My Nutritional Science Blog

[Kyle M]

Not sure if this is the right place to post this but I have been writing a blog for a while now and wanted to share it. I'm trying to make journal quality posts, which has meant there aren't that many of them. I would be glad to get feedback, thanks.
www.nutricrinology.com

 

[Kyle M]

If anyone is interested I gave a talk at the Ancestral Health Symposium last week, trying to bring a Ray Peat metabolic perspective to the paleo crowd:

 

[lollipop]

If anyone is interested I gave a talk at the Ancestral Health Symposium last week, trying to bring a Ray Peat metabolic perspective to the paleo crowd:

Thank you @Kyle M for posting this thread - a place I can direct people who are curious about Paleo/LC versus Ray Peat, and my explanation is not enough - lol.

 

[PakPik]

Hi kyle, thanks for sharing some of your work. I've been reading through your blog and I really like the subjects! -my two favorite subjects are lipids and immune system-. I'm not any sort of expert but I was able to understand nearly everything you wrote, so thanks for the efforts to bring clarity and quality :)

On SREBPs, I had done some reading on how certain oxysterols blocked it, but had no idea PUFAs were able to do that as well or that it was related to blocking proteolytic enzymes. I am really starting to wonder what general biological significance there would be to that effect... maybe the body reads the PUFA as a signal of stress, trauma and scarcity and therefore shuts off production of many sterols as a means of resource conservation, etc (as far as Peat goes, PUFA are the first fatty acids liberated by stress-induced lipolysis, so it would make sense)... Just speculating.

On TLRs and Sat. fatty acids stimulating its effects, there's a 2012 paper "debunking the debunking", I wonder if you've read it or if you have thoughts on its validity: Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways. - PubMed - NCBI

Finally, I am a little confused on your last post where you claim that "mammals and birds, only produce saturated and monounsaturated fatty acids" So, no PUFAs? As far as I know, we are perfectly able to produce Mead Acid, an omega 9 PUFA under certain special conditions. And newborn babies produce Mead Acid.

Really thought provoking discussion on the problems and limitations of receptor theory.

 

[Kyle M]

Good points, I will read that debunking debunking asap. About Mead acid, that is true, I should have been more precise and said that none of the so-called essential PUFA (n-6 or n-3) are produced in warm-blooded animals. I will have to find out how much Mead acid is made, but from what I understand the vast majority of de novo fatty acid production is palmitic and oleic acids.

The PUFA inhibition thing, I don't think the cells are doing anything on purpose, I think it's a physical property of PUFA in colloid, just like pH and heat can be in ranges such that enzymes don't work well. The PUFA in the cytoplasm create an environment that, at the physical level, interferes with the operation of our enzymes. So I would say that organisms that produce it (prokaryotes, plants, some sea animals) produce it to take advantage of that property, not that they have evolved responses to PUFA. The seed has PUFA in it both as an energy source but also as a way to slow down the sprouting enzymes until optimal conditions are achieved, and then the oils gets used for energy which unlocks the enzymes and allows the plant to sprout. It's no coincidence that the rest of the plant has such little oil in it, and that only dormant seeds ever store large amounts.

 

[PakPik]

Thanks for your response.

Yes the vast majority of de novo production is SAFA and MUFA. However, the body still needs a little of PUFA to perform certain crucial functions as far as I understand it -just seeing the whole complex machinery for fatty acid modification and manipulation we have in our cells makes it clear to me-. Whether it should come from exogenous or endogenous PUFA is a whole matter of debate. But it all points that PUFA serves almost a discrete role, being tightly regulated and produced/modified/stored just as needed, whereas SAFAs and MUFAs are used and needed in a more "bulky"way -sorry if this is not clear-. So that doesn't mean that SAFAs and MUFAs are more importnat or desired than PUFAs, it just means that all of them are desired in their respective quantities and functions, and that the body makes a great deal of effort to keep the both more biophysically and phisiologically problematic PUFAs protected and controlled (which of course begins to fail in chronic unfavourable conditions or disease states).

Regarding the inhibiting effects of PUFA, you point out that their interaction with enzymes is more of a physical action, which is true, but I don't think that means that such sort of effects aren't purposeful in the organism. Quite the contrary, I believe, and I've gotten that sort of belief from reading Peat, that (bio)physical influences such as temperature, pH, etc, all act as signals from the environment, exerting their effect physically, helping -ideally- the organism to respond and adapt accordingly. So, cells sensing cold physically respond to it in a meaningful way: cold="let's hibernate in order to not consume our resources too fast"=Blockage of enzymes involved in sterol and hormonal production, etc.... Same thing with with a big flux of free PUFAs in the bloodstream: Free PUFAs="Something really stressful is going on"=Preservation of resources to meet the increased demands of stress and/or in the midst of scarcity=Blockage of enzymes involved in sterol and hormonal production, etc... There are biophysical effects from light and pH that also translate into meaningful, coherent signals in the body. And on and on. The ways organisms respond to the physical interactions they are exposed to are meaningful, purposeful, and you illustrate it well in the case of seeds.

 

[Agent207]

@Kyle M, that was a really enjoyable talk to hear.

What are your thoughts on medium chain triglycerides -within a ch predominant diet- at substituting a portion of overall dietary fat? I mean true mcts C6-C8-C10, no C12. They supply energy on the mitochondria very efficiently, and bypassing lymphatic system. I think from an energy point of view, they can provide part of the fatty needs in a diet, but without most of the negative sides from common fats.

 

[Kyle M]

Yeah I think that is a good way to go, they are also more antimicrobial in the gut than other fats. I'm becoming very influenced by the tyw discussion about endotoxin and fat consumption.

 

[Agent207]

@Kyle M I would like if you could give your thoughts on this quote, its something its been rounding in my head since I read it.

The difference in response is just glucose clearance. In the first case your insulin receptors are taking in the glucose rapidly. In the second case, the fatty acids in your blood stream are causing the insulin receptors to delay, so the glucose is staying in your bloodstream for longer. The reason you feel better is just because your high blood sugar is prolonged. The "peak" refers to the highest postprandial glucose reading within 2 hours of eating, it's unrelated to whether you "feel" it. Protein glycation and all other negative effects of a blood glucose peak will happen regardless of what it feels like to you.

The takeaway: whether you eat the carbs with protein and fat and don't "feel it", or eat the carbs and get a crash, your postprandial glucose peak will be EXACTLY the same, causing EXACTLY the same amount of glycation, just at different times. Your choice of aftereffect is hypoglycemia (first case) or prolonged raised glucose (second case). I'm not saying do one or the other, but biochemically, neither reduces how much your blood sugar gets raised.

I understand the total postpandrial blood glucose will be the similar with or without fat... but, the peak too? I thought in the case of mixing carbs with fat or fiber the peak would be, not just delayed, but someway attenuated in time.

 

[Kyle M]

Hmm, well first of all I'm far from convinced that glucose is the major cause of glycation, despite the name. It just so happens that many people in the Diabetic state with slow glucose disposal and high circulating average glucose tend to have high circulating FFAs as well, many of which are PUFA and will break down and attach to proteins. But even if it were true, a peak of, say, 500 mg/dL that lasted for 10 minutes and then after an hour went down to 120 mg/dL would allow for a lot less glucose to protein interaction compared to a peak 500 mg/dL that lasted for 30 minutes and after an hour went down to 250 mg/dL.
If that person is saying that all of the evidence points to peak being the most important factor in glycation, I would simply suggest that post-prandial glucose peak is related to plasma FFAs and unless that is taken into account it's a very sloppy conclusion made from an insufficient observation.

 

[Emstar1892]

Hmm, well first of all I'm far from convinced that glucose is the major cause of glycation, despite the name. It just so happens that many people in the Diabetic state with slow glucose disposal and high circulating average glucose tend to have high circulating FFAs as well, many of which are PUFA and will break down and attach to proteins. But even if it were true, a peak of, say, 500 mg/dL that lasted for 10 minutes and then after an hour went down to 120 mg/dL would allow for a lot less glucose to protein interaction compared to a peak 500 mg/dL that lasted for 30 minutes and after an hour went down to 250 mg/dL.
If that person is saying that all of the evidence points to peak being the most important factor in glycation, I would simply suggest that post-prandial glucose peak is related to plasma FFAs and unless that is taken into account it's a very sloppy conclusion made from an insufficient observation.

Gosh, thanks for your input..!

 

[Emstar1892]

Anyway. Not sure why a year old comment I made in a dead thread has been brought up but why not. We werent discussing glycation processes there. I was actually making a much simpler point with someone who didn't agree with me that (just going by a simple glucose monitor) the peak is no less, and is often actually higher with PF&C together than just carbs.

 

[Kyle M]

Anyway. Not sure why a year old comment I made in a dead thread has been brought up but why not. We werent discussing glycation processes there. I was actually making a much simpler point with someone who didn't agree with me that (just going by a simple glucose monitor) the peak is no less, and is often actually higher with PF&C together than just carbs.

Haha ok, well in that I agree. There's a lot of variables but yeah if you have quick glucose disposal you might not reach much of a peak as it's getting stuffed into cells so fast, whereas a mixed meal has it's own things going on vis a vis absorption, disposal and the effects of fat on both. Don't get started on endotoxin!

 

[Agent207]

The way I see it, the only benefit of fat with carbs is to keep the amount of blood sugar longer for sustained energy and so avoid a sudden drop that leds to ffa liberation which should be worse; but this comes at the expense of having insulin elevated for longer too, which promotes insulin resistance. But, isnt the liver supposed to take action before this happens?

So the point then, what do you think is optimal? To get sustained blood glucose "externally" through diet with fat added to carbs, or disregard about rapid clearance and let the liver to take care?

Another option would be to replace fiber for fat --> more sustained blood glucose too but without Randle cycle involved.

 

[Kyle M]

I think that it's not as simple as picking glycemia and insulinemia as your metrics and going from there. Certain amino acids stimulate insulin more than others, so if you were getting super technical about it you would have to include those too. There is also the taste system to consider, I think that's probably important physiologically and so mixed meals may be good for that reason. There's also vitamin absorption, endotoxin absorption, the list goes on. I see zero fat and other such extremes as temporary measures to treat something, not an ideal to aspire to.

 

[Kyle M]

Was on the most recent episode of D-rods Generative Energy.

 

[Kyle M]

On TLRs and Sat. fatty acids stimulating its effects, there's a 2012 paper "debunking the debunking", I wonder if you've read it or if you have thoughts on its validity: Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways. - PubMed - NCBI

I finally got around to fully reviewing that paper. Thanks again for showing it to me.

 

[Sucrates]

@Kyle M ,
Thanks for posting the articles, the commentary on TLR and SFAs has been very helpful.

 

[Kyle M]

Linoleic acid causes greater weight gain than saturated fat without hypothalamic inflammation in the male mouse:
http://www.sciencedirect.com/science/article/pii/S0955286316302364

 

[ecstatichamster]

Thanks Kyle. Love that talk you gave. So glad you are here.