DHA supplementation decreases the brain uptake of DHA and AA?

Dynamic PET-MR imaging with 18F-labeled polyunsaturated fatty acid tracers for monitoring the effects of docosahexaenoic acid supplementation in ApoE4-targeted replacement mice 2025

Results: Preliminary static analysis suggests that DHA supplementation decreases the brain uptake of DHA and AA, as measured by SUVs. Kinetic analysis of dynamic PET data, which provides a more accurate assessment of DHA and AA uptake into the brain, enabled the calculation of Irr2TCM K* values. This analysis utilized an image-derived input function and accounted for variations across animals in VB.

You read it here first: DHA is detrimental to your health and make sure you don’t take omega 3 as DHA!

Details on why DHA supplementation is bad: Vitamin O (Omega 3) for athletes - #4 by adssx

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It’s DHover.
Sadly most omega 3 supplements come with at least some DHA…

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Certainly continuous DHA supplementation seems like a clear negative, for many reasons. I personally have never supplemented with DHA (and EPA only in the past couple of years). However.

Fish contains on average more DHA than EPA. Has regular fish consumption been shown to be brain negative? We do know, that supplementing with DHA in addition or concomitantly with fish does not rescue the negative effects of DHA, which would imply that there is nothing special in the fish food matrix that modifies DHA bio kinetics. Or?

Furthermore, as DHA is distributed in more tissues than just the brain, what would be the impact of intermittent DHA bolus (say, once a week)? We know there’s a clear difference in intermittent vs continuous (after all, we do it with rapa), basically a pulsed intake.

An intervention that has a seemingly negative impact acutely, need not have such longer term, or intermittently or dosage dependent - thousands of well known examples - exercise, impact of certain FA on endothelial function, coffee and BP and BG impact and on and on and on. Hormesis too. We all know this.

So a single image tells me something, but not everything. The scientific method means that we need to prove outcomes, not just rely on extrapolation, however tempting that may be.

We already have some outcome studies of DHA supplementation. On the whole, not very encouraging. But. We do not have - that I am aware of - outcome studies exploring other modalities of supplementation, such as once weekly pulsed. And again, what about fish consumption? Is the rest of the stuff in fish so beneficial that it offsets the negative of DHA? I think that needs to be shown, and there is reason to doubt it, as fatty fish has more DHA, yet is supposedly healthier - it needs to be shown. We can speculate mechanistically all we want, but the proof is in the pudding.

Metabolism and functions of docosahexaenoic acid‐containing membrane glycerophospholipids

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Of note: the author of this paper (Hussein Yassine) was behind the failed PreventE4 trial (DHA 2 g/day: PreventE4: evaluating the role of omega-3 in cognitive health and Alzheimer’s disease | VJDementia ). So it seems that he switched his research from ā€œLet’s show that DHA is neuroprotectiveā€ to ā€œLet’s show why DHA is not neuroprotectiveā€.

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This is why we have clinical trials, so people can’t ad nauseam push supplements like DHA on to the masses with their obfuscated health claims.

It’s really simple. The DHA henchmen of the supplement industry just needs to fund clinical trials for their unproven health claims. If it’s dementia, that’s a DHA double blind study on dementia rates. If it’s CVD, it’s a trial on MACE. Mars did a study on CVD and cacao, it’s doable (Though I haven’t read it).

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The dose is used here was hundreds of times more than even generous dosing in humans. I’m not sure how much this study can inform the value or danger of human DHA supplementation.

Check the other thread with the genetic studies and clinical trials.

You’re right that the dose used is crazy high (7 g/kg in mice, equivalent to ~40 g/day for a human?). We need the full paper to understand why they chose that dose.

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Hi adssx, I’m around at 80 kg so x 7 g per kilogram would be 560 g per day without allometric scaling, but even with, the dose would be crazy high. Most people supplement with just a few grams per day.

It’s always a good idea to read the full article before drawing conclusions, but I’m not sure I’m going to take the time for this one. :slight_smile:

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I could be wrong, but I think you’re reading too much into this. They’re talking about a reduced rate of uptake of an incremental labeled dose of DHA after long-term high-dose supplementation. Note the Figure caption: ā€œImages are from the 10-30 min window post injection of the tracerā€. It wouldn’t be surprising if the brain (either the tissue or the BBB) more avidly took up or incorporated incremental DHA when levels are low or physiological, and it took up or incorporated DHA more slowly when highly replete. It would kinda be problematic if it wasn’t.

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So … taking fish in the diet, before Alzheimer’s Changes occur seems to rate reduce those with ApoE4’s (and presumably even better in those without ApoE4’s) getting AD. There is also a solid relationship in those without ApoE4’s. The issue is, once there is MCI or AD, I don’t think we have any evidence of benefit.

From my perspective, the issue with supplements, unless they have phospholipids, or perhaps if money is no object plasminogens, is an issue of brain penetrance, especially in those with ApoE4s.

Pushing levels too high isn’t a great choice and in general I don’t recommend over 1000 mg/day total. The strategy of pushing EPA has some validity, but overall, my assessment - at least how I’m clinically implementing is to favor having fish, and supplement with Omega 3’s with a decent mix of DHA/EPA with phospholipids or plasminogens.

  • A dose-response meta-analysis of observational studies I in Nutrition Reviews found that up to 2 portions of fish per week reduced Alzheimer’s disease (AD) risk by 30% (RR: 0.54–0.89; N = 3 studies) and all-cause dementia by 10% (RR: 0.79–1.02; N = 5 studies) 1.
  • A cross-sectional analysis in JAMA II of 286 autopsied brains showed that seafood consumption (≄1 meal/week) was significantly correlated with less AD pathology in APOE4 carriers, including lower neuritic plaques (β = –0.69; 95% CI: –1.34 to –0.04) and neurofibrillary tangles (β = –0.77; 95% CI: –1.52 to –0.02) 2.
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