Omega-3s: Are “Brain-Boosting” Effects Scientifically Backed? | Hacker News Reader

Omega-3s: Are “Brain-Boosting” Effects Scientifically Backed?

abouttolearn.substack.com

125 pointsmililitre158 comments

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.

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.

> 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?

So basically once your body has all the nutrients it needs to grow or make the things it needs to make, it makes them. Even more extra stuff it doesn’t need, it doesn’t use. Makes sense.

This also appears to apply to the immune system. There’s zero evidence that supplements that are supposed to “boost your immune system” do any such thing. Yes your immune system functions best if you have good nutrition, but that’s it. Even better nutrition just isn’t a thing.

Side rant, sorry, but I had this conversation with a relative during covid, she was touting supplements to ‘boost her immune system’. There’s one way we have found that really does actually boost your immune system, that works with your natural defences by training them specifically to fight a particular disease. Vaccination.

I guess the argument would be that you don't know for sure whether your diet does provide all the nutrients your body needs, so supplements could be used to fill in any gaps. The assumption being that your body will just dispose of any excess safely.

If you spend enough time looking into what micronutrients you need, you eventually figure out that it is actually pretty hard to get them all through diet. But there is essentially no end to the scientifically backed list of beneficial supplements you might choose to take, so if you want to start, there’s not really a rational place to stop, and it can spiral out of control quite quickly. I think the better approach is just to eat a varied diet.

The assumption being that your body will just dispose of any excess safely.

Well worded. From my personal experience, this assumption is dangerous.

About 20 years ago I was having elevated AST/ALT liver enzymes three tests in a row indicating liver damage. Doctor ordered every test to see what was going on but everything came up negative. She asked me if I took a multivitamin which I did. She told me to stop.

Haven’t had elevated liver enzymes since.

What was in that multivitamin you took? Interesting anecdote but I worry you are throwing the baby out.

It was a mass-market Centrum multivitamin.

That’s a perfectly fair point, I took Vitamin D during lockdown because I wasn’t getting enough sunlight. I’m just saying that it makes sense that beyond satisfying your body’s needs there’s no higher plane of health that supplements will take you to.

> The assumption being that your body will just dispose of any excess safely.

Not always. Fat-soluable vitamins (A, D, E, and K) will build up in fat tissue and can lead to toxicity.

Source?

Search for "hypervitaminosis A", for example.

It may also be worth noting that people with excess body fat will absorb fat soluble vitamins into the excess fat and it will not be available for the thousands of functions in the body that need them until the person is fat adapted. Ideally the high priority goal should be to remove the excess fat but until they do they will need more than the RDI of each component. How much more gets complicated as there are not yet any good tests for testing how much was absorbed into the fat.

You would have to take a lot of vitamin D supplements to cause clinical symptoms. Some people have done it, but as a practical matter the risk of hypervitaminosis D from regular multivitamin pills is virtually zero.

Whether those pills actually have any health benefit is a separate issue.

That's the sales pitch for multivitamins and the like; they talk you into a problem but they provide the solution.

Certain vitamins your body will dispose of safely (like vitamin C), but there's others that just build up until they kill you; there's the case of Xavier Mertz [0] who was theorized to have died from an excess of vitamin A after eating his sled dogs' livers.

But the basic rule is: just eat normally / "a balanced diet"; you likely don't need supplements unless you have absorption issues or stick to a specific diet (e.g. vegetarianism / veganism, soylent / diet shakes, or the same thing every day, like the 14 year old who only ate chips and ended up (partially) blind due to a vitamin deficiency [1])

[0] https://en.wikipedia.org/wiki/Xavier_Mertz

[1] https://www.acpjournals.org/doi/10.7326/L19-0361, https://www.cbsnews.com/news/british-teenager-went-blind-fro...

Even that balanced diet will consist of less and less minerals and vitamins as time goes on and growers optimize for vegetable, fruit VOLUME instead of vitamin/mineral contents.

>>>

The level of decline varied depending on the specific nutrients and the type of fruit or vegetable, but it generally ranged from 6 percent for protein to 38 percent for riboflavin. In particular, calcium dropped most dramatically in broccoli, kale, and mustard greens, while the iron content took a substantial hit in chard, cucumbers, and turnip greens. Asparagus, collard greens, mustard greens, and turnip greens lost considerable amounts of vitamin C.

Further studies since then have backed up the case that nutrient levels are dissipating. Research in the January 2022 issue of the journal Foods found that while most vegetables grown in Australia had relatively similar iron content between 1980 and 2010, there were noteworthy drops in certain veggies. Declines in iron content, ranging from 30 to 50 percent, occurred for sweet corn, red-skinned potatoes, cauliflower, green beans, green peas, and chickpeas. By contrast, Hass avocados, mushrooms, and silverbeet (another name for chard) actually gained in iron.

Grains have also experienced declines, experts say. A study in a 2020 issue of Scientific Reports found that protein content in wheat decreased by 23 percent from 1955 to 2016, and there were notable reductions in manganese, iron, zinc, and magnesium, as well.

<<<

https://www.nationalgeographic.co.uk/environment-and-conserv...

Food storage and preservation also has a lot to do with it as well. Oxidation makes a lot of nutrients mostly unavailable, and degradation can happen quickly. Minerals in vegetables aren’t chelated, so while they sit in refrigerated storage, they are still rapidly losing nutrition.

The question is one of optimization. There are arguably optimal doses of particular nutrients (i.e. Vitamin D) that would be extremely hard to achieve through "a balanced diet". Also most people do not and many can not eat a "balanced diet", as that requires a ton of effort to maintain.

To put it another way, if the benefits of exercise were available in pill form on grocery store shelves, everyone would be taking that pill. Saying "you could save some money by just exercising normally!" is making a lot of assumptions about what people are willing and able to do, and frankly you'd be a fool to waste time exercising if the benefits were achievable through a magic pill.

Supplements aren't quite that magical, but they make optimal, hard-to-achieve doses achievable, even on a bad diet. Granted they can also be misused, or doses can be so low/ingredients not bio-available such that they have no impact. They're a tool like anything else, and can be used correctly or incorrectly. Part of what bugs me about the meta-analysis saying "supplements don't reduce all-cause mortality!" is that they lump wildly different supplements with different make-ups, taken in different doses on different schedules from different starting diets with different amounts of discipline/regularity. Of course at a population level the number of people using them wrong probably outnumber the people who do their research and maintain a disciplined approach. Your average person has issues getting their car's oil changed and understanding the difference between synthetic and conventional oil. A skilled individual could properly apply and see benefits from supplements, just as a skilled individual could successfully change their own oil.

And what is a balanced diet? Is it the 1990s food pyramid that I was taught by my doctor to follow?

No, I'd say there's high consensus it's one that satisfies all of your vitamin and mineral RDA's. Also very high consensus it at least includes vegetable staples like broccoli, cucumbers, onions, tomatoes, and green salads with some way of obtaining proteins like meats or beans.

There is also the triage theory of aging where the idea is that when micronutrient levels are low (not low enough to cause acute symptoms but below the recommended daily allowance), they are triaged and used where needed (such as ATP production) at the expense of being used normally. The theory is that this can cause long-term problems such as neural decay, cancer, and other signs of aging.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1693790/

+1 for Bruce Ames. This idea profoundly shaped my thinking a few years ago.

The one nit is I'm not sure how we'd go about testing it.

I wish him being alive at 94 was proof of something but afaik my smoking grandmother with no exercise doing nothing particularly healthy lived that long...

However, she also wasn't doing novel research at age 86. Wow.

Or, in my case, I am 100% certain that my diet is missing many nutrients as I rarely eat fruits or vegetables. I take various supplements and so far things seems to be okay (based on yearly physical and blood work).

I think the "boost your immune system" things are just common deficiencies in modern people.

If most people don't get enough vitamin C or D in regular life, then the advice to boost their immune system with a sufficient does to be non-deficient would function to boost their immune system to a normally healthy level.

Milk sold in the US almost always has vitamin D added to it, because presumably Americans don't get enough sunlight to produce sufficient amounts.

Instant noodles sold in Japan almost always have vitamins B1 and B2 added to them, for presumably similar reasons.

> because presumably Americans don't get enough sunlight to produce sufficient amounts.

UHT denatures vitamin D, hence UHT and Pasteurized milk has lower vitamin D levels before the sterilization process.

I don't know any adults who drink milk. I'm sure some do, but I wouldn't count on that as the solution to Vitamin D deficiency.

White bread and processed grain products in the UK always have things like iron, calcium, vitamins, riboflavin added. I think it's to replace the loss of the nutrient-rich germ from milling.

Never known what riboflavin is, still don't today, but I saw it on the side of a cereal box every day as a child and the word is etched in my mind

Riboflavin is one of the vitamin B complex. I remember it because deficiencies are extremely rare, and there appears to be no practical upper limit on how much you can take, it is virtually impossible to overdose on. I mean, obviously, there is some limit, but it's sky high.

Which makes the supplementation of it a particular joke, in my opinion.

That it was discovered as a "vitamin" at all is probably more to do with it being easy to spot (very brightly colored) and easy to chemically handle and a few other accidents of history more than anything else: https://en.wikipedia.org/wiki/Riboflavin#History (I am editorializing that a bit and I freely admit that.) It certainly doesn't stick out like, say, iron, which has recognizable deficiency symptoms and plenty of people in the real world with them.

You will want k3 if you take d2. Highly recommend getting tested for D deficiency.

Source. I used to have crippling migraines almost every day. I don’t anymore.

I used to get crippling Seasonal Affective Disorder every year, got tested, was badly deficient, and now don’t anymore.

How did you all resolve the deficiencies? Can you link any product you took? I am in need of Vitamin D.

See Dr Berg:

https://youtu.be/NFxQJmvgXOQ

I watched the 4 min video.

Unfortunately Dr Berg seems not to consider the concept of biological half-time. I am sure he know the concept, just forgot to put it into his calculation formula.

He basically assumes that if his patient consumes 2000 IU vitamin D today, then tomorrow his patient has depleted all 2000 IU and has zero vitamin D in patient's blood.

This is obviously wrong.

That guy is a scientologist quack btw.

Here's one example of how incompetent he is: https://www.youtube.com/watch?v=JvKNzLRmzLg

He basically turns low quality listicle nutrition pointers into videos with a whiteboard.

1. Get tested 2. If low, start taking D3 with K 3. Keep taking D3 with K 4. Get tested again 5. Take more if no improvement

I take 5000 IU most days.

You’ve mixed them up - it’s D3 with K2.

FWIW, your gut already synthesizes K2 from K1. K1 is easy to get from green leafy vegetables from spinach to broccoli, though I suppose easy to avoid if you don't eat well.

K2 from dietary doses of meat (MK-4) doesn't change circulating levels of MK-4 — it's basically not bioavailable. Though K2 from fermented products like cheeses and natto (MK-7) is bioavailable.

Doesn't seem like something worth worrying about if you have a varied diet that includes green veggies.

May I ask if you had gut/intestine problems before?

Yes. Had tons of random problems. Ended up being autoimmune Sjogrens and a clotting disorder.

Diet changes and supplements are how I got thing under control for most issues. Blood thinners for Clotting since That’s way to dangerous, and no combination of anything else helped.

LDN covers symptoms when I’m not strict about diet.

Interesting. I had similar symptoms like migraine/brain fog, stiff neck and muscle tension as soon as October (winter in Central Europe) came. Tested for Vitamin D deficiency and had super low levels. Since taking supplements I feel good in winter for the first time in probably 5 years. I'm also a very outdoorsy person, so getting enough sun is not always a sure way wo have high levels of Vitamin D.

"Sun" is definitely not sufficient. Vitamin D synthesis requires UVB exposure [1] and that plummets to effectively zero in the higher latitudes in the winter: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037520/#sec3-n... By "higher latitudes" I mean considered on a global scale; continental Europe is effectively all at these "higher latitudes".

[1]: https://en.wikipedia.org/wiki/Vitamin_D

Look up IIH. High cranial pressure. Comment about stiff neck is a big clue.

I recently got a broad panel of tests done, and found out I was Vitamin D deficient. This was a big surprise to me because I live in the high desert of central oregon, which gets lots of sun even in the winter. I am very active and outside everyday. It is cold however, so my arms are always covered. We are 45 degrees north of the equator.

I was at 20 ng/mL which is considered deficient. 3 weeks of 5,000 IU a day supplementation (162lbs, fit, active male) brought me up to 31 ng/mL, which is just barely up from deficient. I upped to 10,000 IU a day for 1 week, dropped back to 5,000 IU a day, and will test again in two weeks. Everyone is different, but hopefully this gives some helpful numbers for anyone considering supplementing, and whether or not the paltry 1,000 IU commonly advised is adequate for people living at a higher latitude in the winter.

I don’t think that’s what a lot of people think boosting means. Certainly the family member I’m talking about, and the circle of people she associates with and sends breathlessly excited emails about, think these supplements will protect them from pretty much everything. That they don’t just have healthy immune systems, but boosted ones that literally will protect them from coronavirus, flu, even cancer. That’s why I don’t like that term, it’s become a cult byword.

Lot of issues can be autoimmune related. Goal is to calm down the immune system. Not boost it. This is where basics like getting away from sugar are so important.

Immune system isn’t just too much or too little. Can’t simplify it to that. People with autoimmunity are also immunesuppressed at baseline.

Your sort of correct. Lots of drugs like plaquninal are immune modifiers not suppressant.

However shoving large amounts of sugar and basically everything in the American diet is a great way to get the immune system to decide that everything in body is the enemy.

Sugar is pro-inflammatory, and so is omega-6 fatty acids, the consumption of both of which has increased massively within the last 60-70 years. Omega-6 fats have gone from less than 5% of human diet to up to 30% today, thanks to the commercial success of 'vegetable' oils. These two alone probably represent the most conspicuous diet changes that have happened in our societies in recent history and should be obvious suspects when looking at disease factors, imho.

The biggest change in the human diet is the explosion of cheap calories on the food market, especially hyper palatable ones.

If canola oil or even just linoleic acid were so bad for us, we could cause worse health outcomes by intervening them into diets, but that’s not what happens in RCTs.

>> So basically once your body has all the nutrients it needs to grow or make the things it needs to make, it makes them. Even more extra stuff it doesn’t need, it doesn’t use. Makes sense.

I find it really common when researching the benefits of X to run across articles citing research that "X does nothing in healthy people" seemingly to discredit the idea that taking X is a good idea. But if you have a deficiency that research isn't really relevant. Gotta read the qualifiers.

Well, that and high quality, sufficient sleep. That is way harder as you age, and a worthwhile aim of lifestyle modification or supplementation to support it.

I’ve often said that when discussing vitamins, in particular, the general public thinks of them incorrectly like stackable video game power ups. In reality, they are more analogous to essential pieces of the game’s code.

You don’t get super powers by taking a whole bunch, and things start malfunctioning if you lack them.

There is a shit ton of evidence supporting vitamin d3 to fight covid...

There's not, though. There's a ton of evidence that vitamin d _correlates_ with COVID outcomes, but this is vitamin d's superpower: it correlates with good outcomes for just about everything, but nearly every time there's a good high quality study, it turns out to not be causative. A bunch of those vitamin d and COVID studies were fraudulent.

Vitamin d levels are an excellent marker of good health and they can help predict outcomes but supplementing vitamin d doesn't improve those outcomes. Regretfully. (Except rickets, of course.)

Did you even do a single bit of research before boldly stating there is no research done on the supplementation?

https://www.nature.com/articles/s41598-022-24053-4 https://pubmed.ncbi.nlm.nih.gov/35166850/ https://pmj.bmj.com/content/98/1156/87 https://journals.plos.org/plosone/article?id=10.1371/journal...

Yes. There's a ton. Most of it is horribly tainted by correlation effects. Let's consider one of the studies you cited above, which is an observational study from the VA hospitals:

"In the population of US veterans, we show that Vitamin D2 and D3 fills were associated with reductions in COVID-19 infection of 28% and 20%, respectively"

This sounds really awesome, right? Except -- you could also interpret this as "People who are following their doctor's recommendations, going to the pharmacy to fill their prescriptions, and taking them, do better". No kidding - they're probably also taking their other medications and being more generally medically careful!

This is completely consistent with the 99% of vitamin d-related results that show that it correlates with all sorts of positive outcomes.

The high quality interventional studies -- which are actually potentially able to demonstrate causality -- are generally negative. And the larger and better they are, the more likely they are to be negative. One of the largest was the CORONAVIT trial; it was, unfortunately, open-label, but it was large and randomized. (Note that you'd expect the open-label aspect to result in a stronger placebo effect, which .. well, given that they found no benefits, did not occur). https://www.bmj.com/content/378/bmj-2022-071230

The vitamin d & covid horse is pretty dead at this point, which is basically the same as the "vitamin d & x" horse for most values of X other than diseases known to be directly caused by vitamin D deficiency. Which are serious and worthy of treatment. Just don't expect vitamin D to be a miracle cure on the basis of its correlation with everything positive.

There are multiple clinical studies showing that vitamin D supplements can be effective in fighting COVID-19. Some other studies have shown no effect, but overall there seems to be some benefit.

https://vitamin-d-covid.shotwell.ca/

See my reply to the sibling comment.

This is why omega-3s are effective. Your body depends on them to function optimally, and they are found in only a very few food sources, pretty much only fish. The omega-3s found in nuts and plants can convert to the most critical fatty acids, but about ten times less efficiently.

Boost your immune system is so stupid. Which part is it boosting? Fever is an immune response.

Or maybe they mean "increase white blood cell count"?

I mean, that's kind of the gist of supplements as a whole, you only take them if you cannot replicate it using a normal diet/lifestyle.

The biggest example for this IMO is Vitamin D. If you can spend time in the Sun regularly every day, you won't ever need to touch vitamin D. But how realistic is that for most people ?

The only supplement I've encountered so far that has a noticeable effect that cannot be reproduced with any realistic diet is creatine.

Creatine...would say especially if you're male, is such a game-changer. Recently got my dad who is in his 70s to start taking it and it's been enormously positive for him. Really good stuff.

Personally think it's probably equally valuable for women but can't get my wife to take it (worried about the bloating which is a thing).

To your point it would be very difficult to get the equivalent creatine from your diet. Would take a lot of steak.

What benefits did you Dad get from it?

More weight and energy/faster recovery with his circuit training. His overall lean muscle tone has visibly improved.

Haven't asked him about his cardio training but he's moving more weight around than he did before and that's creating benefits for him overall.

Did you look at any of the studies that showed placebo effects comparable to creatine? It is insane, as we know the mechanism for how creatine does its thing. Still, the social effects of being told it is effective seems to be the dominant reason it is as effective as it is.

Have not seen those studies.

Creatine is one of the most studied supplements out there though so would think the empirical data supports it at this point.

I'm speaking anecdotally of course. I used to cycle creatine but now I just always take it. When I'd cycle off I'd lose 5-10 lbs every time. Thats mostly water weight but my lifts would decrease about 10% as well. Not to mention the extra energy (more reps not just more weight)

It makes a significant difference for me.

It is one of the more studied drugs, agreed. We are very confident it works. Which is why the studies that show being told it works is a major driver are insanely interesting and worth checking on.

I lift weights and do other exercise but never took Creatine. Are there benefits that aren't tied to exercise performance specifically as a goal ?

Does it have downsides in the body?

Non exercise performance benefits:

- helps build skeletal support muscles which reduces osteoarthritis and treats osteopetrosis

- helps strengthen the heart muscle

- the brain also uses atp, increased brain function (anecdotally, can help reduce brain fatigue)(Parkinson's, als, Huntingtons, possibly Alzheimer's

Downsides:

Increased load on the kidneys - which combines with an increased load from muscle breakdown (which it can reduce, but most likely the workout with it will increase muscle breakdown) - don't take it and workout hard if you are approaching renal failure.

Some stomach upset, diarrhea, and muscle bloating.

I was reading your comment and wanted to comment about creatine until I saw it added at the end. With over 20 years of gym training and taking massive amounts of supplements, I totally agree. Apart from protein if you can't get enough from food, I find that everything else is either useless or not worth the price.

One of the interesting things you pick up on from reading supplement blogs and fitness forums is that a lot of people have negative reactions to Omega 3 supplements. If you search for “omega-3 depression” you find a lot of stories from people whose depression started or worsened with omega-3 supplements, and resolved later.

This is a particularly interesting find given that the placebo effect would be expected to go in the opposite direction: Many of these people started the supplement because they thought it was going to improve their health, not worsen it. It can take a very long time to recognize the connection between the supplement and side effects.

Several other supplements are common contributors to depressive symptoms. Choline supplements often make irritability and depression worse. This finding isn’t surprising given that cholinergic signaling has been known to be associated with depression for decades and many powerful antidepressants are anticholinergic. Yet you can find a lot of supplement sellers pushing choline supplements as something that automatically improves brain health.

I'm curious as to what papers mention this! Quickly pulling up one related appears to clearly support EPA omega 3 supplementation being a beneficial tool to help with depression.

https://www.nature.com/articles/s41398-019-0515-5

Regardless of personal reports you mention, choline is a very interesting substance due to demonstrated long-term attention benefits in children after being administered to their mothers during pregnancy: https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.2021012...

This is as close to "life-changing" as it gets with these substances.

Metaphor I learned from a biochemist:

You are in a boat with holes in it (holes in this metaphor are nutritional deficiencies).

To prevent the boat from sinking you patch the holes under waterline starting from the largest. The boat continues to sink until all holes under the waterline are patched. You don't stop sinking by patching one hole again and again. After you have patched all holes under the waterline you can prepare for storm (old age, sickness) and patch holes above the waterline. You should start from the lowest and go upward.

lessons:

1. Measure. Blood test can determine if you have deficiencies you need to fix.

2. Once you have fixed one deficiency, fixing it by taking more does not help.

3. Fancy nutrients (phytonutrients, Omega-3) have very tiny effect size if it exists at all. They would be at the bottom of any list (healthy diet, exercise, sleep, right weight). If you don't get enough sleep your immune system and cognition are compromised and supplements don't compensate.

----

ps. Body can synthesize omega-3 if there is enough α-linolenic acid (ALA) available. Aging may impair body's ability to make omega−3 fatty acids from ALA. _IF_ this is the case, omega-3 supplements _may_ help.

> ps. Body can synthesize omega-3 if there is enough α-linolenic acid (ALA) available.

IIRC, ALA is an Omega 3, just one the human body doesn't use for much. The body can synthesize EPA and DHA (which it does use), but humans are pretty bad at that. It's totally conceivable that the rate of synthesis evolved in the context of regular dietary intake of EPA/DHA, so never needed to provide for all the body's needs.

You are correct. Thank you.

Supplements are great because at worst they work like a placebo. There is a ton of evidence that placebos actually work better than real FDA approved stuff (in some cases) because there is a metric tonne of crap we don't understand about the brain itself and it's ability to heal the body.

At best they actually affect the gut microbiome in some way (mostly probiotics) which, in many cases, are also backed by clinical studies that show has effects (placebo controlled). We'll be finding out in the coming years that the gut microbiome is the "second brain" or the brain controlling the brain. Everything from mood disorders to major diseases like ALS to auto-immunity of the thyroid may start with good or bad bacteria in our systems.

This is the cutting edge research, nothing in a book in the last 3 years.

I'd say that, at worst, they can be bad for you. You can overdose some of them. And if you're talking about herbal supplements, it's probably even worse than that, i.e. some of them can actively be bad for you (e.g. St. John's wort if you're taking other medications). And then, there's the problem of quality. Some supplements contain substances they shouldn't contain (e.g. heavy metals or others).

I'm a fan/user of supplements/nootropics, but they shouldn't be taken lightly.

An intriguing read that summarises the findings of multiple sources. Makes one ponder the true effectiveness of other supplements on the market, and whether the $100B+ industry is built on hearsay and deception.

Started my career at a supplement company and it is definitely heresy, deception, and weird derivatives of protein and caffeine.

Selling water / sugar that has been "marketed differently" (read: they lie to you) is a huge industry, yes.

E.g. "Vitamin Water", all kinds of supplements marketed in the fitness industry, even https://en.wikipedia.org/wiki/Homeopathy.

Placebo is a strong thing.

I agree - its hearsay and deception - vitamins and nutrients and dietary supplements are a huge, profit driven, industries - they are not your friend trying to improve your health - they are trying to empty your wallet and nothing else.

No pondering necessary. That entire industry is based on making implications with statements and lobbying to avoid any potential accountability.

Multiple sources can hardly be considered an effective bar to decide if something as a whole is good or bad for you. The author completely misses major pieces of literature around these and citing something that is critical for you body as 'probably good for you' while not covering a single instance of health problems from deficiencies makes it hard to take this seriously.

>The author completely misses major pieces of literature

Can you provide links?

Not who you're replying to but https://www.nature.com/articles/s41398-019-0515-5 from my other comment seems relevant. There are many, curious what apple will link

Anecdotally, I've read a long time ago that fish oil should help with sleep but I didn't start supplementing. Fast forward to this summer, I had big sleep problems, I couldn't keep a normal schedule and when I woke up I had terrible brain fog, took my like 2-3h in the morning to wake up properly and be able to function.

Then I started taking fish oil, I got it by the bottle because I've read pills could have rancid oil and I figured if I directly taste it I will know if it's fresh/well kept.

My sleep problems disappeared overnight.

What brand/product did you buy?

This brand, might be different flavour. https://lysi.com/consumer-products/liquid-cod-liver-oil

I put like 5-10ml in a shot glass and fill the rest with water, just chug it and rinse the glass with water a few times. This way, I can barely taste it and have no fish oil aftertaste, the flavor they add might help too

> They also have antioxidant and anti-inflammatory properties that might help brain function.

I think people take omega-3s for the antioxidant and anti-inflammatory properties. That's the benefit. The "brain boosting" effects, if any, are just a possible bonus.

I've always thought that these types of studies / meta-analysis are conducted in a backward manner. A study is proposed, funded, performed - possibly with a particular objective in mind. The results are published (possibly used in various marketing materials), then almost enviably, methods and rationale are questioned by others post hoc. The end result of the exercise is often no knowledge gained with diminishing public trust in science.

Instead what we should do, is to come up with a study design first, gain broad consensus that the study, if rigorously conducted in accordance to the design, would yield statistically meaningful results.

The challenge here is many studies would likely be infeasible (requiring millions of people or hundreds of years in order to attain a statistically valid result - or both). However, that is useful in it's own right as it would help us to direct resources at studies that do have a hope of increasing knowledge. Infeasible studies will just have to wait until we can accurately simulate biological phenomena.

Anecdotal experience: I was taking an SNRI medication, and when I tried an omega-3 supplement it gave me those unmistakeable brain zaps you get when weaning off of antidepressants. So it definitely did something to my brain!

By the way, paradoxically, people discontinuing antidepressants usually take omega-3 hoping that it will lessen their brain zaps...

Does lack of it have an effect? I couldn't find that in the list.

I like experimenting with different lifestyles to see how I feel. Most of the times there are too many variables to make conclusions. Anyway, I tried going vegetarian for few weeks, then introduced fish to diet and felt noticeably better. Then, I tried remove fish and take fish oil instead. Felt absolutely no benefits. At-least feeling wise. I repeated this experiment multiple times so I am sure it isn't coincidence

And how did you control for placebo?

No control. I don't believe I am affected by placebo.

Interesting - how does one determine if they are “affected by placebo” or not?

If you don't mind, you're not affected.

Or in other words: if you're affected, you don't mind.

(I'm not even joking. If you're researching a substance to use it for others, you definitely need it to control for placebo. But if you're doing it just for yourself, you only need it to work, no matter why. Another story is if it stops working)

This is an great take! I agree placebo is a powerful tool :). Thanks for the conversation

This is a great take! I agree placebo is a powerful tool. Thanks for the conversation

Placebo is a baseline effect. It's a hurdle to clear to show efficacy above the minimum any substance can meet.

I've heard this argument before, i.e., placebo is an effect therefore why not, but I cannot understand why time and money would be committed to an activity or substance that is only as good as any other activity or substance.

Placebo should signal: move along, nothing to see here!

Anecdotally, when I first started taking (6 normal-strength pills a day) of fish oil in college, I quite unexpectedly noticed my "field of view" expanded when I was driving. Previously I'd been exclusively focused on a smallish area immediately in front my my car, but after a few months of Omega 3s, I noticed I was "noticing" and taking into account traffic that was much further down the street.

Though I kinda suspect that was the result of curing a deficiency, because I plateaued and didn't notice other improvements after continued supplementation. It was also very early in the fish oil/Omega 3 craze, so I suspect the food up to that point was generally more deficient in it (e.g. no feed chickens flax to get "Omega 3" eggs).

Doesn't this sound like an inexperienced driver gaining more experience or was there little driving in between?

> Doesn't this sound like an inexperienced driver gaining more experience or was there little driving in between?

Maybe it sounds that way, but it wasn't.

I'd already been driving for 5+ years by that time, and the change happened only after a couple of months of supplementation.

I also used to frequently "zone out" in a particular way during daily life, which also went away around the same time.

Interesting, I actually had an extremely similar experience, except it was when I first took ADHD medicine, and I noticed it most strongly while navigating through the city by foot. "Field of View" is a good sort of description for it though, it was like the amount of information I could passively perceive about my immediate surroundings just increased dramatically.

There are a lot of things that supplements are claimed to help but clearly don't. That being said there are things that have promising scientific research about benefits and this article lacks any information on EPA omega 3s separate from the others which ultimately makes me disregard any conclusion of omega 3s as a whole.

Look into the potential effects of EPA omega 3s specifically on depression and the potential benefits compared to or combined with anti-depressants. Andrew Huberman had it in his episode on anxiety and depression I think.

The impact of omega 3s on adhd is also an interesting area of research.

Using a click bait "brain-boosting" description completely misses the point of many studies that show that certain diets low in different omega 3s cause different problems for people.

Interesting. But omega-3 oils are still good for the joints at least aren’t they, does anyone know?

One of the major problems translating "science to advice" is the need to specify a risk/reward model for the person being advised.

If P(TheScience) = 0.01, but P(GeneralInjury|TheScience) = 0.00000000000...1, and P(GeneralBenefit|TheScience) = 0.5 .... then most people should do "what the science says".

Of course there's P(MyBenefit|TheScience) and P(MyInjury|TheScience) which makes rendering general advise often impossible/unethical.

There's a class of people (eg., neurodivergent, autoimmune problems, etc.) for whom P(MyInjury|...) is "anti-correlated" with P(GeneralInjury|...)

...which leads to more pronounced mistrust regarding medical interventions.

What do you mean by P(TheScience) ?

The confidence we have that the relevant scientific prescriptions are true.

That’s an odd use of notation. Typically P(A|B) is used to denote probabilities of outcomes.

P(A|B) denotes the probability of A, given B: out of all the "possible worlds" where B is true, in what proportion is A true?

P(B) denotes the probability of B given no additional constraints: it's the same as saying P(B|true).

https://en.wikipedia.org/wiki/Bayesian_probability

Oh, prescriptions, that makes a lot more sense. As you rightly point out, science is not prescriptive, only descriptive.

Is this an obedience to authority and child abuse study? You'd have to read the article and then click through on the links to see, unless my internet access is being MITM.

Edit. Didnt see any mention of neutrophils and the effect EPA has on their size and effectiveness, which can also increase brain function in a round about way and no mention of its testosterone enhancing ways which through its mild aromatase inhibition, which then contradicts the oestrogen-choline pathway and the effect choline has on the brain. Contradictions everywhere.

cost of 100 omega 3 capsules (in .gr): ~10 euros, fish and nuts cost about 18 euros per kilo and tend to spoil.

Omega 3 capsules can also spoil, right?

> Omega 3 capsules can also spoil, right?

Yes, they do. An old study suggests an average of 20% of omega-3 fish oil products had excessive oxidation. Or in other words, rancid.

https://academic.oup.com/nutritionreviews/article/80/1/138/6...

Fish are famous for spoiling quickly, but nuts are not.

Eating a lot of fish also brings some risks from microplastic and other pollution, especially if you don't pay attention to where it comes from.

You you can just buy cold pressed flax oil and supplement with that. ~30 USD for ~1L iirc and it has an absolute assload of ALA (omega3)

Hemp seed oil is a good one for omega6 but usually people get enough 6 from diet and 3 is the one we need to boost to get the 3:6 ratio up

https://en.m.wikipedia.org/wiki/Fatty_acid_ratio_in_food

I like flax oil, but it spoils very quickly. I have trouble going through 250ml before it goes rancid.

Do you keep it in a refrigerator?

Maybe I should

ALA must be converted to EPA and DHA, which it does at less than 10% efficiency, so you'd need to consume an assload of it, too. Your best bet is still fish(oil).

and you can actually use up all the various desaturase and elongase enzymes in the process so that 10% upper bound drops markedly as you consume more ALA. Put differently long chain n-3's production definitely isn't linearly dependent on short chain n-3s like ALA and stearidonic acid.

Your efficiency statement brings the requirement to less than a tbsp a day (there's about 7 grams of ALA in a tbsp).

Regardless of the potential nootropic effect discussed in the blogpost, the circulatory system (heart) benefits are pretty well studied and proven: https://www.nature.com/articles/s41467-021-22370-2 though require considerable doses of the DHA or EHA.

Anecdotal evidence time!

I take 3 high strength omega 3 tablets every day. I feel like it sharpens my mind and improves my focus. It might be a placebo but I know when I go off them (sometimes I have a few off months for no real reason) I get bad brain fog and my performance at work slips. With omegas i feel like I sleep better and recover from the gym quicker

I am not an expert in nutrition, but I still have my opinions: I try to consume a lot of Omega 3 via the food I eat: chia seeds, walnuts, etc. I avoid eating foods, like the fish Tilapia, that contain a lot of Omega 6.

I do take one daily Omega 3 supplement I get from my optometrist for a particular vision problem.

reminds me of lecithin which was marketed in the 80s as helpful for the aging brain, turns out, lecithin does not cross the Blood-Brain barrier

The thing is, there are simply too many variables.

Using your example of lecithin, there are numerous studies that show it is effective in improving/reversing fatty liver disease.

https://www.bcm.edu/news/lecithin-component-may-reduce-fatty...

There have been other studies that establish a link between liver health and alzheimers, even that protein from the liver can cause Alzheimer's disease in the brain.

https://www.sciencedaily.com/releases/2021/09/210914152531.h...

That study aims to prove that high fat content in the liver could cause Azlheimer's. So indirectly, taking lecithin may help the brain, even though it doesn't cross the blood brain barrier!

Too many variables.

For what it's worth, 1 egg contains about 3.3 grams of lecithin. Provided one is not averse to eating eggs there should be no need to take it in supplement form. Eggs have the best form of lecithin.

Even if supplementing omega 3 had any meaningful benefit, enough of those supplements are either spoiled or tainted with things like aldehydes that I decided to stop taking them.

https://pubmed.ncbi.nlm.nih.gov/30529885/

Better to just eat meat and eggs.

There was a strange country where the pure Omega-3 "fish fat" was extremely popular, almost every child was fed this in childhood.

Then these kids grew up. And they became tens of millions of idiots who put cans of water in front of TVs so that some charlatan would "charge" this water.

So this Omega-3 is proven not to help the brain. It maybe even harmful. The second assertion has not yet been refuted.

>So this Omega-3 is proven not to help the brain. It maybe even harmful. The second assertion has not yet been refuted.

So I don't recollect all sources but it does appear that for people who understand the nuances ( of which there are not many) it indeed could be harmful.

One source: https://raypeat.com/articles/articles/fishoil.shtml

Reply on news.ycombinator.com