Alfred001

I'm more looking for something that can give me a good list of references that are pertinent to the specific topic, rather than give an answer. I find that as soon as you add some complexity to the topic, the references become increasingly less related to what you're looking for. Like, if you ask how sodium intake affects blood pressure, it will do fine, but if you say how does sodium intake affect blood pressure in people above the age of 60 and with intakes below x, it will just give you references related to the first question and ignore the qualifiers.

I find that LLMs tend to do relatively ok with searching for scientific literature so long as the query is very basic, but as soon as you add a bit of nuance and conditions, it tends to ignore the conditions and ends up giving you only tangentially related literature. Which free LLMs have you found to be the best at this?

I'm putting this in the biology forum because, if this is a legitimate phenomenon, I imagine the explanation would have something to do with epigenetics. Now, this is not a scientific observation, but an anecdotal one, however it's one I've heard a number of people make - people in old photos looked older than modern day people do. That is to say, 18-20 year olds of the 1950s and earlier looked way older than 18-20 year olds of today. Again, I don't know whether this is simply an illusion due to cherrypicking of anecdotal evidence or a legitimate phenomenon, but I've heard a number of people make this observation. Now, I'm sure science hasn't studied this and therefore doesn't have an answer for this, but let's presume that the observation is true to begin with, is there some plausible mechanism, genetic, epigentic or otherwise, that could explain this?

I've heard this claim many times and I'm curious whether this has ever been studied and what has been found. I think I've also heard that it has been refuted or failed to replicate, but I may be making that up.

I'm watching s12e1 of Curb Your Enthusiasm and there's a moment where Larry says to Leon, have you noticed that when you take a picture you don't look nearly as good as you do when you look in the mirror? Because the mirror is how you look to yourself and the photo is how others see you. This is exactly what I've also noticed and hearing LD say that on the show made me realize that this is apparently a universal phenomenon? Have you noticed this as well? I've always been struck by how much more attractive I look to myself in the mirror vs. how I appear in pictures, especially if the picture was taken by someone else and my feeling has always been the one Larry expresses, that the picture is probably how I actually look and how other people see me, whereas when I look in the mirror there's probably some kind of psychological self-esteem maintenance mechanism going on to convince myself I actually look better. Anyway, have others noticed this as well? I'm interested in hearing "no" answers, as well, because I'm curious whether this is really an universal (or at least common) phenomenon.

That some antibiotics may permanently impair fertility in some % of people.

We went over that argument on the 2nd page, it doesn't refute the hypothesis. As I say, the difference in effect size could be explained by the difference in physiology. We see such different effects between species. But, obviously, conclusions cannot be reached based on n=1, but it's the only data we have for amox in humans (that I know of) and it's worriesome. So there's a non-anxious way of reading the data that would say there's no reason for concern here and we don't need human data?

I have been posting for two pages now about all the literature I've read on this subject. I know the subject and that various things affect sperm parameters is not a revelation to me, as I think I've made clear in the thread. What is a revelation is that amoxicillin after a single day of administration caused abnormalities in 90% of sperm. That is a figure you don't see even in animal studies where they're fed long courses of extreme doses, if you know the subject. (Setting aside that spermatogenic arrest can be induced, I'm talking strictly about the rate of abnormalities.) So, with that in mind, I'm curious to see a study showing reversability of amoxicillin's effect on sperm parameters and/or histology of reproductive organs, because the magnitude of the effect makes me wonder. How am I picking and choosing elements from different studies and what conclusions am I making, I haven't arrived at any conclusion? The difference very well may be attributable to physiological differences. The only study of the impact of rifabutin on male fertility showed no effect in mice and baboons and a pretty significant effect in rats. It's possible amox has a more dramatic impact on the human reproductive system than that of the mouse. This is, of course, speculation, because we have (AFAIK) too little evidence. The bottom line is, the only human evidence we have for amox, suggests a pretty dramatic impact on sperm parameters, way out of line with effects commonly observed in animal studies of antibiotics.

They're quite surprising if you look at the literature on this topic. I don't think I've ever seen anything near this degree of malformation (and from day 1!) and in animal studies they often give doses way beyond human ones. Add to that this mice study with amox in which the % of abnormal sperm continued to rise through 30 days post treatment and testicular changes were found with only a 10 day course using a smaller dose than used in that study. Can you explain this? I thought the half life of amox is quite short. I believe a 500-1000mg dose drops down to very low, near zero levels in serum somewhere past the 6th hour.

Ok, someone please tell me I'm misinterpreting something here. https://www.mdpi.com/2073-4409/11/24/4064 This is a young male given a normal course of H. pylori treatment, 2g of amoxicillin, 1g of clarithromycin for 15 days. Look at supplementary table 4. M1-5 are 5 samples taken at 3 day intervals throughout the treatment period, W1-5 are samples taken at 3 day intervals after treatment. Look at number of total sperm and number of normal sperm or simply ration of normal sperm. Only 10% normal sperm on first day of treatment!!!?? And then in the last day of the post-treatment period it has gotten worse, 5%!

None of my assumptions have been challenged and I didn't have any assumptions. You say I could have researched it myself, as if this is a google search. I've read probably over 100 pages of literature at this point. I came here in hope someone might make a valuable contribution and instead I've gotten this. As to your second paragraph - Right, and my question from the beginning has been, does anyone know of evidence of permanent effects or any plausible mechanistic reasoning that would suggest it. Can we now get onto that?

Same source as previous

From Erma Z. Drobnis, Ajay K. Nangia (auth.) - Impacts of Medications on Male Fertility So it seems the researchers studying this are concerned about it as well and it's not just my neurosis. But since you never addressed any of the arguments, rather went ad hominem immediately, and described infertility as a marginal side effect, I don't expect anything will convince you.

https://www.researchgate.net/profile/Erma-Drobnis/publication/321879207_Introduction_to_Medication_Effects_on_Male_Reproduction/links/5be077ee92851c6b27aa09b9/Introduction-to-Medication-Effects-on-Male-Reproduction.pdf And the effect may be permanent (from a different source)

Here's a pretty striking study that bears on this question: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819380/ So a fairly long duration, but a very small dose.

Well, I'm sure because of the review I posted on page 1 and other literature. But how many of those 1000 prescriptions are concentrated in either the elderly, who are more prone to sickness, or are given to men who've already had children and are not trying for more (which can happen as early as your 20s, more often early-mid 30s, meaning a large share of the male population would fall into that category)? In both cases, an effect would not be discovered. Then there is the watering down effect when you consider the 10% of ABs, 50% of time effect. I don't think it's implausible that, assuming those rates, an existence of an effect would be consistent with the infertility numbers we see.

I'm sure some antibiotics have an effect. That's consistent with 100% and 10%. Wait, based on what do we know it's not likely even at 10% + 50%? I've already posted a reference backing up the claim about the effect. What I'm wondering about is whether anyone knows of data on a permanent effect (or has any relevant mechanistic reasoning or speculation, in lieu of data).

Moving the goal posts is valid when we're talking about an unknown effect. We don't know whether 100% or 10% of antibiotics have this effect. Both are possible given the data we have, so there's nothing invalid in discussing the first scenario and then moving to the second.

But this is an argument in my favor.

How do you get to half cases of infertility?

Ok, fair point. But, if you assume 10% of antibiotics reduce fertility in 50% of men who take them and you take into account that antibiotics are probably more often prescribed to older people not trying for children... I'm not sure.

But the exact mechanism is not relevant for the purpose of discovering whether there's a permanent effect. The point is it establishes that there is a clear causal effect. The question I'm wondering about is, is there data that shows a permanent effect. If half of antibiotics make half of people half as likely to conceive (substantial effect), would we make the connection that someone failing to conceive now is failing because he took a course of antibiotics 10 years ago? They are not talking about a permanent effect there, but it makes the point. (source)

I don't think there can be any doubt that the relationship is causal. I've read quite a bit of literature at this point. They take lab animals, give them antibiotics, and you see negative effects on all kinds of parameters of fertility, as well as outcomes (implantations and births). As clearly causal as it gets. Take this study as an example. Four groups of rats, three given imipenem/cilastatin, one control group. The treatment groups see negative effects on sperm parameters and sexual organs relative to control. There are endless studies like that.

If everyone who took an antibiotic became infertile and this was true of every antibiotic, maybe, but if the effect is not that strong, not necessarily. https://www.nature.com/articles/nrurol.2015.145 Now, sulphasalazine actually has a temporary effect, but it goes to the point that effects of medications can be difficult to notice. Here's a review https://www.researchgate.net/profile/Tosin-Titus-Olaniran/publication/373776557_Research_Advances_on_the_Adverse_Effects_of_Antibiotics_on_Male_Fertility/links/64fc46fa90dfd95af620eb67/Research-Advances-on-the-Adverse-Effects-of-Antibiotics-on-Male-Fertility.pdf

But the point is we don't know whether it's for a while or permanently. Were it just for a while, who cares.