A supplement label states how much of a compound is in each capsule. What reaches circulation is a different and usually much smaller quantity, determined by a sequence of physical and chemical obstacles.
Dissolution comes first
A compound cannot be absorbed while it remains a solid particle. It must dissolve in the fluid of the digestive tract before transport across the gut wall becomes possible.
Many compounds of interest dissolve poorly in water, so the quantity that dissolves within the time available sets an immediate ceiling on absorption.
This is why formulation matters as much as dose, and why the same compound in different physical forms produces different results from identical label amounts.
Fat-soluble compounds need fat present
Vitamins A, D, E and K, along with many plant compounds, dissolve in fat rather than water and are absorbed through the same route as dietary fat.
Taken without food, they have no vehicle for that route, and a substantial share passes through unabsorbed regardless of how much was swallowed.
The instruction to take certain supplements with a meal is describing this mechanism rather than offering a convention about timing.
The liver processes before distribution
Blood leaving the intestine travels to the liver before entering general circulation, and the liver chemically modifies many compounds on that first pass.
Some are extensively converted to forms that are cleared rapidly, meaning only a fraction of what was absorbed ever reaches the tissue where it might act.
Compounds that undergo heavy first-pass processing therefore show low bioavailability even when absorption across the gut wall was efficient.
Chemical form changes the outcome
Minerals are sold as salts and complexes that differ in solubility, and these forms are not interchangeable despite carrying the same mineral name.
Iron, magnesium and zinc each have forms that differ substantially in how much is absorbed and in how likely they are to cause digestive discomfort.
Comparing products by the milligram figure alone therefore compares quantities that are not equivalent in what they deliver.
Competition and inhibition inside the gut
Several minerals share transport systems, so calcium, iron and zinc taken together compete, and a large dose of one reduces uptake of the others.
Compounds in ordinary foods also bind minerals and reduce their availability, which is why absorption from a supplement varies with what was eaten alongside it.
Spacing doses apart addresses some of this, but working out what is appropriate alongside prescribed medication is a question for a pharmacist.