Dietary omega-3 <> Supplemental omega-3, one example:
Omega-3 and Risk of atrial fibrillation: Vagally-mediated double-edged sword 2025: “Higher consumption of dietary omega-3 is associated with decreased AF risk. In contrast, pharmaceutical dosing of omega-3 increases AF in a dose-dependent manner, which may be mediated by vagal tone.”
I gave my reasoning above as to why I think it could be harmful. You did not contradict it.
https://www.sciencedirect.com/science/article/pii/S0002916523121356#s0007
For every 0.1 g/day increase in dietary DHA intake, dementia risk drops by 14% and Alzheimer’s risk by 37%. while EPA shows no significant association whatsoever.
There are plenty of studies like this.DHA has always been primarily about cognition, If any APOE ε4 carriers believe DHA is harmful and decide not to take it , I honestly can’t argue with that, and I support their choice. At the end of the day, the Alzheimer’s Association has never claimed that DHA can prevent or treat the disease.
Btw, the PreventE4 preprint’s conclusion is:
For clinicians, these results indicate that DHA supplementation alone does not provide cognitive benefits over 24 months in healthy older adults, though longer-term effects remain unknown. The findings support continued research into personalised, comprehensive prevention approaches and longer-duration omega-3 studies. These findings have implications for clinical practice and prevention strategies. The results suggest that clinicians should exercise caution when recommending DHA supplementation solely for dementia prevention in asymptomatic older adults, as achieving increases in brain omega-3 levels does not guarantee functional benefits over the timeframe studied. The biochemical target engagement without clinical efficacy highlights a gap between biomarker modulation and meaningful clinical outcomes in dementia prevention trials. This disconnect underscores the complexity of translating mechanistic understanding into therapeutic interventions and suggests that single-nutrient approaches may be insufficient for complex, multifactorial diseases like AD.
Their main rescue argument is that 24 months might be too short, as the DHA brain half-life is 2.5 years, so full remodeling may need ≥3 years, and 36 months might have been needed.
Come on… This is a Chinese longitudinal study from 2016… Not adjusted for income or wealth. And as they note: “Moreover, current associations may also have been related to physical activity, tobacco and alcohol use, and unique dietary practices such as vegetarianism, which were not considered in this study.”
Yes, people who eat fish are wealthier, more health-conscious, and they eat less processed red meat. As a result, they have a lower risk of dementia.
This is hypothesis-generating, but you can’t draw any conclusions from it about supplementation.
“Using IVW, EPA was associated with higher odds of IHD (OR=1.05; 95% CI=1.00, 1.10), but the CI included the null value. The WM estimate was similar, and the MR-Egger estimate was closer to the null (OR=1.01; 95% CI: 0.90, 1.11).”
These are not very large effects. For people without IHD, CAC scores of zero past 65 years of age, on LLT including TG lowering statins (my situation), I would not be concerned (my TG are low/normal anyhow). That said, I never supplemented with EPA for CV benefits. I supplement very low amounts of pure EPA (500mg - 2, 3 times a week) for a different set of reasons, including effect on inflammation. Again, what is important is to position each supplement in the context of the rest of your stack and health interventions, and your particular medical profile. Just gobbling up any supplement because “it’s good for x” without looking at if you need it and how it fits with the rest of your interventions is essentially blind gambling.
Looking at ongoing and proposed clinical trials is a good way to gauge where research is heading and what researchers find interesting. So I checked ClinicalTrials.gov. Here are ALL the proposed and ongoing RCTs about omega-3 / PUFAs / fish oil / etc. for cognition/dementia/mental health:
There is also Improvement of Fish Oil in Obesity With Mild Cognitive Impairment, NCT06992726: that just says 1.36 g fish oil without the EPA vs DHA breakdown so I’ll exclude it.
And there’s Lutein, Zeaxathin, and Fish Oil Supplementation, NCT06489873: 7 mg lutein, 14 mg zeaxanthin, and 245 mg fish oil. But they use the EyePromise Screen Shield Pro, which is 98 mg EPA + 73.5 mg DHA. Such low doses + it’s a complex combination so I won’t consider it.
Conclusion:
So the DHA-supplementation hypothesis for cognition seems dead in academia after the failed PreventE4. Researchers are now switching to EPA-only, EPA-strong, or ALA.
*I’ve assumed that phospholipid bound omega 3 is important.
Apologies, but has this paper been discussed:
Effects of krill oil containing n-3 polyunsaturated fatty acids in phospholipid form on human brain function: a randomized controlled trial in healthy elderly volunteers.
“The Findings: Researchers used near-infrared spectroscopy (fNIRS) and EEGs to track brain activity during working memory and calculation tasks. The krill oil group showed a significant increase in oxyhemoglobin levels in the prefrontal cortex and a faster information-processing rate (measured via reduced P300 latency) compared to the placebo. Interestingly, the sardine oil group—despite containing higher total amounts of EPA and DHA—did not show the same level of statistical improvement as the krill oil group, suggesting the phospholipid carrier altered how effectively the brain could utilize the fatty acids.”
Hey, I found Antoine on youtube discussing EPA vs DHA! The thumbnail image @adssx is a little different from his rapamycin.news handle, but great job 
/jk/
Seriously though, are you a strong biohacker interested in the nuances of fishoil, EPA vs DHA, CVD, AD and dementias with tons of associated papers? Let’s see how strong you are. Can you watch 5 hours of video discussing the ins and outs of these issues? Or are you too weak? Put yourself to the test!
Omega-3 Supplements: Helpful or Harmful? (Dr. Matthew Nagra and Geoff Palmer) via Dr. Matthew Nagra, MD
Ok, solid reply. I’ll go for EPA-only for now, and we’ll see what happens with the evidence in the future.
In all honesty, I find it very difficult to believe that DHA at the dose I’m taking would be harmful. However, I think in this game we have to be willing to change our minds about things and take educated guesses. I think you are correct that if we look at the bigger picture, from multiple angles, the argument for supplementing DHA is pretty weak. EPA at least has some evidence.
I don’t have high triglycerides (usually less than 50mg/dl) so I don’t need the TG-lowering effects of fish oil. But again, I am considering that my diet is otherwise absent of any marine omega-3.
On a related note - what are your opinions about EPA/DHA in children? There are various supplements specifically marketed for parents to give children for neurodevelopment and cognition, ADHD and behaviour, visual development, allergy/asthma, etc. They are extremely popular, and just in my kids playground, I’ve heard parents discussing it. I assume that most of the claims are bullshit, or at least highly speculative, but you’ve definitely read more about this than I have. Any thoughts?
Reviewed the video with Gemini’s help, researched related studies and tried to reach conclusions about when / if DHA or EPA have clinically appropriate applications. For such a well studied set of compounds the conclusions are hard to draw with high confidence frankly.
So the guy did a 5h video and did not mention the failed PreventE4 trial?!
We love salmon poke bowls in our family… and a great source of omega 3s…
I’ve never checked. I’ve only been a dad for a few weeks now, so it wasn’t on my radar before 
. However, I assume the data on supplements for kids must be even worse than for adults. And I’m willing to try things and take risks on myself, but less so on others (especially if they can’t understand and discuss the risks). So I would/will be very conservative and probably just stick to established medical guidelines when it comes to kids. There’s a 10y lag between research and medical guidelines and another 10y between guidelines and day-to-day medical practice. So following guidelines is already being 10y early vs the average doctor/patient/parent.
Congratulations!
If there’s not a thread here on parenting for longevity there should be
My specific thoughts on fish are that kids love sushi when it’s introduced at the right time - ie before they go through their “cautious of new food stage”
For obvious Evolutionary reasons kids get fussy when they start walking, before then they typically eat whatever you give them. So going in early with fish and sushi can be transformative. (and could save them from hours of worrying about fish oil supplements! (
I asked you for a FISH with only EPA in it. You posted a bottle of EPA. Lol. My argument is complete.
Also, you say no clinical trials pending on DHA but there’s 1 specifically on targeting increases in brain DHA with the lyso form to better cross the BBB. Good luck getting that through IRB if the consensus was that DHA was harmful. In full disclosure, there are several others that include DHA but you elected not to disclose those.
As for the 2 year duration you claimed was more than adequate to see benefit of DHA, statins take ~2 years in secondary prevention. 2-5 years for primary prevention. I would never expect a lifestyle intervention such as fish oil to have a drastic effect on my health in 2 years. Arguably one of the most successful drugs in pharmacology takes at least that long.
I’m not engaging with you anymore. I agree to disagree. You keep copying the same studies and refuse any evidence to the contrary of your opinion with its old, Asian, “BS”, or simply ignore critiques of the studies you put strong weight in.
Congrats! Hope that doesn’t mean we see you less around here.
Congratulations!
No more sleep for a while 
…
And you can give your kid a huge lifelong brain advantage by raising in a bi or trilingual environment, effortless for the child and fun for the grandparents… start them early with intellectual and neurological stimulation, musical instrument, chess, learning is so much easier at an early age and gives a chance to discover and develop various talents…
Sorry, read too quickly! But again fish consumption <> Omega 3 supplementation
I said no RCT with DHA-only supplementation for cognition or mental health. The Lysoveta ones are EPA-strong (2:1). And yes, they’re looking at brain DHA. Of course, DHA is not bad. The question is whether supplementing with DHA is good (at least with the forms available on the market today).
I searched on ClinicalTrials.gov with the keywords DHA, EPA, omega, PUFA, fish oil, docosahexaenoic, and eicosapentaenoic. I filtered for “Not yet recruiting”, “Recruiting”, “Active, not recruiting”, or “Enrolling by invitation”. I only mentioned those for brain health. I quickly rechecked again and I indeed missed A Clinical Study of Omega-3 on Depression and Cognition, NCT05941754, which is 2g vs 4g EPA-only but the trial has “Unknown status” and will probably never be done.
If I missed some others, please post them instead of making this snarky comment. Here, we assume good faith and try to elevate the level of the debate.
But yes, otherwise you’re right. Still, LDL, hs-CRP, endothelial function, and plaque inflammation improve within weeks / a few months. The PrevenE4 trial examined various biomarkers, but none improved. Maybe they did not look at the right ones (p-tau217 would have been great)? Again, I ask you: what could convince you that DHA supplementation is not beneficial? If nothing, then you hold a religious belief, and you’re not looking at evidence.
Two rational agents cannot agree to disagree. I’m rational. Aren’t you?
I did not criticize studies for being “Asian,” but yes, Chinese papers from 10+ years ago from Tier 3 institutions have a high likelihood of being of poor quality. It’s unfortunately a reasonable first-pass filter. Today, China is leading in biotech and has world-class researchers. Things have changed.)
“simply ignore critiques of the studies you put strong weight in”: what did I ignore? Can you please point me to that? You said the VITAL-DEP “association” was small, but otherwise I don’t think you addressed any of the 10 papers I posted, can you please briefly explain why you disagree with those: