Sunday, April 17, 2011

Palmitic acid: the horror never ends speculation

Back in her PhD days my wife attended a seminar presented by a visiting researcher on some aspect of the inflammatory cascade. It was very technical and focused around the interaction of a certain ligand with its receptor at some critical juncture in whatever process they had devoted the last n years of their life to studying.

The ligand was all-cis-docosa-4,7,10,13,16,19-hexa-enoic acid. No one in the room had any idea what this stuff was, certainly not the extremely intelligent presenter, other than as a molecular key to a molecular lock. It's a stock lab reagent purchased in research grade purity from any one of a number of suppliers. You could equally order cervonic acid.

At the level of reductionism these people can work at there is no need to be aware that all-cis-docosa-4,7,10,13,16,19-hexa-enoic acid is available in gel caps from Holland and Barrett or is present in the nearest can of sardines as the more familiar DHA.

So imagine you are some newbie PhD student. You walk in to the lab and are handed a reading list a mile long. The lab has certain research lines you are going to slot in to, particularly focused around inflammasome activation by fatty acids. You got the post because you had picked up extensive experience with cell culture and inflammation research based around both endotoxin and asbestos, plus a track record of multiple Nature publications from your undergraduate work.

The lab you walk in to has cells in culture which go ballistic on exposure to utterly physiological concentrations of palmitic acid. At least six widely differing cell types behave in exactly the same way. This looks like a generic effect and puts palmitic acid up there with asbestos as a proinflammatory agent. You switch to Flora that very lunch time, and spread it thinly too.

The lab also has an animal house in the basement. The rats are either fed a standard lab chow or a red coloured greasy type of pellet oozing fat. The lab techs feed and water the ratties. Your job is to compare molecular aspects of white blood cell inflammasome activation as the high fat rats get fatter over the weeks. Once a fortnight someone brings you a blood sample to work with but, apart from that, you will never see the rats again...

What do you question? EVERYONE knows that eating fat makes you fat. Fat is fat. Do you give a monkey's about EXACTLY what is in the pellets which stain the tech's hands red when they do the feeding? It's a standard obesogenic high fat diet from www.testdiets.com. All obesity research uses it or something similar...

Would you sit down and work out whether the hydrogen atoms on either side of the central double bond of one type of fatty acid in one constituent of the 5TJN are aligned on the same side or on opposite sides of the bond? You know, cis vs trans configuration...

It's sloppy. It's possible. People will really be able stand up and say, as Ting does:

"The simple message is to avoid fatty foods as much as possible."

They probably have no doubts. They believe. It's complete bollocks of course. But I have this concept of how things work...

Peter

21 comments:

Paul Jaminet said...

The big defect of much academic science is that researchers are over-specialized, and only know their specialty.

They are the blind men who only know their part of the elephant.

If their funding came from some other source besides the leading groups in their field, then scientists would learn a wider range of relevant facts.

Emily Deans, M.D. said...

I just reviewed a bunch of rat binge-eating studies - and all of them were done with vegetable oil. At least the reviewers at the end of the line were honest about it. But this insane focus on simple macronutrient leaves us with a vast quantity of useless studies.

Ned Kock said...

Peter, a little off topic.

I am reviewing an article with data suggesting that alcohol consumption at or above a certain level (21 drinks/week) increases type 2 diabetes risk in men and decreases it in women.

I double-checked it, and the results don't seem to be due to measurement error. Moreover, they have been replicated, in different contexts, a few times.

Have you seen this anywhere? Any idea of the possible reasons?

Aaron Blaisdell said...

In all fairness to the researchers, the "high-fat" diet fed to the rats does seem pretty close to the contemporary SAD diet, and in that context is relevant. But of course, that doesn't give them any right to illegitimately smear saturated fat or even "fatty" foods in general.

blogblog said...

A PhD student learns more and more about less and less until they eventually know everything about nothing.

Isaac Asimov
writer and Professor of biochemistry.

Aaron Blaisdell said...

@blogblog,

I've always loved that Asimov quote. Having gone through that black hole and come out the other side relatively unscathed, I'd add to it "...and then learns less and less about more and more." This would apply only to true scholars who pursue knowledge for its own sake and must always scratch the itch of tugging at each puzzle piece they encounter, no matter where it leads them. This hour-glass shaped system of epistemology certainly characterizes my journey quite accurately. I think this applies to Paul Jaminet, Emily Deans (an M.D.), and good ol' Petro himself (a DVM). This is the fascinating thing about the contemporary internet, the ability to bring us together to catalyze scholarship!

Kurt said...

Great post.

One has to have the insider's experience of seeing the sausage made - actually doing research and publishing - to have any appreciation for how misleading and completely wrong "legitimate" science can be.

It is simply impossible not to be biased, and the biases always determine what you ultimately find to be "true"

Hence the plethora of animal and human studies that "prove" that never-seen-in nature isolates of animal fats like PA are harmful...

It won't ever stop until new questions are asked.

William said...

blogblog, awesome quote
Kurt, I sway between “rite of passage” and the necessity of “seeing the sausage made”

Susanna said...

Peter:
My first blog comment ever, and I've been reading them a long time. You must be interesting.
Question (off your palmitic acid topic, I know): Why do diabetics suffer ketoacidosis but it's extremely uncommon on a ketogenic diet? Is it really the KETONES making the blood acidic....or is it somehow the high blood glucose that affects pH; or is there some kind of hepatic dysregulation that causes overactive ketogenesis in the liver?

youtube.com said...

That is because you don't understand the peer review process. Let me use this comic in order to explain it for you!

Swamp gas.

john said...

ketosis and ketoacidosis are two different concepts. Ketosis is the end process of beta oxidation of fats whose by products stop the liver's ability to make new gluocse......the gluconeogenesis pathway. Diabetic ketoacidosis is the a pathologic state that diabetics find them selves in when they have a ton of leftover glucose in their blood that can be used by the liver or muscles because of hormonal and metabolic issues related to the diabetic disease itself. IE insulin resistance of the liver and muscle and autoimmune destruction of the beta cells by chronically high insulin levels. Ketosis is great for fat loss and body composition changes. Ketoacidosis is something a diabetic has to avoid by monitoring their diet and glucose when they are on insulin exogenously. Other conditions can cause DKA but they are important only for us doctors who treat them. The key os for the lay public who is learning not to ever equate the two because they sound the same. They are radically different and have different consequences.

CarbSane said...

Actually John, ketoacidosis is the result of the over-stimulation of ketogenesis by the elevated free fatty acids prevalent in diabetics.

Stan (Heretic) said...

Peter,

Similar story was I believe mentioned by Mary Enig in one of her articles (if I remember correctly) on the supposed toxicity of erucic acid.

Earlier studies done on redent fed pure erucic acid found it toxic to a heart muscle, while more recent studies done with even a small amount (~10%) of butter added to it showed no toxicity.

It could be similar to the presumed (by some respondents to your blog too) toxicity of vegetable oils, in general.

I suspect that vegetable oils and fats, even palmitate, may indeed be harmful - to vegans and only to them and to other victims of "healthy" eating, who may consume plant fats as their only fats.

Carbs are carbs but fats are not all equal!

Stan

Peter said...

Aaron, yes, had they described the diet as "Western", "Cafeteria" or "High Sucrose" I would give them kudos and EVERYONE interested in high fat diets could just ignore the study and awaited the apology from the CSPI for the millions of premature deaths resulting from switching from animal fat to partially hydrogenated fats.

Hi Susanna,

A ketogenic diet or a prolonged fast will produce ketone levels in the region of 2-3mmol/l with physiologically appropriate insulin levels. DKA will produce ketone levels around 20mmol/l, an order of magnitude higher. DKA requires either absolute insulin deficiency or severe relative insulin deficiency (acute onset insulin resistance coupled with the inability to increase insulin levels) so utterly mangles potassium homeostasis in addition to allowing unrestrained lipolysis/ketogenesis. I don't think the hyperglycaemia per se is the problem with pH...

Swamp gas,

That explains a lot and is a real education. I was puzzled as to how peer review worked. There is a similar situation in which you can try to argue with your PhD examiners. It doesn't matter how wrong they are, if you don't put in their stupid corrections there is that trap door under three years of your life.........

Stan,

I missed that tale. I'm considering if the a mechanism for the toxicity of elaidic acid might be through acting as a palmitic acid mimetic without the ability to fit in to normal physiology. It's an interesting area to speculate. Of course just saying NO would help...

Totally off topic, there's a documentary coming up on R4 looking at Chernobyl 25 years down the road, I think talking to Jaworowski. I enjoyed his rather rant like piece about the accident (if you can call it that, after reading about the stupidity that went on in control room leading up to the explosion). Seems very similar to the Taiwan Co60 observations.

Ned, that's interesting. I can think of possible explanations, is it published? Does it specify the types of drinks involved?

Peter

blogblog said...

Many years ago when I was an undergrad I mentioned an interest in doing a PhD. The lecturer instantly replied 'PhDs only exist to provide universities with a cheap source of labour'.

Stan (Heretic) said...

Peter,

Thanks for Jaworowski paper link!

It is amazing how much distorsion has crept into radiation medicine! It appears to be virtually impossible to challenge an established hypothesis, in this case the Linear Non-Threshold. No matter how many facts to the contrary is shown.

I have to digress a bit and say this, since this topic was raised by Aaron and Blogblog:

- There are several steps in scientific mastery, the ability to pass through a narrow-focus trap and become open-minded again, is but one. That is where many of the medical scientists are failing. The second stage of mastery is real independence, including financial independence.

Without an independent source of income or a side job, a scientist would remain a grant-chasing slave no matter how intellectually open he/she tries to be.

Stan

blogblog said...

@Stan,
the golden age of science from 1650-1950 was all about independent mostly self-funded researchers - Cavendish, Boyle, Hooke, Newton, Darwin and Einstein.

In contrast modern corporatist "big science" such as the Human Genome Project has achieved remarkably little for each (billion) dollar(s) spent.

I would even go so far as to say that the independent unfunded researchers such as Dr Lutz have contributed more to human health than any big science project of the lat 50 years.

Stan (Heretic) said...

blogblog,

Totally agree!

I would also add Drs. Jan Kwasniewski and Robert Atkins to the list.

Ned Kock said...

Hi Peter. Yes, it is published, and I blogged about it here:

http://bit.ly/fL8Rpc

Strange ... but true!

Jeff said...

David Katz appears to be citing this and other studies suggesting that sat fat intake leads to inflammation.

http://www.huffingtonpost.com/david-katz-md/saturated-fat_b_875401.html

Peter said...

Hi Jeff, I can't reply. I maybe be rude on many occasions, but my opinion of the linked article does not want printing. The world is full of idiots. Let them eat grains.

Peter