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Friday, July 16, 2021

Methylene Blue and Lyme


Is there a magic bullet and is it methylene blue?  Methylene has been shown to have activity against malaria/Babesia, Bartonella and Lyme.  It has activity against persister forms of Bartonella and Lyme (borrelia) as well as biofilms.  It is active against coronavirus (Covid).  It has neuroprotective effects, inhibits tau proteins in the brain and therefore may help fight Alzheimer’s disease and other neurodegenerative brain disorders. It has been used with photodynamic therapy to treat cancer, including lung and breast malignancies. The drug is also known to strong psychoactive properties and has been shown to benefit patients with psychiatric illness, including bipolar disorders.

It has serotonergic effects and cannot be taken by patients on antidepressants.

The drug was developed in the late 1800s.  No patents, no money, and no research--may be a problem.  It is not commercially available (orally), but capsules are prepared by some compounding pharmacies.

The most common use in the past century has been the treatment of methemoglobinemia, a relatively rare condition in which oxygen carrying hemoglobin is converted to a non-active form, generally a genetic disorder trigged by an outside agent.

It sounds like the MacGyver of drugs – or Swiss army knife of drugs. 

Lyme patients are not infrequently desperate, suffering despite much standard and experimental therapy, looking for the next thing.

The question is: Is methylene blue (MB) safe and effective for chronic Lyme patients? Is it finally the Holy Grail?

First off, MB has been shown to be safe and effective in humans (malaria).  It was the first synthetic anti-malaria drug, preceding commercial penicillin by about 50 years.  Recent studies employ high doses of the drug administered over 3 days. Malaria has become more resistant to a wide array of therapies and MB has been resurrected and dusted off as if it is something new.  Short term use does not provide cover for long-term usage, the hallmark of Lyme and associated diseases therapy. 

Effectiveness for Lyme patients is inferred from in vitro (test tube) studies (Lyme, Bartonella, Babesia).

Methylene blue has broad spectrum antimicrobial activity against protozoans, bacteria and virus.  Generally I prefer narrow spectrum drugs.  A scorched earth drug may be problematic. I don't think we know anything about its effect on the microbiome, especially with prolonged use. 

MB is undergoing clinical in vivo trials for the treatment of Covid. This adds a log to the evidential fire of drug safety.  The Covid trials employ low doses, MB 100 mg twice daily but for only 5 days. Malaria trials have used higher doses but only for 3 days--10 mg/kg for 2 days followed by of 5 mg/kg for one day.  For example, a typical 70 kg man receives 700 mg for 2 days followed by 350 mg on the third day.

It should be clear that long-term clinical use for non-studied infections is entirely experimental. But at this point there are numerous anecdotal reports which praise MBs efficacy and appear to support safety when used this way.  

I spoke at length with a patient today who is a big fan. He has tried various doses and found 200-400 mg per day to be an effective dose. He has found it works well only as part of cocktail therapy.  One therapy, Zithromax, Rifampin and MB worked well for Bartonella.  For Babesia it has been effective when combined with artemisinin (or Coartem) and primaquine (or tafenoquine).

MB is now part of the Lyme disease armamentarium. It has been in common use, in some corners for more than 2 years. Treatments must always be individualized.  

If the drug is used, I recommend starting with a low dose like 50 mg twice daily and gradually increasing as tolerated.

All drugs have numerous side effects and drug interactions. Please do not purchase MB on the internet and treat yourself. The consequences could be disastrous. Don't have a fool for a doctor and a fool for a patient. 

Methylene blue plays an increasingly important role in the management of tickborne disease and may ultimately have other important clinical applications.  



Wednesday, June 17, 2020

Old drug, new drug: nimodipine

Mary, a 35 years old woman was extremely healthy – until she wasn’t.  The culprit was Lyme disease, an ancient, thin, spiraled bacterium called a spirochete – one that is insidious and opportunistic.  But Lyme disease is more often than not so much more.

Our ability to stave of infection frequently depends on a healthy immune system.

Many factors can adversely impact normal immune function.  Stress is a huge factor.

Lyme and Mary’s immune system had been locked in mortal combat with Lyme for some time. Life stressors mounted and a tipping point was reached. Lyme won the battle and spread throughout her body attacking many organ systems.

These were some of the stressors. Her father died of a sudden heart attack, a child was diagnosed with autism, her husband was emotionally abusive and this led to an ugly divorce.

Mary managed stress by gardening – more and more. Ironic.

The fatigue was overwhelming. It felt like she had been run over by a Mack truck. Mary was diagnosed with chronic fatigue syndrome/CFS, myalgia encephalitis or systemic exertional intolerance disorder – three names for the same thing. She simply could not function. Sleep was miserable, too much or too little. She struggled to get out of bed. She needed help with simple household chores. She rarely got dressed; she no longer put on makeup and she took few showers. Sadly, Mary blamed herself for her poor health. She lost all self-esteem.

Headaches diagnosed as migraine came out of the blue. Pounding, throbbing, ice pick, with temporary loss of vision nausea. The pain was unbearable.  Several doctors were of no help and she seriously considered suicide.  

Symptoms mounted. Doctors said it was psychosomatic. Family members believed the doctors. Mary was abandoned by both family and friends.

Mary had so many symptoms, symptoms which inexplicably came and went.

She frequently felt like she had the flu. She had night sweats, drenching at times.

Her whole body hurt at times. Sometimes the pain was localized to a particular joint or body part.

She experienced frightening cognitive impairments, poor memory, trouble thinking clearly, difficulty finding words. She frequently felt disoriented and depersonalized. She experienced depression, air hunger, sudden bouts of crying, intermittent joint swelling, weakness, numbness and tingling and trouble sitting up and standing.  

With changes in posture, from lying to sitting and then to standing symptoms her heart raced, brain fog increased, she became dizzy, felt she would black out and had to immediately sit down or lie down.

We know Mary has Lyme and Babesia. But she is not going to get better if we treat her only with antibiotics and anti-Babesia drugs.

Migraines:  There are a variety of new ways of treating migraines including those that antagonize calcitonin gene related peptide, a relatively new and sometimes successful therapy. Migraine therapy will be reviewed in detail in the future.

POTS:  With further questioning Mary had problems with her bowels, bladder, vision and temperature regulation.  POTS is a piece of the larger disease, dysautonomia or broken autonomic nervous system. A patient history, exam with measurement of vital signs in different positions can confirm the diagnosis. A tilt table test is unnecessary. There is a close connection between dysautonomia and CFS. Mary’s heart rate only increased by 20 points with standing not the requisite 30. Of course she was too dizzy to stand for long.

There are many effective therapies which usually work when prescribed properly. Described elsewhere.

Even when tests for POTS are negative, patients with chronic fatigue syndrome may benefit from POTS’ therapies including salt tablets and fludrocortisone.

Lyme patients, patients with chronic fatigue syndrome and patients with POTS all complain of brain fog. An old/new drug may be incredibly effective.

The calcium channel blocker nimodipine, which must be prescribed carefully dilates cerebral blood vessels and increases blood flow in the brain treating chronic encephalopathy. Patients with Lyme, POTS and CFS may all suffer with dysregulated blood flow to the brain.

Nimodipine may work well with other neurotropic drugs including Adderall and Namenda.

I have treated Mary for less than a year and she has done very well.

She is back at work, part time, telecommuting and even smiling at times.

Friday, May 8, 2020

Summer flu, Lyme or Covid?

Lyme patients, those suffering with chronic illness must be considered immune suppressed and at higher risk for serious Covid related illness.

There are dangers at the edge of the woods and dangers from neighbors and family.  The world is surreal.  But it is the real world, the one we have to live in.

The Covid nightmare, is in some ways like 911, a watershed event that will forever change our prior naivety regarding person to person transmission of deadly germs.

I am optimistic that meds given early in the course of illness will prove effective. Current candidates include

The summer flu. It has long been acute stage Lyme misdiagnosed by the doc-in-a-box. Now we have another bigger worry.

The presentation of the two illnesses can in some cases be identical:  fever, malaise and achiness. 

Testing should be done, although deficient for both.

Do not get the Covid antibody test. 100 non-vetted companies, tests.  Get the nasal swab sent for PCR which directly identifies the RNA virus. There are still false negatives and you may want to repeat the test.

Lyme testing. Many of us are operating remotely doing telemedicine. That obviates the ability to send specimens to more reliable Lyme labs:  Stony Brook, MDL, IgeneX etc. We have to manage with LabCorp or Quest.  Get the Western Blot test, not the reflex to WB.  Also get C6 peptide.  Coinfection testing must include Babesia duncani, WA1, IFA IGG.

Do not worry too much about poor Lyme blood tests.  Patient history is the most reliable test.

If there is any doubt treat both.   Doxycycline and (ivermectin which many Lyme patient feels has been effective) is a good starting place. If you are worried about sun induced toxic skin reaction, I recommend you stay in the shade and tough it out for at least 3 weeks. This is the only drug that has widespread effectiveness against many coinfections.  Amoxicillin, Ceftin and Minocycline are not adequate substitutes.

Search my blog for more about ivermectin.

Despite what you may have heard or red otherwise, Covid cases and deaths are very underreported.  Same as Lyme.  With Lyme some elected officials have helped promote the cause.  With Coivd, unfortunately, it is the other way around.


Wednesday, April 29, 2020

Telemedicine vist

Telemedicine visit

Your doctor does not want to see you in his/her office. At least your doctor should not want to see you in his/her office. Not now.

We are in the middle of a pandemic – goes without saying. Covid-19 stands for coronavirus disease 2019. Its novel because it is new and something the human immune system has not previously encountered.  We have experience with other deadly coronavirus infections. SARS had a mortality rate of around 15% and MERS was scary deadly with a mortality rate in the smallpox range, 30+ percent. Covid-19 is less deadly but much more contagious. The true numbers of those infected and the mortality rate are to date unknown.

Covid-19 is the dreaded pandemic, more than an epidemic.

An epidemic occurs with rapid dissemination of an infectious illness through a susceptible population. It may be worldwide as occurs yearly with influenza.

A pandemic is worldwide dissemination of a new deadly infectious disease. This is the stuff of sci-fi movies.

A friend’s parents live in a Maryland Assisted Living facility and tested positive for Covid.  Both presented with diarrhea and without fever or cough. Unusual presentations may not be unusual.

A typical physician’s medical examination room is an 8X10 or somewhat larger rectangle with relatively poor circulation. It is a perfect incubation chamber for coronavirus. Infectious particles may persist in air – droplets and aerosols and on incompletely sterilized surfaces. I am more concerned about transmission to patients from asymptomatic medical staff.

Covid is present in at least two thirds of our state’s nursing homes. Family members are barred. The virus is invariably introduced by unwitting staff members.

When possible, and it mostly is, stay at home and stay safe.

Telemedicine in Maryland is defined as a medical encounter with the use of an audiovisual aid such as a computer using a HIPPA approved platform. Telephone calls are excluded from the definition of telemedicine.

State licensure rules regulate the use of this technology for out of state patients. Most states have loosened the rules. But changes in regulations vary tremendously from state to state.

Telemedicine is more personal than phone medicine and feels more like a normal doctor-patient visit. I can get a sense of the patient’s general overall health based on his/her appearance. Objective data is missing but patients can help fill in some of the blanks.  Patients have easy access to home BP devices, oximeters, scales and thermometers. I can look at a throat, rash or swelling. I can see where pain is without having to guess. I can get a general sense of breathing based on observation. And many patients can get an EKG with a wristwatch or other portable device and show me the tracing on the screen. Prescriptions are electronic.

If a patient needs more advanced care, at an ER for example, the platform is extremely helpful vs a phone call. 

Please use the or another similar platform. It’s easy to use and does not require an app. And I can hear much better as well.

Wednesday, March 4, 2020

Mold toxins in perspective, a science based approach

Mycotoxins – the noxious chemical defense of these ancient and troublesome microorganisms.  Recently a  patient showed me a urine test. Mycotoxins were present in high concentrations. The patient was prescribed cholestyramine and the next test was almost clear. He said “his mold level” had improved. He fundamentally misunderstands the problem.

First, we want to know if he is right about his “mold level.” Are there a significant number of pathogenic mold organisms living in our body actively secretin caustic toxins?  Mold is not generally found in our bodies, at least at high or clinically significant levels.

Sure, we are all a waking zoo of microorganisms: bacteria, yeast viruses, perhaps some protozoa but no mold. Although yeasts and mold are cousins and frequently killed by the same drugs they act very differently.

I ask again: why are the toxins found in our urine at measurable concentrations.

Most readers likely believe that the primary source is largely aerosolized spores emanating from hiding places – wet basements and the like.

In actuality the biggest source of mold/mold toxin is food.  Many foods we eat all the time may have high levels of mold. We have all found moldy bread in the fridge at one time or another (I certainly have). Before the putrid green and blue areas appear mold long present. Just not in numbers easily observable to the naked eye. Our berries are covered in mold before the white exudate appears. Mold is present in many foods: cereals, grains, corn, fruit, peanuts and peanut butter, eggs, milk, meat, coffee beans, coffee – especially from our Keurig with its inaccessible wet, warm environs, a perfect culture media, etc.

The more serious, life threatening mold infections, for example aspergillosis of the lung or brain generally occur in those seriously immunosuppressed.  Ordinarily, aspergillus is a common food mold, a good source of aflatoxin and ochratoxins. Another common food mold, penicillin is a good source of ochratoxin. There are many other food molds and food toxins.

Black mold, Stachybotry lives in our homes. It eats cellulose, things like ceiling tiles, tiles and fiberboards. Its spores are aerosolized, along with very noxious trichothecene toxins.

Many mold toxins are xenobiotics recycled from liver produced bile to the intestines and back again endlessly (or perhaps 20 times). Enterohepatic recirculation may be beneficial in some circumstances. In this scenario the liver is assaulted by the same destructive toxins over and over again.

I have written about this system in a few posts. The bottom line is that this process explains why bile acid sequestrants (BAS) like cholestyramine and Wellchol work. Activated charcoal also works because at high concentrations it performs like a BAS. In fact, like the BASs, activated charcoal (24 gm daily) lowered cholesterol by 25%. These drugs grab bile acids and biliary toxins causing excretion through the colon – and the liver makes new bile acids, primarily from cholesterol.

The drugs  lower the overall level of toxins in the blood and therefore spare the liver and kidneys by a second mechanism.

 But we have not fixed or addressed the underlying problem.

Dietary sources of mold and mold toxins are significant.  We may need to seriously change our diets.

We may need to remediate our homes, especially wet basement areas if black mold spores are in the air.

But these molds do not really or should not really take up residence in our bodies.  They are not part of our normal microbiota.  But this in not always the case, especially with deep, chronic infection and immunosuppression.

 Where is the mold then hiding?  Sinuses, lungs and skin are possibilities. Specific antimicrobial therapy is indicated, either intranasally or with systemic agents.  The mold may be eliminated, or numbers significantly reduced. Retreatment may be par for the course.

A lot is made about epigenetics, especially MTHFR variants Genetic variations may interfere with “methylation.” DNA methylation is part of a switching -- turning genes on and off, with far reaching consequences. This is a real phenomenon. Complex and poorly understood.

Eliminating exposure to toxins is the most important part of therapy. You cannot get better if the fundamental problems is ignored.  BASs and vitamins for MTHFR can be given simultaneously- icing on the cake -- not the cake.  MTHFR for another day.

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.