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Posted 19 March 2019 - 10:12 AM
able, on 13 Mar 2019 - 08:35 AM, said:
It has been proven that NR and NMN are almost entirely metabolized in the GI tract and liver.
Yes — whether delivered orally or even via injection, albeit to a lesser degree. So that's still a substantial issue even if SL delivery of NMN is very high (an unproven postulate as of today).
able, on 13 Mar 2019 - 08:35 AM, said:
There is a lot of research on sublingual delivery of other molecules and it is known what is required for a successful sublingual product, and what a typical absorption rate is.
Yes, and that research would suggest that NMN and NR are poor candidates 
. NMN does have a favorable molecular weight (334.22 Da), but it's very hydrophilic, and hydrophilic substances are generally poor candidates for sublingual delivery: they have no ability to cross the mucosal membranes, and while a very small amount may be absorbed instead tend to just dissolve in the saliva and seep down the throat. Instead, good candidates are mildly lipophilic drugs:
"Lipids present in the oral mucous membrane offer the main barrier to the permeability of hydrophilic drugs. On the other hand, well-hydrated connective tissues provide resistance to lipophilic drugs. Thus, the potential transport path across the oral mucous membrane may be either polar or non-polar. Non-polar molecules cross through the lipid regions of the epithelium, while polar molecules travel through ionic channels present in the intercellular spaces of the epithelium, or aqueous pores present in the epithelial cells. ... For efficient absorption through the oral mucosa, the drug must be hydrophobic enough to partition into the lipid bilayer, but not so hydrophobic such that once it is in the bilayer, it will not partition out again.... For this reason, an understanding of a drug’s lipophilic or hydrophilic nature during the developmental stage of the drug product appears to be the most useful index for evaluating its suitability for absorption across the oral mucosa.
http://www.pharmtech...62556?page=full
"Factors affecting the sublingual absorption
Lipophilicity of drug: For a drug to be absorbed completely through sublingual route, the drug must have slightly higher lipid solubility than that required for GI absorption is necessary for passive permeation."
https://innovareacad...Suppl2/1092.pdf
"Lipophilic drugs are better absorbed [via the sublingual route] than hydrophilic drugs."
https://www.scienced...k/9780120885923
"Sublingual administration ... takes advantage of the permeability of the oral epithelium and is the preferred route for a few potent lipophilic drugs, such as nitroglycerin and oxytocin, and even the commonly used oral sedative triazolam"
https://www.scienced...m/science/book/9780323393072
This can be a non-issue when you only need a sub-milligram quantity to be absorbed and you're willing/able to throw a massive overkill dose at the problem, but not when you're using hundreds of milligrams of something and hoping for a better result than a similarly high dose by the enteral route.
able, on 13 Mar 2019 - 08:35 AM, said:
Of course there have been no human studies yet showing if NMN is actually absorbed sublingually.
... nor any animal studies, nor even any tissue-culture models. There is diddley-squat, AFAICS.
able, on 13 Mar 2019 - 08:35 AM, said:
If you actually have reason to believe that NMN, NR, or NAD+ is definitely NOT absorbed at all sublingually, then you might say they are spreading misinformation.
Otherwise, I would suggest it is marketing claims that have not been proven.
The burden of proof lies on the person making the positive claim, especially when s/he has a financial interest in the claim. I think it is fair to say that it borders on misinformation or deceptive marketing to make as definitive a set of assertions as ABN currently does in the absence of any evidence.
They say they're looking to conduct a human absorption trial; that would be admirable, so long as they are hands-off about the design and execution and agree to publication irrespective of the results. I'd encourage all ABN customers to drop them an email expressing this.
Beyond the provocative headline, this thread would seem best-merged into the Sublingual NR and NMN thread. Any objections?
