#41

Does this make sense? An effect size of at least 0.5 would translate into a “medium” effect as indicated by previous studies. Are there any previous studies which indicated a “medium effect” of DHA on on cognition or hippocampal volume? I don’t think so, but I didn’t research it.

Nevertheless, the absolute effect size in the lecanemab trial (monoclonal antibody medication used for the treatment of Alzheimer’s) was only about 0.2, so “small effect”.

Therefore the estimation (or probably better guess) of at least 0.5 sounds unreasonable to me for a prevention trial using a fatty acid as therapeutic agent.

#42

I would agree. Seems like there was some, or perhaps even a lot, of observational data that indicated benefit, along with mechanistic explanations for almost two decades. Unfortunately, it appears this has not panned out in more rigorous testing via RCTs and MRs.

Add in years of recommendations from authorities (AHA, government, etc), and this is probably more entrenched than Resveratrol.

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#43

I don’t know in the US but in Europe health authorities don’t recommend omega 3 supplementation. They just recommend to eat fish. Omega 3 (EPA-only or EPA + DHA) are only approved in people with high triglycerides.

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#44

To be fair, Omega-3 has reduced my triglycerides. Due to your provided information, I am going to look for a supplement with more EPA and less DHA. I’ll try to avoid DHA as much as possible. Thanks @adssx

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#45

Again, thank you for the response and spelling out the evidence.

That said, I think you need to be careful with statements like this one. Yes, I am absolutely distrustful of research from China - especially basic science research. But a meta analysis is something where the source institution shouldn’t matter too much, and the peer review quality of the journal matters more. i.e. whether reviewers bothered to actually check things.

I say this because we’ve already seen how trusting authoritative/prestigious sources with big credentials can be problematic - Attia (Stanford and NIH), Rhonda, Bill Harris etc - because they have more conflicts, biases and staked reputations.

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#46

What’s a low omega-3 index? This older study suggests that 4.4% is adequate to not be associated with brain aging (lower vs. higher was) ( :warning: surrogate? endpoint):

Analyses using the omega-3 index yielded similar results: there was no linear relation to any of the brain MRI measures but low values (Q1 vs Q2–4; below vs above 4.4%) were inversely associated with TCBV [total cerebral brain volume] in all 4 models and positively associated with WMHV [white matter hyperintensity volume] in model A.

Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging 2012

What omega-3 index is adequate, and does EPA only supplement to increase this Omega-3 index enough work, and is it consistent with the optimal amount in association studies or similar with regards to composition of omega-3 index? E.g do we need to look at the EPA and DHA portions of our final omega-3 index and compare it with what’s determined to be optimal, or is it only total index that matters independent of composition?

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#47

I’ve also heard about this before, that the placebo in the Vascepa trial might’ve been harmful. So it’s not a slam dunk for EPA and cardiovascular disease unlike other RCT’s for other compounds. Of course if someone’s indicated then I would of course take it, it’s still good evidence, just takes it down a notch maybe.

image

The icosapent ethyl group had minimal changes in levels of these biomarkers, whereas the mineral oil placebo group had significant increases, including, at 12 months, 11% for oxidized LDL, 22% for hs-CRP, and 29% for interleukin-1β. At 12 and 24 months, the between-group differences were higher for the biomarkers, including 39% for hs-CRP at 24 months.

https://www.jwatch.org/na55103/2022/07/14/reduce-it-trial-result-doubt

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#48

Yes the placebo was shit but I think other trials found similar results and it’s confirmed by Mendelian randomization and association studies. Also seen in animal models. That’s why I’m more confident regarding EPA.

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#49

Results: The overall mean (SD) for the Omega-3 Index in these 10 cohort studies was 6.1% (2.1%), and the HR for a 1-SD increase was 0.85 (95% confidence interval, 0.80-0.91). Median quintile 1 and 5 levels were 4.2% vs. 8.3%, respectively. Based on these values, we estimate that risk for fatal CHD would have been reduced by about 30% moving from an Omega-3 Index of 4%-8%.

Conclusions: These findings support the use of <4% and >8% as reasonable therapeutic targets for the Omega-3 Index.

I find the convincing research against DHA use hard to reconcile with Omega 3 index research. I could not find MRs or RCTs that target omega 3 index specifically. Though I suppose the MRs on omega 3 work as a proxy to blood levels anyways?

Perhaps one should target 8%+ omega index using EPA-only supplementation if needed. Another possibility is that 8%+ omega index only matters as a proxy for sufficient fatty fish intake, and the omega index itself is not actually the risk factor (so supplementing to achieve 8%+ does not help)

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#50

The omega index is the sum of EPA + DHA in the red blood cells. Maybe all what matters is DHA in the brain and serum EPA and therefore the omega 3 index is just a poor proxy? (I don’t know, I might be making things up)

#51

But didn’t PREVENTE4 find that DHA indeed accumulated in the brain but had no effect there?

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#52

This phenotype would basically be high RBC EPA and low RBC DHA. I don’t know if such a study exists comparing it with other ratios.

#53

In these omega 3 index study, did they adjust for income and educational attainment? If not, maybe the omega 3 index is just a proxy for fish consumption which itself is probably associated with higher income and education? It could also be that something else than EPA + DHA is beneficial in fish (starting with: when you eat fish you don’t eat red meat).

There maybe also be subgroups that don’t benefit from supplementation because of some poor processing.

I’d like to see association studies (adjusted for income, education, race, smoking status, alcohol, BMI, physical exercise and comorbidities) looking at serum EPA, DHA, and DPA (separately) and RBC EPA, DHA, and DPA. But from what I remember even the UK Biobank didn’t have that kind of granularity. Maybe the ratios matter as well?

#54

This 2024 study adjusted for income, education, and physical activity and, surprise, they found a U-shape curve for DHA with higher CVD and IHD mortality at high levels: How much omega-3 do you need? - #53 by adssx

Unfortunately, DHA is the only specific omega-3 fatty acid level available in the UK biobank. But we could look at “Non-DHA omega 3 PUFA”. Omega 3 PUFAs = 50% DHA + 25% DPA + 20% EPA + 5% others (mostly ALA). So, “Non-DHA omega 3 PUFAs” would be a good proxy for “DPA + EPA”.

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#55

EPA seems much more important for mental effects than DHA, though people think that because brain has more DHA in it then supplemental DHA is more important. However pretty much all studies using omega 3 that have found positive benefits in things like depression, cognition or ADHD use mainly EPA at higher ratio or only EPA altogether

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#56

Yes, we have a thread about this, and now the mechanism of action might be known: Omega 3 makes me depressed: why? - #124 by adssx

1 Like