Tuesday, January 21, 2020

Barja, an aside

I quite enjoyed Barja's review

The Cell Ageing Regulatory System (CARS)

but found this section a little uncomfortable:







Hmmmmmm. Plant based, healthy fruit and vegetables, bad animal fats. Not my sort of outlook really.

In another of his publications here

Highly resistant macromolecular components and low rate of
generation of endogenous damage: Two key traits of longevity

there is this comment

"It was also found that 6–7 weeks of dietary restriction are enough to decrease MitROS production and 8-oxodG in mtDNA and nDNA in rat liver (Gredilla et al., 2001a )".

Gredialla et al (incl Barja) 2001a is

Effect of short-term caloric restriction on H2O2 production and oxidative DNA damage in rat liver mitochondria and location of the free radical source

Here they found, by eyeball, an approximately 50% reduction of in 8-oxodG in mitochondrial DNA after those six weeks of quite severe caloric restriction:























Now let's compare this with the degree of damage reduction (this time using the term 8-OHdG as the marker rather than oxo-8dG, which appears to be the same thing).

Here's the change in mtDNA damage marker in brain mitochondria using F3666, one of the worst ketogenic diets around:























Just by eyeball I make the drop in mtDNA damage out to be greater than 50% by two days and something like 75% by three weeks. On ad-lib food consumption. No hunger.

Considering that F3666 does not extend longevity in mice (it doesn't shorten lifespan either, despite causing liver damage and it does actually improve health during ageing in rodents) this does, for me, slightly knock some of Barjas core ideas.

Sad but true.

Peter

Wednesday, January 15, 2020

Stearic acid again

Better post this one while I have a few minutes. I picked it up while looking for refs for Gustavo Barja's epic The Cell Ageing Regulatory System (CARS) in which longevity is tied to the Double Bond Index of the mitochondrial inner membrane (Thanks Bob!). BTW it is possible to modify the DBI but, with current data, it looks like you cannot alter the saturated or MUFA percentages, it is replacing omega 3s with omega 6s which mimics the mitochondria of long lived mammals!

Anyway, here is the cocoa butter paper:

Differential effects of saturated versus unsaturated dietary fatty acids on weight gain and myocellular lipid profiles in mice

Here are the diet compositions:
















The line in red is the total percent of calories from linoleic acid in each diet. Here are the body weight changes:
















The bottom two lines are the low fat high carbohydrate diet which happens to come in at just 1% linoleic acid and the cocoa butter diet which comes in at 1.4% of calories as linoleic acid. The high palmitic acid gives the most weight gain as it delivers 4.5% of calories as PUFA. Olive oil is a close second, also with 4.5% linoleic acid. The oddity is the safflower oil diet which is very high in PUFA but only gives intermediate obesity. Quite what is going on here is difficult to say but you have to wonder at what level of omega 6 PUFA that "next level up" signalling (lipid peroxide based) kicks in. No data on that, just a guess/excuse from the Protons perspective. There are a number of other studies showing this phenomenon of limited weight gain with safflower oil.

Still, stearic acid as cocoa butter is still looking pretty good. All of the high fat diets were based around different fat sources placed in to the D1245 background so are equally high in sucrose and starch too, comparable amounts across all of the higher fat diets.

Peter

Thursday, January 02, 2020

Protons (53) a formula

A couple of things came up in emails recently. First is that I never mention that I had a chat with Ally Houston on the Paleocanteen podcast. It was fun. I think I sound like me. It's here

https://paleocanteen.co.uk/peter-dobromylskyj-hyperlipid/

Second is that karl asked if there was a general formula for working out the F:N ratio for assorted fatty acids.

Edit: cavenewt pointed out that for people unfamiliar with the FADH2:NADH ratio concept there is a reasonable introduction at Protons: FADH2:NADH ratios and MUFA. PubMed-ing Dave Speijer and CoQ makes good reading too. End edit.

There wasn't but given a few minutes and some algebra it works out like this for even-numbered, fully saturated fatty acids of carbon skeleton length n:

F/N   =   (n-1)/(2n-1)

So stearate (C18) is 0.486

Palmitate (C16) is 0.484

Caprylate (C8) is 0.467



For MUFA/PUFA you just subtract one FADH2 per double bond (db). This doesn't affect the NADH term.

F/N  =  (n-1-db)/(2n-1)

Oleate (db = 1) is 0.457

Oleate is the MUFA of stearate. Saturated fats allow us to resist insulin, MUFA allow insulin to act.

Linoleic acid, also C18 but with two double bonds, gives 0.429

This is lower than stearate or oleate. The switch for ROS generation occurs between roughly 0.486 (high physiological ROS) and 0.457 (low physiological ROS). LA is lower than oleic acid.

Glucose has an F/N ratio, from memory, of 0.2 so LA is the "glucose-like" of the common fatty acids, in Mike Eades' terminology, and so will fail to generate fatty acid appropriate ROS. Which will allow continued insulin action when it should be resisted. That will make you fat, and the loss of calories in to adipocytes will make you hungry. The exact opposite of stearic acid...

Happy New Year all.

Peter