MediTest

Because it has been such a prominent part of my own illness, I've done quite a bit of research on porphyria. Almost everything in the literature refers to primary genetic porphyria, though there are a few references to secondary (non-genetic) porphyria caused by various liver-destroying processes.

Primary porphyria is a genetic disease in which there is a deficiency of one of eight different enzymes, each of which is required to effect one of the eight sequential steps required to synthesis the iron-containing protein heme. The output at each step is the precursor for the next step of heme synthesis. A deficiency of one of the enzymes can cause accumulation of the precursor from the previous step and prevent the subsequent steps from producing heme.

Normally, finished heme output feeds back to the first of the eight steps, and halts heme production when sufficient heme has been synthesized. 

In primary genetic porphyria, heme production is compromised, and thus sufficient finished heme feedback doesn't occur to halt the continued attempt to make heme, and one of the precursors continues to accumulate.

These precursors, called porphyrins, are highly neurotoxic, though normally they exist only transiently in the heme manufacturing pipeline. In primary genetic prophryia, not all porphyrins are converted to heme and accumulate to excess. When accumulated to sufficient levels, these porphyrins trigger the various manefestations of the various forms of porphyria.

Primary genetic porphyria attacks are triggered when the body is called upon to make an amount of heme that exceeds the limit imposed by the insufficient enzyme level. Most porphyriacs can make sufficient heme for ordinary activities, but are unable to make larger amounts of heme required for exceptional circumstances.

Thus, porphyria is an episodic illness that occurs when the body is occasionally called upon to make more heme than  can be  produced by the compromised  heme-making machinery.

While all cells manufacture some amount of heme, the greatest amount of heme is manufactured during the production of red blood cells. Most of the rest of the body's heme is manufactured by the liver. However, red blood cell production is a relatively steady-state operation, and would thus not be expected to be involved in requirments to make exceptional amounts of heme, and would thus not be expected to be involved in porphyria attacks.

The liver, on the other hand, is involved in large numbers of  processes that are anything but steady state. An examination of classical porphyria triggers such as alcohol consumption, tobacco consumption, intense exercise, illicit and licit drug consumption, and dietary changes show that these are all environmental factors that heavily impinge upon liver function.

Fundamentally, then, primary genetic porphyria is a disease of the liver. 

Switching gears a bit now, Stratton has indicated that Cpn infection causes a disruption of heme manufacture via mitchondrial dysfunction. The pipe-lined steps of heme manufacture are disrupted due to lack of ATP either inside or outside of the mitochondria due to ATP-theft by Cpn, rather than due to enzyme insufficieny. However, the end result is the same as in primary genetic porphyria, namely accumulation of pophyrins.

Thus, Cpn infection could be expected to produce acute porphyria attacks that mimic  the accute attacks seen in primary genetic porphyria, and such Cpn-mediated attacks could be expected to be triggered by classical primary genetic porphyria triggers.

However, Cpn infection also seems capable of interfering with even normo-intensive heme manufacture, and thus can produce background level of porphyrins, even when classical triggers don't exist.

Furthermore, when Cpn-infected host cells lyse as a consequence of Cpn RB destruction via antibiotics, accumulated intracellular porphyrins are released into the blood stream.

Thus, Cpn infection produces three distinct porphyria phenomena:

1. Acute porphyria attacks similar in nature to primary genetic porphyria and which are triggered by classical primary genetic porphyria triggers that induce calls for exceptional amounts of heme. Such Cpn-mediated attacks would be expected to produce elevated porhyrin levels similar to elevations seen in primary genetic porphyria acute attacks.

2. Interference with  normo-intensive heme production, resulting in slightly and chronically elevated porphyrin levels at all times.

3. Pulsed releases of relatively larger amounts of porphyrins than seen in Item 2 above during host cell apoptosis as a consequence of RB destruction due to antibiotic treatment, with such amounts related to the degree of preceding RB destruction.

Finally, based upon the earlier explanation of primary genetic porhyria being fundamentally a disease of the liver, and leaving aside the possibiity of erythroid Cpn infection, I'm going to assert that essentially ALL clinical porphyria phenomena seen in Cpn infection are a function of Cpn infection of the liver specifically. Thus the degree of Cpn liver infection is going to influence the degree of the three Cpn porphyria phenomena.

This explanation would account for the different degrees of difficulty experienced by those undergoing CAP treatment for Cpn infection. In particular, this may explain why many of those with MS (and perhaps certain other Cpn-caused conditions) do not experience the three Cpn porphyria phenomena, whereas those with CFS/CFID/MCS/GWS usually do. That is, people who experience porphyria symptoms have a Cpn liver infection, and those that do not experience porphyria symptoms don't have a Cpn liver infection. 

Most people with CFS/CFID/MCS/GWS/ME most likely have Cpn liver infections since most of these people report porphyria symptoms. Those people with MS and other conditions who do not report porphyria symptoms most likely do not have a concurrent Cpn liver infection.
 

basil. 

 

 

Basil,  You definitely brought the best kind of baggage with you when you walked through this door.  Thank you for this terrific information.  I have a challenge for you.  Suppose someone with unsuspected/undiagnosed MS donates gallons and gallons of blood over a 30+ year period, thereby compelling his bone marrow to frequently rev up RBC production over those years.  Such an individual is later diagnosed with MS and even later experiences NAC flu.  What were the porphyric possibilities in that situation, and what toll might have been paid over that extended period?  Thanks,

 Joyce~caregiver-advocate in Dallas for Steve J (SPMS) / Mpn, EBV, CMV, elevated heavy metals; strong indications of Cpn, gluten+casein sensitive / Wheldon CAP since Aug. '06 - 200mg doxycyline/day + 250mg azithromycin every other day; antivirals; chelation; LDN.

Joyce~caregiver-advocate in Dallas for Steve J (SPMS).  CAP since August 06, Cpn, Mpn, B. burgdorferi, systemic candidiasis, EBV, CMV & other herpes family viral infections, elevated heavy metals, gluten+casein sensitivity. 

Joyce, I'm not sure what the long term porphyric implications of induced red blood manufacture might be. My guess is that it is unlikely there would be any, particularly if you did not experience any symptoms of porphyria after donating blood. I've not run across any published research specifically implicating  red blood cell heme manufacture in porphyric processes, though I haven't actually gone to a medical library yet and studied porphyria in depth.

NAC flu is an issue that is essentially unrelated to porphyria. It is a cytokine-mediated allergic reaction to the proteins released when EBs are killed. EBs, if you remember, are the extra-cellular "spore" form of Cpn, and are metabolically inert until they enter a cell to infect it, at which point they convert to the active RB intracellular form, which is the form that can interfere with heme production. Interestingly enough, I did not have any reaction to NAC, but had a major "flu" reaction 3 days after starting amoxicillin.

I seriously doubt that you did any harm to yourself donating blood, though you must understand that I am not a doctor and I am not an expert.

basil. 

If cats are outlawed, only outlaws will have cats.

Thanks, Basil. A very nice explanation for the, shall we say, porphyrially challenged like myself.

There was that recent research about abnormal liver function and MS that I thought was interesting especially to those of us who think MS is caused by an infection. I do not know if this disruption of liver function that the researchers found in MSers is similar to what secondary prophyria could create. Do you?

Here's the link:  http://tinyurl.com/y89lmb

Lexy

--------------- "Chance favors the prepared mind." --Louis Pasteur Husband treating MS with CAP

Lexy, I found the PubMed abstract of the research article alluded to in your link:

 

Liver test abnormalities in multiple sclerosis: findings from placebo-treated patients.

* Tremlett H, * Seemuller S, * Zhao Y, * Yoshida EM, * Oger JD, * Petkau J.

Faculty of Medicine, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, BC, Canada. tremlett@interchange.ubc.ca

The risk of an abnormal liver test in 813 patients with multiple sclerosis or clinically isolated syndrome enrolled in placebo arms of clinical trials was greater than expected for alanine aminotransferase (ALT) (relative risk [RR] 3.7; 95% CI: 2.3 to 6.0) and aspartate aminotransferase (AST) (RR 2.2; 95% CI: 1.3 to 3.6), although not alkaline phosphatase (AP) or total bilirubin, at first presentation. Abnormal test results were associated with higher body mass index (ALT only), male gender (ALT only), and a relapsing-remitting (vs secondary-progressive) course (ALT and AST only).

PMID: 17030771 [PubMed - indexed for MEDLINE]

 

There's really not enough information in the abstract to draw very many conclusions. The article sounds like it would be interesting to read, though.

 

basil.

If cats are outlawed, only outlaws will have cats.

Basil- as you see, I've linked your post to the Handbook as it's the clearest description of porphyria we have. Good to see your desperate work doing some good somewhere, eh? I'm not sure dividing this up according to strict diagnosis is best, since there is likely some overlap, ie some MS patients who have much more disseminated Cpn and other organ involvement (Raven is a case in point). Now that it's in the Handbook, do you want to edit up your commentary?

I've lately been experimenting with Cimetadine (Tagamet) which has been shown to help in some of the porphyrias. It seems to have a useful effect, but I'm still experimenting. It might be useful to subject it to the Poor Man's Test.

 

Combined Antibiotic Protocol for Chlamydia pneumonia in Chronic Fatigue Syndrome & Fibromyalgia- Currently: 150mg INH, Doxycycline/Zithromycin, 300mg Rifampin, Tinidazole pulses. Northern Ohio, USA

 

CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

Jim, I agree with what you say about strict division. My intent was really to point out that porphyria symptoms are most likely an indication of Cpn liiver infection. I've altered my post to try and clarify that point.

 basil.

If cats are outlawed, only outlaws will have cats.
D W

This is a really useful thread; thanks, Basil, for posting it, and thanks, Jim, for pointing out that the abnormal porphyrins appear to be cell-bound, but are released when apoptosis occurs. This makes good sense to me; in my own case I feel most porphyriac (and have tea-coloured urine) during periods of soft-tissue alteration and subsequent improvement. Apoptosis of unhealthy cells which contain toxins and perhaps bacterial remnants would account for this paradox. One of the pathologies of porphyria is a widespread pro-oxidant effect; one would suggest that antioxidants and agents capable of reversing glutathione depletion would help forestall pathological outcomes. Here is an apposite case-report of a 50 year old man, an exterior worker, who presented with skin blistering; he was found to have porphyria cutanea tarda with underlying Hepatitis C. He was also a heavy drinker. (link) The author gives a good resume of the disease and comments: 'Experimental treatments include 1)high dose Vitamin E, which was orignially shown in the late 1970s to prevent iron induced liver damage in rats; 2)N-acetyl-cysteine, for which there are a few case reports of benefit in patients with HIV (This agent is thought to work by prevention of skin damage from radical species by increasing intracellular glutathione); 3)Pyridoxine, which has been used in other porphyrias with light sensitive eruptions.' It's interesting that all three are recommended supplements for treating chronic C pneumoniae infection. Again, looking at my own experience, I find that, even though I have porphyriac symptoms, my skin is really healthy; all summer I cycled to work in a T shirt and shorts (changing when I got there) and was mildly sunburned but nothing unpleasant. (I covered up when taking doxycycline.) Secondary porphyria is, I am sure, very much underdiagnosed, and is unconsidered: but I am sure it's very common.

Now a question: does chlorella bind to porphyrins in the gut? I have a feeling that it should, but cannot find references.

 

D W - [Myalgia and hypertension (typically 155/95.) Began (2003) taking doxycycline and macrolide and later adding pulsed metronidazole. Improved; normotensive.]

 

D W - [Myalgia and hypertension (typically 155/95.) Began (2003) taking doxycycline and macrolide and later adding metronidazole. No medication now. Morning BP typically 110/75]

Thanks basil,  My only point in mentioning the NAC flu was as a demonstration of Cpn infection.  I would like to say Steve tested positive for it, but I can't.  For some mysterious reason, he was tested for C. psittaci instead of Cpn.  I also wish I knew if his urine was dark and/or foamy back in those days, but I wasn't around for most of those years.

NAC flu is very different for each individual.  Steve's was barely noticeable until he doubled the dosage at the same time he added selenium and vitamin E to his regime.  That precipitated joint aches and a worsening of his MS symptoms.  For me, it was a strong and long respiratory reaction.  You might have had a reaction and didn't realize it at the time.

Joyce~caregiver-advocate in Dallas for Steve J (SPMS) / Mpn, EBV, CMV, elevated heavy metals; strong indications of Cpn, gluten+casein sensitive / Wheldon CAP since Aug. '06 - 200mg doxycyline/day + 250mg azithromycin every other day; antivirals; chelation; LDN.

Joyce~caregiver-advocate in Dallas for Steve J (SPMS).  CAP since August 06, Cpn, Mpn, B. burgdorferi, systemic candidiasis, EBV, CMV & other herpes family viral infections, elevated heavy metals, gluten+casein sensitivity. 

Basil, I don't see how it follows that Cpn-induced porphyria is mostly from the liver.  Even with less heme being synthesized outside the liver than inside it, one still might have a buildup of porphyrins in some other tissue, due to Cpn infection, with the liver for whatever reason remaining uninfected.  Then, either when the Cpn is killed by antibiotics, or there is mass cell die-off for other reasons (perhaps as in an MS relapse), those porphyrins would be released, and might overload the system even though normally that population of cells doesn't contribute much to the porphyrin body burden.

This could, in a fashion, be tested: if it is liver cells whose dieoff produces the porphyria, then one would expect to see elevations of liver enzymes being correlated with elevations of porphyrins.

 Most of the body's heme is made during the process of red blood cell manufacture (85%), and almost all of the rest of the body's heme is made by the liver. Since accumulation of porphyrins results only from the dysfunctional  manufacture of heme, it follows that almost all porphyrin production due to dysfunctional circumstances must be a consequence of red blood cell production or liver function. If we discount erthyroid cell Cpn infection, then it follows that almost all prophyrins seen in a Cpn infection must therefore come from the liver, i.e, a liver infected with Cpn.

 Liver enzymes are rarely elevated in primary genetic porphyria as primary genetic porphyria rarely causes frank liver destruction. In my original post, I outlined three different types of Cpn porphyria phenomena. Only in Type 3 Cpn porphyria, namely rapid release of porphyins due to liver cell apoptosis of infected Cpn cells resulting from CAP (or other reasons as you point out) would one expect to see liver enzymes elevated due to liver cell destruction. In fact, a liver enzyme test might be a good way to assess whether CAP was proceeding too agressively in the case of an infected liver.

 

basil. 

 

 

Primary genetic porphyria rarely causes frank liver damage, and therefore elevated liver enzymes are rarely seen in primary genetic porphyria.

If cats are outlawed, only outlaws will have cats.

Interesting question about Chlorella, David. i was looking at one of Dr. Powell's handouts on Inflammatory Pathway Inhibitors and here's what it says about chlorella:

"decreases IL-6, INF-gamma, 5-LOX, MMP-9, PTP and TNF-alpha. Blocks NFkB .....increases Natural Killer cell activity...."

On this list the top performers that blocked the most inflammatory mediators were Curcumin, Luteolin and Niacinamide.

As for Chlorella being a detoxifying agent, there is a lot of alternative health info out there about that. One article I found:

http://findarticles.com/p/articles/mi_m0ISW/is_265-266/ai_n15622561

Raven

 

Feeling 98% well-going for 100. Very low test for Cpn. CAP since 8-05 for Cpn/Mycoplasma P.,Lyme, Bartonella, Mold exposure,NAC,BHRT, MethyB12 FIR Sauna. 1-18-11 begin new treatment plan with naturopath

I still don't see anything that prevents porphyrins from building up in tissue outside the liver, then being released in quantities great enough to cause problems.

Indeed, I think I've seen Stratton claim that there can be local porphyrias as well as general ones.  For instance, in an MS patient, one might get porphyria in the brain (and thus anxiety) without there being enough porphyrins outside the brain to produce, say, abdominal pain.  I even believe I've experienced that: on some occasions I've had both mild abdominal pain and mild anxiety, but on others stronger anxiety without abdominal pain.  The latter was shortly after taking Flagyl; presumably the released porphyrins hadn't had time to enter the general circulation.  At any rate, that's what I attributed it to at the time.  Let me see if I can dig up the Stratton reference... okay, US patent 6,884,784, page 33:

"The clinical result of the intracellular and extracellular accumulation of porphyrins, if extensive, is a tissue/organ specific porphyria which produces many of the classical manifestations of hereditary porphyria. As the chlamydial-infected host cells lyse, as happens in the normal life cycle of Chlamydia, the intracellular porphyrins are released and result in a secondary porphyria. Moreover, when the chlamydial infection involves hepatic cells, the use of any pharmacologic agents that are metabolized by cytochrome P-450 in the liver will increase the need for cytochrome P-450, which is a heme-based enzyme. Hence, the biosynthesis of heme in the liver becomes increased.  When hepatic cells are infected with Chlamydia species, the decreased energy in the host cell does not allow heme biosynthesis to go to completion and porphyrins in the liver/entero-hepatic circulation are increased. It also has been noted that any host cell infected with Chlamydia species has an increased amount of intracellular porphyrins that are released when antimicrobial agents kill the microorganism."

The patent also states (p.34):

"The diagnosis of chlamydial-associated secondary porphyria may be
difficult as the porphyria may be minimal and tissue-specific."


Liver function tests are already recommended for those following the protocol, for the reason you state.  (Or, more directly, because a number of the antibiotics used have been known to damage the liver on occasion, as has niacin in large doses; but that is likely to be because they kill Cpn infecting the liver.)

In other recent posts, I've pointed out that in all forms of porphyria, porphyrins are  extremely potent systemic neurotoxins, and that they produce extremely broad as well as extensive localized effects once released into the blood stream, regardless of where they originate.

Excepting erythroid cells, porphyrins are not manufactured in appreciable quantities in most cells outside of the liver because heme is not manufacutured in appreciable quantities in most tissues outside of the liver. Unless a cell makes heme in appreciable quantities, then it is not going to be making prophyrins in appreciable quantities.  Period.

One does not get porphyria in the brain or the gut, in the sense that the brain or the gut are sites for significant porphyrin production. It is well documented and accepted medicine that porphyrins arise primarily from the liver. However, both the brain and the gut are substantially affected by the neurotoxic properties of porphyrins once they are released into the blood stream, as are numerous other parts of the body.

 Many, many diseases of specific organs have wide-ranging systemic effects in locations far from the dysfunctional organ, including thyoid dysfunction,  adrenal dysfunction,  pancreatic dysfunction, etc.

 I'm not making this stuff up. I've merely been attempting to distill extensive research regarding porphyria into concise explanations relevant to Cpn infection.

 

basil. 

If cats are outlawed, only outlaws will have cats.

Interesting discussion, Norman and Basil. I had not recalled such detail on porphyria in the patent materials, so it's good to be reminded of it. I'll have to go dig it up and read the whole damned thing again, as now I'm wondering what else I missed in my brain fog.

David- I wondered that about Chlorella also, as it would be nice to have something other than charcoal or Questran to bind porphyrins in the gut, especially since these also bind medications. As far as I know, there are no warnings with Chlorella that it should not be taken with other vitamins or medications because it would bind them. I know that Chlorella is said to bind heavy metals like mercury and lead, and is used for this purpose in various treatments. This would suggest that it's binding capacity isn't lipid based. We need a chemist to look at the molecules in Chlorella and tell us what it might do for porphyrins.

Combined Antibiotic Protocol for Chlamydia pneumonia in Chronic Fatigue Syndrome & Fibromyalgia- Currently: 150mg INH, Doxycycline/Zithromycin, 300mg Rifampin, Tinidazole pulses. Northern Ohio, USA

 

CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

D W

Raven, thanks for the link.

D W - Myalgia and hypertension (typically 155/95.) Began (2003) taking doxycycline and macrolide and later adding pulsed metronidazole. Improved; normotensive

 

D W - [Myalgia and hypertension (typically 155/95.) Began (2003) taking doxycycline and macrolide and later adding metronidazole. No medication now. Morning BP typically 110/75]

 

Eureka!  Thanks to Cpn Handbook and  Basil's wonderfully clear explanations I am finally getting my head around  secondary porphyria and beginning to realise how it could be a very important part of my illness.

You have given me much food for thought and a whole new area of treatment to explore. No doubt, by the time I've assimilated it all and formulated my questions this forum will have moved on to the 'next big thing' and  you'll be able to look back and see me trailing along behind you all desperately trying to fight my way out of the big grey foggy cloud round my brain.  I can't believe how many clues my doctors have missed.

Thank you for sharing it all

'Evolved individuals do not accumulate.

The more they do for others, the more they gain;

The more they give to others, the more they possess.'  (Tao Te Ching)

 

Elinor from England, UK..... on Wheldon protocol for ME/lyme borreliosis , positive for borrelia and Cpn.  Started  Aug 05, stopped Jan06, started again Sept 06.

Elinor ..... from England  on CAP, doxy/roxi/tini  for ME/CFS/lyme borreliosis, positive Cpn and borrelia. Started Aug05, stopped Jan06, started again Sept 06.

So what sort of numbers are we talking about?  Is heme production outside the liver a tenth of that in the liver, a hundredth, or a thousandth (omitting red blood cell heme production from both numbers in the ratio)?  If either of the former, you still have a situation where an accumulation of porphyrins over weeks or months, outside the liver, can be competitive, if released suddenly, with an amount produced by the liver in response to immediate demands.  Even if not enough to cause systemic porphyria, they might be enough to cause a local porphyria, before they dissipate.

(Now that I think of it, I also don't see why you're ruling out Cpn infection of the red blood cell production process, which might be another source of porphyrins other than the liver.)

Why porphyins are really, really bad! 

Norman- these are great questions to run past Dr. Stratton. I'll accumulate them for my next contact with him. Re-reading the pages in the Patent you refer to on porphyria and it's treatment, it's clear that they had a whole bunch of lab measures available at that time for measuring porphyric load that are simply unavailable currently (until the lab goes up again). So, they might have looked at some of these questions of total porphyric load versus local porphyric reactions. It looks to me from the Patent discussion that the liver is considered one of the bigger sources, but other sources are referred to, such as the red blood cells you mention.

Overall, re-reading these materials hammers home the critical importance of porphyria treatment during Cpn treatment, regardless of where the source of the load is coming from:

  • Porphyrins produce a lot of serious and bad symptoms.
  • Porphyrins are neurotoxic and actually damage neurons (independent of the damage Cpn causes).
  • Porphyrins are hugely oxidizing (read-- the opposite of antioxidizing, what we are encouraged to take all those antioxidants for). Their oxidant effect is damaging to our tissues and organs. Porphyrins kill our body organs and cells.
  • Porphyrins help generate B-12 antigens in our body which binds up B-12, leaving us in a B-12 deprived condition even if we appear to have adequate blood levels of it.

There's probably more, but these are the ones I can pull up right now. 

Combined Antibiotic Protocol for Chlamydia pneumonia in Chronic Fatigue Syndrome & Fibromyalgia- Currently: 150mg INH, Doxycycline/Zithromycin, 300mg Rifampin, Tinidazole pulses. Northern Ohio, USA

 

CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

Maybe this is off topic, maybe not. One of the oddest things about CFS is Cheney's observation (quoted in Osler's Web) that about 1/3 of his CFS patients had to have their gall bladders removed within 6 months of the onset of CFS.

When I started with CFS, my gall bladder immediately (within a week or two) began to cause me pain. I hesitantly asked three nurses, the surgeon, and my family doctor if the fatigue was related (hesitantly, because it made no sense to me.) They all assured me the two couldn't be related. The g.b. was removed 2 months later. Finding: one tiny stone. Just one. However, the surgeon also said, "SOMETHING was going on with that gall bladder, the wall was so thick."

I think it bolsters the notion of a C.Pn-liver connection in CFS. I also realize it's hardly a smoking gun proof.

Ron 


On CAP for CFS starting 01/06 (NE Ohio, USA)

Currently: doxy & zith -- continous; metronidazole -- 4days on, 7 days off.

Ron

On CAP for CFS starting 01/06 (NE Ohio, USA)

Began rifampin trial 1/14/09

Currently: on intermittent

Liver Tests & MS - I have read the Tremlett et al paper (Neurology 2006,67:1291-1293). The summary says that for drug free MS patients liver tests may not be within normal ranges and the detailed paper gives full data.  For me a clinical action is that with MS patients a baseline liver assessment (ALT/AST) is taken.  This is needed before starting drugs which could impact liver function. Otherwise abnormal results later could mean that drugs are stopped or impacts on the liver are questioned when in fact drugs are not the problem.  If there is no limit for the number of liver function tests available then if would be useful to test MSers: before starting any drugs; after taking NAC but before adding abxs; after 3 months of abxs.  Never going to happen in the NHS (UK) but could give interesting results ........Mark.

Mark Walker - Oxford, England.
RRMS since 91, Dx 97. CFS from Jan03.  DW Patient-Feb06, started emp CAP(DW) in Mar06, with Copaxone. Pharma Consultant (worked til Jan 03).

Mark Walker - Oxford, England.

RRMS Nov 91, Dx 97. CFS Jan03. Copaxone + continuous CAP (NAC, Dox, Rox) Feb06 to May 07. Met pulses from Jun06. Intermittent Abx from June 07 onwards.

Leap too far - Basil you presented lots of useful and interesting data and then say:
"I'm going to assert that essentially ALL clinical porphyria phenomena seen in Cpn infection are a function of Cpn infection of the liver specifically."  I would want to see liver biopsy data before making such a leap.  The problem is that some website readers will take your thoughts as proven rather than  interesting conjecture.  Personally I did not see any bronze colour when I did a 'poor persons porphyria test' in sunlight during the summer........................Mark.

Mark Walker - Oxford, England.
RRMS since 91, Dx 97. CFS from Jan03.  DW Patient-Feb06, started emp CAP(DW) in Mar06, with Copaxone. Pharma Consultant (worked til Jan 03).

Mark Walker - Oxford, England.

RRMS Nov 91, Dx 97. CFS Jan03. Copaxone + continuous CAP (NAC, Dox, Rox) Feb06 to May 07. Met pulses from Jun06. Intermittent Abx from June 07 onwards.

Mark, when I write, I've tried to distinguish between what I believe are "facts" found in the published medical literature, and my own person suppositions, which is why I use such words as "assert" when I make those suppositions, assuming that most readers here are educated enough to know what "assert" means. For those who might miss the distinction, I'm glad you've emphasized that point.

One reason that I make such assertions, is that I would like to pique the interest of the medical research community to either confirm that I am right or explain why I am wrong based on their superior knowledege of the subject, or if the issues I raise are open questions, to ultimately be stimulated to perform the research to prove or disprove those assertions if they believe the issues I raise are important ones. I would think that liver biopsies coupled with PCR detection techniques would indeed be very very useful. Even used on cadavers such a technique might shed some light on the epidemiology of intracellular liver infection.

basil. 

If cats are outlawed, only outlaws will have cats.

Let me mediate this a bit-- I think this has to do with one's perspective. As a clinical pharmacist Mark's orientation is to state what is known about a drug or condition clearly, and not go too much beyond that in speculation. Basil is orienting from stating what is know about the condition and then speculating as to the meaning of findings and links between them.

As we have such a variety of people finding these pages, it behooves us to clearly mark "this is known" from "Speculations:..."

I don't think "assertions" is clear enough language to mark this, where "Speculations based on these findings might be..." with more clearly ecquivocal language. Then rousing discussion can ensue about possible speculative outcomes. 

Combined Antibiotic Protocol for Chlamydia pneumonia in Chronic Fatigue Syndrome & Fibromyalgia- Currently: 150mg INH, Doxycycline/Zithromycin, 300mg Rifampin, Tinidazole pulses. Northern Ohio, USA

 

CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

Basil's explanation is excellent, and it made me question my porphyria assumptions and ask the same questions as Norman.

Jim, I was curious whether Dr. Stratton had weighed in yet on Norman's questions (repeated below)? Is this something that will have to wait until the Cpn Lab reopens perhaps?

I'm curious about the necessity of major liver infection as a cause of major porphyria episodes. My liver values always look perfect on labs, although, unless I'm on the wrong track with porphyria and need to keep looking for another explanation, I seem to have real problems with symptoms of porphyria. Perhaps standard liver tests aren't enough to go on?

Thanks!

Marysia

 

So what sort of numbers are

Submitted by Norman Yarvin on Mon, 2006-11-20 08:59.

So what sort of numbers are we talking about? Is heme production outside the liver a tenth of that in the liver, a hundredth, or a thousandth (omitting red blood cell heme production from both numbers in the ratio)? If either of the former, you still have a situation where an accumulation of porphyrins over weeks or months, outside the liver, can be competitive, if released suddenly, with an amount produced by the liver in response to immediate demands. Even if not enough to cause systemic porphyria, they might be enough to cause a local porphyria, before they dissipate.

(Now that I think of it, I also don't see why you're ruling out Cpni infection of the red blood cell production process, which might be another source of porphyrins other than the liver.)

 

 

CDC Lyme + 02/06; Cpn, HHV6, and EBV + 03/08. 2 yrs slow improvement on variations of CAP for Lyme. Currently slowly resuming treatment and changing to newly discovered (for me) Cpn protocol after a severe porphyria attack 09/07 on Diflucan.

Heme, porphryns and Questran- oh my!

I'll relay what Dr. Stratton said to me per above. He speculated, based on his understanding of the heme synthasis processes (see references below):

"Fat soluble porphyrins reach the liver and are made water soluble and excreted in the bile. In addition, the cytochromes including cytochrome P450 are heme based. Therefore, there is a lot of heme synthesis going on in the liver. I suspect that the persons who have a reaction to questran probably have liver involvement by Cpn. Those that don’t have a reaction don’t have much liver involvement. The reaction may well be due to reduced cholesterol. The reaction may not be “die off”, but may be increased heat shock proteins because the Cpn is going into persistent phase due to “starvation” conditions. "

Let me mention that he has been suspecting that a lot of "die-off" reaction can be attributed not to LPS endotoxin as much as to HSP60 which is generated by Cpn as a part of cellular life form transformation process.  HS60 is highly inflammatory in nature, moreso than LPS endotoxin. 

More than you ever wanted to know about Heme production in relation to porphyrins:

http://themedicalbiochemistrypage.org/heme-porphyrin.html

Also from a reference (I don't have a link) on porphyria by  Hervé Puy and Jean-Charles Deybach (emphasis added by me):

"Excretion of porphyrins and of
porphyrin precursors Porphyrins and porphyrin precursors are excreted in urine
and/or bile (Table 1). In relation to the total rate of haem
synthesis, excretion of porphyrins is very small;
in other words,
few porphyrins (and porphyrin precursors, ALA, PBG) ‘escape’
during haem formation and therefore are not transformed into
bilirubin. Each day, bone marrow and liver synthesize about
375 mg of haem. In humans, the mean level of ALA excreted
in urine is ~ 3 mg/day; this means that less than 0.5% of ALA
synthesized each day has not been used for haem synthesis [8]... However, urine contains only 30–35% of the total coproporphyrin; the remainder is found in bile...

Before its final faecal excretion, a significant
proportion of protoporphyrin is reabsorbed in the intestine and
may circulate through the enterohepatic system
[13]. However,
it is not yet known how much intestinal microorganisms or food
contribute to the total fecal porphyrin excretion"

Note that different porphyrin cogeners are referred to in the text, so you don't confuse them, as it is taken out of it's context.  

 

CAP for Cpn 11/04. Dx: 25yrs CFS & FMS. Protocol: 200mg Doxy, 250mg MWF Azith, Tini 1000mg/day pulses; Vit D1000 units, Iodoral 50mg, T4 & T3

 

CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

Before its final faecal excretion, a significant proportion of protoporphyrin is reabsorbed in the intestine and may circulate through the enterohepatic system

 Jim - Thanks for posting this! 

 I had actually come to the conclusion that this was the case for my husband after digging in and  reviewing bile formation and the GI tract.  This reference confirms it!

Using Questran has reduced the confusion my husband experiences relative to a Natural Elimination Event by 80 to 90 %.  Dramatic !

Removing porphyrins (and whatever else) from the bile is having a profoundly positive result on our quality of life. 

Now researching the Sasparilla.

 

 

Daisy - Husband on CAP 5/07.   Roxy, Diflucan round three 4-4, Rifampin, Bactrim DS, Mepron 4-6, Prednisone, Novantrone, Doxy, Azithromycin, Flagyl, Mino

Daisy - Husband on CAP 5/07.  Husband died from Acute Myelogenous Leukemia Secondary to the Infusion of Novantrone.  Ie - the treatment with the conventional MS drugs killed him.

Daisy on her own CAP 11/2012. 

Daisy,  Please add burbur to your list too.

Joyce~caregiver-advocate in Dallas for Steve J (SPMS).  CAP since August 06, Cpn, Mpn, B. burgdorferi, systemic candidiasis, EBV, CMV & other herpes family viral infections, elevated heavy metals, gluten+casein sensitivity. 

Joyce~caregiver-advocate in Dallas for Steve J (SPMS).  CAP since August 06, Cpn, Mpn, B. burgdorferi, systemic candidiasis, EBV, CMV & other herpes family viral infections, elevated heavy metals, gluten+casein sensitivity. 

Joyce, why do you mention burbur?  Is it the herb Burbur?  I know that some people use this for helping to deal with Lyme die-off.

Mark 

 

UK Carer of bedridden Severe ME/CFS Feb06. CPN dx. Apr07. Samento 15 drops per day July07.  2400mg NAC 200mg Doxy Jan 08.

UK Carer of bedridden Severe CFS Feb06. Tick bites Summer04.  CPN dx.Apr07. Borrelia dx Sept08. Samento 15 drps daily July07.  200mg Doxy Jan08.  300mg Roxy Apr08 Stopped abx Nov/Dec08. Building up on Supps again.

Still just learning about herbs - sarsparilla and burbur and a few others are believed to help with endotoxin and HSP issues (both with lyme and CPN).  

Loads of antedotal reports on the internet but I am looking for something with at least a little scientific research - even in rats :)

Daisy - Husband on CAP 5/07.   Roxy, Diflucan round three 4-4, Rifampin, Bactrim DS, Mepron 4-6, Prednisone, Novantrone, Doxy, Azithromycin, Flagyl, Mino

Daisy - Husband on CAP 5/07.  Husband died from Acute Myelogenous Leukemia Secondary to the Infusion of Novantrone.  Ie - the treatment with the conventional MS drugs killed him.

Daisy on her own CAP 11/2012. 

Mark,  I tripped over sasparilla and burbur while searching for substances to mop up Lyme neurotoxins.  So far, my search results have been as Daisy describes---alot of discussion and no meat.

Joyce~caregiver-advocate in Dallas for Steve J (SPMS).  CAP since August 06, Cpn, Mpn, B. burgdorferi, systemic candidiasis, EBV, CMV & other herpes family viral infections, elevated heavy metals, gluten+casein sensitivity. 

Joyce~caregiver-advocate in Dallas for Steve J (SPMS).  CAP since August 06, Cpn, Mpn, B. burgdorferi, systemic candidiasis, EBV, CMV & other herpes family viral infections, elevated heavy metals, gluten+casein sensitivity.