Wednesday, June 03, 2020

ARDS and Tucker Goodrich

Tucker has been very, very busy over the last few weeks.

You will need some time. Maybe some coffee.


Total, utter aside:

"Although we initially also identified monoclonal antibodies that appeared to bind exclusively to 4-HNE-LDL, these were lost during the cloning procedure."

The first ever auto immune disease to be tied to a specific human leucocyte antigen receptor subtype was ankylosing spondylitis, linked to HLA B27. The monoclonal antibody was developed by my wife's PhD supervisor working in Prof Ebringer's lab, as part of her own PhD. She lost it during the cloning procedure. It happens. As Tucker says:



Gyan said...

Interesting in that it lays out a mechanism for cytokine storms through oxidation of the membrane lipids.
How much PUFA is in the membrane anyway. Per Wikipedia, the phospholipids have one saturated and one unsaturated (MUFA generally I suppose) fatty acid.

So if one eats a high PUFA diet these PUFA might get fixed into phospholipids instead of being consumed.
But again, some PUFA like AA, DHA are structural in specific tissues like brain is supposed to have significant DHA containing phospholipids.

I do hope MUFA don't present much opportunity to oxidation. I wonder how much PUFA were people in 1918 eating. Tucker's plot gives 3% LA at 1900 rising to 7% by 1990s.

cavenewt said...

"I wonder how much PUFA were people in 1918 eating."

Lard was already being adulterated with cottonseed oil by the 1860s. So possibly more than we might assume.

karl said...

@ Tucker - Impressive digging -

I wonder if they kill people on feeding tubes due to the PUFA in other situations as well?

What is so often missed, is evolution is not like car design - where if you need a wheel - you design one that is a wheel and nothing else - instead, with evolution, many of the bits have multiple functions - (sometimes with competing evolutionary pressures).

I've been convinced for some time that not only the HDLs (many types) but LDL should be thought of as part of the immune system and repair system. I think it is probable that when they saw the weak correlation of LDL with CAD - vessel damage - that they got the arrow of causation backwards. LDL goes up in response to the tissue damage - not the other way round.

I spent quite a bit of time digging into oxLDL (correlated with CAD) - seemed like it was a good idea to lower it if one could - that is what got me on a low PUFA diet - nothing else seemed to change the level - I don't agree that O-3 can compensate for O-6 PUFA consumption. We just shouldn't eat these artificial animal fats - concentrated seed oil is just not human food.

What I don't get - what seems insane - is why tell people to hide under their beds instead of explaining that simple dietary changes can lower BG and PUFA(circulating - not sure how quickly membrane lipids get change out)? In just a day or so people can most likely greatly reduce their death risk from CoVid-19.

When I had CABG - they had me intubated for a long time - had me on a feeding tube. The feeding goop is full of sugar and PUFA. I had been low-carb so my BG shot up - they gave me insulin - I asked (by pointing at letters) why they were feeding me sugar if my BG was high - they changed to a different mix.

We know from work from long ago that viral replication is much faster with high BG - so what I think may be happening - someone gets CoVid-19 - short of breath - hospitalized - intubated - they fill their stomach with sugar and PUFA - people die. There is an MD (in England?) that is avoiding the respirator - thinks he has a higher survival rate that way. I wonder if it is actually the feeding tube that makes the difference? The stories I've heard - they seemed like they were starting to get better - then suddenly ... Was that when they filled the feeding tube?

I am fairly convinced that CAD is mostly caused by NO disruption - low-level-lead, nicotine, PPIs, Stress - I wonder if having damaged endothelial tissue puts ARDS patients at much greater risk.

JR said...


Maybe I can help you a bit. Chris Masterjohn and Tucker Goodrich have covered PUFA's in great detail.

If you stop O-6 pufas today AND you have accumulated a lot of O-6 in your adipose tissue, the turnover is going to take 3+ years. So, as the "poison" O-6 comes together with "antidote" E-vitamin, you better cover that O-6 flow from tissues.

Even is the turnover from cell structures is faster, there is still O-6 available. Do not know the relevance of this, how it may be recirculated...

The tiny little "essential" O-6 you need, can be probably found in any wholefoods that include fats. There is always some O-6 in there.


Passthecream said...

JR - possibly preaching to the choir.

Tucker vs Masterjohn.


Tucker seldom disappoints.

ctviggen said...


For this, "I wonder if having damaged endothelial tissue puts ARDS patients at much greater risk", possibly:

karl said...


The 600 day turn-over people talk about is re adipose tissue - turn over of membrane tissue would be much faster - but not known.

We have talked about the half life of O-6 - particularly LA many times here.

That LA is essential is not a given - the research that is claimed to show this had serious problems. Could be we need a tiny bit - or not.

Frunobulax said...

If you don't know this talk yet, you're gonna love it: (Chris Knobbe on seed oils, Low Carb Denver 2020z).

As for n-3 PUFAs, I wondered if they might be in some sense an antidote to n-6 PUFAs. If we have contradicting studies, chances are that we're missing something fundamental and are not controlling for an essential factor. And the n-6:n-3 ratio comes to mind immediately. There is contradictory evidence that n-3 PUFAs are antiinflammatory, and perhaps they are only if the patients in question have a bad n-6:n-3 ratio. For the rest, we might see even some detrimental effect because n-3 PUFAs are unstable, and not exactly a protons favorite.

Reminds me of the keto vs. paleo discussion. Considering that our ancestors ate around 20% carbs, could it be that the benefits of keto are as marked because keto is the antidote to decade-long high carb eating? If people ate 20% carbs for all their live, unrefined carbs only with fiber, would keto still show benefits or could there even be drawbacks? Guess we'll never know because we lack the study populations, but still, it's something to mull over. But I digress...

Peter said...

Frunobulax, in the past someone suggested to me off-blog that we might have a "carbohydrate allowance" for our life. If you eat that allowance early in life you shorten the remainder of your life. This is an interesting idea. That would fit with your concept of keto as an antidote to decades of early "carb allowance" consumption/squandering. The idea has some merit. And insulin signalling would be core.


Gyan said...

Knobbe says LA is not meant to be burned, but to be used for signaling and as structural fats, "particularly in mitochondria".

Is it correct? Is LA required in mitochondria? What about the Double Bond Index?

Peter said...

Some level of linoleic acid is probably needed for cardiolipin formation. It is essential that cytochrome C can be released when it should be released, apoptosis is a completely essential process. LA allows this. But we probably need less than 4% of it in our diet for these needs to be met...


Gyan said...

Does a complete avoidance of vegetable fat, which might be expected to lower dietary LA to one percent or less, lead to substitution of AA in place of LA in cardiolipin?

LA_Bob said...

Some head-scratching about obesity from 2013

"...such results don’t explain why the weight gain is also occurring in species that human beings don’t pamper, such as animals in labs, whose diets are strictly controlled. In fact, lab animals’ lives are so precisely watched and measured that the researchers can rule out accidental human influence: records show those creatures gained weight over decades without any significant change in their diet or activities."

So are the lab diets as bad as the SAD?

Peter said...

Bob, "History is not kind to authorities whose mistaken dogmas cause unnecessary suffering and pointless effort, while ignoring the real causes of trouble. And the history of the obesity era has yet to be written."

History has a tendency to repeat itself. The essay has some nice observations, I enjoyed it.

Gyan, it's remarkably difficult (but not impossible) to alter cardiolipin species. Oddly enough high fat/sucrose diets tend to reduce PUFA in cardiolipins. What is easy to alter are the lipid species in the inner mitochondrial membranes in which the cardioloipins are embedded.


Frunobulax said...

@Peter gives some LA numbers for grass fed beef, which should be a decent reference what our ancestors ate. As evolution usually builds in some tolerance, I guess we would be fine with 5% or slightly more LA (as percent of total fat). But not 40% or whatever the SAD is.

As we store LA (Guyenet did a study that came up with 25% LA in our lipid cells), we're setting lots of LA free whenever we lose weight. I wonder if that has something to do with the various effects we see if people lose weight, that are often attributed to "detoxing" or whatever. And that may be why our lab work stabilizes only when we're done losing weight, which can take a few years.

I like the carbohydrate allowance idea. I'd say insulin resistance influences how much any carbs count towards this budget. But as a rule of thumb, maybe for someone who is not much into science, this is really catchy.

Passthecream said...

That beef paper: " be aware that the differences in FA content will also give grass-fed beef a distinct grass flavor and unique cooking qualities that should be considered when making the transition from grain-fed beef. "

What's not to like???

Where I live most beef is actually grass fed, only the export stuff is grain finished but now the supermarkets have gotten hold of the idea, they advertise some cuts as 'grass fed' and push the price up. (There is possibly a difference between feeding animals on green pastures versus hay etc ???)

I've mentioned my 2 faced attitude to PUFA, specifically LA, previously -- I rigorously avoid eating any but I use oils for making cooked oil varnish (for musical instruments). That means that I troll through the constituent data of various oils at times and what I am finding is that linoleic acid content is declining in many of the manufactured oils. High oleic varieties are being developed more often probably for the deep frying industries because LA goes rancid very quickly and gums up the works. Just like it does inside people. The most surprising finding last week was that soy oil is often partly hydrogenated, to lower the LA content by saturating it somewhat --- another fabulous varnish ingredient ruined

But that led to another realistion. 'Traditional heart healthy' oil based margarines are hydrogenated. Trans fats are avoidable but oils hydrogenated to the point of semi-solidity shouldn't contain much of those good ol' PUFA. Seems like an own-goal for the people claiming any health benefit.

Gyan said...

Would grain-fed beef have higher LA?
I have read that grain-fed beef has the advantage of being more fatty than the grass-fed beef.
The Stone Age people would preferentially eat the fatty parts and waste the other parts. But as we can't do so, the numerical ratio of animals to men being unfavorable, we have to perforce fatten up the animals to get the requisite fatty meat.