What is bioavailability?
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Bioavailability is the rate and extent to which an active ingredient is absorbed and becomes available at its site of action1. Absolute bioavailability compares a product against an intravenous reference, while relative bioavailability compares one formulation with another1. Solubility, intestinal permeability, metabolism in the gut wall and liver, and food all change how much of an ingested compound reaches the bloodstream2,3,4.
How is bioavailability measured?
The US Food and Drug Administration (FDA) defines bioavailability (BA) as the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action1. For oral products, it is usually measured by sampling blood over time and comparing the resulting plasma exposure profile with that of a suitable reference product1. The area under the plasma concentration curve (AUC) and the maximum concentration (Cmax) are the standard measures of the extent and rate of absorption2.
The reference determines what the number means. A study with an intravenous reference defines absolute bioavailability, while a study comparing one formulation with another gives relative bioavailability1. A relative figure, such as "three times better absorbed", is a comparison with another formulation and does not on its own state how much of the compound reached the bloodstream1.
The plasma profile captures more than absorption alone: it reflects both the release of the substance from the product and any changes to the substance before it reaches the general circulation1.
| Absolute bioavailability | Relative bioavailability | |
|---|---|---|
| Reference | An intravenous reference product1 | Another formulation of the same compound1 |
| What it tells you | The share of the compound that reaches the systemic circulation1 | Whether one formulation delivers more or less than another1 |
| Typical measures | AUC and Cmax2 | AUC and Cmax2 |
| Common use | Characterizing a compound and its route of administration1 | Comparing a new formulation with an existing one1 |
Why do some compounds have low bioavailability?
Two physical properties set the first limits. The Biopharmaceutics Classification System (BCS), adopted internationally through the ICH M9 guideline, sorts drug substances by their aqueous solubility and intestinal permeability2. A substance is considered highly permeable when its absolute bioavailability is 85% or more2.
Federal regulations list further reasons a product may perform poorly: low water solubility, slow dissolution, particle size, crystal form, excipients that help or hinder absorption, absorption confined to one segment of the gut, and instability in parts of the gastrointestinal tract3. The same rule names rapid metabolism of a compound in the intestinal wall or liver during absorption, known as first-pass metabolism3. Curcumin, the main active compound in turmeric (Curcuma longa), is a widely studied example: its poor bioavailability has been attributed to rapid metabolism in the liver and intestinal wall6.
| BCS class | Solubility | Permeability |
|---|---|---|
| Class I | High | High |
| Class II | Low | High |
| Class III | High | Low |
| Class IV | Low | Low |
How does bioavailability work for dietary supplements?
The science is the same, but the oversight is not. Under US law, FDA does not have the authority to approve dietary supplements before they are marketed, and it does not approve supplement labeling, apart from certain claim types such as health claims8. A bioavailability claim on a supplement label has therefore not been reviewed by FDA before sale8.
Nutrients also show how much bioavailability depends on the diet and the person. Iron bioavailability has been estimated at 14 to 18% from mixed diets and 5 to 12% from vegetarian diets in people with no iron stores5. In the same review, the iron status of the individual had a greater effect on iron absorption than the composition of the diet5.
What factors raise or lower absorption from supplements?
Published studies point to a handful of recurring factors. Food is one: drug developers run dedicated food-effect studies because a meal can change absorption1. Accompanying compounds are another, and the formulation itself is a third6,7.
- Single-meal studies tend to overstate the effect of one food component: in multimeal studies with a varied diet, the effect of single enhancers or inhibitors on iron was more modest5.
- In the 1998 Planta Medica study of curcumin with piperine, curcumin alone produced undetectable or very low serum levels in volunteers, and piperine increased its bioavailability by 2000%6.
- Delivery systems such as liposomes and phytosomes are formulations like any other, so a claim about them is a relative comparison that depends on the reference product used1.
| Factor | Example from the literature | Direction of effect |
|---|---|---|
| Dietary fat | In a randomized single-dose study in 50 healthy older adults, peak plasma vitamin D3 was 32% higher when the supplement was consumed with a fat-containing meal than with a fat-free meal4 | Raises absorption of a fat-soluble vitamin4 |
| Enhancers in the meal | Ascorbic acid and muscle tissue increase iron absorption in single-meal isotope studies5 | Raises iron absorption5 |
| Inhibitors in the meal | Phytate, polyphenols and calcium reduce iron absorption in single-meal isotope studies5 | Lowers iron absorption5 |
| Metabolic inhibitors | Piperine, an inhibitor of glucuronidation in the liver and intestine, raised curcumin bioavailability in rats and human volunteers6 | Raises exposure to the compound6 |
| Host factors | Iron status and obesity influence iron bioavailability5 | Varies by person5 |
Is higher bioavailability always better?
No. FDA's guidance points out that a formulation giving significantly higher exposure than its reference could raise safety concerns, while significantly lower exposure could make it less effective1. Greater variability between people can affect both safety and efficacy1.
Curcumin illustrates the point. The National Center for Complementary and Integrative Health (NCCIH) reports that many curcumin products with increased bioavailability are on the market, and that liver damage has been reported in some people who consumed these formulations7. NCCIH also notes that more research is needed to understand how bioavailability affects curcumin's effects7.
How should you read a bioavailability claim?
Start with the reference. A claim based on an intravenous comparison describes absolute bioavailability; a claim based on another formulation describes relative bioavailability1. Look for the measures used, typically AUC and Cmax2, and for whether the study controlled for food, since meals change absorption1,4.
Then check who reviewed the claim. Drug bioavailability data are reviewed by FDA as part of an application1, while supplement labels are not approved by FDA before marketing8. Finally, ask whether the comparison was made in people or only in animals: in the 1998 curcumin study, piperine raised bioavailability by 154% in rats but by 2000% in human volunteers6.
Key takeaways
- Bioavailability is the rate and extent of absorption and availability at the site of action.
- Absolute bioavailability needs an intravenous reference; relative bioavailability only compares formulations.
- Solubility, permeability and first-pass metabolism set the main limits.
- Food, other compounds in the meal and the person's own status all change nutrient absorption.
- Higher bioavailability can change safety as well as effect, as NCCIH reports for curcumin.
References
- Bioavailability Studies Submitted in NDAs or INDs: General Considerations, Guidance for Industry
- M9 Biopharmaceutics Classification System-Based Biowaivers, Guidance for Industry (ICH)
- 21 CFR Part 320 Bioavailability and Bioequivalence Requirements (§ 320.33 criteria and evidence to assess actual or potential bioequivalence problems)
- Dietary fat increases vitamin D-3 absorption
- Iron bioavailability and dietary reference values
- Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers
- Turmeric
- Questions and Answers on Dietary Supplements
Frequently asked questions
What is the difference between bioavailability and absorption?
Absorption is one part of bioavailability. FDA's definition covers both how much of an active ingredient is absorbed and whether it becomes available at the site of action1. A compound can be absorbed and then changed in the gut wall or liver before it reaches the circulation, which is first-pass metabolism3.
Why does bioavailability differ from person to person?
Host factors matter. For iron, the individual's iron status and factors such as obesity play a key role, and iron status generally has a greater effect than diet composition5. Drug studies measure variability between subjects for the same reason, since wide variability can affect both safety and efficacy1.
Does a fat-containing meal improve absorption of every supplement?
Does black pepper increase the absorption of all supplements?
The evidence is specific to particular compounds. Piperine, the active compound of black pepper, inhibits glucuronidation in the liver and intestine and raised curcumin bioavailability in the 1998 study6. NCCIH describes combining curcumin with piperine as one way to improve curcumin's bioavailability7.