Hello everyone,
I recently revisited the effectiveness of my current method for taking 6-Diazo-5-oxo-L-norleucine (DON) and discovered some potentially significant improvements. After discussing it with a researcher from Seyfried’s lab, I learned that DON, like many small molecules and amino acid derivatives, is primarily absorbed in the small intestine. This insight led me to reconsider how I administer DON to circumvent stomach acid breakdown better.
Traditionally, I’ve been taking DON by licking it off parchment paper or using BladePape. Still, I realized this direct intake might lead to significant degradation by stomach acids—up to 50% but until now, I hadn’t considered how to mitigate that problem. Many medications, like Metformin, use an enteric coating to bypass the stomach’s harsh environment, dissolving in the less acidic small intestine where absorption is optimal.
Motivated by this, I found a way to potentially increase DON’s efficacy using a similar strategy. After searching, I adapted a nutraceutical capsule by emptying its contents and refilling it with DON. This enteric-coated capsule should help protect the DON until it reaches the small intestine. I’m eager to start this new method tomorrow and am curious to see if the results are more potent. I am also a bit worried that with more drugs getting into my GI, I might shit my pants in the hyperbaric tank instead of just puking up white foam. OMG, let’s hope not hahah.
Given that a significant portion of DON was likely destroyed by stomach acids previously, this method of direct intestinal delivery might effectively double the bioavailability of the dose. Therefore, I’ll start with a reduced dose of 0.6mg/kg to safely reassess tolerance, considering gastric breakdown may have halved the previous dose of 1.1mg/kg, which was my last “regular” dose. So it feels as if I am back at the beginning and having to start low and work my way up to find my maximum tolerable dose.
Timing the transition of the capsule from the stomach to the intestines can be tricky; this is called ‘gastric emptying’ and is different for everyone. My understanding is that this depends on what food you have eaten, if any, and your bio-individuality, but it can be anywhere from 30 minutes to 2 hours. Based on my experience with Metformin, I estimate it could take about an hour on an empty stomach. You can do tests to figure out your gastric emptying speed, but I suspect I won’t be able to find a doctor to order it. The reason I need to know is so that I can time my dose correctly so that I end up in the HBOT tank when I have a peak plasma concentration of DON. I will ask my GP, but mostly so I can tick that box, not because I expect my anyone to say yes.
Anyway, I am all ready to go for tomorrow with my enteric coated DON-filled capsule of 0.6mg/kg that I will take 2 hours before HBOT. It takes one hour to move from the stomach to the small intestines, and then it takes about two hours after that to reach peak plasma concentration. So, if I am in the tank an hour before peak and an hour after peak, I think I am getting the most out of the combination.
I would love to hear your thoughts or any feedback on this approach. Please share if you see any gaps in my reasoning or have insights from your experiences. Your feedback is highly valued!
Best regards,
Allison
Good luck with this new approach. You are so cool I forget that you are also such a wicked smart nerd! Xoxox
Hey Allison. I’ve been considering the most effective way to take DON as part of a written procedure (incomplete as yet but nearly there and I’ll send it to you once the first draft is complete for your comment). Have you considered putting the powder under your tongue an letting it dissolve? Sublingual administration, I believe it’s a pretty quick way of getting medication direct into the blood stream instead of ingesting it.
Hmm, I have not considered sublingual administration. I’m gagging just thinking about it. I know, or believe anyway, that IV or sub Q is ideal, but I don’t know how to prepare IV DON or reconstitute it given a pure powder. I know I can get a powder and solution combo ready for reconstitution, but it’s in such small amounts that it would only be suitable for mice. It’s also quite a bit more expensive. There are a lot of people interested in this approach, though. DON is a glutamine analogue, so it is likely similarly absorbed into the body to glutamine, which is absorbed in the small intestine. But if it can be delivered as a sub Q, then sublingual might also work. Both deliver meds to the fatty layer directly under the skin, which then disperses to the bloodstream, bypassing the GI system altogether. So maybe?
Depending on your dosing, it could be challenging to hold under the tongue. Monday, I was 36mg, so that is doable, but I have been closer to 90 before, and I can’t see having that much powder under your tongue very fun.
I would love to follow up on what you find out, and I will dig around a little too.