Yep, I think it is. The point is there's almost no history of oral peptides, other than stomachs destroying them.
FTA: "So to summarize the state of the art in oral peptide delivery: there are exactly two FDA-approved products that use permeation enhancers to get peptides into your bloodstream through your GI tract. Both achieve sub-1% bioavailability. Both required over a decade of development, thousands of clinical trial participants, and hundreds of millions of dollars."
Would a sublingual dose be possible/more effective? Research in other (um, yeah, medicinal!) compounds shows that it can be an effective pathway to the bloodstream rather than trying to survive the digestive system.
Local buffering — pH microenvironment control (semaglutide)
One I take, PEP19, apparently is unique in being naturally bioactive. Evidence is early stage, but I get noticably better sleep with it (by some non-drowsiness mechanism), taking 6mg, 3x the recommended dosage for sleep, but the higher dose may promote fat burning and fat browning at night (only 1 study). It only has 10 residues which apparently avoid having typical cleavage points, fragments may retain bioactivity, and it has extreme potency in very small doses so any absorption means a lot.
Despite a plethora of peptides, successes are not common.
abainbridge|19 days ago
FTA: "So to summarize the state of the art in oral peptide delivery: there are exactly two FDA-approved products that use permeation enhancers to get peptides into your bloodstream through your GI tract. Both achieve sub-1% bioavailability. Both required over a decade of development, thousands of clinical trial participants, and hundreds of millions of dollars."
pstuart|19 days ago
Nevermark|19 days ago
Cyclization + N-methylation — lipophilicity, protease resistance (cyclosporine)
D-amino acid substitution — protease evasion (desmopressin)
Permeation enhancers — transient tight-junction opening or membrane fluidization (semaglutide/SNAC, insulin formulations)
Extreme potency — tolerating <1% bioavailability (desmopressin)
Minimizing size to di/tripeptides — exploiting PepT1 active transport (collagen hydrolysates)
Prodrug masking — protecting reactive groups, intracellular unmasking (S-acetyl-glutathione)
Local buffering — pH microenvironment control (semaglutide)
One I take, PEP19, apparently is unique in being naturally bioactive. Evidence is early stage, but I get noticably better sleep with it (by some non-drowsiness mechanism), taking 6mg, 3x the recommended dosage for sleep, but the higher dose may promote fat burning and fat browning at night (only 1 study). It only has 10 residues which apparently avoid having typical cleavage points, fragments may retain bioactivity, and it has extreme potency in very small doses so any absorption means a lot.
Despite a plethora of peptides, successes are not common.
JumpCrisscross|19 days ago