Background: Propofol is a mainstay anaesthetic induction agent. Its use is associated with occasional pancreatitis episodes. I won't wander aside about the poor dog which was referred for cataract surgery and which did eventually recovered from its perioperative fulminating pancreatitis.
Propofol is dissolved in what is essentially Intralipid, a soybean emulsion used for parenteral nutrition. The lipid emulsion gives a transient hypertriglyceridaemia. Hypertriglyceridaemia from any cause is associated with pancreatitis.
Me, being me, would automatically blame the PUFA in the Intralipid. But then I would.
I came across this paper by accident this morning:
Distinctive roles of unsaturated and saturated fatty acids in hyperlipidemic pancreatitis
It's good. The group even give you the glucose concentration used in their cell culture, 0.2%, ie 200mg/dl or around 10mmol/l. Not normal but hardly seriously pathological.
Aside: Less innocent groups keep quiet about glucose concentration and can reliably show endoplasmic reticulum stress and any other nasty attributable to palmitic acid. With how much glucose??? End aside.
This is what they found:
"Unsaturated fatty acids at high concentrations but not saturated fatty acids induced intra-acinar cell trypsin activation and cell damage and increased PKC expression"
So. If you have a genetic hypertriglyceridaemia, say lipoprotein lipase deficiency, and you get acute necrotising pancreatitis (not fun) there is every possibility that it was induced by the high content of polyunsaturated fatty acids in those triglycerides and the FFAs derived from them.
Which means that your cardiologist put you in the ITU. Avoid saturated fats, replace them with polyunsaturated oils. Thank you Public Health England and your equivalents world wide.
The converse might well be that loss of the gene for lipoprotein lipase, or similar loss, might not have been a big deal when humans lived by eating elephants. Or even until corn oil took off as a cholesterol lowering scam.
Peter
I can't see any mention of parenteral nutrition, soybean oil, or colonoscopies without being vividly reminded of the story laid out on the site Roar of the Wolverine. The soybean-specific post, only part of his story, and specifically mentioning Intralipid, is at http://roarofwolverine.com/archives/1557
ReplyDeleteI ran across this site while researching IV ports, but it should be of great interest to anyone with a colon. Second important factoid: don't ever undergo a medical procedure in Florida.
He says in the United States they *require* the soybean oil crap for this usage but allow Omegaven (a fish oil product) to be used only in children and *only after liver damage is caused by Intralipid*; and that in Europe humans are not required to use the soybean oil crap. Have things changed, or perhaps my memory is off…
It's getting a little too easy, isn't it Peter?
ReplyDelete@cavenewt
ReplyDeleteSoybean oil is about 50% LA ...
Also found in baby formula - (real human breast milk is very low in PUFA - drives some researchers crazy - they have not let go of the essential fatty acid mantra)
From wiki:
In the 2002–2003 growing season, 30.6 million tons (MT) of soybean oil were produced worldwide, constituting about half of worldwide edible vegetable oil production..
And this other bit makes me think big-ag knows the public is figuring out the dangers of PUFAs:
Three companies, Monsanto Company, DuPont/Bunge, and Asoyia in 2004 introduced low linolenic Roundup Ready soybeans.
Good, but doesn't explain why my 40% corn oil mice had insulin 2x and leptin 5x to controls. Could it be a repair mechanism?
ReplyDeleteSee here for a similar effect with sunflower:
Deletehttp://yelling-stop.blogspot.com/2018/06/whats-worsecarbs-or-seed-oils.html
It's an immune response. Oxidized n-6 is a homolog to LPS, which also raises leptin and insulin.
Tucker, from the study:
ReplyDelete"Thus advocating diets rich in n-6 PUFA for diabetic patients could accelerate the impairment of myocardial contractility."
As the young people say: OMFG.
How many researchers are actively skewing their research in order NOT to come to such conclusions?
PS:
Randomly googled one of the authors, found his twitter, where he retweeted this:
"Mariëtte Boon
@BoonMariette
Aug 13
Proud of our latest publication in @AJPEndoMetab - only 1 day of high fat diet feeding induces insulin resistance in brown adipose tissue in mice.
Makes you think twice about your X-mas dinner...."
Oh well...
@karl
ReplyDeleteYeah, I know. Born in 1954, I'm sure I was given formula and not breast-fed. Wonder how much Boomer chronic illness has that as a contributing factor...? My parents also smoked and drank (I've never smoked). Makes me amazed and thankful to be relatively hale and hearty, aside from one mystery autoimmune thingy.
Tucker, I like that last table. However, even if I give you ox n-6 is LPS homologue, why would insulin resistance trigger hyperinsulinemia? I thought the causation runs the other way?
ReplyDeleteI am not sure they keep quite about the glucose concentration used. Usually, ready-to-use media are used and the concentration of glucose can be traced back in the manufacturer's technical sheet or simply checked online. So, they just say..." medium XXX was used...." The rest is up to the reader.
ReplyDeletebtw: I am sorry for the parliamentarian crisis you are in atm. It is awful! It feels dictatorial somehow.
Thanks Alex, for you concerns. Me too.
ReplyDeleteThe concentration thing is always an issue. Just browsing Thermo Fisher's site, they sell 40 odd DMEM derivatives. About six or seven have 1g/l glucose, two have no glucose and all the rest have 4.5g/l. I don't think there is a conspiracy. I think every routine DMEM cell culture uses 4.5g/l glucose and no one feels the need to specify.
It's particularly problematic when 4.5g/l, ie 25mmol, is invariably toxic with palmitate and non toxic with PUFA. That is a gift horse that very, very few labs would look in to the mouth of!
And, actually, 25mmol/l glucose with 1000micromolar palmitate is really looking at serious diabetic pathology and may have some relevance to which cells die under the ministrations of the ADA etc. But that's never how it's couched and you have to assume gross hyperglycaemic levels of glucose when you read about palmitate toxicity...
Peter
Nifty study on fasting via Attia. slCAM-1 down nicely, but PUFA up
ReplyDeletehttps://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30429-2?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1550413119304292%3Fshowall%3Dtrue
Peter,
ReplyDeletecan you explain if it is palmitic acid or actually palmitate (which?) is toxic together with glucose and why?
The only tidbit I found was this from wikipedia, which seems to be the old all saturated fats increase LDL story:
According to the World Health Organization, evidence is "convincing" that consumption of palmitic acid increases the risk of developing cardiovascular disease,[18] based on studies indicating that it may increase LDL levels in the blood.
Thanks
Eric
This comment has been removed by the author.
ReplyDeletePalmitic acid and palmitate are the same thing,effectively. They're interconverted as needed in the body.
ReplyDeleteAlt, the question to me is how much of the benefit could be achieved through a ketogenic diet without all the tedious not eating for 36 hours at a time? The control group should have been there and should have been keto…
ReplyDeleteEric, from the protons point of view it is that saturated long chain fatty acids are a large driver of input to the CoQ couple in addition to complex I. Given enough input through electron transporting flavoprotein dehydrogenase the CoQ is present as CoQH2 which provides electrons to travel backwards through complex I and generate ROS which are physiological at low levels but if taken to extremes, ie palmitic acid at 400micromolar with glucose at 25micromolar, rapid badness occurs. There are probably other controls exerted on the electron transport chain by fatty acids but these are proving difficult to pull out of the literature.
Tucker, yep.
Peter
Peter,
ReplyDeletethanks for the attempt to clarify this but after not following here for several months, you lost me :) At least as to how saturated fatty acids do more harm than others.
I guess I will have to read the paper you quoted in a follow on post:
https://www.ncbi.nlm.nih.gov/pubmed/12933690
I also found this:
https://www.ncbi.nlm.nih.gov/pubmed/31383924
Seems to say that oleic acid is plenty good for ailing beta cells, no need to go to nasty PUFA.
Eric, just not making yourself hyperglycaemic leaves you to consume as much palmitic acid, and stearic, as you like. Never blame the fat for what the sugar did!
ReplyDeletePeter
Peter, I am not doing that, just wondering. To my mind, saturated, monounsaturated and polyunsaturated of similar chain length should be on a continuum, which they are not. The El-Assaad-Paper states that oleic acid is the optimum, with palmitic being much more critical and PUFA no so much.
ReplyDeleteThey offer a bunch of potential explanations that don't appear all that convincing.
The other finding in a number of studies is that adding even quite small amounts of oleate to palmitate during cell culture essentially eliminates the palmitate/glucose toxicity. Can't find one to hand but they are about. The only live model I've found is the SCD-1 knockout mouse fed a low fat diet. Almost all fatty acids are then synthesised as far as palmitate/stearate but cannot be desaturated to palmitoleate or oleate. The mice are slim and very healthy unless they are ob/ob diabetics when their beta cells perform apoptosis, presumably from too much ROS generation without the moderating effect of MUFA. For the rest of us dietary MUFA seem irrelevant. Here are the papers
ReplyDeletehttps://www.pnas.org/content/99/17/11482
https://diabetes.diabetesjournals.org/content/56/5/1228.long
There is a lot to think about in both of them and I've not studied them for a decade or so!
Peter
Yeah, the mitigatign effect of oleate was also mentioned in one of the two papers I linked. I saw that and thought one more thing that is hard to understand.
ReplyDeletePalmitate with an FADH2:NADH ratio of 0.49 drives reverse electron transport well. Oleate has an FADH2 of 0.47-ish and doesn't. It doesn't take much oleate added to palmitate to markedly reduce RET. It should take even less PUFA. Unfortunately RET is what stops you getting fat!
ReplyDeletePeter
Just wanted to say I really appreciate the quality of your blog and how you're still at it after more than a decade. I've been reading off-and-on for several years, and I'm always excited to see more posts for me to catch up on :)
ReplyDeleteYou're welcome Jill
ReplyDeleteI'm a nurse anesthetist (assuming they don't exist in Europe) and I remember doing blood draws on patients in the ICU and seeing the fat in the blood in people on propofol drips for long periods. The triglycerides could get very high.
ReplyDelete