Fasting and Flagyl

In my last progress report<, I described the experimenting I'd done with pyruvate, and later glucose. Not long after writing it, I found that the die-off reactions from that regimen had abated to the point where they weren't sufficiently entertaining, and I wanted more. So I started to work Flagyl back in to my regimen. But how exactly to do this was not clear to me. On one hand, Flagyl is only supposed to kill the cryptic formi, and thus it would seem that taking pyruvate or glucose, to raise the germ out of the cryptic form, would diminish the killing effect. On the other hand, Stratton's original message< describing the pyruvate protocol had them being taken together:
... After two weeks of doxycycline if all went well, I'd add metronidazolei 500mg twice a day with 6 grams of pyruvate before that. ...
No rationale for this was stated; but one could suppose, for instance, that the doxycycline and azithromycin that the patient would be on, at that stage of the protocol, would be enough to suppress the germ into a state where metronidazole could kill it, and that pyruvate might provide energy that somehow helped in the killing process.

In any case, that was what I experimented with first: just adding metronidazole, without changing the food part of my regimen, which consisted, at that point, of twice a day eating a sugar-rich meal (half an hour after taking antibioticsi; the purpose of this, as detailed in the last report, was to draw the germs out, by feeding them at the same time as the antibiotics reached their highest level.) For comparison purposes, I varied that by sometimes eating in a normal healthy way (more meals per day, without all the sugar). In both cases I took metronidazole 500 mg twice a day, at the same time as the other antibiotics. (Which at this stage, are minocycline 100 mg bidi, azithromycin 250 mg every other day, rifampin 300 mg bidi, and niacin">i 1 g bid.)

The results seemed, at first, to back up Stratton's original recommendation: I got more die-off (or at least felt worse) on the sugar-rich days. But the difference wasn't huge, and after a while, I started to wonder. For one thing, it seemed like I was feeling the most die-off during the times of day when I was hungriest -- and those times occurred a lot more on the two-meals-a-day sugar-rich strategy, since before eating those big sugary meals, I'd wait until I was rather hungry, so that it'd be easy to stomach them. On the sensible-eating strategy, I didn't let myself get nearly as hungry before eating. Could it be that I had it backwards, and that the simple reasoning I'd started with was correct, and that it was the getting hungry, and being hungry during the half hour after antibiotics but before eating, which was giving me the increased die-off? Could it be that I should starve the germ into the cryptic state to enhance the effect of Flagyl? If so, well -- if just a half hour of hunger plus Flagyl plus the other antibiotics gave me noticeable die-off, then what would a whole day of hunger plus the antibiotics give me? It'd have to be an enormous response.

It was. My oh my, was it. I haven't felt so bad at any time during the protocol. Just one day of fasting, taking the antibiotics twice during that day, and I was feeling very sick indeed. Not only did I not feel like eating, I had trouble even keeping the antibiotics down. Even the next day, I felt a bit woozy. There was no question of taking more Flagyl; I took a few days to recover just from that one-day pulse.

Of course, one can always get sick for various random other reasons -- a passing virus, or something -- so to make sure, I repeated the experiment. The second time, my reaction was still very strong, but enough milder that I could, at the very end of the day, eat a meal just before going to bed; by that time I no longer felt like I'd sick it up. The third time, the reaction was reduced still further, and I could eat earlier. The fourth time, it was mild enough that I felt hungry most of the day; after eating late in the day, I repeated the fasting and Flagyl the next day. But those two days were enough: now I'm resting from them (and catching up on my eating).

This strong but quickly-diminishing response is very encouraging: it suggests that I've hit on the way to quickly get rid of the rest of my infection. But it deserves a big fat red warning: Danger! Don't just jump in and try all this at once! Work up to it slowly. I've been taking antibiotics for years, and have very substantially whittled down my infection level; I probably got rid of upwards of 90 percent of it before I tried this fasting trick. If I'd tried all this at once, at the very start, my reaction, perhaps ten or twenty times as strong, might have seriously injured or even killed me. Besides, your mileage may vary; I've just run a one-rat experiment here, nothing definitive.

Still, I can't help speculating that the variations in response between different people that we've seen on this forum may very largely have been due to their eating habits. I recall Rica, for instance, posting of having gone hungry a lot, due to the need to space out medications and charcoal; and on the whole she has done quite well. This dependence on state of hunger might also explain a lot of the variation from pulse to pulse that people have experienced.

Very cool Norman that you're finding this stuff out.  I appreciate it!  I don't know when or if I'll try it myself, my load is definitely higher then yours was, or so it sounds.  So the timing for me is a  ways off but definitely something to think about trying down the road.  I may have to do it while I'm on vacation from work as I know it would know me on my butt if I were to do it now, probably for days.  Thanks!

best, John

RRMSi/EDSSi was 4.5, 5, 6, 6.5, 6.9999, 6.5 on Wheldon/Stratton Protocol beginning 04/12/2006
naci 4x600 mg/day
doxycycline 2x100mg/day
azithromycin 3x250mg/day MWF
metronidazolei 3x400mg/day then 3x500mg/day

I personaly don't see how taking sugar does anything but feed bacteria. I do, however, feel that cortisol plays a part in this disease. When you are hungry it's probably because of low blood sugar. When this happens, if they are able, the adrenals release cortisol to convert protein and fat into usable energy (more blood sugar).

Perhaps your ABXi are potentiated by cortisol. As I mentioned in another post there is an entire segment of CFSi'ers with "Adrenal Fatigue" many of who have found their cure with long term (6-18 months) of Hydrocortisone replacement therapy (not to exceed 20 mg per day).

Doxyi 100mgx2, Azithromycin 250mg MWF, Probiotics: PB8, JarrowDophilus. CFSi since 2003. Last 5+ years lots of the usual research (Depression, Adrenal Fatigue, HPA, Mercury, Candida, Thyroid, etc.). iherb.com $5 coupon code: HAW103

Hi Norman,

This is an interesting but somewhat unexpected result. It is my belief that Cpni use efflux pumps to eliminate antibiotics (as well as other environmental toxins). These pumps use a lot of energy and when active, they deplete cells of energy they need for their normal functions. One of these functions is making hemei and some steps in heme synthesis require ATP. So it has been my understanding that when heme synthesis failed from a lack of energy, heme precursors (porphyrins) were left over and caused a lot of the side effects that people experience. If this is correct, fasting should have increased side effects (which it apparently did) but this should not quickly abate (which does not seem to be the case).

One thought would be that fasting starved the efflux pumps of energy and antibiotics were able to cross the Cpn cell membrane and kill the organism. Anyway I always appreciate your insightful posts. I just sometimes wish they would align better with my views ;)

- Paul

That's the idea behind using sugar (or pyruvate): feed Cpni, and thereby get it out of the cryptic state and into a state where it can be killed by antibioticsi that target the replicating form. I'm no longer doing that, but it seemed to work fairly well while I was.

As for cortisol, it's not the main tool the body uses to control blood sugar; that would be insulin and glucagon. Cortisol is mainly a stress hormone. Extended fasting is a stress; and, looking it up, it has been reported to increase cortisol<; but on the other hand, eating has also been reported to increase cortisol<. In any case, I think an increase in cortisol would likely do the opposite of what I want here, which is to force Cpn into the cryptic state where metronidazolei can kill it.

I'm also dubious about the "adrenal fatigue" business. Just about everybody feels better and more energized when they get cortisol. But it suppresses immunei function, allowing germs to grow more. Certainly the adrenal glands can malfunction; but it sounds like most of the "adrenal fatigue" people don't really test to make sure their adrenal glands have actually malfunctioned, before they start "replacement therapy". Even if your cortisol levels happen to be lower than average, it may be because they should be lower, in order to help you fight infection, even if that makes you feel bad in the short term.

Perhaps the main reason that I didn't try fasting earlier, was that earlier, it was much more difficult for me to fast: difficult enough that I didn't even want to think about trying it. I do indeed blame that on porphyriai. These days, going without food just makes me hungry, which I can tolerate. I don't like being hungry, of course, but it used to be worse than just feeling hungry: it was a combination of being hungry plus being a bit confused, the confusion probably being from porphyria. Eating food, in such a state, could be such a relief that it was almost like a religious experience.

I expect that the cells which are still infected with Cpni still produce porphyrins when starved, but that there are few enough of them now that they don't excrete enough porphyrins to yield a generalized porphyria. I do still experience some porphyria when I kill lots of them, and porphyrins from the formerly-infected cells get released. (At least that's what I guess is happening.)

Efflux pumps being starved, and thus ineffective, does seem like a possible explanation for the unusual effectiveness I got from fasting. But this website is the only place I've seen any mention of them; searching Pubmed for "chlamydia efflux pumps" got me zero search results. That's just absence of evidence, not evidence of absence; but still, I'd be curious to hear if there's any particular reason why you suppose them to exist. I can see why most bacteria might need them: living in a stream or in soil, they are exposed to all sorts of toxins. But chlamydiae live inside animal cells, where toxins might have been minimal enough to let them lose the genesi to make efflux pumps. So even if most bacteria have them, chlamydiae might not.

Norman, I want to say that your experience;

 "Perhaps the main reason that I didn't try fasting earlier, was that earlier, it was much more difficult for me to fast: difficult enough that I didn't even want to think about trying it. I do indeed blame that on porphyriai<i<. These days, going without food just makes me hungry, which I can tolerate. I don't like being hungry, of course, but it used to be worse than just feeling hungry: it was a combination of being hungry plus being a bit confused, the confusion probably being from porphyria. Eating food, in such a state, could be such a relief that it was almost like a religious experience. " ,

This food urgency, is what I experience for years prior to treatment with CAPi.  Now 33 months on this treatment program has be experiencing hunger as just hunger and as you say I can tolerate it without confusion, irritability and extreme fatigue.  I always had to carry food with me when I went away from home, just incase there was an overwhelming need and urgency to eat.  

  • 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
  • <

> I'm also dubious about the "adrenal fatigue" business.
> Just about everybody feels better and more energized when they get cortisol.

I don't.

> But it suppresses immunei<i< function, allowing germs to grow more.

Yes agree with this.

> Certainly the adrenal glands can malfunction; but it sounds like most of the "adrenal fatigue" people don't really test to make sure their adrenal glands have actually malfunctioned, before they start "replacement therapy".

Actually in general the glands themselves don't malfunction (although they may atrophy due to lack of stimulation). The problem lies further up the HPA-axis.

> Even if your cortisol levels happen to be lower than average, it may be because they should be lower, in order to help you fight infection, even if that makes you feel bad in the short term.

Yes this is possible also. However the healthy response to infection is to raise cortisol (as in the potbelly syndrome), so you have to wonder just how much the lowering of cortisol is by design, and how much due to pathology.

 

Hunter: Don't think - experiment
Good point Norman, about checking the adrenals rather then just staring replacement therapy.  I never did either one but did check cortisol, t4, t3, rt3.  I've settled on that I was just wearing my adrenals down because of the amount of caffeine I was taking at the time and have since gone to just 2 200mg doses a day which is a big change over where I was this time last year.  In addition, I'm using caffeine in much the same way that someone would use pyruvate to try and stimulate cpni back into RB and/or EBi form where I can knock it down much more easily.   So far, I still get a big "smack" when I do this so hopefully that's a good sign.

best, John

RRMSi/EDSSi was 4.5, 5, 6, 6.5, 6.9999, 6.5 on Wheldon/Stratton Protocol beginning 04/12/2006
naci 4x600 mg/day
doxycycline 2x100mg/day
azithromycin 3x250mg/day MWF
metronidazolei 3x400mg/day then 3x500mg/day

HI Norman,

I thought the existence of Cpni efflux pumps was generally accepted but that might just be because I do ;) There is a paper that discusses potential chlamydial efflux pumps, Antibiotic Susceptibility and Treatment of Chlamydia Pneumoniae Infectionsi. In any event Dr. Stratton theorized that Cpn used these for antibiotic resistance over 10 years ago. He found some homologs with BLAST searches which I personally find conclusive but I suppose needs to be proven at some point.

- Paul

Actually in general the glands themselves don't malfunction (although they may atrophy due to lack of stimulation). The problem lies further up the HPA-axis.
Well, where, then? How do you distinguish a real malfunction in the hormonal system from a hormonal system that is doing what it is designed to do in response to a big infection that the body can't eradicate?
Just about everybody feels better and more energized when they get cortisol.
I don't.
So you're taking it in spite of it not making you feel any better, just to fix your lab numbers? (Or for some other theoretical reason?) Or are you not taking it any more?

>So you're taking it in spite of it not making you feel any better, just to fix your lab numbers? (Or for some other theoretical reason?) Or are you not taking it any more?

I only ever took h/c for brief periods. But it gave me major immunosuppression, without making me feel better in any sense.

>Well, where, then?

Presumably the hypothalamus and/or pituitary.

> How do you distinguish a real malfunction in the hormonal system from a hormonal system that is doing what it is designed to do in response to a big infection that the body can't eradicate?

That's a good question. I don't know. I cetainly don't think the hormonal system is malfunctioning in isolation. It's directly related to the infectionsi. It may well be that the hormonal system is designed to fail in this way. It doesn't stop you from feeling absolutely awful though. I guess the important question though is how to reverse it, rather than whether it's a malfunction or a secondary adaptation.

Hunter: Don't think - experiment

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