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Is this info on zinc lozenges accurate?

by philh4 min read27th Jul 201922 comments

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PracticalWorld Modeling
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Podcast: Zinc Definitely Fights Colds, But You’re Probably Using the Wrong Kind

This podcast claims that zinc lozenges are "probably almost essentially a cure for the common cold". But there are many caveats:

  • must be zinc acetate or zinc gluconate (but gluconate is strictly worse)
  • use immediately on getting a cold
  • 18mg zinc per lozenge
  • dissolve in mouth 20-30 minutes
  • take every 2 hours
  • must have metallic taste, astringency
  • must free of anything ending -ate (except stearate) or -ic acid; free of magnesium except magnesium stearate (it's insoluble)
  • only one product on the market satisfies these requirements

The guy sounds to me like he knows what he's talking about. But I don't have the technical expertise to really know. (I think I could detect a mediocre bullshitter, but not necessarily a high level one.) If true, it seems like the sort of information that would be good for more people to know; but also like the sort of information that would be more widely known if it were true. (But I can sketch an argument for why it might not.) The research section at the linked page cites three journal articles of which two are open access, but I haven't looked closely at them.

My own experience is that I got some of these lozenges about a year ago, after reading a transcript of the episode. I thought I'd gotten them too late, but my cold cleared up much faster than I would have expected otherwise. Since then I've been trying to collect more anecdotal data, but my body is stubbornly refusing to even start coming down with a cold. Twice I thought it might be, and I took lozenges and didn't; but I think I took one lozenge on one occasion and three (spaced out) on another, and he thinks they shouldn't be effective enough for that to have worked. I'm not sure what to make of this, except that it shouldn't be much given the sample size.

Unfortunately the transcript has now been removed, and I can't find it on archive.org. I've made notes of the first ~35 minutes (of ~70). If someone could take a look (or listen), and say whether it all seems basically accurate, that would be fantastic. Almost all of it seems consistent with what I think I know, with one surprise that I've bolded. Apologies for the poor formatting.

  • zinc is important to the immune system in ways that are irrelevant to this. If you aren't getting enough, you'll probably benefit from getting more. Good sources are oysters, red meat and cheese.

  • RDA for zinc is satisfied by eating oysters once a week or beef once a day

  • it's more prevalant and also more bioavailable in animal foods than plant foods. So if you mainly eat a plant diet you may benefit from supplements or zinc-rich foods

  • phytate (grains, nuts, seeds are good sources) is "storage house for minerals"; allows plants to germinate & grow when conditions are right. Phytates make zinc less bioavailable in both the meal and supplements

  • but again this is separate from using zinc to cure colds

  • George Eby's 3yo daughter with leukemia had many colds, given 50mg zinc gluconate, refused to swallow, cold disappeared

  • Eby and colleagues published RCT in 1984 showing zinc lozenges could reduce median cold duration 5 days mean duration 7 days; basically cures cold

  • Almost every zinc lozenge on the market is useless for this purpose

  • ionic zinc (+ve charge, free not bound to anything) affects nasal tissue and adinoid tissue (lymph tissue in throat) i.e. two major sites of infection during cold: inhibits activation of viral polypeptides that are used in replication of cold virus; inhibit production in our cells of ICAM 1 (intracellular adhesion molecule 1) which is dock that allows virus to grab hold of cell and enter it

  • zinc products are all salts, not ionic. So we need one that releases ionic zinc in the relevant tissues at the right time

  • zinc interferes with replication of virus. So you need to take it almost immediately after being infected or at the first sign of symptoms

  • cold incubation period ~1 day, no symptoms, contagious; 2-3 days where replication and symptoms are increasing; then it peaks and declines, after 5 days basically undetectable but your symptoms may continue. So if you start using them 2-3 days in, they probably won't do anything

  • tablet or capsule releases zinc into stomach so that's no good

  • nasal sprays can kill your sense of smell

  • zinc released from a lozenge will reach your nasal tissues and throat tissues

  • some say you want a salt that releases ionic zinc at the pH of saliva. But actually it needs to release at pH of your nasal and throat tissues

  • saliva pH is 5; over 100 times more acidic than pH of cellular environment which is 7.4

  • 7.4 is basic, right? "100 times more acidic than [something on the other side of neutral]" seems like a weird thing to say? It sounds to me like "-5°C is 100 times more freezing than +2°C". Also, if I google "pH of saliva" I see 6.2 to 7.6. (I wouldn't be at all surprised to discover I'm just wrong about the acidic/freezing analogy.)

  • lots of zinc salts release ionic at pH 5, only a handful at 7.4

  • of salts in lozenges, only acetate and gluconate release any meaningful amount

  • at 7.4, gluconate is 50% ionic and acetate is 100% ionic. so zinc acetate should be twice as effective

  • most lozenges are neither; only one is acetate

  • zinc in your mouth has a metallic taste (astringent), dries it out. So people try to make zinc lozenges more palatable

  • but the astringency comes from the ionic zinc in your mouth. So if it's not astringent, it's not gonna help.

  • OTOH being astringent doesn't mean it will help, because that's in your saliva not your nose/throat tissues

  • food acids e.g. citrate or tartrate will very tightly bind zinc

  • studies with citrate or tartrate in lozenge seem to suggest it actually makes the cold last longer

  • ionic magnesium delivered to nose/throat tissues will nullify zinc, increase replication of cold virus

  • one product tested found harmful was produced with very high heat in presence of fats, maybe palm oil; high heat produced insoluble zinc waxes with the fatty acids

  • lubricants used in supplements, like magnesium stearate or other stearates, are insoluble; so they don't yield an acid that could bind to the zinc and don't yield much ionic magnesium and don't cause problems

Copper

(Section added 2020-03-09)

I had originally hoped to get some solid confirmation or disconfirmation of the science, and then write up a clearer recommendation post (or not do that, in the case of disconfirmation). That didn't happen, which is fair enough, but it means I haven't written that post.

In the meantime, I've been linking people here for "why I recommend these lozenges", and yesterday SSC linked here too. When I wrote it I optimized for "get something out there", not "include all the information". That seemed fine when I originally wrote this and didn't necessarily expect anyone to actually act on it, but now it's getting more visibility and I'm actively recommending people to act on it.

And in particular, there's a potentially important safety note included in the half of the podcast that I didn't make notes on. Probably not a big deal, but still. Potentially.

So: if you take these, you may want to consider copper supplements. From memory: the podcast host thinks it's probably fine not to, but he does just in case. The ratio of zinc:copper in your bloodstream has a high acceptable range (this says 8:1 - 15:1, and I think the podcast said something similar), and probably most of the zinc in these lozenges isn't entering your bloodstream anyway.

My honest guess is that you don't need to worry. I only got some recently, and I've only taken one so far. But I think I've been remiss not to mention this in writing until now.

Buying

By request, I think all of these links are to the correct product:

Life Extension US

Life Extension Europe

Life Extension UK

Ama­zon UK

Amazon US (The "from the manufacturer" section has a picture of a different product and says something about zinc methionate. But I think the product is correct and that section is just confusing.)

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I recall Rhonda Patrick suggesting the TheraZinc oral spray (citation needed), which contains zinc gluconate. Unfortunately, it's a US-only product. (https://quantumhealth.com/shop/product/therazinc-oral-spray)

2philh1yInteresting! I don't see an obvious reason that wouldn't work based on my current knowledge, and the website sounds like they either know what they're doing or are surprisingly good fakers. But neither of those is very compelling. And I know little-to-nothing about most of the things on the ingredients list. One thing I noticed on the list was "polysorbate", violating But according to wiktionary, -ate usually refers to a derivative of an -ic acid, and it looks like there's no such thing as polysorbic acid. So maybe polysorbate is okay. (And being in a spray might change things anyway. E.g. if it reaches the relevant tissues sooner maybe it makes less difference if there are other things for the zinc to bind to?) A serving (8 sprays) has about half as much zinc gluconate as a lozenge has acetate, so it should be a quarter as effective; except again for the spray thing, which presumably makes up for it some amount. It does seem to be available [https://www.amazon.co.uk/Quantum-Health-Thera-Spray-Ounce/dp/B003EIPCDK] in the UK as well. I'm tempted to buy some for my partner, who finds the lozenges much more unpleasant than I do. (Oh, but on the negative, they make their zinc lozenge [https://quantumhealth.com/shop/product/therazinc-organic-bagged-lozenges] sound about as compelling: "This simple and tasty formula provides 7 mg of zinc in a targeted, bioavailable form. Zinc gluconate is the chelated form that has been used in multiple immune health studies. Our lozenge delivery releases the zinc ions in your throat and mouth for effective immune support." But if the podcast is accurate, it shouldn't work (except generically as a zinc supplement), because you can't eliminate the metallic taste without ruining the effectiveness. And again I don't know much about the ingredients, but I wouldn't be surprised if "natural blood orange" contains vitamin C aka citric acid.)
20 comments, sorted by Highlighting new comments since Today at 3:48 AM

I bought some of these lozenges, and anecdotally, they seem to help me recover from colds faster also.

Are you able to be more specific?

My feeling is that if the podcast is accurate, and you're taking them correctly, the effect should be really pronounced. (For me, the uncertainty is "did I have a cold at all?", except for the first time when I took them too late.)

If you're taking them as recommended and have an effect size like "yeah, this seems to knock a couple of days off, I think", then... while they still seem like good things to recommend, it feels like pretty strong evidence against the main thrust of the podcast. (With caveat that I'm not sure how much individual variance to expect.) E.g. I wouldn't describe them as "these things cure colds" if that's the typical experience.

My model is that viruses grow exponentially in your body, so it's best to nip them in the bud as soon as possible. I've tried to become really good at noticing symptoms of a cold very early on, including subtle body sensations which aren't listed as standard cold symptoms. Then I aggressively respond by: taking it easy, drinking lots of gatorade/water (especially in the middle of the night if I wake up briefly while sleeping), gargling warm salt water, sucking zinc lozenges, etc.

Before I did this, I would get sick and it would take me forever to recover. Since I started doing this, it feels like I'm usually able to nip it in the bud if I'm sufficiently proactive and keep doing this stuff for a bit even when it feels like the cold is probably gone.

It's hard to separate the effects of different things, but intuitively, vitamin C/ordinary supplemental zinc don't feel as helpful as theanine and ashwagandha, and gargling warm salt water seems to help right away. The zinc lozenges feel more helpful than any other supplement, but I wouldn't say they are the most important tool in my arsenal either.

I have not the faintest clue about zinc or your overall question, but this part:

saliva pH is 5; over 100 times more acidic than pH of cellular environment which is 7.4
7.4 is basic, right? "100 times more acidic than [something on the other side of neutral]" seems like a weird thing to say?

pH is basically the (negative) exponent in the concentration of H+; a concentration of 10^-2 gives a pH of 2, a concentration of 10^-7 gives a pH of 7. So moving from 5 to 7 on the pH scale is a factor of 100 in the concentration of H+. That's why they say it's "100 times more acidic". (Also, the neutral point in the pH scale is neutral because that's the concentration at which the positive H+ ions are balanced by negative...usually OH-...ions.)

Thanks!

I take it the concentration of H+ is inversely related to the concentration of negative ions, because if there's a high concentration of both, they'll just bind each other?

And when it comes to producing zinc ions from, say, zinc acetate - the H+ captures the acetate away from the zinc, but the negative ion doesn't then bind the Zn+? (Or at least not quickly enough to stop it binding in the cellular tissue?)

(This probably doesn't have much bearing on the question at hand, I'm just curious.)

I take it the concentration of H+ is inversely related to the concentration of negative ions, because if there's a high concentration of both, they'll just bind each other

For the most part, and to my limited memory of chem...yes.

H+ captures the acetate away from the zinc, but the negative ion doesn't then bind the Zn+

Umm. Hmm. *goes back and reads the relevant parts of your post* I don't know any of this off the top of my head. Let's see... Wiki says zinc acetate is a salt of zinc and acetic acid. Ok, so zinc acetate is already zinc ions and acetate ions. (CH3CO2-). Two of those ions for each Zn, so each Zn ion is Zn+2. You stick the Zn(CH3CO2)2 into the pH 5 saliva solution, which has a lot of extra H+ sticking around. The H+s in the pH 5 solution are already outnumbering any loose negative ions...that's what it means to be pH5. So when you stick the salt in it, the H+s grab the negative acetate ions and tear the salt structure apart. The Zn becomes free-floating ions because there aren't enough negative ions around to bind with them.

If you drop the zinc acetate in a neutral solution, it might still dissolve into ions; sometimes with water, what happens is basically everything just pulls at everything else, and things stay in constant flux instead of settling into neutral compounds. [This is my understanding of what happens with NaCl, for example: you don't get NaOH and HCl so much as you get lots of Na+ and Cl- floating around in H2O with the H+ and OH-, constantly forming and unforming all the possible combinations in insignificant amounts.]

I feel compelled to point out here that low pH values are bad for your teeth. Low pH destroys the protective biofilm and leaches phosphorus and the like out of the teeth, weakening them and leading to cavities. I only know this because I recently proofread a dentist's book all about it. So, like, maybe don't try to lower your saliva pH to get more zinc.


Just a side note on the acid is bad for teeth. For those worried about the health of their teeth in this regard, drink a lot of colas, coffee and the like, I found a tooth paste available on Amazon called APAGUARD m-plus. It's a Japanese tooth paste that includes nano hydroxyapatite, Ca10(PO4)6(OH)2. It works a bit like fluoride in helping to seal the small holes (tubes) and cracks in the enamel but also seem to help rebuild both the enamel and dentine of the teeth. It will also help with bones but if your gums are healthy probably doesn't ever reach that level.

From what I have been able to find, this was developed by NASA to help rebuild the skeletal integrity of astronauts returning to earth. It's also used as a coating for joining artificial joints with the natural bone.

I've been using it for about a year now and it seems to work well for me. The key factor for me was that other "sensitive" teeth tooth pastes my dentist has recommended seem to rely on including a mile pain killer as actually solving the problem. m-plus doesn't list anything as a pain relief component (on Amazon but the labels are all in Japanese which I don't read.)

I've been using the Boka brand of nano hydroxyapatite toothpaste.

It has a pain killer: methylsulfonylmethane.

I'm using it because it seems safer than flouride, but I don't have much evidence, and I wasn't trying to solve any specific problem with it.

Ah, the relevant pH is 7.4, not 5, so with negative ions slightly outnumbering positive. So I guess there's another factor than numerical quantity in why they don't bind the zinc. But "things staying in constant flux" sounds like it could be that factor, thanks :)

must free of anything ending -ate (except stearate) or -ic acid; free of magnesium except magnesium stearate (it's insoluble)

The only product you link violates this. It contains stearic acid...

edit: Chris explains this here: https://chrismasterjohnphd.com/podcast/2016/12/26/zinc-definitely-fights-colds-youre-probably-using-wrong-kind/#comment-48164

" The stearate isn’t a problem. I was trying to simplify. "

Huh, yeah. Thanks for pointing that out.

Annoyingly, "the stearate isn't a problem" doesn't answer the question, which is about stearic acid. I assume he meant to say that stearic acid is fine too, but I've posted a comment there to clarify.

I read your article. Nice work and summary. Thanks for you work.

I wanted to buy some zinc lozenge, especially for my parents (in case of COVID). I made quite a big research on internet and I'm pretty convinced for that. Only one doubt I have - afa magnesium stearate is concerned (because I read that that magnesium generally, in form of ions can increase virus replication). 

I know - in most of sources is that magnesium stearate there is not a problem - for example - I read there is only max 5% of magnesium stearate in a pill/ lozenge (and usually not more that 1,5%). And in magnesium stearate itself is only 4% magnesium. And megnesium stearate is hardly soluable in water (although saliva has a light acidic profile), it falls apart in stomach acid environment and (I think) magnesium ions are not "released" in saliva from magnesium stearate. 

What is more - in some surveys on zinc lozenge effect on cold there were lozenges with magnesium stearate and were successful in shortening cold. And I think, that I read, that some of other anti-viral official medicaments have magnesium stearate (but about that I'm not 100% sure).

So, why have I any doubt in this situation? Because of this sentence in one paper: "Magnesium stearate was not used as a lubricant due to concerns about concentrated magnesium greatly stimulating rhinovirus replication"  ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457799/ ). And this is sentence of George Eby, who wrote couple of papers on zinc-effectivenes.

How do you think?

PS. Afa I'm concerned I think that I anyway buy lozenges for my parents and myself

How do lozenges differ from tablets? If lozenges are out of stock, is sucking on tablets useful?

I don't know and I don't know.

Well, a tablet would be a lot smaller. If they worked at all... I guess either they'd be really low dose compared to a lozenge, and you'd have to suck on many many of them; or they'd be highly concentrated, and then sucking on many many of them seems like a bad idea and sucking on just one seems unlikely to work very well (it's supposed to spend a while dissolving).

If you have specific tablets in mind, you could look at the formulation and see whether, if they were lozenges, they'd be acceptable. I wouldn't be at all surprised if the difference between a tablet and a lozenge is something that would rule out all tablets.

Positive evidence:

Two people besides me on this SSC thread report that zinc works well for them. One uses the same brand listed. The other uses HealthSpan Elite Zinc Defence Lozenges, and I don't see anything in the ingredients list that looks like those shouldn't work.

(Edit: but I now notice the dose seems lower than ideal. Taking lots of them might be sufficient. Slightly more detail in linked thread.)

So maybe there are two products on the market! Some possible explanations for why the podcast host didn't mention them:

  • They might not have been on the market at the time (podcast recorded in 2016, oldest review of the lozenges is from two years ago).
  • I haven't checked whether they ship outside the UK. If not, he might have disqualified them before or after investigating. (Edit: they do seem to ship outside the UK.)
  • He might just not have found them. I don't know how thoroughly he searched.

Negative evidence:

I did get a cold a few months back. (At the end of one day, I realised that I was feeling a bit blergh and decided to take lozenges the next day. Next day I already had a sore throat. I took lozenges anyway, and while I'm not confident it made it go away faster, I do think the symptoms were less unpleasant than my historical colds. I didn't keep a log of them, though.)

(But that's still only one cold in about a year and a half.)

Overall I'm more confident than I was when I posted this.

Can you add a link to the product that fulfills the criteria?

I've put some links in a comment below. I'll edit them into the post as well when I get a chance.

I think these links are all to the correct product:

(LE US) https://www.lifeextension.com/vitamins-supplements/item01961/enhanced-zinc-lozenges

(LE Europe) https://www.lifeextensioneurope.com/enhanced-zinc-lozenges-30-vegetarian-lozenges

(LE UK) https://www.lifeextensioneurope.co.uk/enhanced-zinc-lozenges-30-vegetarian-lozenges

(Amazon UK) https://www.amazon.co.uk/Life-Extension-Enhanced-Lozenges-Vegetarian/dp/B00PYX2SVM/ref=sr_1_1?crid=30H97UHDCVWSB&keywords=enhanced+zinc+lozenges&qid=1564268937&s=gateway&sprefix=enhanced+zinc+lo%2Caps%2C149&sr=8-1 ("You purchased this item on 5 Dec 2018", so unless they changed the product while keeping the same product id, it should be good.)

Not sure what's up with your amazon US link. The description talks about zinc methionate, but the ingredients list in the picture says acetate. I would guess it's correct.

And now I'm even more confused, it appears the two remaining lozenges on the life extension site don't seem to follow the guidelines recommended above, and the "plain lozenges" that were originally recommended, are no longer on the original site nor on Amazon.