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Comment by mistercow | Hacker News Reader

I don’t understand the author’s reading of the literature they cite. They refer to “isolated studies” and then link to a systematic review of 25 studies. They also linked to the same review twice for both memory and attention, which I assume is a mistake, because the review only supports the claim about memory.

But none of these studies are about “brain-boosting”. They’re about preventing or reversing cognitive decline, which is perhaps related, but ultimately different.

No fault to the author of this post for being unable to find evidence focused on healthy adults; anyone who has looked into the evidence around nootropics can tell you that pretty much nobody wants to study that. But it’s important to be clear about what the evidence actually says, and what it doesn’t speak to.

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> anyone who has looked into the evidence around nootropics can tell you that pretty much nobody wants to study that

There's a class of areas where lots of non-experts are interested, but doing studies large enough to detect modest effect sizes with high confidence is too expensive. Nutrition can do either large survey studies, or small controlled experiments. Exercise researchers often have to work with a small number of untrained participants. I would love a citizen science platform for large studies of low-risk interventions operated like a multi-armed bandit setup. "Oh, you're interested improving working memory? Follow regimen X for 90 days and do this working memory test every week." I feel like the hardest parts are getting participants to adhere to their assigned intervention, and preventing participants with a pre-existing agenda from joining.

> I feel like the hardest parts are getting participants to adhere to their assigned intervention, and preventing participants with a pre-existing agenda from joining.

This combined with perverse incentives are why it's not possible. Non-experts with the resources to solve these problems are generally trying to sell you something, and aren't particularly interested in the truth.

Perhaps so. Saying it's "not possible" seems like an overly strong conclusion.

For specific interventions, I think it might be possible to have open, blinded participation. E.g. for supplements which may affect memory:

- Participants sign up to buy a supplement which they know will be one of k generally safe supplements or a placebo

- The specific supplement or placebo they receive it thompson sampled (or similar) from our bandit given data so far, and sent to them unlabeled

- They're only able to receive their next bottle if they complete weekly tests or measurements

The value prop is that you're probably buying a pretty good intervention, even if you don't know which one it is (and perhaps you're getting a discount subsidized by the minority of people who are paying for a placebo at any given time).

For a number of questions related to exercise, people may fall into camps about their prior beliefs, and may self-sabotage if they're in treatment group that goes against their preferences but there isn't a clear thing to sell. E.g. which of a family of training schedules helps people reduce their 10k running time the most?

Thanks for the feedback: will update the second link to point to the correct source, and I think "isolated findings" would be a more accurate word here.

I agree that many of the studies are about cognitive decline, but there's also research on improving cognitive function, which would probably be closer to "brain boosting" category you mention.

For example, from the first source I listed, "Six trials (including 1757 participants) assessed executive function, 5 trials (including 1426 participants) assessed effects of LCn3 on processing speed, and 11 (including 5698 participants) assessed memory. Meta-analysis suggested little or no effect for all of these measures (as well as the subcategories of memory, all moderate- or low-quality evidence; see Supplementary Material for further information)."

"Current evidence supports the finding that omega-3 PUFAs with EPA ≥ 60% at a dosage of ≤1 g/d would have beneficial effects on depression." https://www.nature.com/articles/s41398-019-0515-5

Is this considered brain boosting?

I don't think so, I would consider "brain boosting" something that makes the brain of an healthy person perform better at certain tasks, not something that improves it for people with a disease.

why is it that no one wants to study the effects of nootropics?

I have two hypotheses that came to mind when I read your question:

1. It’s a hard problem to quantify effects on cognitive functioning provided by nootropic supplements. We still have so much to learn about brain function;

2. Nootropics offer patent holders opportunities to make obscene amounts of money. As long as those supplements are (generally) safe to consume. That level of review requires R&D spending, but too much investigation may inadvertently reveal that these money-making “miracle” products are far less effective than the manufacturers claim.

1. is certainly true. to my mind, an accurate quantitative measure of brain function doesn't exist: you run into the fairly intractable philosophical problem of "what is brain function?"

while that is true, not being 100% philosophically sound has never stopped psychology studies before - far from it

2. is also perfectly true, with the caveat that it only applies to beneficiaries of the patents.

so your hypotheses account for beneficiaries of the patents, and scientists who aren't willing to broach the subject of measuring brain function, but what about the complement of those subsets? what about non-beneficiaries who are willing to quantify brain function? are they simply a small enough subset that it justifies the observation? or is there another hypothesis to be found? or perhaps the observation is flawed in itself

> […]or is there another hypothesis to be found?

There most certainly are more hypotheses to discuss. I picked the two which came immediately to mind and passed my personal “plausible enough” check.

Thank you for giving me more to consider!

I don't think 1. is correct. There is a large body of research looking into different dimensions of brain function, and how different conditions impair those functions.

For example, look at the N-back test for working memory. This is popular in the nootropics community, and is widely used in clinical pharmacology research. There are plenty of other tests. Scientists do experiments like "measure how impaired you are on alcohol vs. antihistamines" to compare impairment profiles from different modes of drug action.

You can measure impairment from sleep deprivation, alcohol, etc., so of course you can measure improvement in attention, reaction speed, working memory, spatial reasoning, and so on.

The difficulty with quantifying effects is not that we need to learn about brain function to know how to measure them, it's that nootropics have quite small effect sizes, if any.

I think it's entirely about 2 -- large studies are expensive, and unless your effect size is enormous you need a large study to detect it.

Because people buy it without it being proven and proving anything related to cognitive ability is both difficult and expensive.

This makes doing studies on their effectiveness a neutral to losing scenario.

Either:

The nootropic works. Great, you probably spent a decent amount of money and... The results are still going to be hard to quantify and measure. It may not be good enough results to convince people who already weren't convinced. Might as well not do it and keep making money off people who buy it without scientific studies.

The nootropic doesn't work. Shit. Bury the results and never publish or risk losing a money maker.

this is all true for the producers/sellers of the nootropic, but what about anyone else?

Indeed, it seems to me that a paper proving that nootropics are either harmful or helpful would be quite publishable, which is (unfortunately?) what modern science is all about.

Because most of the time, interest in a topic is a function of plausibility. Most nootropics have little or nothing to indicate they work — not even a hint of something plausible.

Of course, it’s possible the scientific community is overlooking something promising. This has happened before. But that’s a dangerous bet for a career scientist to take.

Practically, if you want nootropics that work, and if you want to consume something whose long term side-effects are actually known, get an adderall prescription. (Or, stop trying to neurotically optimize every detail of your life and go outside.)

Exercisium, diet-amate, and sufficient sleep-adine. Very powerful nootropics.

Way too many variables to control for which makes any scientific findings incredibly difficult to validate. Tough to make a career on it and way to many conflict of interests.

It's too bad because if someone could legitimately find conclusive results that would be really helpful.

It feels like its a part of the medical space that the mainstream part of the medical community has shunned which has allowed for a lot of less scrupulous individuals to take up the mantel (See all the podcasts etc). It's too bad because there is probably something to it but its tough to validate/quantify.

"no one" is a bit of an overstatement.

If I run a quick search on PubMed, there are a handful focused on cognitive enhancement and other effects on healthy brains, e.g. https://pubmed.ncbi.nlm.nih.gov/35366192/

I imagine there aren't many scientists who want to enable their own line of work descending into a doping arms race like some sports can in the absence of anti-doping regulations.

Edit: or if they do catch on to something, a moral panic breaking out and having to do drugs tests on the regular or something

I think it boils down to a combination of:

1) It's hard to sell the output of this research. Your health insurance isn't going to pay $100 a day to make a healthy person smarter.

2) The output of your research is going to be low priority for regulatory approval

3) As both result and cause of the above, there's virtually no existing funding for this kind of research

4) If you succeed, you're going to spark an immediate furor over fairness and the morality of human enhancement (which I'm not saying I personally agree with, but it will happen)

The person you're replying wrote no one wants to study the effects of nootropics in healthy adults.

Sick people with insurance, particularly chronically ill ones, or those with illnesses that threaten their lives, are where I'd imagine the majority of money is made. You could probably argue treating the ill is more psychologically impactful work too. That's going to skew where researcher's focus their attention, especially if their work is funded by private industry.

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