Hacker News Reader

Comment by djoldman | Hacker News Reader

Studies like this always seem to cite stats in a way that's pretty inaccessible to me. This is more clear to me:

* 217,122 participants whose data was extracted from the UK biobank database

* Out of those 217,122, 325 got early onset dementia over an average of 8.3 years

* The vast percentage of data came from exactly one blood draw per person between 2006 and 2010 at the beginning of the biobank study

  Omega-3 Blood      | Hazard Risk      | Rate of Incidence  | Percent Incidence
  Level Quintiles    |                  | Over 8.3 Years     | Over 8.3 Years
  -------------------|------------------|--------------------|------------------
  Q1 (Lowest 20%)    | 1.0              | 193 in 100,000     | 0.193%
  Q4 (High)          | 0.62             | 120 in 100,000     | 0.120%
  Q5 (Highest 20%)   | 0.60             | 116 in 100,000     | 0.116%

View on HN

The most interesting finding is that the non-DHA effect is much stronger than the DHA effect. This doesn't align with the mechanistic explanation. Either this this is a novel and interesting result, or it's more evidence that we're just measuring wealth and health consciousness.

Observational studies like these are useful for guiding future research, but, on their own, they're essentially useless for informing lifestyle changes.

The non-DHA omega-3 EPA are good at preventing perivascular fibrosis and thus a better glymphatic system for the removal of beta-amyloid proteins. EPA also helps produce melatonin which kick off sleep and this whole process.

Natto-serrazime is probably an excellent complement as it is on the other side and is a dissolver. (Noteworthy: Pterostilbene + Glucosamine similar to EPA reduces fibrosis)

The interesting connection is how this is needed when we are older, but not younger. When younger ERa activates more which does this all on its own. This is the connection to why 2/3 of alzheimer's are post-menopausal women and why HRT is important.

Edit: and to tie this to APOE as it is the gene most associated with Alzheimer's. e4/e4 requires more choline so someone with e4/e4 is more likely to be choline deficient. EPA/DHA usually attach to Phosphatidylcholine (PC) when in the blood/brain. PEMT is a gene controlled by ERa to make choline, but from the above less ERa activation and we make less PEMT so less choline and less PC. Choline is the precursor to Acetylcholine (primary neurotransmitter for memory and focus and essential for REM sleep). This is why Choline is known to help with Alzheimer's.

I did a job for some neuroscientists years ago and we found a very strong correlation between microplastics exposure and elevated acetylcholine in a very young sample. They all thought there should be no effect or the effect should be inverted because of oxidative stress. We never resolved the phenomenon though. From what I understand, Acetylcholine elevation in the lipidome is either neuroprotective or neutral. Is there any reason why microplastics exposure would tend to increase acetylcholine?

Depends on the microplastics, but many act as endocrine disruptors that "mimic" estrogen, tricking the body into over-activating ERa and upregulates the PEMT gene and the higher acetylcholine. It could also be that the microplastics can physically bind to or chemically inhibit acetylcholinesterase and that is the reason for the higher acetylcholine. Depending on the cause this is only a short term good thing, but could be downregulating genes.

And then there is D3 + K2 leads to less cancer. Magnesium, we straight up don't get enough

Yeah, we put an awful lot of work into such research and find nothing that doesn't look like either measuring health consciousness or measuring health. (ie, is going to church weekly actually a benefit, or is the ability to attend a weekly social event what's actually being measured.)

So you can reduce your dementia incidence risk from Q1 -> Q5 by a whopping 0.08%-points. But in media you surely will read about a 40% reduction.

*edited: %-points instead of %

Sure, because both are true (although that 0.08% is only over 8 years of known omega 3 consumption - as timescales increase the absolute risk moves towards the relative risk).

That 0.08% reduction would mean approximately 28,000 fewer EOD cases - not to be sniffed at!

> That 0.08% reduction would mean approximately 28,000 fewer EOD cases - not to be sniffed at!

What would it mean for salmon stocks and increased environmental damage?

Depending on where you source your omegas from, potentially zero impact!

To be clear my preference would be to source n3s from algal supplements and, once food safety testing for humans is complete, n3s from GM rapeseed.

In time I hope we end up with lab meat/plant-based meat alternatives that use these n3s so we can get the benefits of fish without the environmental and ethical concerns of getting n3s from fish.

If from menhaden, there's a raging debate on the one hand about trout, the Chesapeake Bay (Maryland and Virginia), the ecology and environment more broadly, and the other hand a Canadian company based in a small rural county in Virginia (Omega Protein, which, BTW, does not provide year-round benefits to all of its employees which creates a drain on already super limited services and supports. Omega Protein is not alone in this.).

I don't know enough about any of this to have an informed opinion, but I do understand that menhaden put Reedville, VA on the map.

This is talking about early onset, which is a particularly terrifying outcome. And yes, 1 in 1000 for a horrible outcome sounds much better than 2 in 1000, doesn't it?

And to be clear, many things that people worry about is less likely than that. Homicides (over an 8 year period about about 0.04 per 1000 people), terrorism (vanishingly small), and on and on.

None of this means that people should stock up on omega-3s, and as likely the study is actually finding a correlation with something else (e.g. wealthier people enjoy more fish rich diets and are less exposed to toxins, or something else), but halving something terrifying that isn't that uncommon is legitimately newsworthy.

The 40% (66%?) is the number that matters. Same way you wearing a helmet reduces your changes of brain damage in a motorcycle accident by 90%, yet you’re not on a motorcycle most of the time.

When it comes time to decide whether or not to take action and what that action should be, I'd say that the total potential risk reduction is more important.

One should weigh the cost of the proposed intervention in time/money/other_expense against the potential benefit. The potential benefit is the total reduction in risk * the magnitude of the unwanted outcome.

40% is less relevant.

The thing is, the 0.08% doesn't capture the total potential risk reduction - only the risk during the timeframe of the study (8 years in this case). Where we're talking about exposures and outcomes that stack over time (exposure to LDL and heart disease being a classic one) the absolute risk is, in my opinion, more misleading than the relative risk.

For example you see this oft-quoted stat about "statins only increase lifespan by 3 days" based off relatively short RCTs, but this doesn't capture the effect of statin use over decades, which is where we see much, much bigger gains.

It seems to me that both RR and AR are things to take into consideration and we have to be mindful of the shortcomings of each.

The reduction in risk is 0.08 percentage points, not 0.08 percent. The "%" symbol always means "percent", not "percentage points". The 0.08 percentage point reduction is a 40% reduction.

EDIT: don't assume the causality

Maybe they wanted to say "down to" instead of "by"?

... over 8 years. Order of magnitude difference if it extrapolates to lifetime.

This could significantly underestimate the real impact. A single point measurement is perhaps a pretty noisy measure of long term average. If we had lifetime averages, the quintiles would be more purely differentiated by the variable of interest, and the risk would be as well.

Or overestimate?

Holding all else equal, noisier estimates bias us towards the null. This is attenuation bias.

However, the estimates are still probably overestimated. Confounding, p-hacking, publication bias, all move us towards larger estimates.

“Still probably” is classic statistical science

I would think that, by default, noise would not have a bias? Adding noise doesn't change the mean, it just increases the variance, right?

It pushes confidence bounds closer to the null hypothesis.

The Wikipedia page on this is not bad: https://en.wikipedia.org/wiki/Regression_dilution

Why are Q2 and Q3 missing. My guess is that they show a higher incident rate than Q1. Let me verify that, oh wait I can't. This article is pointless

Besides there is so much noise here. You ate fish before going to the doctor to get your blood drawn in 2006

also keep in mind, P hacking came about as a means to try to prove racial science.

Where'd you read that? Genuine question

https://www.cambridge.org/core/journals/bjhs-themes/article/...

Racists work really hard to crunch the numbers. Do you think its a new phenomenon?

No, I'm well aware of the eugenics origins of much the current field of statistics (and even the racial etymologies of terms like "regression to the mean"). In fact, I'd say most of our social sciences were originally primarily concerned with eugenics

But the claim that the practice of p-hacking itself has such a specific history seems dubious and I don't quite see how your source backs that up—interesting though it is

Sure, they wouldnt tell you they invented p-hacking.

Reply on news.ycombinator.com