I had a slog through this paper and this paper, trying to tease out a little more on DHA and free radical damage.
DHA enriched brains are substantially protected against the free radical damage which occurs in response to reperfusion after exposure to an hypoxic state. This is unexpected in view of the host of oxidisable double bonds in the DHA molecule. Oxidative damage is what happens if you throw DHA on to cell cultures and challenge them with free radicals. It also happens in your bloodstream when you drink 30ml of fish oil unless you dose up on vitamin E at the same time. So we can say that the DHA per se, in triglycerides and in cells, generates and propagates free radicals. This is probably Bad.
But if you supply DHA (as the ethyl ester injected in to the amniotic fluid) to an intact rat foetus it concentrates it in the brain and you get neuroprotection... How come?
Hydroxyl radicals are one of the nastier oxygen derived free radicals and there is a 70% reduction of their generation in DHA enriched brain tissue from these rat pups.
Supplying oleate enrichment does nothing for hydroxyl reduction and EPA enrichment is not as good as using DHA, despite the conversion of EPA in to DHA... That is, it's not the DHA per se that matters, because the amount of DHA was increased equally by EPA as by DHA but the DHA supplemented rats were better protected than those given EPA.
The explanation is in the phospholipids.
A triglyceride is, quite obviously, a glycerol molecule with three fatty acids attached. DHA here is unstable without vitamin E. A phospholipid is what cell membranes are made up of and consist of that same glycerol molecule with two fatty acids attached but with a very interesting and highly water soluble moiety in the place of the third fatty acid. This is a phosphate group plus a small organic molecule of various types. They make up the lipid bilayer, the phosphate grouping lying either inside or outside the cell in the aqueous phase and the lipids snuggled up in the hydrophobic structure of the cell membrane itself. With beloved cholesterol to regulate fluidity and perform about a million other functions.
The small organic molecules matter. We are interested in ethanolamine and serine, two amino groupings attached to the phosphate to give phosphatidylethanolamine (PE) and phopshatidylserine (PS).
Both PE and PS are the preferred phospholipids to which DHA is attached, and DHA pre treatement (but neither oleate nor EPA) increases the percentage of these phospholipids in the brain cell membranes.
Summary: DHA pretreatment increases DHA, PE and PS and they all live together quite happily.
PS is an iron chelator. Iron is superb for free radical propagation. It can't do this when it's been grabbed by PS.
PE containing phospholipid is an effective antioxidant, it grabs free radicals and there the free radical propagation ends. PE also commonly contains a strange lipid called a vinyl alcohol, making it a substance called plasmalogen. The extra double bond in the vinyl group makes it an effective antioxidant. Not all double bonds are bad.
What conclusions can you draw from this type of experiment, very artificial though it is? The impression I get is that DHA is useful to brain tissue, yet it is clearly unstable on an oxidative damage basis. The obvious answer is that the brain looks after DHA by sticking a set of peroxidation protectors on to the molecule. It can then use DHA for whatever it needs to, without worrying about all of those lipid peroxides which we might see were we to drink 30ml of unprotected fish oil...