Secondary Porphyria: what you should know before starting a CAP

Secondary Porphyria: what you should know before starting a CAP

Cpn induced secondary porphyria

Treatment of Chlamydia infection may exacerbate pre-existing genetic porphyria or more likely cause a secondary acute porphyria by making the intracellular Chlamydia more active or by killing infected cells that already are loaded with high porphyrin levels. Some of what is mis-labeled as a “herx” reaction to treatment, is actually an acute porphyria reaction and not a reaction to bacterial endotoxin which is what a true herxheimer reaction is referring to.

What is Secondary Porphyria? 

 Porphyrias are diseases in which the heme pathway has malfunctioned. They can be genetic or be secondary secondary to another disease process. Part of what is so special about the thoroughness with which Dr. Charles Stratton and his colleagues have studied Chalmydial disease is their discovery that Cpn interferes with the heme pathway, and that many patients with chronic Cpn infections have secondary porphyria to start with, and that this is further exacerbated under treatment. When you understand more about porphyria, it can help you sort out "die-off" as well as chronic symptoms you have, which may be due to heme byproducts-- and how to treat for it.

Heme is a Fe2+ complex. A number of critical cellular functions rely on it and the biosynthesis of heme occurs in all human cells. Toxic compounds called porphyrinogens are formed in one transitional phase of the heme biosynthesis pathway but under normal circumstances are quickly transformed into heme which is not toxic.

The porphyrias are consequences of any impairment of the formation of porphyrinogens or in their transformation to heme. Chlamydiae interfere with this step. Porphyrins then accumulate in the cell itself, and then in the extracellular milieu. Within the mitochondrial matrix, the final steps in the biosynthesis of heme are halted. Depletion of host cell energy by the intracellular infection with Chlamydia species causes additional energy-related complications.

Highly simplified, heme synthesis should look like this:

Heme precursors >> porphrinogens>> transformation to heme >> increased cellular transport including ATP production.

Instead, Cpn interferes with this normal process, and this happens:

Heme precursors >> porphrinogens >> interference with transformation to heme >> build up of unstable heme precursors and porphyrins inside and outside cells >> free radical damage and reduced ATP (energy) synthesis.

Symptoms of Porphyria- 

Porphyria may affect the nervous system or the skin.

When porphyria affects the nervous system, it can cause:

  • chest pain
  • shortness of breath 
  • abdominal pain
  • nausea
  • muscle cramps
  • weakness
  • hallucinations
  • depression
  • anxiety
  • paranoia
  • seizures

When porphyria affects the skin it can cause:

  • blisters
  • itching
  • swelling
  • sensitivity to the sun (which also can be caused by some antibiotics)
  • purple-red-colored urine

Stratton's protocol suggests testing for porphyrins prior to treatment, and initiating nutritional and other interventions prior to starting treatment for Cpn to help prevent or limit secondary porphyria.

"Systemic/chronic chlamydial infections have been noted to have an associated secondary porphyria. Porphyrins, including water-soluble porphyrins (e.g., delta-aminolevulinic acid and porphyrobilinogen) and fat-soluble porphyrins (e.g., coproporphyrin III and protoporphyrin) may produce clinical episodes of porphyria. The presence of such porphyrins in an individual patient with chronic/systemic chlamydial infection can be confirmed pre- and during therapy by appropriate porphyrin tests such as obtaining 24-hour urine and 24-hour stool specimens for porphyrins." (from Stratton & Mitchell's THERAPY OF CHRONIC CHLAMYDIAL INFECTIONS INCLUDING THEIR ASSOCIATED PORPHYRIA AND VITAMIN B12 DEFICIENCY: SEVENTH VERSION

Two other suggestive indicators of porphyria which don't require the more challenging 24 hour collection of specimens is measuring B-12 deficiency both directly and also from blood elements which are affected by B12 such as serum methyl malonate levels and homocystine levels. However Dr. Stratton notes:

Homocystine levels are elevated with B12 and folate deficiency, but can be reduced by folate alone. On the other hand, serum methyl malonate levels are elevated in B12 deficiency and are not changed by folate. Therefore, serum methyl malonate levels are the best indicator of B12 deficiency. 

 Another indicator, according to Dr. Stratton, is high hemoglobin and high hematocrit.

For those already in treatment, to have a rough idea if treatment is overloading them with porphyrigens Dr. Stratton has noted this "Poor Man's Test" of secondary porphyria:

"Poor Man's" Porphyrin Test According to Chuck Strattoni: If people notice dark urine after taking metronidazolei, have them put their urine in a clear glass container and place it outdoors in the sun for several hours. If the color gets darker (i.e., copper-purple color), then it is due to porphyrins. This is the "poor man's porphyrin test".

 Because secondary porphyria is so common in Cpn infections, Dr. Stratton recommends treating for it almost as a matter of course prior to initiating a CAP's, and continuing treatment for it during the whole process of treatment. This involves:

Excerpted from: THERAPY OF CHRONIC CHLAMYDIAL INFECTIONS INCLUDING THEIR ASSOCIATED PORPHYRIA AND VITAMIN B12 DEFICIENCY: SEVENTH VERSION

Charles W. Stratton, MD William M. Mitchell, MD PhD Vanderbilt University School of Medicine Nashville, Tennessee 37232

IMPORTANT DISCLAIMER Currently there are protocols for appropriate clinical trials for the therapy of a number of different forms of systemic/chronic chlamydial infections being prepared at Vanderbilt. The preliminary suggestions for chlamydial therapy that are contained within this document have been gleaned from early therapy for compassionate reasons and may not represent the final therapy. The use of these suggestions is similarly for compassionate therapy of patients suspected of having a systemic/chronic chlamydial infection.

Patient education begins with an explanation of the clinical significance of the test results and the potential for associated effects such as porphyria and vitamin B12 deficiency. Additional laboratory tests may be useful in defining the extent of the chlamydial infection and associated metabolic/vitamin disorders. Initial blood work can be obtained for the following tests: 1) CBC, 2) liver function tests, 3) uric acid, and 4) serum iron studies. Other useful tests include: red blood cell ALA dehydratase, red blood cell PBG deaminase, vitamin B-12 level, serum homocysteine level, and serum methymalonate level. A 24-hour urine and stool may be collected for porphyrins. Step 2: Next, the patient is placed on the antiporphyric regimen and vitamin B12 therapy. This is continued throughout the antimicrobial therapy and is an important component as it minimizes cellular damage and facilitates cellular repair. Step 3: Following initiation of the antiporphyric regimen, the first antimicrobial agent is started.

I. THERAPEUTIC REGIMEN FOR SECONDARY PORPHYRIA Systemic/chronic chlamydial infections have been noted to have an associated secondary porphyria. Porphyrins, including water-soluble porphyrins (e.g., delta-aminolevulinic acid and porphyrobilinogen) and fat-soluble porphyrins (e.g., coproporphyrin III and protoporphyrin) may produce clinical episodes of porphyria. The presence of such porphyrins in an individual patient with chronic/systemic chlamydial infection can be confirmed pre- and during therapy by appropriate porphyrin tests such as obtaining 24-hour urine and 24-hour stool specimens for porphyrins. It is recommended that a therapeutic regimen addressing porphyria should be instituted along with the use of antimicrobial agents. This therapeutic regimen is aimed at controlling the chlamydial-associated secondary porphyria that may be present prior to antimicrobial therapy and/or may be triggered or increased during antimicrobial therapy of the chlamydial infection. This "porphyric reaction" to antimicrobial therapy should be recognized as such and differentiated from an expected cytokine-mediated immune response. Specific measures for the therapy of porphyria as derived from published medical literature on porphyria are employed and include:

1. High Carbohydrate Diet Approximately 70% of the daily caloric intake should be in the form of complex carbohydrates such as those found in bread, potato, rice, and pasta. The remaining 30% of calories in protein and fat ideally should be in the form of white fish or chicken. 2. High Oral Fluid Intake Drink plenty of oral fluids in the form of water (e.g., bicarbonated water or "sports-drinks" [water with glucose and salts]). This helps flush water-soluble porphyrins. Moreover, dehydration concentrates porphyrins and makes patients more symptomatic. The color of the urine should always be almost clear rather than dark yellow. 3. Avoid Red Meats Red meats, including beef and dark turkey as well as tuna and salmon contain tryptophan and should be avoided as much as possible. 4. Avoid Milk Products Milk products contain lactose and lactoferrin, both of which should be avoided as much as possible. 5. Glucose, Sucrose and Fructose Glucose is an important source of cellular energy: cellular energy is reduced with chlamydial infections. Increasing the availability of glucose provides optimal conditions for the cells to produce energy. However, sucrose is not the best way to increase the glucose availability. Sucrose is a mixture of glucose and fructose. Fructose is the sugar contained in fruit. Because high levels of fructose act as a signal to the liver to store glycogen, an excess of fructose may temporarily reduce the availability of glucose at the cellular level. Fructose should be avoided as much as possible. Instead, "sports-drinks" containing glucose (as well as containing important cations/anions) can be used. Glucose tablets also can be used. 6. Avoid Alcohol. Alcohol is a well-known aggravator of porphyria and should be avoided as much as possible.

Vitamins/Antioxidants/Supplements 7. B-Complex Vitamins Glucose is needed by host cells that are infected by chlamydiae. The availability of glucose to the host is assisted by taking B-complex vitamins. These include folic acid (400 mcg twice per day), vitamin B-1 (thiamin 10 mg twice per day), vitamin B-2 (riboflavin 10 mg twice per day), vitamin B-5 (pantothenate 100 mg twice per day), vitamin B-6 (pyridoxine 100 mg twice per day or pyridoxal-5 phosphate 25 mg twice per day), and vitamin B-12 (5000 mcg sublingual three to six per day). 8. Antioxidants Antioxidants and related agents should be taken twice per day. These should include vitamins C (1 gram twice per day) and E (400 units twice per day) as well as L-carnitine (500 mg twice per day), ubiquinone (coenzyme Q10; 30 mg twice per day), biotin (5 mg twice per day), and alpha-lipoic acid (400 mg twice per day). Bioflavinoids (also called proanthocyanidins of which pygnoginol and quercetin are two examples) are very effective antioxidants. Selenium (100 mcg twice per day) should be taken with the vitamin E. L-Glutamine (2 - 4 grams twice per day), querceten (400 - 500 mg twice per day), glucosamine (750 - 1000 mg two or three times per day) and chondroitin sulfate (250 - 500 mg twice per day) should also be included.

Antiporphyrinic Drugs 9. Benzodiazapine Drugs The specific benzodiazapine drugs used depends, in part, on the symptoms. For example, if panic attacks are the problem, xanax (0.5 mg three or four times per day) can be used. If sleeping is a problem, restoril (30 mg at night) can be used. 10. Hydroxychloroquine Hydroxychloroquine (100 - 200 mg once or twice per day) is often used to treat porphyria. For patients with symptoms of porphyria, a single 100 mg dose of hydroxychloroquine may be tried. If this trial dose relieves the symptoms, hydroxychloroquine may be continued. The hydroxychloroquine dose must be adjusted for each patient. This is done by increased the dose slowly, starting with 100 mg every other day, then slowly increasing to a maximum dose of no more than 200 mg twice per day. Most patients do well on 100 mg once per day. Visual/eye exams should be done periodically as per manufacturerís recommendations (See PDR).

Miscellaneous 11. Oral Activated Charcoal Activated charcoal absorbs fat-soluble porphyrins. Treatment with oral activated charcoal, which itself is nonabsorbable, binds these porphyrins in the gastrointestinal tract and hence prevents them from being reabsorbed in the small intestine. Start with 2 grams (eight 250 mg capsules) of activated charcoal taken three times per day on an empty stomach (i.e., 2 hours after and 2 hours before a meal). Gradually increase this to 4 grams taken three times per day. Much more activated charcoal can be safely taken; up to 20 grams six time a day for nine months has been taken without any adverse side effects. It is important that this charcoal be taken on a completely empty stomach without any food, vitamins, or medications taken within 2 hours before or 2 hours after charcoal ingestion as the charcoal may absorb the food, vitamins, or drugs as well as the porphyrins. Activated charcoal can be obtained from <puritanspride.com>.

II. THERAPEUTIC REGIMEN FOR VITAMIN B12 DEFICIENCY Many patients with systemic/chronic chlamydial infection appear to have a subtle and unrecognized vitamin B12 deficiency at the cellular level. This functional B12 deficiency can be documented in an individual patient by obtaining both a vitamin B12 level (usually normal or low) and serum homocysteine and methylmalonate levels (one or both of these metabolites will be elevated). This vitamin B12 deficiency can corrected by high-dose vitamin B12 therapy as follows: 1. Vitamin B12 Therapy Prior to Chlamydial Therapy Adults normally have approximately 3,000 mcg of vitamin B12 in body stores, mostly in the liver. Initial vitamin B12 therapy before chlamydial therapy includes replacement therapy for any vitamin B12 deficit in these body stores. Therefore, over the first several days of antiporphyrin therapy, 6,000 mcg of parental (intramuscular or subcutaneous) vitamin B12 is given. For each of the next 3 weeks, 6,000 mcg of parental vitamin B12 is given once per week. 2. Vitamin B12 Therapy During Chlamydial Therapy Chlamydial antimicrobial therapy is associated with increased need for vitamin B12. Therefore, 6,000 mcg of parental vitamin B12 (3,000 mcg in each anterior thigh) is given once per week while the patient is receiving antimicrobial therapy for systemic/chronic chlamydial infection. This is in addition to the 5,000 mcg of sublingual vitamin B12 taken three times each day. 3. Vitamin B12 Therapy Post Chlamydial Therapy Following the completion of antimicrobial therapy of systemic/chronic chlamydial infection, the vitamin B12 and serum homocysteine/methylmalonate levels should be rechecked. If the methylmalonate level remains elevated, it suggests a continued vitamin B12 deficiency. Oral therapy with 5,000 mcg of sublingual cobalamin three times per day should be continued. After several months, 6,000 mcg of parental vitamin B12 may be given as a therapeutic trial. If the patientís energy is not increased by the parental dose, continued therapy with sublingual vitamin B12 is probably adequate. Periodic trials of parental vitamin B12 can be used to assess the sublingual therapy.

For years, vitamin B12 languished as the vitamin that cures anemia. Hardly any research was done into what this vitamin could do for non-anemic people. It turns out that it may do a lot. New studies show that the right amount of B12 can protect against dementia, boost immune function, maintain nerves, regenerate cells and more. B12 is in the news because it lowers homocysteine and protects against atherosclerosis. It's also vital for maintaining methylation reactions that repair DNA and prevent cancer. One of the crucial areas for B12 is the brain. It's not surprising that people with B12 deficiency develop mental disorders. The vitamin is crucial for the synthesis or utilization of important neuro-factors including monoamines, melatonin and serotonin. In addition, B12 is absolutely critical for the function and maintenance of nerves themselves. B12 is needed for methylation reactions that maintain these cells, and enable them to function. B12 contributes to brain function by lowering homocysteine. Homocysteine is a toxic by-product of methionine metabolism that can damage neurons. Importantly, homocysteine interferes with the methylation reactions critical for brain function. Studies show that people with elevated homocysteine can't think.

Jim K Wed, 2006-02-08 11:18

How Cpn causes porphyria: pdfs of Stratton/Mitchell Articles

How Cpn causes porphyria: pdfs of Stratton/Mitchell Articles

 Two downloadable pdf files are included here for those who want more detail on Cpn and secondary porphyria. 1) This link will download an important and classic article by Dr.'s Stratton & Mitchell called

The Pathogenesis of Systemic Chlamydial Infections: Theoretical Considerations of Host Cell Energy Depletion and Its Metabolic Consequences

 Download   Alternate DownloadIt explains in detail the impact of Cpn cellular parasitism on ATP depletion and on heme synthesis and resulting porphyria.  2) This link will download an excerpt from Stratton & Mitchell's Patent #6,884,784 specifically on the cellular biology of Cpn and porphyria. A succinct and clear explanation for those of us who are biology geeks.

Excerpt from Stratton & Mitchell's Patent #6,884,784 on Cpn & Secondary Porphyria

Download Patent Excerpt

Jim K Sun, 2006-03-19 14:14

Secondary Porphyria in Cpn: Extracts from Stratton/Mitchell Patent

Secondary Porphyria in Cpn: Extracts from Stratton/Mitchell Patent

I thought this should be available to Cpnhelp users. This is extracted from the Mitchell/Stratton (Vanderbilt) patent:Secondary Porphyria In Cpn• Extracted and edited from: US Patent Issued on June 29, 2004• Chlamydia is a parasite of normal energy production in infected eukaryotic cells. The energy shortage also causes the host cell mitochondria to attempt to synthesize certain critical enzymes involved in energy production in order to increase energy production. The energy (ATP) shortage produced by Cpn infection results in incomplete heme production and resulting porphyrins.Because Chlamydia also prevents this synthesis from completing, these enzyme's precursors, called porphyrins, build up in cell and often escape into the intracellular [mileau] milieu. Porphyrins readily form free-radicals, that, in turn, damage cells. Thus, there is an obligate secondary porphyria that accompanies many chlamydial infections. • Impact of porphyrins on the body:Inadequate energy- Host cells have insufficient energy available for their normal functioning. • Neurotoxicity- Porphyrins are highly neurotoxic and produce oxidative damage to cells.• Tissue damage from oxidation- If these reactive oxygen species (porphyrins) are released into the extracellular space, as seen in acute porphyria, autooxidation of surrounding tissue may result. … Reactive oxygen species have been noted to disrupt membrane lipids, cytochrome P-450 (impairing metabolism of drugs and toxins) and DNA structure (increasing cancer risk).• Impairment of liver function- 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. 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. 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 (resulting in worsening of the porphyria!). • Chronic oxidative stress- the accumulation of porphyrinogens/porphyrins in human tissues and body fluids produces a condition of chronic system overload of oxidative stress with long term effects particularly noted for neural, hepatic and renal tissue.. If reactive oxygen species are released into the extracellular space, as seen in acute porphyria, autooxidation of surrounding tissue may result. Long term effects particularly noted for neural, hepatic and renal tissue.• Glucose disruption—described under treatment below.• Accumulation in tissues and cells of porphyrins- 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. • (symptoms of porphyria here)• Sub-clinical B-12 deficiency (i.e. not measurable by blood levels of B-12). The pathogenesis of chronic/systemic chlamydial infection is unique in that the intracellular infection by this parasite results in a number of … unrecognized concomitant … metabolic/autoimmune disorders including secondary porphyria with associated autoantibodies against the porphyrins. Cross reaction with Vitamin B12 can result in a subclinical autoimmune-mediated Vitamin B12 deficiency. These associated disorders often require diagnosis and preventive and/or specific adjunctive therapy.• 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. 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.• …chlamydial-associated secondary/obligatory porphyria, symptoms of which can actually increase during antimicrobial therapy of the chlamydial infection. This porphyric reaction to antimicrobial therapy should be recognized as such and differentiated from the expected cytokine-mediated immune response precipitated by antigen dump during anti-chlamydial therapy.• • Diagnosis• The diagnosis of chlamydial-associated secondary porphyria may be difficult as the porphyria may be minimal and tissue-specific.• The measurement of 24 hour urine porphyrins is not sensitive enough in every case of chlamydial infection to detect the secondary porphyria caused by chlamydial infection.• There may not be an abnormal amount of porphyrinogen precursors and porphyrins in the blood, urine, or stool.• • D. Reducing Porphyrin Levels• Therapy for this secondary porphyria, which is adjunct to anti-chlamydial therapy, involves at least three strategies: a) Supplement the cellular energy supply to mitigate cell malfunction and the formation of porphyrins; b) reduce the levels of systemic porphyrins; and c) mitigate the harmful effects of the porphyrins.• Dietary and pharmaceutical methods can be used to reduce systemic porphyrin levels (both water-soluble and fat-soluble).• It is recommended that a patient suffering from porphyria avoid milk products. Milk products contain lactose and lactoferrin, and have been empirically shown to make symptoms of porphyria worse.• Patients should also avoid Red meats, including beef, dark turkey, tuna and salmon as they contain tryptophan which worsens porphyria (see below).• Glucose disruptiono Red meats, including beef, dark turkey, tuna and salmon, contain [tryprophan] tryptophan. Increased levels of tryptophan in the liver inhibit the activity of phosphoenol pyruvate carboxykinase with consequent disruption of gluconeogenesis. This accounts for the abnormal glucose tolerance seen in porphyria. o (Ed: in addition to which, Cpn induces its host cell to absorb more glucose from the blood stream so it can produce more ATP. In wide spread Cpn infection this can produce low blood sugar more rapidly than otherwise, such as when patients fast or skip meals).• Intake of glucose gives short term energy boost to depleted cells (increasing ATP and lessening porphyrin production), and in the case of infected liver cells (major producer of heme in the body) glucose shuts down further immediate heme production.• Plenty of oral fluids in the form of bicarbonated water or "sports drinks" (i.e., water with glucose and salts) should be incorporated into the regimen. This flushes water-soluble porphyrins from the patient's system. Drinking seltzer water is the easiest way to achieve this goal. The color of the urine should always be almost clear instead of yellow. It is noted that dehydration concentrates prophyrins and makes patients more symptomatic.• Activated charcoal can be daily administered in an amount sufficient to absorb fat-soluble porphyrins from the enterohepatic circulation. Treatment with activated oral is charcoal, which is nonabsorbable and binds porphyrins in the gastrointestinal tract and hence interrupts their enterohepatic circulation, has been associated with a decrease of plasma and skin porphyrin levels. Charcoal should be taken between meals and without any other oral drugs or the charcoal will absorb the food or drugs rather than the porphyrins. For those who have difficulty taking the charcoal due to other medications being taken during the day, the charcoal can be taken all at one time before bed. Taking between 2 and 20 grams, preferably at least 6 grams (24×250 mg capsules) of activated charcoal per day (Perlroth et al., Metabolism, 17:571-581 (1968)) is recommended. Much more charcoal can be safely taken; up to 20 grams six times a day for nine months has been taken without any side effects.• For severe porphyria, chelating and other agents may be administered, singularly or in combination, to reduce levels of porphyrins in the blood. Examples of chelating agents include but are not limited to Kemet (succimer; from about 10 mg/kg to about 30 mg/kg); ethylene diamine tetracetic acid (EDTA); BAL (dimercaprol; e.g., 5 mg/kg maximum tolerated dosage every four hours), edetate calcium disodium (e.g., from about 1000 mg/m2 to about 5000 mg/m2 per day; can be used in combination with BAL); deferoxamine mesylate (e.g., from about 500 mg to about 6000 mg per day); trientine hydrochloride (e.g., from about 500 mg to about 3 g per day); panhematin (e.g., from about 1 mg/kg to about 6 mg/kg per day), penacillamine. Quinine derivatives, such as but limited to hydroxychloroquine, chloroquine and quinacrine, should be administered to the patient daily at a dosage of from about 100 mg to about 400 mg per day, preferably about 200 mg once or twice per day with a maximum daily dose of 1 g. Hydrochloroquine is most preferred. The mechanism of action of hydroxychloroquine is thought to involve the formation of a water-soluble drug-porphyria complex which is removed from the liver and excreted in the urine (Tschudy et al., Metabolism, 13:396-406 (1964); Primstone et al., The New England Journal of Medicine, 316:390-393 (1987)).• E. Mitigating the Effects of Porphyrins• Antioxidants at high dosages (preferably taken twice per day) help to mitigate the effects of free radicals produced by porphyrins. Examples of suitable antioxidants include but are not limited to Vitamin C (e.g., 1 gram per dosage; 10 g daily maximum); Vitamin E (e.g., 400 units per dosage; 3000 daily maximum); L-Carnitine (e.g., 500 mg per dosage; 3 g daily maximum); coenzyme Q-10 (uniquinone (e.g., 30 mg per dosage; 200 mg daily maximum); biotin (e.g., 5 mg per dosage; 20 mg daily maximum); lipoic acid (e.g., 400 mg per dosage; 1 g daily maximum); selenium (e.g., 100 µg per dosage; 300 µg daily maximum); gultamine (e.g., from 2 to about 4 g per dosage); glucosamine (e.g., from about 750 to about 1000 mg per dosage); and chondroitin sulfate (e.g., from about 250 to about 500 mg per dosage).• The above-mentioned therapeutic diets can be combined with traditional or currently recognized drug therapies for porphyria. In one embodiment, benzodiazapine drugs, such as but not limited to valium, klonafin, flurazepam hydrochloride (e.g., Dalmanc™, Roche) and alprazolam (e.g., Xanax), can be administered. Preferably, sedatives, such as alprazolam (e.g., Xanax; 0.5 mg per dosage for 3 to 4 times daily), can be prescribed for panic attacks and flurazepam hydrochloride (e.g., Dalmane™, Roche or Restoril™ (e.g., 30 mg per dosage)) can be prescribed for sleeping. The rationale is based upon the presence of peripheral benzodiazepine receptors in high quantities in phagocytic cells known to produce high levels of radical oxygen species. A protective role against hydrogen peroxide has been demonstrated for peripheral benzodiazipine receptors. This suggests that these receptors may prevent mitochondria from radical damages and thereby regulate apoptosis in the hematopoietic system. Benzodiazepines have also been shown to interfere with the intracellular circulation of heme and porphyrinogens (Scholnick et al., Journal of Investigative Dermatology, 1973, 61:226-232). This is likely to decrease porphyrins and their adverse effects. The specific benzodiazipine will depend on the porphyrin-related symptoms.• The rationale for benzodiazepines) is based upon the presence of peripheral benzodiazepine receptors in high quantities in phagocytic cells known to produce high levels of radical oxygen species. A protective role against hydrogen peroxide has been demonstrated for peripheral benzodiazipine receptors. This suggests that these receptors may prevent mitochondria from radical damages and thereby regulate apoptosis in the hematopoietic system. Benzodiazepines have also been shown to interfere with the intracellular circulation of heme and porphyrinogens (Scholnick et al., Journal of Investigative Dermatology, 1973, 61:226-232). This is likely to decrease porphyrins and their adverse effects. The specific benzodiazipine will depend on the porphyrin-related symptoms.• Cimetidine can also be administered separately or in combination with benzodiazepine drugs. Cimetidine has been shown to effectively scavenge hydroxyl radicals although it is an ineffective scavenger for superoxide anion and hydrogen peroxide. Cimetidine appears to be able to bind and inactivate iron, which further emphasizes its antioxidant capacity. Cimetidine also is an effective scavenger for hypochlorous acid and monochloramine, which are cytotoxic oxidants arising from inflammatory cells, such as neutrophils. Cimetidine thus would be expected to be useful for the therapy of free-radical-mediated oxidative damage caused by chlamydial porphyria. Recent studies in Japan have found that cimetadine is effective for treating porphyria. The recommended amount of cimetadine is about 400 mg once or twice per day.

Jim K Thu, 2008-05-01 22:59

Porphyria......?

27 Apr 2018
Author
farandwide
Title

Porphyria......?

Body

I've read several posts on Porphyria, including the interview with Dr. Stratton (I think is who it was).  I'm still left wondering what I can do to combat porphyria as I definitely have it going on and it's something I want to deal with.As far as I know, the only thing that can be done is the following...

Comments

Don't forget:

  • avoid sucrose and fructose, seek glucose.
  • Red meat, tuna, and dark turkey are verboten, too. Chicken, fish, nuts, and eggs -- and, as you say, not too much of them.
  • Alcohol is a real promoter of porphyria as well.

I've never been quite sure whether the dairy prohibition is because of porphyria or because of rendering the doxy ineffective, so I didn't include that.

Now, what else -- I'm sure that's not everything.

Ron

On Stratton protocol for CFS starting 01/06 (NE Ohio, USA).

RonOn CAP for CFS starting 01/06 (NE Ohio, USA)Began rifampin trial 1/14/09Currently: on intermittent

John- Other than those the only other one suggested is low-dose Plaquinal (125mg two or three times a week). Severe porphyria requires IV Hematin, which is a human blood product, very expeinsive and only obtainable for proven porphyric condition (mostly genetic in origin).

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

D W

Cimetidine has been used in both hereditary and secondary porphyrias [Horie Y, et al., Cimetidine in the treatment of porphyria cutanea tarda. Intern Med. 1996 Sep;35(9):717-9.] It is very inexpensive.

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]

Thank you for posting this.

http://www.journalarchive

Kim's been having die-off reactions and and we're hoping to supplement the charcoal she takes at night.

I looked Cimetidine up and found out that it's sold as Tagamet, which is an over the counter heartburn/ulcer medication. I further followed up to try and find out what the dosage might be. The way Tagamet is sold, dosage is:

Tablets for Oral Administration : Each light green, film-coated tablet contains cimetidine as follows: 300 mg-round, debossed with the product name TAGAMET, SB and 300; 400 mg-oval Tiltab® tablets, debossed with the product name TAGAMET, SB and 400; 800 mg-oval Tiltab® tablets, debossed with the product name TAGAMET, SB and 800. I found this at: http://www.rxlist.com/cgi/generic/cimet.htm

I'm hoping you might be able to recommend a dosage and or any other thoughts about taking this to help relieve die-off reactions. Thank you, Ken

PS: I've also been looking into Oregano oil as noted in the CPn handbook. I checked this out at the Vitaminshoppe and found Oregano oil is mixed with olive oil, is this what folks are using? I'm not sure how much to use if we try this also. Is anyone using Oregano Oil? Are softgels ok?

In pursuit of ABXDon't Allow What You Know To Get In The Way Of What Might Be

Hi Ken, I am using the oregano oil in liquid form.  I put 1 -2 drops in my morning vitamin cocktail drink!

I believe it helps keep yeast in check!

CFIDS/ME 26yrs, FMS, IBS, EBV, CMV, Cpn, chronic insomnia, Lymes, HME, Natural HRT peri-M, NAC 2.5 gm, 6-07 Doxy 200 mg day pm, Azith 375 mg M/W/Fday, Pulse#9 750mg 5.5 day, 4-25-8

CFIDS/ME, FMS, MCS, IBS, EBV, CMV, Cpn, H1, chronic insomnia, Chronic Lyme, HME, Babesia, Natural HRT-menopause, NAC 2.4 gm,Full CAP 6-2-07, all supplements+Iodorol, Inositol-depression, ultra Chitosan, L lysine Pulse#27 04-19-10 1gm Flagyl/day-5 days<

 Are you smooshing all your vits into a drink? I keep reading that you shouldn't do this as it can affect the potency, but others say it's OK with some coatings and not with others. Confused.

Berkshire, UK. Diagnosed RRMS Feb 4th 2008.

NAC 2400mg. All supplements. Doxy 200mg. Zith 250mg M/W/F.
No GP/Neuro support. Self medicating with help from David Wheldon.
Started CAP 20th April 2008.

Berkshire, UK. Diagnosed RRMS Feb 4th 2008.NAC 2400mg. All supps. Doxy 200mg. Zith 250mg. Metro 400mg.No GP/Neuro support. Self medicating with help from David Wheldon. Started CAP 20th April

Thanks for all the replies, I'm glad to get the additional information.

I was also thinking that vitamin B12 counteracts porphyria due to being similar in molecular structure to a porphyrin but I can't remember if that's the case.  Does that sound correct? 

all my best

John

RRMS/disability 4.5 on Wheldon Protocol since 04/12/2006

best, JohnRRMS/EDSS was 4.5, 5, 6, 6.5, 6.9999, 6.5 on Wheldon/Stratton Protocol beginning 04/12/2006nac 4x600 mg/daydoxycycline 2x100mg/dayazithromycin 3x250mg/day MWFmetronidazole 3x400mg/day then 3x500mg/day

More on glucose & porphyria-

Glucose has been the standard treatment for serious porphyric attachs, usually IV. This quote explains it further:

Intravenous administration of glucose (a pure form of carbohydrate) is part of the standard treatment of acute attacks of porphyria. Glucose is given by vein because the stomach and intestine usually do not function properly during an attack, and material taken by mouth is not properly propelled through these organs. Glucose and other carbohydrates can repress the pathway for synthesis of herne in the liver. As a result, the overproduction of prophyrin precursors and porphyrins is repressed by carbohydrate administration. 

http://theaipforum.tripod.com/

The site above has some excellent dietary guidlines for porphyria.

From the Cpn Handbook, Mitchell and Stratton note further:

Increasing the availability of glucose provides optimal conditions for the cells to produce energy. However, sucrose is not the best way to increase the glucose availability. Sucrose is a mixture of glucose and fructose. Fructose is the sugar contained in fruit. Because high levels of fructose act as a signal to the liver to store glycogen, an excess of fructose may temporarily reduce the availability of glucose at the cellular level. Fructose should be avoided as much as possible.

 I think the molecular symetry of B12 is accurate but speculative about it's function. I think it's strong methylation effects and that it is used up rapidly for this purpose in porphyria is the original idea.

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

On B12 from David Wheldon-

I'll add this nice bit from David Wheldon's site on B12:

High-dose sublingual Vitamin B12 (methylcobalamin) should be taken; initially 4000 - 5000 micrograms several times a day, reducing to once daily after three months. This is to flood the system with methylcobalamin as there is often a functional B12 deficit, as evidenced by raised serum methylmalonate or homocysteine. Vitamin B12 (together with B6 and folate) counteracts the hyperhomocysteinaemia which frequently accompanies chronic Chl pneumoniae infection and which is thought to cause connective tissue damage. Excess homocysteine is a potent neurotoxin with activity against cortical and hippocampal neurones. [1. Kruman II, Culmsee C, Chan SL, et al., Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci 2000;20:6920-6:] [2. Den Heijer T, Vermeer SE, Clarke R, Oudkerk M, Koudstaal PJ, Hofman A, et al. Homocysteine and brain atrophy on MRI of non-demented elderly. Brain 2002;126:170-5:] [3. Leblhuber F, Walli J, Artner-Dworzak E, Vrecko K, Widner B, Reibnegger G, et al. Hyperhomocysteinemia in dementia. J Neural Tansm 2000;107:1469-74.] An excellent review of Vitamin B12 and multiple sclerosis can be recommended here: [Miller A, Korem M, Almog R, Galboiz Y. Vitamin B12, demyelination, remyelination and repair in multiple sclerosis. J Neurol Sci 2005 Jun 15;233(1-2):93-7.]

http://www.davidwheldon.co.uk/ms-treatment.html 

 

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

Hi John

Most of us try very hard to avoid or consume as required. I never had any luck avoiding milk and cheese. I do not eat much red meat (maybe a couple of ounces a couple of times a month) and my preferred fowl has always been dark but I have conformed to the rest for the most part. But I do eat lots of cheese, - 3 to 4 ozs a day at least - lots of raw vegetables, few eggs, very few fried foods and lots of fish. I always take all my supplements and abx. We have to have some freedom to indulge and it appears that for Paron and me, it may be dairy. As for porphyria, I took charcoal my last pulse (I have not needed it for a few months!) because I was so obviously having a really, really good one but it does get lots, lots better!

 

Rica PPMS  EDSS 6.7 at beginning - now 2.  Began CAP Sept, 2004 with Rifampin 150 mg 2xd, Doxy 100 mg 2xd, added regular pulses Jan 2005. Jan 2006 switched to Doxy, Azith,  cont. flagyl  total 39 pulses NC USA

3/9 Symptoms returning. Began 5 abx protocol 5/9 Rifampin 600, Amox 1000, Doxy 200, MWF Azith 250, flagyl 1000 daily. Began Sept 04 PPMS EDSS 6.7 Now good days EDSS 1 Mind, like parachute, work only when open. Charlie Chan  In for the duration.&am

Hi Rica, thank you for writing me on this topic.  You may not be aware, but this is an old thread of discussion that I haven't touched since May of 2006, or so I believe.  Be that as it may, I am glad that you brought it up as there is a question I've had brewing on the topic of porphyria for a bit.

I don't know if it was Jim K or Eric or someone else who created it, but there was a post some time ago that summarized the effects of porphyria.  I noted that the way in which I experience porphyria wasn't on the list which makes me wonder if what's going on with me is really porphyria at all.  It seems to coincidental not to be but that may be the case.

In my case, I get the symptoms I thought/have believed were porphyria after eating.  Indeed, taking glucose before eating seems to alleviate much of it unless I really eat a lot.  My symptoms are that I become more lethargic, less coordinated, sometimes to the point where I have to be very careful with walking as I tend to drag my right foot which is exacerbated after eating.

I had talked about these symptoms in another thread some time ago and had mentioned that if I begin drinking lots of water after having eaten, it tends to more quickly relieve these symptoms.  I believe it may have been Jim K who suggested that the water was sweeping away water soluble porphyrins, which sounds likely to me.

Anyway, to summarize, I'm wondering whether or not these symptoms are actually porphyria or something else.  I think DW posted earlier on this thread about an imbalance in homocysteine or some such in people with MS.  I wonder if it's that instead, but have no real clue.  I guess the best thing I can do to have a better idea and understanding is probably do the poor man's porphyria test and see for myself. 

all my best

John

RRMS/EDSS 4.5 on Wheldon Protocol (nac, doxycycline, azithromycin, metronidazole) since 04/12/2006

best, JohnRRMS/EDSS was 4.5, 5, 6, 6.5, 6.9999, 6.5 on Wheldon/Stratton Protocol beginning 04/12/2006nac 4x600 mg/daydoxycycline 2x100mg/dayazithromycin 3x250mg/day MWFmetronidazole 3x400mg/day then 3x500mg/day

John, the symptoms you describe just sound to me
like a person recovering from multiple sclerosis digesting his food.  Your
body is concentrating on digesting the food rather than bothering about whether
you drag your foot a bit.  Although I can now use a knife and fork very
well, towards the end of the meal I can lose  lot of strength in my wrists
and fingers and make really heavy going of cutting up the remaining food. 
I can then drag my feet whereas previously I wasn't simply because I can't be
bothered not to.  For a few minutes I just want to close my eyes. 
Half an hour later, digestion nearly finished, I am back to my normal, alert
self........Sarah
 
An Itinerary in Light and
Shadow
Wheldon regime since August 2003, for very aggressive SPMS.  Intermittent therapy after one year. 2006 still take this, now two weeks every three months.  EDSS was about 7, now 2. United Kingdom.

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

Sarah       

I'm at a loss to decide whether or not you're right about it being a digestive energy issue.  It doesn't seem to be as when I take glucose before eating, it does alleviate the problem either entirely or mitigates it to a great degree.

Also, for those of you following this thread, my reponse to Rita yesterday stated I take glucose before eating.  As one might expect, taking it after eating has no effect, or at least, has no effect on me when I've done that in the past.  Definitely take it before eating, and at least about 10 minutes and not much less or more.  The longer the time, the less the effect, the shorter the time, the less time your body has to respond to it before responding to digestion/eating.

all my best

John

RRMS/EDSS 4.5 on Wheldon Protocol (nac, doxycycline, azithromycin, metronidazole) since 04/12/2006

best, JohnRRMS/EDSS was 4.5, 5, 6, 6.5, 6.9999, 6.5 on Wheldon/Stratton Protocol beginning 04/12/2006nac 4x600 mg/daydoxycycline 2x100mg/dayazithromycin 3x250mg/day MWFmetronidazole 3x400mg/day then 3x500mg/day

Neat to pop this discussion up again accidently. John, putting together Sarah's comment about energy going into digesting food and some comments made by Dr. Stratton: since Cpn is an ATP (energy molecule) parasite there's less available for other cellular and organ functions. Any other heavy use of ATP such as muscle activity or even digestion (active transport processes) will leave some cells at a deficit and incomplete heme... ie porphyria can result. Isn't there some old saw about the energy to digest celery is more than it provides, hence the perfect diet food?

Another factor- Cpn up-regulates the host cell to absorb more glucose from the bloodstream, so it can make more ATP for the Chlamydia. So these big blood sugar crashes, which then result in more porphyria, all get rolled up together.

Your symptoms are familiar to me from times past, but without the foot-drop:"...lethargic, less coordinated, sometimes to the point where I have to be very careful with walking." My kids used to call me a klutz because I was always banging into things, especially when low blood sugar and porphyric from die-off.

CAP for Chlamydia pneumonia since 11/04. 25yrs CFS & FMS- Currently: 150mg INH, 300mg Rifampin, 200 Doxycycline, 500mg mwf Azithromycin, plus 500mg Tinidazole 2x/day pulses every two weeks. Whew! That's a lot!

John said he takes the glucose after eating...I thought the glucose was supposed to be taken before eating. Which is right?

Joyce~caregiver-advocate in Dallas for Steve J (SPMS) / Cpn indicated by reactions; Mpn, EBV, CMV positive; elevated heavy metals; gluten+casein sensitive / Wheldon CAP since Aug. '06 - doxycycline+azithromycin+flagyl pulses; 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        

See my last reply to Sarah.  I take glucose before eating, not after Image removed. 

all my best

John

RRMS/EDSS 4.5 on Wheldon Protocol (nac, doxycycline, azithromycin, metronidazole) since 04/12/2006

best, JohnRRMS/EDSS was 4.5, 5, 6, 6.5, 6.9999, 6.5 on Wheldon/Stratton Protocol beginning 04/12/2006nac 4x600 mg/daydoxycycline 2x100mg/dayazithromycin 3x250mg/day MWFmetronidazole 3x400mg/day then 3x500mg/day

 It depends-- some people (Ella for example) need the glucose to help suppress porphyric nausea and get back appetite. John appears to be needing it after eating to avoid blood sugar drop and porphyria from the energy it takes to digest! At least that's the hypothesis. We see all kinds of twists and turns in this.

CAP for Chlamydia pneumonia since 11/04. 25yrs CFS & FMS- Currently: 150mg INH, 300mg Rifampin, 200 Doxycycline, 500mg mwf Azithromycin, plus 500mg Tinidazole 2x/day pulses every two weeks. Whew! That's a lot!

Jim's right, when Ella is in a porphyric state, and she is about to eat when hungry her mouth starts to water to such an extent that it pours out of her mouth, and she feels very sick.   When she is feeling this way now, she takes a glucose tablet and the symptoms stop more or less immediately.  If she ignores the symptoms she usually sicks up what she has eaten some 10 minutes after eating.

This does not happen very often now but she still gets the following symptoms: stomach hunger and the feeling of nausea at the same time.   She has to make an effort to eat, as she does not feel like putting food in her mouth, but if she does she usually manages to keep it down.  

Michele: Wheldon CAP1st May 2006 for ailments including IBS, sinusitis, alopecia, asthma, peripheral neuropathy. Spokesperson for Ella started Wheldon CAP 16th March 2006 for RRMS. Sussex UK

Michèle (UK) GFA: Wheldon CAP 1st May 2006. Daily Doxy, Azi MWF, metro pulse.

Red

Hi all, just reading again about secondary porphyria and came across something interesting in Dr Stratton's article The Pathogenesis of Systemic Chlamydial Infections: Theoretical Considerations of Host Cell Energy Depletion and Its Metabolic Consequences that just didn't sink in before.

Forgive me if you understood this before, but although I'd read the article before I guess I didn't catch this. In the last paragraph he mentions the implications of Cpn infection of liver cells and states:

"Moreover, if chlamydiae were to infect hepatic cells, the use of any pharmacologic agents that are metabolized 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 is increased. If hepatic cells were infected with Chlamydia species, the decreased energy in the host cell would not allow heme biosynthesis to go to completion, and porphyrins in the liver/entero-hepatic circulation would increase."

He also goes on to mention that when the antimicrobial agents kill the Cpn the accumulated intracellular porphyrins would be released. Luckily I managed to catch this concept the first time I read it prior to beginning treatment.

The concept of increasing the need for P-450 by pharmacologic agents intrigues me in that I've noticed Vit D3 seems to increase porphyria symptoms for me. I recently read that apparently Vit D3 synthesis also requires P-450 enzymes in the liver and kidney:

CYTOCHROME P450, SUBFAMILY IIR, POLYPEPTIDE 1; CYP2R1

CYTOCHROME P450, SUBFAMILY XXVIIB, POLYPEPTIDE 1; CYP27B1

I'm wondering if increased need for P450 might be a good part of the reason Vit D3 seems to increase porphyria symptoms (in addition to its pro-apoptosis effects)?

BTW, I've also noticed caffeine seems to increase porphyria symptoms greatly for me now that I've added Vit D3 (particularly on flagyl pulses), and I just read that apparently P450 CYP1A2 is involved in caffeine metabolism:

CYTOCHROME P450, SUBFAMILY I, POLYPEPTIDE 2; CYP1A2

Does this make sense?

On Combined Antibiotic Protocol for Cpn in Rosacea since 01/06

Treatment for Rosacea

  • CAP:  01/06-07/07
  • High-Dose Vit D3, NAC:  07/07-11/08
  • Intermtnt CAP, HDose Vit D3:  11/08-01/09
  • HDose Vit D3, Mg, Zn: 01/09-

Amazing, Red. Could this be one of the reasons that D is not metabolized in Cpn infected bodies because of this liver enzyme being in short supply?
"I recently read that apparently Vit D3 synthesis also requires P-450 enzymes in the liver and kidney"

BTW, caffeine is a big trigger for porphyria for me---but I seem to have musch less porphyria these days.

What a complex puzzle. Thanks for th elinks,
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

Red

Gosh, interesting question Raven, but I'm not sure what if anything might cause a short supply of the P-450 enzymes involved in Vit D metabolism. I'll see if I can find anything.

Up to this point caffeine has been more of a help than a problem for me, but I'm now wondering if cutting it out might help with some of my remaining (and sort of still increasing) porphyria symptoms. I'm currently trying to cut it out slowly (one half mug at a time)...

On Combined Antibiotic Protocol for Cpn in Rosacea since 01/06

Treatment for Rosacea

  • CAP:  01/06-07/07
  • High-Dose Vit D3, NAC:  07/07-11/08
  • Intermtnt CAP, HDose Vit D3:  11/08-01/09
  • HDose Vit D3, Mg, Zn: 01/09-

Red, the short story is that you are correct about both Vitamin D and caffeine being sources of making you sick, and your belated understanding of the role of Cpn in causing porphyria due to mitachondrial ATP theft.

Both Vitamin D and caffeine require Phase I hepatic metabolism. In order to become bioactive, Vitamin D undergoes Phase I hepatic hydroxylation followed by another hydroxylation by the kidneys. Finally, when the body is done with Vitamin D, the liver hydroxylates it a third time to allow it to be excreted.

Phase I hepatic metabolism first involves the synthesis of one or more of several different P450 isoenzymes. These isoenzymes have a half life of only a few seconds at most, and therefore can not be stored. In fact, they are synthesized upon demand, and the trigger for their synthesis is the presence of the substance that must be metabolized.

Every one of these isoenzymes contains a heme entity, which itself must be manufactured upon demand. It is this induction of heapatic heme manufacture that ultimately results in porphyria for those of us who are prone to it.

Porphria is a consequence of heme synthesis gone awry. Once triggered, heme synthesis takes eight sequential steps. If all goes well, completed heme falls out of the bottom of the synthetic pipeline and feeds back to signal the first step to halt, thereby halting all subsequent steps.

If something goes wrong at one of the eight steps once the process starts, and finished heme does not result, the process does not stop, and intermediate precursors pile up at one or more of the steps. These precursors are called porphyrins, and are EXTREMELY potent radical oxygen species that are EXTREMELY neurotoxic, bringing on terrible systemic nervous system disruption and a consequently broad array of symptoms when released into the bloodstream.

Cpn infection is one of the things that can damage the heme making machinery. Cpn sets up shop near the mitochondria and steals their ATP output, which is the body's principal source of energy. This ATP theft also clobbers the ability of mitachondria to perform their role in heme manufacture, since as it turns out, half of the steps to make heme occur INSIDE of the mitachondria.

Cpn liver infection is thus particularly vicious because the liver is needed to metabolize many of the very substances that one needs to cure the infection, but because of damage by Cpn, those substances trigger porphyria. Nice survival mechanism, hey?

Vitamin D, caffeine, alcohol, tobacco, about 80% of all pharmaceuticals, many food substances, and many endogenous substances require Phase I metabolism for activation and/or elimination. Those of us who are prone to porphyria must be extremely careful with the drugs we take and some of the foods we eat. Substances that are good for healty people, like blueberries and cruceriferious vegetables (for example), can be bad for us. And substances that might normally be unhealthy for healthy people, like grapefruit juice and cimetidine (for example), can be beneficial for us.

Vitamin D made me extremely ill, and not just from its antibiotic effect, which is what lead me to do the research that made me realize that Vitamin D is just one more substance that can trigger porphyria.

basil.

If cats are outlawed, only outlaws will have cats.

The quantities of Vitamin D involved are low enough that I doubt that the need to synthesize enzymes to modify Vitamin D has much to do with porphyria. Only micrograms of Vitamin D are present; in comparison, gluconeogenesis needs to operate on gram quantities, since it's generating the main fuel used by the body. (Avoiding gluconeogenesis is the reason for eating glucose to stop a porphyria attack.)

Red

Thanks so much Basil. I cannot tell you how helpful this information is. It really confirms my suspicions that Vit D3 seems to be causing porphyria symptoms for me too through this method (rather than just through apoptosis mechanisms). I found immediately upon starting Vit D3 that I became extremely alcohol intolerent. This explains why. I believe I now (after 6 months of 4000iu of Vit D3) that I've reached a point where I may be intolerent of caffeine as well. I'll continue to try to eliminate it slowly from my diet (to avoid withdrawal symptoms).

Here's another question for you, glucose tabs seem to almost immediately provide relief of my symptoms (within @ 20 minutes or so). But within a couple of hours I notice greatly increased congestion symptoms that last for @ 8-12 hours or so. High carb meals seem to do the same. While I'm worried about candida/yeast problems, the quick onset of these symptoms (and then clearance) doesn't seem to make a lot of sense along these lines. I'm wondering if the increased glucose/carbs sets off some kind of inflammatory or oxidative type reaction with the porphyrins (to eventually help scavenge and clear them), but haven't been able to find much on this. Does this make any sense?

Thanks again so much as always....

On Combined Antibiotic Protocol for Cpn in Rosacea since 01/06

Treatment for Rosacea

  • CAP:  01/06-07/07
  • High-Dose Vit D3, NAC:  07/07-11/08
  • Intermtnt CAP, HDose Vit D3:  11/08-01/09
  • HDose Vit D3, Mg, Zn: 01/09-

Red, glucose and cimetidine provide me immediate relief as well when I realize I'm becoming porphyric. Actually, this immediate relief is not something I really expected, because I've always been under the impression that porphyrins are long-lived chemicals that are difficult to eliminate. And yet, such immediate relief would contradict that impression. Perhaps the body has the ability to deal with a certain amount of porphyrins rather handily, but if that amount is exceeded, the porphyrins accumulate.

Regarding the congestion, one thing that could happen is that if you are prone to blood-sugar instability, a big dose of glucose or carbs could cause your insulin to rapidly spike and then drop, along with a rapid drop in blood glucose. This would be consistent with the time frame of your congestion onset. The above is a form of hypoglycemia disorder. Regarding symtoms that can result from the above process, I found this:

"The symptoms of 'hypoglycemia' (the term we will continue to use here) are many. They consist of fatigue, irritability, nervousness, depression, insomnia, flushing, impaired memory and concentration. Anxieties are common as are frontal or bitemporal headaches, dizziness, faintness or actual syncope. There is often blurring of vision, nasal congestion, ringing in the ears, numbness and/or tingling of the hands, feet or face. Excessive gas, abdominal cramps, loose stools or diarrhea are common. Many complain of leg or foot cramps. These are the chronic symptoms of this condition and are present even during periods of normal blood sugar."

I'm wondering if you perhaps have any of the above symptoms besides just the nasal congestion.

basil.

If cats are outlawed, only outlaws will have cats.

Red

Thanks Basil.   Many of these symptoms are VERY familiar to me, and I've always been more than a little sensitive to foods high in sugars so potentially this explanation makes a lot of sense in my case too.

I think I'll continue to try to cut out caffeine and try bumping up my intake of complex carbs a bit to see if I can reach a happy medium state between porphyria and congestion/inflammation. 

Thanks again and take care... 

 

On Combined Antibiotic Protocol for Cpn in Rosacea since 01/06

Treatment for Rosacea

  • CAP:  01/06-07/07
  • High-Dose Vit D3, NAC:  07/07-11/08
  • Intermtnt CAP, HDose Vit D3:  11/08-01/09
  • HDose Vit D3, Mg, Zn: 01/09-

Thanks basil for the information on Hypoglycemia.  I have this disorder and keep the simple carbs down to a dull roar.  I see, like many other ailments, there are cross over symptoms - CFIDS/ME.

When my intestinal flora gets out of what I know because I crave sugar.  It is a challenge being on abx & keeping the balance as in the past I have had a candida problem (I just did a cleanse in February).

The change in the diet recommended during the protocol I feel will have me gaining alot of weight?  When I am able to do more exercise I increase the complex carbs accordingly.

I hope I will be ok; I continue down the path

Mad CAPper

With Christ in Faith

Ruth 

CFIDS/ME, FMS, MCS, IBS, EBV, CMV, Cpn, H1, chronic insomnia, Chronic Lyme, HME, Babesia, Natural HRT-menopause, NAC 2.4 gm,Full CAP 6-2-07, all supplements+Iodorol, Inositol-depression, ultra Chitosan, L lysine Pulse#27 04-19-10 1gm Flagyl/day-5 days<

 Basil- Reading your post on the azith thread:

Finally, I personally have suffered repeated porpyria attacks triggered by CAP, even though none of the substances I take require Phase I metabolism (and therefore would not be porphyria triggers). My attacks are not simply the result of porphyrin release from liver-cell apoptosis, but full blown, out-of-control, continuous-porphrin production attacks that can be stopped only by taking large amounts of gluecose and cimetidine (a P450 inhibitor).

It got me thinking: could apoptosis and dump of intracellular porphyrins require Phase 1 processing by the liver, ie how are the fat soluble porphyrins processed by the liver? That would put a big demand on the liver which would trigger immediate porphyrin attack, and round and round.

CAP for Chlamydia pneumonia since 11/04. 25yrs CFS & FMS- Currently: 150mg INH, 200 Doxycycline, 500mg MWF Azithromycin, 500mg Tini daily (Continuous protocol)

Jim, I think you may have hit the nail on the head. Phase 1 processing is usually the first step in converting fat soluable compounds into water soluable compounds, with Phase 2 conjugation being the second and final step.

The body has very very poor(almost non-existent) mechanisms for eliminating fat soluable compounds, hince the need for conversion to water soluability.

I too just recently briefly wondered about the fat soluable porphyrins and whether they would undergo Phase I metabolism. But I didn't pursue the thought like I should have. But you did.

That is, you've hypothesized that the body would attempt to utilize Phase I metabolism for the inital step in converting fat soluable porphyrins into water soluable compounds. However, this attempt at conversion would result in either triggering and/or sustaining a self-perpetuating porphyria attack.

In the case where a porphyria attack had not yet started, but in which a person was prone to secondary porphyria attacks, if CAP-induced apoptosis of infected liver cells released too much intracellular porphyrins from diseased liver cells, then a secondary porphyria attack would be triggered, actually producing new porphyrins on top of the porphyrins released by the CAP. Furthermore, such an attack would be self-sustaining until abated by treatment with glucose/cimetidine/Panhematin, producing far more porphyrins than those originally dumped by cell apoptosis.

This hypothesis very neatly explains why CAP induces self-sustaining secondary porphyria attacks. Based on my own experience, and others here, I've simply never believed that the amount of porphyrins dumped by cell apoposis was enough to make people as sick as they get. Furthermore, I have no doubt that CAP has triggered self-sustaining porphyria attacks in myself, and others here. One reason for this belief is that glucose and cimetidine should have no effect on porphyria symptoms produced by simple porphyrin dumping as a consequence of cell apoptosis, and yet myself and others have reported that these remedies bring relief from CAP-induced porphyria symptoms.

I really think you may have discovered a very important piece of the puzzle.

If this is all true, then this would also be one of the mechanisms that would sustain primary (genetic) porphyria attacks as well. Experimentally, this hypothesis shouldn't be too difficult to prove. Perhaps a murin model with induced porphyria cutanea tarda could be used. Once the mice are made PCT with the appropriate toxin, fat solulable porphyrins could be injected and it could be easily determined if a self-sustaining porphyria attack resulted.
I wish I had the money to fund the research.

I would be very, very interested in what Charles Stratton has to say about all of this.

Great thinking! I'm jealous that I didn't figure this out myself!

basil

If cats are outlawed, only outlaws will have cats.

yikes, all this talk about the liver & porphyrins.  scary.  I am glad I backed off the flagyl/metro as my liver, gallbladder, spleen area was very sore.  I guess that is porphyrin attack as after I cut the doseage in 1/2, about 4 days I had less pain in that area.

The Nasty Cpn already triggered my Hemochromatosis - excess iron storage.  My inner Physician has been working overtime for years, I blame everything on the bacteria!! lol

My best wishes

With Christ in Faith

Ruth 

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Some more thoughts on porphyria and Cpn

27 Apr 2018
Author
basil
Title

Some more thoughts on porphyria and Cpn

Body

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.

Comments

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

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

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

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.

RonOn CAP for CFS starting 01/06 (NE Ohio, USA)Began rifampin trial 1/14/09Currently: 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

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

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. 

Neurovisceral Features of Acute Porphyria Attacks

Neurovisceral Features of Acute Porphyria Attacks Jim K Sat, 2007-12-22 10:11

Chanced upon this link available above, to excerpts to a text on the Diseases of the Liver and Bile Ducts.  I have used this text while pondering my own set of circumstances, it is quite technical in nature, not an easy read.  I was surprised to find so much of it open for examination on the internet.  Thanks Jim for providing this link.  

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

Jim, You might peruse the files located under the images tab/at the top of the page and see what else might be found that could use an additional easy to find location.   I found a lot of graphic type files located here;  http://www.cpnhelp.org/image/tid/80  by first visiting this page;  http://www.cpnhelp.org/image and clicking on the Chlamydia Pneumoniae Pictures file this is added for for anyone elses who might like to browse around. 

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

Bumped into this post again.  Been a while since it surfaced so here it is again.   Louise

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

Book excerpt from: HERE