The Randle Effect In Action (human Study)

[haidut]

This was a human study and it directly confirms Peat's views on what causes insulin resistance - elevated fatty acids, through the Randle effect, block oxidation of sugar. It would have been really helpful if the study looked at what happened after restoration of "normal" diet - i.e. how long did it take to restore glucose oxidation.
I am beginning to wonder if drugs like metformin, which increase fat oxidation, hinder rather than help recovery from insulin resistance and type II diabetes.
Another conclusion from this study would be that if optimal fat intake exists it would be below 55% of daily calories, which also matches Peat's preference for lower fat diets.

http://www.sciencedaily.com/releases/20 ... ce+News%29

"...Hulver and his colleagues found that muscles' ability to oxidize glucose after a meal is disrupted after five days of eating a high-fat diet, which could lead to the body's inability to respond to insulin, a risk factor for the development of diabetes and other diseases. To conduct the study, healthy college-age students were fed a fat-laden diet that included sausage biscuits, macaroni and cheese, and food loaded with butter to increase the percentage of their daily fat intake. A normal diet is made up of about 30 percent fat and students in this study had diets that were about 55 percent fat. Their overall caloric intake remained the same as it was prior to the high fat diet. Muscle samples were then collected to see how it metabolized glucose. Although the study showed the manner in which the muscle metabolized glucose was altered, the students did not gain weight or have any signs of insulin resistance."

 

[jaguar43]

A lot of Ray Peat followers believe if they suppress Free Fatty acids with aspirin or niacinamide. They won't be able to lose weight. And yet study after study shows that free fatty acids can cause type 2 diabetes and insulin resistance, which is associated with central obesity.

Bromocriptine is a perfect example of lowering free fatty acids and other diabetes causing chemicals to reverse type 2 diabetes and lower body fat.

I guess the cultural cliches induced by the low carb ideology is going to take a lot longer to disappear. Even within this forum and others alike.

 

[north]

Wasn't inflammation involved in the inability to oxidize glucose as well? IIRC didnt you do a high aspirin period of 2 weeks which restored that ability? Or is that a different "symptom"/scenario?

Thanks, interesting find!

 

[haidut]

Wasn't inflammation involved in the inability to oxidize glucose as well? IIRC didnt you do a high aspirin period of 2 weeks which restored that ability? Or is that a different "symptom"/scenario?

Thanks, interesting find!

Yes, there is a human study of 2 weeks high aspirin dose (7g daily) restoring insulin sensitivity. However, the patients in that study did NOT lose weight, which shows that you can be obese and have good insulin sensitivity. So, I think that for the people who want to lose weight but are not insulin resistant taking aspirin may not provide much benefit unless they take in doses that uncouple mitochondria. I think for those people high dose caffeine will probably be better in terms of weight loss.
Btw, I have noticed that lowering or blocking serotonin is very thermogenic. If I take a little cypro (as little as 1mg) then even tiny dose of thyroid (1/8 grain) makes me sweat a lot, as does a small meal or simply walking. Peat said that serotonin is the most powerful temperature suppressor and it is what makes animals hybernate by making them cold and slowing down their metabolism. On that note, dopaminergic drugs like the bromocriptine mentioned above, as well as lisuride, cabergoline, pramipexole, etc would also be expected to be helpful of restoring metabolism and improving insulin sensitivity. I posted a study on low dose cabergoline causing 6kg pure fat loss in a matter of 2 months, combined with complete restoration of insulin sensitivity, testosterone, and adrenal function. So, another confirmation of Peat's ideas I guess. He often asks people what they think of trying a dopaminergic drug like bromocriptine when thyroid does not seem to be working for them. If serotonin is high that probably prevents thyroid from doing its magic.

 

[narouz]

Btw, I have noticed that lowering or blocking serotonin is very thermogenic.

I was wondering about niacinamide over in the other thread
about raising metabolism, temps, pulse.

Some have recommended it for that purpose,
but I can't say I've noticed anything obvious when I've taken it.

 

[haidut]

Btw, I have noticed that lowering or blocking serotonin is very thermogenic.

I was wondering about niacinamide over in the other thread
about raising metabolism, temps, pulse.

Some have recommended it for that purpose,
but I can't say I've noticed anything obvious when I've taken it.

I think it would have to be decent drop in serotonin to get the thermogenic effect. I get a very similar effect when I take 5g of BCAA with food, especially protein. Protein on its own is thermogenic but nothing compared to the hours of sweating and hitting 99+ degrees on the thermometer when I combine protein with BCAA. With cypro, eating any food makes me very warm and adding thyroid just makes me feel like I am melting. So, definitely a point for Peat and how hypothermic serotonin is.

 

[narouz]

Btw, I have noticed that lowering or blocking serotonin is very thermogenic.

I was wondering about niacinamide over in the other thread
about raising metabolism, temps, pulse.

Some have recommended it for that purpose,
but I can't say I've noticed anything obvious when I've taken it.

I think it would have to be decent drop in serotonin to get the thermogenic effect. I get a very similar effect when I take 5g of BCAA with food, especially protein. Protein on its own is thermogenic but nothing compared to the hours of sweating and hitting 99+ degrees on the thermometer when I combine protein with BCAA. With cypro, eating any food makes me very warm and adding thyroid just makes me feel like I am melting. So, definitely a point for Peat and how hypothermic serotonin is.

Thanks!
I'll have to re-post that over on the raising metabolism thread,
the one exploring Peata's question to Peat.
When one starts talking in terms of "melting,"
I think we can safely believe some thermogenesis is afoot.

 

[haidut]

Btw, I have noticed that lowering or blocking serotonin is very thermogenic.

I was wondering about niacinamide over in the other thread
about raising metabolism, temps, pulse.

Some have recommended it for that purpose,
but I can't say I've noticed anything obvious when I've taken it.

I think it would have to be decent drop in serotonin to get the thermogenic effect. I get a very similar effect when I take 5g of BCAA with food, especially protein. Protein on its own is thermogenic but nothing compared to the hours of sweating and hitting 99+ degrees on the thermometer when I combine protein with BCAA. With cypro, eating any food makes me very warm and adding thyroid just makes me feel like I am melting. So, definitely a point for Peat and how hypothermic serotonin is.

Thanks!
I'll have to re-post that over on the raising metabolism thread,
the one exploring Peata's question to Peat.
When one starts talking in terms of "melting,"
I think we can safely believe some thermogenesis is afoot.

Yep, a milder version would be to ingest 20g-30g of protein and add 5g of BCAA. For more pronounced thermogenesis, take 1mg-4mg cypro and then 1-2 hours later have a meal and if you want try adding some thyroid. The thyroid is probably optional since the first time I did it temperature went over 100 and that is not for the faint of heart. But it does illustrate Peat's point nicely.

 

[Spondive]

Great thread!! Haidut awesome as usual..I tried Bcaa at that dose and it triggers my ocular migraines..I might try again..using purebulk

 

[narouz]

Yep, a milder version would be to ingest 20g-30g of protein and add 5g of BCAA. For more pronounced thermogenesis, take 1mg-4mg cypro and then 1-2 hours later have a meal and if you want try adding some thyroid. The thyroid is probably optional since the first time I did it temperature went over 100 and that is not for the faint of heart. But it does illustrate Peat's point nicely.

You are an intrepid Peat experimenter, haidut!
(Though not a Urea Pioneer, I don't think. )

I use or have tried all of those things,
but not at the same time.
Now you've inspired me to re-try them/re-combine them! :)

The cypro part...
that will take me some working up to.
It makes me really sleepy/groggy for a while.

Do you think
doing little short bursts of those supplements/combos
might help nudge up and 'reset' heat/metabolism?

 

[Amazoniac]

Isn't excess heat a way to dispose excess energy?
That seems undesirable to me, am I missing something?

 

[narouz]

Isn't excess heat a way to dispose excess energy?
That seems undesirable to me, am I missing something?

From a Peat pov...
he's very pro heat creation.
In excess of what mainstream med thinks, of course.
He has a different "normal" in mind as optimal.

 

[Amazoniac]

Generating heat is surely more challenging for warm blooded animals, since we tend to transfer our heat to the cooler environment. But excess heat to me seems that you are not able to oxidize nutrients efficiently and a lot of the energy is lost to the environment. Maybe I'm missing something..

 

[narouz]

Generating heat is surely more challenging for warm blooded animals, since we tend to transfer our heat to the cooler environment. But excess heat to me seems that you are not able to oxidize nutrients efficiently and a lot of the energy is lost to the environment. Maybe I'm missing something..

Peat has talked about the theory of aging
where energy conservation is the key idea:
you live at a slow metabolic rate, you live longer.
So the theory goes.
That is why probably most doctors would look at a temp of 99
and a pulse of 90
and diagnose hyperthyroidism. :)

 

[sweetpeat]

I get a very similar effect when I take 5g of BCAA with food, especially protein. Protein on its own is thermogenic but nothing compared to the hours of sweating and hitting 99+ degrees on the thermometer when I combine protein with BCAA. With cypro, eating any food makes me very warm and adding thyroid just makes me feel like I am melting. So, definitely a point for Peat and how hypothermic serotonin is.

Is this the same as uncoupling? I think I’ve achieved this a few times, but wasn’t sure what was happening. Do you also feel somewhat swollen? This happens especially in my fingers and my rings will get too tight. I thought perhaps somehow I had raised my estrogen level and was retaining water. But estrogen wouldn’t create heat, would it? If it is uncoupling, it IS a bit uncomfortable, especially on a warm day.

 

[answersfound]

It's so interesting about the heat. My dad walks around our house in under wear at night during the winter. He is never cold. He takes 200 mg of Amitriptyline per day for 30 years so I guess his serotonin is very low from that. He is on a bunch of other meds so maybe something else is affecting it, but I'm not sure what else it could be.

 

[SQu]

/

Is this the same as uncoupling? I think I’ve achieved this a few times, but wasn’t sure what was happening. Do you also feel somewhat swollen? This happens especially in my fingers and my rings will get too tight. I thought perhaps somehow I had raised my estrogen level and was retaining water. But estrogen wouldn’t create heat, would it? If it is uncoupling, it IS a bit uncomfortable, especially on a warm day.

Could it be flushing? I retain water, have too much estrogen, and have been flushing. my temps remain low. Peat's article on flushing might help you determine this. It is confusing because apparently underlying the sensation of heat is a drop in temperature due to the estrogen.

 

[sweetpeat]

Could it be flushing? I retain water, have too much estrogen, and have been flushing. my temps remain low. Peat's article on flushing might help you determine this. It is confusing because apparently underlying the sensation of heat is a drop in temperature due to the estrogen.

I don't think it's flushing. I always take my temperature when this happens and I'm always in the 99's with a pulse in the 90's, like haidut describes. My sinuses get clearer and my breathing feels different somehow. And I feel like I'm cooking from the inside out. The effect can last for several hours, whereas flushing (for me) is usually just a few minutes. Caffeine and thyroid are two things that have done this for me. But I know that they can also cause stress/adrenaline responses in people so that's why I wasn't sure what was happening. I didn't know how to tell the difference between uncoupling vs. a stress response. I thought the high temps were supposed to be a good thing, but the swelling confused me. Then I found this in a blog post about side effects of DNP (an uncoupler):

Water retention- this is very closely associated with heat. When the vasodilation occurs due to the rise in body temperature, blood vessels expand, causing an increase in blood volume and subsequent water retention. Also, an increased blood volume leads to decreased pressure, which would lead the body to try to store more sodium and cause even more water retention.

Also, this is from Andrew Kim's most recent blog post:

“Uncouplers” are usually seen as good and desirable for wight loss but they do so by disrupting the delicate balance in the respiratory proteins alluded to above. The classical uncoupler 2,4-dinitrophenol, an acidic aromatic compound, for instance, as an electron donating cardinal adsorbent disturbs the electronic balance of the respiratory proteins as to impair the delicate oscillatory nature of the respiratory proteins through which ATP is generated. In effect uncouplers favors the state in which the ATP generating enzyme becomes active, opposing the effect of ATP. And in the absence of potassium the continued exposure to uncouplers blocks respiration, leaving the cell in adead, swollen state. Extra potassium is vital whenever uncouplers are involved. The swelling caused by uncouplers such as thyroid hormone, for instance, are almost immediately reversed by potassium (and ATP). Insulin, on the other hand, parallels the effects of ATP.

So, it sounds like more potassium would help with the swelling when/if uncoupling is happening?

 

[SQu]

In my case pulse in the 90s does not feel like adrenalin either. It would be very interesting to see if potassium makes a difference.

 

[RPDiciple]

A lot of Ray Peat followers believe if they suppress Free Fatty acids with aspirin or niacinamide. They won't be able to lose weight. And yet study after study shows that free fatty acids can cause type 2 diabetes and insulin resistance, which is associated with central obesity.

Bromocriptine is a perfect example of lowering free fatty acids and other diabetes causing chemicals to reverse type 2 diabetes and lower body fat.

I guess the cultural cliches induced by the low carb ideology is going to take a lot longer to disappear. Even within this forum and others alike.

lovely. But want high doses of niacinamide inhibit some fat loss?