Consider Taking Zinc Every Time You Travel

by ElizabethAceso Under Glass3 min read1st Oct 202137 comments

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Zinc lozenges are pretty well established to prevent or shorten the duration of colds. People are more likely to get colds while travelling, especially if doing so by plane and/or to a destination full of other people who also travelled by plane. I have a vague sense you shouldn’t take zinc 100% of the time, but given the risks it might make sense to take zinc prophylactically while travelling.

How much does zinc help? A meta-analysis I didn't look at very closely says it shortens colds by 33%, and that’s implied to be for people who waited until they were symptomatic to take it: taken preemptively I’m going to ballpark it at 50% shorter (including some colds never coming into existence at all). This is about 4 days, depending on which study you ask.

[Note: only a few forms of Zinc work for this. You want acetate if possible, gluconate if not, and it needs to be a lozenge, not something you swallow. Zinc works by physically coating your throat to prevent infection, it’s not a nutrient in this case. You need much more than you think to achieve the effect, the brand I use barely fits in my tiny mouth.]

Some risk factors for illness in general are “being around a lot of people”, “poor sleep” and “poor diet”. These factors compound: being around people who have been around a lot of people, or who have poor sleep or diet, is worse than being around a lot of well-rested, well-fed hermits. Travel often involves all of these things, especially by air and especially for large gatherings like conferences and weddings (people driving to camp in the wilderness: you are off the hook).

I struggled to find hard numbers for risk of infection during travel. It’s going to vary a lot by season, and of course covid has confused everything. Hocking and Foster gives a 20% chance of catching a cold after a flight during flu season, which seems high to me, but multiple friends reported a 50% chance of illness after travel, so fill in your own number here. Mine is probably 10%.

If my overall risk of a cold is 10%, and I lower the duration by 50%/4 days, I’ve in expectation saved myself 0.4 days of a cold, plus whatever damage I would have done spreading the cold to others, plus the remaining days are milder. Carrying around the lozenges, remembering to take them, and working eating and drinking around them is kind of inconvenient, so this isn’t a slam dunk for me but is worth best-effort (while writing this I ordered a second bottle of zinc to sit in my travel toiletry bag). It’s probably worth a lot for my friends with a 50% risk of illness, have unusually long colds, or live with small children who get cranky when sick. You know better than me where you fall.

Things that would change this cost-benefit estimate:

  • Seasonality
  • Personal reaction to zinc, or beliefs about its long term effects
  • Covid (all the numbers I used were pre-covid)
  • Different estimates for risk of illness during travel
  • Different estimates for the benefit of zinc
  • Personal susceptibility to illness

Caveats: anything that does anything real can cause damage. The side effects we know about for zinc lozenges are typically low, but pay attention to your own reaction in case you are unlucky. I remain an internet person with no medical credentials or accreditation. I attempt to follow my own advice and I’ve advised my parents to do this as well, but sometimes I’m rushed and forget.

ETA: I originally wrote this aimed at friends who already believed zinc was useful but hadn't considered prophylactic use, and as such didn't work very hard on it. I mistook some rando meta-analysis for a Cochrane review, and didn't look further. There's a pre-registered study that has come out since showing no effect from zinc. There could be other studies showing the opposite, I haven't looked very closely. Plausibly that makes publishing this irresponsible- you definitely should judge me for mistaking a review that mentioned Cochrane for an actual Cochrane review. OTOH, writing too defensively inhibits learning, and I want to think my readers in particular are well calibrated on how much to trust off the cuff writing (but I hindered that by mislabeling the review as from Cochrane).

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Copying my comment from the original site:

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

I feel like as a community we have too much reliance on this one podcast for our zinc usage. I'd love for someone to do an independent analysis.

I don’t think it is worth listening to “a podcast host” on medicine in any circumstance, tbh.

Elaborating, I thought that wouldn’t even be controversial - “I heard it on a podcast” fairly universally precedes advice and ideas that range from questionable to outright false, and maybe out of a dew dozen pieces of scientific or medical knowledge I’ve received anecdotally from heardonapodcast none of them have checked out when I looked.

And that advice in particular really doesn’t mesh with any sort of biochemistry I know of - it’s the exact kind of folk medical advice that wouldn’t work.

Why do you think that?

That’s not a Cochrane review? It’s a review in a different journal. The author apparently wrote a paper criticizing a cochrane review on this topic, which was then withdrawn. That’s weird.

I’m not sold on the meta analysis tbh. Publication bias can happen, lots of things can happen, and it’s well within the realm of “aggregate 15 studies of 80 people each” that have not replicated in the past. Especially given the high doses of zinc.

Shouldn’t this be a rec for a N95 instead? Those will probably reduce respiratory viruses much more than 33%

Shouldn’t this be a rec for a N95 instead?

I'm confused by your framing. Masks are neither perfect nor costless, and I never suggest zinc is a total cure alleviating the need for any other. But your phrasing very strongly implies that one must choose one, and that N95s have been conclusively proven superior.

N95s are, at a rough guess, significantly more effective, and have the massive benefit of not being something you put in your body, which can go wrong a lot of ways (the claimed loss of taste side effect, or just general mild dysfunction)

You're right about the Cochrane review, that was a mistake on my part. I agree that it has wide error bars, and if you think it's exaggerated in general or for you in particular you'll probably make a different decision.

It’s not just personal, in general taking medical advice from reviews in areas you’re not expert in, especially when you haven’t read the review, is probably not great, and as described elsewhere this really doesn’t feel like the sort of thing that would work (compare to magnesium for headache / low energy, which definitely biologically seems somewhat reasonable, although I’m still somewhat iffy on it). That together with personal anecdotes being the sort of thing that Chinese traditional medicine and energy therapy has by bucketloads, and my experience with meta analyses like that regularly falling apart (5-httlpr had a stronger meta analysis with p=0.0001 and four hundred studies, most of which were positive, and then just got executed by a large well done study, https://slatestarcodex.com/2019/05/07/5-httlpr-a-pointed-review/) and priming, with thousands of studies and meta analyses that was also fake and I don’t mean this insultingly because I’ve done this in the past too ... a lot ... smh ... but if you didn’t look closely at the study, it’s probably one of the tens of thousands of bad studies and bad meta analyses that get published so much because so many people want to do them). So I’m pretty confident that the current evidence base for zinc shouldn’t be enough to conclude anything,. And neutral on if it works. But it probably doesn’t because most treatments don’t.

I looked for preregistered trials and found this in 2020 - https://bmjopen.bmj.com/content/10/1/e031662.abstract - preregistration massively helps with both publication bias, post analysis bias, study design, and many other tricks one can do. It found

Results There was no difference in the recovery rate between zinc and placebo participants during the 10-day follow-up (rate ratio for zinc vs placebo=0.68, 95% CI 0.42 to 1.08; p=0.10). The recovery rate for the two groups was similar during the 5-day intervention, but for 2 days after the end of zinc/placebo use, the zinc participants recovered significantly slower compared with the placebo participants (p=0.003). In the zinc group, 37% did not report adverse effects, the corresponding proportion being 69% in the placebo group.

Conclusions A commercially available zinc acetate lozenge was not effective in treating the common cold when instructed to be used for 5 days after the first symptoms. Taste has been a common problem in previous zinc lozenge trials, but a third of zinc participants did not complain of any adverse effects. More research is needed to evaluate the characteristics of zinc lozenges that may be clinically efficacious before zinc lozenges can be widely promoted for common cold treatment.

Which I find much, much more persuasive. Also note the side effect rate and the (admittedly, subgroup, so it is probably meaningless) lower rate of recovery for takers.

I note that that study used lozenges with orange flavoring, which according to the podcast I think we'd expect not to work. (Presumably it contains citric acid, at minimum.)

... what? Read the study. It mentions the potential interaction with citric acid, and avoids it;

The zinc lozenge was a commercially available zinc acetate lozenge with 13 mg elemental zinc per lozenge (University Pharmacy, Helsinki, Finland). The lozenge weighed 0.9 g and had a diameter of 13mm. The lozenges contained isomaltulose, sorbitol, magnesium stearate, orange and peppermint flavours and sucralose. The instruction of the commercial package for patients with common cold is to dissolve slowly six lozenges per day in the mouth, which

Now, this study does use mannitol. And mannitol is one of the things mentioned by some studies as blocking zinc’s action. So maybe we’re out of the water! But wait - four of the eight studies in the meta analysis have acidic flavoring - “lemon and lime oils”, “peppermint oil”, “tannic acid”, etc. even worse, glycine is also mentioned as a zinc binder that hurts its action - yet many of the studies it cited use glycine!

Also, one study this meta analysis cites concludes that “zinc gluconate should not be used to treat cough due to high side effects”.

That said, it’s not clear at all. Maybe a particular combination of excipients did randomly manage to make some trials fail and others succeed! But that’s what you’d expect to happen in a case of no effect but publication bias and excuses. Which seems more likely?

I confess that reading these studies in any depth makes my eyes glaze over. But I did see the first mention of citric acid in the paper (out of two, according to ctrl-F) before writing my comment, and it doesn't say they avoid the interaction. The mentions are

Several randomised trials have been carried out to test whether zinc lozenges might have treatment effects on the common cold but the findings are mixed. Eight studies have reported significant benefits of zinc lozenges,1–9 whereas 12 studies did not find benefit;9–15 one report published six9 and another two separate trials,10 and one study was published in two separate reports.2 3 Zinc ion can tightly bind to a number of substances, such as citric acid, potentially preventing the release of free zinc ions from lozenges in the oropharyngeal region. Therefore, the formulation of a zinc lozenge is crucial in determining whether a particular lozenge is efficacious. Shortcomings in the formulations and low doses could explain most of the negative findings.16–19

Eby commented that the majority of zinc lozenges on the US market in 2008 were expected to be ineffective against colds.16 Most of the zinc lozenges he surveyed contained citric acid, which binds zinc ions, and many lozenges had such low doses of zinc that they were unlikely to have any pharmacological effects. Thus, although there is evidence from several trials that properly composed zinc lozenges may shorten the duration of colds,1–9 a patient with ordinary common cold cannot easily materialise the benefit by zinc lozenges available from a drugstore, a problem further supported by our findings on the 5-day zinc acetate treatment.

Neither of these says that they used a lozenge without citric acid. I assumed that citric acid was part of the orange flavoring.

Now, this study does use mannitol. And mannitol is one of the things mentioned by some studies as blocking zinc’s action.

(Not important, but I assume you mean "sorbitol" here.)

That said, it’s not clear at all. Maybe a particular combination of excipients did randomly manage to make some trials fail and others succeed! But that’s what you’d expect to happen in a case of no effect but publication bias and excuses. Which seems more likely?

Yeah, it's a big confusing mess. Given the state of the literature, if I tried the lozenges and they didn't work, I wouldn't be too surprised. Nor would I be shocked if I tried some lozenges with citric acid and they did work. But

  1. The literature doesn't seem to seriously engage with the podcast's "here are a bunch of ways you can fuck up a zinc lozenge, but don't do any of these and it'll be fine" hypothesis? Maybe I just haven't looked closely, but the studies generally seem to be comparing one brand of lozenge against placebo, not one brand against another. The meta-analyses seem to group studies by salt or dose, not by "does the podcast's hypothesis predict this will work". Which isn't necessarily unreasonable, but I think it does mean that a big confusing mess isn't as big a red flag as it might be otherwise.

  2. This is something anyone can test for themselves fairly cheaply. I've tested it for myself, and I'm fairly confident it works for me. (At least the "these lozenges work" part, not the "these other lozenges don't work" part.) This seems like a reasonable way to proceed, in the face of a big mess of evidence and a cheap way to test for oneself.

I looked for orange flavor online, especially in bulk on alibaba and flavor supply, as well as smaller consumer packages, and it seemed to in basically every case mean orange essential oils, which I don’t think have citric acid as it is hydrophilic (https://en.m.wikipedia.org/wiki/Orange_oil). If said oil did give citric acid, so would the lemon oil. No clue exactly though.

You didn’t look closely, correct. The literature does engage with the “mannitol, sorbitol, citric acid, glycine, and many others may cause past studies to not find an effect”. At least five of the eight studies referenced in the meta analysis, the meta analysis itself, the other paper, and many other studies make statements to that effect and are designed to avoid it. It’s still a mess though.

As for testing yourself - unless you do a blinded, well done, long term, controlled self experiment a la Gwern, it’s so easy to make a mistake that it probably is meaningless. I have over the internet seen hundreds of “this worked for me!” with many different methods of confirmation and levels of confidence - most of them ended up being very wrong. Here, Gwern takes magnesium - sees a benefit or signs of benefit - then does several detailed and careful self experiments and finds it causes significant harm. https://www.gwern.net/nootropics/Magnesium There are so many other examples.

Fair enough re: flavoring. (I did have a quick look myself earlier, but didn't find anything. Thanks for being more thorough.)

The literature does engage with the “mannitol, sorbitol, citric acid, glycine, and many others may cause past studies to not find an effect”. At least five of the eight studies referenced in the meta analysis, the meta analysis itself, the other paper, and many other studies make statements to that effect and are designed to avoid it.

To clarify, do they do "we tested a zinc lozenge with some of these things and a zinc lozenge without (and maybe also a placebo)"? That's the kind of thing I meant by taking it seriously. If we want to compare condition A and condition B, my sense is we can learn a lot less from "study on condition A, study by different group on condition B" than a study comparing them directly.

As for testing yourself—unless you do a blinded, well done, long term, controlled self experiment a la Gwern, it’s so easy to make a mistake that it probably is meaningless.

Eh, honestly I just don't think this is true in this case. There are ways I could have made mistakes - it's possible that

  • The first cold I took them for just got better really fast naturally.
  • And then I didn't catch one for a year and a half, despite twice thinking I was coming down with one.
  • And then when I did get one, it had fast onset and unusually light symptoms. Or I just didn't remember what it was like to have a cold by then.

Or maybe I got more colds than that and completely forgot about them. I acknowledge that this kind of thing is possible. I don't think it's super likely. I definitely don't think it's likely enough that I should consider my experience meaningless.

Also what’s going on here? The evidentiary standard and level of evidence is much lower for pro zinc evidence - this (very incorrect) speculation that could’ve been corrected by reading more than two paragraphs of that article, for whatever reason, was much better received than mine. Several times you guys have clearly referenced studies without reading them, and your post got 10 to 1 vs mine that actually read the papers!

To clarify voting: users have different vote strengths based on karma, and the ability to give a "strong" or "weak" vote. My own weak vote is worth two points, and my strong vote is worth 8. If you hover over a comment's score, you can see how many people voted on it. (More info.)

I have two comments currently at +10, "I note that that study..." and "it will wash off over time...". Both of them have only two votes, my own +2 vote and someone else's +8. I'm curious myself why someone (or possibly two different people) thought these comments were worth a strong upvote. But they both have only one person voting for them other than my own default vote.

(For myself, I've upvoted the article, and philip_b's "I have common cold...", and have my own default votes. I initially downvoted your "I don't think it is worth..." but retracted that vote after you edited. I've made no other votes in this thread currently.)

Oh. I can’t hover, makes sense

Do you have a tool you use to grab pre-registered studies in particular?

uh.

google scholar? you just search the word? preregistered.

you're right, pre-registration is very useful, that study does make me less confident in zinc and this advice. I appreciate the addition. 

Something that may not be obvious is that when I say "here's this cochrane review/meta-analysis", I expect readers on LW and my own blog to be well-calibrated on how strong that evidence is (not very). This was not an attempt to make a conclusive case for Zinc, but to suggest a particular use case to people I knew were already sold on the general benefits (plausibly wrongly- and I think they would all appreciate it if someone did a more comprehensive review). 

Cochrane reviews in particular are actually, like, literally, the gold standard for medical reviews. They are notorious for finding that “there is weak or no evidence”. So them finding positive is not “well calibrated for not very”, which is why I was genuinely shocked to read that, and correctly found it wasn’t.

Is there some material I can read on the case for zinc? On this site?

I have common cold (or something similar) about 10 times a year and this saddens me a lot. Due to this and philh's posts, I've just ordered the recommended zinc which will in expectation last me about 14 months. Feel free to ask me later if I noticed any effects.

Zinc works by physically coating your throat to prevent infection, it’s not a nutrient in this case. You need much more than you think to achieve the effect, the brand I use barely fits in my tiny mouth.

Huh? I'm trying to picture what that would look like and I'm imagining a jawbreaker candy. That's not that what you mean, is it?

And why would the size matter if the goal is to coat your throat? A larger size would mean more contact with your mouth, but not your throat.

I think she’s taking the Life Extension ones, I saw those mentioned on a page linked from SSC in the early part of the pandemic and ordered a bunch (mostly because they were all out-of-stock at the time then suddenly a few months later I received several packages, whoops).

But yeah they’re about the size of a jawbreaker but cylindrical and you suck on them instead of chewing and you don’t eat or drink for 15 minutes after if you’re using them as directed. My mouth does feel very coated when it’s done and tastes kind of bitter for awhile.

On the LE bottle it tells you to not take them for more than three days straight and to take them with copper (because zinc depletes copper over time).

I'm assuming you need enough raw physical material to cover your mouth, which means either you either need one big one or multiple small ones.

I’m reading “coat” to mean “water with dissolved zinc will reach the side of your throat, and then the concentration of the ions does something or another”. A bit iffy on that, tbh. Do any other drugs of atomic ions work like that? It doesn’t exclude it, biochemistry can get weird, but...

Also wouldn’t the constant swallowing and cycling of mucus make any coating wash off?

Also wouldn’t the constant swallowing and cycling of mucus make any coating wash off?

It will wash off over time, but you take several a day.

Wouldn’t it wash off much faster than six hours though?

(I can’t see the starch or cellulose in pill binders mixed with zinc “physically coating” the throat, because solid matter tends to go down it)

A question occurs to me after reading the comments.

Is the implication here that most/many common cold  infection pathway is via the throat rather than the nose?  

I don't think so- it would have a bigger effect if that were true. 

For covid in particular the hypothesis was that it prevented transition between an annoying but harmless-to-most upper respiratory infection, to a very serious lower respiratory infection. I don't know if that panned out for covid or if it transfers to other viruses, but it seems very plausible. "Nasal infection unaffected but progression to lungs inhibited" is an extremely specific prediction that should be fairly easy to measure but I couldn't find anything on it in a few minutes on google scholar, which I find very disappointing.

Russians can buy the lozenges recommended by both Elizabeth and philh on iherb: iherb.com/pr/life-extension-enhanced-zinc-lozenges-peppermint-30-vegetarian-lozenges/87151

Isn't getting a flu vaccine an even better strategy?

Most common colds are not flu.

Why not both?