Food effects

You have certainly heard that it is recommended to take certain medicines or vitamins with or without food. But are there differences between these two conditions when the same dose of a drug or vitamin is taken? Yes, and these differences are called food effects. Compound uptake (absorption) into the human blood stream may be different when it is administered with or without food. Food effects can be positive or negative, in other words: under fed conditions (with food) the absorption of certain compounds may increase or decrease compared to fasting state (without food). Compound absorption will finally have an impact on bioavailability and the therapeutic effect of a drug. It is therefore important to investigate food effects on medicines.

What are the differences between the fasting and fed states?

Stomach: When a medicine is taken without food it is usually swallowed with a glass of water. On that basis the fasted stomach comprises 250 ml of fluid with a low pH of about 1.6 and small amounts of bile salts and phospholipids. These components come from regurgitation from the upper small intestine. Food administration changes the environment of the stomach drastically. The fed stomach has a pH above 4 and comprises a mixture of food components such as fats, proteins and carbohydrates.

Intestine: the fasted intestine comprises a fluid with a pH of about 6.5. Apart from salts the fluid incorporates significant amounts of bile coming from the gal bladder. Bile components are able to put poorly soluble substances into solution. After food ingestion the pH in the intestine decreases to values lower than 6. The gal bladder excretes larger amounts of bile in order to put ingested fats into solution. Therefore the fed intestine incorporates digestion products such as free fatty acids, mono- and diglycerides.

What are the drivers for drug absorption?

Following key drivers are responsible for drug uptake into the human or animal body: drug solubility, dissolution and permeability. If one or more of these factors are considerably influenced by diet intake, food effects can take place. Especially BCS class II and IV drugs show food effects, because their solubility (and permeability for class IV) depends on the surrounding environment, such as pH, bile salt concentration and digestion contents.

Examples of food effects

Positive food effects occur when drug absorption is better in the fed state than in the fasted state. In the fed state higher concentrations of bile components as well digestion products are seen as contributors for drug dissolution. A good drug example for positive food effects is danazol (see picture below).

Higher absorption of danazol under fed conditions was attributed to better dissolution of the drug in fed intestinal fluid (FeSSIF) than in fasted intestinal fluid (FaSSIF) (picture below).

By contrast, negative food effects take place when drug absorption is lower in the fed state compared to the fasted state. Furosemid shows this effect due to its decrease in dissolution after food intake.

How to predict food effects?

It is possible to predict food effects by investigating solubility, dissolution and permeability of a drug or drug product under simulated fasted and fed state environments. Biorelevant Media such as FaSSGF, FaSSIF, FeSSGF and FaSSIF are generally used for this purpose, because they closely represent the real conditions of the human fasted and fed stomach and intestine.


Vibeke H Sunesen et al.: Effect of liquid volume and food intake on the absolute bioavailability of danazol, a poorly soluble drug (2005)

Sandra Klein: The Use of Biorelevant Dissolution Media to Forecast the In Vivo Performance of a Drug (2010)

Marasanapalle et al.: Investigation of some factors contributing to negative food effects (2009)

Jef Stappaerts et al.: Human and simulated intestinal fluids as solvent systems to explore food effects on intestinal solubility and permeability (2014)