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.

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

1. 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. 
2. All of the data on the impact of nasal nitric oxide is on covid; maybe NO is less effective on other viruses.
3. If nasal nitric oxide is so great, why did evolution give us the nasal NO concentration it did?
   1. 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. 
4. 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.