Monday, November 28, 2022

Coconut oil and obesity

Over the past six months or so I've spent a lot of time thinking about all sorts of things. Two of my main irritating problems are the obesogenic effects of diets high in fully hydrogenated coconut oil or butter oil, at least for rodents.

These matter for me because rodents (other than the C57Bl/6 mouse) mostly have perfectly normal mitochondria and so provide a reasonable model for extrapolation to humans.

I cannot explain these via the F:N ratio of the lipids so they then challenge my whole hypothesis. I guess the first possibility is that I am simply incorrect so should abandon my pet ideas. Possible, but not easy.

Second is that the medium chain triglycerides in coconut oil (and butter?) are handled differently from longer chain lipids. They certainly are, with limited penetration in to chylomicrons and marked diversion to the liver via the portal vein as free fatty acids. The liver "sees" them, adipocytes don't. To some degree, nothing in biology is 100%.

Also the fate of medium chain fatty acids in peripheral cells, when they do get there, may be different to longer chain fatty acids. I am reminded of the very poor insulin secretagogue effect of octanoate on the isolated pancreatic preparation in

The Insulinotropic Potency of Fatty Acids Is Influenced Profoundly by Their Chain Length and Degree of Saturation

which makes octanoate look worse than linoleic acid in promoting insulin secretion (and presumably the same applies to generating insulin resistance in target cells). This would fit with medium chain fatty acids being obesogenic despite their desirable F:N ratio, but without any insight as to how or why.

The final possibility is that the effect of linoleate oxidation differentially affects high and low fat diets. Under low fat diets the ability to resist insulin comes, in my opinion, from the input of electrons via the glycerophosphate shuttle converting an NADH input to an FADH2 input to the electron transport chain. From fatty acids it's all about NADH vs FADH2 at electron transporting flavoprotein dehydrogenase. Do these mechanisms kick in at identical levels of caloric ingress or are there subtleties of high vs low fat diets?

So lots of pondering and no answers.

I have extracted a little more information from this paper

The group didn't measure the linoleic acid content of the diets they fed but their intervention diets were composed of materials with very tightly defined LA contents, so their calculated amounts are likely to be accurate.

Here we have the growth rates of mice on chow (5001 "vivarium" rodent food termed Viv) or on an high fat diet based on fully hydrogenated coconut oil + 2% of calories LA or partial replacement of coconut oil to give 10% of calories from LA. Here are the growth curves:

The impression here is that the blue line of the fully hydrogenated coconut oil diet (+2% LA) is more fattening than the (grey line) Vivarium chow, though not as badly as the orange line of the 10% LA diet.

You could start to think about all of the differences between 5001 and the various high fat diets but the simplest is to extract the LA contents from Table 1:

which lets us label the growth graphs with the LA contents thus:

An interesting question might be where 4% LA (Surwit-like) diet might have placed the growth curve, even more interesting would be to almost half the LA% to the 1.2% supplied by 5001.

That's not something that is easy to find. Obviously there is a certain amount of work with linoleic acid free diets used to show the problems and benefits of essential fatty acid deficiency in rodents, usually based around fully hydrogenated coconut oil. I quite like this one where borderline essential fatty acid deficiency is remarkably protective against systemic lupus in a mouse model using non-hydrogenated coconut oil

So limiting linoleic acid to levels present in non hydrogenated coconut oil (less than 1% LA) allows growth and health in this model while producing zero obesity using approx 40% of calories from coconut fat.

So it appears that the obesogenic effect of coconut oil based diets is not intrinsic to the MCT content but some obesogenic effect of linoleic acid on this background is present at 2% of caloric intake and spectacularly so at 10% of calories.

Here's a little histopathology for those PUFA-philes who follow any of the conventional diet gurus on 'tinternet. If you like soybean oil as a health food, you go for it, fine by me!

Liver histopath after 35 weeks on 5001 chow. Red dots are lipid:

On fully hydrogenated coconut oil with a mildly obesogenic 2% of calories as soybean oil derived linoleic acid:

and on a cardiological nirvana of 10% calories from soybean oil derived linoleic acid:

Clear balloon cells are very poorly liver cells. Now, I wouldn't wish such a liver architecture on to anyone but if I was pushed in to a corner I might consider Prof Risérus, lead author of

as being a possibly deserving recipient.

Co-authors Walter Willett and Frank Hu might be candidates too.



Puddleg said...

This experiment might help answer some of those questions

In any case it's good to see experimenters resting the extremes in humans.
A little pedantry here - it's wrong to call MCFAs in natural TGs MCTs. An MCT is all-MCFA and this rarely if ever happens in nature. Also MCTs are made with C8-10 whereas MCFA (I believe) includes up to C14.

Tucker Goodrich said...

I've been pondering similar questions, Peter.

There are clearly some confounders to effects of LA, such as DHA, the dairy fat Mozaffarian patented, and perhaps others, like the MCFA in the paper George links to above. (I hate hypercaloric diets. Show me that the effect exists on a non-excessive diet...)

It also seems that a middle range of LA + fat is worst, for reasons I'm not entirely clear on, as shown in Speakman's paper (Hu et al., 2018: 10.1016/j.cmet.2018.06.010).

George: Do you think someone should tell the authors of that paper looking at LCSFA-HFD that 18:1 is not a SFA? It's the vast majority of the fat they're labeling SFA... Sigh.

Steve said...

I'm probably remembering this incorrectly, but isn't the difference in protein in the diets significant too? Isn't the difference (20% vs 24%) somewhere near the cutoff for those experiments that show that most organisms will eat until their protein requirements are met? The diets are iso caloric, so the HF mice will be hungrier.

Also, protein calories aren't usually burned for ATP production so the HF are getting ~4% more energy calories per day in spite of being possibly hungrier.

lapis_exilis said...

"Now, I wouldn't wish such a liver architecture on to anyone but if I was pushed in to a corner I might consider Prof Risérus, lead author of Dietary fats and prevention of type 2 diabetes as being a possibly deserving recipient. Co-authors Walter Willett and Frank Hu might be candidates too.". - Peter reveals his vicious side, mwahaha! ;)

Jokes aside though, I have definitely been wondering about butter. I'm no scientist of any kind, I just know that when I indulge - i gain weight like crazy, even on nearly 0 carb diet. N = 1, but reading this makes me feel a little less insane, which is nice :)
- shade

cavenewt said...

OK, dumb question. I'm curious about the significance of hydrogenated coconut oil. Is that different from the stuff we buy at the grocery store to cook with?

Gyan said...

Welcome back Peter.
Hopefully you would comment on the mysterious situation with excess deaths in the Western countries. Is it some kind of vaccine- reinfection interaction as has been recently posited?
For instance by blogger Radagast at rintrah. nl

Eric said...

Peter, glad you're back! From what I hear, Walt Willett is stick thin.

lapis, I eat butter (and full fat cheese) like crazy (easily more than bread by weight) and am doing fine. I get the impression I put on weight when our nut jar is filled with a fresh and tasty mix and I eat a couple of handful per day. When the mix is not nice but not obviously bad enough to throw out, I eat few if any and tend to lose weight.

There's three kinds of coconut oil that I am aware of. There's the (virgin and organic) kind that comes in jars. It is semi-transparent, and you can easily get a spoon full when it is at room temperature. According to wikipedia, it is only 92% saturated on average, with 5 - 10 oleic and 1 - 2.5% linoleic.

Theres the kind for frying and cooking that (here in Germany) comes in cubes wrapped like butter in aluminum coated paper. It is also semi-transparent. According to the nutrition label, it is 92% saturated. When refridgerated, it is certainly much more brittle than refridgerated butter. I just left the remaining piece out to see what it is like at room temperature.

Then there is fully hydrogenated coconut oil. It comes in bars with ridges like chocolate and is fully opaque / white. It shatters almost like glass when cold and stays very hard at room temperature. According the label, it is 97% saturated.

cavenewt said...

Thanks, Eric. I am in the US and I've never seen the second two kinds you mentioned. I buy coconut oil by the gallon and it's the virgin and organic kind. "Room temperature" can be relative. In the summertime my "room temperature" is 80 to 90°. My coconut oil melts at 76° so it's only really solid in the wintertime, and even then it's easy to scoop spoonfuls out.

I was curious why they would use hydrogenated coconut oil in these studies, but if it's commoner in other parts of the world maybe that's why, or they wanted to boost the saturation level or something…

Eric said...

After leaving the second kind out for a few hours, I now think it is the same as the first, though maybe not organic and virgin.

Passthecream said...

CaveNewt, hydrogenated coconut oil is to coconut oil as margarine is to other vegetal oils except there is little if any trans fat in fully hydrogenated CN oil. There is approx 6% oa and 2% la in natural coconut oil and fully saturating this via hydrogen + catalyst gives the soft natural oil a hard waxy consistency. This is known in Au as Copha(tm), used to make chocolate crackles, childhood treats which I think should be included in these mouse diet experiments.

Fat plus sugar plus cocopops. Do not try this at home.

Unknown said...

I've missed reading your blog Peter! Now that I'm on a holiday break, I'll be soaking up some hyperlipid!

Unknown said...

I wonder how much of a wild rat / mouse is nuts and seeds. Is this really seasonal such that fattening up periodically is just "part of the plan". Or are there things in whole nuts / seeds / foods that balance out the LA part? I'm just trying to figure out if people eating nuts is just as strange as eating french fries or nuts are actually K to eat.