I'm not a specialist but I think there are some stapled peptides that do show appreciable uptake, so the blog post is not a complete history; this review reports bioavailability of up to 70% for some agents.
Nielsen DS et al. 2017. Orally Absorbed Cyclic Peptides. Chemical Reviews.
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.
Sublingual is even harder. The sublingual mucosa is thin but selective. It strongly favors molecules that are small, lipophilic and uncharged. Semaglutide is about 8-10x too big, highly polar and charged.
Injection is really the only method with any substantial bioavailability. BUT, low (<1%) bioavailability does not necessarily mean useless.
They probably didn't, they just took the bet that this was one of the crimes that are currently legal, like crypto scams, environmental crimes, bribery, and tay evasion for the rich.
Some of the most profitable ventures this century have been objectively illegal, but when you know you won't go to prison for violating the law, why would you care to follow it?
human dissection (grave robbing)
translating the Bible into English
silk production outside of China (death penalty for exporting worm eggs)
rubber production in Asia (seeds smuggled out of Brazil)
the Underground Railroad
heliocentrism
AIDS treatment (see Dallas Buyers Club)
Needle exchange programs for IV drug users
Ridesharing/airbnb/napster (obvious ones)
SF gay marriage licenses (in defiance of CA law)
> The process of chlorinating water was first done illegally.
I tried to find a source on this but it doesn't seem to be true? The first chapter of this book describes the history of chlorination: https://upload.wikimedia.org/wikipedia/commons/f/fd/Chlorina... (which is a source Wikipedia cites) and it doesn't appear to mention anything about illegally chlorinating water. After looking in that book I asked ChatGPT to find a source for the claim, and it reported the claim was false. Chlorination was initially controversial but I can't find anything claiming it was illegal?
I'm not a specialist but I think there are some stapled peptides that do show appreciable uptake, so the blog post is not a complete history; this review reports bioavailability of up to 70% for some agents.
Nielsen DS et al. 2017. Orally Absorbed Cyclic Peptides. Chemical Reviews.
https://sci-hub.ru/10.1021/acs.chemrev.6b00838
It’s a great read but is this really the history of oral peptides?
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.
Sublingual is even harder. The sublingual mucosa is thin but selective. It strongly favors molecules that are small, lipophilic and uncharged. Semaglutide is about 8-10x too big, highly polar and charged.
Injection is really the only method with any substantial bioavailability. BUT, low (<1%) bioavailability does not necessarily mean useless.
It would be hilarious if people wound up snorting or boofing their GLP-1s (≧▽≦)
I'm not sure why the hims investors ever thought that this was legal
They probably didn't, they just took the bet that this was one of the crimes that are currently legal, like crypto scams, environmental crimes, bribery, and tay evasion for the rich.
Some of the most profitable ventures this century have been objectively illegal, but when you know you won't go to prison for violating the law, why would you care to follow it?
The process of chlorinating water was first done illegally.
Also:
> The process of chlorinating water was first done illegally.
I tried to find a source on this but it doesn't seem to be true? The first chapter of this book describes the history of chlorination: https://upload.wikimedia.org/wikipedia/commons/f/fd/Chlorina... (which is a source Wikipedia cites) and it doesn't appear to mention anything about illegally chlorinating water. After looking in that book I asked ChatGPT to find a source for the claim, and it reported the claim was false. Chlorination was initially controversial but I can't find anything claiming it was illegal?
The charitable assumption is that investors weren't aware it was a problem.
Appreciate the perspective on the risk of dubious formulations. Consequences are far more than cosmetic.
Informative article but I feel like it could have benefited from a paragraph about what Hims is. I had never heard of them before.
thanks, needed this for a mogging session later
great read!