Treating Lyme & Related Diseases - Disulfiram Treatment

Disulfiram is a very promising intervention in chronic lyme. The aldehyde problem likely would affect many people with chronic lyme. This particular patient has lived in a toxic mold infested dormitory for 10 months, and only recently got out of the dorm, and also stopped her supplements which included P5P, zinc, etc. one month before starting the Disulfiram.

Need to check KPU and B’s and taurine, cysteine levels, GSH before starting on Disulfiram.

[Robert Hedaya, MD, ABPN, DLFAPA, IFMCP]

Patient Comment

Dihydromyricitin, Auto-Brewery Syndrome, Yeast Infections

I have also heard that dihydromyricitin is useful for clearing aldehydes, and is available from Amazon. Dihydromyricetin . . . a flavonoid component of herbal medicines, counteracted acute alcohol (EtOH) intoxication, and also withdrawal signs in rats including tolerance, increased anxiety, and seizure susceptibility;

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292407/

In struggling with the same problem described above, I came across this article on Auto-Brewery Syndrome, which I suspect is not rare in chronic lyme patients who have undergone years of antibiotic treatment. The article offers an alternative explanation for what may be an intrinsic difficulty with disulfiram treatment of chronic lyme patients, namely that many may have excess aldehyde production due to persistent yeast infections.

Auto-brewery syndrome or gut fermentation syndrome is a condition in which ethanol is produced through endogenous fermentation in the gastrointestinal (GI) system.

https://www.ncbi.nlm.nih.gov/books/NBK513346/

In my experience, the only way to tolerate disulfiram for a person with a severe, chronic yeast problem is to combine many types of antifungal treatment with strict adherence to a ketogenic diet - not more than a gram or two of carbs at a time. Maybe this will improve with NAC, taurine and dihydromyricitin, but I'd sure be interested in any other ideas you come up with about this problem! Also, if anyone can comment on the extreme allergies and food sensitivities that seem to be associated with disulfiram use that would be much appreciated too.

LLMD Comment

Quite a complex metabolism and pharmacokinetics. I speculate that CS2, one of its breakdown products, may be important in anti-borrelial effects and including ? good penetration in to biofilm. It is on the order of the size of CO2. Sulphur sits directly below Oxygen on the Periodic Table.

LLMD Comment

I have heard from several who have used DSM.

All have had to start on tiny doses, and because it has a long half life, can start with twice a week!

Seems to take a VERY long time to be able to raise the dose- months!

But by the time they can tolerate a full dose, and maintain it for 6 weeks, they seem go into a full remission.

I always recommend an aggressive GI yeast cleanout before starting this to minimize GI alcohol production.

I even gave copies of Dr. Liegner's article to pharmacists who were puzzled by the uptick in DSM prescriptions.

Will be interesting as more gain experience.

LLMD Comment

One of my patients reported many fewer side effects on Teva disulfiram than with another generic (he didn’t remember the name of the other manufacturer).

Patient Comment

The reaction described is consistent with MCD…Mast Cell Disorders…which there is a high rate in Lyme/Bartonella patients. Just because you have a reaction does not mean it is an allergy.

Claritin is the weakest of the three antihistamines, so Allegra or Zyrtec should be considered in these patients. Compounded Ketotifen may be very helpful. If the Disulfiram is a tablet…then wash the dye coating off…even if it is coated in white. The inactive ingredients can be very problematic.

Disulfiram for Lyme Facebook

https://www.facebook.com/disulfiramforlyme/

LymeNet Post By Patients

On The Disulfiram Protocol

http://flash.lymenet.org/scripts/ultimatebb.cgi/topic/1/137824?

Patient Comment

CAN A DRUG USED TO TREAT ALCOHOLISM BE THE NEXT TREATMENT FOR LYME DISEASE? So this is intriguing….A drug used to help alcoholics stop drinking alcohol has been identified as killing all forms of Borrelia in the laboratory, as well as having efficacy against Babesia. Looking for better ways to treat Borrelia, Dr. Kim Lewis of Northeastern University began testing Disulfiram (Antabuse) on Borrelia in his lab after learning that it has antimicrobial and antiparasitic properties. His research found that the Disulfiram killed the spirochetal form of Borrelia, the cyst form, and it dissolved the biofilms. He presented his findings at a conference in 2016. Some patients who had heard about the effectiveness of the drug against all forms of Borrelia began asking their doctors to prescribe it to them.

For the past couple of years, an increasing number of patients worldwide have begun taking Disulfiram for the treatment of their chronic Lyme disease and Babesia symptoms. They have been reporting the results on a Facebook page called “Disulfiram for Lyme Support Group (Antabuse)”. What is happening worldwide is a real field study with brave patients leading the way for us to learn from their use of the drug to treat Lyme and Babesia. Each day, the administrator of the site asks patients to check in with information on how they are doing. They have been logging the information and have been able to provide some insights.

This is a new use for this old drug and proper dosing is yet to be proved. There is a controlled study being formed by Columbia University and patients can learn if they qualify for the study by reading the information found at this link:

https://clinicaltrials.gov/ct2/show/NCT03891667

One of the concerns that patients on the Facebook page have expressed about the Columbia University study is the dosing. The study plans to dose participants at 500 mg per day of Disulfiram. No mention is made as to whether they are starting the patients on a much lower dose and then increasing over the course of a few weeks to reach the 500 mg daily. The patients taking Disulfiram are adamant that it must be started with very low doses – some are starting at 125 mg once every three days, while others are starting at 62.5 mg once every three days and working up from there. The consensus on the Facebook page is that if a person has to work while taking the Disulfiram, then the lower dose is recommended. It appears as though the drug is to be taken for a period of about four to six months, but again, there are no clear guidelines since this is a new use for Disulfiram.

Die off of the bacteria can be intense with this drug, according to the many patients reporting in to the Facebook page. Some of the patients have experienced some neuropathy - a potential side effect - and later posts have indicated less of this side effect when patients go very “low and slow”. A smaller number have experienced some brain fog, and many report feeling fatigued.

However, for many of the patients reporting in, the results are very astonishing – chronically ill patients for years feeling much better, clearer of mind, and many without relapses after stopping the drug. The treatment duration is thought to be approximately four to six months.

We are in the infancy of discovering whether Disulfiram will be a viable replacement for antibiotics in the treatment of Lyme and Babesia. It is really exciting to see the changes made by the patients reporting in on Facebook, but it is also clear that the improvements have come at a cost of having to go through some extensive herxheimer reactions. Each patient is encouraged to follow recommendations for detoxing and to set their own pace. I would encourage anyone considering trying Disulfiram for the treatment of Lyme and/or Babesia to spend time reading the posts on the Facebook page, because there is so much to be learned from the pioneers who have been brave enough to try this new treatment. Please have a detailed discussion with your medical provider before starting this medication - not all treatments are for all people.

One thing is clear – no alcohol can touch the patient’s body when taking Disulfiram. Remember, the drug has been used to treat alcoholism. When we drink alcohol, our bodies convert it to acetaldehyde (a toxin) before it gets converted to acetyl acid (non-toxic). Disulfiram does not allow the conversion from acetaldehyde to acetyl acid, so if alcohol is consumed, or if it touches your body, you become loaded with the toxic acetaldehyde. Some patients who did not change their personal products have reported getting a headache after using shampoo with alcohol in it, or getting sick from using toothpaste with sugar alcohols in them. It takes vigilance to ensure that you do not consume any alcohol or let any alcohol touch your body when taking Disulfiram.

Since Candida also puts off acetaldehyde, which will not be converted to the non-toxic acetyl acid while on Disulfiram, it makes me wonder if doing a Candida cleanse before starting Disulfiram would be a good idea. Many people have leaky guts and Candida overgrowth due to improper diets – primarily diets high in carbohydrates and sugar, which feed Candida. There has been some talk on the Facebook page about cleaning up the diet before starting the drug, and it seems like doing something to reduce Candida might be a good idea, too. Time will tell.

It has also been noted in the Facebook page that certain supplements may be contraindicated when taking Disulfiram, and I recently read that drinking green tea is not recommended while taking the drug.

Discussions about the use of Disulfiram are on the agenda of all of the Fall conferences on tick-borne diseases. I think we are going to be hearing a lot more about the use of this old drug for a new purpose.

The first case studies published in a medical journal were recently published by Dr. Kenneth Liegner, who practices in New York. His paper highlights three cases of chronically-ill patients with tick-borne diseases who were treated with Disulfiram. His paper is here:

https://www.ncbi.nlm.nih.gov/…/PMC6627205/pdf/antibiotics-0…

Dr. Daniel Kinderlehrer, who practices in Denver, Colorado, also published a post on his experience with using this drug in the treatment of tick-borne diseases. His post is here:

https://www.lymedisease.org/disulfiram-kinderlehrer/…

Dr. Kim Lewis’ original conference presentation where he talks about his laboratory findings can be found within this YouTube video:

https://www.youtube.com/watch?v=hCGZL7Wa6bc

Another incredible resource is the following video in which Dr. Leigner spends over two hours answering questions about Disulfiram for the treatment of Lyme disease and what is known at this time:

https://www.youtube.com/watch?v=8COpz0YQGHU

Link to information here- https://www.facebook.com/thomas.grier1?__tn__=%2CdC-R-R&eid=ARBJT00e5RggSipNrPfY7c2apFDRavANeR8wCugGyVHgHB7Za8u-25jzJxv5egqAN2xCu4SOUaPnmBlU&hc_ref=ARRDIrkxEofnXlSOYr5EwRMM4lZb9MyUGJmiKCfiknhiQn_7xS4B4OLO4hh7FMXHXbg&fref=nf

LLMD Comment

The impact of aldehyde processing and what it may mean for the Asian population.

Physiol Rev. 2014 Jan; 94(1): 1–34. doi: 10.1152/physrev.00017.2013: 10.1152/physrev.00017.2013

PMCID: PMC3929114 PMID: 24382882

Targeting Aldehyde Dehydrogenase 2: New Therapeutic Opportunities

Che-Hong Chen, Julio Cesar Batista Ferreira, Eric R. Gross, and Daria Mochly-Rosen Department of Chemical and Systems Biology, Stanford University, School of Medicine, Stanford, California; Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil; and Department of Anesthesiology, Stanford University, School of Medicine, Stanford, California

Abstract A family of detoxifying enzymes called aldehyde dehydrogenases (ALDHs) has been a subject of recent interest, as its role in detoxifying aldehydes that accumulate through metabolism and to which we are exposed from the environment has been elucidated.

Although the human genome has 19 ALDH genes, one ALDH emerges as a particularly important enzyme in a variety of human pathologies. This ALDH, ALDH2, is located in the mitochondrial matrix with much known about its role in ethanol metabolism.

Less known is a new body of research to be discussed in this review, suggesting that ALDH2 dysfunction may contribute to a variety of human diseases including cardiovascular diseases, diabetes, neurodegenerative diseases, stroke, and cancer.

Recent studies suggest that ALDH2 dysfunction is also associated with Fanconi anemia, pain, osteoporosis, and the process of aging. Furthermore, an ALDH2 inactivating mutation (termed ALDH2*2) is the most common single point mutation in humans, and epidemiological studies suggest a correlation between this inactivating mutation and increased propensity for common human pathologies.

These data together with studies in animal models and the use of new pharmacological tools that activate ALDH2 depict a new picture related to ALDH2 as a critical health-promoting enzyme.

I. INTRODUCTION Throughout their lifespan, every organism is exposed to numerous damaging agents. Some are formed endogenously, while others accumulate following ingestion of food or exposure to environmental pollutants. There are three sets of active responses to these damaging events. The first set provides a shield from these damaging agents by quickly detoxifying them through enzymatic reactions

8/6/2019 Targeting Aldehyde Dehydrogenase 2: New Therapeutic Opportunities

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929114/?report=printable 2/77

or through sequestration of these agents (e.g., phase I and II detoxifying enzymes). The second set of responses involves a damage repair system (e.g., proteolysis, DNA repair), and the third set activates programmed cell death (e.g., apoptosis), thus preventing propagation of the injury. It is not surprising that many diseases are associated with a failure of one or more of these three sets of protective mechanisms.

Many recent reviews cover literature on the repair mechanisms and on programmed cell death activation (52, 92, 263, 328). In this review, we focus on one detoxifying enzyme that provides a critical shield from damaging agents that arise both endogenously and exogenously from exposures to the environment: aldehyde dehydrogenase-2 (ALDH2).

However, many other detoxifying enzymes have also evolved. The best characterized detoxification enzymatic system (also termed phase I system) is encoded by the cytochrome P-450 gene superfamily, consisting of 57 different genes, that encode the enzymes involved in ∼75% of all drug metabolism in humans (103, 104, 340).

Aldehyde dehydrogenase (ALDH) is another gene superfamily of phase I oxidizing enzymes that is responsible for the detoxification of biogenic and xenogenic aldehydes.

Over the years, the field of ALDH research has been frequently reviewed and updated. Notably, Dr. Vasilis Vasiliou's laboratory at the University of Colorado's Health Sciences Center has maintained a database of the ALDH gene superfamily for public viewing at www.aldh.org. Table 1 lists these ALDHs and some of their characteristics.

LLMD Comment

For People of Color

Genetic polymorphisms of humans affecting the tolerance for the effects of this drug have been well surveyed among a wide range of ethnic groups, including 35–45% of East Asians (i.e., Chinese, Japanese, Korean, and Taiwanese) (59, 99).

The presence of lower baseline enzyme activity, of the enzyme that is blocked by disulfiram is manifested by a significantly increased risk of stronger symptoms at lower doses of the characteristic facial flushing, headaches, nausea, dizziness, and cardiac palpitations after consumption of alcoholic beverages.

Aldehydes

From Dr. Frances Jurnak

“We generally think of glucose as a cyclic molecule, whereas the cyclic form is in equilibrium with a linear form which is an aldehyde I suspect, but haven’t researched it thoroughly enough, that diabetic complications are due in part to aldehyde damage and that ketone diets partially improve health by minimizing aldehyde damage.

Alternative approaches would be to supplement with NAC and taurine to neutralize metabolically formed aldehydes that are not cleared rapidly enough by normal cellular mechanisms.

I think that proper attention to aldehyde toxicity would initiate the revolution that psychiatry needs to be more effective. I believe this approach could help treat at least 50% of psychiatric illnesses.

Dr. Jurnak,

Thank you for your lengthly response. I will digest it and respond. It is rare, in my opinion, these days to find such a well done review so, my hats off to you. I do a fair bit of lecturing, (scheduled to talk in Chicago and Stockholm in April) and Denver in July. These talks are geared toward psychiatric disorders and neurodegenerative disorders. No one (I am not in the ASD world) is talking about aldehydes, so I need to understand the relevance, and figure out how to test. Ideas welcome!

I will be traveling tomorrow and then I will be at an HBOTconference for several days. I look forward to reading your response and probably will have some questions.

Are you teaching outside of the university at all?

Bob

Robert Hedaya, MD, ABPN, DLFAPA, CFM

www.wholepsychiatry.com [1]

Clinical Professor, Georgetown University Hospital

Faculty, Institute for Functional Medicine

On Jan 1, 2019, at 1:44 AM, jurnak <jurnak@uci.edu> wrote:

Dr. Hedaya,

Thank you for your kind comments about my review on the “Pivotal

Role of Aldehyde Toxicity…”

As to your questions, there are three B6 vitamer forms: pyridoxine

(PN), which belongs to the alcohol class; pyridoxal (PL), which

belongs to the aldehyde class; and pyridoxamine (PM), which belongs

to the amine category. It is my understanding that PN mostly

converts to PM, which then converts to PL. P5P (or PLP) is the

phosphorylated form of PL. Some papers, though I can’t find the

sources now, claim that PN is first converted into PM, and then into

PL.

Some people have a difficult time converting PN into PM or PM

into PL. For these people, the best B6 supplement form to use is

P5P (PLP) even though the P5P form is initially dephosphorylated to

PL as it passes through any membrane for cellular absorption. After

the neutral form (PL) passes through the membrane, the phosphate

group is again added back within the cell by the protein pyridoxal

kinase.

So why give the P5P form if it is first dephosphorylated

into the inactive form (PL) to pass through the membranes? The

answer seems to be that one potentially problematic step is

eliminated in the conversion of PN to PM or in the conversion of PM

to PL. It is difficult to know a priori if a person has any

difficulty in converting PN to PL, so I have always used a

combination of PN and P5P (PLP) as the supplement. Otherwise, the

choice can be made by trial and error. Although I can’t find a

good publication that summarizes what I have just stated, the

following web site shows the different B6 vitamer structures:

http://www.newworldencyclopedia.org/entry/Vitamin_B6

To answer your second question, P5P is a reactive aldehyde, but the

P5P form is generally bound to something in the body, such as a

specific B6-dependent protein. PL and P5P are not found in free

forms unbound to other molecules, unlike both PN and PM, which are

found in free forms unbound to other compounds in the body. So the

binding of P5P to a select B6-dependent protein protects P5P from

damaging other molecules, unless these molecules are toxic

aldehydes.

In writing the review you read, I was always curious as to why so

many ASD children benefit from vitamin supplementation, at least

according to their parents, if not their physicians. Well, I

finally have some answers and am working on another, shorter, more

readable review. Here is a quick synopsis. Most people think that

reactive oxygen species (ROS) do a lot of damage, which they do, but

RORs are short lived (micro to nano seconds) and can be neutralized

by antioxidants, such as vitamins C and E.

However, when the

oxidative stress is high enough to overcome the normal cellular

antioxidant mechanisms, the ROS reacts with the lipid membranes,

creating the very toxic lipid aldehydes, which live for 1 to 2 days,

pass through the original cell membrane, and damage neighboring

cells. When the oxidative stress becomes so great, the cell goes

into survival mode to prevent the spread of the lipid aldehydes to

neighboring cells.

In essence, the original stressed cells uses

everything it has to neutralize these toxic aldehydes, including (1)

reacting with and inactivating key proteins; (2) binding to and

eventually mutating DNA, and (3) reacting with many smaller

biomolecules, such as glutathione, which are effluxed as an

aldehyde-glutathione complex, out of the cell and into the urine

(similar to what NAC does in acetaminophen poisoning). The next

biomolecules to recruit in helping to neutralize the toxic aldehydes

are the B vitamins, with P5P being the most active in this sense

because it is an aldehyde, which likes to condense with other

aldehydes.

I found published papers, which independently show that

P5P neutralizes aldehydes created by oxidative stress in bacteria,

fungus, plants, and animals. Although the other B vitamins are not

aldehydes per se, they all share a chemical motif, which can react

with aldehydes, though they are less reactive than P5P. So in the

event that the cell runs out of P5P to neutralize the aldehydes,

then the other B vitamins are called in to help the situation.

These is sporadic data, which demonstrate that most B vitamins can

neutralize toxic aldehydes under high oxidative stress conditions.

Presumably these B-aldehyde condensation products are effluxed from

the cell, but do not show up as just one strong peak of a B vitamin

in the urine, because there are plethora of different aldehydes to

which they bind. This process would, of course, leave the cell

deficient in B vitamins, used in critical metabolic processes. One

can give high doses of B vitamins to replace the lost B vitamins,

but I think a better approach is to supplement with one or both

aldehyde scavengers, NAC and taurine, which are known to neutralize

toxic aldehydes.

I had it wrong in my review, but taurine is

neither an antioxidant or reacts through its S group. Instead,

another chemical group on taurine serves to neutralize toxic

aldehydes. So the approach that I have taken and am recommending to

others is to supplement with high doses of NAC and/or taurine to

scavenge out the toxic aldehydes and then to supplement with

moderate doses of B vitamins and their activating minerals, to

replace the micronutrients that have been lost.

This approach should work well in any case in which oxidative stress

occurs, whether for genetic or environmental reasons. One

consideration, however, is that the pharmacokinetics of both NAC and

taurine are not impressive. Both have short half-lives, of the

order of .5 to 1.5 hours. To circumvent this problem, it is

possible to purchase slow release forms of NAC from Jarrows, I

believe.

As for the taurine, I have it specially compounded with a

slow release factor. Also from the existing known pharmacokinetics,

I believe that NAC works best for most organs, but if the source of

the oxidative stress is in brain cells, then taurine will work best

because it more readily passes the BBB.

As you know from my review, I think that ASD is just one disorder

that is caused by aldehyde toxicity. I am estimating that toxic

aldehydes play a role in 50% of other disorders, such as depression,

ADHD, TS, OCD, schizophrenia, and over the longer term, cancers,

Parkinson’s and Alzheimer’s. A major source of oxidative stress

is genetic, but I have found that infections of all types –

bacterial, viral, fungal, etc. can increase oxidative stress and

cause a depletion of B vitamins in the oxidatively stressed cells,

thus leading to neurological problems 0 to 3 months after the

infection, as was recently reported in a medical journal. There is

no doubt in my mind that PANDAS and PANS phenomena are really caused

by B vitamin depletion after an infection. When I first discovered

the likely pathway that was causing motor tics, I gave

B1 and Mg and tics were gone in 30 hours! If I stopped

these supplements, the tics returned. I was able to trace the B1

deficiency to a problem with errant genes associated with

alcoholism.

If you are dealing with psychologically disturbed patients, it is

particularly important to determine if familial alcoholism is

present among any relatives. I have found that the Eastern European

population often carries a promoter mutation, which keeps the ADH4

gene turned on. In the absence of imbibing ethanol, the AHD4

protein is promiscuous and cleaves retinol and norepinephrine,

leading to immune problems, as well as inattentive ADHD, depression,

and anxiety. One way to check for this is to measure the

norepinephrine metabolites in the urine as well as the

norepinephrine in the blood. If there are low concentrations in the

blood, but high levels of metabolites in the urine, then the data

suggest that there is high norepinephrine turnover, consistent with

a promoter error in the ADH4 gene. The best way to treat for this is

to supplement with cod liver oil containing the retinol form of

vitamin A – at least 8000 IU daily. (Beta-carotene is not vitamin

A and does not serve help this problem).

I have seen remarkable

improvements in all the symptoms listed with this retinol treatment.

Please keep in mind that a vitamin A deficiency doesn’t always

result in night blindness because in this genetic case, there is

little retinol but plenty of retinal (an aldehyde) needed for

vision.

I sincerely hope that psychiatry does a lot more to investigate the

beneficial properties of selective micronutrients. I have heard of

the emerging field of Nutritional Psychiatry but I would argue that

one cannot eat their way out of some of these genetic and

environmental problems – one must use higher concentrations than

what is available in a typical good diet.

I have only scratched the surface of what I have learned. I am

working on a few medical reviews and one day hope to write a general

audience friendly book called “Stinky Feet and Other Clues… to

the Causes of Neurological Problems”

Don't hesitate to contact me if you have any other questions. Happy

New Year to you.

Frances Jurnak, Ph.D.

Professor Emerita of Physiology and Biophysics

School of Medicine

University of California, Irvine

Children & Disulfiram

Basal Ganglia Infarction in a Child With Disulfiram Poisoning

Disulfiram for Alcohol Use Disorders in Adolescents

Last Updated- January 2020

Lucy Barnes

scc