In this presentation Dr. David Perlmutter discusses the widespread misuse of antibiotics in the United States and highlights emerging evidence that common bactericidal drugs can damage human mitochondria. He explains the endosymbiotic theory that mitochondria originated from bacteria, making them susceptible to antibiotics that target bacterial processes. Perlmutter reviews a laboratory study in which human mammary cells were exposed to ciprofloxacin, ampicillin, and kanamycin, resulting in marked increases in reactive oxygen species, hydrogen peroxide, lipid peroxidation, and DNA oxidation (8‑OH‑dG). The antioxidant N‑acetylcysteine (NAC) was shown to blunt much of this oxidative damage without compromising the antibiotics’ antibacterial activity. He notes known clinical toxicities of these drug classes (ototoxicity, nephrotoxicity, tendon injury) and stresses that mitochondrial injury has been largely overlooked. While he does not prescribe NAC, he urges more judicious antibiotic use, invoking the medical principle “do no harm.” The talk concludes with a call for clinicians and patients to consider mitochondrial health when prescribing or taking antibiotics.
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Hello everyone, Dr. David Perlmutter here. Welcome to the program. I've talked quite a bit about the dangers of antibiotics, and again, let me just be clear that there is certainly a time and a place when we need antibiotics. They can be life-saving. We recognize that our own Centers for Disease Control and Prevention indicates that about 30% of antibiotics used in America are used inappropriately, so prescriptions written for reasons that really are not justifiable. We generally think that the risks of antibiotics include the creation of antibiotic-resistant organisms, making it difficult to treat certain infections, and as we've now learned, there are risks imparted on the gut bacteria that happen when antibiotics are used. Otherwise, you know, we generally consider that taking antibiotics isn't going to have an effect on our cells because, hey, our cells are not bacterial cells. But it turns out that the mitochondria within each of our cells, the energy harvesting part of our cells that powers the cells— you may have as many as 1,000 mitochondria in every brain cell— may have been derived from bacteria. In fact, that endosymbiotic theory was developed by Dr. Lynn Margulis in 1968. So there's many characteristics of the mitochondria that look a lot like bacteria. For instance, the DNA of the mitochondria is in a circular pattern, which isn't like it is within our cells. And many other factors make us think that in fact these mitochondria were once free-living bacteria. And new research is actually demonstrating that certain antibiotics, certain very commonly used antibiotics, may actually damage mitochondrial function. When we recognize that mitochondria are really important considerations in things like Alzheimer's and Parkinson's, for example, then this adds a new level of relevance in terms of our considerations with reference to how safe our antibiotics might or might not be. Let's take a look at this study. This is a very intriguing study, and it's entitled Bacterial Rather Bactericidal. I'll explain antibiotics induce mitochondrial dysfunction and oxidative damage in mammalian cells. Bactericidal means it kills bacteria, and what the researchers are telling us is that these antibiotics are disruptive to the function of. the mitochondria. They took human mammary cells and they gave them— they put in their environment Cipro, ampicillin, or kanamycin, which is an aminoglycoside. These are the fluoroquinolones, the beta-lactams, and the aminoglycosides are very commonly used classes of antibiotics. When looking at the reactive oxygen species, or the free radicals if you will, the percentage change over control You see in the untreated group, which is at the very left side of both of these graphs, the gray, that there was no increase of these reactive oxygen species. But when the Cipro in green, the ampicillin in tan, and the kanamycin in red were given, a dramatic increase in the production of these reactive oxygen species, or free radicals, at both 6 hours and 96 hours. Looking specifically at hydrogen peroxide, again, a pretty dramatic increase production at the 96-hour point. Looking at the damage to fat or lipid peroxidation, that happened more acutely and then did tend to taper off at the 96-hour point. But something actually very intriguing happened here. What could cause this dramatic reduction in the damage to the lipids or the fat, the free radical damage. And what happened was they added something to the experiment by putting NAC in the environment. So what we see here is that NAC was able to reduce the damage to the fat brought on by the free radicals in the presence of these antibiotics. Similarly, when looking at 8-OH-DG, that's a marker of damage by free radicals to DNA. Again, a significant reduction after NAC was added. The researchers stated that with the belief that antibiotics specifically target bacteria, the consequences of how they interact with mammalian cells have largely been overlooked. Despite instances of known adverse effects including ototoxicity, damage to the ear, kidney damage, and tendon damage. In other words, we've always been taught that the antibiotics have no effect upon our cells, but only on bacterial cells. And again, as I mentioned, this endosymbiotic theory that mitochondria were once actually free-living bacteria themselves. That we've got to begin considering these potential damaging effects upon our mitochondria from commonly used antibiotic— antibiotics. By giving NAC, the researchers found that some of these damaging effects could be abrogated or ameliorated while having little effect on the ability of the antibiotics to do their job, and that is to take care of getting rid of dangerous bacteria. So all in all, a very interesting study. So this is an eye-opening report, isn't it? It reveals that at least in the laboratory and in the cells that were studied, these human mammary cells, that some very common classes of antibiotics actually and significantly damage mitochondrial function, and we see a dramatic increase in the free radicals, the damaging free radicals that are created when these cells are exposed to this mitochondrial toxin in the form of commonly used antibiotics. Beyond that, I think what was very interesting is that the mitochondrial function was preserved when an antioxidant was added, an off-the-shelf antioxidant that is available in health food stores called NAC. So there's no real recommendation here about using NAC when you take an antibiotic. I don't think we're able to connect those dots yet. I think though the main take-home message here is that we've got to be judicious with our use of antibiotics and really practice under the idea of above all, do no harm. Now that we understand that mitochondria may be at risk, when exposed to antibiotics, it adds yet another level of our concern about the capricious use sometimes of these types of drugs. Well, I hope you found that interesting. I think it's a really interesting study. Thanks for joining us. I'm Dr. David Perlmutter.
