagen degradation.

One theory as to how fluoroquinolones cause cellular matrix and collagen degradation (and tendon ruptures, and the hundreds of other symptoms of fluoroquinolone toxicity) is by selectively increasing expression of matrix metalloproteinases, or MMPs.

The article, “Clinical implications of matrix metalloproteinases” notes that:

“Matrix metalloproteinases (MMPs) are a family of neutral proteinases that are important for normal development, wound healing, and a wide variety of pathological processes, including the spread of metastatic cancer cells, arthritic destruction of joints, atherosclerosis, pulmonary fibrosis, emphysema and neuroinflammation. In the central nervous system (CNS), MMPs have been shown to degrade components of the basal lamina, leading to disruption of the blood brain barrier and to contribute to the neuroinflammatory responses in many neurological diseases.”

Information about the effects of fluoroquinolones on the cellular matrix, collagen, and MMPs can be found in these articles:

Though un-doing the damage caused by MMP expression from fluoroquinolones is easier said than done, there are some natural MMP inhibitors that may be helpful.

Chondroitin sulfate inhibits MMPs. Several marine animals contain chondroitin sulfate, and it can be found in shark cartilage, sea cucumbers, as well as marine heparin extracted from shrimp and sea squirt (source). According to the article, Angiogenic inhibitor protein fractions derived from shark cartilage, “Shark cartilage has been proven to have inhibitory effects on the endothelial cell angiogenesis, metastasis, cell adhesion and MMP (matrix metalloprotease) activity.”

A “floxie” friend reported that he had been helped immensely by supplementing shark cartilage. (I honestly have really mixed feelings about suggesting that shark cartilage may be healing because I like sharks, but that’s beside the point, and I don’t want to withhold information from you because I feel uncomfortable about consuming shark byproducts.)

For those who (like me) aren’t comfortable supplementing shark cartilage, some other natural supplements that are MMP inhibitors include (source):

  • Soybean Seeds
  • Citrus Fruits
  • Berries
  • Curcumin
  • Green Tea
  • Black Tea
  • Grapes

Those things certainly fall into the “worth a try” category. Unfortunately, I haven’t heard of anyone having dramatically positive results from eating berries or grapes, but they probably won’t hurt you, and are likely worth trying.

It is also worth noting that tetracycline antibiotics including doxycycline (NOT a fluoroquinolone), are also MMP inhibitors. The article, Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells, notes how tetracycline antibiotics are bacteriostatic, not bactericidal, and how bacteriostatic antibiotics don’t cause the damage that bactericidal antibiotics inflict, and may even mitigate the damage caused by them. Low-dose doxycycline (or another tetracycline antibiotic) may help to inhibit MMPs and therefore mitigate damage and even promote healing. (Ask your doctor before starting this method.)

Though MMP activation is related to connective tissue breakdown, all fluoroquinolone toxicity symptoms, as well as cancer, arthritis, neuroinflammation, and more, to say that they are “bad” is overly simplistic. Everything in biology and health is complex and multifaceted. There are intricate feedback and feed-forward loops in many inputs. There are no easy or simple answers or cures.

With that said, MMP inhibitors may be helpful. Shark cartilage helped my friend, and it, or the other MMP inhibitors noted, may help you.

Though our bodies are complex, and there doesn’t seem to be a “magic bullet” that cures fluoroquinolone toxicity (or any other complex multi-symptom illness), there are things that can help push your body back to a state of health, and MMP inhibiting food and supplements are on that list.