#413

“All things being equal (and they certainly are not) you should not expect outward signs for 6 years (it took a while to get like this…it’ll take a while to get back)”
Sage advice.

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#414

New doxy research…

Newsweek: Common Drugs May Pave Way to Extending Human Lifespan.

The one with doxycycline

In their first experiments, the team used doxycycline, which was shown to make worms live longer. A smaller dose made them live 72.8% longer, whereas a larger dose made them live 63.64% longer compared to worms not treated with anything, in the control group. The control worms lived around 11 days, while the ones treated with a small dose of doxycycline lived 19 days and the ones given a bigger dose lived 18 days.

The team also used a special kind of light to check the amount of a pigment called lipofuscin, which increases as worms get older. After treating the worms with doxycycline for 13 days, they found that a smaller dosage reduced lipofuscin by about 50%, and a larger dose reduced it by about 90%.

Testing with azithromycin

In the next set of tests, the team used azithromycin. Their results showed that when they treated the worms with azithromycin, their lifespan increased.

A smaller dosage made them live 50% longer, whereas a larger dosage made them live 17% longer compared to worms in the control group. The control worms lived around 12 days, while the ones treated with azithromycin in small dosage lived 18 days and the ones which took a bigger dosage lived 14 days.

“This supports the theory that mitochondria are heavily involved in the aging process, although this remains a highly debated topic,” said the researchers in their study.

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#415

The paper

Mitochondria-targeting antibiotics extend lifespan in C. elegans

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#416

It looks to me like doxycycline vs azithromycin, doxycycline wins.

This is good because doxy has a long safety record and has been used by some daily for years.

Vitamin C is the loser here. IMO: Vitamin C is just another vitamin that is generally abundant enough in our diets. The hype for vitamin C started by Linus Pauling has never completely gone away. It is probably overrated even as an antioxidant.

“we found that some studies suggest an increase in lifespan, other studies failed to observe any beneficial effect of vitamin C on longevity and some studies even reported a decrease in lifespan following vitamin C supplementation”

Sunday will mark the end of my DAV experiment.

I noticed absolutely nothing subjectively and I don’t know what blood tests I should look to for improvements.

I know some people are concerned about antibiotic resistance and changes in the gut microbiome. It is not easy to change the gut microbiome hence the need for such things as fecal implants. The effect of probiotics is not very great or perhaps none at all.

Below is one the best studies I have seen comparing gut microbiomes between 100 mg doxycycline users and non-users. It also shows the limited, if any effect of probiotics.

“We observed diminished levels of Escherichia in the doxycycline group, which corroborates previous results obtained by culture of human fecal samples during 100 mg daily doxycycline regimens [8]. In this small population sample, the prevalence of travel diarrhea was comparable between the two groups with and without doxycycline. However, in larger populations, doxycycline malaria prophylaxis protected against travel diarrhea [10]. Our results support the hypothesis that doxycycline may have restored antimicrobial properties against enteropathogenic bacterial strains and protect against travel diarrhea by direct inhibition of Escherichia.”

After approx. 5 weeks of daily 200 mg dosing (2x100 my bowel movements and stools are normal.

At the end of my DAV experiment, I plan on dropping the vitamin C and azithromycin. I am going to take doxy at 100mg/day for some time because of its possibilities and the fact that I now have a lifetime supply.

Possibly a little serendipity here as it appears, from the paper Joseph referenced, that in the case of doxycycline, the lower dose was as effective at extending lifespan than the higher dose.

Since I am not trained in any of the medical or biological sciences, maybe some other members could weigh in on the results of the study.

This is the paper that the article Joseph pointed referenced

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#417

FWIW

I will be doing my modified DAV Therapy once a week{for 7 days] per quarter{every 12 week’s].

azithromycin 250mg 3 days
doxcycline 100mg 2x per day
Vitamin C 2g - 4 to 6 hour’s after either

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#418

Plan on doing same but with 1/2 the dosage of Doxy and AZI. Vit C I do take 2g daily anyway (will keep it that way).

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#419

I finished my 5-week DAV “therapy”.
Because my biological rhythms, bowel movements, food intake, etc. vary, I now look at the 5-week results and say: Nothing to report. Everything seems normal after 5 weeks. No subjective changes anyway.

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#420

Brilliant reply! Thank you! I am a few days from completing my 5 week DAV. Had a nasty bout of illness two weeks ago, so maybe the clear out. Also kept up my D&Q and Rapa.

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#421

Just a note and a tip for eveyone on the protocol,

The DAV protocol is specifically IV Vitamin C not oral Vitamin C. This is because in low doses and orally vitamin C is an antioxidant while in large IV doses it is a pro-oxidant. The pro-oxidant effect is what eradicates the CSC. Some studies point to the protective effect of antioxidants in the tumor microenviroment so if that’s what your targeting with the DAV combo , I would consider switching to IV and at higher doses.

Hence in regard to your protocol and eradicating CSC, it only works at the high dose IV vitamin C which in the cancer world is 1-2g/kg IVC. This coupled with oral doxy or azithromycin (ideally IV and not oral) has been shown multiple times anectodally and in studies to eradicate CSC.

Best of luck.

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#422

I have a mild URTI right now. If I go to my local doctor, he’ll probably put me on the DAV therapy as a normal procedure.

#423

You can approximate 50g IV Vitamin C (over 24 hours), the usual dosage in cancer studies, with 1 gm Lipo Vit C every 3 hours : In studies (using Livon Brand Lipo Vit C) the blood and tissue concentrations were similar. LivOn Lipo Vit C is around $36 for 30 1gm packets (currently a Bogo sale lowers that to $36 for 60 1gm packets). The Renue ForScience Lipo Vit C (Cellg8 manufactured) probably has similar potency, normally $34.95 for 60 gm, (currently running a 25% Black Friday discount till 11/27 lowers that to $27.20 for 60 gm).

#424

I commend their effort and hope they continue to research this, I just hate “movements” that do not allow people to publish possible negatives of any therapy, it so unpersuasive.

However, DAV decreased median lifespan, and in isolation doxy was much more effective.
image

image

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Antibiotics that target mitochondria extend lifespan in C. elegans
#425

Seems Doxy + Azi is not a winning combo here.

#426

Azithromycin also worked better than the combination except in higher doses.

image

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#427

How does a 25uM translate in mg?

#428

Thanks for pointing that out, but the authors are trying to patent an oral combo D+A+C.
“Taken together, our evidence supports a novel combined metabolic strategy to better eradicate CSCs. More specifically, we demonstrate that the inhibitory effects of Doxycycline on the CSC population can be potentiated by combination with another FDA-approved antibiotic, Azithromycin, and a dietary supplement, namely Vitamin C (a mild pro-oxidant).”

“all three components of the DAV triple combination of Doxycycline (1 μM), Azithromycin (1 μM) and Vitamin C (250 μM), should be administered at the same time.”

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It looks like the combo D+A is 63% as effective as the triple combo.

From the same paper:

“The ascorbate radical is normally very stable, but it becomes more reactive especially in the presence of metal ions, including iron (Fe), allowing the ascorbate radical to become a much more powerful pro-oxidant.”

Maybe we should take an iron supplement along with the protocol to obtain the benefits of oral vitamin C, or not.

Apparently, the authors think the oral vitamin C works because: (They speculate)

“Therefore, we speculate that as mitochondria are particularly rich in iron, they could become a key target of the pro-oxidant effects of Vitamin C, driving mitochondrial oxidative stress and new mitochondrial biogenesis.”

Do you think that the oral vitamin C might work after all and do you have any idea what the oral dose might be?

1 Like
#429

Oral Vit C is primarily excreted once the maximum absorbable dose is achieved.
“At doses above 1 g/day, absorption falls to less than 50% and absorbed, unmetabolized ascorbic acid is excreted in the urine”.

As I have been through this with the many cancer clinics in the world due to family members with cancer being treated, I can say without a doubt cancer stem cells are the hardest to kill and I would not come at them with an oral dose.

So I would not have any reccomendation on an oral dose because, even if you take oral vit c every hour to increase plasma concentration you will be excreting it quickly and irritating the gut. I used to believe in liposomal vit c but many cancer clinics had conflicting thoughts on it.

Only way to know if you are really reaching peak plasma levels orally is to measure your plasma, but bloodwork for Vit C is unfortunately not accurate as the Vit C oxidizes when exposed to oxygen, meaning when the blood is drawn the Vit C oxidizes giving false results.

" Serum whole blood are unstable at room temperature, with losses up to 15% and 20% within 2 h. To assess the in vivo vitamin C status, it is crucial to avoid ex vivo artefacts, i.e., the oxidation of vitamin C (ascorbic acid) to dehydroascorbic acid (DHA) and subsequent irreversible hydrolysis of DHA to 2,3-diketogulonic acid. For this reason, samples have to be handled quickly after drawing blood to obtain a reliable vitamin C result."

Anyways, there is not even a comparison between IVC and oral Vit C. That is why many cancer clnics only recommend IVC and in high doses.

Keep in mind gut irritation from oral doses, and that you simply cannot reach comparitive peak plasma levels similar to that of 50g - 100g IV doses, to cause the strong pro-oxidant effect that is able to kill CSC (which is from the oxidation of iron creating H2O2 (peroxide) as a byproduct). With IVC, unless you have a G6PD deficiency , you can be certain that you are reaching max plasma levels without doing much harm.

You can get high dose IVC pretty much everywhere in the US as there are a bunch of wellness clinics out there now. It costs anywhere from $200-$400 for IVC in the US in my experience. In the EU it is of course a fraction of that price.

Redox Interactions of Vitamin C and Iron: Inhibition of the Pro-Oxidant Activity by Deferiprone - PMC.

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#430

I have no medical or biology background, so I am picking your mind.

This is a rather long thread so you may have missed my posts and others concerning DAV therapy. There is a patent claiming anti-aging properties, senolytic properties, blah blah blah
Personally, I did the DAV protocol using 1 gram of ascorbyl palmitate.

I did the protocol for its supposed anti-aging properties as I have no cancer that I am aware of.
As a retrospective look after completing the DAV protocol, I noticed no subjective effects. After ~4 weeks, I had pre-scheduled blood work done and everything was normal.

As for the patents:
Apparently, they think ascorbyl palmitate can be used orally.

“ascorbyl palmitate is an ester of ascorbic acid and palmitic acid commonly used in large doses as a fat-soluble Vitamin C source and an antioxidant food additive. Embodiments of the present approach may use ascorbyl palmitate as a pro-oxidant.”

Some other studies think doxycycline and oral vitamin C can be used to treat doxycycline-resistant cancer cells.

“Vitamin C in this context was between 100 to 250 µM, which are within the known achievable blood levels, when Vitamin C is taken orally.”

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#431

In regard to it being a senolytic, I need to do more research. I can only speak on the cancer side of things.

  1. Side note: I also don’t like how many studies use Vitamin C interchangeably with ascorbic acid (honestly I do it myself for simplicity). Ascorbic Acid is what most “Vit C” supplements and IV’s contain, and they work differently than actual Vitamin C from Camu camu, acerola cherry etc…

Here’s a thread about that: WHAT’S IN YOUR VITAMIN C ? - Liebowitz Longevity Medicine
For example, I take this Vitamin C supplement because it is actual vit c and doesn’t irritate the gut. (Pure Radiance C® Capsules | Natural Vitamin C | Pure Synergy®)

  1. In the same study you quoted in Oncotarget it says the following which is my point.

" It is worth noting that Vitamin C plasma levels vary considerably with the route of administration. For instance, pharmacokinetic studies performed by different research groups have assessed that, after oral administration, Vitamin C plasma levels reach concentrations of ~70-220 μM [reviewed in reference [30], which represents the maximum tolerated oral dose. By contrast, Padayatty and co-workers found that, compared to oral intake, intravenous administration results in 30- to 70- fold higher plasma concentrations of Vitamin C [31]. Furthermore, consumption of 5 to 9 servings of fruits and vegetables per day allows plasma levels of Vitamin C to reach up to 80 μM at steady-state, with peak values of 220 μM [31]. Remarkably, an **intravenous infusion of Vitamin C can reach plasma levels of 15,000 μM (i.e., 15 mM). Interestingly, doses of up to 50 grams per day, infused slowly, didn’t exhibit any toxic side effects on cancer patients [30]. These observations suggest that intravenous administration of Vitamin C may have a role in cancer treatment, as this route allows higher plasma concentrations than those achievable with the maximum tolerated oral dose."

  1. To ensure you are getting a pro-oxidant effect IV is always reccomended as we need to be certain we are eradicating CSC and not protecting them. How do you know what your serum peak level when taking oral ascorbic acid and that you reached the max blood concentration? You don’t. But you can bet you reached 30 - 70 times what you could have gotten orally, in an IV.

Plus, there is a line of thought in cancer, that antioxidants support the tumor microenviroment by preventing apoptosis through scavenging free radicals. Let’s say someone was going to do a pro-oxidative treatment (high dose IVC or ozone) or is on some sort of cancer drug (anthracyclins, platinum based drugs etc…), and they decide to supplement with oral ascorbic acid. You are basically negating the effects of the treatment while giving protection to the CSC.

To reach oxidative potential and to ensure that it has reached the CSC and caused maximal death to CSC the dose would need to be high enough. I just have too many concerns with oral ascorbic acid, as it is not even close to effective and potent as IVC.

Anyways, I might’ve not answered your question completely, but in dealing with cancer, cancer cells adapt to whatever you throw at them. The patients usually do not have much time left, so we have to filter and find the most effective options with the least side effects and most comfort otherwise it is just a waste of time. Patients prefer a IV over oral supplementation which inevitably will cause bad diahrrea and stomach upset. Ultimately the decision comes down to multiple factors. One of which is because Vit C serum testing isn’t accurate, economical or practical, we need to be certain we are hitting the CSC.

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#432

Thanks for taking the time to respond.