(TLDR: Recent Cochrane review says zinc lozenges shave 0.5 to 4 days off of cold duration with low confidence, middling results for other endpoints. Some reason to think good lozenges are better than this.)
There’s a 2024 Cochrane review on zinc lozenges for colds that’s come out since LessWrong posts on the topic from 2019, 2020, and 2021. 34 studies, 17 of which are lozenges, 9⁄17 are gluconate and I assume most of the rest are acetate but they don’t say. Not on sci-hub or Anna’s Archive, so I’m just going off the abstract and summary here; would love a PDF if anyone has one.
Dosing ranged between 45 and 276 mg/day, which lines up with 3-15 18mg lozenges per day: basically in the same ballpark as the recommendation on Life Extension’s acetate lozenges (the rationalist favorite).
Evidence for prevention is weak (partly bc fewer studies): they looked at risk of developing cold, rate of colds during followup, duration conditional on getting a cold, and global symptom severity. All but the last had CIs just barely overlapping “no effect” but leaning in the efficacious direction; even the optimistic ends of the CIs don’t seem great, though.
Evidence for treatment is OK: “there may be a reduction in the mean duration of the cold in days (MD ‐2.37, 95% CI ‐4.21 to ‐0.53; I² = 97%; 8 studies, 972 participants; low‐certainty evidence)”. P(cold at end of followup) and global symptom severity look like basically noise and have few studies.
My not very informed takes:
On the model of the podcast in the 2019 post, I should expect several of these studies to be using treatments I think are less or not at all efficacious, be less surprised by study-to-study variation, and increase my estimate of the effect size of using zinc acetate lozenges compared to anything else. Also maybe I worry that some of these studies didn’t start zinc early enough? Ideally I could get the full PDF and they’ll just have a table of (study, intervention type, effect size).
Even with the caveats around some methods of absorption being worse than others, this seems rough for a theory in which zinc acetate taken early completely obliterates colds—the prevention numbers just don’t look very good. (But maybe the prevention studies all used bad zinc?)
I don’t know what baseline cold duration is, but assuming it’s something like a week, this lines up pretty well with the 33% decrease (40% for acetate) seen in this meta-analysis from 2013 if we assume effect sizes are dragged down by worse forms of zinc in the 2024 review.
But note these two reviews are probably looking at many of the same studies, so that’s more of an indication that nothing damning has come out since 2013 rather than an independent datapoint.
My current best guess for the efficacy of zinc acetate lozenges at 18mg every two waking hours from onset of any symptoms, as measured by “expected decrease in integral of cold symptom disutility”, is:
15% demolishes colds, like 0.2x disutility
25% helps a lot, like 0.5x disutility
35% helps some (or helps lots but only for a small subset of people or cases), like 0.75x disutility
25% negligible difference from placebo
I woke up at 2am this morning with my throat feeling bad, started taking Life Extension peppermint flavored 18mg zinc acetate lozenges at noon, expecting to take 5ish lozenges per day for 3 days or while symptoms are worsening. My most recent cold before this was about 6 days: [mild throat tingle, bad, worse, bad, fair bit better, nearly symptomless, symptomless]. I’ll follow up about how it goes!
Update: Got tested, turns out the thing I have is bacterial rather than viral (Haemophilius influenzae). Lines up with the zinc lozenges not really helping! If I remember to take zinc the next time I come down with a cold, I’ll comment here again.
I agree, zinc lozenges seem like they’re probably really worthwhile (even in the milder-benefit worlds)! My less-ecstatic tone is only relative to the promise of older lesswrong posts that suggested it could basically solve all viral respiratory infections, but maybe I should have made the “but actually though, buy some zinc lozenges” takeaway more explicit.
Does anyone know of a not peppermint flavored zinc acetate lozenge? I really dislike peppermint, so I’m not sure it would be worth it to drink 5 peppermint flavored glasses of water a day to decrease the duration of cold with one day, and I haven’t found other zinc acetate lozenge options yet, the acetate version seems to be rare among zing supplement. (Why?)
According to a podcast that seemed like the host knew what he was talking about, you also need the lozenges to not contain any additional ingredients that might make them taste nice, like vitamin C. (If it tastes nice, the zinc isn’t binding in the right place. Bad taste doesn’t mean it’s working, but good taste means it’s not.) As of a few years ago, that brand of lozenge was apparently the only one on the market that would work. More info: https://www.lesswrong.com/posts/un2fgBad4uqqwm9sH/is-this-info-on-zinc-lozenges-accurate
That’s why the peppermint zinc acetate lozenge from Life Extension is the recommended one. So your only other option might be somehow finding unflavored zinc lozenges, which might taste even worse? Not sure where that might be available
Note that the lozenges dissolve slowly, so (bad news) you’d have the taste around for a while but (good news) it’s really not a very strong peppermint flavor while it’s in your mouth, and in my experience it doesn’t really have much of the menthol-triggered cooling effect. My guess is that you would still find it unpleasant, but I think there’s a decent chance you won’t really mind. I don’t know of other zinc acetate brands, but I haven’t looked carefully; as of 2019 the claim on this podcast was that only Life Extension brand are any good.
I have a vague memory of a post saying that taking zinc early, while virus was replicating in the upper respiratory tract, was much more important than taking it later, because later it would have spread all over the body and thus the zinc can’t get to it, or something like this. So I tend to take a couple early on then stop. But it sounds like you don’t consider that difference important.
Is it your current (Not asking you to do more research!) impression that it’s useful to take zinc throughout the illness?
My impression is that since zinc inhibits viral replication, it’s most useful in the regime where viral populations are still growing and your body hasn’t figured out how to beat the virus yet. So getting started ASAP is good, but it’s likely helpful for the first 2-3 days of the illness.
An important part of the model here that I don’t understand yet is how your body’s immune response varies as a function of viral populations—e.g. two models you could have are
As soon as any immune cell in your body has ever seen a virus, a fixed scale-up of immune response begins, and you’re sick until that scale-up exceeds viral populations.
Immune response progress is proportional to current viral population, and you get better as soon as total progress crosses some threshold.
If we simplistically assume* that badness of cold = current viral population, then in world 1 you’re really happy to take zinc as soon as you have just a bit of virus and will get better quickly without ever being very sick. In world 2, the zinc has no effect at all on total badness experienced, it just affects the duration over which you experience that badness.
*this is false, tbc—I think you generally keep having symptoms a while after viral load becomes very low, because a lot of symptoms are from immune response rather than the virus itself.
I woke up this morning thinking ‘would be nice to have a concise source for the whole zinc/colds thing’. This is amazing.
I help run an EA coliving space, so I started doing some napkin math on how many sick days you’ll be saving our community over the next year. Then vaguely extrapolated to the broader lesswrong audience who’ll read your post and be convinced/reminded to take zinc (and given decent guidance for how to use it effectively).
I’d guess at minimum you’ve saved dozens of days over the next year by writing this post. That’s pretty cool. Thankyou <3
I ordered some of the Life Extension lozenges you said you were using; they are very large and take a long time to dissolve. It’s not super unpleasant or anything, I’m just wondering if you would count this against them?
On my model of what’s going on, you probably want the lozenges to spend a while dissolving, so that you have fairly continuous exposure of throat and nasal tissue to the zinc ions. I find that they taste bad and astringent if I actively suck on them but are pretty unobtrusive if they just gradually dissolve over an hour or two (sounds like you had a similar experience). I sometimes cut the lozenges in half and let each half dissolve so that they fit into my mouth more easily, you might want to give that a try?
Interesting, I can see why that would be a feature. I don’t mind the taste at all actually. Before, I had some of their smaller citrus flavored kind, and they dissolved super quick and made me a little nauseous. I can see these ones being better in that respect.
The 2019 LW post discusses a podcast which talks a lot about gears-y models and proposed mechanisms; as I understand it, the high level “zinc ions inhibit viral replication” model is fairly well accepted, but some of the details around which brands are best aren’t as well-attested elsewhere in the literature. For instance, many of these studies don’t use zinc acetate, which this podcast would suggest is best. (To its credit, the 2013 meta-analysis does find that acetate is (nonsignificantly) better than gluconate, though not radically so.)
(TLDR: Recent Cochrane review says zinc lozenges shave 0.5 to 4 days off of cold duration with low confidence, middling results for other endpoints. Some reason to think good lozenges are better than this.)
There’s a 2024 Cochrane review on zinc lozenges for colds that’s come out since LessWrong posts on the topic from 2019, 2020, and 2021. 34 studies, 17 of which are lozenges, 9⁄17 are gluconate and I assume most of the rest are acetate but they don’t say. Not on sci-hub or Anna’s Archive, so I’m just going off the abstract and summary here; would love a PDF if anyone has one.
Dosing ranged between 45 and 276 mg/day, which lines up with 3-15 18mg lozenges per day: basically in the same ballpark as the recommendation on Life Extension’s acetate lozenges (the rationalist favorite).
Evidence for prevention is weak (partly bc fewer studies): they looked at risk of developing cold, rate of colds during followup, duration conditional on getting a cold, and global symptom severity. All but the last had CIs just barely overlapping “no effect” but leaning in the efficacious direction; even the optimistic ends of the CIs don’t seem great, though.
Evidence for treatment is OK: “there may be a reduction in the mean duration of the cold in days (MD ‐2.37, 95% CI ‐4.21 to ‐0.53; I² = 97%; 8 studies, 972 participants; low‐certainty evidence)”. P(cold at end of followup) and global symptom severity look like basically noise and have few studies.
My not very informed takes:
On the model of the podcast in the 2019 post, I should expect several of these studies to be using treatments I think are less or not at all efficacious, be less surprised by study-to-study variation, and increase my estimate of the effect size of using zinc acetate lozenges compared to anything else. Also maybe I worry that some of these studies didn’t start zinc early enough? Ideally I could get the full PDF and they’ll just have a table of (study, intervention type, effect size).
Even with the caveats around some methods of absorption being worse than others, this seems rough for a theory in which zinc acetate taken early completely obliterates colds—the prevention numbers just don’t look very good. (But maybe the prevention studies all used bad zinc?)
I don’t know what baseline cold duration is, but assuming it’s something like a week, this lines up pretty well with the 33% decrease (40% for acetate) seen in this meta-analysis from 2013 if we assume effect sizes are dragged down by worse forms of zinc in the 2024 review.
But note these two reviews are probably looking at many of the same studies, so that’s more of an indication that nothing damning has come out since 2013 rather than an independent datapoint.
My current best guess for the efficacy of zinc acetate lozenges at 18mg every two waking hours from onset of any symptoms, as measured by “expected decrease in integral of cold symptom disutility”, is:
15% demolishes colds, like 0.2x disutility
25% helps a lot, like 0.5x disutility
35% helps some (or helps lots but only for a small subset of people or cases), like 0.75x disutility
25% negligible difference from placebo
I woke up at 2am this morning with my throat feeling bad, started taking Life Extension peppermint flavored 18mg zinc acetate lozenges at noon, expecting to take 5ish lozenges per day for 3 days or while symptoms are worsening. My most recent cold before this was about 6 days: [mild throat tingle, bad, worse, bad, fair bit better, nearly symptomless, symptomless]. I’ll follow up about how it goes!
Update: Got tested, turns out the thing I have is bacterial rather than viral (Haemophilius influenzae). Lines up with the zinc lozenges not really helping! If I remember to take zinc the next time I come down with a cold, I’ll comment here again.
This is actually a crazy big effect size? Preventing ~10–50% of a cold for taking a few pills a day seems like a great deal to me.
I agree, zinc lozenges seem like they’re probably really worthwhile (even in the milder-benefit worlds)! My less-ecstatic tone is only relative to the promise of older lesswrong posts that suggested it could basically solve all viral respiratory infections, but maybe I should have made the “but actually though, buy some zinc lozenges” takeaway more explicit.
David Maciver over on Twitter likes a zinc mouthwash, which presumably has a similar mechanism
If you email the authors they will probably send you the full article.
Does anyone know of a not peppermint flavored zinc acetate lozenge? I really dislike peppermint, so I’m not sure it would be worth it to drink 5 peppermint flavored glasses of water a day to decrease the duration of cold with one day, and I haven’t found other zinc acetate lozenge options yet, the acetate version seems to be rare among zing supplement. (Why?)
Earlier discussion on LW on zinc lozenges effectiveness mentioned that other flavorings which make it taste nice actually prevent the zinc effect.
From this comment by philh (quite a chain of quotes haha):
That’s why the peppermint zinc acetate lozenge from Life Extension is the recommended one. So your only other option might be somehow finding unflavored zinc lozenges, which might taste even worse? Not sure where that might be available
Note that the lozenges dissolve slowly, so (bad news) you’d have the taste around for a while but (good news) it’s really not a very strong peppermint flavor while it’s in your mouth, and in my experience it doesn’t really have much of the menthol-triggered cooling effect. My guess is that you would still find it unpleasant, but I think there’s a decent chance you won’t really mind. I don’t know of other zinc acetate brands, but I haven’t looked carefully; as of 2019 the claim on this podcast was that only Life Extension brand are any good.
Thanks for putting this together!
I have a vague memory of a post saying that taking zinc early, while virus was replicating in the upper respiratory tract, was much more important than taking it later, because later it would have spread all over the body and thus the zinc can’t get to it, or something like this. So I tend to take a couple early on then stop. But it sounds like you don’t consider that difference important.
Is it your current (Not asking you to do more research!) impression that it’s useful to take zinc throughout the illness?
My impression is that since zinc inhibits viral replication, it’s most useful in the regime where viral populations are still growing and your body hasn’t figured out how to beat the virus yet. So getting started ASAP is good, but it’s likely helpful for the first 2-3 days of the illness.
An important part of the model here that I don’t understand yet is how your body’s immune response varies as a function of viral populations—e.g. two models you could have are
As soon as any immune cell in your body has ever seen a virus, a fixed scale-up of immune response begins, and you’re sick until that scale-up exceeds viral populations.
Immune response progress is proportional to current viral population, and you get better as soon as total progress crosses some threshold.
If we simplistically assume* that badness of cold = current viral population, then in world 1 you’re really happy to take zinc as soon as you have just a bit of virus and will get better quickly without ever being very sick. In world 2, the zinc has no effect at all on total badness experienced, it just affects the duration over which you experience that badness.
*this is false, tbc—I think you generally keep having symptoms a while after viral load becomes very low, because a lot of symptoms are from immune response rather than the virus itself.
Thanks!
I woke up this morning thinking ‘would be nice to have a concise source for the whole zinc/colds thing’. This is amazing.
I help run an EA coliving space, so I started doing some napkin math on how many sick days you’ll be saving our community over the next year. Then vaguely extrapolated to the broader lesswrong audience who’ll read your post and be convinced/reminded to take zinc (and given decent guidance for how to use it effectively).
I’d guess at minimum you’ve saved dozens of days over the next year by writing this post. That’s pretty cool. Thankyou <3
I ordered some of the Life Extension lozenges you said you were using; they are very large and take a long time to dissolve. It’s not super unpleasant or anything, I’m just wondering if you would count this against them?
On my model of what’s going on, you probably want the lozenges to spend a while dissolving, so that you have fairly continuous exposure of throat and nasal tissue to the zinc ions. I find that they taste bad and astringent if I actively suck on them but are pretty unobtrusive if they just gradually dissolve over an hour or two (sounds like you had a similar experience). I sometimes cut the lozenges in half and let each half dissolve so that they fit into my mouth more easily, you might want to give that a try?
Interesting, I can see why that would be a feature. I don’t mind the taste at all actually. Before, I had some of their smaller citrus flavored kind, and they dissolved super quick and made me a little nauseous. I can see these ones being better in that respect.
Do you have any thoughts on mechanism & whether prevention is actually worse independent of inconvenience?
The 2019 LW post discusses a podcast which talks a lot about gears-y models and proposed mechanisms; as I understand it, the high level “zinc ions inhibit viral replication” model is fairly well accepted, but some of the details around which brands are best aren’t as well-attested elsewhere in the literature. For instance, many of these studies don’t use zinc acetate, which this podcast would suggest is best. (To its credit, the 2013 meta-analysis does find that acetate is (nonsignificantly) better than gluconate, though not radically so.)