Disturbing Levaquin Findings – Dr. Mark Noble, Part # 2

Note: This is Part 2 of a two part series covering academic research with Dr. Mark Noble of the University of Rochester. Read Part 1 here.

In this article, Part 2, Dr. Noble reports to us, in his own words, disturbing Levaquin toxicity findings that he discovered.  His findings became the impetus for pursuing further FQ research and our team has been working with him since.

Dr. Noble:

“After discussing the potential toxicity of Levaquin and other fluoroquinolones with you, we initiated analysis of Levaquin on the precursor cells that generate the myelin–forming oligodendrocytes of the CNS. Our past studies indicate that these cells are particularly useful for detecting potential CNS vulnerabilities, as our knowledge of how to grow these cells in tissue culture is so extensive that results we obtain in a tissue culture dish are virtually always predictive of what we will find in vivo. Of greatest relevance to considering the neurotoxic effects of fluoroquinolones in a surprising number of individuals, the in vitro studies we conducted on these cells and on other cells of the central nervous system were completely predictive of the adverse effects of chemotherapeutic agents on cells of the CNS.

The results obtained in our preliminary studies are quite disturbing. Applying Levaquin to CNS precursor cells at a concentration less than that thought to occur during the patient treatment, we already found some hint of a vulnerability. As individuals taking Levaquin are also likely to be taking other compounds, we also combined this antibiotic with a variety of over-the-counter anti-inflammatory agents. We found a striking combinatorial effect when Levaquin was combinDr Noble smalled with naproxen, the active ingredient in Alleve. By itself, neither compound caused a striking reduction in cell numbers after 24 hours of exposure. When applied in combination, however, there was a greater than 65% reduction in numbers of cells, a very toxic effect at such a short exposure period. This combinatorial effect was not only seen when Levaquin was combined with the naproxen, but also was seen when Levaquin was combined with prednisone. Thus, both a steroidal anti-inflammatory agent and a non-steroidal anti-inflammatory agent are able to cause marked toxicities for CNS cells when they are applied in combination with Levaquin. These results indicate that the combination of Levaquin with other agents is going to be of particular importance to examine.

We also initiated analysis of the molecular effects of exposure to Levaquin, naproxen or a combination of the two; the studies revealed a potential mechanism of action and reinforced concerns about the importance of studying Levaquin in combination with other agents. Two of the outcomes are of particular concern. In one set of experiments we found that the combination of Levaquin and naproxen causes a dramatic (>80%) reduction in the levels of cell surface receptors that are required for normal division of the precursor cells that make myelin–forming oligodendrocytes and that also are required for normal development of neurons in the hippocampus, a part of the brain that is of central importance in learning and memory. These reductions have been shown by our previous studies to be caused by oxidative stress. In addition, we found that exposure to these compounds causes a marked elevation in two proteins that are known to be induced by oxidative stress. These proteins (called p21 and p27) are well-studied indicators of cellular stress, and are known to cause division to cease in a wide range of precursor cells. There was a 240% increase in levels of p27 and a 400% increase in levels of p21 in cells exposed to this combination of agents. Such findings provide the clues necessary to initiate an efficient analysis of the molecular mechanisms underlying Levaquin–mediated toxicity.

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.”

As you can plainly see, Dr. Noble’s findings are indeed disturbing. We know that fluoroquinolones are toxic in and of themselves, but how many unsuspecting people are taking them in combination with over the counter non-steroidal anti-inflammatory agents or with prescription steroidal anti-inflammatory agents? His experiments showed anywhere from 65% to 80% damage to neurological cellular mechanisms.

The tide is turning. The toxicity profiles of these drugs are getting harder and harder to ignore.

We want to thank Dr. Noble for listening to us in the past when we approached him in 2010, and his continued work researching fluoroquinolone toxicity. Our group will continue to work closely with Dr. Noble, and other researchers in our communities’ goal of exposing the true impact that FQs are having on our society.

Stay tuned to My Quin Story as I will be sure to inform the FQ community of any pertinent developments with Dr. Noble, Dr. Golomb, Dr. Bennett, and other pertinent issues.

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Admin

...damaged by fluoroquinolones in 2007 at age 46. Prior to, a healthy law enforcement official. Now an amateur FQ researcher, author, and blogger.

11 Responses

  1. Traci Walt says:

    I always want the doctors and/or researchers to come back with information that will hopefully prevent others from taking a fluoroquinolone, however the information is sometimes very overwhelming to those of us that have already taken and trying to find the way out of the nightmare. Thanks Dr. Noble and Dave for doing the research and objectively dispensing. It may scare me, but I’d rather know that be in the dark.

    • Admin says:

      Thank you Traci. Yes it is sobering indeed but please hold on to hope. There are a few researchers that are looking at novel ways to compensate for some forms of this damage. I will be sure to report on those when I can.

  2. What part of the fluoroquinolone is potentiated by the NSAID? Is it the carboxylic acid molecule? I always assumed so. But I’m now wondering if it’s the fluorine. Do you, or Dr. Noble, know?

    Thx,
    Lisa

    • Admin says:

      Lisa, if I may be so presumptuous to speak for a few others, although quite puzzling there is probably at least a balanced potentiation (or something close) taking place. It should be easy enough to eliminate as there will be an experiment done eventually with Nalidixic acid and steroidals. Back in the day, not many people were popping NSAIDS with Neggram so it will be interesting indeed.

      On a side note, flourine is a major player in lysosomal issues and in the long run, I believe, will figure into potentiating chronicity.

      • Dr. DB Gorski says:

        Thank you for helping to bring factual science to bear on this issue. I will be keen to find out what a combinatorial effect of Neggram and steroidals would yield. I would reckon to say that they will find a reaction as well. As the earlier comment mentions, I cannot imagine the first generation being any more potent than the following so added fluorine would almost have to have a potentiating effect.

  3. BK says:

    An internet search led me to this article in its ref to Dr. Noble. As a student that has worked with Dr. Noble as part of the great collaborative learning experience he has created at the University of Rochester, I have great admiration for him and his science. His methods are impeccable and for the most part I have always found his synopses very accurate. I have heard him briefly speak of your group with admiration and respect that a group of individuals, lay persons, if you will, to the field of neurobiology, were able to articulate this valid argument that has large scale implications. I wish you success in your endeavor.

    • Admin says:

      Thank you BK for your comments. I too believe Dr. Noble is a great man and scientist. I am glad that he has chosen to work with us and value his insight tremendously. I am sure that with a mentor such as him you will definitely succeed in your endeavors as well.

  4. Marci says:

    I don’t know how I found this website but really NEED to keep abreast of all this information. I took Levaquin early May of 2015 and have severe tendonitis all over my shoulders to my finger tips, chest, neck, legs and Achilles tendons. I’m confused by the research about the CNS. Will this hit that area as well. What is my prognosis? I take Aleve when the discomfort is so high and I need to take the edge off. Should I stay away from Aleve??????

    • Admin says:

      I am sorry that you have had an adverse event to Levaquin. These reactions can be very fluid and changing and there are no set predictable patterns. Some people have symptoms that are strictly confined to tendons, muscles, and joints while others have neurological events of either the CNS, PNS, or ANS and yet others have combined events. NSAIDS are contraindicated for use with certain population while you are taking the fluoroquinolones and, for some, can increase the risk of an adverse event. Having said that, toleration of NSAIDS after an adverse event is quite individual. I know many that regularly take NSAIDS, including ALEVE, to help their pain issues and to avoid taking stronger medications. Again, Dr. Noble’s research seems to show that NSAIDS should not be taken while a person is taking a fluoroquinolone because while doing so it can increase that level of neurological damage that can be done if the person has an adverse event.

      There is great speculation as what the mechanism is that causes the increase adversity with NSAIDS. It is possible that metabolites (partially metabolized molecules of the initial drugs, Levaquin and Aleve) combine to form a lethal cocktail of some kind, or through inhibition of the CYP enzymatic process an interaction occurs. However this propensity for damage has been seen my researchers, that is why NSAIDS are contradicted in the literature for senior population due to risk of tendon rupture. Dr. Noble’s research, along with a lot of anecdotal information from the thousands in the FQ community, indicates that NSAIDS, when taken at the same time with other FQ’s, can also worsen or cause neurological events as well.

      Other than certain steroid usage, I know of no floxed person, who permanently damage themselves after their initial reaction by taking a NSAID. It is such an individual thing. Many times, people just become more sensitive to all sorts of medications afterwards and find the many medications increase their symptoms. Mostly, when stopping the offending medication many folks return to baseline.

  5. Georgia Glaser says:

    Thank you for printing this. Floxed Mar 09 at the age of 62.

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