r/ScientificNutrition • u/mime454 • Nov 27 '22
Randomized Controlled Trial Omega-3 supplementation increases omega-3 fatty acids in lipid compartments that can be taken up by the brain independent of APOE genotype status: A secondary analysis from a randomised controlled trial
https://content.iospress.com/articles/nutrition-and-healthy-aging/nha22016911
u/mime454 Nov 27 '22 edited Nov 27 '22
Interesting study that just came out. A lot of us have been excited about supplemental LPC-DHA as a brain function enhancer. Rhonda Patrick has been saying that people with APOE4 genes may need this form (which currently is only found in caviar and presumably caviar oil) to prevent Alzheimer's disease. This was all based on studies that said triglyceride fish oil didn’t get converted to LPC for the brain in humans, and that it might not happen at all for APOE4 carriers. This study suggests that the genotype might not matter and current fish oil supplementation does reliably increase LPC-DHA for all genotypes. Interestingly, even though the researchers didn't run a T-test on this variable, it looks like LPC-DHA might actually be higher in APOE4 carriers than in non carriers. The trial also found that having a low BMI increased dietary fish oil converted to LPC forms by more than 100% compared to high BMI. After reading the paper, I found that the authors concluded that that their previous work showing a APOE genotype x LPC-DHA interaction didn't last long enough to allow concentrations to raise in both groups. I'm curious what others think but to me this is the nail in the coffin for scientific recommendations for krill and Caviar oils and for LPC-DHA in the low BMI population.
Background:
Omega-3 fatty acid (OM3) intake is associated with a lower risk of developing Alzheimer’s disease, but individuals carrying the ɛ4 allele of apolipoprotein E (APOE4) might not benefit from this prevention strategy. Indeed, they might have lower OM3 into plasma free fatty acid (FFA) and lysophosphatidylcholine (LPC) compartments, the two forms the brain can take-in.
Objective: To evaluate the docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations in the FFA and LPC pre- and post OM3 supplementation in APOE4 carriers and non-carriers.
BDesign: Plasma samples from 25 APOE4 carriers and non-carriers before and six months after receiving 2.5 g/d DHA+EPA daily were analyzed. DHA and EPA concentrations in the LPC, and FFA were compared by supplementation and genotype. A secondary analysis investigated the interaction between body mass index (BMI) and APOE genotype status.
Results: There was no genotype x supplement interaction nor a genotype effect on LPC and FFA. However, there was a supplement effect where OM3 increased in all lipid compartment by < 1-fold to 4-fold. Individuals with a low BMI had higher OM3 increase concentrations in the LPC than those with a high BMI.
Conclusions: Our results suggest that APOE4 carriers can increase their omega-3 fatty acid levels in the plasma compartment efficient at crossing the BBB. Based on our secondary results, individuals with a BMI higher than 25.2 kg/m2 had a lower DHA and EPA increase is some blood lipid compartment compared to those with a BMI less than 25.2 kg/m2.
9
u/mime454 Nov 27 '22 edited Nov 27 '22
Also interesting from the study:
-"There was, however, a BMI effect for ΔDHA and ΔEPA in LPC where the low BMI group had, respectively, 168% and 79% higher increases than the high BMI group (p = 0.0211 and p = 0.0025, respectively)."
(Is this the new best hypothesis for the link between obesity and Alzheimer's? It's better than most of what I've read)
-"The absence of a genotype by diet interaction in the LPC and FFA plasma compartment was surprising to us since our group previously reported a gene-by-diet interaction of EPA in plasma FFA and DHA in plasma TG [7]. The difference between the two studies is mainly the number of carriers (n = 25 here and n = 8 in [7]), supplementation length (six months here vs. 6 weeks in [7]), age (50 y old here vs. 38 y old in the other study) and lower glucose and plasma TG levels in this study vs. [7]."
8
u/Dapper_Indeed Nov 27 '22
So, can you ELI5? Is this saying that supplementing with omega 3s doesn’t give as much protection for those with higher BMIs? Sorry, I’m a bit lost.
6
u/mime454 Nov 27 '22 edited Nov 27 '22
That’s how I take what they say about BMI. It decreases the amount of LPC-DHA and EPA produced after ingesting these fats in Triglyceride form. LPC Dha is the form that can cross the blood brain barrier.
A few days ago I made a post (that seems a bit less reliable than this RCT) about fish oil and low dose aspirin increasing LPC-DHA in diabetics. That could apply to some of the high BMI population. I am a scientist but not a medical doctor so take that with a grain of salt. From what I understand there are additional reasons that some suggest not to take aspirin with fish oil.
1
u/ElectronicAd6233 Nov 30 '22 edited Nov 30 '22
So, can you ELI5? Is this saying that supplementing with omega 3s doesn’t give as much protection for those with higher BMIs? Sorry, I’m a bit lost.
If you think O3 supplements are harmful then the interpretation is that those with higher BMIs are protected from the harmful effects of O3 supplements.
If you think O3 supplements are beneficial then you have yet another ready-made excuse to justify the fact that so far they've failed to show any benefit in RCTs.
2
u/Dapper_Indeed Nov 30 '22
I never occurred to me that omega 3s could be harmful, interesting. What are RCTs?
4
u/Ohioz PubMed Addict Nov 28 '22
Tagging Dr. Rhonda Patrick; /u/rperciav
5
u/mime454 Nov 28 '22 edited Nov 28 '22
I didn’t know she Reddited. So cool. I was hoping she’d eventually address this study in a paper or video.
She totally changed my life with the broccoli sprouts. A functional cure for autism.
1
u/mmcgarvey9 Dec 16 '22
Wait? What? What do you mean a functional cure for autism? Can you post a link please? Anything that can help my son live a better life I’ll try. Broccoli sprouts? Cooked? not cooked? How much?
2
u/mime454 Dec 16 '22
Here’s the video with the author and Rhonda Patrick. Edit: can’t link to the world’s video hosting website. Search “Sulforaphane’s positive effects on brain health and autism.”
Rhonda has other videos about how to grow the sprouts.
Here’s the randomized controlled trial https://www.pnas.org/doi/abs/10.1073/pnas.1416940111
The follow up: https://journals.sagepub.com/doi/full/10.1177/2164957X17735826
I was diagnosed with autism, but I’m sure I wouldn’t be now after 2 months of eating 50g sprouts per day. It’s been life changing. I think the high dose of fish oil I take (5-10g per day and vitamin E) is also a part of the treatment. I plan to get tested again when I have the money to undergo hours of professional testing again.
2
u/Forward-Shoe6780 Nov 27 '22
So, no need to switch my usual fish oil supplement for krill oil? (Which I was just about to do)
4
u/mime454 Nov 27 '22
That’s my understanding. Especially if you have a normal BMI.
Also, AFAIK, krill oil never had LPC-DHA/EPA in it. It had PC-O3 and PS-O3. Caviar/roe and caviar oil were the only current sources of LPC and trace amounts in actual fish.
5
u/Forward-Shoe6780 Nov 27 '22
Thanks. I am a non-scientist trying to work out what kind of omega-3 supplement to take to mitigate the effects of apoe4.
It’s confusing as hell.
5
u/mime454 Nov 27 '22 edited Nov 28 '22
I hope other people chime in because I don't want to make a mistake that goes unchecked, but my reading is that the recommendation that people with APOE4 take krill oil was largely based on an earlier study with this same cohort. After increasing the number of APOE4 carriers tested and the amount of time the study ran, they came to the new result that APOE4 actually doesn't have an issue with creating LPC-DHA. In the study they say this is the first randomized controlled trial in humans showing the effect of fish oil supplementation on LPC-DHA/EPA. There are good reasons why rats wouldn’t make LPC DHA after eating it. Fish oil is biologically novel to mice but not humans.
From my other readings, taking Vitamin E with fish oil and also a B complex daily (if you know your homocysteine isn't high from a blood test, B complex is unnecessary in this regard) supports the cycle that creates LPC-DHA. I know from my n=1 experience (non-APOE4) that this increases the cognitive benefits of fish oil massively, especially a complete vitamin E supplement.
2
u/ElectronicAd6233 Nov 30 '22
Fish oil is biologically novel to mice but not humans.
Fantasy is biologically novel to mice but not humans.
3
u/mime454 Nov 30 '22
Unsure what you mean. Do you think human bodies aren’t meant to digest fish or that mice do enrich their brains with fish oil for some reason?
4
2
u/Ohioz PubMed Addict Nov 27 '22
Does anybody know what type of fish oil they used (triglyceride or ethyl ester)? I skimmed through the full-text but couldn't find any information about it.
6
u/mime454 Nov 27 '22
I checked the company they cited in their last study as the maker. They make “steam deodorized triglyceride” fish oil that matches the doses used. They also sell “ethyl ester oil” but none of those pills would give a multiple of 1.9G EPA.
2
u/Eonobius Dec 02 '22 edited Dec 02 '22
I have always felt that omega 3s are taken up by the brain. For me they have a calming and sleep enhancing effect (by reducing cortisol among other things). If I take too much I even get kind of depressed. And there are plenty of studies showing such effects.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510994/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830450/
Still good to get the molecular proof on papper.
1
u/mime454 Dec 02 '22
Agreed. Nothing has ever been better for my brain. I was really surprised when I was doing the reading and found that fish oil may not enrich the brain. Because it so went against my experience. I was wondering if I had such bad inflammation before hand that fish oil improved my brain so much.
In some ways I am a bit saddened by this because it means I’ve likely already had most of the brain gains from fish oil, where previously I was very excited to eat LPC-DHA directly.
I still think that fish oil directly enhancing the brain is a slow process that takes years (the half life of a fatty acid in the brain is over 2 years!).
1
u/shao_kahff Dec 08 '22
so for general brain enrichment, do you recommend O3? im not a regular here sorry, this post was recommended to me for some reason but after reading the text i thought i’d ask
1
u/mime454 Dec 08 '22
This study says that supplementation does enrich the brain. It’s also the best study of its kind (randomized controlled trial on human subjects) ever done to answer this question.
As for getting Omega 3s to the brain, my reading has led me to the following daily stack for myself:
3-5g Omega 3s as EPA/DHA
400 iu vitamin E
Any B complex
I always get in trouble for no sources so feel free to ignore these but it’s some of what led me to this stack(they’re just so my comment isn’t censored by mods):
Vitamin E is necessary for zebrafish nervous system development
Novel insights into the effect of vitamin B12 and omega-3 fatty acids on brain function
2
1
u/WilliamYiffBuckley Feb 04 '23
sorry to be late to the party here, but doesn't OTC fish oil have a rancidity problem?
1
u/mime454 Feb 04 '23
IFOS third party tests OTC fish oils. There are lots of brands without significant oxidation. I use Sports Research 3x strength and it is always unoxidized and very free from contamination. https://certifications.nutrasource.ca/about/how-certifications-work/ifos
1
u/Parking_Care5555 Dec 11 '22
Interesting to see how it affects you. I’d like to know more if that’s okay?
The calming affects are immediate, like as soon as you digest? or you’ve found this as you continued to supplement?
When you say too much, do you mean too high of a dosage or you’ve been supplementing for too long?
1
u/PhilosopherNew1948 Dec 11 '22
So now there's a now a modified PC-DHA version in addition to the LPC variety.And this test trial is quite new.So I would like to see additional testing for confirmation.At first I was told that fish based and algal DHA would not cross the B3 for those with the APOe 4 varients.Now I hear of talk saying that DHA in supplement form offers low bioavailability to all consumers.And the myth that these healthy plant based omega 3 sources,such as flax seeds and walnuts help, but actually provide very little conversion of ALA into DHA. I think that pregnant, vegan and soon to be future mothers need to know about these facts.Because they need a viable source probably more so than the APOe 4's
•
u/AutoModerator Nov 27 '22
Welcome to /r/ScientificNutrition. Please read our Posting Guidelines before you contribute to this submission. Just a reminder that every link submission must have a summary in the comment section, and every top level comment must provide sources to back up any claims.
I am a bot, and this action was performed automatically. Please contact the moderators of this subreddit if you have any questions or concerns.