Submitted by Jim K on Wed, 2006-02-08 11:18

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:


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 <>.

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.