Secondary Porphyria from antibacterial treatment

[Guest guest]

Hi all-

I got into providing this info for a discussion of

" neuro herx " on the Lyme Strategies list and thought

it might add to the discussion here on herx vs immune

cytokine release from bacterial die off vs bacterial

endotoxin vs etc, etc. Now we can add porphyria to the

list of things to sort out when we react to abx. So

I'm posting the info drawn from the sources noted.

Jim

Kurt, et al—

Below is info on secondary porphyria taken from the

two sources identified in the links. The second source

is from and Stratton’s patent materials, on

public record at the US patent office. Worth reading

relating to Chlamydia problems, but also for their

meticulous and brilliant science on creating a

depthful and multifaceted approach to treating this

disease.

I think I’ll break this up into two posts in case it’s

too long.

The description of porphyria (related to multiple

chemical sensitivity and chemical exposures) sure

sounds a lot like the “neuro herx” described on this

list doesn’t it?

Secondary Porphyria Part I-

From:

http://www.mcsrr.org/resources/articles/S5.html

A secondary porphyrinuria or coprophyrinuria is a

porphyrin abnormality that occurs secondarily to some

other disease which usually test positive for some but

not all of the diagnostic markers associated with true

porphyrias.

The broader term " porphyrinopathy " is used here to

refer to any disorder of porphyrin metabolism,

inherited or acquired. The porphyrinopathies being

seen in chemically-sensitive patients do not fit the

patterns of any known type of inherited porphyria.

This suggests that they may be the result of an

acquired abnormality, due either to the direct effects

of a chemically-induced porphyrinopathy or the

secondary effects of some other disease.

The " acute " porphyrias always display neurological

symptoms affecting the central, peripheral and/or

autonomic nervous systems. These may include any

combination of abdominal pain, nausea, vomiting,

constipation, seizures, headaches, difficulty

concentrating, personality changes, weakness and

aching in muscles and joints, unsteady gait, poor

coordination, numbness/ tingling of arms and legs,

retaining fluids, rapid heart rate, increased blood

pressure, increased sweating, and intermittent fever.

Acute and chemically-acquired cases also show

increased sensitivity to a long list of exposures that

may both bring on symptoms and make them worse. These

include certain medications (the focus of much

porphyria research), toxic chemicals (such as PCBs and

dioxin), alcoholic beverages (including beer and

wine), other liver diseases (like Hepatitis C and

cancer) as well as more subtle factors like hormonal

changes and a low carbohydrate diet. (Skipping meals

and dieting make symptoms worse, while chemicals that

mimic the female hormone estrogen are known to trigger

acute porphyrias--both of which may contribute to the

higher incidence of acute porphyrias in females.)

Some persons with " acute " types of porphyria excrete

porphyrin substances in the urine and/or stool only in

response to exposures that make them ill. Their tests

are more likely to show changes in the first 2 to 3

days after the onset of a reaction. Thus, urine and

stool testing is most sensitive and accurate during

that time.

Secondary Porphyria Part I-

From:

http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO2 & Sect2=HITOFF & p=1 & u=%2Fneta\

html%2FPTO%2Fsearch-bool.html & r=1 & f=G & l=50 & co1=AND & d=PG01 & s1=stratton & s2=chlamyd\

ia & OS=stratton+AND+chlamydia & RS=stratton+AND+chlamydia

[0179] Treatment of Chlamydia infection may

[exaserbate] exacerbate secondary porphyria by

increasing the metabolism of cryptic Chlamydia or by

accelerating the death of infected cells with elevated

intracellular porphyrin levels.

[0199]…The potential for secondary effects such as

porphyria should then be screened. For example, this

can be evaluated by performing one or a combination of

the following tests: 1) complete blood count (CBC);

2) Liver function tests; 3) Uric acid; 4) Serum iron

studies; 5) IgM and IgG antibodies to

coproporpyrinogen-III and Vitamin B12; and, 6) ALA

dehydratase and PBG deaminase. Urine and stool

samples should also be tested for presence of

porphyrins, preferably using 24 hour samples.

[0181] C. Therapies to Enhance Cellular Function

[0182] Glucose is an important source of cellular

energy. Glucose levels can be enhanced by diet and

through vitamin supplements as described below.

[0183] A high carbohydrate diet should be maintained

to promote production of glucose (Pierach et al.,

Journal of the American Medical Association,

257:60-61 (1987)). Approximately 70% of the caloric

intake should be in the form of complex carbohydrates

such as bread, potato, rice and pasta. The remaining

30% of the daily diet should comprise protein and fat,

which should ideally be in the form of fish or

chicken.

(ed. Absolutely avoid red meats! Worsens porphyria)

[0181] C. Therapies to Enhance Cellular Function

[0182] Glucose is an important source of cellular

energy. Glucose levels can be enhanced by diet and

through vitamin supplements as described below.

[0183] A high carbohydrate diet should be maintained

to promote production of glucose (Pierach et al.,

Journal of the American Medical Association,

257:60-61 (1987)). Approximately 70% of the caloric

intake should be in the form of complex carbohydrates

such as bread, potato, rice and pasta. The remaining

30% of the daily diet should comprise protein and fat,

which should ideally be in the form of fish or

chicken.

[0188] Multivitamins containing the B complex vitamins

should be administered daily (e.g., one or multiple

times), preferably in excess of RDA, to enhance

glucose availability. Hepatic breakdown of glycogen

with generation of glucose is assisted by taking

these multivitamins that contain the B complex

vitamins. Pyridoxine minimizes the porphyrin related

porphyrial neuropathy. B complex vitamins include

folic acid (e.g., 400 .mu.g per dosage; 1200 .mu.g

daily maximum); vitamin B-1 (thiamin; e.g., 10 mg per

dosage; 30 mg daily maximum); B-2 (riboflavin; e.g.,

10 mg per dosage; 30 mg daily maximum); B-5

(panothenate; e.g., 100 mg per dosage; 300 mg daily

maximum); B-6 (pyridoxine; e.g., 100 mg per dosage;

300 mg daily maximum) or pyridoxal-5-phosphate (e.g.,

25 mg per dosage; 100 mg daily maximum) and B-12

(e.g., 500 .mu.g per dosage; 10,000 .mu.g daily

maximum). The preferred method of administration is

oral for the majority of these vitamins (twice daily),

except for B-12 for which sublingual administration

(three-times daily) is preferred. It has been

discovered that one important effect of this secondary

porphyria in some patients is the production of IgM

and IgG antibodies against coproporphyrinogen-III.

These antibodies cross-react with Vitamin B12

(cobalamin) and can thus cause a deficiency. Vitamin

B12 supplementation (e.g., parenteral cobalamin

therapy) can remedy the deficiency.

[0189] D. Reducing Porphyrin Levels

[0190] Dietary and pharmaceutical methods can be used

to reduce systemic porphyrin levels (both

water-soluble and fat-soluble).

[0191] 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.

[0192] 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.times.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.

[0193] 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/m.sup.2 to about

5000 mg/m.sup.2 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. Intravenous

hematin may also be administered. 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)).

[0194] To reduce severe porphyric attacks during

therapy for chronic Chlamydia infections, the use of

hemodialysis, plasmapheresis, chelating agents and/or

intravenous hematin may be needed. Any one of these or

a combination thereof can be used to treat the

patient and is well within the knowledge of the

skilled artisan how to carry out these adjunct

therapies.

[0195] E. Mitigating the Effects of Porphyrins

[0196] 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 .mu.g per dosage; 300 .mu.g 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).

[0197] 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.TM., 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.TM., Roche or

Restoril.TM. (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.

[0198] 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.