Pyruvate ponderings, and experiments

About a year ago, there were several posts here introducing an experimental pyruvate protocol against Cpni. The general idea of the protocol is to awaken Cpn from its cryptic state (aka "persistent state"), so that it can be killed using antibioticsi other than metronidazolei or tinidazole. Killing it in the replicating state is argued to be less inflammatory, on the grounds that when it is in its cryptic state, Cpn expresses a lot of the highly inflammatory protein hsp60.

I figured that I should try this new protocol out, since it offered a promise of a quicker treatment schedule, but was a bit hesitant to, since the old protocol was working fine for me, and since the theory of the pyruvate protocol didn't seem anywhere near complete. Some parts of it, though, seem fairly well nailed down. That more hsp60 is expressed in the cryptic state seems to be well-established in the scientific literature, although the difference isn't night and day: according to this paper, it's a factor of four or less, depending on how the cryptic state is induced -- in most cases, about a factor of two. Likewise, that hsp60 is generally highly inflammatory seems reasonably well established. A caveat to this, though, is that anecdotally, some people have little response to pulses of metronidazole, even though they seem to end up benefiting from them; to those people's immunei systems, hsp60 might not be particularly inflammatory, and so they might not benefit much from using pyruvate. (Immune system variations of this sort are quite common: the whole purpose of the adaptive immune system is to learn to recognize molecules of disease germs, and that learning process produces different results in different people. Even the innate immune system can differ from person to person in the molecules it recognizes, due to genetic differences.) But although some people may not react much to hsp60, I don't seem to be one of those people; my reactions to metronidazole have always been strong and immediate. So the pyruvate variation is particularly attractive to me. Besides, my personal experience had been consistent with the idea that metronidazole offered a worse gain-to-pain ratio than the other antibiotics: the level of improvement I experienced from starting on the bacteriostatics was greater, relative to the discomfort they first caused, than I later got from metronidazole. After a while, continuing on the bacteriostatics wasn't doing much, and to progress further, I needed metronidazole; but although there were gains from the metronidazole, they weren't as large relative to the discomfort I experienced.

But my first step wasn't to try pyruvate itself. It seemed to me that if there is a better gain-to-pain ratio from killing Cpn in the replicating state, then the first step should be increasing the antibiotics which target the replicating state. That, for me, meant adding niacini and then rifampin, and suspending the metronidazole pulses. (I kept taking the minocycline and azithromycin I'd been on.) Besides being (at least in theory) less inflammatory when they do kill Cpn, they also help suppress it and keep it from growing. The combination of a tetracycline and a macrolide (such as my minocycline plus azithromycin) is commonly described, here, as suppressing Cpn, and forcing it into the cryptic state; but it's not absolutely perfect in doing so; none of the medications we use are absolutely perfect. Adding rifampin, which attacks yet another stage in the same process (the transcription of RNA from DNA, which has to be done before the RNA is used to make a protein) improves the shutout. Also, at least one group (see this paper) has found that neither rifampin nor azithromyin has any effect on Cpn infecting monocytes. That is what the niacin is for; Stratton has found that it helps clear Cpn from monocytes and macrophages. Rifampin and niacin (or INHi) have commonly been deferred to a final stage of the protocol, but I see no reason for this; it seems better to introduce them earlier, and, when something is necessary to ameliorate die-off reactions, delay the metronidazole or reduce the dose of it.

After a month or so of rifampin (and a liver function test to make sure that my liver wasn't objecting), when reactions started to subside, I started trying pyruvate. But there were a couple of things in the pyruvate protocol that I felt like modifying, and indeed modified right from the start. The first was the interval of time between taking the pyruvate and taking the antibiotics. According to the posts here, the idea was to wake the Cpn up with pyruvate, then an hour later take antibiotics to kill it. One hour was not the universal figure; there was a post or two saying that Sriram, if I recall correctly, was recommending half an hour. But I don't like giving bacteria even half an hour's head start. Any growth they can get in during that hour means more killing has to be done. Also, it isn't clear to me that a head start would be necessary or beneficial. The idea seems to be to whiplash the chlamydiae, yanking them first in one direction then in another. But bacteria often can respond quite fast to changing environments; it's hard to whiplash something so small. There is another general class of possibilities, which seem like an equally good fit to the meager evidence available, which is that instead of whiplashing the chlamydiae, what kills them is getting mixed messages: the energy supply says go, while the antibiotic says to stop, and this confuses their metabolisms enough to kill them, whereas if both indicators were pointing at 'stop', no confusion would exist. Or, put differently, if the chlamydiae are dormant already due to lack of energy, then antibiotics may not damage them much. For many bacteria, dormancy is a good way of resisting antibiotics: when the cellular machinery is shut down, throwing a monkey wrench into it does no damage. This is seen in biofilms, where dormancy is the chief mechanism of resistance, in tuberculosis, where it is the reason why treatment must continue for a year or so, and even in Cpn itself -- or, at least, there are hints of that: the above-linked paper finding a lack of effect of antibiotics on Cpn in monocytes also found that Cpn was naturally suppressed, and slow-growing, when it infected those cells.

The other thing I wondered about was: why pyruvate in particular? The first step of energy production from glucose is the splitting of the glucose molecule into two pyruvate molecules. So why not glucose? It's two orders of magnitude cheaper than pyruvate, it tastes better, and so it can easily be taken in much greater quantity than the six grams recommended for pyruvate. Besides, it has no calcium, and thus can be taken at the same time as antibiotics, whereas pyruvate is mostly available in the form of calcium pyruvate, which shouldn't be taken anywhere near tetracyclines. A bit of looking into biochemistry offered a possible answer to this question: the splitting of glucose into pyruvate requires two molecules of ATP. Thus pyruvate could jump-start the process of generating ATP, in cells that are desperately short of it to begin with.

But this possible advantage of pyruvate seems pretty marginal. For one thing, it doesn't mean that a lot of pyruvate would be better than a lot of glucose: a cell that was so desperately short of ATP that it couldn't make any more, even with loads of glucose around, is a cell that would quickly die, since ATP is used for just about every piece of cellular machinery that requires a power input. So such cells are not likely to be around in the first place. The jump-starting idea doesn't seem like it'd be much use on the other end of the spectrum, either: you can't jump-start a car whose problem is that it ran out of gasoline. Glucose is a main energy source, which the body normally uses at a rate of hundreds of grams a day. Six pills is nobody's idea of a meal, even if they are large pills. The pyruvate might even be grabbed by the liver and used to make glucose, if the body is low on glucose; all absorbed food has to go through the liver before it reaches the rest of the body, and I've seen pyruvate listed as one of the starting materials the liver can use for gluconeogenesis. (But I haven't looked into this in detail; I mention it only as a possibility.) It's only between those two extremes that pyruvate seems like it could have much advantage over glucose.

I quickly realized that if I arranged my schedule as seemed natural around taking pyruvate an hour before antibiotics, I'd end up every day in the second of those situations: hungry (and thus low on glucose), with a few grams of pyruvate vainly attempting to provide enough energy for me. That's because my morning schedule would be:

  • wake up, and take pyruvate.
  • wait an hour, and take rifampin, minocycline and niacin.
  • wait another hour, and then eat.

    Not only would this sabotage the jump-starting idea, I don't like being hungry. If I were to try to fix this by moving up the meal, and eating at the same time as taking pyruvate, then there wouldn't be enough separation between the calcium pyruvate and the minocycline: one hour is enough on an empty stomach, but not enough on a full stomach. In a full stomach, everything sloshes around and mixes; it then empties only as fast as the intestines below it can handle the input. So there'd still be calcium in the stomach when the antibiotics went down an hour later. (There is a way to get around this problem, which is to delay the minocycline until later in the day; but I didn't think of it at the time.) As for the second hour of delay, that would be necessary to separate the rifampin from food.

    There are other possible advantages of pyruvate, which I wondered about. It might, for instance, be able to bypass some of the body's mechanisms for regulating blood glucose, and thus deliver extra energy, over and above what can normally be supplied. But this seems unlikely, since pyruvate is generally a molecule that the body recognizes. Besides, insulin, the main regulatory molecule for glucose, doesn't prevent glucose from being dumped into the blood; instead it increases the rate at which glucose is taken out of the blood and into cells. That is, it's blood glucose which it regulates, not cellular glucose -- and Cpn lives in cells, not in the blood. (But maybe there's another regulatory mechanism which applies?) Another possible advantage might be if yeast didn't like pyruvate. But this seems unlikely: it would be strange if human mitochondria could use pyruvate but yeast mitochondria couldn't.

    For these reasons, the first thing I tried out was taking glucose, rather than pyruvate, and taking it at the same time as my morning and evening doses of pills. I didn't want to give the bacteria a head start, and I figured that even if glucose did less than pyruvate, I could compensate by taking more of it. At one point I weighed the spoonfuls of glucose I was ladling on to my morning cereal: they came to about 50 grams. Yes, that's a lot: it's 200 calories' worth, about a tenth of my daily energy supply. Although glucose isn't as sweet as sugar is, the resulting bowl of cereal is still disgustingly sweet. Taking everything together, at the same time, simplified logistics; it violated the standard dictum never to take rifampin at around the same time as a meal, but I'd looked into that and found that it wasn't too horribly important.

    Adding glucose did indeed seem to have quite a strong enhancing effect on the die-off reactions I was experiencing. I also tried sugar, which seemed to have a similar effect. This might seem to contradict people's experiences, reported here, of using glucose successfully for mitigating die-off reactions. But there is no contradiction. When you are short on glucose, it helps to take some of it, in order to keep levels in the normal range. I, on the other hand, was pushing my glucose levels as high as I reasonably could (and then some), not just taking a bit of it when I felt low.

    This extreme glucose-eating is obviously something that anybody who is diabetic should not try, and which people who suspect diabetes or might be near to diabetes should try only with great caution. It's also something that people who have had fungus problems should be very leery of trying. For my own part, though, looking through people's anecdotes on these forums, it seems that people who have fungus problems, or think they do (the exact nature of those problems is not always clear), generally had those problems even before starting antibiotics. I, in contrast, have generally had a problem-free gut. As for diabetes, one precaution I took was to have my blood glucose levels tested during the times when I expected them to be the highest -- that is, an hour or an hour and a half after eating the glucose. (Glucose is part of the 'complete blood count' that is routinely ordered.) My glucose levels were out of the "normal" range, but that range is for fasting people, and I'd just been doing the precise opposite of fasting; for someone who was trying to put himself through a glucose tolerance test, the levels (109 mg/dL in one test, 117 mg/dL in another) were very comfortably low.

    My next step, after doing the above for a couple of months or so, was to add a bit of pyruvate to the mix. The one antibiotic I was taking that was incompatible with it was minocycline; so when I took pyruvate, I delayed taking minocycline by two hours, to separate it from the pyruvate. Minocycline is not one of the short-lived antibiotics, and the dosing strategy with it is to take it twice a day, so as to keep blood levels consistently high; so delaying it like this doesn't make much difference. The pyruvate seemed to further increase reactions; I settled on 4 grams at a time, finding that when I was already using lots of glucose, more pyruvate than that didn't seem to have much effect. Indeed, I can't really say for sure that the pyruvate had any effect, when added to monster amounts of glucose; my reactions have varied enough, from day to day, that what I observed from it could just be random chance. I've been taking it mainly on the chance that there might be more to the jump-start idea than I think. (Another thing that has complicated my observation of die-off reactions is that the effect of any given dose of stuff has been diminishing over time, in me. This is as it should be: any given germ can only die once. But it still complicates observation.)

    At first, all I'd proven was that I could make myself feel bad using glucose and pyruvate -- and feeling bad is not much of an achievement, in itself, even though it did have all the usual patterns which I associate with die-off. (For instance, in die-off, things that get sore, like my back or my neck, are things that had problems even before I started antibiotics; things like my elbows, which I've never had any problems with, have remained good throughout. There is also a characteristic taste/smell of die-off.) At first, the die-off symptoms were bad enough that I had to start using activated charcoal again. (I didn't absolutely have to, but it felt better to.) But I only used charcoal for a month or so; after that, the die-off lessened, and after a couple of months I started feeling pretty seriously good.

    My next change was to go to the reverse of the standard recommendations, and take pyruvate (and glucose) after the antibiotics, by an amount of time varying between half an hour and an hour. (I didn't know the right interval, and so was not particularly disciplined in keeping the interval constant.) The reason for this change was so that I could take the rifampin and niacin on an empty stomach, making the spike in their blood levels quicker and higher. Although the half-life of rifampin is pretty short, it still lasts longer than glucose (and presumably pyruvate), so this delay doesn't detract from the goal of having the rifampin and the glucose spike at the same time. It might even help; when sugary food is eaten, the body starts raising the blood glucose level in anticipation, even before the meal makes its way into the bloodstream. This change had the desired effect: giving me more die-off symptoms than I'd had when taking everything at once.

    The last modification, as of about three weeks ago, has been not to take the niacin at the same time as the antibiotics, but to delay it until ten minutes before the meal. I'd been supposing, without seriously thinking, that niacin had a half-life similar to rifampin's; but when I got around to looking it up, I found that it's actually much shorter: less than an hour. So it seems appropriate to take it much closer in time to the meal; ten minutes still seems like enough time to give it a decent head start down the pipe. In any case, this new modification seems to increase the effect of the niacin; I've even gotten an occasional flush from it, whereas before, flushing had become minimal: just a bit of tingling, with little or no visible color change. (I've generally gotten flushes whenever I've increased the peak level of niacin, and also whenever I've done something else to increase the intensity of treatment; adding rifampin, for instance, provoked some flushing at first.)

    In any case, my current schedule is:

  • take rifampin, minocyline, and (if it's the day for it) azithromycin
  • after twenty minutes or so, take niacin
  • after another ten minutes, take pyruvate, and then glucose and whatever food I care to eat, followed by vitaminsi and supplementsi.

    In any case, I've been liking the results of this. It is, of course, optimized to make me feel bad in the short term, and indeed does so. But the short term seems much shorter than it was with metronidazole. I wake up each morning ready for more punishment; and despite my best efforts to make myself feel bad, on the whole I'm feeling substantially better. With metronidazole, there was more of a long tail-off, where even after a month I'd still be feeling the effects of a pulse, as a sort of mild general debility. At the end of a pulse, I was always grateful to stop. I think there is probably something of a long tail-off even with the pyruvate/glucose boosting; but it is much less than with metronidazole. At any rate, some things, such as joints, take a long time to heal; hurt to those has never gone away fast, and the current regimen is no exception to that (although on the whole, they too are feeling better).

    I'd attributed the delayed reactions from metronidazole to delayed die-off; but I've started to doubt that: a month is quite a while for bacteria to still be dying off, or even for infected cells to be dying off in response to bacterial die-off. Besides, these days I'm getting the same sorts of immediate reactions, with much less of a long tail. I'm wondering, now, whether the long tail of metronidazole's effects is due to some sort of autoimmune reaction. The mainstream researchers who blame autoimmunityi for the various diseasesi we suffer from are shortsighted in ignoring the possibility of infection, but they aren't studying nothing; there is a very substantial autoimmune component, even if it's not the root cause. And there has been some talk about hsp60, in particular, being a cause of autoimmune reactions -- talk which I haven't paid much attention to, but which now seems more interesting. A month seems about right for the time scale of the decay of an autoimmune reaction.

    Since I started antibiotic treatment rather early (I did not wait for conventional medicine to fail me, but rather took it at its own word that it would do so), and have been on it for a while, my improvements recently have been more a matter of minor things, or things that at least sound minor, than of anything dramatic. Quickness of thought has improved; my back is at the stage where I seldom have to think of it at all, as is my neck -- whereas before treatment, I had to take a lot of care of those two body parts. In addition, I'm experiencing a sort of general ease and lightness of motion, of the sort that people describe as "walking on air". But the continued reactions to antibiotics tell me I'm not done yet.

    Although I like the results, this is not something I can recommend to people as a recipe, even if it does survive whatever criticism might be leveled at it. What I've conducted is what is known as a "one-rat experiment"; there is no claim of general applicability or repeatability here. Note also that this schedule is designed for maximum impact. I was not a sad sack even when I started antibiotic treatment; and now, after about three years of it (albeit going relatively slowly), I'm at the stage where my bacterial loadi is much reduced, and so cranking up the intensity of treatment is tolerable and desirable. People who are in worse shape than me should definitely not jump in to the full-blast treatment.

    But although this stuff doesn't seem ready for prime time, it seems worth exploring its implications. "There is an art, it says, or rather, a knack to flying. The knack lies in learning how to throw yourself at the ground and miss. [...] Clearly, it is this second part, the missing, which presents the difficulties." -- The Hitchiker's Guide to the Galaxy This treatment bears some resemblances to the above quote. For one thing, there is the end feeling of "walking on air" (which is really, of course, just the feeling that healthy people consider normal, made odd only by unfamiliarity). For another, there is the trying to maximize misery (in the form of die-off symptoms), in order to achieve that end feeling, yet the fact that only certain very specific ways of "throwing yourself at the ground" work. And, lastly, the whole thing may seem as improbable as flying would be, at least to today's doctrinaire medical people. But that, I think, is just due to strangeness; to me, it seems to fit well with other knowledge, explaining some things which I'd wondered about for a while.

    One question which I'd had about Cpn was under what circumstances it wakes up and starts replicating. As I've argued here before, it's clear that most of the time, most of the chlamydiae have to be in the cryptic state; if most of them were replicating most of the time, they'd quickly grow so numerous as to kill their host. But then what prompts them to come out of the cryptic state? Stress is one likely answer; when the body is stressed, the immune system relaxes its vigilance. But there can be more than one answer; and another possible answer is the availability of energy.

    That would explain, for one thing, why cell cultures can survive for extended periods with a Cpn infection, as Stratton has found them to -- why the infection doesn't just eat through the cells until none are left, killing cells as it finishes its reproductive cycle and emerges from them in the form of EBs -- and why the infection, in cell cultures, can be so subtle as not to be noticed. There is no immune system in such cultures (at least not in the usual cultures of epithelial cells), so stress couldn't be an explanation (at least not via immune system suppression). But if one hypothesizes that lack of energy can cause Cpn to enter the cryptic state, then one could get a stable situation: if many cells are infected, the infection runs out of energy and has to enter the cryptic state, while if few cells are infected, the infection has energy to grow and to infect more cells. This explanation also requires that whoever maintains those cultures adds only about enough glucose to feed uninfected cells, and that infected cells need more glucose than uninfected ones; but those assumptions seem natural.

    It would also help explain some things about the relationship of diet to heart diseasei, and to various other diseases. The advocates of high-fat (Atkins) and ultra-low-fat (Pritikin) diets don't agree on much; but they agree on the undesirability of eating lots of high-glycemic carbohydrates at one sitting. It should perhaps be explained that the "glycemic index" of a food is a measurement of the rise in blood glucose an hour after eating it; "high-glycemic" carbohydrates are those which are absorbed quickly. Glucose, and other sugars, are absorbed fastest. Starches are not far behind; the distinction which is often made between simple carbohydrates (sugars) and complex carbohydrates (starches and such) doesn't make much difference nutritionally, since the enzymes that break up starches into sugars operate very fast. What does slow down absorption a lot is for the sugar or starch to be embedded in something that takes a while to digest, as in a piece of fruit or vegetable, which retains a lot of its structure even when chewed thoroughly. Absorption is also slowed a lot if the carbohydrate is mixed in with a lot of other food, and thus has to wait a while in the stomach before being digested. Eating vegetables with a meal, for instance, dilutes it and slow its absorption -- which is good if one believes the theory that big pulses of glucose are bad. But the reason for that theory has always been unclear to me. The explanations I've seen (from the advocates of both diets, and also from mainstream medicine sources) go through various consequences, but trail off before getting to anything that is obviously harmful. Insulin rises; fat is stored -- but those things, in themselves, are just another expression of the basic truth that eating more calories makes you gain weight; they say nothing about why this particular form of calories would be especially harmful. But if Cpn wakes up and replicates during pulses of blood sugar, it would completely explain the recommendation to avoid carbohydrate pulses; most of the diseases people try to avoid via these diets have been linked to Cpn, as has obesity itself.

    Another thing this would help explain is why diabetes, with its poorly-controlled blood sugar levels, is so damaging, and contributes so much to cardiovascular disease.

    It would also explain why bariatric surgery (weight-loss surgery) is helpful. That category of surgery does not include liposuction, nor other surgical removal of fat; bariatric surgeons consider liposuction to be cosmetic surgery, not weight-loss surgery. Instead it is stuff like stomach stapling, or surgery to insert a constrictive band around the stomach, or stomach bypassing. Such surgeries have been put through placebo-controlled studies, and been found to help people lose weight, and to help with some of the diseases associated with obesity. Surgeons, these days, are starting to do those operations even on children who are severely overweight. Patients who go through bariatric surgery are given recommendations for diet; but the one thing the surgery does, mechanically, is to stop people from eating a lot of food at one time. It doesn't limit the total amount of food they can eat; that remains the same. It just limits the amount they can eat at one sitting. Since dietary recommendations can be given even to people who aren't operated on, and since when they are, they don't seem to be much use, the success of the surgery indicates that eating a lot at one sitting is unhealthy.

    Of course, that overeating is unhealthy is not at all a new or surprising idea; it's part of our traditions. Likewise, it's a traditional idea that eating lots of sugary food is unhealthy, and that eating vegetables with a meal is healthy. But the reasons for these traditions had never been clear to me. Sugars are a basic nutrient, which the body uses a lot of. As for large meals, in human history, food has often been scarce; a gene that made it unhealthy to eat a lot at one sitting would have been evolutionally disfavored, since at many points in history (and prehistory), it made sense to eat what one could of a food source that would otherwise rot or be eaten by animals. But if Cpn wakes up and grows when one eats a lot of quickly-absorbed carbohydrates, then these traditional ideas of what constitutes unhealthy eating are explained completely. They don't have to apply to everyone; they just have to apply to the infected; but enough people are infected with Cpn to explain the existence of the traditions. And if the responsible genes are in Cpn, rather than in humans, then human evolution can't weed them out.

    Another thing this set of ideas would explain is some of the variance we've seen between different people's responses to antibiotic treatment. A cautious, prudent diet may be just the thing to ameliorate die-off symptoms; but it may hinder treatment in the long run, by not luring out Cpn to be killed by antibiotics. People here commonly blame adverse responses to carbohydrates on "fungus problems"; but although fungus problems certainly exist (if a problem responds to Diflucan, then it is probably a fungus problem), it is worth considering Cpn's response to carbohydrates, too, as an explanation. Also, the mere timing of meals, relative to antibiotics, may play a role in the differences between people's responses.

    Lastly, for drawing Cpn out of the cryptic state, there is another substance that seems like it might be useful: tryptophan.

  • Previous reports on my case can be found here, here, here, here, and here.
    Norman, Once again, you've given me enough to read and study for an entire evening. Thanks again for your intelligent and cogent posts. I kind of like stretching my brain (Wink now that it's working again, that is).

    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 Norman. Your review of the protocol that you are using is most useful. I've only just started my treatment and just joined this network. I'm encouraged that I'll find here very useful recommendations and common experiences. Straight away I asked my self - How can I speed this up? You see, I am hoping for a 12 month treatment. But I've had CFSi for 20yrs, that's probably not realistic. In Australia, there are so few doctors who know enough about CP to be of much help. So I'm my own researcher and physician to a degree.

    Leanne

    Norman, its becoming clearer now, thank you!!............Sarah

    An Itinerary in Light and Shadow

    Completed Stratton/Wheldon regime for aggressive secondary progressive MSi in June 2007, after four years, three of which intermittent.   Still improving bit by bit and no relapses since finishing treatment.

    Norman, did you ever try Tinidazole instead of metronidazolei from any of your pulses?  Tinidazole has been OK for me in many respects.  I have not substitute minocycline for doxycycline but may need to do that in the future. And I may substitute clarithromycin for roxithromyin or azithromycin because it is a daily dosed medication and available easily here in the USofA.  I am using calcium Pyruvate have been for a number of months now mid-afternoon for an energy booster in my mid-afternoon energy sink hole and it works for me in that application.   I have not used it for augmenting the intensity of abxi effect as it has been done in some instances by members physicians for their personal treatment plans.   I am satisfied with the progress of the basic Stratton/Wheldon CAPi for my abxi treatment at present, as it has allowed me some time to begin to participate once again in a more functional lifestyle.  Guess that may be because I have been ill with CFSi for many, many years and my onset of trouble was not an acute experience or was it a rapidly reached diagnosis as it is for some folks with MSi in the early stages.  

    It is wonderful to hear your process and I am very glad that this is working for you and may give some insight to others here to ponder.   I will be looking forward to reading your continued personal insights.   

    • CAPi(TiniOnly): 06/07-02/09 for CFSi
    • MethylationProtocolSupplements: Started08/08
    • Intermtnt CAP: 02/09-02/10
    • Full MethylProtocol & LDNi 02/09
    • Off CAP: 02/10, cont LDN & MethlyProtocol support

    Norman- I always appreciate your thoughtful, clear observations and well reasoned suppositions and experiments. This experiment is the epitome of them all. I particularly appreciate your care in noting the difference between reason and supposition from observations and what we factually know from scientific data, the latter of which is so little.

    Not understanding the chemistry as you do, it never occurred to me  to question why pyruvate and not glucose directly. Assuming the health issues with glucose are accounted for, it certainly is a cheaper an more efficient way of stimulating Cpni growth. I'll have to try it and see.

    One of the criteria that Dr. Stratton felt was useful in this type of protocol is to use shorter half-life antibiotics, so that you are gearing up replication the most by amping up the ATP (glucose or pyruvate) when there was little or no replication-inhibiting abxi in the cell to hold Cpn in cryptic state. Both niacini and rifampin qualify for this, and you might further experiment with this by changing your longer half life abxi (azith and minoi) for shorter varieties. This was part of my switch to roxyi since I was playing with the pyruvate protocol at the time, and roxy is shorter half-life than azith. Biaxin also meets this criteria, as does doxyi.

    I've thought similarly about tryptophan, since that is one of the main ways of inducing cryptic state in the lab (tryptophan starvation) and of feeding to re-ignite cryptic to replicating form. I also suspect that some of the sleep and mood problems in Cpn related CFIDSi is from tryptophan depletion by Cpn. Timing is the issue here, since tryptophan may induce sleepiness and is usually taken at night for this reason, so if you have some thoughts about this let me know. It may be enough to take it before bedtime and let your morning abx dose get at the replicating phase, although this violates your principle of not letting it be stimulated to replication too long before kicking it's butt. 

    All in all you've stimulated much to think about. I'll pass this on to see what Dr. S might have to add.

     

    CAPi for Cpni 11/04. Dxi: 25+yrs CFSi & FMSi. Currently: 250 aithromycin mwf, doxycycline 100mg BIDi, restarted Tinii pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

    Hi Norman, Lots to chew on here...thanks for the mind-meal.

    Joyce~caregiver-advocate in Dallas for Steve J (SPMSi).  CAPi since August 06, Cpni, Mpn, B. burgdorferi, systemic candidiasis, EBVi, CMV & other herpes family viral infectionsi, elevated heavy metals, gluten+casein sensitivity. 

    No, I've never tried tinidazole. Its advantage in causing milder reactions seems like it might be due to being less effective in killing Cpni; maybe not, but in any case I've been leery of it.

    As for clarithromycin, I might try that; but the switch to it seemed largely predicated on the idea of waking the bacteria up and then suddenly slamming them with antibioticsi; a pulse of antibiotics is necessary for that. Though that's possible, I find it more plausible that the effect is from simultaneously waking the bacteria up and subjecting them to antibiotics; for that, antibiotic pulses aren't necessary (although if your antibiotic is of the pulsed sort anyway, like rifampin is, you should make sure its pulses coincide with the pulses of pyruvate).

    I haven't done a head-to-head test of these two theories, which could be done by comparing the reactions I get from taking pyruvate an hour before antibiotics against the reactions I get from taking it at the same time or half an hour later. I've just done the latter things, and found that they seem to be effective in increasing die-off, and in the long run in making me feel better. If I'm right, then taking pyruvate an hour before would result in some overlap of the two pulses, but a bunch of unnecessary bacterial growth, and thus die-off symptoms without as much progress in clearing the infection. But to judge that progress, I'd have to do a rather long test -- at least a month, and probably much more; and I don't care to. Judging die-off symptoms could be done quicker, but die-off symptoms aren't what we're after. I also somewhat doubt my own ability to judge my long-term progress; it's not something that's easy to measure. Only when there's a rather large degree of progress (or regress) does the signal emerge from the noise enough that I get confident about it. And it's especially easy to misjudge when I start off disliking one of the theories, and liking the other, as is the case here.

    There's nothing exclusive about the two theories, of course: it could easily be a little bit of both.

    No, no - no pulsing of rifampin!

    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

    By 'pulsing', as regards rifampin, I don't mean that rifampin should be pulsed like metronidazolei is in the CAPi; I just mean that since rifampin's half-life is only about three hours, what you get when you take it on the usual schedule (once or twice a day) are pulses of it, rather than continuously high blood levels.

    I picked out the following 6 assertions from that 5000 word tome:

    1. People have varying responses to flagyli, could be due to different immunei reactions to HSP60

    2. Instead of whacking chlamydia, pyruvate works by sending mixed messages

    3. Why pyruvate, why not glucose?

    4. Flagyl pulses have a very long tail - due to autoimmune reaction?

    5. Cautious diet may alleviate symptoms, but in long-run doesn't lure out Cpni to be killed by abxi

    6. Tryptophan?

     

    1 wasn't something I'd considered, and it seems plausible. But it would be very difficult to quantify this vis-a-vis how much of the variation in responses is simply due to e.g. degree of illness. But interesting nevertheless.

    2 I think could well be true. It certainly explains the fact that the chronology (pyruvate or abxi) doesn't seem to matter much.

    3 you pretty much answer yourself. Glucose seems to be working for you, but there are real risks for those of us who aren't as healthy as you.

    4 is the real problem with pulsing - the long tail. I don't know if it is an autoimmune reaction but I certainly think it is a runaway (over-?) reaction. If it is autoimmune, given that higher doses of Vitamin Di will drag out pulses much much longer, does that mean D is potentiating autoimmunityi?

    5 is the gem in all this. Its probably the core question regarding Cpn treatment, and so deserves its own thread.

    6 I mention because Jim said that tryptophan may induce sleepiness, but surely tryptophan gets converted to 5-htp. I take 5-htp during the day and at night. During the day it increases neurotransmitters and if anything wakes me up. At night I seem to get some conversion to melatonini, but the effect is subtle. Has anyone actually experienced sleepiness firsthand from supplemental tryptophan taken during the day?

     

    Hunter: Don't think - experiment
    My guess with vitamin Di would be that it increases die-off in the first place, and thus increases the consequences of die-off, rather than doing anything that specifically promotes autoimmunityi.

    As for tryptophan, that gets converted to a variety of things, most of which I am only dimly aware of. But as regards 5-HTP, this caution is probably worth reading.

    Norman- great link on dangers of 5-HTP use. Sounds like the thing to do is stick to tryptophan if you are going to use any of these serotonin precursors either for sleep or depression. And given the cautions in the original Vanderbilt patent for serotonin and porphyrins, probably not the first choice in any case. I've put it on a seperate page so as not to space on your thread as the info is of interest to the discussion and hard to locate: http://www.cpnhelp.org/tryptophan_serotonin_chla

     

     

    CAPi for Cpni 11/04. Dxi: 25+yrs CFSi & FMSi. Currently: 250 aithromycin mwf, doxycycline 100mg BIDi, restarted Tinii pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

    Some of the background information in that patent text quote seems to come from the world of stroke and heart attack treatment; that's the sort of place where one finds references to "the post-ischemic neurological score" -- ischemia being lack of blood flow, as is produced by a heart attack or stroke, and "post-ischemic" implying that the ischemia would be a brief incident rather than an ongoing problem. While ischemia is a possible factor even in a slow Cpni infection, strokes and heart attacks do much quicker and more intense damage. So lessons from that world don't necessarily carry over; one would have to look hard at the numbers.

    The bit about tryptophan interfering with gluconeogenesis, on the other hand, is definitely relevant. Still, if you're eating plenty of glucose or starches, you might not need to worry about gluconeogenesis, since your liver might not need to do much of it.

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