Tuesday, December 24, 2019

Stearic acid: Skinny-skinny vs skinny-fat

This paper came up in comments to the last post:

Dietary Stearic Acid Leads to a Reduction of Visceral Adipose Tissue in Athymic Nude Mice

I think we can say that, at least in athymic nude mice (which do not seem to be derived from the C57Bl/6 strain), omega 6 PUFA do not cause obesity when compared to either a low fat or high stearic acid synthetic diet (ie the low fat arm is equally synthetic, not more "food-like" ie not chow). At least when you look at total body weights:

So omega 6 PUFA appear to get a free pass here. The actual composition of the diets is in Table 1 of this previous paper and all four contain generous amounts of starch and equal amounts of sucrose:

Dietary Stearate Reduces Human Breast Cancer Metastasis Burden in Athymic Nude Mice

However if you dexa scan the mice you find that the low fat, corn oil and safflower oil groups all have reduced lean mass (probably muscle) and increased visceral fat mass compared to the stearate group. A picture is worth a thousand words so here are some postmortem images with the size of the inguinal fat pads outline by the authors of the paper (no need for me to doodle on this one!). Fig 3:

I really like these images.

Now, cavenewt questioned the relevance of weight/fat alterations from stearate compared to other potential health effects, particularly its affect on cancer metabolism.

The third paper from this same group is

Prevention of carcinogenesis and inhibition of breast cancer tumor burden by dietary stearate

I've been through all three papers and searched on "insulin". The group appears to have no concept that insulin has anything to do with adipocyte size or cancer progression.

A slight handicap when it comes to insight.

In the stearate-visceral fat paper there is a single measurement made of plasma insulin/glucose. Insulin does not vary between diet groups but glucose is significantly lower in the stearate group. I have been unable to work out if the measures were fasting or fed, or even what time of day the samples were taken (ie when the mice were killed). I think that with glucose values in to 200-250mg/dl range these were probably "fed" glucose and insulin levels. The paper does not give us the measured insulin levels, merely that there was no statistically significant difference between groups. But insulin levels come with such huge standard deviations that getting a p value below 0.05 with small group sizes is not going to happen. A ns result does not automatically mean that there were no differences.

Of course a single insulin measurement at one terminal time point tells us nothing about the long term 24h exposure to insulin of the mice, of their adipocytes or of their cancer cells.

So we have to, once again, look at the significance of the changes in fat distribution to attempt to gain insight in to overall insulin exposure. I spent quite some time looking at visceral fat and its significance early last year in this post:

On phosphorylation of AKT in real, live humans. They're just like mice!

and on how stearate might avoid systemic hyperinsulinaemia here:

Dairy and diabetes

Visceral fat is a surrogate for chronic hyperinsulinaemia, particularly fasting hyperinsulinaemia. While I consider non-inflamed visceral fat to be completely benign, or even beneficial for controlling the hunger of fasting, the insulin which maintains that visceral lipid storage is not benign. Chronically elevated insulin (or, more accurately, insulin signalling) should drive both visceral fat storage and xenograft tumour growth in the mice. Probably in humans too.

Happy Solstice and assorted mid-Winter celebrations. If you live in the northern hemisphere that is. Not that I envy those with a Solstice-on-the-beach-without-wooly-hats-and-gloves situation!



karl said...

So a quick browse of sources of stearic acid.

Reagent grade is quite expensive.. there is 'food grade' available.

Search terms: stearic acid food grade

What I find claims it comes from plants - from Malaysia.. Just want to note here that 'food grade' does not mean food safe... it is not a well defined term. Sort of means if it touches your food not likely to cause harm.

The other bit -- moving from 16 C long chains to 18:

16:0 palmitic acid (Hexadecanoic acid) 62.9°C F:N ratio of about 0.48 That's 15 FADH2s and 31 NADHs - oxidizing . (palm oil - Butter, cheese, milk and meat also have some)
17:0 Margaric acid (Heptadecanoic acid) - in Milk
18:0 Stearic acid (Octadecanoic acid) 69.3°C Found in Cocoa
Stearic acid is the only long chain saturated fatty acid that does not raise LDL cholesterol(can't find reference?).
Also - stearic acid has been shown associated with increases in Lp(a)

Looking at a bit about de novo lipogenesis pathway
( this paper says "Similarly, stearic acid may promote adiposity ..." More of the usual correlative:causation confusion? quotes papers focused on insulin sensitivity )

It makes me wonder if this tail end of DNL - where C16.0 can go to C16:1n-7 C18:1n-7 or 18:0 18:ln-9 16:ln-9 might actually be part of regulatory loop - or effected by genetic variations?

cavenewt said...

Peter, thank you for the Christmas gift of addressing my question. Am now 3/4 done with radiation treatment for hormone+ breast cancer. I don't glow in the dark yet but am getting a nice tan line, and as yet no unpleasant side effects like the dreaded fatigue, for which I can possibly thank years of low-carbing and more stringent keto since diagnosis.

Also thanks to keto is the ease with which I can hold my breath for DIBH (https://en.wikipedia.org/wiki/Deep_inspiration_breath-hold) which is how they get your heart out of the line of fire during zaps. When reading about breath-holding in hyperlipid comments in the past, and Navy SEALs experimenting with keto for that purpose, I never expected to benefit from it myself. Life is endlessly interesting.

Lots of folks on the Croissant diet subreddit (r/saturatedfat) are discussing sources of stearic acid—apparently the easily available food-grade (in US anyway) is half palmitate and has the food consistency of crayons but with a higher melting point. Preferring whole-foodish sources to supplements, I've been eating strictly ungulate protein, and cacao nibs with morning tea—but will get some cacao butter which seems a higher stearate %, though the nibs do become habit-forming and are nicely crunchy.

Alex said...
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Stylooke said...

Peter, thanks for the excellent blogs. Do you have any idea on the F/N ratio of medium chain fats (C12 in particular)? These as known do not require the carnitine shuttle which makes me wonder how they factor in, as I'd assume they get preferentially oxidised over the LCSFs. Ray peat has made the claim that farmers tried to fatten their cattle with coconut oil, and that this also made them leaner rather than fatter.

karl said...

I read through the papers again - there are a couple of points:

The fatty acid types have an elephant sized confounding variable - to their credit, the authors come clean on it:
"Limitations of this study are that the corn oil and safflower oil diets contained fatty acids largely in the form of triglycerides while the stearic acid diet used non- esterified stearic acid. Also we did not prove that dietary stearic acid per se caused the reduction in visceral adipose tissue."

Once again one of the most basic scientific method restrictions about an experiment is it should have ONE variable.. How much extra would it have cost to get reagent grade bottles of the other fatty-acids?

The problem once again is that they don't seem aware that LPL moves fat in to fat cells. HSL moves fat out of fat cells. insulin is known to activate LPL in adipocytes HSL is inhibited by insulin - thus being in the form of a triglyceride ester sort of matters.. a lot I would think.

An other bit is while they noticed a difference in apoptosis - they didn't seem to consider that apoptosis is a mitochondrial function. (apoptosis starts by collapsing the mitochondrial membrane). Sort of a protons issue - ya think?

The narrative they were selling seems not to consider alternate pathways of causation - but whatever. I sure wish this had been a better controlled experiment - we are not going to ground our understanding with out chemically defined diets.


That being said - if we assume the difference is the C18 fatty acid -( I don't think we really can - but just to explore a moment) The stearic-acid mice had less fat - more muscle - lower BG.. Good stuff in my mind. The lack of difference in weight means that the stearic-acid must have move more. Having more muscle mass could account for the better BG levels.

Another bit to consider - they are looking at cancer - yet miss the huge correlation of BG - I tend to believe that high BG helps cancers out-grow the immune system. A good example that one can usually pick several narratives of causation. The reduction of cancer could be due to several things - not so simple.

cavenewt said...

“A high-corn-oil diet strongly stimulates mammary carcinogenesis, while a high-extra-virgin-olive-oil diet has a weak effect, through changes in metabolism, immune system function and proliferation/apoptosis pathways”


Kind of sucks that they did not consider a high-saturated-fat diet to go along with the polyunsaturated and monounsaturated and low-fat ones.

Peter said...

cave, you’re welcome. Overall I tend to think that Ron Rosedale has a point with his ideas about growth factors (insulin, IGF-1) being essential for tumour progression. But the tumour can’t progress without the metabolic changes to allow unrestrained anabolism, especially the abortion of the TCA and the diversion of citrate from the mitochondria to cytoplasm. And failure to generate ROS (ie PUFA ingestion/oxidation) to signal apoptosis in cancerous cells. This latter is probably how stearate works in addition to its effect to lower systemic insulin.

karl, they did talk about this. Happily these folks https://www.ncbi.nlm.nih.gov/pubmed/24286356 used a high stearic acid TAG with pretty much the same effect on visceral fat. The BG levels are quite interesting but I have to do a lot more thinking about that one. The stearate people appear to have almost no insight in to what they have achieved!

Alex, what gave you the idea that polyphenols do any good for anything? Yes, it’s the stearic acid!

Hi Stylooke, MCTs are interesting. I think they fall between palmitic acid and oleic acid, I did work it out once. However they are treated very differently. They are largely diverted to the liver from the gut, most LCFAs pass as chylomicrons down the thoracic duct and bypass the liver to get to adipocytes directly. MCTs are directed to the liver and what are not converted to ketones or oxidised directly emerge as palmitic acid, which is almost as good as stearic acid. Obviously palmitic acid has many of the benefits of stearate, just not quite so good.

The other fascinating point is that C8 is a major controller of flux through the ETC. Shorter FFAs (or their derivatives, the carnityl or CoA esters) do nothing but C8 is a significant inhibitors of complex III (from memory). Sadly the paper stopped at C8 but I would expect longer FFA derivatives to do much the same. Probably dependent on the length and saturation of the FFA. This aspect become crucial in avoiding excess delta psi when fasting, ie if FFAs are at 2000micromol/l that is a near infinite supply of delta psi substrate, which must be regulated… Not a hot research topic nowadays, sadly.

Sorry all for the typos which I will probably spot once I hit publish.


Peter said...

cave, finding anything good about palmitic acid is career suicide for a researcher. Stearate appears to be just about acceptable as a "good" fat but no one dares find this effect from palmitate, the devil incarnated in lipid form...


BigWhiskey said...

Peter, thanks for your time on the KetoCantina podcast.

cavenewt said...

This is kind of off-topic, but I was afraid that if I commented on the relevant post —"Fiber, inulin and cancer" at http://high-fat-nutrition.blogspot.com/2008/02/fiber-inulin-and-cancer.html—no one would see it.

I was interested to see the comments there about the carcinogenicity of inulin, a fructo-oligosaccharide. For several years I have taken inulin daily as a prebiotic. I also use konjac noodles when I want to make something like spaghetti. Glucomannan, the polysaccharide in konjac, is also a prebiotic. I just wonder what folks think about inulin versus other, non-fructose-derived pre-biotics like konjac.

They both appear to be good for the gut's mucosal lining, at least in some mice: "Konjac glucomannan polysaccharide and inulin oligosaccharide enhance the colonic mucosal barrier function and modulate gut-associated lymphoid tissue immunity in C57BL/6J mice". https://www.researchgate.net/publication/337112697_Konjac_glucomannan_polysaccharide_and_inulin_oligosaccharide_enhance_the_colonic_mucosal_barrier_function_and_modulate_gut-associated_lymphoid_tissue_immunity_in_C57BL6J_mice

(I have the full text if anyone is interested. There appears to be a lot of data regarding diets.)

Stylooke said...
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Stylooke said...

Thanks Peter for your thorough answer, seems theres still lots to discover! I'm not quite on board yet with taking isolated/hydrogenated stearic acid as it seems rather unnatural (not to mention lacking in any micronutrients!, but I guess I'll be increasing my chocolate intake )

Passthecream said...

Peter, two years ago I could get whole pieces of beef suet including the kidney just for the asking from my local butcher because it was a waste product but the abbatoirs don't leave them in the frames any longer. Too much demand for it I suspect.

Do you know what the suet quantities are in sheep and deer? Lamb is the local staple and deer is a feral pest where I live, at least the ones which haven't been roasted and rendered in our bushfires will still be.

Peter said...

No idea re quantities in a carcass. My main source of suet is now the fat around the hearts which I can still get at Morrisons. Nice roasted... Never waste the fat!


Passthecream said...

I've just made contact with a local deer and goat hunter so I will find out soon what they yield. I wish I could post some to you. If you can somehow get hold of it the Australian 'York' brand dripping is hard, waxy and comes from grass fed cattle. Lamb flaps are very cheap here and they can be rendered.

davemoriarty2 said...

How does this compare to papers like https://diabetes.diabetesjournals.org/content/63/7/2222 which say that in overfeeding, pufa causes more lean muscle and less fat gain than SFA. I know that SFA and low carb will limit hunger and therefore spontaneous overfeeding would be rare, but what if one's goal is to gain weight as opposed to lose it. Would they have to reconsider having a predominantly SFA fat composition diet?
Thanks so much

Peter said...

Hi dave,

I’ve looked at a number of the “muffin overfeeding” studies over the years. Your comment about overfeeding vs spontaneous weight gain is quite correct.

The question about what to do if you actually want weight gain is interesting. Anecdotally, normalising metabolism to increase weight in pathologically underweight people is spontaneous on LC eating and the period of weight gain here would not qualify as “overfeeding” to me.

What would happen in people with specific targets re bodybuilding or weight constrained athletic competition is a big unknown to me. Clearly you could use PUFA, look great and have great composition and pay the price in modifying your mitochondrial inner membrane composition, that might well work. Using PUFA would allow continued insulin signalling and, given the correct manipulation in terms of exercise, might well result in anabolic effects on muscle outweighing anabolic effects on adipocytes. Would this be good for you long term? That I don’t know. My impression (utterly ungrounded in any facts) is that elite athletes seem to have little concern about taking life shortening drugs if it gives them an edge, why worry about mitochondrial membrane composition?

Interestingly PUFA based diets also give faster weight loss and more uncoupling. Is that good or bad? On an evolutionary basis? Interesting thoughts.


karl said...


Once again - they are actually comparing palm oil vs sunflower oil combined with a muffin.. They do state that the "... the nature of this “lean tissue” is unclear." Might not be muscle.

They state "Dietary intake was assessed by 4-day weighed food records" - we know from other work that such records don't work. ( I assume the rest of the diet was uncontrolled) ..

They were actually looking at liver-fat content - could be that the difference has to do with more fat storage in adipose tissue due to the PUFA - but with the low N - confounded variables, I would not draw any dietary conclusions from this. Even the authors noted some of the limitations of the study. (vit E for one) - The subjects were selected for being lean at the start. (I would give credit for disclosing the limitations as well as they do - not typical of dietary papers).

Anyway - if I was going to overeat something for strength training - it would be protein.

I would wait for an actual controlled study with chemically defined diets - as usual - most nutrition papers don't provide actionable information.

The actual paper is at:

davemoriarty2 said...

Peter and Karl,

My concern is that the anabolic effect of PUFA in this case is not only drastic (the SFA groups gain mostly non-lean mass), but also not reserved for athletes and bodybuilders. It seems that regular people who overfeed get these same effects.
As someone who is 5'9" and 140lbs, gaining weight and muscle is something I'm interested in for both the asthetic and strength effects (no desire to become a bodybuilder), but it seems these results are repeated in several studies.

For myself, I have noticed that eating to appetite, even before shifting to a higher SFA and lower sugar and PUFA diet due to other issues, was not enough to gain weight, and that I almost needed to force an overfeeding state. This seems to remain true, but I would not want to continue if most of this weight will be fat. Is it possible that trying to override the natural satiety of SFA by purposely overeating is something not considered by this model of health and metabolism?

Thanks to both of you,

karl said...

I hear what you are saying - but I am not sure we can trust much of the research - they seem to be "looking for" a result ( eating red meat is evil) and they find it. For some reason those studies seem to always have added excess carbohydrates as part of the mix. I am biased - but I see a definite agenda in what research gets grant money.

I can say that I lift - eat low carb - eat mostly sat-fats - avoid PUFA - and I'm not having weight problems (did in the past eating carbs). My take is that eating sat-fats reduces my hunger. I don't think forced feeding is the norm.

But - I would also say that there is MUCH - very MUCH - we don't know - very little high quality research that doesn't trigger my junk science warning lights.

Most of the successful weight lifters do supplement with pure protein (read the labels). One has to gain weight to gain strength - and that means eating enough protein. (because I am low-carb - I have to be sure to get enough salt-potassium-magnesium as well).

I started off with decades of back problems - defied my MD's advise and started doing bar-bell training (as opposed to exercise) - (look up Rippetoe) once I could squat half my weight - the pain was gone. (pain is a great motivator) At 65 I can squat 275lb - my fasting BG went from 96 to 84 as I made gains. Even if I eat some carbs my postprandial BG doesn't go up past 110 anymore. Having good strength - muscle mass - seems like a very good idea. I think MD's should advise people to be able to squat their body-weight as a minimum.

Peter said...

Actually davemoriarty2, it looks too me that you are in an utterly ideal position to run an n=1 experiment. You won't kill yourself acutely with a bottle of corn oil... Not sure I'd do it long term but a month should let you track fat % even on something as simple as a set of impedance scales, without doing any lasting damage.


ashe higgs said...

Extra muscle is a great disposal site for blood glucose.

davemoriarty2 said...

Hi Peter,

Thanks for your response. I have not been adding the corn oil, but just some white rice and peanut butter here and there on top of high SFA and low sugar. Still no veggie oils.

I was wondering on a more general sense, if one wants to first and foremost take care of their liver, can liver fat only be reduced on a weight loss or maintenance? For example, if one is avoiding sugar and veggie oils and is eating right for their liver, but is putting on a few pounds out of choice, is this getting in the way of the liver healing?

Thank you again,

Peter said...

Hi Dave,

Having pondered for a while I would expect that although you might well increase liver lipid by overeating and produce some degree of hepatic insulin resistance using beef dripping, the question is whether this might be pathological or physiological. Systemic moderate elevation in insulin (secondary to reduced hepatic extraction) would build some fat in adipocytes and some muscle too, which is what you want. Also, if you do manage to accumulate significant amounts of hepatic lipid, does it matter? Can you damage liver tissue by peroxidising palmitic acid? I think not. With PUFA, generating lipid peroxides is a mater of amount, rather than if at all. Adding extra palmitate, by paid overfeeding, to a background of hearthealthypolyunsaturates might be more of a problem.

The papers on supplementing PUFA without paid overfeeding are few and far between and extraordinarily poorly done. Except the Sydney Diet Heart Study and the Minnesota Coronary Experiment, both of which killed enough people that they were buried for decades. The studies that is, not the people. Though I guess the people were too.


cavenewt said...

Sorry, what is "paid overfeeding"? Forced overfeeding, perhaps?