Metronidazole - shouldn't we be concerned that the question of carcinogenic potential hasn't been settled?

[StringJunky]

2 minutes ago, Alfred001 said:

Yeah, the situation right now seems to be that there's evidence suggestive of a carcinogenic effect in humans (in vivo). Some studies find no effect, but others do find an effect. As the review article states, it's a controversial question and it seems to me that it's crazy and irresponsible to be so widely prescribing a drug which seems to have a carcinogenic effect of unknown potency.

Right now metro is part of the regimen that most guidelines recommend as the first line treatment for H pylori and the tendency is to prescribe increasingly higher doses (because metro resistance is becoming increasingly prevalent and you need a higher does or duration to overcome it).

MTZ is an important drug with pretty wide applications for a drug from what I can see. Maybe that adds to a systemic reluctance to probe deeper, given decisions are based on cost-benefit we bang on about.

 

2 minutes ago, CharonY said:

As you might have missed it, matched studies in the 90s short-term treatments in children did not find an effect. Conversely, long-term treatment with a rather wide range of antibiotics have been associated with increased cancer risk (in part because of how they affect our gut microbiome). As such, I am still not sure why you pick out this specific antibiotic, as what we discuss here is applicable to many of the others as well. 

Or again to make the point, no drug is safe, and if you want to be concerned at this level, you should be concerned about all of them.

Even there, it's not the mtz causing the cancer, is it?. The mtz kills the microbiome, then the gut is open to anything carcinogenic.

[Alfred001]

19 minutes ago, CharonY said:

You keep repeating the assertion that we need to know absolute risk levels, but as I mentioned many, many times, this is not how it works. You look at whether folks taking a drug have worse or better outcomes, as I and SJ have been saying. 

Jesus Christ, how do you not understand that it's the same thing? If you make a study and compare a group in which H pylori was not eradicated to a group in which it was eradicated with metro you're gonna know the absolute risk lmao.

Quote

You look at whether folks taking a drug have worse or better outcomes, as I and SJ have been saying. 

So where is the study that did that? Where is the study that established what % of people who take metro for H pylori end up with cancer vs what % of untreated patients get cancer?

And this is all ignoring the fact that METRONIDAZOLE IS NOT THE ONLY ANTIBIOTIC IN THE WORLD. It's not metro or don't treat the infection. You can treat it with different antibiotics.

12 minutes ago, CharonY said:

As you might have missed it, matched studies in the 90s short-term treatments in children did not find an effect.

I'm genuinely baffled as to why you're bringing up a single study when I quoted two reviews of the literature. Yes, not every study has found an effect. Many have. You can't arrive at a conclusion based on one study.

Edited November 3, 2023 by Alfred001

[iNow]

I’m reminded of when a toddler comes at me swinging and I just put my palm on their forehand to hold them back until they wear themselves out 

[CharonY]

4 minutes ago, Alfred001 said:

If you make a study and compare a group in which H pylori was not eradicated to a group in which it was eradicated with metro you're gonna know the absolute risk lmao.

That is the very definition of relative risk. The drug can have an extreme high risk for causing cancer, but as long as the treated condition has an even higher one it might be better to use it. 

5 minutes ago, Alfred001 said:

And this is all ignoring the fact that METRONIDAZOLE IS NOT THE ONLY ANTIBIOTIC IN THE WORLD. It's not metro or don't treat the infection. You can treat it with different antibiotics.

You don't seem to understand why certain ABs are used. They are used based on efficacy, taking the bacterial species in consideration as well as local resistance patterns. Why do you think did I mention clarithromycin. I have posted a few papers already and you are free to read up more on why folks are using certain therapies. 

10 minutes ago, StringJunky said:

Even there, it's not the mtz causing the cancer, is it?. The mtz kills the microbiome, then the gut is open to anything carcinogenic.

It is a bit more difficult and not all act the same way. I would have to read up more to see what is known about mechanics or whether most of the data is outcome based. 

But what is known about long-term the culprit seems to be (in part) our immune system. Massive disruptions in the intestinal microbiome is associate with inflammation which in turn is linked to cancer-promoting pathways. However, it is not precisely my specialty and I am not familiar with the latest knowledge in that link.

[Alfred001]

6 minutes ago, CharonY said:

That is the very definition of relative risk. The drug can have an extreme high risk for causing cancer, but as long as the treated condition has an even higher one it might be better to use it. 

1. OMG, my point is that if you know the relative risk you're NECESSARILY gonna know the absolute risk.

2. How many times are you going to repeat this. It's not a difficult concept, I get it.

Again I ask you, show me the study which shows cancer risk is higher in untreated H pylori relative to metro treatment. Why did you ignore that question?

6 minutes ago, CharonY said:

You don't seem to understand why certain ABs are used. They are used based on efficacy, taking the bacterial species in consideration as well as local resistance patterns. Why do you think did I mention clarithromycin. I have posted a few papers already and you are free to read up more on why folks are using certain therapies. 

Again, metro is not the only AB used in H pylori treatment.

Edited November 3, 2023 by Alfred001

[Alfred001]

On 11/3/2023 at 1:58 AM, Alfred001 said:

1. OMG, my point is that if you know the relative risk you're NECESSARILY gonna know the absolute risk.

2. How many times are you going to repeat this. It's not a difficult concept, I get it.

Again I ask you, show me the study which shows cancer risk is higher in untreated H pylori relative to metro treatment. Why did you ignore that question?

Any response to this, @CharonY?

[CharonY]

Scroll up to the papers I provided as a starting point. But to repeat myself:- antibiotics regimen have shown overall reduction in cancer risk, including metronidazole treatment (though not specifically testing for that). Combined with the fact that earlier studies in humans did not showed a strong effect, suggest that the relative higher risk is to have H. pylori infections. Since you might also have missed it, the treatment is selected by multiple indicators, including local resistance, potential side effects/allergies and so on. 

 

[Alfred001]

2 hours ago, CharonY said:

Scroll up to the papers I provided as a starting point. But to repeat myself:- antibiotics regimen have shown overall reduction in cancer risk, including metronidazole treatment (though not specifically testing for that).

Which paper has shown reduction in cancer risk with metronidazole treatment relative to no treatment? And did it take into account gastric cancer only or all cancers?

2 hours ago, CharonY said:

Combined with the fact that earlier studies in humans did not showed a strong effect

The reviews I posted showed increased incidence of cancer after metronidazole treatment.

2 hours ago, CharonY said:

suggest that the relative higher risk is to have H. pylori infections

Again, source for this claim?

2 hours ago, CharonY said:

Since you might also have missed it, the treatment is selected by multiple indicators, including local resistance, potential side effects/allergies and so on. 

Again, metro is not the only AB used in H pylori treatment, so relevance to cancer risk? Also, penicillin allergies are considered when selecting ABs for H pylori treatment, no other AB commonly used for H pylori treatment has allergy issues associated. Also, metronidazole generally has the highest rate of resistance, higher even than clarithromycin (although, granted, resistance can be overcome, but the point is moot to begin with).

[CharonY]

On 7/13/2023 at 12:46 PM, Alfred001 said:

But have the studies been done? Is there an adequately powered study with adequate followup that allows us to conclusively say there is no increase in cancer risk or that it is trivially small? Or is it simply that we haven't done the studies so we don't know how much we are potentially increasing people's risk of cancer?

I have answered that before and also explained why there are generally no such studies (or very few). You cannot easily prove a negative. The papers that I shared have shown the link between bacterial infections and cancers, and the fact that AB treatment reduces risk. I have also already mentioned that long-term AB treatment is associated with increased cancer risk. And again, the reason why we accept this risk is because the dangers are higher of not treating it. And you can again repeat the claim that this does not satisfy you and I can again repeat that this is how medical treatments work, you choose the lesser poison. And then I am going again to point to the paper in the 90s where they follow-up folks some 30k folks for 7 years and did not find elevated risks and then you will say that this does not satisfy you and demand a better study. 

And then I will say again that you are missing the point, as all medications are dangerous and harmful to various levels and you have to look at medical outcomes (again pointing to long-term risks of cancer and other diseases during AB treatments).

If health risks of H. pylori were unchanged after AB treatment, ABs should not be indicated. And if there are other ABs that are equally effective with fewer known harms (and again, this could be just because they have not been found yet...) they would generally be used instead (but from what I know, resistance patterns are often what determines the selection nowadays).

And yes, sometimes it takes a while for the regulators to change recommendations, but so far there has been no smoking gun to show worse outcome in folks taking the treatment. And then we probably start the next page with again the same arguments. So unless there is a new argument coming I see this issue as resolved (if not to your satisfaction, but so is life).

[Alfred001]

You keep ducking. Your claim is the risk of not treating is greater than the risk of treating with metronidazole. Ok, provide a study that proves that.

Show me a study that compared an untreated group with a metro-treated group and found less incidence of cancer in the metro treated group.

If you don't have that study then you can't make the claim that your whole position is based on.

Don't obfuscate and change the subject as you just did. Do you or do you not have such a study?

[iNow]

You’re being absurd 

[Alfred001]

45 minutes ago, iNow said:

You’re being absurd 

Explain.

[iNow]

No

[Alfred001]

22 minutes ago, iNow said:

No

If you're gonna talk shit then you should have the balls to debate and back it up, otherwise stfu punk.

EDIT: Yeah, downvote my post, but UNDER NO CONDITIONS engage, pussy 😄 You know it wouldn't go well for you.

Edited November 10, 2023 by Alfred001

[TheVat]

 

There is a slight cancer risk from any diagnostic using X-rays.  Also from moving patients to specialized treatments by air travel (stratosphere increases exposure to radiation).  It's not that difficult to weigh relative risk and use such technologies. So it is with antibiotics et al.  If I have tetanus or gangrene (anaerobic bacteria), I definitely will risk the metro.  Especially given exposure would not likely be more than a week.  Common sense is applicable here.  Rather than name-calling.

[Alfred001]

8 minutes ago, TheVat said:

 

There is a slight cancer risk from any diagnostic using X-rays.  Also from moving patients to specialized treatments by air travel (stratosphere increases exposure to radiation).  It's not that difficult to weigh relative risk and use such technologies. So it is with antibiotics et al.  If I have tetanus or gangrene (anaerobic bacteria), I definitely will risk the metro.  Especially given exposure would not likely be more than a week.  Common sense is applicable here.  Rather than name-calling.

Seriously guys, is there a single person on this forum who can reason well?

This point has been made ad nauseum by Charon alone, let alone all the other people who've brought it up. Like AD NAUSEUM.

Yes, it's a cost benefit analysis. To make that cost benefit analysis, we need this:

1 hour ago, Alfred001 said:

You keep ducking. Your claim is the risk of not treating is greater than the risk of treating with metronidazole. Ok, provide a study that proves that.

Show me a study that compared an untreated group with a metro-treated group and found less incidence of cancer in the metro treated group.

Understand? In other to make the cost benefit analysis you need to know what the cost is and what the benefit is. We know what the benefit is, but we don't know what the cost is.

So I've asked Charon for a reference for his claim about the benefit being greater than the cost at least twice on this page alone and notice how he's ducked it both times, because he doesn't have it and he was just making a claim with no evidence for it. (love it when people debate in good faith!)

Also, you're reprimanding me for name calling? Who started the uncivli behavior here? Me or the guy who jumps in with snarky comments, never contributes anything to the debate and then behaves immaturely when asked to back his snarky remarks up.

Edited November 10, 2023 by Alfred001

[StringJunky]

I've linked 2 American, a UK, and one from the European Medines Agency. Fill yer boots.

Assessing the benefit:risk ratio of a drug - randomized and naturalistic evidence - NIH

Enhancing Benefit-Risk Assessment in Regulatory Decision-Making - FDA

Risk:benefit analysis of drugs in practice - BMJ

https://www.ema.europa.eu/en/about-us/what-we-do/regulatory-science-research/benefit-risk-methodology#:~:text=The benefit-risk methodology project,benefits and risks of medicines. - EMA

[John Cuthber]

On 11/2/2023 at 9:05 PM, Alfred001 said:

???

That's what we'd debated for two pages. You claiming no effect exists or is so small as to not matter, me saying that, as the paper says, there's inadequate evidence to know how big the effect is.

I did not say that no effect exists.
I said that if there was a big effect, we would know about it.
 

[TheVat]

https://academic.oup.com/cid/article/26/2/384/508233

 

In vitro mutagenic activity and carcinogenic potential of metronidazole in certain animals raised concerns about its possible carcinogenicity in humans. We studied the late incidence of cancer after metronidazole use among persons enrolled in the Group Health Cooperative of Puget Sound, Seattle, a health maintenance organization. Randomly selected nonusers were matched on a one-to-one basis for age, gender, and year of enrollment to persons who used metronidazole on an outpatient basis during the period January 1975 to December 1983; 5,222 metronidazole user/nonuser pairs, for whom the median follow-up was 12.6 years, were analyzed. Forty-nine percent, 39.2%, 9.8%, and 2% of users had 1, 2–4, 5–9, and ⩾10 prescriptions or refills of metronidazole filled, respectively. The late (after the first 7 years of follow-up) incidence of cancer was nearly identical among users and nonusers (652 and 662 per 100,000 person-years, respectively; relative risk, 0.98; 95% confidence interval, 0.80–1.20). Age-gender stratified analysis did not reveal any association between metronidazole use and cancer. These data support no association between short-term exposure to metronidazole and cancer in humans. Although the results are reassuring, they may not extend to subjects who have used metronidazole for prolonged periods; further epidemiological studies should focus on these individuals.

[Phi for All]

12 hours ago, Alfred001 said:

If you're gonna talk shit then you should have the balls to debate and back it up, otherwise stfu punk.

EDIT: Yeah, downvote my post, but UNDER NO CONDITIONS engage, pussy 😄 You know it wouldn't go well for you.

!

Moderator Note

Take the weekend off, take care of yourself, and if you come back to engage with this thread, do so with civility. 

 

[Alfred001]

On 11/10/2023 at 1:39 PM, John Cuthber said:

I did not say that no effect exists.
I said that if there was a big effect, we would know about it.

That's almost exactly what I said in the VERY POST you were responding to.

Quote

That's what we'd debated for two pages. You claiming no effect exists or is so small as to not matter, me saying that, as the paper says, there's inadequate evidence to know how big the effect is.

At this point I'm beginning to think you're trolling me. There's no way anyone can be this... I can't say what else I might get another warning. Like literally in the paragraph you're correcting me on I said virtually the exact same thing as your correction.

And we would know about it, how? Again IN THE VERY POST YOU WERE RESPONDING TO I quoted what the paper said.

Quote

That's what we'd debated for two pages. You claiming no effect exists or is so small as to not matter, me saying that, as the paper says, there's inadequate evidence to know how big the effect is.

Is there some way to make the font bigger? I'm afraid in the next post John will tell me, YEAH, BUT IF THE EFFECT WAS BIG WE WOULD KNOW ABOUT IT. Anyone wanna bet that's gonna be his next post?

Yeah, if the effect was 100% we would know about it, great argument!

Anyway, I'm done engaging with you. If anyone has an intelligent point to make on the topic or can bring actual evidence to the table like TheVat, I'm happy to continue this discussion.

On 11/10/2023 at 3:39 PM, Phi for All said:

!

Moderator Note

Take the weekend off, take care of yourself, and if you come back to engage with this thread, do so with civility. 

 

Hmm... why am I getting warned and not the guy who started the incivility? (literally his only contribution to the thread) Anyway, doesn't matter...

On 11/10/2023 at 3:16 PM, TheVat said:

https://academic.oup.com/cid/article/26/2/384/508233

Great find! This is, for a stark break from the norm, a valuable contribution to the thread.

However, can someone explain what I'm not getting in this part:

1,336 and 564 cancers among users and non-users in at least 15 years of followup? Doesn't that mean there were 1900 cancers in 1219 people??? More cancers than people? I mean I know a person can get cancer multiple times, but THAT many multiple times? I doubt they counted recurrences as individual cancers and even if they did... Or am I completely misinterpreting things?

Also, incidence of cancer in 15 years of CANCER-FREE followup... what? What am I not getting here?

And then thirdly, 2.38x more cancer among metro users, how is that not significant? Ok, I see that the CI ranges from sub-1 to 6.12, but isn't that CI so wide as to be meaningless? And how likely is it that a 2.38x difference in 15 years is just down to chance???

Also, the limitations here are a bit worrisome, especially the absence of data on dose, duration and compliance.

Edited December 3, 2023 by Alfred001

[John Cuthber]

I'm still saying that, if the effect was big enough to matter, we would have found out about it.
To be blunt, we would have found out the same way we learned that there was a problem with thalidomide.
We would have noticed the victims.

Let's flip this on it's head.

If, as you suggest, the stuff is causing significant harm, how come things like the yellow card scheme (not to mention a stack of ambulance chasing lawyers) have not noticed it?
 

[Alfred001]

Prospects for clinical introduction of nitroimidazole antibiotics for the treatment of tuberculosis

This paper provides an excellent review of the evidence.

Quote

Obviously, there remain significant and troubling
questions surrounding the issue of genotoxicity of MET and
its metabolites. Several prominent authors have argued that
sample sizes are too small and individual variation in
metabolic profile are washing out any observable genotoxic
effects [3].

EDIT: Ok, they say later on in the paper that they think there is good evidence that it doesn't have a significant carcinogenic effect in man.

Which isn't not to say there isn't one:

Quote

Beard
and colleagues reported in 1979 an analysis of 771 women
treated with MET (750 or 500 mg per day for 10 days) for 11
years and then in a subsequent publication for up to 25 years
post treatment (15-25), and found that cancers in all sites
were slightly elevated in the MET group but that only lung
cancer was statistically significant – 12 cases were observed
compared with 3.5 expected, the standardized morbidity ratios were 2.5 after adjusting for smoking (95% confidence
interval 1.3-4.4) [168, 169].

Edited December 3, 2023 by Alfred001

[Alfred001]

This paper critiques some of the studies used to arrive at the "no significant effect" conclusion in the earlier review:

https://onlinelibrary.wiley.com/doi/abs/10.1111/hel.12575

Quote

However, whether the use of metronidazole increases
the risk of human cancers remains controversial, because no data are
available from well-designed epidemiological studies demonstrat-
ing an increased risk of cancer associated with either short-term or
long-term use of metronidazole. Earlier studies using health insurance
or prescription data reported an increased risk of lung cancer (stand-
ard mortality ratio, 2.5; 95% confidence interval, 1.3‐4.4) and uter-
ine cervix cancer (relative risk, 2.8); however, these studies might be
limited by short follow-up periods and missing information regarding
patient characteristics, patient compliance with treatment, or other
confounding variables, making their findings inconclusive.22,23

 

[CharonY]

Yet their conclusion remains that sensible use of metronidazole is backed by evidence, in part because there is no strong evidence of added metronidazole over other antibiotics for short-term use:

Quote

Results: At present, metronidazole resistance has not been a serious issue in Japan in large part due to its restricted use. Emerging evidence from randomized controlled trials demonstrates higher eradication rates for metronidazole than for clarithromycin, supporting its use in both first‐line and second‐line eradication therapies. Among the reported adverse effects, there has been lingering concern over the potential carcinogenicity of metronidazole in humans. However, the possibility of an increased cancer risk is not limited to metronidazole; the long-term use of antibiotics has been linked to increased risk for some site-specific cancers. However, recent prospective studies have suggested that short-term exposure to antibiotics is not associated with an increased cancer risk.
Conclusion: Sensible use of metronidazole backed by research evidence could maximize the benefits associated with H pylori eradication in Japan.

Also from the same paper:

Quote

Allowing for methodological limitations of the epidemiologic studies exploring the carcinogenic effects of metronidazole on humans, it can be concluded that the concern regarding the increased risk of cancer seems to not be limited to metronidazole; long-term antibiotic use may be associated with an increased risk of certain site-specific cancers. However, the increase in the risk of cancer associated with a short period of exposure to metronidazole, such as the 1-week period of use for H pylori eradication, is negligible.