What is bioavailability?

Bioavailability is the percentage of a substance that actually makes it into your bloodstream and becomes available to produce effects. When you take a substance orally, not all of it reaches your brain — some is destroyed by stomach acid, some is metabolized by liver enzymes before reaching circulation ("first-pass metabolism"), and some simply isn't absorbed.

Bioavailability is expressed as a percentage:

100% bioavailability = the entire dose reaches circulation (by definition, intravenous injection = 100%)
50% bioavailability = half the dose reaches circulation; the rest is lost to digestion and metabolism

Why bioavailability matters for microdosing

Dose accuracy

If a substance has 50% oral bioavailability, you need to take twice as much orally to get the same circulating dose as you would through a 100% bioavailable route. This is why the "effective dose" depends not just on the amount you take, but on how you take it.

Route of administration matters

Route	Bioavailability	Onset	Notes
Oral (swallowed)	Variable (20–80%)	30–90 min	Most common for microdosing; affected by food, stomach pH
Sublingual (under tongue)	Higher than oral	15–45 min	Bypasses first-pass metabolism
Oral (dissolved)	Volumetric dosing	30–60 min	Gold standard for precision
Insufflation (nasal)	High	5–15 min	Not typical for microdosing

Variability is the enemy

For microdosing, consistency is more important than maximizing bioavailability. This is why:

Volumetric dosing is recommended — dissolving in liquid provides the most consistent bioavailability
Taking capsules on an empty stomach reduces variability
Consistent timing relative to meals helps standardize absorption

Factors that affect bioavailability

Substance-specific

Chemical stability in stomach acid — some compounds degrade in acidic environments
Molecular size and lipophilicity — affects absorption through gut lining
First-pass metabolism — liver enzymes (especially CYP450 family) can metabolize a significant portion before it reaches the brain

Individual

Genetics — CYP450 enzyme variants affect metabolism speed
Age — liver function and gut absorption change with age
Body composition — affects distribution of lipophilic substances
Gut health — microbiome and gut lining integrity affect absorption

Contextual

Food — eating before dosing generally slows absorption and may reduce peak bioavailability
Stomach pH — antacids, proton pump inhibitors can alter absorption
Other substances — caffeine, grapefruit juice, and certain supplements can affect CYP450 enzymes

Practical tips for consistent bioavailability

Dose on an empty stomach (or consistently with light food) — reduces variability
Use volumetric dosing — the substance is already dissolved, so absorption is more predictable
Consistent timing — same time of day, same relationship to meals
Sublingual option — holding a liquid dose under your tongue for 1–2 minutes before swallowing can increase bioavailability
Avoid grapefruit juice — it inhibits CYP3A4 enzymes and can unpredictably alter drug metabolism

Bioavailability