Tuesday, March 17, 2020

ARDS and linoleic acid

Adult Respiratory Distress Syndrome is topical at the moment. In the comments to the last post I wondered whether omega six fatty acids, especially linoleic acid, might be a driver of ARDS, which is one of the most intractable ITU problems in response to major infection/trauma/inflammatory insults.

Tucker came up with this abstract

Plasma fatty acid changes and increased lipid peroxidation in patients with adult respiratory distress syndrome

and I peeked at the related papers to find this gem:

An increase in serum C18 unsaturated free fatty acids as a predictor of the development of acute respiratory distress syndrome

Again, only an abstract and mostly describing a pilot study. But here is the critical statement:

"Increases in unsaturated serum acyl chain ratios differentiate between healthy and seriously iII patients, and identify those patients likely to develop ARDS".

That is, the more linoleic (and oleic) acid you have as FFAs in your bloodstream, relative to my beloved palmitic acid, the more likely you are to develop ARDS. Which carries a high risk of death.

That was 1996.  The work will have been done before that, so we have known that linoileic acid is bad news for well over 20 years.

If you are a Standard American on the Standard American Diet, or anyone else in the world poisoned by a cardiologist-promoted PUFA based diet, any weight loss through illness will release significant amounts of linoleic acid from your adipocytes. That might just trigger ARDS in the aftermath of a viral pneumonia.

There's a lot of it about.

Peter

BTW Steve Cooksey has a rather nice post up citing a lot of the refs featuring how to maintain an effective innate immune system, so as to avoid the viral pneumonia in the first place. It's a good read.

36 comments:

Lukas said...

Do you have any estimates on the turnover rate of the human fat depot without going through fasting? Meaning if you change your diet only, how long would it take for PUFAs to be replaced?

Peter said...

Hi Lukas, these are big unknowns. I looked for some time to find which FFAs predominate under fasting and the only paper I could find was rats and FFA species "became more saturated" or the like. That is logical. Adipose turnover has been suggested to be around five years in humans but that may well be on an insulinogenic diet. It's possible that on a ketogenic diet turnover might be a lot faster but I have no data. Plus, if you are a choletserophobe on a ketogenic diet you are going to mainline PUFA anyway. If you are in an ITU and need parenteral calories you are going to get Intralipd, intravenous soy oil, literally mainlined.

Peter

cavenewt said...

Lukas

The seminal work on this seems to be "Dynamics of human adipose lipid turnover in health and metabolic disease", 2011 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773935/

Other articles tend to cite that one. Most of the work of course involved obesity.

"In and Out: Adipose Tissue Lipid Turnover in Obesity and Dyslipidemia" 2011 https://www.cell.com/cell-metabolism/comments/S1550-4131(11)00389-5

"Tracking human fat turnover with carbon dating" 2019 https://stm.sciencemag.org/content/11/511/eaaz4961.full

"Dynamics of adipose tissue turnover in human metabolic health and disease" 2018 https://www.researchgate.net/publication/327943713_Dynamics_of_adipose_tissue_turnover_in_human_metabolic_health_and_disease

karl said...

@Lukas

I can't put my hand on the link to the paper right now - but there was a bit that the half life of LA was 600 days.. could be it is slower than other fatty-acids - as it concentrates in fat tissues - the tissues would become more insulin sensitive - so slower to release.

But here is another link I found in my notes about PUFA and T-cells..
https://academic.oup.com/ajcn/article/84/6/1277/4649361

You don't want a suppressed immune system - despite what some narratives say.

I've thought this slow half-life is a big problem - if people eat low PUFA to lose weight - it could take a decade for results.. not encouraging. This global uncontrolled experiment of feeding the public huge quantities of PUFA is brought to you by the makers of ...

Frunobulax said...

Do you have more information on oleic acid? Animal fats have a high content in oleic acid, and frankly whenever a study differentiates between OA and LA it seems that LA is the culprit while OA is neutral or beneficial.

I would find it surprising if we would react adversely to a fatty acid (OA) that occurs a lot in animal fats (~50% content in tallow/lard and 25% in butter). At the very least, the presence of saturated fat should neutralize this. (LA is a completely different matter of course, and I do think it's poison if consumed in high quantities.)

Hap said...

https://link.springer.com/article/10.1007/BF02536624

Please see
Hap

Passthecream said...

Hap - is that a good thing or a bad thing?

Ivo said...

Have you seen https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357182/#!po=45.6989

Supplement LA or AA? In vitro only?

Passthecream said...

I guess that stored human triglycerides have a mix of various fatty acids attached to the one glycerol backbone (sorry, I haven't read all those linked papers yet). But I was wondering about what happens to stored fat types during eg the potato diet when weight loss is quite rapid, or any other high fat-burning ie catabolic regime???

As to excess pufa leaving cell membranes, that must be a relatively slow process. It probably goes in much more readily than it leaves.

Peter said...

Hi Hap,

Arachidonic acid, EPA and DHA are essentially signalling molecules. If they are ever present in amounts well in excess of the cell’s needs they are destined to peroxisomes for conversion to caprylic acid which is then transferred to mitochondria. What is done with them in terms of conversion to signalling molecules may well depend on the cellular environment. It’s becoming clear from COVID-19 that an inflammatory response is, unsurprisingly, beneficial. Hard to say the same about bulk linoleic acid which can represent the vast majority of your calorie intake if some clown sets you up with a central line to infuse Intralipd.

Hi Ivo,

It is certainly interesting that LA and AA are viral toxic in cell culture. Happily, unlike humans, cell culture does not demonstrate ARDS. It’s interesting that the authors didn’t seem to expect this result. I certainly would not have.

As an aside, elevated % of plasma FFAs as omega 6 PUFA, on a population basis are undoubtedly associated with improved all cause mortality outcomes and lower HbA1c. When you look at acute pancreatitis or ARDS or the Sydney Diet Heart Study or the Minnestota Coronary Experiment it is difficult to see anything good about PUFA other than healthy user bias. But maybe that just sour grapes from me.

Hi Frunobulax,

I can’t see direct toxicity being likely with oleic acid damage either. As you say, LA is a different matter.

Pass, again I don’t have the data (not had chance to follow cave’s links). My guess is that weight loss = low insulin and saturated fats should be released preferential as low insulin means we need physiological insulin resistance to spare glucose for the brain. I think any technique of weight loss should do this.

Peter

cavenewt said...

Ivo, from that article: "In this regard, our data suggested that optimal coronavirus replication required a specific composition of cellular lipids and any disruption could decrease the efficiency of coronavirus replication."

Despite the technical nature of the article, a lot of people must've taken it to heart. The vegetable oil shelves at my grocery store were completely wiped out.

Ivo said...

After they watch the Dr. Wodarg video they will want their money back. https://youtu.be/p_AyuhbnPOI

Peter said...

Ivo, nice video.

Time will tell, hopefully he is correct.

Peter

cavenewt said...

Along those lines, ran across this today. I've long respected John Ioannidis, so this is making me really scratch my head and wonder what to believe.

"A fiasco in the making? As the coronavirus pandemic takes hold, we are making decisions without reliable data"

https://www.statnews.com/2020/03/17/a-fiasco-in-the-making-as-the-coronavirus-pandemic-takes-hold-we-are-making-decisions-without-reliable-data

Peter said...

Yes cave, I read that one too. Ultimately we will need a body count when all is settled and it can be compared to an average or a bad flu year. It's quite normal to run out of mortuary space at my local hospital in a bad flu year so refrigerated storage gets brought in. There has also been a long term policy of not putting critically ill patients on to ventilators unless there is a realistic chance of weaning them off after successful treatment. Traumatising n=1 experience of unwean-able patients tends to sharpen your anaesthetist's decision making about instituting ventilation in the ITU. Always has done, it's not new to this pandemic.

Peter

DLS said...

fast and clean adipose turnover please!!! 3 months ago i choose to eliminate all pufa, increased my long-chain SFA intake... and rapidly lost body fat, then gained a bit back, all my pains are gone, so adeus crunchy peanuts... its time to say goodbye! so 5 years? that's seems ridiculous Peter, i bet ( hope) it takes my a fraction of the time... still doing IF intermittent fasting 4 times a week or more + good ol regular keto + 0 carbs most days + the "sane" pkd parts ( more organ meat, liver, cow fat) not ready 2 dive in a pool of chicharrones and raw shit or give up butter, cream, cheese. my only true crime now is coke no sugar/ caffeine / artificial sweeteners... also not ready to give up the sweetness! i do expect to hear they are the root off all evil soon...

cavenewt said...

DLS, I'm sure there could be a large range of turnovers based on eating habits and other factors. If one has a large depot content of PUFA there could be Herxheimer reactions as it is released (there was an entire episode of House MD based on this concept, one of my favorites actually). Peter pointed out that there may be preferential releases of saturated fat…This would be a fascinating subject to explore.

Peter said...

cave,

Yes, but we mustn't forget Sauer's work and 13-HODE released by fasting in rats fed a typical omega-6 rich diet pre fasting...

Hi DLS!

Peter

Justin said...

I'm just glad I have plenty of quail, chickens, sheep and an incubator! Not to mention 10 new lambs on the ground! BTW, it's blogs like yours that inspired me to start my own farm.

DLS said...

Hi Peter! Silent reader, never left! Dat friday 13 shit sounds nasty... heres hoping my past/present super hi sfa intake spares from some of that lovely pufa damage @ while gasting... also pufa in the form of peanuts ( vit e?) No deep refried transShit made with corn oil
... time will tell, so far im great! Xo

Passthecream said...

My pretend apocalypse shopping wasn't too difficult this week. There was no TP of course, no bread or flour and not much chicken (yawn to all of those!). But I came away with a big lump of fatty beef roast and a dozen blocks of grass fed dripping which are the cheapest bulk calories on offer, and almost as many blocks of butter. No-one seemed to be paying much attention to the saturated fats, lipophobia works in your favour sometimes. This isn't very different to my usual fortnightly lipid shopping anyway. There's rice and masa harina in the cupboard if I get a carby substrate yearning.

Lamb flaps (ribs plus belly cuts) will continue to be cheap and available here since they are regarded as only fit for pet food. Woof!

Ivo said...

I raise you a 100 tins of Brazilian corned beef!

JasmineJohend said...

This guy has been reporting on the virus for some time. He predicted panic buying way back in Jan and his many followers continue thanking him as they had started stocking supplies then.He is very much doom/gloom and believes lockdowns are the only way to flatten the curve.He believes it will get a lot worse, very depressing https://youtu.be/yOIvGIukZhk

Passthecream said...

Sober reality.

Kajus said...

It has a strong antibacterial effect, and can kill both bacte­ria and viruses.

https://www.breatheology.com/nitrogen-oxide-pleasant-poison/?fbclid=IwAR0FOtvhySrppRrrtvFWxhDqlOFeywAFT9R7PXj7OXvpdqR_wcIvjCIzH5k

Justin said...

https://www.evolutamente.it/covid-19-pneumonia-inflammasomes-the-melatonin-connection/

Bob Johnston said...

So going to the ICU may actually be making your chances of recovery worse. Holy hell.

Peter said...

Bob, that's not how I'd view it. Being loaded with hearthealthyPUFA will transfer you from supplementary oxygen to IPPV in the ITU to try and manage ARDS. You probably ended up on supplementary oxygen due to the consequences of hyperglycaemia/hyperinsulinaemia/PUFA aka metabolic syndrome, as in hearthealthyeating via Public Health England.

Peter

Stuart said...

I'm astonished that they're still using soy oil in parenteral nutrition despite the knowledge that it causes liver failure in long-term patients, when there's a safe alternative in fish oil. See what this guy has to say about it
THE TRUTH ABOUT SOY
http://roarofwolverine.com/archives/1557
The high percentage of glucose in the solution does a number on your arteries too
THE EFFECT OF SUGAR ON ARTERIES
http://roarofwolverine.com/archives/1377

With regard to the high number of deaths in Italy (and increasingly in Spain) although 28% of all men might be smokers today I'd bet that the % of smokers and former smokers in the senior male cohort was a lot higher. Add in a diet high in olive oil and you have a perfect storm.

Peter said...

My other bugbear about intralipid is that it is the vehicle for propofol used as a sedative in the ITU. I get the impression that this is not being used/not available in the current situation because there are reports of patients needing physical restraint, so I'm assuming no sedation. Doesn't sound pleasant.

Peter

cavenewt said...

Stuart—I read the entire Wolverine site years ago and it made an indelible impression. Not only in terms of the effect of sugar and soy oil, but also the story of how he landed in the hospital in the first place (a botched "routine" colonoscopy). A friend of mine is the editor of a prestigious pathophysiology textbook. She advised to never get health care in Florida.

Peter—out of curiosity I looked up propofol. "... Its uses include the starting and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation." If Intralipid is the vehicle used for it, and the soy oil may be a recipe for poor outcomes in terms of ARDS, maybe the physical restraint is preferable.

Peter said...

cave, propofol is a near miraculous anaesthetic induction agent. Those of us brought up on thiopentone and methohexitone would never want to go back. But it really is intravenous soybean oil and I would not want this for myself in the ITU. But then I absolutely would not want to be awake/conscious during IPPV at the time that my lungs finally failed. The reports from Italy suggest that this is not a pleasant process.

As Stuart commented there are IV lipids based on fish oil or MCT oils. The later might be a better option. Solubilised beef dripping would obviously be the best option but I'm not holding my breath 'til that one arrives!

Peter

Justin said...

Peter, sorry if I missed any relevant posts on this. I just started following you after a multiple year hiatus. Do you have links to papers specifically looking at ARDS and propofol administration? I understand how linoleic acid can be converted to arachidonic acid which can potentially lead to increased levels of arachidonate-derived proinflammatory metabolites through the ecosonoid pathway. If you have posted anything recently and I have missed it, I apologise. Thanks again for such an awesome blog!

Peter said...

Hi Justin,

I'd never made the connection between propofol and ARDS until about a week ago and currently it's only the observational studies tying plasma FFA PUFAs to ARDS (a friend sent me the full text of the abstract I linked to, ask if you'd like it). However propofol induction is well recognised as a trigger for pancreatitis https://high-fat-nutrition.blogspot.com/2019/08/who-gave-you-pancreatitis.html and there is some concern over enteral vs parenteral feeding in severe pancreatitis with poorer outcome from parenteral (containing Intralipid) https://www.ncbi.nlm.nih.gov/pubmed/24687866. Parenteral feeding is much simpler to set up than enteral, placing an enteral tube in the small intestine is a lot more complex than placing a central venous line. I'm not up to speed about the current alternatives to propofol for ITU sedation, it was pretty popular when I was still active in anaesthesia. Midazolam has its own problems. There is some interest in medetomidine. Perhaps it could be done... Have to say I've not hunted particularly hard as yet.

Peter

Justin said...

Thanks a lot for the respond Peter! Having fed lambs with a feed tube hundreds of times, I can only imagine what it would be like to snake a tube past both the esophageal and pyloric sphincters in a human! Thanks for the links and look forward to spending some time reading them.

Justin

DrCate said...

18 months.