So, based on my own understanding of the model here, wouldn’t it make more sense to take ~1g/1g of each, considering diminishing returns for marginally more of each?
On the other hand, maybe EPA and DHA share an enzyme/receptor/pathway through the BBB (blood-brain barrier; or a shared bottleneck elsewhere) such that it’s the ratio that determines how much of each actually gets through. In that case, we’d see inversely correlated absorption after a shared bottleneck is hit.
Unesterified DHA freely passes the BBB [39,61], and it appears that the brain derives most of its DHA from the unesterified FFA pool in blood [55].
I don’t know to what extent supplemental DHA remains unesterified, but if it does, then its absorption is unlikely to compete much with EPA anyway. And this study says large amounts (for mice) of DHA and EPA readily pass through the BBB, hence no shared bottleneck there.
The Clup of [(14)C]-DHA or [(14)C]-EPA was not saturable at concentration up to 100microM, suggesting that these compounds crossed the BBB by simple diffusion.
But this study very weakly hints at a possible shared bottleneck in the stomach, if I understand it vaguely right, but they gave 3g/d of EPA or DHA to two different groups. And 3g is higher than what we’re considering, so the shared bottleneck might not apply for our doses.
This can all be further complicated if there’s a shared bottleneck between omega-6 fatty acids and EPA/DHA, just like there is for ALA[1].
ALA is considered an essential nutrient because humans lack the n-3 desaturase enzyme required for its production. However, it could be argued that DHA is also an essential nutrient due to inefficiencies of the 5-desaturase and 6-desaturase enzymes (FADS1/2) needed for its biosynthesis, and the competition for these enzymes by the omega-6 (n-6) PUFA linoleic acid (LA; 18:2n-6). LA is typically consumed in high amounts in modern diets, which exacerbates the increase of n-6 PUFAs, as well as the decrease of n-3 PUFAs, that are incorporated in peripheral and neural tissues [18]. Therefore, many researchers conclude that preformed DHA consumption is required for reaching and maintaining ideal brain DHA concentrations and related neurological functions [19,20,21].
In conclusion, there might or might not be a shared bottleneck. Who knows. I’m still inclined to go for something that’s either ~1:1 or EPA-heavy given that EPA->DHA conversion seems high throughput.
So, based on my own understanding of the model here, wouldn’t it make more sense to take ~1g/1g of each, considering diminishing returns for marginally more of each?
On the other hand, maybe EPA and DHA share an enzyme/receptor/pathway through the BBB (blood-brain barrier; or a shared bottleneck elsewhere) such that it’s the ratio that determines how much of each actually gets through. In that case, we’d see inversely correlated absorption after a shared bottleneck is hit.
This study says
I don’t know to what extent supplemental DHA remains unesterified, but if it does, then its absorption is unlikely to compete much with EPA anyway. And this study says large amounts (for mice) of DHA and EPA readily pass through the BBB, hence no shared bottleneck there.
But this study very weakly hints at a possible shared bottleneck in the stomach, if I understand it vaguely right, but they gave 3g/d of EPA or DHA to two different groups. And 3g is higher than what we’re considering, so the shared bottleneck might not apply for our doses.
This can all be further complicated if there’s a shared bottleneck between omega-6 fatty acids and EPA/DHA, just like there is for ALA[1].
In conclusion, there might or might not be a shared bottleneck. Who knows. I’m still inclined to go for something that’s either ~1:1 or EPA-heavy given that EPA->DHA conversion seems high throughput.
Bonus question: If you don’t consume much less omega-6 than average, will you get enough DHA with just ALA?