I'm creating this to hopefully bring light to HU6 so we can see it enter the UGL scene as soon as possible. TLDR; BAM15 not good, HU6 good.
Currently, the most promising mitochondrial uncoupler in the market seems to be BAM15. BAM15 shows high selectivity in the liver and adipose tissue, but it has never been tested in humans, has a seemingly short half life in mice, and is often taken at completely inefficient doses.
Just by using equivalent doses from rodent studies we'd need at least 1g per day before it really starts to have a roughly 10% increase in RMR. But it may get even worse. The mouse liver is roughly 12x more metabolically active than the human liver, so it would be expected that BAM15, which is liver selective, is more effective in mice. But, because of this, it's also likely that BAM15 has a far longer half-life in humans, maybe 10x as much or more. Unfortunately, we have no determination on this, and we don't know the actual bioavailability in humans. From personal anecdote, I can say I was noticeably still hotter after an acute 5g dose roughly 16-20 hours later, where otherwise I haven't noticed any increase in sweating from an acute 2g dose. So I would think at least the half-life is considerably longer. Not saying this dose is needed at all, I was simply using it to test if it was actually working and half-life hypothesis, as normal likely effective doses would not cause hyperthermia.
All of that to say, we really don't have any idea how much is needed. Because of this uncertainly, it's dosed randomly in the UGL. I can say for certain your 50mg tablets aren't doing shit- it's not even close to what is needed.
HU6 is a drug slated to enter phase 3 trials for multiple metabolic conditions. It is simply a prodrug to DNP, practically eliminating systemic effects by concentrating the effects at the liver in therapeutic doses. DNP is so dangerous because it is active in virtually all tissue, which is why you sweat it out, why it likely causes cataracts through metabolic disruption, and has no therapeutic ceiling.
HU6 is tested in humans and presents a similar side effect burden to BAM15. Studies noted no increase in body temperature, with the most common side effect being flushing (30% vs. 10% in placebo). HU6, like any other uncoupler is great for diabetes, NAFLD, visceral fat, preservation of lean mass, etc.
Doses in humans (once daily) and corresponding TDEE increases are estimated to be the following:
150mg > +10%
300mg > +20%
450mg > +30%
Personally, I doubt it actually scales so linearly because of its selectivity and this is just an estimate the researchers came to. The real question is at what dose do the effects become systemic so we can avoid it; that is unexplored.
More details on study results: https://www.rivuspharma.com/wp-content/uploads/2023/10/Rivus_LancetGE_Publication_PR.pdf
So not only does HU6 not require massive doses, but it also doesn't require fats for absorption either like BAM15.
The chemical structure would also imply that it's probably not that complicated to synthesize either, but I'll leave that to smarter minds than me.
Hopefully we see in the UGL soon, or maybe even coordinate a custom raw synthesis group buy if the price is right. In any case, please stop wasting money on microdoses of BAM15 (and SLU, shit is dumb af.)
Currently, the most promising mitochondrial uncoupler in the market seems to be BAM15. BAM15 shows high selectivity in the liver and adipose tissue, but it has never been tested in humans, has a seemingly short half life in mice, and is often taken at completely inefficient doses.
Just by using equivalent doses from rodent studies we'd need at least 1g per day before it really starts to have a roughly 10% increase in RMR. But it may get even worse. The mouse liver is roughly 12x more metabolically active than the human liver, so it would be expected that BAM15, which is liver selective, is more effective in mice. But, because of this, it's also likely that BAM15 has a far longer half-life in humans, maybe 10x as much or more. Unfortunately, we have no determination on this, and we don't know the actual bioavailability in humans. From personal anecdote, I can say I was noticeably still hotter after an acute 5g dose roughly 16-20 hours later, where otherwise I haven't noticed any increase in sweating from an acute 2g dose. So I would think at least the half-life is considerably longer. Not saying this dose is needed at all, I was simply using it to test if it was actually working and half-life hypothesis, as normal likely effective doses would not cause hyperthermia.
All of that to say, we really don't have any idea how much is needed. Because of this uncertainly, it's dosed randomly in the UGL. I can say for certain your 50mg tablets aren't doing shit- it's not even close to what is needed.
HU6 is a drug slated to enter phase 3 trials for multiple metabolic conditions. It is simply a prodrug to DNP, practically eliminating systemic effects by concentrating the effects at the liver in therapeutic doses. DNP is so dangerous because it is active in virtually all tissue, which is why you sweat it out, why it likely causes cataracts through metabolic disruption, and has no therapeutic ceiling.
HU6 is tested in humans and presents a similar side effect burden to BAM15. Studies noted no increase in body temperature, with the most common side effect being flushing (30% vs. 10% in placebo). HU6, like any other uncoupler is great for diabetes, NAFLD, visceral fat, preservation of lean mass, etc.
Doses in humans (once daily) and corresponding TDEE increases are estimated to be the following:
150mg > +10%
300mg > +20%
450mg > +30%
Personally, I doubt it actually scales so linearly because of its selectivity and this is just an estimate the researchers came to. The real question is at what dose do the effects become systemic so we can avoid it; that is unexplored.
More details on study results: https://www.rivuspharma.com/wp-content/uploads/2023/10/Rivus_LancetGE_Publication_PR.pdf
So not only does HU6 not require massive doses, but it also doesn't require fats for absorption either like BAM15.
The chemical structure would also imply that it's probably not that complicated to synthesize either, but I'll leave that to smarter minds than me.
Hopefully we see in the UGL soon, or maybe even coordinate a custom raw synthesis group buy if the price is right. In any case, please stop wasting money on microdoses of BAM15 (and SLU, shit is dumb af.)
