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Foundation Staff
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Posted: Mon Nov 1st, 2004 00:34 |
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What should I know about Minocycline?
Forms of minocycline
Minocycline hydrochloride (HCL) is the generic name for an antibiotic in the tetracycline family. It is usually referred to as simply minocycline.
It is fine to use the generic form, minocycline, which is also the cheapest.
Minocycline is no longer covered by patent and is, therefore, also marketed under several trade names. It is fine to use any of these brand (trade) name products:
-Minomycin
-Minocin
-Arestin
-Akamin
-Aknemin
-Solodyn
-Dynacin
-Sebomin
-Alti-Minocycline
-Apo-Minocycline
-Novo-minocycline
-PMS-Minocycline
-Myrac
Minocycline may be obtained in capsules or tablets. Tablets are more convenient to divide with a tablet splitter.
Dose level is important
The starting dose of Minocycline is 25mg. Do not use less. There is no advantage to starting at a tiny dose and it may even be detrimental. Taking tiny doses of minocycline keeps the concentration down to the level where it works the best and may account for reports of continued difficulties with intolerable immunopathology by noncompliant members who thought that tiny doses of minocycline were better.
Minocycline is ramped in increments of 25mg. The antibiotic dose needs to be changed a significant amount to alter the immune system response. Ramping up minocycline by a dose smaller than 25mg may be detrimental for the same reason.
There are no bacteria which will be missed using 25mg because the 48 hour dosing interval ensures that the dose in your body has decayed away to a tiny value between each dose of minocycline.
The immune system can *get used to* a dose level and stop responding. The dose may need to be changed up or down to provoke more immunopathology.
The maximum dose of minocycline throughout the protocol is 100mg. If you give too high a dose the immune system shuts down, and doesn't kill all the bacteria.
Response time varies
Some folks report an immune response to minocycline approximately 2 hours after they take a dose. If you look at the graph below, you will see that the concentration levels of minocyclines are very similar at 2 and 16-18 hrs.
So you are, in essence, passing thru the same region of the concentration curve coming and going. That is when you feel the immunpathology because this is an effective level of mino to kill your bacteria.
About 2 hours after you take the minocycline the concentration goes through the MIC (minimum Inhibitory Concentration) and then the amount of antibiotics in the blood stream gradually falls to zero, like in this graph below (for 200mg):
For example, the 50mg dose decays away to 1/10 of that in the 48 hours between dosing intervals. That is why the MP is so forgiving of small errors in dose or interval.
Pulsing the dose
'Pulsed' means that minocycline is taken every 48 hours to allow the concentration to wane between doses.
"That is the secret of the MP. Back in the 70's I studied the way drugs worked, and my research group successfully treated both cryptorchidism and infertility without surgery, by applying pulses of the hormones LHRH and GnRH at exactly the correct intervals. Take a look at this early paper.
The reason the MP's pulsatile dosing of minocycline is so effective at killing bacteria is that I noticed there was a range of plasma concentrations where the combination of minocycline and Benicar was most effective.
Only as the concentration decays away does the minocycline have the greatest effect on some of the bacteria. Take a look at the above graph and you can see that with 48hour dosing the concentration of minocyline in the blood varies over a very wide range.
While if minocycline is taken in the non-MP way, twice a day, the concentration does not pulse very much, but builds to a high, steady-state, value.
So the reason you get worse immunopathology on day 2 is because those particular bacteria killed are susceptible at the lower concentrations, on day 2. You will find other times, as you continue with the protocol, where the immune system response increases on day 1, as well. I suspect it depends on which bacteria are being hit and where they are located.
Minocycline 's half life in plasma is about 17 hours. But the tissue concentration half-life might be very different from that. ~Trevor Marshall, Ph.D
Variations in the pulsing schedule
48hrs is not an absolute cutoff for determining an immune system reaction. At the end of 72hrs the level of minocycline may be low enough to be especially effective. Also, the immune system sometimes seems to continue functioning better even without minocycline 'on board'.
"If 5 days works best for you at any point, then 'run with it' and if 2 days works best, then use that. Until immunopathology finally disappears, you will have to keep up a steady bug-kill. No more killing than is comfortable. Everybody has to figure out their own pace." ~Trevor Marshall, Ph.D
Some find 3 day dosing intervals achieves more tolerable symptoms. Don't let symptoms go to intolerable. Take your dose at a shorter time if necessary to hold your symptoms at tolerable.
The importance of ramping up
It is important to start at a 25mg and ramp up in 25mg incredments (until 100mg) because effective bacteria killing will occur when blood concentrations of minocycline are risng and falling. Different doses of minocycline target different pleomorphic bacteria and we know that there are over 50 different species identified so far.
Everyone will probably react a little differently to different doses of minocycline depending on the bacterial species, bacterial load and the function of the immune system at that time.
Time of administration
There is no set time of day to take minocycline. As you learn what your pattern of immune system reactions tends to be, you can alter the schedule of your minocycline to time it so that your exacerabtion in symptoms will be at the most convenient time for you.
For example, some people take it at bedtime to sleep through some of the immunopathology. Others figure taking it in the morning will mean they sleep through the worst immune system reaction on the second night. Still others take an increased dose just before their days off from work because they can toleratemore immunopathology when they are not working. It's a very individual thing and one of the reasons why the MP is a tolerable treatment plan.
You may take minocycline at the same time you take Benicar.
Food and minocycline
Food slightly reduces blood levels of minocycline, but the effect is not significant. Unlike other tetracyclines, minocycline may be taken with or without food and is only slightly affected by meals containing dairy.
If you have gastric upset, then you may take it with any food. The gradual increase in dosage will guarantee that the intracellular bacteria are exposed to varying dosages to achieve the maximum affect.
Taking minocycline with dairy products or calcium may alter its absorption. Take this into consideration only if you need to eliminate any variable that might be affecting immunopathology. In that case, take your minocycline dose one hour before or two hours after consuming dairy products or other foods high in calcium. Otherwise, it is okay to take minocycline with food.
Shelf life
Minocycline has a shelf life of two years if kept in a cool, dry place. We don't know of any problems concerning minocycline degradation in air (oxidation), just water (hydrated oxidation) and that is a problem with all the tetracyclines (and with other antibiotics as well).
Fanconi syndrome has been reported to occur as a result of drug ingestion. Well-recognized ingestions include those with outdated tetracycline and aminoglycoside antibiotics, such as gentamicin. This tetracycline toxicity is probably caused by anhydro-4-epitetracycline, a degradation product that is formed when the drug is stored for long periods or kept in a moist environment. The metabolite decreases oxidative metabolism and energy production.
Side effects
Once you understand the immunopathology resulting from killing Th1 pathogens, minocycline's so-called side-effects are shown up for what they are - immunopathology - and they disappear as you get rid of he pathogens.
"The reports that Minocycline can induce lupus are laughable. Exactly how does a complex immune disease arise from the actions of a bacteriostatic antibiotic? Such a suggestion is ridiculous.
The same goes for the suggestion that minocycline induces autoimmune hepatitis. Show us the beef, please - the molecular mechanisms.
Remember that it was not too long ago that the majority of physicians agreed with the statement below. That consensus didn't make it any more correct...
In order to comprehend the discoveries springing from the cracking of the genome, today's physicians need to have a good understanding of modern science. It is tough for us to expect this, as many have not been even taught the basics of molecular biology. The alternative is for them to listen to those who are accepted as well grounded in science. Many physicians find that just as hard to swallow, as the profession trains them to present medicine, and its practitioners, to the public as infallible." ~Dr. Marshall
'Allergy' to minocycline
Your inability to tolerate minocycline previously does not mean that you will be unable to take the MP antibiotics. Keep in mind that the effectiveness of the antibiotics against the bacteria that are driving your Th1 inflammation means that you will get an immunopathologic reaction. This is to be expected and should not be interpreted as a side effect, adverse reaction or intolerance. See I'm allergic to an antibiotic on the Protocol. Is there a substitute?
Acute infections
This classic paper explains why Minocycline is one of the few antibiotics effective against MRSA (Methicillin Resistant Staph Aureus)
http://www.ncbi.nlm.nih.gov/pubmed/9126205
and another:
http://www.ncbi.nlm.nih.gov/pubmed/17116438
See also:
Can I use doxycycline instead of minocycline?
Is pulsed minocycline alone effective?
Tetracyclines are all different at the molecular level
Why doesn't the MP use some of the other antibiotics?
The antibiotics selected for the MP are unique
How do I take a low dose of minocycline when the capsules only come in a larger dose size?
Is it safe to take medication that has expired?
Won't the bacteria become immune/resistant to the antibiotics if I take them a long time?
Won't I develop a yeast infection if I'm on antibiotics long-term?
Low doses of antibiotics more effective
Why and when do you recommend taking minocycline frequently?
.............
Last edited on Wed Nov 5th, 2008 07:27 by Foundation Staff
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Foundation Staff
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Posted: Tue Dec 4th, 2007 18:00 |
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[filelink]
Minocycline Studies
The use of Minocycline in Sarcoidosis:
Ohtsuka S, Yanadori A, Tabata H, Yamakage A, Yamazaki S.
Sarcoidosis with giant parotomegaly.
Cutis. 2001 Sep;68(3):199-200.
PMID: 11579785 [PubMed - indexed for MEDLINE]
This case showed improvement with Minocycline in another non-caseating granulomatous disorder;
Olivier V, Lacour JP, Castanet J, Perrin C, Ortonne JP.
[Cheilitis granulomatosa in a child]
Arch Pediatr. 2000 Mar;7(3):274-7. French.
PMID: 10761605 [PubMed - indexed for MEDLINE]
Minocycline for ALS
Minocycline Delays Disease Onset and Mortality in a Transgenic Model of ALS
Neuropharmacology Vol.13 No 8 12 June 2002 Ludo Van Den Bosch, Petra Tilkin, Griet Lemmns and Wim Robberecht Laboratory of Neurology, Campus Gasthuisberg, Herestraat 49, B-3000, Leuven, Belium
Minocycline for the treatment of sarcoidosis: is the mechanism of action immunomodulating or antimicrobial effect?
Note that one of the authors is Prof. Eishi, who spoke at our 2006 LAX conference.
You know, they are awfully close to asking the correct questions, but having to rely on an observational experiment has misled these researchers. There are too many variables in their experiment, and they don't seem to understand that.
So let me tell you what I think.
First, I am not happy with the conventional view of minocycline blocking the 30S ribosome as explained in this description from the Max Planck ribosome group.
http://www.riboworld.com/antib/30santib-eng.shtml
What worries me is that the Kd is not as high as I would like to see. That is why 5 alternate binding sites are suggested by the Max Planck group.
So, if minocyline does not act principally by attacking the 30S ribosomal subunit, then how does it work?
Well, I am also not impressed with the standard DMARD actions which have been published in the various neurology journals. The problem is that we ourselves don't see it acting as a DMARD. It almost universally increases the IP in the MP.
My current interest is in the the effect of Minocycline on the levels of Caspase-3. This protease breaks apart the VDR receptor structure and thus limits the ability of VDR to do gene transcription. Mino is known to inhibit Caspase-3 activation:
http://www.ncbi.nlm.nih.gov/pubmed/15990464?dopt=Abstract
http://www.ncbi.nlm.nih.gov/pubmed/16638021?dopt=Abstract
This is in line with our observation that Benicar has to administered more frequently in people who are sick, than in people who are not so sick. There has to be a more-rapid turnover of VDR, otherwise once activated by the Benicar the VDR would stay intact and viable. But they don't seem to do that.
Another protease which can degrade VDR is Ubiquitin, so the situation is not completely clear-cut, but my best guess right now is that minocyline indeed has activities beyond microbicidal. However, the researchers you cite have not yet begun to plumb the depths of those activities 
..Trevor.. Oct 16, 2008
Last edited on Thu Oct 16th, 2008 23:00 by Foundation Staff
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