9 days into dramatic improvement

[David Staup]

A bit more than a week ago I started taking about 5 mg of Diphenhydramine (Benadryl) every 3 hours and the results have been dramatic! I have seen improvements both physically and mentally.

I do not, as yet, understand the mechanism but can difinitively say that all signs that I atribute to apoptosis have been greatly reduced even while I have increased my activity level. I did reach and exceed my new limits (and am paying for it) but even that has been different. I'm being vague here so as not to seed expectations.

google benadryl and mitochondria or ATP or apoptosis and there is info there, I just can't figure out the links...Biologist are you out there?

If you want to try this, here is how I do it courtesy of a poster on the mito group:

dye free "liqui-gels" contain 25 mg, pierce one end with a sterolized pin or needle, squeeze out one drop into a "one gulp" amount of drink, put the pin back into gelcap hole and store for next dose. you will get 5 or 6 doses.

David

[Biologist]

Interesting, David. Keep us posted.

Biologist

[David Staup]

Day 15

I still don't understand the mechanism whereby the benadryl meadiates the apoptosis but clearly the point at which apoptosis occurs has been raised. I estimate that I have between 2 and 3 times as much energy available for use as I did before.....and I know why!

apoptosis requires energy (ATP)!

*http://www.fasebj.org/content/19/13/1783.full

I can't believe I never tripped to this before, everything makes so much more sense knowing this.

Not only is apoptosis initiated by ATP depletion, but the process further depletes ATP....cascade effect. When I raised the bar on apoptosis I immeadiatly had that energy available and the symptoms of apoptosis disappeared.
What are the global effects caused by high levels of apoptosis?

dehydration....
my liquid requirements are now normal, I don't get dry mouth at night, I don't have to pee at night.

electrolyte imbalance....
I have been able to cut back on electrolyte replacement.

constipation, intestinal dysmobility, illeus.....
I have had a "normal" BM every day since starting the benadryl!!! This is up from every 2 or 3 days at best and they have all been in the goldielocks zone... not to hard, not to soft! This has not happened EVER since statins!

Joint pain....
just brief episodes corrisponding to the 2 times I passed my new limits...this is most encouraging

Dark, cloudy, and foamy urine....

except for 2 times that occured after I knowingly went to far, my urine has cleared. More importantly my recovery time was JUST TWO DAYS. That compares to weeks before....

sleep disturances....
so far these have remained at relatively low levels



There is one effect, that I would not have associated with apoptosis, that has also disappeared (so far); myoclonic jerks

*http://house.wikia.com/wiki/Myoclonic_jerk


there are effects that have increased with my increased activity:

I have vasiculations in my calves that increase or decrease depending on activity level, those have increased...as they would have before

my neuropathy signs have also increased....I may up my B vitamins

Pitosis (droopy eye)....
this too has gotten more noticable with increased activity

my cognative issues are reduced and more noticable at the same time. It's funny, my memory is working well enough that I remember when I've forgotten things...no simple way to describe this and I have yet to tax my percieved improvement to determine exactly what my new limits are...I'm hopeful


That pretty much covers all my observations so far.

David

[Biologist]

Good to hear, David.

I know diphenhydramine is a powerfully bioactive molecule. Keeping your dosage as low as possible for your symptoms might be a good idea. I'm too busy to do much Internet reading on it now, but I hope you continue to report on it.

Biologist

[David Staup]

Day 25

I have repeated going past my new limits but rather than dropping to absolute minimum activity I tried dropping to my old normal. That did not work. It also extended recovery time when I did go to minimun it took 4 days to recover versus 2 the first time. That is still far better than the weeks it would have taken before I started the benadryl. While I have had a BM every day they have tended to harder and dryer at times following extended periods of overdoing it.

I estimate my improvement to have moved me from 6 to 7% of pre statin to 15%. while that may not seem to be much, it makes a world of difference to me.

Also I have halved the total daily dose by doubling the time between doses to 6 hours...


Now on to the mechanisms involved!!!


Statins cause mitochondrial swelling which can lead to cell death (necrosis and/or apoptosis):

"http://www.google.com/#sclient=psy-ab&hl=en&q=statins+and+mitochondrial+swelling&oq=statins+and+mitochondrial+swelling&aq=f&aqi=&aql=&gs_l=serp.12...78297.80406.1.84250.7.7.0.0.0.0.156.764.5j2.7.0...0.0.w6fU
MvohP0U&psj=1&fp=1&biw=994&bih=541&bav=on.2,or.r_gc.r_pw.,cf.osb&cad=b

Many of the cells that live have mito dysfunction. Reference Golumb et al

Mitochondrial dysfunction causes mitochondrial swelling that can lead to cell death (necrosis and/or apoptosis):

"http://www.google.com/#sclient=psy-ab&hl=en&q=mitochondrial+disease+and+mitochondrial+swelling&oq=mitochondrial+disease+and+mitochondrial+sw&aq=0w&aqi=q-w1&aql=&gs_l=
hp.1.0.33i21.3329.16063.2.19875.21.20.0.1.1.0.219.2573.9j8j3.20.0...0.0.ERqmH1RdaB0&psj=1&fp=1&biw=994&bih=541&bav=on.2,or.r_gc.r_pw.,cf.osb&cad=b


and finally some antihistamins INHIBIT mitochondrial swelling:

"http://www.sciencedirect.com/science/article/pii/0006300261904498

from link above:

"1. It is shown that a number of antihistamine drugs which prevent liver injury inhibit mitochondrial swelling at concentrations at which they do not affect electron transport or oxidative phosphorylation."

sometimes I amaze even myself!

David

[David Staup]

Ok, lowering the dose to every 6 hours was a mistake, went to every 4 hours and my energy and symptom levels are as last reported.

I am not the first to recognise the benifits of some antihistamines in a wide spectrum of diseases that are ultimately rooted in mitochondrial dysfunction or excessive apoptosis such as MS and other autoimmune diseases:

*http://www.ctsaip.org/create-pdf.cfm?id=5893


It is used along with some cancer drugs...

*http://www.ncbi.nlm.nih.gov/pubmed/16248764

There is also some conflicting evidence that antihistamines promote some cancers...you should consider this and do your own research if those cancers are in your family.


It's used in immune deficiency diseases to prevent apoptosis of T-Cells


there is way more on antihistamines and apoptosis out there. In some cases they promote apoptosis and in others it inhibits apoptosis, it boggles the mind.


*http://www.google.com/#hl=en&gs_nf=1&gs_mss=antihistamines%20and%20apopto&cp=28&gs_id=2a&xhr=t&q=antihistamines+and+apoptosis&pf=p&sclient=psy-ab&oq=antihistamines+and+apoptosis&aq=f&aqi=&aql=&gs_l=&pbx=1&bav=on.2,or.r_gc.r_pw.,cf.osb&fp=58e514120196b500&biw=1005&bih=540


David

[tyyosh]

David,
How is this going? I am back here reviewing the next wave of supplements and found your posts. Does the Benadryl make you drowsy?

Thank you

[David Staup]

Not at this dose..more alert if anything.

It is going pretty much as reported previously. The neuropathy has pretty much settled back to normal. I have also learned I have a higher heat tolerance, I can function up to current levels at temps maybe 4 to 6 degrees F. I stopped, for now, testing my new upper limits and have maintained a pace roughly 50% higher than before without problems.

I live in Texas so the heat is beginning to limit outside activities, other than short walks, to mornings on most days so for the next couple of months I'll just be maintaining.

I'm still doing research and am astounded at the number of diseases where this therapy could be of benifit. I took the paper of the MS study, with a description of the effects, to my lawyer's secretary, whose husband has MS, and asked her to take it to his doctors. She noted the difference in me right away and said she was going to pick up some benadryl on the way home. This will get out eventually.

I also have another possible antihistamine with the same properties, atarax should also work but I have not tested it.

David

[tyyosh]

I just got the regular mass email from Dr. Mercola's site and he has an article about dementia... following links from there, he has an article that says that anticholergenics (which includes Benadryl) deplete acetylcholine and therefore can make Alzheimers and dementia more likely or worse. Yikes!

[David Staup]

At the NORMAL dose maybe and beyond a point in alzhimers maybe...

But I can say definitively that, at these doses, MY cognative difficulties have improved dramatically. following is one of the reasons I started taking it, a post in responce to my first question about benadryl:

" My father's doctor had him take Benadryl when he had Parkinson's (which seems to be mito related in our family). My dad didn't have any
allergies, but it seemed to help with cognitive issues.

I have always been very sensitive to allergy medications, probably
because they tend to increase adrenaline which makes me worse. But I
have started using a very small amount of Benadryl (a few drops from the
dye-free capsules) and so far am fine. It really helped me with my
constant sleepiness which is the opposite of what you would expect from
Benadryl."

That in addition to the following responce is what started my experiment:

"My son has had WONDERFUL results with both natural and over the counter histamine blockers. He has had seizures for 9 years that were never controlled by medicine and most medicines made him 100% worse. We tried the histamine blockers that the neuro's had always told us to stay away from. The 2 that has made the biggest difference is dye free benedryl and atarax. YOU DO NOT TAKE THESE 2 Together. Both these do cross the blood brain barrier and for my son this is what HE NEEDED. HE IS NOW SEIZURE FREE first time in 9 years!!! The medical world has had no clue what happened to my son."

Since listening to conventional medical propaganda and suffering because of it I have tended to do my own research and experimentation. Chuckle, statins are still touted by most and Mercola's propaganda is just as bad in many cases..........

It's very simple to test this for yourself, you decide

David

[David Staup]

First responce from an MS group


Yes, my wife, who was diagnosed with MS in 2006, has been taking 5 mg of Benadryl every four hours for about three weeks now. She has experienced a dramatic increase in energy, an end to persistent conjunctivitis (redness of the eyes), and has not needed to apply her metronidazole cream for rosacea. She has also been able to stop taking Tramadol three times daily for back pain. The pain is still there, but it is more easily treated with the occasional NSAID or 5 mg of Valium. Here is a link to a patent application .pdf covering this treatment in greater detail. It is very technical, but it might be interesting to physicians and others with a scientific background. My wife takes slightly less than half a teaspoon of generic children's Benadryl (diphenhydramine) every four hours.

*http://bit.ly/NRE0BI

David

[Biologist]

Hi, David.

I have been experimenting using Benadryl ( *http://en.wikipedia.org/wiki/Diphenhydramine ) some recently partly due to your interest and findings. Some comments and observations:

* I am very sensitive to it. I am wanting to find the smallest dosage that will work as an antihistamine for me (chronic rhinitis/sinusitis) as the side effect of making me sluggish in the day is an issue. Ironically, while it makes me sleepy, it does not seem to work well getting me to sleep at night.

Taking it along with pseudoephedrine ( *http://en.wikipedia.org/wiki/Pseudoephedrine ) may be a good idea for some people; and some formulations use to use the combination of the two. This is a decongestant and is a bit of a stimulate which may counter the drowsiness some. As you may know, you must sign for this stuff at the pharamacy as it can be converted in the lab to methamphetamine. The alternative you can still buy "over the counter" does not work for me; and is reportedly a non-bioavailable form of the active ingredient in pseudoephedrine. I get the real stuff. Others may want to see how a combination may work for for them.

* tyyosh mentioned benadryl blocks acetycholine. I think that is true and is the root cause of the sluggishness it causes. This might help: *http://en.wikipedia.org/wiki/Huperzine_A
I have used it off and on and buy it here: *http://www.iherb.com/Huperzine-Huperzin. I have little doubt the molecule (from hyperzine) is biologically active, but have limited faith that it is necessarily in a form that is active in all supplements -- maybe not in the ones I buy. I will likely try more brands in the future if I can find them to see if some are better/stronger than others. I cannot tell if it makes me smarter or not. If it does, it is nothing major. There are many places to get it online, but I do not know about supplement retail stores as I have never tried to find it there. I would like to find a lab that works with it and get some there. Not likely.

* I have heard that benadryl may impede Human Growth Hormone secretion. That may or may not be true. If so, it would be a downside, and a reason to use lower dosages. Maybe it is just an hypothesis that it effects HGH.

* You mentioned your wife's eye redness. It appears its antihistamine properties of restricting blood vessels (by blocking histamine in the capillaries) may be helping a long time issue of mine of the whites of my eyes being a bit red at times. I had forgotten it serves that purpose.

According to your experience and research, it is good to know that it may be good for other things too such as statin damage. So that has help inspire my interest in trying it again.

Thanks.

Biologist

[David Staup]

Hey Biologist,

I have a study that states low doses do not affect oxidative phosphoralation implying to me that normal doses do, which would also make you sleepy. No one who has tried the lower dose has experienced drowsieness, most feel more alert....everyone is different.

We have been discussing even lower doses on the mito forum....I suspect lower doses will still work and will be experimenting later.

David

[Biologist]

David,

I have watched this video several times recently and think there are sections of it you might appreciate, if not the whole thing. Let me know what you think about it sometime. No hurry.

*http://www.youtube.com/watch?v=ZW3zrA1VuBA&feature=related

Biologist

[Biologist]

David, go to time marker 36:30 on the video.

He states that increasing glutathione levels lessens muscle wasting. I now take melatonin at night just for increasing glutathione levels and I make sure I take selenium regularly for the same reason.

Back to Benadryl, I now am taking it is small dosages throughout the day. Thanks for the idea.

Biologist

[David Staup]

This explains, to me, why melatonin had the opposite effect on me. When I tried it I became "not drowsey":

Glutathione is not an essential nutrient (meaning it does not have to be obtained via food), since it can be synthesized in the body from the amino acids L-cysteine, L-glutamic acid, and glycine. The sulfhydryl (thiol) group (SH) of cysteine serves as a proton donor and is responsible for the biological activity of glutathione. Cysteine is the rate-limiting factor in cellular glutathione synthesis, since this amino acid is relatively rare in foodstuffs.

Glutathione is synthesized in two adenosine triphosphate-dependent steps:

The (necessary) synthesis requires ATP....so taking it reduced usage.

Also there is this:

"Abstract
Glutathione deficiency produced by giving buthionine sulfoximine (an inhibitor of γ-glutamylcysteine synthetase) to animals, leads to biphasic decline in cellular glutathione levels associated with sequestration of glutathione in mitochondria. Liver mitochondria lack the enzymes needed for glutathione synthesis. Mitochondrial glutathione arises from the cytosol. Rat liver mitochondria have a multicomponent system (with Ks of approx. 60 μM and 5.4 mM) that underlies their remarkable ability to transport and retain glutathione. Mitochondria produce substantial quantities of reactive oxygen species; this is opposed by reactions involving glutathione. Glutathione deficiency leads to widespread mitochondrial damage which is lethal in newborn rats and guinea pigs, animals that do not synthesize ascorbate. Glutathione esters and ascorbate protect against the lethal and other effects of glutathione deficiency. Ascorbate spares glutathione; it increases mitochondrial glutathione in glutathione-deficient animals. Glutathione esters delay onset of scurvy in ascorbate-deficient guinea pigs; thus, glutathione spares ascorbate. Glutathione and ascorbate function together in protecting mitochondria from oxidative damage"

Wow... the combination of low dose benadryl and gluthathione should do two very important things.....

1. Reduce the oxidative damage that triggers apoptosis (gluthathione)

2. Inhibit apoptosis in "triggered" cells


What made you choose this route? Gluthathione is available as a suppliment?

I'm puzzled a bit, as yet, on what to look for when I try this...this is going to take me a while to process.....Thanks

David

[Biologist]

David, you can buy the supplement, but experimentation has shown for years that it does not work -- it does not make it through digestion and does not raise blood levels. Glutathione levels can be raised with vitamin D, alpha lipoic acid and N-acetylcysteine. I supplement all three. Another good way to preserve it is to cut you mercury load. I am methodically removing amalgam fillings these days. It needs to be done correctly though. I found a biological dentist.

Biologist

[David Staup]

I had all my teeth pulled because of amalgam fillings as soon as I was aware of the connection, three years ago now. There are risks even with the new methods.

As it turned out my dentist's wife is statin damaged and we discussed all this at length.

Keep me updated on effects.

David

[David Staup]

I just remembered, I had found a study, funded by COORS the beer company that showed the link between amalgams and raised levels of cholesterol.

I havent found the study but I did find a PDF about the study:

http://www.terfinfo.com/Files/Cholesterol%20News%20Article.pdf

[David Staup]

Biologist

Take a look at this:

David,

I wanted to share a recent experience with you that is along the lines
of the Benadryl.

Several years ago I had tried taking a little DHEA to see if it would
help with low energy. I had a blood test and was within normal range,
but wanted to see what would happen. I believe I was taking about 15-20
mg. It made me extremely jumpy and angry, just like you'd see with high
estrogen or testosterone levels, so I stopped right away.

In 2003 when I contracted neuroinvasive West Nile Virus I developed
extensive damage to nerve roots in my spine.. At first the nerve damage
affected my entire torso, but over several years it seemed to heal
somewhat it localized more and appears to be a lesion in my thoracic
spine with total nerve loss at the T-10 region. This was so specific
that it only affected one very small section of my intestines and caused
gastroparesis. I could not sleep lying down unless I had not eaten
since afternoon. If there was any food in my upper GI tract I would wake
up with excrutiating pain and vomiting. The main treatment is an
implanted vagus nerve stimulator which I declined. EMGs showed such
severe axonal damage it didn't even pick up any electrical impulse in
that area.

This past year I started having some menopausal symptoms like hot
flashes and decided to revisit the DHEA since I didn't want to use
hormone replacement therapy. I took about 5 mg a day and it did relieve
the symptoms. I realized how much it had helped when I ran out for a
couple of weeks. So last week I started taking it again and decided to
double the dose. I didn't realize until a few days later that I was
using the higher potency capsules, 50 mg instead of 25, so I was getting
about 10 mg per day. I got up early one morning to go for a walk and was
greatly surprised to find I could walk up a long hill without getting
winded. I walked 1 1/2 miles and hardly felt it. But what was most
surprising was that my back and abdominal pain from the nerve damage had
improved quite dramatically. I could even lie down for a short time and
not get the nausea and bloating.

First I looked to see if DHEA could replenish the myelin sheath which is
what was damaged in my spine. I found many references:
*http://www.ncbi.nlm.nih.gov/pubmed/18501592
*http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001051

Then I looked to see if DHEA could possibly improve Pulmonary Arterial
Hypertension which I had also developed from viral infection. That would
explain my higher level of exercise tolerance. I found that they were
conducting clinical trials because it had been so effective.
*http://www.ncbi.nlm.nih.gov/pubmed/20206649

It's interesting that the nerve damage is related to over-expression of
apoptosis, but the pulmonary hypertension from under-expression in the
vessels - the proliferation is what causes PH. So the DHEA seemed to
have a modulating effect on both my conditions.

Again, I think when you go with a lower dose you let the body determine
how it's going to use the compound. When I tried taking DHEA many years
ago the dose was just too high for me since I had high levels of
estrogen and it was probably being shunted that direction. Now that I
have low estrogen levels my body seems to be using it in a more diffused
way. This is probably true for men and testosterone related to DHEA
intake. If you do a search on PubMed for DHEA and apoptosis there are a
lot of interesting studies. Since we have so much Parkinson's in my
family which is probably mito-related and DHEA has been used as a
treatment, it made me wonder if it might be exerting the same protective
effect as the Benadryl.

I doubt that I could ever find a neurologist who would follow this line
of reasoning. I have tried to see a doctor at the University of
Colorado's MDA clinic, but because I refused to see his partner who is a
total jerk, I'm now on their black list and they won't give me an
appointment. I have been very active in promoting the MDA for several
decades since they treat the muscle disease that runs in my family, but
to punish someone because we want a choice in doctors is ridiculous.

Anyway, thought that might make some interesting reading for you. It was
discussed a little on the forum and I seem to recall you mentioned
pregnenolone. I'm using the Swanson Vitamins DHEA 50 mg capsule and
taking small doses.



There are conflicting lines of evidence that dhea in small doses increases glutathione or decreases it.......?????

David