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#41
My main concern with ISRIB (or more potent variations like ISRIB-a15, if for some reason they’re easier to get) is lack of ADME information for humans. @Luminary , how do you monitor your dosing to know you’re achieving your goals? Is there some sort of identifiable sign of overdose?
I found this good mice-to-human dose calculator: Practical PK Calculators
This gives the range of doses for ISRIB that were mentioned here: https://www.alzdiscovery.org/uploads/cognitive_vitality_media/ISRIB.pdf
Mice | Human (For 70 kg human)
.1 mg/kg = 0.569 mg (unsuccessful at this dose)
.25 mg/kg/day = 1.423 mg
2.5 mg/kg/day = 14.23 mg
5 mg/kg/day = 28.46 mg
There really is no good long-term safety or toxicity info. I did read that 5 mg/kg/day (28.46 mg) showed increased mortality and was lowered to 2.5 mg/kg/day. Personally, I have taken it only a few times at 10-20 mg, but I guess this would indicate it is probably best to be more conservative in dosing, as even 0.25 mg/kg produced some positive benefits in studies.
As for positive benefits, I only based my perception of that on the feeling of being in good cognitive shape the last few days. I can not give any solid evidence that those feelings are real.
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ISRIB is quite interesting, pretty cool to see a few people here experimenting with it. Been thinking of giving it a go 
So far what I’ve seen in the studies is that it is to be used as a “reset” type intervention. 2 or 3 doses over 3 to 6 days and repeat once or twice a year.
I’ll be digging in to the available papers over the next couple of weeks.
Please keep us updated on what you are finding.
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Note(!): I just would like to add that do NOT use plastic/painted measuring spoons for the DMSO. DMSO will act as a solvent for any impurities and you will absorb a ton of toxins. Glass/stainless steel measuring spoons are required if used orally. And also, the FDA has not approved any oral usage of DMSO. The 10 percent dilution for usage is practiced for experimental therapies apparently. So, be safe about all of this, whoever tries it.
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I would also like to add a general word of caution here about suppliers… be careful with this stuff.
I was at the Longevity Center Rountable conference this week and there was a presentation by Dr. Jordan Shlain, who started and runs a network high-end concierge medical clinics (Private Medical) for the wealthy. He has many of the tech millionaires and billionaires in the SF Bay Area, and so he gets people who see and know Bryan Johnson and want to try things like that. But Jordan Shlain has been in business for something like 20 years, isn’t a “longevity doctor”, and operates a slightly more traditional concierge medical clinic that focuses on preventative medicine, but also treats traditional ailments and disease processes people encounter.
But - since he serves the tech wealthy, many of his clients are interested in “longevity therapies” and trying them with other doctors in the SF Bay Area, or more broadly.
One of his clients came in after talking with a “longevity doctor” who had recommended the guy do injections of L-Carnitine. The client wanted Dr. Shlain to buy the compound for him (I guess it was only sold to doctors) but Dr. Shlain had never heard of this procedure before or supplier, and he was skeptical. So, he told the guy the first thing they should do is order the product/liquid and get a trusted lab to do an analysis on it to validate what the product actually was.
When they did the lab analysis on the product they found all sorts of chemicals that were not listed on the product’s label. Moreover, some of these chemicals were psychoactive compounds that would have a significant impact on how the person would perceive how he felt (i.e. he’d “feel great”, but it was from these additional compounds, not necessarily the L-Carnitine). So it seems vendors may be adding compounds to trick customers into thinking they are getting a great result from the product, when in fact they are getting an effect from things that are added in). So, you’d be getting more than you bargained for, and might get deceived into continually using a product because of its perceived “beneficial effects” which are not real.
Key Take Away: Be skeptical, and do validation lab testing with a good 3rd party lab of any unusual products, prior to use. See below for this example:
The Product:
What was actually in the product:
By the way, @AlexKChen when I saw you at the Longevity Summit you mentioned you had a new supplier for ISRIB. Is it the one you mentioned earlier in this thread, or a completely new one, and can you please post it if its completely new.
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Faulty Mitochondria Trigger Insulin Dysfunction in Pancreatic Cells, but ISRIB Restores Blood Sugar Control in Mice
Key Takeaways:
- Faulty mitochondria in insulin-producing cells trigger a stress response that disrupts blood sugar control, per a University of Michigan study.
- An experimental drug, ISRIB (Integrated Stress Response Inhibitor, ISRIB), reversed insulin defects in mice by silencing mitochondrial distress signals.
- The same mechanism was seen in liver and fat cells, suggesting a systemic link to type 2 diabetes.
Mitochondria
Affecting hundreds of millions of people worldwide, type 2 diabetes is often associated with problems in insulin production and utilization. A team of researchers from the University of Michigan has uncovered a new mechanism connecting mitochondria to dysfunction in insulin-producing cells.
