This archived forum used to be called 'Peatarian' (in reference to Ray Peat).

Journal club: Uncoupling with controlled-release DNP ameliorates high-fat-induced diabetes and steatosis in rats

New study in science showing how uncoupling with a special controlled-release dinitrophenol formulation can be helpful to treat over-eating associated syndromes:

Controlled-release mitochondrial protonophore reverses diabetes and steatohepatitis in rats
Science, Published Online February 26 2015
http://www.sciencemag.org/content/early/2015/02/25/science.aaa0672

Given the deaths observed with usual DNP (which has a very small therapeutic range) extreme caution should be applied before generalizing this to humans. The safety and efficacy of this controlled-release DNP formulation in humans remains to be shown.

It is still unclear to me whether uncoupling in people, that dont have any overeating-associated problems (obesity, fatty liver, type-2 diabetes), is beneficial in the long run. I remain sceptical.

asked Mar 3, 2015 by Bukowski
edited Mar 3, 2015 by Bukowski

2 Answers

I wrote about this last September, and was shouted down in the raypeatforum for being a fattist. Now it has 7500 shares on Facebook, and even a share here.

Things to think about: A controlled release generally is the same as taking divided doses throughout the day.

Coffee has the same effect of uncoupling if the appropriate dose can be found, which may be different for each person.

I would suggest everyone try uncoupling, if only to experience it. It's the same effect you get (high CO2) when climbing at very high altitude.

answered Mar 3, 2015 by visionofstrength

Can we make a master list of "uncouplers"? I found your post on RPF that lists the following:

Vitamin E
Aspirin
Niacinamide
Vitamins D and K
Thyroid hormone (which?)
Progesterone
Pregnenolone
DHEA
coffee at 4X strength mixed with nonfat milk
fructose
coconut oil

Any others? It would also be good to find dosages of all these.

I think urea and magnesium bicarbonate belong on the list, along with sodium chloride and thiamine and the other B vitamins, red light and carbon dioxide. Maybe also the electron-withdrawing molecules: K2-MK4, emodin, lapachol, tetracyclines, selenium, methylene blue, CoQ10 and alpha lipoic acid.

For dosages (Peat thinks) you should experiment for yourself (Peat thinks) to bowel tolerance, which includes headache, nausea, constipation or diarrhea.

I started to do a draft of "Ray's Daily Allowances" on the forum, and ask for responses, but once again got shouted down by a so-called moderator, who is really more of a mockerator.

Would you mind posting that draft on this forum, if you get time? I doubt it will get shut down and some of us will no doubt find it interesting. Thanks.

This thread by Haidut in RPF (love his posts) about thyroid surrogates is pretty good and could be a starting point:
http://www.raypeatforum.com/forum/viewtopic.php?t=3480

Wouldn't using thyroid as an uncoupler be potentially safer? The problem with DNP is figuring out the right dose and of course being confident about the purity of the product. Would be good to get hold of this CRMP stuff !

Bodybuilders use it for very short periods of time but the high dose they use makes it a hellish experience. Even running a 'low' dose protocol can be tricky as the heat production tends to build up with use but stops pretty quickly once you discontinue usage. I'd think DNP would be useful even for non-overeating associated obesity and general metabolism tuning as long as dosage, purity and the controlled release aspects were addressed.

answered Mar 3, 2015 by inflamed

I think Peat and Broda Barnes suggest thyroid first, but if the liver is damaged or there is too much metabolic stress, T3 gets converted to reverse T3, and T4 may even backfire, because T4 can increase the adrenalin pathway.

If I lived in a place where DNP was legal, I'd want to start out with 15 mg eight times a day, and increase gradually, while keeping my head cool and avoiding hyperthermic activity.

My main worries would be the impairment of energy production in sensitive tissues, the depletion of nutrients along with the increased metabolism and potential increases in oxidative stress when the electrons cant be adequately transfered onto the oxygen to form water together with protons. Those things could create all kinds of unforeseen downstream effects.

Agree, CB. I think you see this biphasic response to all the uncouplers, caffeine, aspirin, DNP, and others. Too little uncoupling is just as bad as too much. There can be no perfectly safe answers from the nanny state or its corrupt wardens.

It is an experiment that each of us can do for ourselves.

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