Introduction

I’ve talked previously about my concerns with nutritional deficiencies in effective altruists who go vegan for ethical reasons, especially those who don’t have a lot of contact with the broader vegan culture. No one else seemed very concerned, so I launched a tiny project to test people in this group and see if they were in fact deficient. This is a report on the latest phase of the project. 

To cut to the chase:

• It was very easy to find lots of deficiencies, although due to a severely heterogenous sample and lack of a control group this doesn’t provide useful information about if veganism is at fault.
• Finding these deficiencies probably leads to useful treatment, but not as much as I’d hoped.
• There are still a lot of operational issues to work out. My guess is that the ideal would require more work (to encourage participants to act on their results) or less (by focusing on education but not providing testing). 
• I am currently looking for a co-founder to properly investigate the impact of veganism on nutrition. 

My main question here was “is there low-hanging fruit in treating nutritional deficiencies in this group, and if so how do we pluck it?” An important part of that is “how prevalent are deficiencies?”, but I had substantially more uncertainty around “do people treat deficiencies you find?” and “does the treatment lead to improvements in anything we actually care about?” That prioritization (and budget issues) led the experimental design to focus on operational issues and outcomes, and deprioritized getting the kind of clean data that would let me compare vegan and non-vegan outcomes. Similarly this write-up is mostly focused on showing the problem exists at all and building metis of investigation and treatment, rather than estimating prevalence. 

Which is to say to to everyone planning on @ing me to complain about the sample size, heterogeneity, or mediocre statistics: you are right that this sample is not very informative about base rates of deficiencies in vegans or anyone else. If someone claimed it was, they would be committing an epistemic sin. However, this particular post is focused on “how much effort is it to get nutritional issues addressed, and is that effort worth it?”. Given that, any complaints about the terrible sampling will be considered to be offers of assistance in running the much larger study that could answer the prevalence question. 

Background 

(if you’ve read the previous posts, this will be review)

Last year I worked in a co-working space focused on existential risks, which is anything that might really end everything. Because x-risk is a popular topic within the effective altruism movement, many participants in the space were EAs. Another big topic within effective altruism is animal suffering, especially farmed animal suffering. This has led many EAs in the office to go vegan or at least vegetarian for ethical reasons, without making animals the focus of their lives. And when I asked them, many had put no thought into how to give up animal products in a healthy way.

Which of course would have been fine if they were eating well. My personal opinion is that most people’s optimal diet contains small amounts of animal products, but lots of people are eating suboptimally for lots of reasons and I don’t consider it my problem. But the number of fatigue and concentration issues were… I don’t actually know if they were high. I don’t know what baseline to compare them to. But it wasn’t low enough to reassure me. Neither did the way the vegans talked about nutrition, and in particular the fact that more than one person was doing keto vegan and still wasn’t investigating nutrition. 

None of this meant there was necessarily a problem, but I was suspicious. So I got a small grant to solve this with numbers. 

First I tried broad spectrum testing, which led me to identify iron deficiency as the main concern.

Then I did a short investigation into the actual costs of iron deficiency, which motivated a number of people to get tested, some of whom got in touch after the fact. 

In my last post I implied I was stopping the project, and wrote next steps as if someone else would be doing them. I ended up getting a follow on grant so pushed forward with round two on my own, which is what this post is about. 

Round 2 concrete steps

I followed the steps laid out in my previous post almost exactly.

1. I brought in a company to draw blood from participants in the Lightcone office. This was expensive, probably 2-4x having people buy lab orders online, which is still more expensive than doctor-ordered tests with insurance.
   1. I say I brought them in – I in fact hired someone to handle the company and interface with participants. Aaron Silverbook was great, pretty much best case scenario for hiring a subcontractor, although still not as good as an invested co-founder.
2. Based on previous results and nutritional folk wisdom my test priorities were ferritin (the best proxy for iron), B12, and Vitamin D. I threw in some other iron tests because they were very cheap.
3. We had applicants fill out a form detailing their diet and any fatigue issues.
4. Aaron picked 20 participants and made a schedule for testing them. Prioritization was: Fatigue issues > vegan > vegetarian > whoever happened to be in the office that day.
   1. This was my favorite part of having a contractor because scheduling involved some very intense math around prioritization and availability and from my perspective it was no work at all.
   2. Prioritizing people with fatigue issues probably made the immediate impact higher, and was useful for estimating the upper bound of possible impact, but ruined the sample for calculating base rates. It means I can’t really compare vegans vs. omnivores, because both were selected for having potentially-nutrition-caused problems. I had hoped to maybe compare vegans with fatigue to omnivores with fatigue, because the tired vegans had more nutritional issues that would be pretty suggestive, but ultimately didn’t have enough data to bother.
   3. I flat out didn’t have enough money to do a good study capable of establishing high confidence prevalence rates, even if that had been my primary goal. Putting aside sample size, good sampling requires getting representative participants, many of whom have no reason to get tested. They’re not intrinsically motivated, so you have to pay them to get tested. 
5. The company comes into the office. There are a bunch of day-of headaches that Aaron handles beautifully and I am completely uninvolved with because he is good at his job.
6. Results go out. Some participants received results over email, some were told to go to the company’s portal, some may never have gotten a notification at all. More on this in the Difficulties section.
7. I ask Aaron to get results from participants to me, for analysis. This goes less well- I wasn’t sufficiently clear on what information I wanted in the form, and he’s gotten busy with other stuff and had less time to devote to my project, which has already gone longer than anticipated due to issues with the lab. Response rate is poor- we eventually get 13 people out of 20.
8. I send out a second form asking for more information, and a bunch of emails harassing people to do both forms. Response rate continues to be poor, only 8 people this time. 
9. 3 months after testing I followed up with the people with the worst scores to see if they had gotten treatment.

Project Difficulties

Other People’s Fault

I cannot say enough bad things about BayAreaPLS, the company we hired to come into the office and do testing.

First and most importantly, they just forgot to run the ferritin test for half the participants. They did the other tests, there was no reason to not do that one in particular, they just… didn’t. Their initial attempt to make up for this was an offer to not charge me for tests they didn’t do. I pushed back fairly hard and they agreed to some actual discounting. It’s been 2.5 months and they have yet to send me that follow-up invoice, which I guess is technically good for me but makes me feel worse overall.

Second, the results were hard to retrieve. Some participants never got results at all even after following the instructions, and I have no way to debug whose fault that is. Others didn’t bother to retrieve results because it was too hard. The happiest people were the ones who got their results over email, which is a HIPAA violation the company claims to have done by accident. Much like the lack of the second invoice, the emailed results are technically good for me but leave me more concerned about the company.

Even for people who did get results it took almost two weeks, which was not great for momentum.

Lastly the company used different deficiency thresholds for different people. They say this was based on sex and age, but they didn’t get that information from everyone (sounds like incompetence on their part), so some people got a list of thresholds. It ended up creating a moderate amount of confusion and friction, especially because I couldn’t tell what variation came from age/sex (which I mostly want to ignore) vs. the norms of a particular test (which I very much don’t). People are slow to act on results in general so the additional friction was quite costly. 

My Fault or Inherent Difficulties

Not all of these were literally caused by me, but they all fall under “my responsibility to anticipate and handle”.

I mentioned in my last post that some participants were kind of insistent on getting a lot of help from me, even after I explicitly told them something was outside my bailiwick and needed a doctor. I tried to fix that this time by hiring Aaron. That worked on that one issue, but made it harder to catch new problems. If the plan had been for people to directly show me their results and receive coaching I would have caught the missing test values much earlier. I’m not sure there is a way to have someone available enough to get all the relevant questions from participants without also having to deal with a bunch of irrelevant ones, including inappropriately persistent ones. The difference between the two just isn’t obvious with the knowledge most participants have, and emotions run so high around health stuff.

It’s hard to estimate the rate of acting on results because the people who don’t act are less likely to fill out the follow-up surveys, but my sense is it’s not good, and probably <50%. I also strongly suspect the rate of acting on results would have been higher if there had been in-person follow-up. 

The guidelines I sent participants emphasized vitamin D and ferritin because it didn’t occur to me anyone could see an anemia result on the page and not rush to treat it, but at least two people scored as anemic and, as of three months later, had not treated it. 

The lab obeyed HIPAA enough to only send results to participants, not directly to me, so I needed participants to forward them. Of 20 participants, 13 did so. Only 8 participated in the separate follow-up questionnaire (arguably my fault for asking for two separate forms, but there was good reason to ask for results quickly and do the follow-up a little later). 20 people with varying motivations for testing was never going to be strong evidence for anything systemic, but the low response rate makes it even harder to draw conclusions.

My emails to participants sometimes went to spam, possibly due to use of BCC, which was necessary to meet the privacy commitments I made in the application.

What were the total costs? 

As a ballpark:

• ~$270 per participant (if they had done all the tests for everyone).
• 0.5 hours per participant, including follow-up and the disruption to their schedule. If you want to be really conservative you could call this an hour to account for the disruption from transitions.
• ~10 hours of Aaron’s time
• ~20 hours of my time
• $30 per deficient person for supplements (not covered by the study)

If you value everyone’s time roughly the same, that means that to break even we need to save one person 30 hours + ~$5700 (ignoring the information gained). 

If you want to complicate that math you can add any of: discount rate on time or money, exchange rate between ops time/my time/participant time, cost of unnecessary or counterproductive treatment, knowledge gained from this round can make the next round cheaper, the fact that most of my time went to a write-up that shouldn’t really be billed to participants, but a better program would have spent more time with participants.

Results and Benefits

Test Results

I should remind you here that the sample was a mix of 20 ethical EA vegans, vegetarians, people with fatigue issues, and people who happened to be in the office. Even a very large sample wouldn’t be perfectly predictive unless you had the exact same mix of participant types, and this sample was tiny. So the right way to look at these results is “is this enough to think there’s a problem?” and “did people do helpful things with the information?” not “at what exact rate does this population develop ferritin issues?”

With those caveats, here is the data from participants that reported back. I have ferritin results for 8 people and all other results for 13. 

• 85% reported energy problems
• 15% were honest-to-god anemic
• 65% had low ferritin (30% clinically deficient) (none of the anemic people had ferritin tests done, so there is no overlap between this group and the anemics. There were non-anemic people without ferritin tests, so I assume this is a coincidence)
• 60% had low vitamin D (15% clinically deficient)
• A total of 80% had low scores in at least one of hemoglobin, ferritin, or vitamin D
• 0% had low B12 (many were on supplements, but I haven’t correlated that with serum B12 levels because at this sample size and heterogeneity there is no point)

Some of the non-reporting was random due to the lab’s incompetence, but it’s not impossible unhealthy participants were more likely to report back. If you want to be extremely conservative and assume every missing value was A+ healthy, the results are still quite concerning: 

• 10% anemic
• 25% low-in-my-opinion ferritin, 10% clinically deficient (still no overlap with the anemics)
• 35% low-in-my-opinion vitamin D, 10% clinically deficient
• B12 is still great, good job everyone

I Lead This Horse To Water – You Won’t Believe What Happened Next

But finding results isn’t very meaningful if no one acts on them. Of the 8 people who filled out the follow-up survey, 75% changed either diet or supplements, and 1 additional person kept going with supplements they would otherwise have dropped. I assume this is overreporting because people who changed things are more likely to respond, but if you assume none of the nonresponders did anything that’s still 30% of people changing something.

Of the 5 who changed something and answered the relevant question, 40% said they thought they saw an improvement (~1 month after they received results). I don’t consider that particularly strong evidence in either direction- it can take time for deficiencies to heal, but it’s also easy to placebo yourself into seeing an improvement that isn’t there. The real test will be the six-month follow-up. 

Three months after testing I followed up with the two identified anemics to make sure they were getting treatment. Neither was, despite having health issues plausibly caused by anemia. They’ve both indicated vague plans to follow up now that I’ve pushed them on it. 

Is in-office testing worth it?

I believe this round of testing was better than not doing in-office testing, but there is a lot of room for improvement.

My absolute wild-ass-guess is that this saved between one and ten people (out of twenty participants) from anemia or a moderate iron deficiency, and this improved their life and productivity by 10% to 100% (mean around 20%). I acknowledge these are large ranges, but some problems are bigger than other problems. I’m ignoring vitamin D entirely here because I haven’t even attempted to quantify its value and its ardent fanclub has poisoned the literature.

Even in the worst case, a 5% chance at a 10% improvement is a big deal, so I think this was obviously worth it from a participant perspective. I think it’s a toss-up if it would be worth it for apparently healthy omnivores: my expected value for them is much lower, but people don’t always realize they’re operating at a deficit and catching them requires testing actually-healthy people as well.

I said above that we needed to save someone 30 hours + $6000 for the project to break even. Even one successfully treated anemic will blow that out of the water, so I don’t feel the need to do the more complicated math with discount rates and relative value of time, especially because any future round should either be less work or have a higher response rate.

Of course “break even” isn’t a very high bar. To go even further out on a limb: the median case of mild anemia easily costs someone two hours/day (source: had anemia one time).  This testing easily caught the anemia at least six months before it would otherwise have been caught (because everyone who was going to get tested on their own did so when I published my iron post).  That is, at a bare minimum, 360 hours someone otherwise wouldn’t have had. That’s a pretty great return rate for 40 hours (my time + Aaron’s time + participant time) +$6000.

Was the project overall worth it?

I would bet on yes, although a lot of information has yet to come in. 

I expect this project to have 6 lasting impacts:

1. The treated health problems of participants.
2. The secondary impact via participants’ work. 
3. Public blog posts I write. My iron deficiency post, which motivated many people to get tested themselves, quite possibly more than received tests directly.
4. Knowledge of how to do this more in the future. 
5. Influence on Effective Altruism vegan culture.
6. Animal suffering averted by making veganism more sustainable for participants.

#1 is what I calculated above, and think was already a sound success although not resounding.

#2 and #3 require making assessments of all individuals who received testing from the project or due to blog posts I wrote. That’s a combination of “vast amounts of missing information” and “judging individual merit” that makes it really uncomfortable to talk about in a public post. 

To be totally honest I’m on an “everything is bullshit” kick right now so deep in my soul I don’t think this paid off, but intellectually I think my standards are too high and this was a better project than average project in the space of existential risk. 

#4 and #5 depend on other people following up on this project. I absolutely believe they should, for all the other reasons but also because the return via #6 seems pretty good- health reasons are a common reason vegans go back to eating meat [It was hard to find a good source, but this shitty source says 26%. I’ll acknowledge that’s probably an overestimate, since health is the most virtuous reason to go back to eating meat.]

I can’t estimate #6 myself. I’m not familiar enough with vegan literature to sort good from bad here, and it wasn’t my main goal.

Then there are costs. The total grant was for a little less than $25k. I didn’t track my time very closely to avoid depressing myself, but my compensation is going to work out to a fraction of my normal hourly rate. If you count foregone client work you could argue the true cost was as high as $50k. 

My gut feeling is the project was straightforwardly worth it if you don’t track the foregone work. If you do, impact is dependent on having at least one of:

• At least one of the impaired and successfully treated participants goes on to do high-impact work.
• The iron post inspires at least 40 tests total, with a similar rate of finding and treating problems.
• Follow-up projects exist and do good work. 
• This work leads to more veganism, and you value that a lot. 

So can we blame veganism for the deficiencies?

This study doesn’t say anything one way or the other, which means I still think yes but you shouldn’t change your opinion based on the results. The sample is too small and skewed to compare deficiency rates in vegans and nonvegans. There were energetic omnivores with deficiencies and tired vegans with perfect scores so it’s clearly not deterministic. 

Next steps

I see three possible follow ups to this project:

Nutrition blogging

This is my default, although I don’t plan on writing many of these because there is only so much low hanging fruit and people have a very limited attention budget.  I have to be very judicious in what I suggest.

Mass testing to investigate deficiencies in effective altruism populations

Get the money to test a large enough representative sample, and run the tests with a proper control to actually estimate the cost of nutritional veganism. 

This is most useful if there are EA vegan leaders who won’t act on nutritional concerns now but would if the study demonstrated a problem. If this is you, I would love to talk to you about what you would consider sufficient to act on. 

Assuming the demand for this information is there, I still don’t think I want to run this project alone. First, it is a lot of work. Second…I know I said “assuming demand is there”, but I can’t picture a scenario where demand exists but no animal EAs consider this project worth working on. A collaborator would be both proof of investment and much better positioned than I am to get the information acted on. 

To that end, here is an ad for a co-founder. I will post it on this blog in a few days.

In office testing with real nutritional counseling

This can work, but only in a limited number of situations. You need a reason  (uninformed veganism, high fatigue rates) to suspect nutritional issues in lots of people sharing a space. There needs to be a reason people aren’t getting tested themselves that won’t also inhibit follow up (probably lack of money and existing relationship with a doctor). And even then it’s more of a hits-based model than a sure thing.  

My decision is easy because the office I was working out of closed, and in general I think most of the people in the bay area I would want to help have already been reached. The market is saturated for at least a year. There are other offices elsewhere in the world, and if you want to run this yourself I’m happy to act in an advisory capacity (especially if you share data), but it can’t really be an ongoing project in any one city. 

Conclusion

I finished most of this post planning on it being the end of my part of the project. I had hopes I would convince someone else to pick up the torch, and maybe even act as an advisor, but it seemed like the biggest problem was participant motivation, which I don’t feel equipped to solve. It was while I was writing this that I realized I wasn’t ready to let the broader issue of vegan nutrition go. I still believe the problem that offended my morals and epistemics is there and worth acting on.

But doing so is still very annoying, which is why I’m looking for someone to partner with on this. Someone who can handle the parts I’m bad at, point out where I’m wrong, and interface with the vegan EA community to get the results acted upon. If you’re interested, please reach out to elizabeth@acesounderglass.com.

Thank you to the Survival and Flourishg Fund for funding this research, and Lightcone Infrastructure for hosting the grant and testing. I inflicted this draft on a number of people but want to especially thank Gavin Bishop. Daniel Filan didn’t beta read this post but he did vegan-check my co-founder ad and suggest the title “I Lead This Horse To Water – You Won’t Believe What Happened Next”.

Introduction

Reducing consumption of animal products is a choice with both moral and practical consequences. Last summer I found myself in contact with many vegans who cared a lot about the moral consequences, but had put little effort into learning about or managing the practical consideration of removing animal products from their diet. I’ve suffered a lot due to bad nutrition, so this made me very concerned. With a grant from the Survival and Flourishing Fund, I launched small a pilot project to give nutritional tests to 5 vegans and near-vegans from the Lightcone Office, which they could use to choose supplements that would hopefully improve their health.

My long-term goal was for everyone to have accurate information on their personal nutritional costs of veganism and make informed choices about how to handle them, with the first line solution being supplements. My goal for the pilot was to work out practical issues in testing, narrow the confidence interval on potential impact, and improve the nutrition of the handful of people. This report is on phase 1: getting the testing done and supplements started. It is aimed at people who might want to run a similar program at scale; if you are interested in running this for yourself I recommend checking out Tuesday’s post on iron deficiency.

Tl;dr: I found rampant iron deficiencies, validating the overall concern. The procedure I used has a lot of room for improvement. 

The Experiment

I gave nutrition tests to 6 people in the Lightcone office. 

The ideal subject was completely vegan, had never put any effort or thought into their diet, and was extremely motivated to take a test and implement changes. This person does not volunteer for studies, so I ended up with 4 vegans or near-vegans who had put somewhere between 0 and a lot of thought into their diet, 1 vegetarian, and 1 extremely motivated omnivore I used to test out the process.  In addition, one hardcore vegan contributed results from private testing. I did not poll the ~vegans on their exact diets.

Unless otherwise stated the results exclude the omnivore.

I gave each of these six people a Genova Metabolomix+ test, ordered from walkinlabs.com, with the iron add-on. This test was selected for being recommended by doctors I trust (in part because they prefer urine to blood testing), having extremely easy-to-read results, being nearly comprehensive (with the unfortunate absence of vitamin D), and because I hoped urine collection at home would be easier than blood draws at a lab. Foreshadowing: I was wrong about that last part.

I also gave people the option of an add-on to determine what variant of the MTHFR gene they have. MTHFR can affect how one processes certain B vitamins, and certain variants can necessitate a more expensive form of supplements.

Several people (although not everyone) scored with undetectably low iron. I offered them follow-up blood tests, which one person accepted. An additional vegan contributed blood test results without urine results.

As of publication all subjects have received their first round of results and started supplements of their choosing. 

The original plan was to retest in 3-6 months after people began supplements, using the same urine tests.

My initial predictions

I expected the big shortages to be B12, iron, and vitamin D, the first of which has very few* natural vegan sources and the latter two of which are scarce, although not absent, in vegan sources. This makes it pretty unfortunate the original test did not include vitamin D. 

[*B12 is naturally found in some (but not all) seaweeds and algaes, in at least one kind of mushroom, and in nutritional yeast. It’s also added to many wheat products in the US, so if you eat enough wheat and aren’t going out of your way to get unfortified wheat that’s a strong source]

Relative to the mainstream I wasn’t very concerned about protein consumption. Vegan proteins are a little less abundant, a little harder to digest, and have a less ideal distribution of amino acids, but are basically fine as long as you don’t pile on additional constraints.

One reason I was concerned was that lots of people I polled were piling on additional constraints, like keto or gluten-free, and still not doing anything to manage nutrition. I expected a smattering of deficiencies from these people, and to a lesser extent from everyone, as their restrictions and tastes cut off random nutrients. These could have been in any almost nutrient.

I expected everyone to be fine on vitamin C because it is abundant in both produce and processed food (where it’s used as a preservative).

Results

(including only vegans and near-vegans)

1. ¾  vegan testers had severe iron deficiencies in their urine tests.
   1. The one who didn’t had both a stunning dietary intake of iron, and a parent who 23andMe believes to have a genetic predisposition to excessive absorption of iron.
   2. An additional vegetarian tester was not deficient.
   3. One of these retested with a blood test and scored low normal (~30). However this person was already taking iron supplements at the time of the test. 
   4. A bonus blood-only participant tested between 13 and 20, meaning they’d be considered deficient by some standards but not others.
2. There were no B12 deficiencies, probably because everyone was already on B12 supplements. 
3. One tester had a lot of deficiencies, including vitamin C, to the point I suspect it’s a problem with digestion rather than diet. 
4. Everyone had at least one amino acid deficiency, including the person eating over 100g of protein/day. I don’t know how big a deal this actually is.
5. The urine test did not include vitamin D.  Of the 2 blood tests, both had low-normal vitamin D.
6. Excluding the person with across-the-board deficiencies, there were scattered other deficiencies but nothing else to consistently worry about. People were mostly in their tests’ green zone, with occasional yellow and red.

What does this mean?

Only one near-vegan out of 5 had solidly good ferritin levels. As I discuss here, that’s a very big deal, potentially costing them half a standard deviation on multiple cognitive metrics. 

There’s no control group, so I can’t prove that this is a veganism problem. But I’m quite suspicious.

There were no other consistent problems, so broad-spectrum testing is probably overkill for people with no known problems. 

Retrospective on the project

What worked

I consider the core loop of the study as vindicated as can it be at this stage. 

• Deficiencies were identified, and the primary one was one of the three I predicted.
  • And another of the three, B12, was probably absent because people treated it preemptively. Note that people were inconsistent in what they took so I can’t say definitively what they were on during testing.
• In the counterfactual timeline the shortages were probably identified much later if at all. No one who participated had any plans for testing, including people with obvious symptoms and people whose doctors had previously recommended testing.

This will be less impressive if supplementation doesn’t turn out to fix anything, but it’s an extremely solid start.

Other things that went well:

• Having the room in my budget for unplanned additional testing, so I could add in serum iron tests when it became obvious they were necessary.
• Creating a shopping list with links. I was worried this was somehow taking advantage of people (since I used affiliate links), but removing a decision and several steps from the ordering process seems to have been pretty crucial. 
• Bypassing the need for doctors’ visits to get a test. Given how long it took people to order tests I think doctors’ appointments would have killed the project entirely. 
• The Lightcone ops team was extremely cooperative and got all of the vitamins I suggested into the office.

Difficulties + possible changes

Potential changes are framed as recommendations because I am deeply hoping to hand off this project to animal advocates, who caused the veganism in the first place. 

1. The test ordering workaround was not as good as I had hoped
   1. I’d originally hoped to just hand participants a box, but they had to order the tests themselves.
   2. In order to get iron + genetics tests people had to call rather than order online. This is non-standard for the provider and two people had to call twice to insist on what they wanted.
   3. Tests took a long time to ship, and a long time to return results after shipping. The lab alleges this is a supply chain issue and there’s nothing to be done about it. 
   4. Those two together turned into a pretty big deal because they made it very hard to plan and people lost momentum.
   5. In combination with the results showing few problems beyond iron I recommend deemphasizing full spectrum urine tests and focusing on blood tests for iron (and vitamin D), and making those convenient, perhaps by bringing a phlebotomist to the office.
   6. Another option would be to bring in a medical practitioner, who can order tests for other people, to manage tests so the office can be stocked with them. This of course fails to solve the problem for anyone not in the office.
   7. There are home tests for vitamin D and iron specifically, but I have no idea if they’re any good.
2. Ideal test subjects (completely vegan, never done nutritional testing or interventions, promptly puts in the effort to do these tests and act on them once I suggest it) were even thinner on the ground than anticipated.
   1. I knew there wouldn’t be many, but I didn’t think it would be so hard to get five people pretty close to that profile. 
   2. I loosened restrictions and still consistently found problems, so recommend lowering the eligibility bar for testing in future rounds, especially since that was always the plan. The strict requirements in this round were an attempt to make the signal as loud as possible.
3. Getting everyone tested was like herding cats. Beyond the problems with the test distributor, some participants needed repeated reminders to order, one lost a test, results went missing… it was kind of a nightmare.
   1. One advantage of focusing on blood tests would be to cut down on this, especially if you bring the phlebotomist to the office.
4. At points I was uncomfortable with the deference some participants showed me. I was as clear as I possibly could be that this was a best-effort from a knowledgeable amateur kind of thing; they were responsible for their own health and I was a nonexpert trying to provide some logistics help. I nonetheless got more than one person bringing me problems not even related to the nutrition project, and insisting I tell them what to do.
   1. Recommendation: bring in a skilled nutritionist. They can both give better advice than me and devote more time to helping people. 
5. I initially misread the protein results (which are delivered in terms of “how deficient are you?” rather than “what’s your current level?”, making 0 the best possible score). Luckily I knew I was confused from the beginning and no one had taken any actions based on my misinterpretation. More broadly, I’m just a woman who’s had some problems and read some stuff, I expect my suggestions to be better than nothing but far from the maximum good it would be possible to do.
   1. Recommendation: bring in a skilled nutritionist
6. I underestimated the amount of time and especially emotional labor this project would need. I was hoping to bluff my way through that until people got on supplements, at which point the improvements in health would be their own motivation. I think I always overestimated how well that would work, but it was especially wrong because all the problems with the tests drained people’s momentum.
   1. Recommendation: I still think you should bring in a skilled nutritionist
7. Many of the participants were moving frequently and not in the office by the time their results came in (because they took so long…), so they had to buy supplements themselves. Given the option I would have selected people consistently in the office, but as mentioned I was already managing trade-offs around participants.
   1. Recommendation: ask for more money to give everyone their first month of supplements and a convenient pill planner.

Next Steps

I previously planned to give people the same urine test 3-6 months after they started supplements. That no longer seems worth it, relative to the cheaper and more convenient blood tests. 

It’s not actually clear a formal follow-up is that useful at all. I initially planned that because I expected a wide range of shortages such that literature reviews wouldn’t be helpful. But there was only one real problem, and it has a richer literature than almost any micronutrient. So I don’t think another 5 people’s worth of scattered data is going to add much information. 

So the next step for this as a project would be mass blood testing for B12, iron, and vitamin D. 

Feeling motivated?

If this has inspired you to test your own nutrition, I haven’t done anything you can’t do yourself. Both the urine and blood tests are available at walkinlabs.com, and if you have a doctor they’re quite likely to agree to testing, especially if you’re restricting meat products or fatigued. I have a draft guide of wisdom on supplementation I’ve picked up over the years here, although again, I’m not a doctor and only learned how to digest food last May, so use at your own risk. 

Thank you to the Survival and Flourishing Fund for funding this project, Lightcone for hosting, and all the participants for their precious bodily fluids.

In brief

Recently I became interested in what kind of costs were inflicted by iron deficiency,  so I looked up studies until I got tired. This was not an exhaustive search, but the results are so striking that even with wide error bars I found them compelling. So compelling I wrote up a post with an algorithm for treating iron deficiency while minimizing the chance of poisoning yourself. I’ve put the algorithm and a summary of potential gains first to get your attention, but if you’re considering acting on this I strongly encourage you to continue reading to the rest of the post where I provide the evidence for my beliefs.

Tl;dr: If you are vegan or menstruate regularly, there’s a 10-50% chance you are iron deficient. Excess iron is dangerous so you shouldn’t supplement blindly, but deficiency is easy and cheap to diagnose with a common blood test. If you are deficient, iron supplementation is also easy and cheap and could give you a half standard deviation boost on multiple cognitive metrics (plus any exercise will be more effective). Due to the many uses of iron in the body, I expect moderate improvements in many areas, although how much and where will vary by person. 

Note that I’m not a doctor and even if I was there isn’t good data on this, so it’s all pretty fuzzy. The following is an algorithm for treating iron deficiency that I’ve kludged together from various doctors. I strongly believe it is a lot better than nothing on average, but individuals vary a lot and you might be unlucky. 

1. Take a serum ferritin test. If you have a doctor they will almost certainly say yes to a request, or you can order for yourself at walkinlab.com
2. If your results show a deficiency (<20ug/L), increase iron intake through diet or supplements such as Ferrochel, taking the default dose once per day, with a meal.
   1. The definition of deficiency can vary by study, lab and goal. I picked <20ug/L because it’s the highest level I have concrete evidence is insufficient, but personally believe people are likely to benefit from iron beyond that and am taking pills accordingly.
3. If you experience negative effects after taking the pills, stop immediately. Give yourself a week to recover, then you can try other brands, be more careful to eat with a full meal, etc. 
4. If you are experiencing the symptoms of iron poisoning (listed below), stop pills and see a doctor now. Iron poisoning is a very big deal, which is why step 1 of this algorithm is “get tested” not “gobble pills”.  Unfortunately several of these are pretty generic, but I’m never going to feel bad about telling people with seizures to seak medical attention:
   1. Nausea
   2. Vomiting
   3. Abdominal pain
   4. Dizziness
   5. Low blood pressure and a fast or weak pulse
   6. Headache
   7. Fever
   8. Shortness of breath and fluid in the lungs
   9. Grayish or bluish color in the skin
   10. Jaundice (yellowing of the skin due to liver damage)
   11. Seizures
   12. Black or bloody stools
5. Retest at 8-12 weeks, ideally at the same lab as before.
6. Continue to retest every 8-12 weeks.
7. If you increase by 20ug from your starting value without noticing any improvements to your cognition or overall energy levels; low ferritin is probably not your bottleneck.
   1. If you believe it’s not a problem at all, quit.
   2. If you believe it is a problem but another problem is limiting your gains, stay on a maintenance dosage but don’t put more time into managing this. Verrrrry roughly, divide your current dosage by your currently monthly gains (so If you take one RDA/day and gain 10ug/month, your result is 0.1), and take that much. This hopefully keeps you from losing ground, without gaining so quickly it could become a problem.
8. If you’re getting improvements, keep going until those taper off. I personally would exercise caution and investigate the downsides of iron once I reached 80ug/L, but I’ve never gotten close to that so it hasn’t come up. 
9. Continue to retest and adjust until you’ve found a dose on which your values are stable and healthy.

[Note: I provided links to supplements because I found people follow through more when I do, and because it’s easy to buy worthless supplements. There are other good supplements out there and if you have a reason to prefer one, take that instead. Links are affiliate.]

Research summary

Iron’s most famous use in the body is in hemoglobin, which your blood uses to transport oxygen. Oxygen is extremely important [citation needed], so it makes sense that low hemoglobin (aka anemia) gets a lot of attention, and everyone agrees anemia is very bad. But what the studies I read found was that even among people who started with adequate hemoglobin, a low ferritin score still predicted they would benefit from supplementation. And it’s not because of a bad definition of “adequate”; people saw benefits even when their hemoglobin didn’t change. So what else does iron do? 

Iron is one of a small number of elements that can safely accept electrons in reduction-oxidation reactions. Free electrons are quite damaging, so iron’s ability to safely contain them is important. Some specific usages:

• The enzyme catalase, which converts caustic H2O2 to harmless water.
  • Fun fact: Catalase is the least important enzyme whose name and purpose I can recall offhand. Other enzymes achieved that status by being very important (DNA polymerase), or having self explanatory names (carbohydrase), but catalase achieved this by sounding kind of similar to a song I was into the summer I took microbiology, and I made up alternate lyrics about the enzyme.
• Multiple points in DNA synthesis and repair, including keeping DNA polymerases in their correct shapes.
• Myoglobin: similar to hemoglobin it binds oxygen, but instead of blood it stays in muscles, holding oxygen in reserve until it is needed.
• Regulation of many components of the immune system.
• Proline and lysyl hydroxylases, both used to build collagen.
• Please enjoy this list of 80 enzymes that use iron as a cofactor.

I’d say “that’s a lot” but honestly it’s not, everything in the body is like this, it was not built to be understood.

Standard tests for anemia only look at hemoglobin. Ferritin tests are considered to be a much better measurement of cellular iron levels. There’s suspicion, although not proof, that your body prioritizes hemoglobin production above other uses of iron, so it will undersupply these other uses in order to maintain hemoglobin levels. This suggests that if you have normal hemoglobin but low ferritin, additional iron will find many uses. Unfortunately, those uses and their effects are so varied I can’t really predict what any particular person will experience.

There are any number of studies showing correlations between low ferritin and low functioning, but I don’t find those very useful. The people in those studies might have any number of deficiencies for multiple reasons, or low ferritin levels could just be a proxy for poverty. In my research I stuck to actual experiments, with controls, that gave iron to subjects and checked for an improvement in function, not just test scores. Unfortunately, there were not that many of them.

The only study I liked on the cognitive effects found an absolutely enormous effect. Successful iron supplementation led to improvements averaging >0.5 standard deviations in attention, learning, and memory. I have qualms about this study and expect the results are cherrypicked, but it’s also not necessarily the full size of the effect, because they stopped after a set amount of time rather than waiting for effects to plateau.

There were multiple studies on iron supplementation and exercise. In a nutshell: everyone’s endurance improves when they exercise. Giving people with iron deficiency but not anemia (IDNA) iron supplements increases that effect. In the strongest study, people treated for iron deficiency for 6 weeks improved their 15km time by 10%, compared to 5% in the control group. Another study (which didn’t involve exercise training) showed no improvement in time to complete a given distance, but did find the treatment group used about 5% less energy while doing so. 

Iron deficiency rates vary a lot by population, but with the patterns you’d expect. Vegans are more deficient than vegetarians, who are more deficient than omnivores. People who regularly menstruate (or give blood) are more likely to be deficient. I found the baseline rate of omnivorous men in rich countries to be somewhere between 0-11%. For a female omnivore it’s 9-22% (these numbers include people already taking supplements; it’s presumably higher if you don’t). Young female vegans who were not already supplementing were at least 50% deficient, plausibly more. Data for non-supplementing male vegans was not available, but let’s ballpark it at 5-25%, based on the ratio between men and women in the general public.

People in poor countries are much more likely to be iron deficient and anemic, due to poor diet and more physical exertion. 

Caveats

I am not a doctor, my most relevant credential is a BA in a different part of biology, the fact that I couldn’t find a decent resource and had to make it myself is a sign of civilizational inadequacy.

Normally not being a doctor inhibits me from giving medical advice, but I am going to go ahead and say that iron poisoning is extremely bad and not that hard to induce with pills, don’t do that. Iron poisoning is why you need to be careful your kid only gets one multivitamin a day, and why men can’t use women’s multivitamins (which should actually be “menstruator’s multivitamins”, since the relevant issue is monthly blood loss). 

The papers are very finicky and boring and this was really important, so I’ve tried to frontload my conclusion. This is a delicate balancing act of readability and accuracy. I did my best but some trade-offs are unavoidable. 

This lit review was done with a focus on people with low iron intake, especially vegans. None of the studies I looked at filtered on dietary intake versus absorption issues. This means they probably underestimate the impact of supplementing for healthy people.

Do not take the dosages in the studies literally, especially if you don’t menstruate. The right dosage depends on the form and your personal needs. I suggest operating based on RDA percentages rather than raw chemical weights.

Details

Definitions

There are a lot of ways to measure iron and iron-related levels in the body. The two most important are hemoglobin (the protein red blood cells use to carry oxygen) and ferritin (the protein your cells use to store oxygen, but also present in blood). There are some other numbers I’m going to ignore.

Hemoglobin and ferritin are both testable via blood sample, and the tests have something called “reference ranges”, which are supposed to be the healthy range of values. Whether the ranges actually capture that is a matter of great controversy, with various people alleging the minimum is what you need to avoid hardcore deficiency diseases, but won’t get you optimum functioning, to people claiming low scores are fine and anyone who says otherwise is a psyop from Big Vitamin. And then there’s individual variation.

Hemoglobin’s reference range is 120g/L-170g/L.  Ferritin’s reference range starts between 10 and 20 ug/L, and ends at 150-200ug/L, depending on who you ask.  It’s possible to have low hemoglobin (aka anemia) without an iron deficiency or vice versa. Low hemoglobin with adequate iron typically means you’re having trouble manufacturing hemoglobin and is beyond the scope of this post. Low iron with adequate hemoglobin is more controversial. Top explanations include “the tests aren’t that good”, “you’re deficient but your body is prioritizing hemoglobin production”, “you’re about to develop anemia” and “low iron is fine, actually”.  

Impact Data

When looking at studies I used the following selection criteria:

• Examining iron deficiency without anemia. We can assume that anemic cases will benefit more from iron, unless the anemia is unrelated to the iron deficiency.
• No co-morbidities.
• On adult humans (in practice this almost always means women).
• In the developed world.
• RCTs only, no correlational studies.

This didn’t leave a lot of studies, and I had to accept some other flaws. 

Mental

Murray-Kolb and Beard (2007)

This study was by far the best study of cognitive function, maybe the only one that tested an intervention rather than merely looking at correlations. I don’t love it. The data presentation is obviously leaving a lot of information out, I assume to dramatize results. But those results are very dramatic. 

This study allowed for mild anemia (hb < 120 but >105), but separated anemic and non-anemic subjects. The paper, uh, doesn’t mention its threshold for iron deficiency; another paper from the same authors set it at serum ferritin <=12ug/L, which is in line with the aggregated averages.

The study included a double control group that started with sufficient iron and hemoglobin. Each group (no deficiency (n=42), iron deficiency without anemia (n=73), and iron deficiency with anemia (n=34)) was split into treatment and placebo groups. 

Iron supplementation increased ferritin levels in everyone. People with iron deficiency without anemia (IDNA) increased serum ferritin (sFt in the table) 2.5x more than their placebo group; people with iron deficiency and anemia (IDA) improved ferritin levels almost 4x more than their placebos. Neither group got anywhere close to the ferritin levels of the no-deficiencies group. The treatment group was given 160 mg of ferrous iron daily.

In baseline cognitive testing, IDNA women scored about the same or slightly worse as healthy women, and IDA women scored much worse than both. This is probably an underestimate of the effect, because the study was heavily recruited from students at a single university, who can be expected to be selected for the same range of competence.

The study separately evaluated treatment-group women who had increased ferritin levels from those who didn’t. The former group had large improvements in their cognitive test results, the latter very modest ones. I think separating out non-responders is fair: if there’s a problem interfering with iron absorption that doesn’t tell you anything about the effect of increasing ferritin levels, and I am studying this mostly for the benefit of people with insufficient dietary intake.

Among ferritin responders, attention, memory, and learning increased from .5 to .75 standard deviations (although somehow that .75 is at p<0.07). That effect size is the equivalent of 7.5-12.5 IQ points or 1.1-1.6 inches in height. Of course the test could be bullshit, but it’s not out of line with anecdotes I hear. Additionally, the treatment groups did not reach the ferritin levels of the healthy group, indicating potentially more gains to be had.

Hemoglobin responders also saw more improvement than non-responders, but the effect size was smaller than with ferritin, indicating an effect of iron beyond increasing hemoglobin.

(Note that the axis has changed from performance to time required, making negatives good. Yes, I am suspicious that they presented total score for one metric and time to completion for another).

Physical

Zhu and Haas (1998)

20 women with normal hemoglobin (Hb >120 g/l) but low ferritin (serum ferritin <= 16 ug/l) were given 135 mg ferrous iron supplements for eight weeks and instructed to take with citrus juice. 17 women were given placebos as a control (random assignment, double-blinded). They were given both blood and athletic tests before and after treatment.

Treatment group hemoglobin and iron binding capacity were unchanged. Serum ferritin was up 250% for the treatment group (compared to 30% for the control). Their athletic test results did not improve any faster than the controls, however they needed less energy (2.0kj/min) and oxygen (5%) to get those same results. 

Hinton et al (2000)

22 women with normal hemoglobin (Hb >12 g/dl) but low ferritin (serum ferritin <= 16 ug/l) were given 100mg ferrous iron supplements for six weeks. 20 women were given placebos as a control (random assignment, double-blinded). They were given both blood and athletic tests before and after treatment.

Iron supplementation did not change hemoglobin or iron binding capacity levels, but did increase serum ferritin by about 50%, and transferrin saturation by 70%. Note that their ending ferritin levels (19.4) were still barely above the bottom of the reference range, indicating there was probably much more room for growth. 

The control group went marginally up on some measurements and marginally down on others, I’ve treated their changes as noise.

Both treatment and placebo groups were given 4 weeks of exercise treatment; the treatment group showed about double the athletic improvement. Endurance saw a bigger improvement than initial performance.

Brownlie et all (2004)

~20 women, with serum ferritin concentration < 16 ug/L and a hemoglobin concentration > 120 g/L were given 100mg ferrous iron/day for 6 weeks. Of that, 4 weeks also included exercise training.

Once again we see an improvement in ferritin but not hemoglobin or binding capacity.

The treatment group experienced ~30% more improvement in their trial times than the control, or 800% if they started with elevated ferritin. I’m suspicious of this posthoc subgroup analysis, but on the other hand, the bar in this graph is very big.

Hinton and Sinclair (2006)

The good news: this study has men! I did not think I was going to find any of those!

The bad news: this study has 20 people, total.

No meaningful change in hemoglobin or binding capacity, near doubling of serum ferritin in the treatment group, 15% drop in ferritin in the control group. 

Results are basically identical for the control and placebo groups.

Prevalence Data

Estimates for the prevalence of iron deficiency vary a lot by study and population. 

In the first paper I found, the estimate was 9-22% among menstruating women in the general public, and 1-2% among adult men (non-menstruating women were not included but I expect “do you lose 2-4 tablespoons of blood every month?” and “do you occasionally host demanding parasites?” to be more important than hormones or gender identification). Note that this number includes both anemic and non-anemic iron deficiency. 

Vegans are at much more risk. One German study of vegan women found a median serum ferritin level of 14 ug/L, a level that is above their reference range and LabCorp’s but below the cut-off in several of the studies cited above. They found 40% of young women fell below their threshold for deficiency (12ng/ml) and 11% of older women (presumably mostly post-menopausal) did so. Women taking iron supplements were excluded from this study.

A second German study (why are they all from Germany?) that allowed supplements and had an even gender split found rates of iron deficiency slightly lower in vegans than omnivores, but both had higher means than anyone in any of the impact studies I found. Nonetheless, 10% of vegans were iron deficient.

My own study (data forthcoming) had 3-4 male vegans and a deficiency rate of 25%-75%, depending on how you count. 

Thank you Survival and Flourishing Fund for funding this research and Lightcone Infrastructure for providing a home for it.

Thanks to Andrew Rettek for help making my normally very in-the-weeds style more accessible.