Do Oral Peptides Actually Work? Bioavailability Explained

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Do Oral Peptides Actually Work? Bioavailability Explained

Most oral peptides do not survive the trip. Your stomach acid exists to break proteins down into amino acids, and a peptide is a chain of amino acids, so putting one in your stomach is handing it to the exact system designed to dismantle it.

So more recently, they've come out with the GLP-1 type in creatine drugs like Ozempic and Wigovie that are oral. That raises a reasonable question, which is if the big pharmaceutical companies can make a peptide work orally, why can't everything else?

The answer lives in two separate hurdles, and a drug has to clear both.

When this goes into my digestive tract, AKA it sits in stomach acid, is the amino acid going to survive long enough for it to make it to the second part, which is actually making it through the barrier in your gut to absorb into your bloodstream? This is the challenge.

Hurdle one is chemical. Hurdle two is physical, because even an intact molecule still has to cross the gut wall, which is a selective barrier that lets small things through and keeps large things out, and peptides tend to be large.

Most of the time when you're talking about any type of oral pharmaceutical drug, the consideration that they make is that the bioavailability typically drops by a certain percent because of those considerations. That drop is baked into the dose on the label before it ever reaches you.

And most of the time, if you're making an oral-based drug, especially of peptides, we understand that the whole purpose of your stomach acid is to break proteins down into their original amino acid form so that they can be absorbed and digested. Your body is not making an exception for the expensive molecule.

Most of the time, these pharmaceutical companies, what they're doing is they're formulating some sort of mechanism to protect the amino acid chain while it's being digested. Think of it like a coating, or a carrier molecule that rides along and shields the chain, or a compound that briefly loosens the gut barrier so something larger can slip through.

And that's where most of the research and development comes from. The peptide itself was solved decades ago. The delivery is the hard part, and it costs billions.

And this is exactly why there's a conversation about is TB-500 taken orally actually bioavailable? Most of the time, the answer is no.

If a company is selling an oral prescription drug, there is a delivery system behind it and a clinical dose built around the losses. But the dose is not the same as the injectable dose. It's not a one-for-one versus if you're injecting it from a biophilized vial that's reconstituted, because an injection skips both hurdles entirely and lands the full amount in circulation.

Now, when we start talking about research-grade drugs, most of the time, that's kind of up in the air of whether or not it's bioavailable. Nobody spent the money on a delivery system. The powder is the powder.

A good example would be the one that we recently did a video on where I talked about whether or not SLUPP332 was viable if you were taking it orally. And after doing the research on the molecule and trying to figure out whether or not this was actually bioavailable and if it could be absorbed through your gut, the answer was basically maybe.

And if it is because it's a fat-soluble molecule, the only way to get a chance at ensuring that this was something that you could absorb, you'd have to make sure you eat it with a high-fat meal, like with breakfast, with like eggs and whatever. Fat-soluble compounds hitch a ride on dietary fat through the gut wall. No fat in the meal, no ride.

And that's exactly why the timing and when you take certain vitamins and minerals matters.