#136

Speaking of spamming…

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#137

I do that “cheap insurance” thing by taking rapamycin with a bunch of supplements, exercising, and having a non-damaging diet.

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#138

Publication from Pfizer

Summary

 A clinical trial ALLOZITHRO1 which investigated long-term azithromycin to prevent bronchiolitis obliterans syndrome (BOS) in patients who underwent allogenic Hematopoietic Stem Cell Transplantation (HSCT) for hematological malignancy was terminated early after an increased risk of relapses was seen in patients taking azithromycin compared with placebo.

 Although it is not clear how azithromycin could have contributed to the observed higher rate of hematological relapses, in the study, it is concluded that long term azithromycin exposure following HSCT may include risks which exceed the anticipated benefits.

 Azithromycin is not authorized for prophylaxis of BOS in patients undergoing HSCT.

Background on the safety concern

The French Clinical trial entitled ALLOZITHRO “Evaluation of the efficacy of azithromycin to
prevent bronchiolitis obliterans syndrome after allogenic hematopoietic stem cell
transplantation” (NO EudraCT: 2013-000499) sponsored by the French academic institution
belonging to Hospitals in Paris, “Assistance publique des hopitaux de Paris”, investigated
whether early prophylactic azithromycin would improve airflow decline-free survival 2 years after
HSCT.

Study design:
This study was a randomized placebo controlled parallel group trial conducted in
19 academic transplant centers in France. Enrolled patients were 16 years or older who were
undergoing HSCT due to hematologic malignancy. The enrollment period was February 2014 to
August 2015. A total of 480 patients were randomized: 243 patients were to receive
> azithromycin (250 mg) 3 times weekly for 2 years; 237 patients were to receive placebo for two
years, starting at the time of conditioning regimen. The immunomodulating effects of
azithromycin therapy were evaluated when used for the long term prevention of BOS.

Results: The ALLOZITHRO study treatments (azithromycin/placebo) were terminated on the
> 26th December 2016 i.e. at thirteen months after completing recruitment

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#139

Right, its mainly lab studies, but with a glimmer of clinical evidence from the doxycycline study that made me consider it (later contradicted by the study you linked to showing increased cancer relapse rate)

"Our clinical pilot study aimed to determine whether short-term pre-operative treatment with oral doxycycline results in reduction of CSCs (cancer stem cells) in early breast cancer patients.

Methods: Doxycycline was administered orally for 14 days before surgery for a daily dose of 200 mg. Immuno-histochemical analysis of formalin-fixed paraffin-embedded (FFPE) samples from 15 patients, of which 9 were treated with doxycycline and 6 were controls (no treatment), was performed with known biomarkers of “stemness” (CD44, ALDH1), mitochondria (TOMM20), cell proliferation (Ki67, p27), apoptosis (cleaved caspase-3), and neo-angiogenesis (CD31). For each patient, the analysis was performed both on pre-operative specimens (core-biopsies) and surgical specimens. Changes from baseline to post-treatment were assessed with MedCalc 12 (unpaired t-test) and ANOVA.

Results: Post-doxycycline tumor samples demonstrated a statistically significant decrease in the stemness marker CD44 (p-value < 0.005), when compared to pre-doxycycline tumor samples. More specifically, CD44 levels were reduced between 17.65 and 66.67%, in 8 out of 9 patients treated with doxycycline. In contrast, only one patient showed a rise in CD44, by 15%. Overall, this represents a positive response rate of nearly 90%. Similar results were also obtained with ALDH1, another marker of stemness. In contrast, markers of mitochondria, proliferation, apoptosis, and neo-angiogenesis, were all similar between the two groups’

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#140

In that study it says the following:

Azithromycin therapy was consistently associated with an increased risk of AHF in patients with preexisting CVD (risk ratio [RR], 1.48 [95% CI, 1.06–2.06]).

The comparison wasn’t between vaccinated and unvaccinated people, but it’s true that those with preexisting cardiovascular disease were associated to have a higher rate of acute heart failure using Azithromycin.

A 2020 JAMA study showed the following assosciation:

Results The study included 7 824 681 antibiotic exposures, including 1 736 976 azithromycin exposures (22.2%) and 6 087 705 amoxicillin exposures (77.8%), among 2 929 008 unique individuals (mean [SD] age, 50.7 [12.3] years; 1 810 127 [61.8%] women). Azithromycin was associated with a significantly increased hazard of cardiovascular death (hazard ratio [HR], 1.82; 95% CI, 1.23-2.67) but not sudden cardiac death (HR, 1.59; 95% CI, 0.90-2.81) within 5 days of exposure. No increases in risk were found 6 to 10 days after exposure. Similar results were observed in patients within the top decile of cardiovascular risk (HR, 1.71; 95% CI, 1.06-2.76). Azithromycin was also associated with an increased risk of noncardiovascular death (HR, 2.17; 95% CI, 1.44-3.26) and all-cause mortality (HR, 2.00; 95% CI, 1.51-2.63) within 5 days of exposure.

It was also from a diverse population based on data from Kaiser Permanente:

Kaiser Permanente California consists of 2 regions, Northern California and Southern California, with a combined membership of more than 8.2 million individuals. The demographic profile of the Kaiser Permanente California membership is racially, ethnically, and socioeconomically diverse and closely resembles the underlying populations of Northern and Southern California

The association they speculate is because of cardiac arrythmias:

Reports of an association of erythromycin, one of the first macrolide antibiotics, with QT interval prolongation and cardiac arrhythmias first appeared more than 20 years ago.16-19 Subsequently, cardiac arrhythmias have been reported for clarithromycin and azithromycin, and macrolide antibiotics, as a class, are now known to cause QT prolongation in some at-risk populations.20 In most of the case reports of macrolide antibiotic use and cardiac arrhythmias, patients had other factors that put them at an increased risk for cardiac arrhythmias, including underlying cardiac disease (ie, bradycardia, congestive heart failure, baseline QT prolongation, cardiomyopathy, atrial fibrillation, and myocardial ischemia), metabolic anomalies that increase the risk of arrhythmia (ie, hypokalemia, hypocalcemia, hypomagnesemia, and hypoxia), or concomitant use of other medications known to prolong the QT interval.21

#141

Is it still a ‘no brainer’ based on your translated patent application and mechanistic study? It took me 5 minutes of googling to find these possible ‘downsides’ with one of the antibiotics used.

Do not do things because others do so, instead carefully review the evidence, risk vs reward. Ask yourself what type of evidence are behind the claims. In fact you should ask a doctor and not take recommendations from people on the internet, period, and not people who wonder if it’s okay to inject coconut water.

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#142

Chill dude :sweat_smile:

You found a study that shows a relapse in cancer on a very limited number of patients and a very specific cancer. The same study did not show any increase in relapse in other cancers. All of the patients also underwent a specific cell transplant therapy beforehand. It is not really useful. Azithromycin Is still used in dose of 1500 mg/week for longterm pneumo prophylaxis in other patients without known adverse effects.

Heart arrhythmia is also a know side effect of azithromycin and it shouldn’t be used as a primary antibiotic in certain patients and azithromycin’s heart toxicity is dose dependent and I still don’t know how your findings would be decisive in wanting to try low dose combination therapy that includes azithromycin in subclinical dose?

But yes, I guess you have to be right and people who want to try it based on some “stupid” patent application and mechanistic studies must be fools.

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#143

A clinical trial with 480 patients and a 60% relative increase is “limited amount of patients”?

I never said that, although I do think that.
Just be honest that you don’t know if it’s going to work for sure, that there are downsides with taking two antibiotics, and don’t say it’s a ‘no brainer’ if it’s clearly controversial to take antibiotics like this and especially with this level of evidence.

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#144

In my view and opinion, yes it is.

As I am on this{the DAV Therapy)

Modified the dose to my view and have been on it since September 25, 2023

And will continue till the end of October 31,2023

36 days is the total amount planned I am already past the half way mark with no issues.

I will post it again;

“This is the place where those that say in can not be done take a backseat to the people doing it”

~ Laura Flanders

And I am doing it.

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#145

Well, I read the study, don’t remember exact numbers, but the subset where increase was statistically significant was just less than 60 patients and relative increase meant just over 10 patients. While it is significant increase the sample was still very small and on a very specific two blood cancers.

Of course nobody knows if it is going to work, but it is same with rapamycin, statins or PCSK9 inhibitors. Sometimes the data is stronger, but you still need a leap of faith.

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#146

You’re comparing rapamycin with ITP and human studies (Mannick), statins with many clinical trials, as well as PCSK9 inhibitors with clinical trials as well, with this?

I don’t think you understand the hierarchy of evidence well enough since you do a comparison like this.

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#147

I do understand it quite well, but I do also understand biases behind it and also why for some mechanistically sound concepts there is almost impossible to find funds to do further study evaluations.

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#148

I am doing it to kill senescent cells only- nothing else. But this form with all the scary post is making me rethink my decision to continue although I consider myself healthy! But I can find 20 papers on Rapa that have scary side effects too!

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#149

Thanks Joseph let’s do this! I finish Nov 1!

I appreciate all the concern about the side effects but seriously on this form? IMO most all taking Rapa are taking a risk, you really never know what lurking in our bodies and DNA.

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#150

So why are you comparing a mechanistic study with clinical trials then? As if no one has more information about a drugs efficacy based on a clinical trial compared to mechanistic studies?

Rapamycin doesn’t have a post-market warnings from the FDA as I showed in a thread about this.

image

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#151

Thank you for your concern! Peace!

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#152

I appreciate being made aware of any apparent potential dangers of taking Azithromycin. However we need to keep things in context. The DAV therapy that people are trying here uses a total of 10 Azithromycin 250mg doses over a period of five weeks. That is nowhere close to the standard antibiotics regimen where any potential for elevated risk has been observed. In fact the trial cited that was aborted had been using “long term” Azithromycin therapy. It would appear yet again that it is probably the dose that makes the poison.

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#153

“in patients with preexisting CVD (risk ratio [RR], 1.48 [95% CI, 1.06–2.06]).”

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#154

The dose with increase in cancer relapse and death was 250 mg azithromycin 3 times weekly. The translated article protocol does 250 mg two times a week. Not sure why you call that subclinical dose, if it’s only 34% lower than the dose showed to increase cancer relapse and death from long term use in a clinical trial.

It calls into question the ‘efficacy’ of this therapy if a 50% higher dose for one of the drugs increases cancer relapse and death in a clinical trial. Nothing extraordinary as it’s typical for mechanistic studies to fail or even be harmful as a therapy is studied further.

Yes, there might be people with CVD here so for them it’s good to know and not an automatic ‘no brainer’ as it apparently is for some.

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#155

I finish November 17 exactly 1 week after my birthday. :grinning:

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