Q: “I’ve been thinking about the advantages of caffeine as an uncoupler, similar to T3, and I wonder what your opinions are on such a substance compared to T3. Obviously, T3 (or NDT) possesses similar uncoupling benefits without the negative effects on sleep quality (and possibly brain development). Aspirin, while possessing the positive benefits of mitochondrial uncoupling, fails to affect circadian rhythms and sleep quality to the degree of caffeine.
Do you feel as if the effects of caffeine on sleep are temporary and that they vanish with time as adenosine receptors adapt to the stimulus? You would know, as you have reported taking upward of 1200 mg caffeine per day. I’m a huge fan of caffeine, but I do notice that it negatively affects my sleep and am curious as to whether NDT is a favorable alternative in your opinion, or if this effect will degrade with time.”
A (Georgi Dinkov from Idea Labs DC): “In my experience, caffeine initially made me very wired but after about a week on the high dose it started making me sleepy, probably due to the upregulation of the adenosine receptors. As an uncoupler, aspirin with baking soda (to protect the gut) is probably the safest in terms of not affecting heart rate and/or sleep much. Adding a few milligrams of methylene blue to the aspirin dramatically increases this effect. Methylene blue itself is an uncoupler at concentrations higher than 0.5uM, which can be achieved with a dose of a few milligrams. Hence, combining it with aspirin.”
Q: “I felt almost psychotic after being on an 800 mg dose [of caffeine]. Aspirin and baking soda seems to work for me, although I only get 2 mg [vitamin] K2 from EstroBan daily, and eventually the 2 g uncoupling dose [of aspirin] causes rectal bleeding. I thought your recommended dose for MB is 20-30 mg? There must be some synergism between salicylic acid and MB that I’m missing for a low milligram dose of the former to “dramatically increase” aspirin’s effects, or rather the MB just possess a very dynamic range for uncoupling. I’m curious to try Oxidal, simply for its contents of benzoic acid [as another uncoupler].”
A: “I think my posts said that a dose of 5mg MB daramatically increased aspirin’s uncoupling effects. I doubt I have recommended 20mg – 30mg since at that dose it may increase serotonin. Can you point me to that thread please?”
Q: “Since starting my aspirin regimen, I’ve found that I’m maintaing a lower body-fat percentage with relative ease. What do you think is a safe ceiling dose of MB? I’ll start with 500 mcg, then 1 mg, then 1500 mcg on a week by week basis until I reach my ideal 10% body fat. The power of this information is quite overwhelming, and it’s amazing how modern medicine demonizes uncouplers as toxic and dangerous, while I have never felt so alive as I do now. I wish you the best.”[The post in question addressing methylene blue on the Ray Peat forum, titled Methylene Blue (MB) Uncouples Respiration]:
“This was an in-vitro study, but knowing the effects of MB in vivo makes it very plausible that MB is indeed a respiration uncoupler similar to DNP.
“…In tightly coupled, succinate-respiring mitochondria, addition of MB resulted in an acceleration of state-4 respiration, resulting in the overall decrease of RCR values, indicating the uncoupling of oxidative phosphorylation (OXPHOS) (Fig. 3). Significant inhibition of OXPHOS was apparent after the addition of just 0.5 μM MB, whereas, mitochondria exposed to 5 μM MB demonstrated a much stronger inhibition. Our selected range of MB was based on recently published data reporting a mean concentration of MB [5 μM] attained in plasma after a single 100 mg intravenous bolus injection , a typical daily dose administered to patients receiving IFO.”
The optimal concentration is achieved by a 100mg IV dose of MB, which is kind of high. However, you should be able to see results even from just 0.5microM, which is achievable after an oral dose of about 20mg-30mg.”
A: (Georgi Dinkov from Idea Labs DC) “Ray says the the optimal dose of MB is about 1mg daily (or lower) but he also said that even very high doses of hundreds of milligrams showed no side effects. I personally took 15mg for 2 weeks with no issues whatsoever.”