Nudging My Way Out Of The Intellectual Mosh Pit

As part of my ongoing effort to improve my cost/benefit ratio on social media, I’m nudging myself away from intellectual mosh pit platforms like Facebook and Twitter, and towards blog posts, articles, videos essays, etc. Really longform consumption (e.g. books) remains about the same, my limitations on that are mostly my insistence on fact-checking nonfiction and very narrow tastes in fiction, this post is about changing what I reach for when I’m bored in a line. Towards that goal I have made a few changes, which I list here roughly in ascending order of how much effort they were:

  • Put all of my screens in greyscale. If you only try one thing on this list, make it this one. It takes five seconds to test once you have instructions, and the relief for me was immediate and has lasted days so far. Every time I have to turn color on to look at graphs I resent it. 
  • Discovered the existence of Focus Mode for android, which allows you to use the internet but disables notifications.
    • All of the Focus Mode instructions require several clicks into a deep menu. You can access it more easily by enabling the relevant fast-access card, using the instructions for older Android phones above. 
  • Moved all my short-OODA-loop apps off my phone home in favor of long-OODA-loop apps.
    • The newly defavored apps include obvious candidates like Twitter, but also all messaging apps and Chrome itself.
    • The new stars include my article aggregator, as well as very long-form content like Kindle, Audible, and PodCatcher.
    • The home screen continues to hold non-content-consumption apps I want to access quickly, like Maps, Calendar, etc. 
  • Resumed use of a read-it-later tool, which lets me save cool articles I see on social media to be consumed when I’m in a better head space (I can’t switch between reading microblogs and regular blogs quickly – different headspace ).
  • Switched to an RSS reader that lets me read things out of order without marking earlier articles as Read.
  • Combined my RSS feeds, email newsletters, and saved articles in a single service (that lets me read in any order) so I can choose from all my essay-length options at once. This was a stupid amount of effort and yak shaving and it’s not pretty but I got it working. Most of this post will be about that.

How to Combine All Article-Length Content

The following instructions work with both Inoreader and Feedly. I eventually chose Inoreader but it was a close call and your mileage may vary.

  1. Import your existing RSS feeds to Inoreader.
    1. Feedly instructions.
  2. You have two options for saving arbitrary content to your new aggregator. 
    1. Inoreader has a built-in feature to do this with a Chrome plugin, but there’s no way to see saved articles and RSS articles in the same list. So if that’s important for you…
    2. Sign up for Pocket, the leading read-it-later app, and configure Pocket to put your saved articles on an RSS Feed, then add that RSS feed to Inoreader per normal.
      1. Install the save to Pocket extension in your browser to make it easy to add to the feed as you come across things you want to read at some point (note: not available for Android, so I have to manually copy the URL and open the Pocket app).
        1. All articles in the saved-to-Pocket feed will show in Inoreader as having the same author (“my content feed”) and they won’t have the body of the article, only the title and header image. I really care about having all of my articles in the exact same place, but if you don’t, just using save-to-Inoreader will save you several steps.
  3. You also have two options for newsletters.
    1. Set up forwarding using Inoreader’s built-in system.
      1. This is a Pro feature, so it’s $6/month. 
        1. Feedly version ($12/month)
      2. You will either need to set up a new email for every subscription (which Inoreader supports, although you’ll need to upgrade past 20 subscriptions) or they will all be listed as having the same author.
    2. Or use a newsletter-to-RSS conversion tool like kill-the-newsletter.com, and add the resulting RSS feed to Feedly. Unless substack lets you configure separate emails for each subscription this will still require you to set up forwarding.

Tada! With a mere 20 minutes of work and a small monthly fee you have a system that combines all of your article-length-content in one place. Inoreader and Feedly both support Youtube channels and podcasts as well, although I haven’t tested those out.

Rejected Options

Pocket

Pocket bafflingly doesn’t support RSS input. You can hack it with IFTTT or Zapier, but each RSS feed counts as its own applet so you reach the $10/month plan very quickly. This is slightly cheaper than the Feedly pro plan but more than Inoreader, plus paying Inoreader gets rid of ads.

Pocket allows you to forward individual emails to it, but because Gmail requires forwarding address confirmation you can’t automate forwarding to pocket from Gmail. You could fix this with a newsletter-to-RSS converter and then IFTTT/Zapier, but that’s a lot of work.

Feedly

I originally settled on Feedly before making one final sweep and choosing Inoreader instead. The driving concern was that Feedly required me to be on tier 3 ($12) rather than Inoreader’s tier 2 ($6). Inoreader’s browser plugin was also better, letting you subscribe while on a blog’s homepage, where Feedly requires you to not only go to its own page to add feeds, but track down the actual feed URL rather than figuring it out from the blog’s homepage URL (which is surprisingly hard because RSS is out of favor and most readers can guess, so the RSS feed is rarely displayed prominently).

I do like the Feedly Android app a little more; Inoreader has not adjusted to Pixel’s lack of a back button and eats the replacement gesture, but I liked the webapp more so stuck with Inoreader. 

Feedly Pro+ (required to get newsletter forwarding) boasts an AI assistant I assume is terrible. Inoreader has easily accessible filters and prioritization rules that I haven’t tested. Between the two of these I predict I get more value out of Inoreader, but I could be wrong.

Lastly, Feedly promised me a trial and immediately charged me for an annual subscription, so they can die in a fire. 

Everyone Else

This is a spreadsheet where I went through every read-it-later service I could find, looking for RSS native support. None of them had it. It is possible there is another RSS reader with better bookmarking or newsletter support, but I am exhausted and Inoreader is working so I stopped looking.

An Observation of Vavilov Day

Content note: this post contains discussion of starvation.

I aspire to be a person who does good things, and who is capable of doing hard things in service of that. This is a plan to test that capacity.

I haven’t been in a battle, but if you gave me the choice between dying in battle and slowly starving to death, I would immediately choose battle. Battles are scary but they are short and then they are over.

If you gave me a chance to starve to death to generate some sufficiently good outcome, like saving millions of people from starvation, I think I would do it, and I would be glad to have the opportunity. It would hurt, but only for a few weeks, and in that time I could comfort myself with the warm glow of how good this was for other people.

If you gave me a chance to save millions of people by starving, and then put food in front of me, I don’t think I could do it. I would do okay for a few days, maybe a week, but I worry that eventually hunger would incapacitate the part of my brain that allows me to make moral trade-offs at my own expense, and I would wake up to find I’d eaten half the food. I want to think I’d manage it, but if the thought experiment gods didn’t let me skip the hard part with more proactive measures, I’m not confident I could. 

During the siege of Leningrad, scientists and other staff of the Institute of Plant Study faced the above choice, and to the best of our knowledge, all of them chose hunger. 12 of them died for it, the rest merely got close (English language sources list 9 deaths, which is the number of scientists who died in service of the seed bank but not the total number of people). They couldn’t kill themselves because they were needed to protect the food from rats and starving citizens. Those survival odds are better than the certain death of my hypothetical, but they didn’t have the same certainty of impact either, so I think it balances out.

That’s heroism enough, but a fraction of what’s present in this story. Those scientists worked at an institute founded by Nikolai Vavilov, a Soviet botanist who has the misfortune to be right on issues inconvenient to Joseph Stalin. Vavilov’s (correct) insistence that his theories could feed Russians and those of Stalin’s favored scientist couldn’t got him arrested, tortured, and sent to a gulag, where he eventually starved to death. 

The seeds Vavilov and his staff protected now cover 80% of the cropland of Russia. Credit for scientific revolutions is hard to apportion, but as I reckon it Valilov is responsible for, at a minimum, tens of millions people living when they would have starved or never born, and the number could be closer to a billion.

Nikolai Vavilov is my hero.

Nikolai Vavilov | Biography & Facts | Britannica

In honor of Nikolai Vavilov, I’m doing a ~36 hour calorie fast from dinner on 1/25 (the day before Vavilov died in the gulag) to breakfast on 1/27 (the end of the siege of Leningrad). Those of you who know me know this is an extremely big deal for me, I do not handle being hungry well, and 36 hours is a long time. This might be one of the hardest things I could do while still being physically possible. Moreover, I’m not going to allow myself to just lie in bed for this: I’m committing to at least one physical activity that day (default is outdoor elliptical, unless it’s raining), and attempting to work a normal schedule. I expect this to be very hard. But I need to demonstrate to myself that I can do things that are at least this hard, before I’m called on to do so for something that matters. 

If this story strikes a chord with you to the point you also want to observe Valilov + associates’ sacrifice, I’d enjoy hearing how. I have enough interest locally (bay area California) that there’s likely to be a kick-off dinner + reading the night of the 25th. It would also be traditional for a fasting holiday to end in a feast, but 1/27 is a Thursday and other people have normal jobs so not yet clear how that’s going to shake out. 

Thanks to Clara Collier for introducing me to the story of Vavilov and his institute, Anna Tchetchetkine for finding Russian-languages sources for me, and Google translate for being so good I didn’t need Anna to translate any further.

Internet Literacy Atrophy

It’s the holidays, which means it’s also “teach technology to your elderly relatives” season. Most of my elderly relatives are pretty smart, and were technically advanced in their day. Some were engineers or coders back when that was rare. When I was a kid they were often early adopters of tech. Nonetheless, they are now noticeably worse at technology than my friends’ 3 year old. That kid figured out how to take selfie videos on my phone after watching me do it once, and I wasn’t even deliberately demonstrating. 

Meanwhile, my aunt (who was the first girl in her high school to be allowed into technical classes) got confused when attempting to use an HBOMax account I’d mostly already configured for her (I think she got confused by the new profile taste poll but I wasn’t there so I’ll never be sure). She pays a huge fee to use Go Go Grandparent instead of getting a smartphone and using Uber directly. I got excited when an uncle seemed to understand YouTube, until it was revealed that he didn’t know about channels and viewed the subscribe button as a probable trap. And of course, there was my time teaching my PhD statistician father how to use Google Sheets, which required learning a bunch of prerequisite skills he’d never needed before and I wouldn’t have had the patience to teach if it hadn’t benefited me directly. 

[A friend at a party claimed Apple did a poll on this and found the subscribe button to be a common area of confusion for boomers, to the point they were thinking of changing the “subscribe” button to “follow”. And honestly, given how coy substack is around what exactly I’m subscribing to and how much it costs, this isn’t unreasonable.]

The problem isn’t that my relatives were never competent with technology, because some of them very much were at one point. I don’t think it’s a general loss of intelligence either, because they’re still very smart in other ways. Also they all seem to have kept up with shopping websites just fine. But actions I view as atomic clearly aren’t for them.

Meanwhile, I’m aging out of being the cool young demographic marketers crave. New apps appeal to me less and less often. Sometimes something does look fun, like video editing, but the learning curve is so steep and I don’t need to make an Eye of The Tiger style training montage of my friends’ baby learning to buckle his car seat that badly, so I pass it by and focus on the millions of things I want to do that don’t require learning a new technical skill. 

Then I started complaining about YouTube voice, and could hear echoes of my dad in 2002 complaining about the fast cuts in the movie Chicago.

Bonus points: I watched this just now and found it painfully slow.

I have a hypothesis that I’m staring down the path my boomer relatives took. New technology kept not being worth it to them, so they never put in the work to learn it, and every time they fell a little further behind in the language of the internet – UI conventions, but also things like the interpersonal grammar of social media – which made the next new thing that much harder to learn. Eventually, learning new tech felt insurmountable to them no matter how big the potential payoff. 

I have two lessons from this. One is that I should be more willing to put in the time to learn new tech on the margin than I currently am, even if the use case doesn’t justify the time. Continued exposure to new conventions is worth it. I have several Millennial friends who are on TikTok specifically to keep up with the youths; alas, this does not fit in with my current quest for Quiet

I’ve already made substantial concessions to the shift from text to voice, consuming many more podcasts and videos than I used to and even appearing on a few, but I think I need to get over my dislike of recordings of my own voice to the point I can listen to them. I made that toddler training montage video even though iMovies is a piece of shit and its UI should die in a fire.This was both an opportunity to learn new skills and manufactured a future inspiration when things are hard.

Second: there’s a YouTube channel called “Dad, How Do I?” that teaches basic householding skills like changing a tire, tying a tie, or making macaroni and cheese. We desperately need the equivalent for boomers, in a form that’s accessible to them (maybe a simplified app? Or even start with a static website). “Child, how do I…?” could cover watching individual videos on YouTube, the concept of channels, not ending every text message with “…”, Audible, etc. Things younger people take for granted.  Advanced lessons could cover Bluetooth headphones and choosing your own electronics. I did some quick math and this is easily a $500,000/year business.

[To answer the obvious question: $500k/year is more than I make doing freelance research, but not enough more to cover the difference in impact and enjoyment. But if you love teaching or even just want to defray the cost of video equipment for your true passion, I think this is promising.]

My hope is that if we all work together to learn things, fewer people will be left stranded without access to technical tools, and also that YouTube voice will die out before it reaches something I care about.

Quick Poll: Booster Reactions

Lots of people are getting covid boosters now. To help myself and others plan I did an extremely informal poll on Twitter and Facebook about how people’s booster side effects compared to their second dose. Take home message: boosters are typically easier than second shots, but they’re bad often enough you should have a plan for that.

The poll was a mess for a number of reasons, including:

  • I didn’t describe the options very well, so it’s 2/3 freeform responses I collapsed into a few categories.
  • There was a tremendous variation in what combination of shots people got.
  • It’s self-reported. I have unusually data-minded friends which minimizes the typical problem of extreme responses getting disproportionate attention, but it doesn’t eliminate it, and self-report data has other issues.
  • I only sampled people who follow me on social media, who are predominantly <45 years old, reasonably healthy, reasonably high income, and mostly working desk jobs. 
  • I specified mRNA but not the manufacturer; Moderna but not Pfizer boosters are smaller than the original dose.

Nonetheless, the trend was pretty clear.

Of people who received three mRNA shots from the same manufacturer, comparing their second shot to their third:

  • 12 had no major symptoms either time (where major is defined as “affected what you could do in your day.” It specifically does not include arm soreness, including soreness that limited range of motion)
  • 2 had no major symptoms for their second shot but had major for their third
    • Not included in data: one person who got pregnant between their second and third shot
  • 23 had major symptoms for their second shot, and the third was easier
    • This includes at least one case where the third was still extremely bad and 2-3 “still pretty bad, just not as bad as the second”
    • Three cases fell short of  “major symptoms” for the second, but had an even easier third shot
  • 11 people had similar major symptoms both times
  • 2 had major symptoms for second shot, and third was worse

Of people who mix and matched doses

  • 2 had no major symptoms either time
  • 4 had no major symptoms for their second shot but had major symptoms for their third
    • Not included: 1 reported no symptoms for the first two and mild symptoms for the third
  • 4 had major symptoms for their second shot, and their third was easier
  • 2 people had major symptoms both times
  • 1 had major symptoms for their second shot, and their third was worse

Dear Self; We Need To Talk About Social Media

Last year I discovered, much to my chagrin, that always-on internet socializing was costly for me. This was inconvenient both because I’d spent rather a lot of time singing the praises of social media and instant messaging, and because we were in the middle of a global pandemic that had made online socializing an almost physical necessity. I made the decision at the time to put off changing my social media diet, and that was correct. But now there is in-person socializing again, and I’m changing how I use social media and messaging. I wanted to talk about this process and how great it was for me, but kept being nagged by the thought that the internet was full of essays about how the internet is bad, all of which I ignored or actively fought with, so what was going to make mine so special? 

I decided to use the one thing I had that none of the other writers did: a detailed understanding of my past self. So I wrote a letter to past me, explaining how social media was costlier than she knew (even though she was right about all of the benefits), and how she could test that for herself to make a more informed decision. To help as many Elizabeths as possible, I tried to make the letter cover a wide range in time, although in practice it’s mostly focused on post-smart-phone life.

Dear Past Elizabeth,

I know you have read a lot of things calling social media bad. Your reasons for disagreeing with them are correct: social media has been an incredible gift to you, you have dodged many of the problems they’re describing, and you’re right to value it highly. You’re also right that many of the people bragging about how hard they are to communicate with are anti-socially shifting the burden of communication to other people.

But.

Social media (and always-on instant messaging, which is a different, mostly worse, problem) has some costs you’re not currently tracking. I would like to help you understand those costs, so you can make different choices on the margin that leave you happier while preserving the benefits you get from social media, not all of which you’ve even experienced yet (is it 2015 yet? Approximately every job you get from this point on will have your blog as a partial cause. After 2017 you won’t even have interviews, people will just say “I read your blog”).

To be more specific: you have indeed curated your feed such that Facebook is not making you angry on purpose. You are not ruining relationships getting in public fights. You are not even ruining your mood from seeing dumb stuff very often. Much of what you see is genuinely interesting and genuinely connective, and that’s great. The people you connect with are indeed great, and you are successfully transitioning online connections into offline. I’m not asking you to give that up, just to track the costs associated with the gains, and see what you can do on the margins to get more benefits at less cost. To that end I’m going to give you a model of why internet socializing is costly, and some tools to track those costs.

I’m not sure how far back this letter is going, so I’m going to try to address a wide range of ways you might be right now. Also, if it’s late 2019 or early 2020, you can just put this letter on a shelf for a bit. If it’s mid 2020 and you’re confused by this, congratulations on being in the better timeline.

Currently you’re calculating your costs and benefits by measuring the difference in your mood from the time you receive a notification to the time you act on it. It’s true that that change is on average positive, and sometimes exceedingly so. But it ignores the change from the moment before you received the notification to the moment after. Notifications are pretty disruptive to deep thoughts, and you pay that cost before you even notice. But momentary disruptions aren’t even the whole cost, because the knowledge that interruptions could come at every time will change your mental state. 

It’s as if you had a system that delivered electric shocks to notify you that food was newly available. You are right that you need food to live, and a system that delivers it to you is good. But electric shocks are still unpleasant, and fear of electric shocks will limit the states you will allow your brain to get into. You can’t write off the costs of electric shocks just because food is good, and because most criticisms of the system focus on the food being bad. I know you’re on board with the general principle behind this analogy, because you already believe it for open offices, and that people who find open offices costless are fooling themselves. I’m so sorry to be the one to tell you that you are exactly the same, only with messaging instead of shared offices.

The easiest way to see this is to get yourself in a state where you can’t be interrupted, and observe your mood then. There is an incredibly beautiful, relaxing state I call Quiet that you are definitely not experiencing often enough. Once you have reached that state, you can observe how your mood changes as you move into a state where you can be interrupted, and again as you are interrupted. 

Noticing these changes and their signifiance requires a certain minimum level of ability to emotionally introspect. If you don’t have this yet, developing it is your highest priority- not just for concerns around social media, but for your life in general. Building emotional introspection was a very gradual process for me, so it’s hard to give you instructions. In this timeline I had guidance from specific individuals which may not be replicable, but something in the space of somatic experiencing therapy is probably helpful. Waking the Tiger and The Body Keeps the Score are the classically recommended books. They’re pretty focused on trauma, which is not actually the goal here, but oh well. Other people report success doing this with meditation, but it never seemed to work for me. 

Once you have that awareness, you want to practice getting in and out of Quiet so you can notice the changes in your feelings. I’ve included a few activities for producing Quiet, just to gesture at the concept, and a longer list at the end of this letter. 

Unless otherwise stated, a given activity needs to be the only thing you are doing, and you need to have disabled all potential interruptions, including self-inflicted interruptions like Facebook. For tasks that use electronics, this means either putting them in airplane mode or having a dedicated device that doesn’t get notifications. 

  • Put your phone on airplane mode and connect it to a bluetooth keyboard, so you can write without fear of interruption. 
    • Eventually you can buy a thing for this. It’s fine but not amazing. 
  • Learn a physical skill. Drawing on the Right Side of the Brain is good for absorption, and once you achieve a minimum skill level you can watch tutorials on youtube as long as you turn off every source of interruption.
    • Some of the frustration of drawing can be alleviated by getting an electronic device for drawing. I looked into this, and an iPad just is the best choice. You might want to have one of these ready to go by February 2020.
  • Read a book you’re really into (Kindle or physical). 
    • FYI, you should reread things more often. The hit rate on new books is quite low and some of your favorites are really good
  • If it’s an activity that leaves your hands open and you absolutely need something to do with your hands you can add in jigsaw puzzles, coloring, cardio exercise, or low-end cleaning work. 
    • Exercise in general is pretty good for Quiet, and you can even put on some entertainment, but it needs to be a single work you commit to, not all purpose access to your phone.

After you absorb yourself in one of these for a while (20-90 minutes), you’ll be in a very different state. Calmer, more focused, more serene. The volume on the world will be turned down. You’ll feel more yourself and less mixed with the rest of the world. Also you’ll crave Facebook like a heroin junkie. Give in to that. You just gave a weak muscle an intense workout and it’s appropriate to let it rest. As you do that, pay attention to which parts of you feel what ways. Something will be gained by using Facebook, but also something will be lost, and this is a time to learn those patterns so you can optimize your choices in the future. 

My guess is as time goes on you/I will build the muscle and spend more time in Quiet and less in noise. To be honest I haven’t gotten terribly far in that process, but it seems like the kind of thing that happens and I just can’t imagine the correct amount of online socializing for us is zero.

So far what I’ve talked about is mostly the dangers of apps that give notifications: alerts that draw your attention and thus incur a cost even if you dismiss them. You might be thinking “that doesn’t apply to social media, if I keep it closed by default and l only look when I feel like it.”. First of all, you are wrong. This is because you are not a unified agent: parts of you will want to check FB while other parts are hurt by it, and removing the option to do so will enable the FB-impaired parts to more fully relax (just like it’s easier to relax in an office with a door). But second, even if that weren’t true, social media has some inherent costs even when every individual post is incredibly valuable.

This is hard to describe and I’m mostly hoping you’ll notice it yourself once you pay attention and have something to contrast it with. But to gesture at the problem: every topic switch means booting up a new context, new thoughts, stores of existing information etc. Social media means doing this once every 4 seconds. You’ve avoided a lot of the classic pitfalls by studiously not reacting when Facebook showed you bad opinions, but by teaching it to only show you interesting things you’ve made the intellectual mosh pit aspect worse. At least Facebook gives you breathers in the form of baby photos: Twitter is non stop interesting dense things. 

Oh yeah, you’re gonna get into Twitter in 2020, and it will be the right decision. Yes, I’m very confident about 2020 in particular.

Anyways, I’m pretty sure the ideal amount of high-stimulus jumping between topics is not zero, but I’ve yet to get low enough to find the optimum. If you achieve Quiet and find yourself craving the stimulation of social media, and it feels good during and after, I think you should trust that. But I don’t think you’re capable of an informed decision on the tradeoff until you get more information.

In addition to the activities mentioned, a few tips and tricks that might make this whole process easier for you:

  • As you scale down your current process, you’ll lose the thing that makes you answer email and texts in a timely manner. Make sure to create a new habit of actually answering emails and texts at a chosen time.
  • You’re gonna worry that making yourself unreachable will make you miss messages that are genuinely urgent and important. There is a phone setting to let messages from certain people through, or any phone number that calls 2x in 15 minutes. It’s okay to use that. Your friends are not monsters, they will not abuse the privilege.
  • In general, you should be open to having more electronic devices that only do one thing: I know it seems dumb when your phone or laptop can already do the thing, but it really does change how you relate to the activity.
  • I’ve had off and on success with screen bedtime, in which I can stay up as late as I want, but I can’t look at a screen after a certain time. It provides a natural end to the day while respecting energy levels.
    • Kindles are not screens.
    • At some point you’re gonna start requiring podcasts to fall asleep, but you can preserve the spirit of screen bedtime by putting the phone in airplane mode ahead of time.
      • You’re not wrong that some horror podcasts have very soothing narrators you can fall asleep to. But somehow the only periods where I frequently wake up with nightmares are also the periods where I frequently fell asleep to horror podcasts. It’s not 1:1 causality but I do think it’s worse for us.
    • While we’re at it: the point of things you do after and just before going to bed is to help you fall asleep. Right before sleep is not the all purpose reading hour. Please pay enough attention to notice that reading deeply upsetting recent history books in bed disrupts your sleep.
  • Transitioning from noise to Quiet can be hard. You might think to skip the unpleasant transition phase by pursuing Quiet when you first wake up. I have yet to figure out how to pull this off: I’ll lie there half asleep indefinitely before getting the energy to read a book, audio will put me back to sleep. I have a sneaking suspicion that the disruptive chaotic nature of social media/messaging is also what makes it good for transitioning from half asleep to mostly awake. 
  • You are the only one who likes the Zune and the replacement will not be as conducive to unitasking. Unfortunately the realities of hardware support probably mean you can’t dodge this by stocking up ahead of time. I’m sorry, please enjoy the time you have.
  • Don’t go to Netflix or other streaming sites and look for something to entertain you. Maintain a watchlist on another site, and when you’re in the mood for a movie, figure out what kind of thing you’re in the mood for ahead of time and look for something on your list. This will prevent some serendipity, but the world is going to get much better at making things that look like they are for you but never pay off.
  • You’ll definitely enjoy work more if you turn off sources of interruptions.
  • Does that seem infeasible right now?  Does it seem like it won’t matter because your co-workers can just find you at the physical workplace you go to most days? I have such good news for you. The conconcordance between your brain and your work environment is going to get so much better. There will still be tension between “following a single train of thought to the end” and “following up on the multiple paths that train lays down”. I haven’t solved this one yet. But you have no idea how much less bullshit your work life is going to become.

To recap: I am suggesting the following plan:

  1. Try some of the activities on the Quiet list.
  2. If you don’t notice the difference between them and the intellectual mosh pit that is your day, train the ability to notice subtle mood differences, then go back to 1.
  3. Track the change in feeling between Quiet and a return to social internetting. 
  4. Do what feels good from there.

I hope this helps you become happier and more productive at a faster rate than I did,

  -Elizabeth, 2021

PS. please buy bitcoin

More Quiet activities

  • Feldenkrais (and only feldenkrais. No podcasts, no audiobooks, no tv. Sometimes you like to have close friends in the room while you do this to keep watch for monsters). Your starter resource for this is Guide To Better Movement; after that you can search on Youtube. As a bonus, feldenkrais is also on the list of things that will help you develop your ability to notice your own mood.
  • Video games work but also require a lot of executive function and that’s your ongoing bottleneck resource so I don’t strongly recommend them. Horror remains an unusually good genre for this, and your algorithm of playing the top 10% of puzzle games works pretty well.
    • Avoid anything that you need to tab out of to look stuff up, which will unfortunately hurt Subnautica, a game otherwise made just for you, significantly.
  • Diary writing.
  • Watch a single episode of a TV show without multitasking. 
    • Horror is especially good for this because the damage done by an interruption is so palpable.
    • I know this is hard because even very good movies can be just not stimulating enough. There’s no fix for that right now because your audio processing is so mediocre, but in a few years that’s gonna fix itself for no obvious reason and you’ll be listening to podcasts at 2x like it’s nothing. Once that happens you can use Video Speed Controller to speed things up. Don’t overuse this, you’ll ruin your goal of creating Quiet if you go too fast, but a 10-20% speed up is often unnoticeable.
    • Remember to either be in airplane mode or use a dedicated device that doesn’t have messaging on it.
  • Horror podcasts are also great, especially Magnus Archive if that’s around yet.
    • 20-30 minutes is the ideal length to start experiencing Quiet, which makes podcasts better than movies. Also they have a much better ratio of “time to figuring out if it is good” to “time after you know it’s good”.
    • TV horror anthologies meet the time constraint but just seem much worse on average than podcasts. More things to go wrong I guess.

Future Review: Screen Extenders

I recently got to try my co-working space’s laptop screen extender, a Xebec Tri-Screen

Xebec Tri-Screen 2

It was amazing and also obviously both too big and too small. The screens are 10.1, enough to take notes but not really read them, yet too heavy for my laptop hinge to support, so I could use it on a table but not my lap, and it drew power faster than the laptop could resupply.

I went looking for competitors, but space is thin. A lot of the listings on Amazon seem sketchy, with serious grammar and vocabulary errors, even when the company itself has a solid proofread website. Some of them require permanent adhesives on your laptop, which isn’t ideal for the shared device at the office. I assembled everything in a spreadsheet here, but they all require major compromises.

If you have informed opinions on any of these, or see one I missed, please let me know. I realize my magic larger and higher resolution but somehow lighter and less power-hungry screen doesn’t exist yet, but surely there must be something somewhere else on the pareto frontier.

I Don’t Know How To Count That Low

Back when I was at Google we had a phrase, “I don’t know how to count that low”. It was used to dismiss normal-company-sized problems as beneath our dignity to engage with: if you didn’t need 100 database shards scattered around the globe, were you even doing real work? 

It was used as a sign of superiority within Google, but it also pointed at a real problem: I once failed a job interview at a start-up when I wondered out loud if the DB was small enough to be held in memory, when it was several orders of magnitude lower than when I should even have begun worrying about that. I didn’t know the limit because it had been many years since I’d had a problem that could be solved with a DB small enough to be held in its entirety in memory. And they were right to fail me for that: the fact that I was good at solving strictly more difficult problems didn’t matter because I didn’t know how to solve the easier ones they actually had. I could run but not walk, and some problems require walking.

It’s a problem, but it can be a pleasant kind of problem to have, compared to others. Another example: my dad is a Ph.D. statistician who spent most of his life working in SAS, a powerful statistical programming language, and using “spreadsheet statistics” as a slur. When I asked permission to share this anecdote he sent me a list of ways Excel was terrible.

YARN | ♪ Here's an itemized list Of 30 years of disagreements ♪ | Hamilton  | Video gifs by quotes | 9d9bc627 | 紗

Then he started consulting for me, who was cruelly unwilling to pay the $9000 license fee for SAS when Google Sheets was totally adequate for the problem (WHO HAS FOOD AT HOME NOW DAD?!?).* 

My dad had to go through a horrible phase of being bad at the worse tool, and found a lot of encouragement when I reframed “I could have done this with one line in SAS and am instead losing to this error-riddled child’s toy”  to  “I didn’t know how to count that low, but now that it matters I am learning”. And then he tried hard and believed in himself and produced that analysis of that informal covid study that was wonderful statistically and super disappointing materially. And I retrained on smaller numbers and got that job at that start-up.

These are the starkest examples of how I’ve found “I don’t know how to count that low” useful. It reframes particularly undignified problems as signs of your capacity rather than incapacity, without letting you off the hook for solving them. Given how useful it’s been to me and how little I’ve seen of it in the wild, I’d like to offer this frame to others, to see if it’s useful for you as well.

*If any of you are going to bring up R: yes, it’s free, and yes, he has some experience with it, but not enough to be self-sufficient, I knew Sheets better, and I knew it was totally adequate for what we were doing or were likely to do in the future.

Appendix: I know you’re going to ask, so here is his abbreviated of grievances with Excel. Note that this was Excel in particular; I have no idea if it applies to Google Sheets. I also would allow that this must have been years ago and Excel could have gotten better, except AFAIK they never fixed the problem with reading genes as dates so they get no benefit of a doubt from me.

I attended a talk by a statistician at Microsoft.  He said that Microsoft had decided that there was no competitive advantage in making Excel statistics better because no statistician used it for serious problems except for data entry, so:

1. he was the only statistician at Microsoft
2. he knew of seven serious statistical problems in Excel, but they wouldn’t give him the money to fix them.
3. Excel’s problems fell into two categories:
3a. terrible numerical analysis:  it was widely verified if you took a number of single-digit numbers and calculated their standard deviation, and then took the same numbers and added a million to them, the standard deviation was often different, when it should be exactly the same.
3b.

statistical errors – like not understanding what you’re copying out of a textbook and getting it wrong.

Thanks to Ray Arnold and Duncan Sabien for beta-reading, and my dad for agreeing have his example shared.

Quick Look: Altitude and Child Development

A client came to me to investigate the effect of high altitude on child development and has given me permission to share the results. This post bears the usual marks of preliminary client work: I focused on the aspects of the question they cared about the most, not necessarily my favorite or the most important in general. The investigation stops when the client no longer wants to pay for more, not when I’ve achieved a particular level of certainty I’m satisfied with. Etc. In this particular case they were satisfied with the answer after only a few hours, and I did not pursue beyond that.

That out of the way: I investigated the impact of altitude on childhood outcomes, focusing on cognition. I ultimately focused mostly on effects visible at birth, because birth weight is such a hard to manipulate piece of data. What I found in < 3 hours of research is that altitude has an effect on birth weight that is very noticeable statistically, although the material impact is likely to be very small unless you are living in the Andes.

Children gestated at higher altitudes have lower birth weights

This seems to be generally supported by studies which are unusually rigorous for the field of fetal development. Even better, it’s supported in both South America (where higher altitudes correlate with lower income and lower density, and I suspect very different child-rearing practices) and Colorado (where the income relationship reverses and while I’m sure childhoods still differ somewhat, I suspect less so). The relationship also holds in Austria, which I know less about culturally but did produce the nicest graph.

This is a big deal because until you reach truly ridiculous numbers, higher birth weight is correlated with every good thing, although there’s reason to believe a loss due to high altitude is less bad than a loss caused by most other causes, which I’ll discuss later. 

[Also for any of you wondering if this is caused by a decrease in gestation time: good question, the answer appears to be no.]

Children raised at higher altitudes do worse on developmental tests 

There is a fair amount of data supporting this, and some even attempt to control for things like familiar wealth, prematurity, etc. I’m not convinced. The effects are modest, I expect families living at very high altitudes (typically rural) to be different in many ways from lower altitudes (typically urban) in ways that cause their children to score differently on tests without it making a meaningful impact on their life (and unlike birth weight, I didn’t find studies based in CO, where some trends reverse). Additionally, none of the studies looked specifically at children who were born at a lower altitude and moved, so some of the effects may be left over from the gestational effects discussed earlier. 

Hypoxia may not be your only problem

I went into this primed to believe reduced oxygen consumption was the problem. However, there’s additional evidence that UV radiation, which rises with altitude, may also be a concern. UV radiation is higher in some areas for other reasons, which indeed seems to correlate with reductions in cognition.

How much does this matter? (not much)

Based on a very cursory look at graphs on GIS (to be clear: I didn’t even check the papers, and their axes were shoddily labeled), 100 grams of birth weight corresponds to 0.2 IQ points for full term babies.

The studies consistently showed ~0.09 to 0.1 grams lower birth weight per meter of altitude. Studies showed this to be surprisingly linear; I’m skeptical and expect the reality to be more exponential or S shaped, but let’s use that rule of thumb for now. 0.1g/m means gestating in Denver rather than at sea level would shrink your baby by 170 grams (where 2500g-4500g is considered normal and healthy). If this was identical to other forms of fetal weight loss, which I don’t think it is, it would very roughly correspond to 0.35 IQ points lost. 

However, there’s reason to believe high-altitude fetal weight loss is less concerning than other forms. High altitude babies tend to have a higher brain mass percentage and are tall for their weight, suggesting they’ve prioritized growth amidst scarce resources rather than being straight out poisoned. So that small effect is even smaller than it first appears.

There was also evidence out of Austria that higher altitude increased risk of SIDS, but that disappeared when babies slept on their backs, which is standard practice now.

So gestating in Denver is definitely bad then? (No)

There are a billion things influencing gestation and childhood outcomes, and this is looking at exactly one of them, for not very long. If you are making a decision please look at all the relevant factors, and then factor in the streetlight effect that there may be harder to measure things pointing in the other direction. Do not overweight the last thing I happened to read.

In particular, Slime Mold Time Mold has some interesting data (which I haven’t verified but am hoping to at least ESC the series) that suggests higher altitudes within the US have fewer environmental contaminants, which you would expect to have all sorts of good effects.

Full notes available here.

Thanks to anonymous client for commissioning this research and Miranda Dixon-Luinenburg for copyediting.

Long Covid Informal Study Results

Introduction

Yesterday* I talked about a potential treatment for Long Covid, and referenced an informal study I’d analyzed that tried to test it, which had seemed promising but was ultimately a let down. That analysis was too long for its own post, so it’s going here instead. 

Gez Medinger ran an excellent-for-its-type study of interventions for long covid, with a focus on niacin, the center of the stack I took. I want to emphasize both how very good for its type this study was, and how limited the type is. Surveys of people in support groups who chose their own interventions is not a great way to determine anything. But really rigorous information will take a long time and some of us have to make decisions now, so I thought this was worth looking into.

Medinger does a great analysis in this youtube video. He very proactively owns all the limitations of the study (all of which should be predictable to regular readers of mine) and does what he can to make up for them in the analysis, while owning where that’s not possible. But he delivers the analysis in a video rather than a text post ugh why would you do that (answer: he was a professional filmmaker before he got long covid). I found this deeply hard to follow, so I wanted to play with the data directly. Medinger generously shared the data, at which point this snowballed into a full-blown analysis.

I think Medinger attributes his statistics to a medical doctor, but I couldn’t find it on relisten and I’m not watching that damn video again. My statistical analysis was done by my dad/Ph.D. statistician R. Craig Van Nostrand. His primary work is in industrial statistics but the math all transfers, and the biology-related judgment calls were made by me (for those of you just tuning in, I have a BA in biology and no other relevant credentials or accreditations).

The Study

As best I can determine, Medinger sent a survey to a variety of long covid support groups, asking what interventions people had tried in the last month, when they’d tried them, and how they felt relative to a month ago. Obviously this has a lot of limitations – it will exclude people who got better or worse enough they didn’t engage with support groups, it was in no way blinded, people chose their own interventions, it relied entirely on self-assessment, etc. 

Differences in Analysis

You can see Medinger’s analysis here. He compared the rate of improvement and decline among groups based on treatments. I instead transformed the improvement bucket to a number and did a multivariate analysis. 

Much better (near or at pre-covid)1
Significantly better0.5
A little better0.1
No change0
A little worse-0.2
Significantly worseCuriously unused
Much worse-1.2

You may notice that the numerical values of the statements are not symmetric- being “a little worse” is twice as bad as “a little better” is good. This was deliberate, based on my belief that people with chronic illness on average overestimate their improvement over short periods of time. We initially planned on doing a sensitivity analysis to see how this changed the results; in practice the treatment groups had very few people who got worse so this would only affect the no-treatment control, and it was obvious that fiddling with the numbers would not change the overall conclusion.

Also, no one checked “significantly worse”, and when asked Medinger couldn’t remember if it was an option at all. This suggests to me that “Much worse” should have a less bad value and “a little worse” a more bad value. However, we judged this wouldn’t affect the outcome enough to be worth the effort, and ignored it. 

We tossed all the data where people had made a change less than two weeks ago (this was slightly more than half of it), except for the no-change control group (140 people). Most things take time to have an effect and even more things take time to have an effect you can be sure isn’t random fluctuation. The original analysis attempted to fix this by looking at who had a sudden improvement or worsening, but I don’t necessarily expect a sudden improvement with these treatments.

We combined prescription and non-prescription antihistamines because the study was focused on the UK which classifies several antihistamines differently than the US. 

On row 410, a user used slightly nonstandard answers, which we corrected to being equivalent to “much improved’, since they said they were basically back to normal.

Medinger uses both “no change” and “new supplements but not niacin” as control groups, in order to compensate for selection and placebo effects from trying new things. I think that was extremely reasonable but felt I’d covered it by limiting myself to subjects with >2 weeks on a treatment and devaluing mild improvement. 

Results

I put my poor statistician through many rounds on this before settling on exactly which interventions we should focus on. In the end we picked five: niacin, anti-histamines, and low-histamine diet, which the original analysis evaluated, and vitamin D (because it’s generally popular), and selenium (because it had the strongest evidence of the substances prescribed the larger protocol, which we’ll discuss soon). 

Unfortunately, people chose their vitamins themselves, and there was a lot of correlation between the treatments. Below is the average result for people with no focal treatments, everyone with a given focal treatment, and everyone who did that and none of the other focal treatments for two weeks (but may have done other interventions). I also threw in a few other analyses we did along the way. These sample sizes get really pitifully small, and so should be taken as preliminary at best. 

TreatmentNiacin, > 2 weeksSelenium, > 2 weekVitamin D, > 2 weekAntihistamines, > 2 weeksLow-histamine diet, > 2 weeksChange (1 = complete recovery)95% Confidence Interval n
No change000000.04± 0.07140
Niacin, > 2 weeks10.23± 0.0791
Selenium, > 2 weeks10.24±0.0788
Vitamin D, > 2 week10.15±0.05261
Antihistamines, >2 weeks10.18± 0.06164
Low histamine diet10.18±0.06195
Niacin, > 2 weeks, no other focal treatments100000.15±0.211
Selenium, > 2 weeks, no other focal treatments010000.05±0.064
Vitamin D, > 2 week, no other focal treatments001000.07±0.08106
Antihistamines, >2 weeks, no other focal treatments000100.08±0.1326
Low histamine diet, > 2 weeks, no other focal treatments000010.13±0.1444
All focal treatments111110
Niacin + Antihistamines, >2 weeks1100.33± 0.0738
Niacin + Low Histamine Diet, > 2 weeks100010.29±0.1036
Selenium + Niacin, no histamine interventions11000.05±0.1917
Niacin, > 2 weeks, no other focal treatments, ignore D10000.13±0.1219
Selenium, > 2 weeks, no other focal treatments, ignore D01000.16±0.1218

1 = treatment used

0 = treatment definitely not used

– = treatment not excluded

Confidence interval calculation assumes a normal distribution, which is a stretch for data this lump and sparse but there’s nothing better available.

[I wanted to share the raw data with you but Medinger asked me not to. He was very fast to share with me though, so maybe if you ask nicely he’ll share with you too]

You may also be wondering how the improvements were distributed. The raw count isn’t high enough for really clean curves, but the results were clumped rather than bifurcated, suggesting it helps many people some rather than a few people lots. Here’s a sample graph from Niacin (>2 weeks, no exclusions)

Reasons this analysis could be wrong

  • All the normal reasons this kind of study or analysis can be wrong.
  • Any of the choices I made that I outlined in “Differences…”
  • There were a lot of potential treatments with moderate correlations with each other, which makes it impossible to truly track the cause of improvements.
  • Niacin comes in several forms, and the protocol I analyze later requires a specific form of niacin (I still don’t understand why). The study didn’t ask people what form of niacin they took. I had to actively work to get the correct form in the US (where 15% of respondents live); it’s more popular but not overwhelmingly so in the UK (75% of respondents), and who knows what other people took. If the theory is correct and if a significant number of people took the wrong form of niacin, it could severely underestimate the improvement.
  • This study only looked at people who’d changed things in the last month. People could get better or worse after that.
  • There was no attempt to look at dosage.

Conclusion

For a small sample of self-chosen interventions and opt-in participation, this study shows modest improvements from niacin and low histamine diets, which include overlap with the confidence interval of the no-treatment group if you exclude people using other focal interventions. The overall results suggest that either something in the stack is helping, or that trying lots of things is downstream of feeling better, which I would easily believe.

Thank you to Gez Medinger for running the study and sharing his data with me, R. Craig Van Nostrand for statistical analysis, and Miranda Dixon-Luinenburg⁩ for copyediting.

* I swear I scheduled this to publish the day after the big post but here we are three days later without it unpublished, so…

Niacin as a treatment for covid? (Probably no, but I’m glad we’re checking)

Introduction

This article contains an interview with a doctor who believes NAD+ is the secret to covid’s heavy morbidity and mortality toll. The description was unusually well done for internet crackpottery. This is hard to convey rigorously, but it had a mechanistic-ness and the right level of complexity about it, and it made the right level of promises for a treatment. None of this is to say it’s definitely correct, but it had a bunch better chance of being correct than your average alt-covid-cure scribbled out in crayon. So I did some checks on it.

[Didn’t you say the risk of long covid was small? NO I SAID IT WAS TOO SMALL TO MEASURE AGAINST THE DELUGE OF CRAP THAT HAPPENS TO US EVERYDAY THAT IS NOT THE SAME]

*ahem*

This post is organized as follows:

  • Description of theory. 
  • Long section defining terms. These are all useful for understanding the claims I check later on, but depending on who you are they may not be helpful, and you may find the contextless infodump kind of a drag. Feel free to skip if it’s not useful to you personally, and know that it’s there if you need it.
  • Deep dive onto particular claims the article makes.
  • Does it work?
  • Is it safe?
  • My personal experience with the protocol 
  • Some meta

This is your reminder that my only credential is a BA in biology and I didn’t specialize in anything relevant. It is a sign of civilizational inadequacy that this post exists at all, and you should think really hard and do your own research before putting too much weight on it.

For those of you would like to skip to the take home message: science is very hard, I’m glad they’re running larger studies to follow up on all of these because that’s a reasonable thing for a rich society to do, but I’m not super hopeful about this protocol.

The Theory

As described by Dr. Ade Wentze:

There is an extremely widely used coenzyme in your body, NAD. The more active form of this compound, NAD+, is depleted by covid (converted to NADH). In people with a preexisting deficiency or difficulty rebounding after depletion, covid infection results in a persistent NAD+ deficit. This is bad in and of itself, but causes additional problems when your body tries to make up for it by requisitioning all your tryptophan to make more. Tryptophan is also a precursor for serotonin, so this leads to either low serotonin or activation of mast cells to release their serotonin stores, accompanied by histamines (which cause allergies and other issues). 

Background

There is a lot of vocabulary in that theory and in the supporting claims, which I go over here. If you’re reading for conclusions rather than deep understanding I would skip this.

NAD+

Nicotinamide adenine dinucleotide is a coenzyme that plays an essential role in hundreds of chemical reactions in your cells, including many relating to processing energy and genetic transcription.  This is a mixed blessing as a foundation for crackpot theories go: something involved in hundreds of processes across every kind of tissue in your body can cause almost any symptom, which is great because long covid has a lot of symptoms to cover. On the other hand, it can cause almost any symptom, which means it’s hard to disprove, and you should distrust things in proportion to the difficulty to disprove them. Alas, sometimes core processes are impaired and they do express that impairment in a range of unpredictable ways that vary across people, but it’s also an easy home for crackpots. 

NAD+ has two major components, one made from either tryptophan or aspartic acid (both amino acids), or by altering niacin.

Niacin

Like many vitamins, niacin aka vitamin B3 refers to a few different closely related compounds (most commonly nicotinic acid, nicotinamide, nicotinamide riboside, and inositol nicotinate, but there are others) that are almost but not quite interchangeable.

Chemical structures of niacin compounds: (a) nicotinamide; (b) nicotinic acid; (c) nicotinamide adenine dinucleotide (NAD þ ); (d) nicotinamide adenine dinucleotide phosphate (NADP þ ) (source)

Niacin is commonly prescribed for treating high cholesterol, although a metareview found it did not reduce overall mortality and may contribute to the development of type-2 diabetes. 

Severe niacin deficiency is called pellagra, and can be caused by either insufficient consumption or problems processing the vitamin. Pellagra is mostly defined as niacin deficiency but can also be caused by tryptophan deficiency, which you may remember is another path to manufacturing NAD+. Pellagra can cause diarrhea, dermatitis, dementia, and death, which are not a great match for acute or long covid. Niacin supplementation treats pellagra, often within a few days.

SIRT1

Sirtuin 1, also known as NAD-dependent deacetylase sirtuin-1, is a protein that regulates the expression of some genes in ways that haven’t yet been made clear to me but seem to be associated with aging (more SIRT1 is associated with better outcomes, although we haven’t broken down cause and effect). As indicated by its name, it’s dependent on NAD+ to operate, which means NAD+ is involved in the regulation of expression of some genes via some mechanism, which means niacin is involved in the regulation of expression of some genes via some mechanism.

SIRT1 is downregulated in cells that have high insulin resistance and inducing its expression increases insulin sensitivity, suggesting the molecule is associated with improving insulin sensitivity.

SIRT1 may be upregulated by selenium.

PARP

Another many-purposed enzyme whose activities include DNA repair, killing cells that are beyond repair. PARP requires NAD+ as a coenzyme.

Individual Claims

Groups with low NAD+ suffer more from covid

NAD+ declines with age

NAD+ does definitely decline with age but so does literally everything bad in your body, so I don’t find this very compelling.

Correlation between NAD+ levels and Age in (A) Males (B) Females (source)

Obese people have lower NAD+ levels, leading to worse outcomes

Yes, although obese people tend to do worse on a lot of metrics. However, that paper highlights that SIRT1 seems to be involved in this correlation somehow.

Diabetics have worse NAD+ levels

Yes, although diabetics also have more immune problems generally (definitely Type 2, some pop sites said the same for Type 1 and that’s believable but I didn’t quickly find a paper I liked that backed the claim).

Low selenium is associated with bad outcomes in covid

The post cites Zhang et al, which took advantage of high variations in selenium consumption in China to do a natural experiment. Variations in the population selenium levels do seem insanely correlated with the overall cure rate (defined as not dying). The study took place in February 2020 so neither data collection nor treatment was very good, but damn that is interesting.

Moreover, this study, which came out several months after the blog post was published, took advantage of the same variation and came to the same conclusion, with a much larger sample size and much more reasonable case fatality rate (1.17% in areas with no deficiency to 3.16% in severely deficient areas, P = 0.002). (Note: several authors on that paper are also named Zhang, but I assume that’s because it’s a common name in China).

Some pharma company thinks selenium is promising enough to launch a trial for it, although recruitment hasn’t started yet.

The pre-print servers are littered with natural experiments highlighting correlations that failed as interventions, but this is very strong for a correlation.

Niacin just generally seems to help lung damage

That is indeed what their citation says, however that paper’s only source looked at the effect of niacin on lung damage in hamsters deliberately induced with a chemotherapy drug, and it’s not obvious to me that that translates to damage from infection or immune reaction. There are some other scattered studies in rodents, combining niacin with other substances, none of which looked at damage from infectious disease.

The treatment for NAD+ deficiency is niacin

Their citation backs this up: niacin supplementation led patients (n=5) and controls (healthy people given the same supplementation, n=8) to increased NAD+ levels, and arguably increased strength, although with that much variation and such a small sample size I’m not convinced. Martens et al supports this with modest benefits seen in n=24 subjects.

A few minutes investigation found some other studies:

  • Dietary niacin deficiency led to NAD+ deficiency in baby rats. This paper works damn hard to hide its sample size but I think it was 10-15 per treatment group.
  • The same author exposed some rats (n=6 per treatment group) to excess oxygen and found that those with a niacin deficient diet had less NAD+ in the lungs and responded less to the damage caused by excess oxygen, but had the same wet/dry ratio as their well-fed friends (wet/dry ratio is a measure of lung health).
  • Ng et al found that in catfish liver NAD increased linearly with dietary niacin supplementation, but health returns like size and mortality dropped off between 6 and 9 mg/kg. They further found that tryptophan supplementation could not make up for a niacin deficiency (in catfish).

Plus niacin is so well established as a treatment for pellagra that no one bothers to cite anything for it, and that does seem to mediate through NAD+.

Nicotinic acid may act as a one of a kind bioenergetic “pump” of inflammatory molecules out of cells

They link to a preprint which has since been taken down, and I could not find it on my own. 

NAD+ problems have been indicated in chronic fatigue syndrome

Everything has been indicated in chronic fatigue syndrome; I’m not looking this up.

Low serotonin -> mast cell activation -> histamine release

Mast cells indeed produce serotonin, in mice. Note that that paper highlights fluoxetine as a way to reverse serotonin deficiency in mast-cell-deficient mice, and since the article was published fluoxetine has shown promise as a covid treatment. However this study says that while serotonin-producing mast cells are common, humans in particular don’t have them while healthy (although it still shows serotonin affecting mast cell movements). This appears to be an area of some controversy.

Mast cells releasing histamine in response to allergens is uncontroversial. Moreover, histamines and serotonin are stored in the same compartments (in mice). Second source (still in mice). 

Some Guy did an informal study based on this theory and it worked

Some guy (Birth name: Gez Mendinger) did indeed report this, and I have to say, for an uncredentialed dude on youtube recommending OTC supplements to treat a nebulously defined disease, this guy looks really credible, and his reasonably good analysis was quite promising. He shared his results with me, and it continued to look promising when I first dug into it with assistance from a statistician, but the deeper we drilled the less promising it looked (details). By the end, the most I could say is “yeah, worth a harder look”, but the history of things that look promising in small, poorly organized studies that wilt under large, well-organized ones is just too dismal to ignore. 

Mouse study shows low NAD+ hurts you via SIRT1

The interview also cites this mouse study featuring a direct NAD+ drip and a slightly different coronavirus. They show improved symptoms but not viral load. They don’t list the sample size anywhere I can find, judging from the low-resolution graph it looks like 7 mice in the control group and maybe 12 in the treatment group? Except for the embolism test which had many more mice.

(apologies for poor image quality, the PDF was crap)

(note: that article was up when I started this post but disappeared before I verified the SIRT1-specific part of the claim)

Quercetin increases NAD+ levels 

Yes, in rats and mice. Specifically, it speeds up the transition from NADH to NAD+

Male pattern balding and low vitamin D are both associated with poor covid outcomes and low NAD+.

The balding citation does indeed say that, but it only looked at hospitalized patients so it’s useless. Moreover, balding is associated with a testosterone derivative, and testosterone weakens the immune system. But when I went to find some cites for those, I found that within hospitalized patients, low testosterone was associated with worse outcomes. However these patients were already hospitalized, so the causality could easily go the other way.

Meanwhile I found several folk-wisdom level comments indicating a link between NAD+ and male pattern balding, but nothing rigorous.

Low vitamin D does seem to be associated with poor covid outcomes, maybe, but treatment doesn’t seem to help (at least not if you wait until patients are hospitalized). 

Chang and Kim assert that Vitamin D activates the NAD-SIRT1 pathway in fat cells in vitro, which if it held up elsewhere would be even stronger evidence for the overall theory than this claim attempts. Byers et al found that vitamin D did not protect guinea pigs against the NAD+ depleting effects of mustard gas. This is not a slam dunk.

Covid depletes NAD+ by activating PARP

Curtin et al lay out a theoretical case for using PARP-inhibitors to treat covid-caused ARDS.

Heer et al “we show that SARS-CoV-2 infection strikingly upregulates MARylating PARPs and induces the expression of genes encoding enzymes for salvage NAD synthesis from nicotinamide (NAM) and nicotinamide riboside (NR), while downregulating other NAD biosynthetic pathways” (notably, the forms not used in the protocol), “overexpression of PARP10 is sufficient to depress cellular NAD and that the activities of the transcriptionally induced enzymes PARP7, PARP10, PARP12 and PARP14 are limited by cellular NAD and can be enhanced by pharmacological activation of NAD synthesis”, “MHV induces a severe attack on host cell NAD+ and NADP+.” (MHV being used as a model)

Long covid and Pellagra share a lot of symptoms, including hyponosmia

Scattered claims pellagra causes hyponosmia but you have to look really hard, it doesn’t show up on any of the common descriptions. I checked in Spanish and didn’t find anything either.

Sen (published only last month) suggests that serotonin deficiency causes anosmia and other neuro symptoms in covid. They propose a different method for the depletion (ACE2 is a mechanism for moving serotonin into the cell), but it’s not mutually exclusive with Wentzel’s theory (that NAD+ depletion causes the body to use up tryptophan trying to produce more NAD+).

Your body hijacks tryptophan to make NAD+ at the expense of serotonin

Tryptophan can indeed be used to make NAD (albeit niacin is better) and serotonin. How your body prioritizes under a given set of circumstances is anyone’s guess.

NAD+ and the immune system

Probably at least some of long covid stems from autoimmune issues, as witnessed by the fact that it’s much more common in women and sometimes helped by steroids. The post and paper don’t make any claims on this beyond the effect of NAD+ on mast cells, which are implicated in autoimmune disorders, but out of curiosity I did some quick googling and found that NAD+ downregulate inflammation via CD4 cells (in mice) and activating SIRT1, the pathway mentioned previously (still in mice).

The Paper

Not that good. Feels associational rather than mechanistic. However Bordoni et al (published after the cited paper) found covid-19 was associated with diminished SIRT1- but Pinto et al found covid-19 upregulated SIRT1 and cite another study claiming that under conditions of energetic stress (which would imply low NAD+), SIRT1 substitutes for ACE2 (the receptor covid uses to enter the cell. Smith suggests that downregulating SIRT1 is good for fighting covid. So SIRT1, NAD+, and covid are probably related, but the first two items are very common so this isn’t damning.

Notably, this paper doesn’t explain why covid would deplete NAD+ more than other infectious diseases, which is an enormous hole.

Does it work? 

The mechanism and empirical data are definitely enough to merit more rigorous follow-up studies (which are in progress) and definitely not slam dunks. But you may need to make a decision before that’s in, so the real question is “should I take this stack if I get sick? Should my parents?”

My tentative answer is: the prescribed stack probably won’t physically hurt you (but see the next section), and it’s fairly cheap, so the limiting factor is probably “what do you have the energy to try”. This is a better thing to try than the interventions whose proof was actively made up or have been investigated and discarded, but there undoubtedly are or will be equally probable things floating around, and choosing between them will be a matter of taste..  

If you do end up giving this a shot, for covid long or acute, I invite you to preregister your complaints and intention with me (a comment here or email elizabeth@acesounderglass.com), so I can create my own little study. If you don’t feel like doing that I still encourage you to announce the intention somewhere, as a general good practice (I did so here). 

So you’re saying it’s safe then?

Anything that does anything is dangerous to you in sufficient dosages. If you’re considering an unverified supplement stack, you should carefully investigate the potential side effects of each substance and consider it in light of what you know of your own health (especially other medications you’re taking). Consider talking to a doctor, if you have a good one.

If any of you are thinking “oh niacin’s a water-soluble vitamin it must be fine”: that’s a pretty good heuristic but it doesn’t hold for niacin in particular.

My experience

As mentioned previously, I acquired lingering progressive chest congestion/inflammation from (probably) my covid vaccine. It’s always possible there was another reason but the timing and symptoms really do not match anything else. 

Since I never had covid (probably), my reaction can’t come from the infection itself, only my immune response to it. Since the theory doesn’t specify a mechanism that’s not disqualifying, but they do make it sound like it starts as a covid problem not an immune problem.

I started this supplement stack before doing any deep verification. The original blog post pattern matched to the kind of thing that was worth trying, everything on the list I either knew was generally safe or confirmed with a quick check (my doctor later confirmed my opinion on safety without endorsing the stack for any particular use), and I had a lot of client work to do. Shoemaker’s children go barefoot, and all that.  So by the time I was writing this I had been on the recommended supplement stack (and some other things besides) for 3 weeks, and was beginning to wean down. 

Overall: my chest pain got better but the timing fits better with attribution to a different intervention. The rash I got on matches very well with the supplement stack. I nonetheless was craving it after I weaned off, so probably there’s at least one thing in it I need, which hopefully isn’t the same as the thing causing the rash. 

[Alert twitter readers may have questions, since I previously was more positive on the stack. I had a major regression when I got a non-covid cold, and had to go back on the other treatment]

Interestingly, my tolerance for niacin increased and then plummeted. Originally I could take 250mg (the smallest size I could find in the right form) with only very mild flush, and that got better over time, to the point I tried 500 mg once (a mistake). But around week 3 my flush was getting worse. Lowering the dose helped, but it’s getting worse again, so I’m continuing to titrate down. This is extremely consistent with filling up NAD+ reserves over time, although very far from conclusive.

Meta

I was originally much more positive on this treatment/theory. I gave it more credit on Twitter, but that’s nothing compared to the excited messages I sent a few friends after an initial lit review. I wrote several much more positive versions of this post (and the forthcoming study analysis), but there kept being one more thing to check, until I talked my way down to what you see here. Some of my downgrade stemmed from asking better statistical questions, but some of it was just the emotional process of talking myself down from something that initially looked so promising, but ultimately had a similar amount of holes to many other things that looked equally promising and failed to pay off. This represents dozens of hours of work from me and my statistician, for the very disappointing result of “fringe treatment probably doesn’t do very much but can’t rule it out”. Reality is infinitely disappointing

Thanks to Alex Ray and my Patreon Patrons for partially funding this investigation, and Miranda Dixon-Luinenburg⁩ for copyediting.