Omega-3 Supplements May Increase Risk of Cognitive Decline, Scientists Warn

#41

There are several weaknesses of the study in question

  • they didn’t control for any underlying comorbidities.
  • no control for socioeconomic status, education, social involvement
  • the treatment group started at first report of taking fish oil. They never reported dose, duration, did they even stay on the fish oil?
  • the 2023 ADNI study was stronger and showed the opposite effect

The study deserves consideration but isn’t practice altering in my opinion.

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#42

This is one of the several papers pointing to the risks of omega 3 (esp. DHA) supplementation: Omega-3 Supplements May Increase Risk of Cognitive Decline, Scientists Warn - #2 by adssx

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#43

The authors noted that they used commercially available fish oil, suggesting that lipid peroxidation may be a contributing factor and that there is no need for undue concern.

#44

Concerns are not limited to commercially available fish oil (e.g., VITAL-DEP used Omacor/Lovaza and found increased depression): Omega-3 Supplements May Increase Risk of Cognitive Decline, Scientists Warn - #2 by adssx

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#45

I’m depressed that you hate fish oil so much.

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#46

I just consider it one of those iffy supplements, where the benefits, if any, might not offset the negative side effects.

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#47

We’re here to try to look at the scientific evidence. If you prefer to make jokes: there’s Reddit for you. Otherwise, you’re more than welcome to review the evidence and give your opinion. I would love to be wrong on DHA supplementation (EPA seems fine/beneficial).

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#48

It kind of sucks that most supplement shops still only sell EPA+DHA or DHA-only omega 3 supplements despite the current evidence. They are free to sell that vibe-supplementers along with resveratrol and spermidine but it would be nice of them to take science-based people into account aswell.

#49

you can get EPA only.

#50

I wonder if this is because EPA-only is a prescription drug, and to avoid lawsuits (at least in Europe and MENA, in the US, EPA-only formulations seem more widely available).

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#51

In the uk it is not a prescription drug

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#52

It is: https://www.medicines.org.uk/emc/product/12964/smpc

#53

Yes and I posted a critique of the study but you simply ignore anything that doesn’t fit your agenda. Also, quite hard to believe you feel a significant effect from a single fish oil capsule. Does eating salmon make you lazy and depressed as well? I’m sorry but a single fish oil capsule doesn’t move the needle strong enough 1 way or another for me to truly believe someone feels the effect of it. Long term I can believe it. Single pill… nope. There are several studies showing fish oil benefits depression as well as meta-analysis but you haven’t posted any of those in your quest to report the unbiased science.

Massive doses in mice and shaking their brains doesn’t negate the bulk of epidemiologic, prospective/retrospective data, and meta analysis arguing that fish oil may have a benefit or perhaps no/minimal effect. Furthermore, a lot of longevity “experts” in this space and I don’t see anyone else sharing your view? If anything, they are exposing the flaws of the recent study that you haven’t commented on. Dementia study not looking at vascular heath? Education? Hypertension? LDL? Socioeconomic status? Past medical history? Sounds well controlled…

Your hypothesis was generated because the google autofill of sleepy was in the top hits and there’s a Reddit thread about it? Thank you for recommending Reddit to me.

#54

Yeah, that’s exactly why I’ve said before that Omega-3s are the most complicated anti-aging compounds out there. You’d probably need to sift through hundreds of papers just to make the right call, and you have to scrutinize every single one of them. A meta-analysis just can’t cut it for this kind of thing.

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#55
#56

What are you saying? I’m talking about the dozens of studies that point to detrimental effects of DHA supplementation that I posted here: Omega-3 Supplements May Increase Risk of Cognitive Decline, Scientists Warn - #2 by adssx

My own experience with DHA supplementation is purely anecdotal and it’s just what led me to dig deeper into that compound. What matters is the evidence above.

Regarding so-called “experts”. I emailed some of them the above papers and most did not answer (even though they were answering before when I was telling them things aligned with their views). I emailed Matt Kaeberlein and he said first “I don’t really disagree with your position, although I don’t find the evidence against DHA to be all that convincing. Having said that, I haven’t closely read all the latest literature in this space, mostly because of time constraints and also because I get frustrated at how poorly many of these studies are designed and/or analyzed. […] I do agree the evidence for benefit from supplementation tilts toward EPA for many outcomes, at least for now. The one I take is 3:1 EPA:DHA.” I then sent more evidence and he said: “You’ve convinced me I need to become more informed on this topic. Now I just need to find the time to do it!” I think later on he mentioned rapamycin.news in a podcast (@RapAdmin might know better) and said he was changing his view on omega 3 supplementation thanks to interactions here (iirc).

Regarding other “experts”, think about what Charlie Munger said: “Show me the incentive and I’ll show you the outcome.” Do you think someone who has recommended omega 3 supplementation for years if not decades to thousands of followers has an incentive to look at the evidence against omega 3 supplementation? Even worse for those “experts” who sell omega 3 supplements or include them in their own branded supplements.

So you can make up your own mind by looking at the raw data: the original papers. Instead of blindly following “experts” whose incentives might not be aligned with yours.

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#57

I tried getting Gemini and Claude to review the studies referenced on this thread and to expend the potential sources for making an informed conclusion for when and if EPA or DHA supplementation is supported.

TL;DR - sometimes EPA helps, maybe skip it outside those few areas.

Oral omega-3 supplementation must be strictly tailored by clinical phenotype, as standard commercial use is often ineffective or potentially harmful.

Summary of Key Findings on Omega-3 Suitability

When Appropriate:

  1. Secondary Cardiovascular Prevention: High-dose purified EPA (4 g/day icosapent ethyl) is indicated on a statin background for patients with elevated triglycerides (\ge 150 mg/dL) and established cardiovascular disease or diabetes.
  2. Prodromal Alzheimer’s Disease (MCI): Isolated omega-3 fails, but structured multinutrient formulations (Fortasyn Connect/Souvenaid) providing DHA and EPA alongside uridine, choline, and antioxidants show significant slowing of cognitive-functional decline and brain atrophy over 36 months by synergistically feeding the Kennedy pathway.
  3. Major Depressive Disorder: EPA-predominant formulations (\ge 1 g/day) serve as effective clinical adjuncts.
    When Neutral or Harmful:
  4. Primary Prevention & Cognitive Decline: Standard supplementation does not prevent cognitive aging in healthy older adults. In the ADNI cohort, late-life omega-3 supplement use was associated with accelerated cognitive decline mediated by longitudinal FDG-PET cerebral glucose hypometabolism, potentially due to docosahexaenoic acid hydroperoxide (DHA-OOH) lipid peroxidation inducing mitochondrial dysfunction.
  5. Genetic Subgroups (APOE4): High-dose DHA (2 g/day) successfully increases brain DHA but shows no cognitive or structural benefit in cognitively unimpaired $APOE\ \varepsilon4$ carriers.[1]
  6. Brain Trauma / TBI: High-dose EPA is contraindicated following repetitive mild TBI; it suppresses post-injury angiogenic signaling and impairs microvascular repair, triggering blood-brain barrier instability and cortical perivascular tauopathy.[2, 3]
  7. AF & Longevity Risk: Doses >1 to 1.5 g/day increase atrial fibrillation risk in high-CVD populations.[4] Furthermore, fish oil fails to extend lifespan in rigorous heterogeneous mouse models (ITP).

The 20 Most Important Studies for Omega-3 Efficacy & Safety

  1. REDUCE-IT (2019)
  • Findings: Established that 4 g/day of pure EPA (icosapent ethyl) reduces major adverse cardiovascular events (MACE) by 25% in statin-treated patients with elevated triglycerides.
  • Link:(ClinicalTrials.gov)
  1. STRENGTH (2020) [4]
  1. JELIS (2007) [5]
  1. RESPECT-EPA (2024) [4]
  1. ASCEND (2018)
  1. VITAL (2019)
  1. VITAL-Cognitive Substudy (2022)
  1. AREDS2 Cognitive Substudy (2015)
  1. MAPT (2017)
  1. Liao et al. (ADNI Analysis, 2026) [6]
  1. Albayram et al. TBI Study (2026) [2, 3, 7]
  1. PreventE4 (2025) [1]
  1. ADCS DHA Clinical Trial (Quinn et al., 2010) [8, 9]
  1. Karolinska OmegAD Trial (Freund-Levi et al., 2006)
  1. OmegAD CSF Study (Freund-Levi et al., 2014)
  1. LipiDiDiet 36-Month Trial (Soininen et al., 2021) [10]
  1. NIA Interventions Testing Program (Strong et al., 2016)
  • Findings: Standard medical-grade fish oil failed to extend lifespan in genetically heterogeneous mice, with the high-dose (50,000 ppm) actually shortening male lifespan by 18% at one site due to lipid peroxidation.
  • Link:(Fish oil supplements, longevity and aging - PMC)
  1. Gencer et al. Atrial Fibrillation Meta-Analysis (2021) [4]
  1. Rancho Bernardo Study (Lopez et al., 2011)
  • Findings: Long-term observational data showing that high dietary and plasma DHA levels were associated with a 72% to 73% lower risk of all-cause dementia and Alzheimer’s disease.
  • Link:(Checking your browser - reCAPTCHA)
  1. Witte et al. Clinical Trial (2014) [11]
  • Findings: 2.2 g/day fish oil for 26 weeks improved executive functions, enhanced hippocampal grey matter volume, and preserved white matter microstructural integrity in healthy older adults.
  • Link:(Checking your browser - reCAPTCHA)
#58

Thanks @John_Hemming this is exactly my point: they market it as EPA only but in reality check the ingredients they added 100 mg DHA. This the case for all the “pure EPA” / “Mega EPA” / whatever seems EPA only that I found in EMEA. Sometimes the same brand sells real EPA only in the US (and you can import it from iHerb) but in Europe they sell those ersartz. My assumption is that EPA only in Europe got some kind of protection due to the existence of that Rx product. I might be wrong but I don’t see any other explanation.

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#59

Even more so when the vast majority of papers looking at “omega 3” are low-quality small studies from Iran, China or else (with all due respect to those countries). Meta-analysis: Garbage in, garbage out.

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#60

Thanks a lot @zebit0 for doing the work! I’ll do it later with ChatGPT 5.5 and send the link. I agree with Gemini’s and Claude’s conclusion (unfortunately!).

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