Means to enhance absorption of Doxycycline and other means to enhance CAP

As a CAPi for Cpni is to be maintained over many months, the abxi can pose a problem to organs like liver and kidneys, as those are part of the elimination route. Higher doses also carry a higher risk of other side-effects. Hence, enhancing the effect of abxi taken is beneficial.

 FIR sauna has been discussed, and in Lyme, even small increases of temperature multiplies the effect of investigated abx (ceftriaxone: MIC one eitght; penicillin: MIC one sixteenth, when temp increases from 36C to 38C).  [Reisinger et al:  Antibiotics  and Increased Temperature against  Borrelia burgdorferi In Vitro; Scand J  Infect Dis 28:  155  157,  I996] As far as I understand,all forms of body temperature rise may be beneficial, also warm/hot baths as well as exercising. The question is if there is a similar effect for Cpn. 

 Tetracycline has been mentioned as being less absorbed when taken with food, especially milk and realted products, whereas doxycycline is thought not to be affected similarly. However, in one study the picture isn't as clear in my view. Even if the drop in serum concentration for Tetracycline if taken with food was considerable (about 40%, worse with food containing protein), the similar drop for Doxycycline was about 28%. Converesely, one can enhance serum concentration towards 40% by taking it on emtpy stomach. Like taking 140mg instead of 100mg (I've done this first with Doxy, then with Minoi; minimal gut reactions from Doxy none from Mino). [Welling et al: Bioavailability of Tetracycline and Doxycycline in Fasted and Nonfasted Subjects; ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Mar. 1977, p. 462-469]

  There are similar results for physical activity after taking abx, and even if some of the effect of increased plasma levels are from reduced excretion and reduced intercellulari plasma volume, not all is. Some seems to come from enhanced absorption. Peak serum concentration 6.5 μg for exercise vs 4.8 μg for rest, and similar for the serum level time integral 106 vs 81 μgh/ml. [Ylitalo: Effect  of Exercise on  the  Serum Level  and Urinary  Excretion of Tetracycline,  Doxycycline  and  Sulphamethizole; Europ. J. clin. Pharmacol. 12, 367-373, 1977]

 Most likely some of the effects are overlapping, but taking abx a few hours after the last meal and then exercising a bit as possible followed by sauna or a hot tub or alternating the last measures (exercise and sauna/hot tub) may be a good way to boost a CAP.  Then there is the question if these effects are present in other abx, both from the same class (like Minocycline which I am currently taking), and from other classes (I saw it mentioned that Azithromycin is thought to be absorbed better on empty stomach, e. g., no reference, though)?

 On top of these measures to enhance the uptake and effect of abx, there is the wide range of nutrition and supplementsi to enhance the CAP. In all, the difference between a CAP employed in different ways can be considerable.

 THe problem is to get everything together, to sort out the relative importance of different measures. From reports here in the forum, the blogs etc, it is also obvious that the effects differ between persons. 

Nord, The caveat, always, is whether it's a good idea to 'enhance' the antibiotic protocol. Some people get slammed by a minimal dose of doxyi; more 'effective' doxy absorption might cause greater problems. When we suggest folks 'ramp up' their doses of medicine, it is for just this reason.

Now, for people who tolerate the meds well, or who are far into their treatment, maximizing the effectiveness of the meds might be more appropriate.

Also, while it's often more effective to take meds on an empty stomach, few here have found they can tolerate doxy (particularly) on an empty stomach.  If a little food helps to keep the medicine down, that's preferable to losing its benefit entirely by retching it up.

You have to trust that the doctors who devised these protocolsi took into account the average efficacy of the meds; if they wanted us to have higher concentrations of, say, doxy, they would have prescribed 300mg/day, rather than 200mg. 

It's similar to adding exercise, or heat. Many people simply can't tolerate it, and exhausting one's meager energy stores does nothing to enhance the effectiveness of the capi in the long run.

Basically, this is a series of trade-offs and accommodations. Every one of us learns what we can and can't tolerate and implement as time goes on. I think these enhancements are something to keep in mind as the patient adapts to the full protocol, or becomes stalled after months or years on treatment, but they could be a bit too much of a good thing for the beginners.

The difference between what we do and what we are capable of doing would suffice to solve most of the world’s problems. Mohandas Gandhi

Thank you for this Nord, was an interesting read. I try to sauna and excercise every other day for detox but seems it may help with abxi as well...I might try the minoi on an empty stomach but i couldnt with the doxyi....Do you know anything about biofilm busters ? I need to read up on it, anybody know a product you can order that is good ?
Treating PPMSi with Azithromycin 250 mg every other day, Doxyi 100 mg BiDi, Coconut oil 4 times daily,  five flagyli pulses. Been sick since June 2009. Having good success and very few symptoms.
I don't know of a product but you may be interested in a previous discussion about biofilms here<. I do use a mouthwash called Biotene which claims to have some biofilm busting properties.

speedbird

MacK, you sound a bit troubled by my post, sorry if it is so, and thank you for the comments. I am fully aware of the need to go slowly, although having a tendency for impatience, I'll probably keep lookning ahead. :-) If your concern mostly is for others, that my points seem like advice, I apologize, and am willing to put a warning to the beginning at the top of the thread.

As for the ability to take Doxyi on an empty stomach, that is of course individual, and I think it is rather self-evident that the ability to keep the medication is of highest importance (not much point in trying to enhance the absorption of somthing that is not present :-). I'd even go further, and say that if one is to stay on the protocol as long as required one has to take care as to minimize the discomfort and avoid negative reactions as much as possible without sacrificing too much effect.

To me, these points as well as the other you mention, are a bit of background understanding (hopefully, readers have at least read the "Getting started" pages. What induced my post was the revelation that the difference between Tetra and Doxy in terms of absorption with food vs when fasting is not as huge as one may think from general advice (prescribing guidelines for physicians etc). I am certain that the inventors, Stratton and Wheldon are fully aware of this and have taken it into account when designing the protocolsi. Still the alternatives you mention, 200mg vs 300mg, differ about the same as a 200mg dosis taken with food or when fasting, add exercise and the difference is probably even larger (I am not aware of studies of the different combinations of measures).

Then the bodywieght is not yet mentioned, adding even more to the range of possible plasma concentrations of a given dosis. 50mg taken by a 100 lbs person when fasting while physically acitve could be similar to or more than 300mg for a 300 lbs person taken with a large meal and resting afterwards, in terms of plasma concentration. So while the protocols are very carefully designed, out of the need for simplicity, there are additional information like this that one can use to make finer adjustments. If one feels it is too complicated, then just ignoring it is fine, of course. I am not suggesting that this should be followed, and by this the heading "...enhance CAPi" is a bit misleading, perhaps, if one interprets "enhance" in a simple "ever valid improvement" way.

For me personally, my way is to experiment, starting low and adding to see the reactions. Having been easily fatigued for the last twelve years, I know a little bit of the importance of energy preservation, but also the necessity to use the energy available wisely. For me this includes continously including physical activity, as it will be beneficial if not overdone (this is much more easily done when ill, I was just reminded last week by "crashing" energy-wise after riding a bicycle for a few miles). I have taken both 100mg doxy and minoi bidi fasting, both for a couple of weeks, and if not doing anything stupid and adding supporting measures, it works. Perfectly for mino and without too much discomfort with doxy. Taking a brisk walk afterwards is actually one way for me to support the stomach. Even doing this with 200mg doxy first thing in the morning and the go off cycling has worked. Regrettably, I still don't have energy or low enough levels of headache to allow for jogging or running, but the time will come for that, too (it has been a great way to counter occational dyspepsia in the past).

Of course one's background means a lot. I was used to be physically active before turning ill, and have been training to eliminate a neuroi-developmental issue I have since infancy (and have improved something that is "impossible" to affect after childhood). This gives me a head start, and my "illness" is close to irrelevant compared to sufferers of MS here (I am hugely impressed by the persistencei and motivation among you, sheer beauty in my view), even if some of the symptoms have triggered the thought that perhaps I was heading in a similar direction.

 Getting the quick relief from just a month of CAP has made me realise that I was actually more ill, and the it has affected my life more, than I admitted. I also had a few years when I could take up running and built some fitness, this adds to make me able to take a lot more adverse reactions from treatment, I think (compared to people with a longer continous decline).

Jesper, i thougth about linking in you post on your search for imroving the efficinency of the treatment when writing the post, and am glad that you found it useful. As biofilms are often several microbes living in symbiosis, a CAP is good in this repsect. The reason is that the symbiosis can be in the form of bacteria lacking sensitivity for one abxi producing substances protecting other that would have been killed by the same abxi. If then several abx are taken at once the chance is higher that all the protecting (or protection producing) bacteria in the biofilm will be eliminated. The area where one suspects biofilm and the involved microbes is probably of importance, but generally improving health and immunei function is probably a good basis.

There are several natural substances that eliminate biofilms, and that work in synergy with conventional abx. Garlic, Curcumin, are a couple of examples. Curcumin is both anti-inflammatory and antimicrobal. It can relieve gastric problems and probably also those from taking some medications (especially those causing dyspepsia) [Prucksunand C, Indrasukhsri B, Leethochawalit M, Hungspreugs K. Phase II clinical trial on efect of the long turmeric (Curcuma longa Linn) on healing of peptic ulcer. Southeast Asian J Trop Med Public Health 2001;32:208-215.] I think this is a good addition while on tetras. Bilberry is another potent gastric healer :-). Garlic perhaps, too, but it has been shown to irritate the stomach as well. Seems a bit like a double-edged sword. Potent antimicrobal, though.

Borrelia/Cpni arthritis: joint, skin, eye, CNSi, respiratory, UG involvment; fatigue. Borrelia Elisa&WB IgGi, and CPn IgG and IgA pos, HLA-B27 neg. CAPi 5/9/2010 -> 3/2016 2017: some signs and symptoms returning, Borrelia?

Thank you Nord, will look a little deeper into that when i feel i have time. I suppose youve already read about taking green tea with abxi to boost them, just thought it was worth a mention, however i do not know if it helps with all abxi and against cpni, but i take it with all my abx.
Treating PPMSi with Azithromycin 250 mg every other day, Doxyi 100 mg BiDi, Coconut oil 4 times daily,  five flagyli pulses. Been sick since June 2009. Having good success and very few symptoms.
I'm getting nauseated just thinking about taking doxi on an empty stomach. I don't think I'll be doing that! I will try to time it so I take it before exercise though. That should be easy.

Thank you Nord for your advice on speeding things up. We're all at different stages all around the world on this site, so it helps to read tips.

through trial and error I've found many activities that are helping me recover with confidence and peace, rather than grief.

For example:

An Epsom Salt bath a wonderful detox.

Starting an aklaline diet has helped me deal with the acidic side effects of all the medications. Drinking about 35 litres of aklaline water a week has been life-changing!

Starting the day with stretching and breathing.

Green juices with Organic Spirulina and Pea Protein for breakfast. And plenty of vegies and protein through the day.

Geting back in touch with nature- cherishing the sounds of native birds and caring for plants and beautiful flowers.

I hope everyone is able to find some remedies to ease the pain and length of their recoveries.

I found a figure on Minocycline concentrations when taken fasting or non-fasting; according to drugs.com food reduces plasma levels about 10% http://www.drugs.com/pro/minocycline.html< So, for those finding Doxycycline difficult to take in sufficient doses, minocycline offers tvo benefits: less discomfort and less reduction in plasma concentration if taken with food. I've changed back to Mino as it seems a little better than Doxy against Borrelia.

Jesper, I was aware of anti-inflammatory and antimicrobal activity of green tea, but had missed the synergistic action with (conventional) abxi, thank you! One has to be careful, as some substances act conterintuitive. Most anti-iinflammatories enhance abxi or if also antimicrobal act synergistiacally. Surprisingly, though, Quercitin seems to support clamydiae, at least alone: Törmäkangas L, et al: In vivo treatment of acute Chlamydia pneumoniae infection with the flavonoids quercetin and luteolin and an alkyl gallate, octyl gallate, in a mouse model.; Biochem Pharmacol. 2005 Oct 15; 70(8). I use to drink green tea in the afternoon, but did an experiment with taking some after the evening abx together with some garlic, turmeric and black pepper. Got a clear reaction.

 Sunnivara, sorry that you have trouble with the Doxy, hope you find a way to keep it, or see comments on Mino.

Aussie, thank you for the tips! Regrettably, I've not been into bathing a lot during my adult life. I love to be in water, a hot epsom salt bath sounds like the thing to do, detoxing and reinforcing the abx (at least against the Lyme) at once. I've already cut back on some of the worst acidic foodstuffs (e g coffee). I have been on a different healt related journey where I learnt a bit about general healt-supporting activities. Used to do some qi-gung in the morning and evening, with additional stretching. Meditation and breathing was also central, as well as the getting in touch with nature. Love to listen to nightingales (sp?) singing in light spring rain/drizzle, wind, the sea, watching great views...  Was also contemplating depth mental/emotional approaches, recall that great enhancements of immunei function have been reported/claimed (but I was seeking deep stress reduction/enhanced whole brain processing). 

 

Borrelia/Cpni arthritis: joint, skin, eye, CNSi, respiratory, UG involvment; fatigue. Borrelia Elisa&WB IgGi, and CPn IgG and IgA pos, HLA-B27 neg. CAPi 5/9/2010 -> 3/2016 2017: some signs and symptoms returning, Borrelia?

Word of warning here. I tried taking my doxyi before my workout the other day. I was fine during my workout but shortly afterwards I got extremely nauseated, almost threw up. I was much more nauseated than I normally get from taking doxy. What I think happened was, during exercise, the body diverts blood away from the stomach to supply more oxygen to heart, lungs and working muscles. Digestion basically stops. The doxy caps just sat there in my stomach. Then, when I stopped exercising, a rush of blood flow returned to the stomach and the doxy hit me all at once. It was very unpleasant. So the moral of the story is, make sure you take your doxy far enough ahead of your workout that it gets past your stomach before you exercise.

Sunnivara,

I think a more likely possibility of what occurred is that the combination of exercise and taking the antibiotic killed or shut down more Cpni than you are used to or were expecting. Rather than not try it again, I would argue you should do this but moderate your exercise initially and slowly build it up to where you want it.

- Paul

 Hi,

I think Paul is right by saying that  more cpni is killed with exercice by making abxi more effective.

I  also want to add that exercise make porphyriai much worse and usual symtoms of that is nausea, back pain, rapid heartbeat, cheast pain, headacheas and much more. I think a lot of our symptoms are porphyria.

So dealing with porphyria is very importent. I remember one member here writing  that she had to limit her husbands walks because if he exercised to much his porphyria got much worse.

Best Wishes from Maria

Cpni since sep 2006. Autoimmune thyroid,hypofunction.levaxin,b12+folic acid">i.All classic cpn,porphyriai and toxinsymtoms.Not able to work.Selftreating cpninfection with AllicinMax(garlic), NACi, high vitamin D3. CAPi for over 3 years. Back to work and life

I think it s Sunnivara who is right, i mean doxyi does not kill anything, its only  a bacteriostatic so there is no die off with it, only perhaps more inflammationi if cpni is turning into a cryptic formi.
Diagnosed with MSi on March 2009, started CAPi on Jan 2010. Doxyi 200mg- Roxyi 300mg- NACi and all major supplementsi.

Hi Shahbah,

Doxycyclinei is capable of killing Cpni given enough time. However you are probably correct in the second part of your statement. It is possible/probable that Cpn uses efflux pumps to remove tetracycline class drugs. The reason for this is that Cpn is susceptible to it in both the RB and Cryptic state. And tetracycline is something we probably are exposed to quite a bit. It is made by common soil bacteria, streptomyces, and we probably come in contact with it often from this and it growing on grains. Also it is used on livestock so we may be additionally exposed. Pumping out a molecule such as tetracycline uses a lot of ATP and I think depletion of ATP is what triggers the cryptic state and subsequent increased production of HSPi-60.

As a related note, almost 2000 years ago Nubians were apparently using tetracycline. It appears from the amounts they ingested from a beer they made, this was intentional. And I think the combination of alcohol and tetracycline would be a very good combination against Cpn although we have better options today.

Ancient Nubians Made Antibiotic Beer<

- Paul

Also Metronidazolei (Flagyl etc) plasma levels are affected by similar food intake. Spénard et al:
Effects of food and formulation on the relative bioavailability of bismuth biskalcitrate, metronidazole, and tetracycline given for Helicobacter pylori eradication.; Br J Clin Pharmacol. 2005 Oct;60(4):374-7.  http://www.ncbi.nlm.nih.gov/pubmed/16187969<

It has been mentioned in another discussion (http://www.cpnhelp.org/improvement_again#comment-61168<)  that exercise is immunosuppressive. This is true soon after more intense training (much research is probably on this--athletes, with the presumption of a linear relationship from rest to hard training, from sedentary lifestyle to an "athletic" one), and for persons balancing on the verge of over-training (elite athletes--those people are likely always "soon after training" physiologically), not overall for people doing moderate exercise with appropriate recuperation. A couple of free-access papers on this: http://www.ncbi.nlm.nih.gov/pubmed/19955864<
http://www.ncbi.nlm.nih.gov/pubmed/19336500<

Borrelia/Cpni arthritis: joint, skin, eye, CNSi, respiratory, UG involvment; fatigue. Borrelia Elisa&WB IgGi, and CPn IgG and IgA pos, HLA-B27 neg. CAPi 5/9/2010 -> 3/2016 2017: some signs and symptoms returning, Borrelia?

Those papers on the benefits of moderate exercise are largely talking about exercise performed before infection, which isn't relevant to people in the grip of a chronic infection, who have lost their opportunity to do stuff before infection. The first paper references exactly one human study where they tested moderate exercise during an infection, in a controlled study -- and found that it made no difference. The rest are studies of people who exercised for long periods, most of the exercise thus being in the non-infected state. (And then there's the epidemiology, which is complicated by the fact that healthy people like to exercise more than unhealthy people do, and so the correlations that are detected can be from causation in the reverse direction.) They do have some mouse data indicating that moderate exercise helps, but even there, their hypothesis is that
"moderate exercise induces a level of stress hormones that down-regulates excessive inflammationi within the respiratory tract and aids in activating innate anti-viral immunity shifting the immunei response towards a Th2 profile (Fig. 4), thereby balancing the Th1/Th2 responses to prevent an excessive Th1 immune reaction to these pathogens."
So even though moderate exercise helped, they think it helped by decreasing inflammation. That's still an effect in the opposite direction from my own experiences, which are that moderate exercise when taking Flagyli increases its inflammatory effect. In both cases the result of moderate exercise may ultimately be beneficial, but I can't use their results to explain my own experiences; instead I have to rely on some other idea, such as that the exercise helps Flagyl kill the germs, that more of them thus die off and become visible to the immune system, and that this yields more inflammation.

The second paper is even less supportive, saying that

"Although the ‘J’-shaped curve hypothesis relating the amount of exercise and risk of disease has been accepted by athletes, coaches and scientists, the available evidence is insufficient to support it."
(That "J-shaped curve hypothesis" is the one you're invoking: that moderate exercise helps, while severe exercise hurts.)
That study on metronidazolei does indeed give numbers for enhanced concentration from taking it while fasting which are larger than I'd guessed (in the other thread). I'd said "10% or less", but eyeballing Figure 2 of the paper, it looks more like a 20% or 30% difference in area under the curve. That's still not enough, on its own, to explain the dramatic increase in effect I get from taking it while fasting, but it's bigger than I'd thought. (And yes, I'd missed the numbers for increased concentration from exercise that you'd posted in the first post of this thread -- although you didn't say which antibiotic those numbers are for; is it doxycycline?)

One thing I've done recently with my own dosing, to increase the effect, is to time it so that the drugs have their peak concentrations coincide. Specifically, I do this for rifampin, Flagyl, and niacin">i. Rifampin is the slowest to be absorbed, reaching its peak after about two hours; so I take it first. (I've actually found that I need to take a little bit of food with it -- just a bite of cheese, or something -- to get it to move down the digestive tract; otherwise it can be even more than two hours before it starts appearing in the urine.) Then after an hour I take Flagyl, which is absorbed faster. Then after another hour, niacin, which is absorbed very fast. The idea is to subject the germ to a simultaneous attack from all directions. It seems to work.

The figures in the fourth paragraph of the first post are for Doxycycline, the effect is less for Tetracycline, but stronger for Sulphamethizole.

Exercise was said to be of high intensity (HR of 130-140), which is actually not even given the long duration (4h), but it was still high enough to possibly delay gastric emptying (they started the exercising 30 min before administration). It would be interesting to see how lower intensities, and shorter durations affect the levels (I have a strong suspicion that there is a bit of 80:20; even a short bout of activity can make a measurable difference, and waiting a bit between taking antibioticsi and starting exercise is probably good for quick gastric emptying).

One reason for me to look into this was that the LLMD wanted me to have IV Tetracycline and Metronidazolei, and I wanted to avoid it (and only take only one tetracycline: Doxycycline _or_ Minocycline), and looked for ways to mimic the effect as much as possible (with Metro taken on empty stomach, I actually see little reason to take it IV, and possibly even less with a little exercise after ingestion). The extent of the differences in plasma levels surprised me a lot, and your finding that it is not as important for Rifampin is rather funny (the facts are in reverse of the most recommendations, but perhaps more caution with Rifampin is understandable).

Your experimentation is very interesting! (http://www.cpnhelp.org/pyruvate_ponderings_and_e< post for passers-by), I will try it soon (now in a Tinidazole pulse, aiming for tendays; perhaps trying Metronidazole before glucose or niacin">i experiments). Perhaps some of the effect of fasting is the combined much sharper rise and higher peaking (the high C'(t) and Cmax). 

Doesn't maltodextrin reach the intestine quicker than glucose (or one should take glucose with a lot of water, I've read 6% glucose as the highest concentration; more slows gastric emptying), and Vitargo even being absorbed quicker (but perhaps not with the morning cereal ;-). Possibly not worth the price, though (four times).

Isn't water (lukewarm or at least not cold) a better bet (possibly a little salt added) for gastrich emptying (your Rifampin absorption), I thought solids slow gastric emptying (but I have similar experience: that even a bit solid food gan trigger emptying, but I have thought that that is due to kickstarting production of gastric fluid). Of course, drinking a lot can reduce plasma concentration a bit, but it potentially has many benefits when taking a lot of drugs (reduced risk of gastric irritation, -ulcers, kidney stones etc).

Borrelia/Cpni arthritis: joint, skin, eye, CNSi, respiratory, UG involvment; fatigue. Borrelia Elisa&WB IgGi, and CPn IgG and IgA pos, HLA-B27 neg. CAPi 5/9/2010 -> 3/2016 2017: some signs and symptoms returning, Borrelia?

I'd tried a glass of warm water with rifampin; it didn't help nearly as much as the bite of food did. Besides just getting the stomach to empty, the other thing that may be going on with rifampin is that the bite of food helps to generate enough acid to dissolve it. (This is something I got out of debating pKa with Paul: I ran across a paper saying that rifampin dissolves better at low pH.) In any case, when I take a little food (as I said, just a bite; not enough to get anywhere near satisfying hunger, and probably not enough to significantly interfere with absorption), the rifampin color seems to hit the urine faster, and also the pill doesn't stick around in my stomach (where, in the absence of food, it seems to irritate it and eventually, after a few hours, prompt vomiting, which sometimes has brought up the remnants of a poorly-dissolved pill).
By the way, I haven't done enough experiments to be really sure of anything regarding rifampin and the bite of food. Please take what I've said about my experiences there with a grain of salt.

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