Nitty gritty time. I've been touting the benefits of omega 3 fatty acids from the beginning of the blog, but I haven't really gone into exactly what those marine-animal derived PUFAs are doing up there, and why they are so important. Fortunately, one of the papers I'm reading for the Alzheimer's series has an excellent discussion. (1)
If you recall, the brain has a heck of a lot of cell membranes, and cell membranes are made out of fat. The fat content of the brain is a little different than the rest of the body - the only PUFAs allowed into the healthy brain in any appreciable amount are the omega 3 DHA and the omega 6 derived (or obtained directly from animal foods) arachidonic acid (AA). In addition, while AA is found in equal amounts all over the brain, DHA is found predominately in the gray matter. That's where our thinking takes place.
Let me explain a bit about the actual structure of these molecules, and that may clarify some things. It will be helpful for you to consume some wild-caught salmon before reading this as the DHA helps the transcription factors of your hippocampus in the process of making new memories.
Saturated fats and cholesterol make rather boring cell membranes all on their own. Their structure is pretty straight, and they line up rather like this:
PUFAs have unsaturated bonds, which make them rather kinky. Add some PUFAs to a cell membrane and you suddenly get this:
The unsaturated bonds break up the structure a bit, and molecular biologists call this "increasing membrane fluidity." Important membrane proteins, such as ion channels, depend on the presence of PUFAs to be incorporated correctly into the membrane. If all is well, the PUFAs serve as part of "lipid rafts" that are required for transport of protein and signals through the membranes, the formation of synapses, and maintaining the integrity of the neuronal membranes. Lipid rafts. Whee!!
We can make a bit of DHA from ALA (an omega 3 found in plants, such as flax), but the process is horribly inefficient. Otherwise, DHA is made by photosynthetic algae eaten by krill or fish or oysters, etc. - which we eventually consume. We cannot make DHA ourselves in useful amounts. The amount and ratios of PUFAs in our brain are dependent upon what we consume in our diet.
AA is important in the brain - it initiates and maintains the inflammatory cascade, which is a critical function. But AA is a different kinky shape than DHA and the overall membrane functioning is quite different if we have a ton of AA compared to DHA. The paper notes here that "it is intriguing that the dramatic increase in the prevalence of [Alzheimer's disease] in the last century not only parallels the increase in average lifespan, but also an increase from 2 to more than 20 of the ratio of omega 6 to omega 3 PUFAs in the average Western diet."
Our brains are designed to run on fish oil. We really shouldn't be operating the all-important noggin too far outside the design specs, or nasty things tend to happen.
In the next couple of posts we will explore a bit more about DHA vs AA in the pathology of Alzheimer's, and also figure out why the randomized controlled trials of omega 3 fatty acids in dementia have, so far, been a bust.
(PS - Dr. BG had a couple of recent blog posts on the topic of our fish-eating ancestors - similar points to mine though made with considerably more flair!)
You know, I almost talked about membrane fluidity and fatty acid composition in our book. If I'd realized all it needed was i's and L's I might have done it!ReplyDelete
But EPA and DHA -- especially DHA -- are unique mainly in that they don't have any real shape. They have so many double bonds that can twist and bend so easily, they change conformation very rapidly and under the slightest pressure fold up into tiny balls or slither out of the way. This is what makes salmon oil so slippery, especially at body temperature.
So a DHA-filled membrane is barely a membrane at all. Rather a unique structure. A biological extreme. The membrane equivalent of a soap bubble. They don't even have a letter in the alphabet for it; even M has only three bends.
And this is what human consciousness depends on? No wonder we're in trouble.
I love dem kinky lipids! Our farmer's market has a fish monger with an awesome array of fresh fish. Most of the summer I've been cooking black cod or mahi mahi in my skillet once a week, but which easily lasts for 2-3 meals. Even my kids love it! (and that's nothin to shake a stick at, as I know you know, Emily). I also go through about 2 cans of sardines and 2 cans of smoked oysters a week for lunches and stuff. Love feeding my noggin what it needs!ReplyDelete
Good morning - how lucky am I that a few hours after posting, I get two comments from two PhD docs in different fields with different expertise? That's why I'm sure the blogging gig will allow us to make some real contributions. And there is no ivory tower - some of the best ideas and links have come from readers without advanced degrees (that I'm aware of).ReplyDelete
Paul - perhaps I should have called them "squiggly-wiggly" rather than "kinky." But as you see, my graphics skills are hardly up to the task. I do love the idea of slippery lipid rafts and membrane proteins moving and grooving. The review paper I'm looking at seems tied to this theory that the different shapes of AA and DHA are important in the cleavage of amyloid precursor protein. That DHA covers up or blocks the bad cleavage sites, whereas AA preferentially selects for the gamma secretase that snips APP into alpha/beta amyloid => aggregation, plaque, bad news. I'd be interested in your thoughts.
Aaron - I couldn't find any sardines at Whole Foods the other day! I'll pick up some smoked oysters the next time I go to the store. My kids love salmon. Actually, they love veggies too as long as I cook them in enough (pasture) butter.
YUMMM more reason to keep up the kipperings and sardines!!! SHAME, though i cant find the skin & bone in sardines anymore theyre all skinless boneless tins :( i want my WHOLE fish! while i dont understand most of this blog i sure do love to read it!ReplyDelete
AA has only 4 double bonds, DHA 6, so DHA is quite a bit more squiggly-wiggly. The lipid rafts use cholesterol as a stiffener, the cholesterol prevents the fatty acids from changing conformation. So DHA and AA in lipid rafts are rather different from DHA and AA in ordinary membrane. The lipid rafts tend to have a lot of transmembrane proteins. The lipid-protein-carbohydrate interactions at these microdomains can be very complex and thinking about it makes my head hurt. Maybe I need more DHA.
I found a nice picture of a lipid raft here:ReplyDelete
Are fish oils worthy to consume as a supplement then, or do we only get kinky from the more natural state fish?ReplyDelete