Monthly Archives: August 2014

Fluoroquinolones Linked to Type 2 Diabetes

Diabetes Article Graph Pic

Fluoroquinolone antibiotics and type 2 diabetes mellitus Telfer, Stephen J. Medical Hypotheses , Volume 83 , Issue 3 , 263 – 269

Please read Fluoroquinolone Antibiotics Linked to Diabetes on Hormones Matter.

http://www.hormonesmatter.com/fluoroquinolone-antibiotics-diabetes-risk/

And here is the source article, “Fluoroquinolone antibiotics and type 2 diabetes mellitus” – http://www.medical-hypotheses.com/article/S0306-9877(14)00217-5/fulltext

The thought that fluoroquinolones cause cellular damage and magnesium depletion to the point that they increase the risk of type 2 diabetes is frightening, for sure.  There is quite a bit of evidence that dietary adjustments can influence type 2 diabetes significantly though.  So, that’s a reason for some hope.

The role of magnesium depletion in FQ toxicity described in “Fluoroquinolone antibiotics and type 2 diabetes mellitus” helps to explain why magnesium is the supplement that seems to help floxies almost across the board.  Magnesium is necessary for hundreds of enzymatic reactions.

A hopeful thing about the article, “Fluoroquinolone antibiotics and type 2 diabetes mellitus” is that it is a huge help in building a case against the makers of fluoroquinolones.

Smart, resourceful, intelligent people are working on this.  Change will happen.  It will.  It must.

 

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False Idols

Planet

Thou shall not worship false idols.

I’ve been thinking about the commandment not to worship false idols a lot since getting floxed.

We, as a society, and probably as individuals too, look to pills to fix us.  We look to pharmaceuticals to cure us when we are sick.  We worship the pills as if they are magical, and good, and as if they will remove all problems from our lives.  There is a systematic lack of questioning about whether or not drugs are actually good – whether the benefits outweigh the costs.  We have faith – blind, baseless faith – that all drugs do more good than harm, that adverse effects are transient and rare, that there is enough knowledge about the workings of the human body to anticipate how a drug is going to affect cells and how those effects are going to change the health and well-being of the person who takes them, etc.  (To their credit, scientists do try to make drugs safe and understand how they work – but there is a lack of willingness to admit that we know far too little about the workings of the human body to be messing with it like we are.)

We worship doctors as if they are Gods.

I wonder if there is something profoundly broken about this way of thinking.  And I wonder if there are some deep lessons to be learned in thinking about where our worshipping of false idols is taking us.

What happened in our floxed bodies is chemical.  I don’t think that any of us got sick because of God’s spite or vengeance, or because any of us worship the “wrong” God.  (There is NOTHING about getting poisoned that is your fault.  Nothing.)  Likewise, what it will take to fix us is chemical, and I don’t think that faith is going to be able to repair our broken cells.

But I also think that it is destructive and wrong to worship pharmaceuticals and doctors.  They can be helpful and they can be guides – but they are not Gods.

I used to believe that adverse reactions are rare, antibiotics are benign, when a drug does harm a doctor can fix it, the FDA is ensuring drug safety, diseases are well understood, the pharmaceutical industry is working hard to find cures to the ills that plague humanity, etc.  I no longer believe any of those things.  I have lost my faith.  Getting hurt – then gaining a little knowledge about how drugs work – will do that to you.

I don’t claim to know who or how (or even if) we should worship.

But I don’t think that pharmaceuticals or doctors should be worshipped.  They are powerful – there’s no denying that.  Unchecked power has never led to good though.  In politics, unchecked power leads to corruption and tyranny.  In medicine, unchecked power leads to poisoning – which leads to chronic disease and suffering.

Drugs aren’t the only false idol that are worshipped to the point of destruction and pain.  The oceans, rivers, land, animals and humans are being hurt in the pursuit of fossil fuels.  Money – the ultimate false idol – the one that none of us (myself included) seems capable of getting out from under the enchantment of – is pursued to the point of inducing pain, destruction and suffering of the earth and all her inhabitants.

When we, collectively (seriously, no individual blame here), worship false idols, we get poisoned.  Our earth and our bodies are being poisoned as we worship money and power and chemical concoctions that we don’t realize the consequences of.  It is a shame – a crying shame.  My heart and soul ache for us all.

 

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Dr. Robert Rountree’s Presentation about Mitochondria

mitochondria diagram

I highly recommend that you watch this –

http://www.viddler.com/v/703896d9?secret=27514482

It’s a video of Dr. Robert Rountree giving a presentation about mitochondria. It’s fascinating!

Fluoroquinolones damage mitochondria. Here are my posts about fluoroquinolones damaging mitochondria –

There are more interesting posts about mitochondria on Hormones Matter, and probably some other sites too.

I try to make this complex information a bit more comprehensible than it is in journal article format, but if you want to read through some source articles on how fluoroquinolones damage mitochondria, here are some good ones:

Also, at roughly minute 26 of Dr. Rountree’s presentation, he mentions the link between cardiolipin damage and autoimmune diseases. Here is an article about how fluoroquinolones affect cardiolipin –

Journal of Medical Microbiology, “Comparison of the Effects of Subinhibitory Concentrations of Ciprofloxacin and Colistin on the Morphology of Cardiolipin Domains in Escherichia Coli Membranes

Dr. Rountree is brilliant and I don’t mean to be critical, but I think that some of the graphs toward the end of the presentation need to be re-drawn. From what I understand from reading the above articles, and others on mitochondria, the effects of ROS (reactive oxygen species – also known as oxidative stress), are not linear. When mitochondria experience a healthy amount of stress – through exercise, for example – there is an adaptive response. It is actually likely that the initial response of mitochondria to fluoroquinolones is an adaptive and healthy one – that could explain some of the experimental results that show a healthy or adaptive response of cells to fluoroquinolones. It is only after the threshold for damage is crossed that a maladaptive/unhealthy response begins. And once that maladaptive/unhealthy response begins, well, it’s bad news because the cell perpetuates damage on itself in the “vicious cycle” of mitochondrial damage. This article explains the phenomenon of a threshold for mitochondrial damage well –

Molecular Interventions, “Mechanisms of Pathogenesis in Drug Hepatoxicity Putting the Stress on Mitochondria

Can the cycle of cellular damage be stopped? I think so. If feeling good is an indicator of health, I know so. As always, I hope the same for all of you!

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Antibiotics After Fluoroquinolone Toxicity

Antibiotic

People often ask about what they should do to treat infections post-flox.  Here are my tips.

First, please INSIST on getting your infection cultured and confirmed before you take any antibiotics.  As anyone who has had an adverse reaction to an antibiotic can tell you, antibiotics are not benign drugs.  They have side-effects (HERE is the 43 PAGE warning label for Cipro/Ciprofloxacin).  Some of those side-effects are life-altering and/or life-threatening.  You don’t want to put any drugs into your body unless you absolutely need them.  A culture should be done to confirm that an infection is present before you take an antibiotic – no matter what.

Because antibiotics have been shown to wreak havoc on the microbiome and bactericidal antibiotics damage mitochondria – and because both microbiome disruptions and mitochondrial dysfunctions are linked with every chronic disease there is – I highly recommend looking into some non-pharmaceutical options first.  Garlic has been shown to have antibiotic qualities and to be more effective against biofilms than many antibiotics.  For urinary tract infections, D-mannose has effectively helped thousands of people get rid of their infection.  Some other non-pharmaceutical remedies for urinary tract infections can be found HERECoconut oil has been shown to have anti-bacterial qualities and it may be good for treating skin and GI infections.  Colloidal silver not only has anti-bacterial qualities on its own, it also has been shown to increase the effectiveness of pharmaceutical antibiotics when used in conjunction with them.  Andrographis is an herb that has antibiotic qualities.

If non-pharmaceutical options aren’t working and you need an antibiotic to get rid of your confirmed infection, here are the antibiotics that I recommend along with reasons as to why I recommend them (or not).

  1. Most Floxies seem to do well with doxycycline and other tetracyclines. Tetracyclines are bacteriostatic antibiotics that, “stops bacteria from multiplying but does not kill them.” (source)
  2. Several Floxies have taken Z-pack’s without incident
  3. Amoxicillin seems to be about as benign as antibiotics get. So, it’s not harmless, but it’s well tolerated generally.
  4. Penicillin seems to be well tolerated – unless you’re allergic to it.
  5. Cephalosporins seem to be well tolerated

There are probably some other antibiotics that are fine for Floxies, I just haven’t heard about them.  Please feel free to leave a comment below if there is an effective and relatively safe one that I’m missing.

Here are the antibiotics that I recommend avoiding because they have side-effects that are similar to those of fluoroquinolones, and because many Floxies react badly to them –

  1. Macrobid / Nitrofurantoin
  2. Flagyl / Metronidazole
  3. Bactrim / Trimethoprim / Sulfamethoxazole
  4. Augmentin

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Fluoroquinolones – Cipro/Ciprofloxacin, Levaquin/Levofloxacin, Avelox/Moxifloxacin, Floxin/Ofloxacin and a few others – should be avoided entirely unless you are dying and make the decision that getting “floxed” is preferred to death.  Every warning label for every fluoroquinolone says that people who have an existing hypersensitivity to a fluoroquinolone should not take them again.  “Ciprofloxacin is contraindicated in persons with a history of hypersensitivity to ciprofloxacin, any member of the quinolone class of antimicrobial agents, or any of the product components.” (Warning Label)

Before you take an antibiotic, or any pharmaceutical for that matter, I highly recommend that you look up the review for that drug on http://www.askapatient.com/ and look it up on http://www.peoplespharmacy.com/.  Also, look up the drug’s warning label.  Be informed.  Make an informed decision.

Here is a list of antibiotics – http://en.wikipedia.org/wiki/List_of_antibiotics  I didn’t get close to going through all of them.  But I hope that this post gives you some guidance when/if you are faced with an infection.

I’m not a doctor, so please take this advice for what it’s worth.  Doctors should be consulted when you have an infection.  The internet should be consulted too though, because doctors aren’t capable of knowing everything and informed consent is really important.

 

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Crowdfunding Floxie Hope

Floxie.Hope.1800.72.dpi

I’m asking for support of Floxie Hope.  Thank you very much for your consideration!

I’m trying crowd-funding.  The basic premise of crowd-funding is that many people each give a little money to support a cause or organization because they find value in it.

I’m a bit biased, but I think that a lot of value is offered through Floxie Hope.  The stories of healing and recovery offer hope and tips to those going through the horror of fluoroquinolone toxicity. The posts offer information that Floxies can share with their families and friends to help spread the word about the dangers of fluoroquinolones. The posts also help friends and family members to understand what is experienced when the fluoroquinolone toxicity bomb goes off in a Floxie’s body.  The Links & Resources page links to articles explaining the science behind fluoroquinolone toxicity – and gives Floxies something that they can show to their doctors to help them to understand what is happening in the Floxie’s body.  People have reached me through the “contact me” link and I hope that I have helped them through offering guidance and support.

I hope that everyone who visits Floxie Hope gains knowledge, strength, community, information, support, and even amusement.  I hope that it makes the journey through fluoroquinolone toxicity a little bit easier to bare.

If you would like to support Floxie Hope, here is a link to support Floxie Hope monetarily:

 

support button 2 72dpi

 

Additionally, there are lots of non-monetary ways that you can support Floxie Hope.  I greatly appreciate everyone who:

  1. Shares posts and articles about fluoroquinolone toxicity on social media
  2. Comments on Floxie Hope (a huge THANK YOU to everyone who has helped to form a community of support on Floxie Hope)
  3. Talks to your friends and family about the dangers of fluoroquinolones

It’s a good site.  If you agree, please donate a few dollars through the link above, spread the warning to those you love, and/or spread the hope to those who are suffering.

Thank you for your time, consideration and support – in whatever form it takes!

Wishing you hope and healing,

Lisa

 

P.S. – If you are in a giving mood, here are some other organizations that are providing value to the Floxie community, who will also appreciate support/money:

 

 

Cellular Oxidative Damage from Fluoroquinolones

banner-biochem

Here are some thoughts about what is/was going on in our floxed bodies.

First, here’s my typical disclaimer.  I’m not a doctor or scientist.  I’m doing my best to put together this information, but I could be wrong.  I do my best to be right and I back up my assertions with peer-reviewed journal articles.

As I mentioned in Article Breakdown – “Mechanisms of Pathogenesis in Drug Hepatotoxicity Putting the Stress on Mitochondria,” I believe that this paragraph describes much of what occurs in floxed cells:

“Increased steady-state levels of mitochondrial superoxide, arising from reduction of Sod2 activity in the Sod+/−mice (i.e., approximately half the wild-type activity), may be exacerbated by drugs that directly target the ETC [e.g., the complex I inhibitors flutamide and troglitazone (122)]. The increased amount of superoxide raises two considerations. First, superoxide that escapes dismutation to hydrogen peroxide cannot cross the inner mitochondrial membrane and can oxidize [Fe-S]-containing enzymes (e.g., aconitase and complex I/III subunits). Alternatively, superoxide can rapidly react with mitochondrial nitric oxide (NO) to form peroxynitrite (ONOO−). For example, the fluoroquinolone antibiotic trovafloxacin (TVX), a typical DILI (drug induced liver injury) associated drug, raises steady-state levels of NO in hepatocellular mitochondria (unpublished data). The mechanisms are not known, but TVX also increases cytosolic (non-ferritin-bound) Ca2+, likely activating the Ca2+-dependent mitochondrial NO synthase (123) to produce ONOO−. Peroxynitrite is dangerous for a number of reasons: i) under acidic conditions, it can be degraded to form the extremely reactive hydroxyl radical; ii) it may directly cause the nitration of aconitase, Sod2, and the [Fe-S]-containing subunits of ETC complexes; and iii) it can induce mitochondrial permeabilization (Figure 4B) (124). This superimposed oxidative/nitrative stress could ultimately push the cell across the threshold to observable injury.”

SUPEROXIDE DAMAGE OF MITOCHONDRIAL DNA

Superoxide is a powerful oxidant that is quite toxic.  Per “Mitochondrial matrix reactive oxygen species production is very sensitive to mild uncoupling,” “ROS are produced continuously as a by-product of aerobic metabolism.  Superoxide can be produced as a result of the one-electron reduction system within the mitochondrial electron transport chain.  Superoxide can then be converted into hydrogen peroxide (H2O2) by superoxide dismutase (the Mn isoform in the matrix and cu, Zn-superoxide dismutase in the cytosol).  H2O2 can be converted into highly reactive hydroxyl radicals (OH-) by the Fenton reaction, and can cause lipid peroxidation.” More info about superoxide can be found here – http://en.wikipedia.org/wiki/Superoxide

In properly functioning cells, superoxide dismutase (SOD) converts superoxide into hydrogen peroxide (H2O2) and water.  Unfortunately, fluoroquinolones deplete cellular SOD.  In “Oxidative Stress Induced by Fluoroquinolones on Treatment for Complicated Urinary Tract Infections in Indian Patients” it was found that, for human patients with urinary tract infections and treated with various fluoroquinolones, “There was substantial depletion in both SOD and glutathione levels particularly with ciprofloxacin.”

Without sufficient SOD, as noted above, superoxide “cannot cross the inner mitochondrial membrane and can oxidize.”  Oxidization within the mitochondrial membrane is harmful because it damages mitochondrial DNA (mtDNA) and starts the vicious cycle of oxidative damage to mitochondria.  (This “vicious cycle” theory is described in “Oxidative stress induces degradation of mitochondrial DNA” – “According to this theory, the production of ROS by mitochondria leads to mtDNA damage and mutations which in turn lead to progressive respiratory chain dysfunction and to a further increase in ROS production as a consequence of this dysfunction. The exponential escalation of these processes is commonly referred to as a ‘vicious cycle’, and the theory predicts that the rise in mtDNA mutations and ROS eventually reach levels that are incompatible with life.”  It should be noted that whether or not this theory is true for how aging works is contentious.  The vicious cycle of damage done by ROS does occur in mitochondria though.)

THE NITRIC OXIDE / PEROXYNITRITE (NO/ONOO-) CYCLE

Additionally, “superoxide can rapidly react with mitochondrial nitric oxide (NO) to form peroxynitrite (ONOO−).”  The ways in which peroxynitrite are dangerous are noted in the paragraph from “Mechanisms of Pathogenesis” at the beginning of this post.

Dr. Martin L. Pall, Professor Emeritus of Biochemistry and Basic Medical Sciences at Washington State University describes the NO/ONOO- (nitric oxide / peroxynitrite) cycle in his web site, http://www.thetenthparadigm.org/index.html.  Here is a diagram from The Tenth Paradigm describing the NO/ONOO- cycle –

ONOO cycle

Here is Dr. Pall’s description of the above diagram:

“Fig. 1 legend.  Vicious (NO/ONOO-) cycle diagram.  Each arrow represents one or more mechanisms by which the variable at the foot of the arrow can stimulate the level of the variable at the head of the arrow.  It can be seen that these arrows form a series of loops that can potentially continue to stimulate each other.  An example of this would be that nitric oxide can increase peroxynitrite which can stimulate oxidative stress which can stimulate NF-kappaB which can increase the production of iNOS which can, in turn increase nitric oxide.  This loop alone constitutes a potential vicious cycle and there are a number of other loops, diagrammed in the figure that can collectively make up a much larger vicious cycle.  The challenge, according to this view, in these illnesses is to lower this whole pattern of elevations to get back into a normal range.  You will note that the cycle not only includes the compounds nitric oxide, superoxide and peroxynitrite but a series of other elements, including the transcription factor NF-kappaB,  oxidative stress, inflammatory cytokines (in box, upper right), the three different forms of the enzymes that make nitric oxide (the nitric oxide synthases iNOS, nNOS and eNOS), and two neurological receptors the vanilloid (TRPV1) receptor and the NMDA receptor.”

The NO/ONOO- cycle provides a reasonable explanation for why it feels as if a bomb has gone off in the body of the floxie.  It also is an explanation as to why the adverse effects of drugs that damage mitochondria and cause oxidative stress are not transient.  There are feedback loops within the cells that perpetuate the damage.

Here is Dr. Pall’s table of signs of the NO/ONOO- cycle –

Explanations for Symptoms and Signs

Symptom/Sign Explanation based on elevated nitric oxide/peroxynitrite theory
energy metabolism /mitochondrial dysfunction Inactivation of several proteins in the mitochondrion by peroxynitrite; inhibition of some mitochondrial enzymes by nitric oxide and superoxide
oxidative stress Peroxynitrite, superoxide and other oxidants
PET scan changes Energy metabolism dysfunction leading to change transport of probe; changes in perfusion by nitric oxide, peroxynitrite and isoprostanes
SPECT scan changes Depletion of reduced glutathione by oxidative stress; perfusion changes as under PET scan changes
Low NK cell function Superoxide and other oxidants acting to lower NK cell function
Elevated cytokines NF-kappaB stimulating of the activity of inflammatory cytokine genes
Anxiety Excessive NMDA activity in the amygdala
Depression Elevated nitric oxide leading to depression; cytokines and NMDA increases acting in part or in whole via nitric oxide.
Rage Excessive NMDA activity in the periaqueductal gray region of the midbrain
Cognitive/learning and memory dysfunction Lowered energy metabolism in the brain, which is very susceptible to such changes; excessive NMDA activity and nitric oxide levels and their effects of learning and memory
Multiorgan pain All components of cycle have a role, acting in part through nitric oxide and cyclic GMP elevation
Fatigue Energy metabolism dysfunction
Sleep disturbance Sleep impacted by inflammatory cytokines, NF-kappaB activity and nitric oxide
Orthostatic intolerance Two mechanisms:  Nitric oxide-mediated vasodilation leading to blood pooling in the lower body; nitric oxide-mediated sympathetic nervous system dysfunction
Irritable bowel syndrome Sensitivity and other changes produced by excessive vanilloid and NMDA activity, increased nitric oxide
Intestinal permeabilization leading to food allergies Permeabilization produced by excessive nitric oxide, inflammatory cytokines, NF-kappaB activity and peroxynitrite; peroxynitrite acts in part by stimulating poly ADP-ribose polymerase activity

Sounds pretty familiar, doesn’t it?

STOPPING THE NO/ONOO- CYCLE

What can be done to stop the NO/ONOO- cycle?  How can one heal when cells are reinforcing the damage done to them over and over again?

Here are Dr. Pall’s recommendations – http://www.thetenthparadigm.org/therapy.htm

Additionally, a very smart and appreciated floxie noted in a comment on this site, that uric acid has been shown to decrease peroxynitrite.  Per the article, “Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis,” “Uric acid, the naturally occurring product of purine metabolism, is a strong peroxynitrite scavenger, as demonstrated by the capacity to bind peroxynitrite but not nitric oxide (NO).”  (There has been some debate about whether floxies want to increase or decrease nitric oxide.  I think that we want to increase NO because too much of it is converted into peroxynitrite.  Here’s an article on how NO helps with tendon healing – “The role of nitric oxide in tendon healing.”)  Uric acid.  The stuff that causes kidney stones and gout – it’s a powerful antioxidant that scavenges peroxynitrite.

The role that uric acid plays in getting rid of toxic peroxynitrite makes sense to me on a personal level because of a couple of things that have made me feel significantly better post-flox – brewer’s yeast and uridine supplements.  Both brewer’s yeast and uridine are high in purines, which are converted into uric acid in the body.  I always thought that the purines and uric acid were a necessary evil and that the good done by brewer’s yeast had to do with its high amino acid and/or B vitamin content.  Now I’m thinking that the necessary evil was actually the active ingredient.

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Here are a couple more articles about the role of uric acid in peroxynitrite neutralization (thanks again to the floxie friend who pointed them out):

There is a very real risk of kidney stones and gout when consuming too many purines that lead to excess uric acid.  Even though brewer’s yeast has helped me immensely, I feel quite conflicted about it.  I don’t want a kidney stone and gout would probably make my flox-induced peripheral neuropathy look like a cake-walk.  Now that I’m feeling well, I’m probably going to cut way down on my brewer’s yeast consumption.  I really don’t know which are worse – the diseases of too much uric acid (kidney stones and gout) or the diseases of too little uric acid (“patients with MS have significantly lower levels of serum uric acid than controls” and peroxynitrite is associated with lots of other nasty diseases – like cancer and Alzheimer’s).  This isn’t exactly a great predicament.

Another consideration is that fluoroquinolones deplete cellular magnesium and proper amounts of cellular magnesium are necessary for 300+ enzymatic reactions.  (Fluoroquinolones may inhibit and deplete enzymes through means other than depletion of cellular magnesium too.)  If one doesn’t have the enzymes to metabolize uric acid, well, too much isn’t a good thing.  Too much peroxynitrite is bad too though.

I wish that the answers were more clear.  I hope that this post at least gave you some information with which you can make an informed decision!

In researching this post, I stumbled upon this interesting web site – http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/R/ROS.html  It is noted on the site that uric acid is an antioxidant and that, “Perhaps the long life span of some reptiles and birds is attributable to their high levels of uric acid.”  Bird shit and reptile blood are full of the stuff.  If there is a cure for fluoroquinolone toxicity, it’ll probably come from bird turds or alligator blood.  Great.

 

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