Introduction
[Reminder: I am an internet weirdo with no medical credentials]
A few months ago, I published some crude estimates of the power of nitric oxide nasal spray to hasten recovery from illness, and speculated about what it could do prophylactically. While working on that piece a nice man on Twitter alerted me to the fact that humming produces lots of nasal nitric oxide. This post is my very crude model of what kind of anti-viral gains we could expect from humming.
ETA 6/6: I made a major error in this post and its numbers are incorrect. The new numbers show that matching Enovid’s nitric oxide content, or even getting close enough for a meaningful effect, takes way more humming than anyone is going to do.
I’ve encoded my model at Guesstimate. The results are pretty favorable (average estimated impact of 66% reduction in severity of illness), but extremely sensitive to my made-up numbers. Efficacy estimates go from ~0 to ~95%, depending on how you feel about publication bias, what percent of Enovid’s impact can be credited to nitric oxide, and humming’s relative effect. Given how made up speculative some of these numbers are, I strongly encourage you to make up speculate some numbers of your own and test them out in the guesstimate model.
If you want to know how nitric oxide reduces disease, check out my original post.
Math
Estimating the impact of Enovid
I originally estimated the (unadjusted) efficacy of nitric oxide nasal sprays after diagnosis at 90% overall reduction in illness, killing ~50% of viral particles per application. Enovid has three mechanisms of action. Of the papers I looked at in that post, one mentioned two of the three (including nitric oxide) a second mechanism but not the third, and the other only mentioned nitric oxide. So how much of theat estimated efficacy is due to nitric oxide alone? I don’t know, so I put a term in the guesstimate with a very wide range. I set the lower bound to ⅓ (one of three mechanisms) to 1 (if all effect was due to NO).
There’s also the question of how accurate the studies I read are. There are only two, they’re fairly small, and they’re both funded by Enovid’s manufacturer. One might reasonably guess that their numbers are an overestimate. I put another fudge factor in for publication bias, ranging from 0.01 (spray is useless) to 1 (published estimate is accurate).
How much nitric oxide does Enovid release?
This RCT registration uses a nitric oxide nasal spray (and mentions no other mechanisms). They don’t give a brand name but it’s funded by the company that produces Enovid. In this study, each application delivers 0.56 mL of nitric oxide releasing solution (NORS) (this is the same dose you get from commercial Enovid), which delivers “0.11ppm [NO]*hrs”.
There’s a few things that confusing phrase could mean:
The solution keeps producing 0.11ppm NO for several hours (very unlikely).
The application produces 0.88ppm NO almost immediately (0.11*8, where 8 hours is the inter-application interval), which quickly reacts to form some other molecule. This is my guess, and what I’ll use going forward. It won’t turn out to matter much.
Some weirder thing. ETA 5/25: Thomas Kwa points out that the registration says “0.11ppm*hrs” not “0.11ppm/hr”. I’m on a tight deadline for another project so haven’t been able to look into this; it definitely seems like my interpretation is wrong, but I’m not sure his is right. I’ve reached out to some biology friends for help.
How much nitric oxide does humming move into the nose?
Here we have much more solid numbers. NO concentration is easy to measure. Individuals vary of course, but on average humming increases NO concentration in the nose by 15x-20x. Given baseline levels of (on average) 0.14ppm in women and 0.18ppm in men, this works out to a 1.96-3.42 ppm increase. More than twice what Enovid manages.
The dominant model is that the new NO in the nose is borrowed from the sinuses rather than being newly generated. Even if this is true I don’t think it matters; sinus concentrations are 100x higher than the nose’s and replenish quickly.
Estimating the impact of humming
As far as I can find, there are no published studies on humming as an antimicrobial intervention. There is lots of circumstantial evidence from nasal vs. mouth breathing, but no slam dunks. So I’m left to make up numbers for my Guesstimate:
Paper-reported decline in illness due to spray (0.9)
Proportion of effect due to NO (0.33 to 1)
Adjustment for publication bias (.01 to 1)
Adjustment for using prophylactically rather than after diagnosis (0.75 to 2.5) (set this to 1 if you want to consider post-diagnosis use)
Bonus to humming due to higher NO levels and more frequent application (1 to 5)
I capped the results so they couldn’t suggest that the effect size was less than 0 or greater than 1, and then applied the nasal-infection discount.
Proportion of infections starting in the nose (because infections in the throat should see no effect from humming) (0.9 to 1) (set this to 1 if you believe the spray effect estimate already includes this effect)
From that I get an estimate of effect of 0 to 0.98, with an average of 0.67. This is of course incredibly sensitive to assumptions I pulled out of my ass. If you prefer numbers from your own ass, you can enter them into my model here. For comparison, microcovid.org estimates that masks have an efficacy against of 33% (for thick, snug cloth masks) to 87% (well-sealed n95s).
How to hum
Here is what I’ve advised my elderly parents, and will use myself once I find a way to keep it from activating the painful nerve damage in my jaw:
This really is normal humming, just be sure to exhale entirely through your nose.
If you google “how to hum” you will mostly get results on singing exercises, which I think are suboptimal. This very annoying video has decent instructions on how to hum with your lips sealed.
Higher pitch (where the vibration lives more in the nose and less in the throat) should be more effective, but making it easy to do is probably more important.
You only need to do one breath per session, after that you face diminishing returns.
Once per hour is probably overkill, but it’s also easy to remember. Alternately, pick a trigger like entering a room or opening Twitter.
A beta reader asked if it was worth waking up in the middle of the night to hum. I’m still not a doctor, but my immediate reaction was “Jesus Christ no”. Sleep is so important, and once per hour is a number I made up for convenience. However if you happen to wake up in the middle of the night, I expect that’s an especially valuable time to hum.
The less time between exposure and humming, the better. Since you can’t always know when you’ve been exposed, this suggests humming during and after every high risk event, or making it an everyday habit if you find it cheap.
How long after? For Enovid I made up a plan to use it for one full day after the last high risk period, which my very crude math estimates gives your body an extra day to ramp up your immune system.
Are there downsides?
Everything with a real effect has downsides. I’m struggling to come up with ones that won’t be immediately obvious, like vibrating a broken nose or annoying your spouse, but I’ve been surprised before.
One possible source of downsides is that the nitric oxide was more valuable in the sinuses than the nose. This doesn’t worry me much because sinus levels are 100x nasal levels, and judging from the exhalation experiments sinus levels completely recover in 3 minutes.
The barest scraps of other evidence
This (tiny) study found that Bhramari Pranayama (which includes humming) reduced sinusitis more than conventional treatment. But the same size of 30 (per group) and lack of a no-treatment group makes this hard to take seriously.
There appeared to be a plethora of literature that nasal breathers had fewer respiratory infections than mouth breathers. I wouldn’t find this convincing even every study showed a strong effect (because it’s over such a long time period and impossible to track causality), so I didn’t bother to investigate.
Some dude may or may not have eliminated his chronic rhinosinusitis (inflammation of nose and sinuses) that may or may not have had an infectious component by humming, which may or may not have worked by increasing nasal nitric oxide. He used a very different protocol that to my eye looks more likely to work via sheer vibration than by nitric oxide, especially because a lot of his problem was located in the sinuses.
Reasons to disbelieve
If my model is correct, humming is the equivalent of finding a paper sack full of hundred dollar bills on the ground. Both the boost from humming and the immune function of NO have been known for decades; medical research would have to be really inadequate to produce so little data on this.
All of the data on the impact of nasal nitric oxide is on covid; maybe NO is less effective on other viruses.
If nasal nitric oxide is so great, why did evolution give us the nasal NO concentration it did?
I love me a good evolution-based argument, but I think they’re at their weakest for contagious diseases. Relative to the ancestral environment we have a much easier time finding calories to fuel our immune system and diseases with which to keep it busy, so we should expect our immune systems to be underpowered.
If humming has any effect outside the nose, it has got to be tiny.
Conclusion
Hourly nasal humming might be as effective as masks at reducing respiratory infections. The biggest reasons to disbelieve are the paucity of data, and skepticism that society would miss something this beneficial. If you’re the kind of person who looks at an apparent hundred dollar bill on the ground and gets excited, humming seems like an unusually good thing to try. But if the pursuit of loose bills feels burdensome or doomed, I think you should respect your instincts.
I have an idea for how to generate more data on humming and respiratory illnesses, but it requires a large conference in winter. If you’re running a conference with 500+ nerds, in your local winter, with a majority of attendees coming from locations in local winter, I’d love to chat. You can reach me at elizabeth@acesounderglass.com.
If my interpretation is right, the relative dose from humming compared to NO nasal spray is >200 times lower than this post claims, so humming is unlikely to work.
I think 0.11 ppm*hrs means that the integral of the curve of [edit: nasal] NO concentration added by the nasal spray is 0.11 ppm*hr. This is consistent with the dose being 130µl of a dilute liquid. If NO is produced and reacts immediately, say in 20 seconds, this means the concentration achieved is 19.8 ppm, not 0.88 ppm, which seems far in excess of what is possible through humming. The study linked (Weitzberg et al) found nasal NO concentrations ranging between 0.08 and 1 ppm depending on subject, with the center (mean log concentration) being 0.252 ppm, not this post’s estimate of 2-3 ppm.
If the effectiveness of NO depends on the integral of NO concentration over time, then one would have to hum for 0.436 hours to match one spray of Enovid, and it is unclear if it works like this. It could be that NO needs to reach some threshold concentration >1ppm to have an antiseptic effect, or that the production of NO in the sinuses would drop off after a few minutes. On the other hand it could be that 0.252ppm is enough and the high concentrations delivered by Enovid are overkill. In this case humming would work, but so would a 100x lower dose of the nasal spray. Which someone should study inasmuch as you still believe in humming.
Can you clarify this part? The liquid is a reactive solution (and contains other ingredients) so I don’t understand how you calculated it.
I agree the integral is a reasonable interpretation and appreciate you pointing it out. My guess is low frequent applications are better than infrequent high doses, but I don’t know what the conversion rate is and this definitely undermines the hundred-dollar-bill case.
My prior is that solutions contain on the order of 1% active ingredients, and of things on the Enovid ingredients list, citric acid and NaNO2 are probably the reagents that create NO [1], which happens at a 5.5:1 mass ratio. 0.11ppm*hr as an integral over time already means the solution is only around 0.01% NO by mass [1], which is 0.055% reagents by mass, probably a bit more because yield is not 100%. This is a bit low but believable. If the concentration were really only 0.88ppm and dissipated quickly, it would be extremely dilute which seems unlikely. This is some evidence for the integral interpretation over the instantaneous 0.88ppm interpretation—not very strong evidence; I mostly believe it because it seems more logical and also dimensionally correct. [2]
[1] https://chatgpt.com/share/e95fcaa3-4062-4805-80c3-7f1b18b12db2
[2] If you multiply 0.11ppmhr by 8 hours, you get 0.88ppmhr^2, which doesn’t make sense.
Yeah I definitely misread that ppm/hour. I’m unsure how to interpret *hrs, that seems nonsensical. I’m under a tight deadline right now but have reached out to some bio friends for help. Assuming this doesn’t turn out to be a typo, I’d like to give you a bounty for catching this, can you PM me your paypal info?
I have received a bounty on paypal. Thanks for offering, as well as for laying out the reasoning in this post such that it’s easy to critique.
Wait if 0.11ppm*hr is the integral, doesn’t that suggest the total amount is 0.11ppm? My biologist friends have failed me but that’s this twitter comment’s interpretation.
on the reagent math: I believe the methycellulose is fairly bulky (because it’s sold separately as a powder to inhale), which makes the lower about of NO more believable.
I don’t know what you mean by “total amount” because ppm is a concentration, but that tweet’s interpretation agrees with mine.
The wording ppm*hour being a typo for ppm/hour does not make sense to me because that would be dimensionally very strange. That could mean the concentration increases by 0.11 ppm per hour every hour, but for how long? A single dose can’t cause this increase indefinitely. The only ways that I could see exposure being measured sensibly are:
ppm * hour (NO concentration of nasal air, integrated exposure over time, it is unspecified whether the concentration is 0.11 ppm for 1 hour or 19.8 ppm for 10 seconds or whatever)
ppm (NO concentration of nasal air, peak)
ppm (NO concentration of nasal air, average over the 8 hour interval between doses)
ppm (concentration of the 0.56ml of nasal spray, so 0.11 ppm would be 0.06 nL or 0.06 µg or something of NO delivered).
The spray is clearly delivering a set amount, but describing it in ppm. Since the volume and density of air inside then nose isn’t changing, you can treat the change as a count rather than concentration.
My understanding of the tweet’s model is that [actual released amount] * [8 hours] = 0.11ppm, so [released amount] = 0.11/8.
I still don’t understand your number. Could you expand the equation behind “If NO is produced and reacts immediately, say in 20 seconds, this means the concentration achieved is 19.8 ppm”?
I made a prediction market.
https://manifold.markets/ms/in-a-year-will-i-believe-humming-re?r=bXM
This is pretty cool. I think the fact that the cost is so low is almost a bit worrying. Because of reading this article, I’m likely to hum in the future due to “the potential non-trivial benefits compared to probably minuscule side effects and very low costs”.
In some sense you’ve just made this my default operating hypothesis (and hence in some sense “an idea I give life to” or “enliven”, and hence in some sense “a ‘belief’ of mine”) not because I think it is true, but simply because it kinda makes sense and generalized prudence suggests that it probably won’t hurt to try.
But also: I’m pretty sure this broader meta-cognitive pattern explains a LOT of superstitious behavior! ;-)
Yeah when I was writing this part of me kept saying “but humming is so cheap, why shouldn’t everyone do it all the time?”, and I had to remind myself that attention is a cost. This is despite the fact that it’s not cheap for me (due to trigeminal neuralgia; I’ll probably stick with enovid myslf) and attention is a limiting reagent for me. The too-cheap-to-meter argument is really seductive.
I skimmed the blog post you linked, and it seems like the evidence is compatible with NO also helping elsewhere in your body, beyond just the nasal area?
Beets may increase NO. Canned beets are cheap, convenient, and surprisingly easy to find in stores. I like this smoothie.
I suppose this could also be an argument for varying the pitch of your hum.
I haven’t looked into it; seems plausible it helps, but since it’s a signalling molecule I’m wary of amplifying it too much.
The best known amplifier of NO in the bloodstream is viagra. My understanding is they haven’t found general health effects from it, despite looking really hard and first investigating it as a treatment for heart disease.
My understanding is that viagra increases the rate at which NO is used by the body, but does not produce excess NO.
I hum all the time anyway.
I was thinking that there must be a population of people that do tend to hum often. If the theory is any good then one might try to identify those members of the humming population and do a study on health/wellness.
The first, second, and third considerations in such a study would be ruling out other directions of causality:
Does having a sore throat make people hum less?
Does being healthy make people happy, and therefore inclined to hum more?
Does humming correlate with being in a choir, which may also cause respiratory diseases to be spread more often (in the absence of precautions)?
Does living in close quarters with lots of other people make them likely to stop you from humming, and also make them more likely to pass diseases onto you?
Does having this happen early in life give you a stronger immune system or at least plenty of immunity to common diseases?
Do certain cultures have attitudes towards humming and also attitudes to hygiene that are causally relevant?
...
I would be extremely, extremely skeptical of any study on the subject other than a randomized intervention.
Yes, I suspect doing any type of study (on this or anything else) should inform on much more than some simple H0 rejected type conclusion. Seems like that type of approach, the narrowly focused one, to inquiries into if relationships exist or not is a sure way of not learning as much or sheding light on knowledge/information that would be available.
How would this stack with other ways of increasing NO, for example taking L-arginine?
Possible pseudoscientific downside here:
I have often read that if you’d like to make your voice deeper, humming deeply helps quite a lot. Which means I’d expect the opposite to be true if you’re humming high. That’s a downside or an upside depending on who you are and what you want.
Again, I DON’T KNOW THIS TO BE TRUE. BUT IT SEEMS VAGUELY BELIEVABLE TO ME
When learning to sing, humming is used to extend your range higher. Not sure if it’s used to extend it lower.
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Hopefully, the review is better than karma at judging enduring value. If we have accurate prediction markets on the review results, maybe we can have better incentives on LessWrong today. Will this post make the top fifty?