Stratton's Treatment Recommendations

[Guest guest]

Someone on the MS forum sent me a Word doc which is a

handout Stratton et al offer for their treatment

protocal, pending their completed research. This

person noted: " Some of it, like the

antibiotic regimen, needs updating- he's currently

using Minocycline/Zithromax/Flagyl (with, " consider

Amoxicillin as well " ), but what this handout does

have, is the current instructions for managing the

treatment of the infection- diet, supplements, etc. "

I'm hoping I can get this in on one email, if not I'll

break it up as it's long. Wheldon sent me a draft of a

paper he's submitting for publication, and I'll pass

on what I glean from it also.

THERAPY OF CHRONIC CHLAMYDIAL INFECTIONS INCLUDING

THEIR ASSOCIATED PORPHYRIA AND VITAMIN B12 DEFICIENCY:

SEVENTH VERSION

W. Stratton, MD

M. , 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.

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 tryprophan 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 manufacturer’s 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

patient’s 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.

See the following note and web site for additional

information on B12. Sublingual B12 can be obtained

from <puritanspride.com>.

Below is an introduction from the article: " Vitamin

B12: Surprising New Findings " by Terri

The whole article can be found at:

http://www.lef.org/magazine/mag2000/dec2000_report_b12_1.html

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.

III. THERAPEUTIC ANTIMICROBIAL REGIMEN

When the presence of chlamydia in the blood is

detected by blood culture and/or serum PCR and active

infection is suspected per elevated IgM and IgG

antibody titers, a presumptive diagnosis of systemic/

chronic chlamydial infection can be made. The

antimicrobial regimen described is directed primarily

against the cryptic form of chlamydia, which explains

the use of some agents that are not active against

replicating organisms.

Step 1: 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. The

antimicrobial agents are given in a stepwise fashion

in order to minimize side effects. The first agent is

amoxicillin (500 mg) and is given only once for the

first week. It is then given daily twice a week (e.g.,

Monday and Friday) on the second week, daily three

times on the third (e.g., Monday, Wednesday, and

Friday), and once daily on the fourth week. The same

schedule is followed for the second dose of

amoxicillin until 500 mg of amoxicillin is given twice

per day. The amoxicillin is then combined with

probenecid (500 mg). The same schedule is used for the

probenecid until it is being given twice per day. If

the patient is penicillin-allergic, penicillamine (125

mg q 12 hours) can be substituted for the amoxicillin.

As mentioned, it is best to start the amoxicillin

first and then gradually add the probenecid. Again,

this is done by giving amoxicillin once per day on

only one day for the first week, then twice a week,

three times a week and then every day. The amoxicillin

is then increased to twice per day using the same

schedule. The probenecid is added using the same

schedule. The patient is closely monitored on these

first two agents for side effects. These agents are

continued for the entire course of chlamydial therapy.

Step 4: After the patient has adjusted to the

amoxicillin/probenecid therapy, additional

antimicrobial agents directed at cryptic and

replicating chlamydiae are added. These agents, like

the amoxicillin and probenecid, are introduced very

gradually, being given initially once per day on only

one day per week. Once an additional agents is well

tolerated (This may take 2-4 weeks or longer.), the

antimicrobial combination is increased to twice per

week, given on Monday and Friday with continued

monitoring for side effects. After 2-4 weeks or more

of this twice-per-week combination therapy, the

antimicrobial combination is increased to three times

per week, given on Monday, Wednesday, and Friday. This

triweekly combination therapy is continued until

tolerated before being increased to daily therapy.

The additional antimicrobial agents that can be added

to the amoxicillin/probenecid (or penicillamine)

include a number of choices. These include rifampin

(300 mg twice per day) azithromycin (250 mg MWF),

clarithromycin (500 mg twice per day). Note that the

azithromycin is given only on Monday, Wednesday, and

Friday due to its long half-life. The combination of

amoxicillin, rifampin, and azithromycin seems to work

quite well.

Step 5: The duration of antimicrobial therapy may take

months to years and is based on the results of

repeated testing for the presence of chlamydiae.

Repeat blood tests for chlamydia are recommended every

six months. The goal is a negative blood culture or

whole blood PCR for chlamydia (Blood collected in

citrated tube.), negative IgM titers (< 1:50), and low

IgG titers (< 1:200) (Blood collected in red top

tube.).

IV. ANTI-INFLAMMATORY AGENTS

Chlamydial cell wall includes lipopolysaccharides

(LPS) which can produce an inflammatory response as

cell wall LPS is released when chlamydia are killed.

In addition, the major outer membrane protein (MOMP)

of chlamydia has been found to be a potent inducer of

cytokines. These antigens (LPS and MOMP) released by

chlamydial cell death can produce an Herxheimer-like

inflammatory response that may be prolonged. As this

inflammatory response is related to chlamydial cell

death, it may be present over many months. It can be

minimized by adding the antimicrobial agents in a slow

stepwise manner. This prolonged inflammatory response

may be a problem for which anti-inflammatory agents,

up to and including steroids, may be useful. In

particular, newer anti-inflammatory agents such as

Celebrex (200 mg once per day) appear to be very

useful in this regard.