Tuesday, August 25, 2020

So you want some DHA?

It seems like a very long time ago (only last year!) that George Henderson posted links in comments to the blog* about the absolutely crucial work done by Gibson and colleagues, documented in this paper

*Ooooh look, I just noticed how to link to comments. I'm so tech savvy!

Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids

Another aside: Paywalled. If anyone has a few pence looking for a home Alexandra Elbakyan might be a good destination. I didn't say that. End aside.

It is impossible to say how good this work is. It's very good.

I'm no hyper-enthusiast for DHA. It's a tool. It does a job. Saturating yourself with the stuff is very likely to be a Bad Thing. This is perhaps best exemplified by the fierce negative feedback exerted by all of dietary C18 VLCPUFA precursors (omega 6 and omega 3s) on its synthesis (I would assume the same happens for arachidonic acid as well). The conversion of alpha linolenic acid to DHA is, for rats at least (and I would go with for humans too), very, very easily achieved by simply getting close to eliminating linoleic acid from the diet and also keeping ALA low, under 3% of calories. Here's my favourite figure from the paper, already tweeted and blogged by George:

These are the DHA levels in phospholipids, presumably LDL and HDL secreted by the liver, extracted from plasma after three weeks of dietary intervention in Hooded Wistar rats.

"We conclude it is possible to enhance the DHA status of rats fed diets containing ALA as the only source of n-3 fatty acids but only when the level of dietary PUFA [ie all combined PUFA*] is low (less than 3% of energy)."

*My insert for emphasis.

Does anyone begin to recognise a pattern to PUFA requirements here?


Random aside. Rats. Have they been scavengers of the small amounts of edible tissue left on mammoth carcasses after humans had finished with them? Are rats evolved to be opportunist high fat, low PUFA adapted facultative carnivores? Now that's an interesting and useless thought but might help explain why they behave exactly as humans do on Surwit diets compared to low PUFA Surwit-like derivatives. Well, the idea entertains me. But then I like rodent studies...


Passthecream said...

Peter - tweaks = duplicity with certitude!

Fwiw when I was growing up we didn't leave a lot of mammoth bits lying around (has anyone contemplated mastodons?) but living next to a watercourse we often came across rats' nesting areas in our garden, sheds etc. The main food related debris in those was snail shells and almond shells plus hollowed out stones of fruit such as peaches and plums, and various seed bearing grasses, a mix of significantly fatty food sources. They also loved chewing up the old tallow candles my father kept in his shed and any bits of soap lying around, ditto.

Snails seem to average around 20% sfa plus mufa as a proportion of total fa. Good source of cholesterol like other molluscs and crustaceans.


Peter said...

Pass, My personal experience with domestic rats is that they thrive on a diet of plasterboard and electrical insulation. I have noted that they've sometimes dug up the remains of a chicken carcass from where I bury the ones which die of old age...


Tucker Goodrich said...

Ramsden: "Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools"


Peter said...

That's cool Tucker, puts humans exactly on to the surface plot from Gibson's rat paper, where an increase in ALA from 0.5 to 1.5 markedly increases plasma DHA. It fascinates me that further increases in dietary ALA, ie drinking varnish aka linseed/flax oil to 12% of calories will lower DHA to only 1% of plasma fatty acids. assuming the data continue to hold. On a 2000kcal diet you would need less that 30g of flax oil a day to become profoundly DHA deficient, assuming no dietary DHA...

I love rat papers and, obviously, Ramsden is a hero!


Peter said...

Oh, and DHA to around 2% of plasma lipids using flax oil on a background of LA at around 6% of dietary calories. But I suspect a lot of people will actually have LA up at 18% of dietary calories. Heart healthy!


Tim Thorpe said...

> The main food related debris in those was snail shells

Would second that, there is a parasite (Rat Lungworm) where the adult/egg/larval
cycle is between rats, rat faeces, snails, and whoever fancies Escargot with
parsley (sometimes your dog, as Peter will know). That could only evolve if
the snail part of their diet was significant and stable.

Our lawn-rat is sometimes seen trotting around randomly, then suddenly getting
a scent and digging, quickly. It leaves craters of about 1cm. I think this is
grubs, maybe the ones which make "daddy-long-legs". I assume that's another
high-fat delicacy.

Abu Dhabi said...

This is very interesting, as it provides an explanation of why EPA/DHA supplementation is the wrong way to approach a low n-3 index.

ctviggen said...

Assuming n-3 is valuable, it also makes one wonder how much is really necessary to get a benefit, if n-6 is low.

cavenewt said...

@Tim Thorpe, I'm trying to puzzle out how the parsley figures in.

Peter said...

Hi Abu,

Taking a fish oil capsule on a diet with 10% of calories as linoleic acid looks about as sensible as taking a vitamin D capsule and expecting the benefits of being a heliophile in summer!

Not worthless but far from ideal...


Purposelessness said...

Interesting about the tweaks - it's the same everywhere it seems. Every lab I had the pleasure to work in had certain tweaks - way more benign than in nutrition research, but then again they are as far removed from that discipline as possible - but the old guard knows that certain procedures don't work as written and have work arounds and tweaks. And if too much of the old guard leaves at once, even old seemingly tried and true methods simply don't work anymore.

Peter said...

Purp, I have to say I have long wondered about Deborah Clegg, able to reduce rodent food intake using intracerebral insulin at Cincinnati (as a first author) but unable to replicate this in Novo Nordisk's lab with Jessen and Bouman.

Does she not know about the tweak or does she know but not dare use, or even suggest its use, outside of the lab where it is probably routine and unquestioned? Wouldn't you like to know?


Robin said...


Elmumo said...

Thanks Peter. Quite interesting. I havent read the paper (I probably should before asking), but how do they know the increase in circulating DHA in plasma is a result of conversion (i.e. synthesys from ALA), and not simply as a result of the body mobilising stored DHA from cells (e.g. brain cells)? If it is the latter, this graph then would not reflect an increase in total DHA.

Peter said...

Hi Elmumo,

The paper didn't use any sort of tracer system, which is what you would need. The whole drive of modern research is to supply more DHA. Trying to find details of it's catabolism, let alone putative efflux from the brain, is hard.