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Monday, February 24, 2020

Detoxing and science and doctors

I talked to a patient today who is mad. Mad at doctors who are unprofessional, disrespectful and who disparage other doctors. This is what I recommend.  Calmly call out the doctor's misbehavior. Be the grownup. Rise above the petulant, entitled child who never grew up.  This describes many doctors.  My patient wants to be proactive, respond to ill=treatment form doctors.  Something about ratings in Apps. No comment.

If you are like me you sometimes grab an orange from the basket, hold it under the faucet for a few seconds, peel and eat it.  Perhaps you grab a waxed apple and do the same. You should scrub the fruit with a natural detergent. Your produce is likely grown in an invisible stew of things like the widely used pesticide 1,3 dichlorpropene banned in the European Union, Roundup, Organophosphates, Arsenic related and others to name a few.  Big agra-business makes the oranges and apples shine – with more chemicals.  The FDA assures us the levels of toxins and carcinogens are safe. Organic produce has less of the same but is exposed to the same contaminated water table and soil, our toxic biosphere.  The FDA tells us the levels of these entirely safe.  The Mayo Clinic suggests natural products used by organics farmers are not proven safer than unpronounceable chemicals known to quickly kill white mice.  Who told them that?

Weeds, like unwanted bacteria are becoming increasingly resistant to the usual pesticides calling for more drastic measures. Nice. 

This is not my usual topic and I know little about the subject and have much to learn.  But I hear a lot about detoxing. This what it might mean to me. 

Enter the word Xenobiotic.

You already know about probiotics and antibiotics. 

Xenobiotics are foreign, non-biological substances which may be toxic to tissues including liver and kidneys. Very bad toxic substances we ingest daily. 

Likely the doctor has never heard the word.  Give them scientific source material. 

Xenobiotics can be difficult to eliminate and cycle endlessly through enterohepatic re-circulation.
This is where activated charcoal comes in.  It waits in the intestines for the toxin laden bile, grabs the xenobiotics and eliminates them through the colon. Charcoal and cholestyramine eliminate mold toxins (mycotoxins) the same way. They may also eliminate your expensive medicines. Follow directions. 

Frequently sage allopathic doctors, especially infectious disease experts, jump down the gullets of Lyme patients who say they are “detoxing.” The word detoxing is foreign to mainstream medicine and practitioners. It raises the antennae of doctors who are quick to denounce such talk as voodo pseudoscience.  

Lyme bacteria do not have toxins they will opine. 

It’s true Lyme bacteria lack the endotoxins of pathogenic gram-negative bacteria. That’s not at issue. 

I always try to teach patients how to talk to doctors. The answer is, “Of course not. The chronically ill patients may have difficulty with toxic xenobiotics (look up the word doctor). General inflammation challenges the ability of the overworked liver and kidneys to remove the toxic chems.  And doctor, if you are content with paraquat and roundup in your diet it doesn’t apply to you.” (Less snarky -- unless the doctor is a narcisistic, arrogant piece of excement).

The doctor may come away realizing there is something here to learn. Nah. 

In general, don't mention detoxing. Its not worth it. 

Charcoal helps with Herxeimer reactions because it binds cytokines. This can be further explained if the doctor if she/he is still standing in the exam room. This straightforward, unassailable science. 


A lot of doctors don't like science. Ironically they are quick to lable those with whom they disagree anti-science. Old news. 

Don't be angry with doctors. Set realistic expectations. Unless they attack me. Then go for the jugular. JK.

Organic foods  are better.  GMOs are not the problem. They are the bright, shiny object which distracts. A discussion for another day.

Friday, February 21, 2020

DSF, dose, activated charcoal managing the Herxheimer reaction

My patient is feeling optimistic. The best she has felt in years.  Disulfiram/Antabuse, AKA DSF is the game changer.  She takes a tiny amount.  I prescribed 10 mg compounded capsules, a very low dose. She started with one capsule every 4 days and has increased the dose to 2 caps, 20 mg daily. She reacts to this small dose, significantly.

She feels OK the first day of disulfiram pulse. The second day she is assaulted with a variety of symptoms: fatigue, brain fog, muscle/joint pain, shooting pains, muscle twitching, head pressure, etc. She feels increasingly better over the next 4 days and the cycle repeats.
She is happy. No longer depressed. Really happy.

She tells me she manages the second day Herxheimer reaction with doses of activated charcoal.
I’m naturally skeptical.  Everything has to make sense. Scientifically and logically.

Herxheimer reactions are modulated by the immune system, something like a cytokine storm. This is all very complicated so let’s not get lost in the weeds. These cytokines are a complex set of proteins which regulate activity of the immune system (traffic the immune system). When Lyme is killed cytokines and the immune system are kicked into high gear. This leads to inflammation, too much inflammation, a bad thing. We need to reduce cytokine activity and/or cytokines themselves.

It’s exciting to learn that activated charcoal is incredibly effective at binding cytokines. When blood is filtered through activated charcoal cytokines are removed.

How does that help us? Blood has to be removed from your body and filtered. Not likely. Activated charcoal is the “universal antidote” and good for reducing bloating and gas. It stays in the gut. It does not get into the blood where cytokines live.

Ah ha. Like cholestyramine, it interferes with the natural recycling of bile (from the liver) to the intestines and back to the liver. OK. And..

A published study looked at oral charcoal in mice loaded with malaria and treated with an intravenous antimalarial drug.  Charcoal reduced brain swelling and reduced key cytokines. Gut only charcoal did all this. 

Cytokines may be cycled through enterohepatic pathway and processed through the intestines.  Charcoal may be there waiting to gobble them up. (Conjecture on my part).
I finally have an idea why Wellchol/cholestyramine lowers C-reactive protein. CRP is cytokine driven.

Normal functioning of the enterohepatic pathway impacts the concentration of medicines, toxins and other substances present in serum. I discussed this in another post. Messing with the enterohepatic re-circulation of bile can do good and bad things. This is a very complex and vital part of our physiology.

The best treatment for Herxheimer reactions may be antioxidants (oxidative stress) and activated charcoal.

I do listen to my patients and believe what they say. I worry that many desperate patients are taken advantage of by various scams. I worry about overpromoted nostrums, a mass placebo effect.  Think-- The Emperor’s New Clothes.

My patient today snickered at my skepticism.  I am humbled.  She was right and I was wrong.

I still want people to stop think Herxheimer reactions are caused by toxins and cholestyramine/Wellchol and charcoal remove toxins. Speaking of  toxins specific to the Herxheimer reaction. This does not make scientific sense. (I am not saying other toxins are not removed, I am speaking of the mechanism of the Herxheimer response).

Yes, the best starting dose (and ending up dose) of disulfiram is variable.  Starting low is a good idea. 10 mg seems to be a good starting place, for sensitive patients. Options include 25 mg, 62.5 mg and others generally are well tolerated.  Gradually increasing the dose likely mitigates damage caused by an overly eager immune system.

Take home points:  DSF, start low.  Herxheimer reactions -- antioxidants and charcoal.
Also, if you had a bad reaction with a higher dose of DSF you may do well with a small starting dose.

Thursday, February 13, 2020

CFS, SEID, (a little POTS?)

If you treat Lyme you see boatloads of patients with chronic fatigue syndrome and many with POTS. CFS, myalgia and encephalitis has been renamed SEID, systemic exertional intolerance disorder. Many patients with SEID have orthostatic intolerance.  When they stand up for any period of time they feel the need to sit down or lie down. Is there a connection we are missing?

POTS, postural orthostatic tachycardia syndrome is a manifestation of dysautonomia, a broken autonomic nervous system. This important part of the nervous system does many things. With POTS with focus on a cardiac manifestation.

A lot of disorders are diagnosed based on cutoffs. The numbers are somewhat arbitrary. For example, POTS is diagnosed when supine pulse goes up 30 points with standing.  Perhaps a lying down heart rate goes from 60 to 90 when a patient stands, and stays there and may increase.

A patient may need to stand for 15-20 minutes before the change occurs.  Some patients are tortured with a tilt table test (not originally designed to diagnosed POTS).

Today I saw a 54 year old male I have been following for a number of years.  His main problem has been crippling fatigue.  Maybe he has Lyme, not clear.  Antibiotics were a little helpful (or placebo effect). With high viral titers, EBV and HHV6 the antiviral Valcyte helped, for a while. Maybe. Always looking for the next thing he asked me to prescribe rituximab (kills EBV?). NO WAY. He is always looking for a new cure. He tends to overdo exercise when he feels better and relapses.. Treatment for mast cell activation disorder has been somewhat helpful. 

Today he is feeling the best he has felt in 10 years -- normal.  How did we get there?

When he changed position lying to standing his pulse only increased about 12 points. No POTS by standard criteria.

I wondered what would happen if I treated him for POTS.

I didn't make many changes.  He has high blood pressure.  I changed his BP med, an ARB, Cozaar, a standard go to BP med to Coreg.  Coreg is an alpha/beta blocker and has been shown to help POTS. Normal B blockers should not be used.  I started him on salt (only started  one gm NaCl) and he added more to food. ( crazy in a patient with HTN, right?)

The change in pulse corrected.  His blood pressure did not go up.  Only a small subset of blood pressure patients are salt sensitive, especially blacks and the elderly.

Will it work for others? I don't know. I don't  know if it will continue to work for him.

The experience of one patient may be a fluke and mean nothing.

Both POTS and CFS are poorly understood.  They share certain features.

Mast cell activation syndrome may overlap as well in many cases. The diagnosis is usually clinical.

This therapy must be done slowly with careful patient monitoring.

A  little dysautonomia, a little POTS, a spectrum, continuum? Maybe. Medicine is frequently gray. Black and white cut off points should be looked at critically.

A thought.

Tuesday, February 4, 2020

Lyme update 2020: Key points



Eradication

We go back to the three legged monster I described so many years ago. The tickborne monster has legs of Lyme, Babesia and Bartonella.

For the first time Lyme has been eradicated in an animal model (murine/mice).  Dr. Zang of Hopkins was successful with a daptomycin based 3 drug cocktail: daptomycin, ceftriaxone and doxycycline. These 3 FDA approved drugs are well known and well used. Short of human studies, considered repurposing of vetted drugs may be considered. 

IV therapy is preferred and/or the standard of care in specific cases: sometimes indications are gray.  The risks of IV therapy include infection and venous access line and possible sepsis, thrombosis/blood clots and pulmonary embolism.  The use of intravenous antibiotic does not decrease the likelihood of C. difficile infection. The mainstay of intravenous antibiotic therapy has been Rocephin for many years.  Other antibiotics frequently employed include Flagyl, azithromycin and doxycycline.  Treatment incorporating daptomycin is new and has been well tolerated.  The drug itself is actually quite old.  It has been reserved for serious, resistant infections in many institutions and infectious disease experts have cautioned against first line therapy or other inappropriate use.

The primary indications for intravenous therapy include: Acute/subacute neurological disease ranging from encephalitis, meningitis to peripheral neuropathies including Bell’s palsy and others; acute inflammatory arthritis nonresponsive to oral therapy; Lyme carditis.  Patients with chronic Lyme encephalitis, /neuroborreliosis with cognitive problems are frequent candidates.  Patients who fail aggressive oral therapy, suffering with a multisystem disorder and poor quality of life are candidates.  The choices available for oral therapy are evolving.  As a general rule, IV antibiotics and oral antibiotics should be started and added one ag a time. The anticipated duration of therapy is always completely unknown. Every case is different.

Antabuse

Antabuse/disulfiram may be a game changer. In Vitro studies (Stanford University) demonstrated efficacy against Lyme spirochetes, round forms and biofilm forms. Antabuse has been used for more than a century as an antiparasitic, a commercial agent used for rubber manufacturing and for treating alcoholism.  Antabuse inhibits degradation of acetaldehyde, a toxic intermediary of alcohol metabolism.  Alcohol with disulfiram is a miserable experience one will never forget.  There are better ways to treat alcohol abuse. Antabuse has new life as a Lyme killer.  Antabuse has been effective against resistant forms of bacteria, including Staphylococcus (including biofilms) in-vitro. It seems to have a narrow spectrum against gram positive bacteria and should be easier on the gut. 

Side effects and tolerability described in older literature regarding aplicability for alcoholism does not to apply to our experience with Lyme patients.  For example, rare neuropathy described in alcoholics is not rare for Lyme patients. Herxheimer reactions are common and frequently severe; lower doses of the drug is required.

One option is to cut a 250 mg tabs into quarters enabling initial treatment with 62.5 mg. Compounding allows for more flexibility. Disulfiram can be compounded to any dose you like, for example, 10 mg or 25 mg. A target dose of 250 mg is frequently effective. Some patients claim that the 500 mg dose is more effective. I still combine disulfiram with traditional antibiotics for an optimal response. 

In my experience disulfiram does not eradicate Babesia. In many cases Lyme and Babesia are mysteriously linked. When Lyme clears and remits Babesia too may recede into remission. This may give the appearance the drug kills Babesia. 

Babesia

The malaria like red blood cell parasite is very problematic.   B. duncani and other unidentified organisms are very troublesome. Full eradication should be the goal.  Recurrences can be very difficult since the parasite often returns resistant to an arsenal of anti-Babesia drugs. Most “virgin” Babesia cases respond to Mepron. It is important to start with 10 cc or 2 tsp twice daily with fat. The 5 cc dose frequently recommend is inadequate. Mepron must be used with Zithromax.  Zithromax has the unique ability to concentrate inside cells at an incredibly high level. Other drugs like Biaxin, doxycycline, Bactrim and clindamycin are not effective.   I recommend more than one anti-Babesia drug even when Mepron appears effective. Bellwether symptoms:  night sweats, air hunger, random tearfulness are important but Babesia may cause many other symptoms as well. Coartem is my next favorite agent. It includes a much more bioavailable and effective artemisinin derived component, artemether. 

My third preferred agent is tafenoquine (well tolerated excluding G6PD deficiency). It comes in 2 forms.  Krintafel comes in 150 mg tabs and is used as a single dose for Malaria, repeated at intervals, e.g. weekly and  Arakoda, approved for malaria prevention.  The 100 mg tab is approved for daily use for malaria prevention. 

How long is Babesia treated? We say until symptoms are gone.  I have seen many cases of hoped for cure relapsee. I currently treat for 4 months beyond the point of complete remission if possible.  . 

Bartonella

This small bacteria lives in the cells that cover the inside of blood vessels. The bacteria may occupy red blood cells after infection until they "Uber" into blood vessel lining cells (endothelial cells).  Bartonella persistern forms have been observed.  Complex antibiotic cocktails with multiple bacteriostatic antibiotic, including tetracyclines, macrolides, rifamycins and sulfa drugs do not eliminate the bacteria. Bactericidal drugs, including gentamicin and daptomycin have proved effective. (only by injection, IV or IM). Quinolones should be avoided for safety reasons.