BIOAVAILABILITY MATTERS

What Bioavailability Actually Means

In pharmacology, bioavailability is the fraction of an administered dose that reaches systemic circulation in unchanged form. For an intravenous drug, bioavailability is by definition 100 percent -- the whole dose is in circulation immediately. For an oral drug or supplement, the fraction can be anywhere from essentially zero to nearly 100 percent depending on how well the molecule survives the gut, gets absorbed across intestinal membranes, and avoids first-pass hepatic metabolism on its way to the rest of the body.

Bioavailability is the single biggest predictor of whether a labeled dose translates into a functional effect. A 1,000mg labeled dose at 1 percent bioavailability delivers about 10mg to circulation. A 100mg labeled dose at 50 percent bioavailability delivers about 50mg. The smaller dose with the better delivery format wins by a factor of 5x in this case. Label numbers, on their own, are nearly meaningless without bioavailability context.

(I had to confront the bioavailability question early, before the formula made sense to me.)

The Numbers Are Worse Than Most People Realize

For many polyphenol-class supplement ingredients (flavonoids, catechins, anthocyanins, etc.), the absolute oral bioavailability is in the low single digits as a percentage. DHM at roughly 4 percent in standard formulations is actually middle-of-the-pack for the family¹. Plain oral glutathione is below 1 percent because of the gamma-glutamyltransferase cleavage problem in the gut³. Many curcumin formulations are around 1 percent without enhancement strategies. Most flavonoids are in the same general range.

This means that for most ingredients in this category, more than 90 percent of what you swallow never reaches the cellular compartments where the labeled mechanism is supposed to act, in the published pharmacokinetic data at least.

What Solving Bioavailability Looks Like

There are three engineering approaches to the bioavailability problem. The first is raising the input dose to overcome the haircut. The second is improving the formulation chemistry (lipid nanocarriers, sustained-release tablets, self-emulsifying systems, etc.), which the published DHM drug-delivery review covers across multiple format chemistries². The third is co-administering with a delivery agent that helps the molecule cross gut and cellular membranes -- which is what fulvic acid does in the H180 formula through chelation chemistry.

For SAG specifically, the engineering solution is a chemical modification (acetylation at the sulfur position) that protects the molecule from gut enzymes that would otherwise break it apart⁴. Different problem, different solution.

What a Label Number Cannot Tell You

A label states how much of an ingredient is in the capsule, not how much reaches circulation. For DHM, that second number has not been measured in people, so no DHM label can show it, ours included.

What This Page Is Not Claiming

We are not claiming all polyphenol supplements are useless or that bioavailability is the only thing that matters. The claim is narrower -- bioavailability is the most underappreciated number in supplement formulation, and the labeled dose is not the delivered dose. Choosing supplements that take bioavailability seriously is the single most useful filter in the category.

For the DHM-specific bioavailability story, see DHM Bioavailability. For the SAG delivery-format story, see SAG Intracellular Delivery.