The term dose-response describes the relationship between the dose of a substance or stimulus and its effect. A dose-response study explores the dose-response relationship between an intervention and an outcome in terms of the efficacy and/or safety of a substance or stimulus.


    What is dose-response?

    Dose-response refers to the relationship between the dose of a substance or stimulus and its effect on an outcome of interest in a specific organism. Dose-response relationships can be simple and linear, but are often complex and nonlinear. For example, a dose-response relationship often means that a response tends to get larger as the dose increases. However, there is typically also a maximal response reached at a particular dose.

    What is a dose-response study?

    A dose-response study is a useful way to determine the efficacy (pharmacology) and/or safety (toxicology) of a substance or stimulus that humans or other organisms are exposed to. Such substances and stimuli can include drugs, foods, supplements, pollutants, pathogens, temperature, light, and more.

    For example, to determine the dose of supplement A that has the greatest efficacy for increasing HDL cholesterol (HDL-C), a group of people with metabolic syndrome would be randomized to receive 0, 25, 50, 100, 200, or 400 mg of supplement A per day for 6 weeks, and the researchers would measure HDL-C before and after 6 weeks of treatment. To understand the dose-response of supplement A on HDL-C, the investigators would construct a dose-response curve like the one below (Figure 1), which displays the change in HDL-C after 6 weeks of supplementation with the different doses of supplement A. The dose-response curve in Figure 1 indicates that the lowest dose of the substance (25 mg/day) is insufficient to cause a response, whereas increasingly higher doses eventually lead to a maximal response. Specifically, 0 and 25 mg/day of supplement A have no effect on HDL-C, while 50, 100, 200, and 400 mg/day increase HDL-C after 6 weeks of treatment. However, there is no further increase in efficacy beyond 200 mg/day of supplement A, suggesting that there is no reason for people with metabolic syndrome to take a dose greater than this level.

    Figure 1: A dose-response curve for supplement A

    Note that this is an example of a simple dose-response relationship. A real dose-response study would also be designed to determine the toxicity of supplement A at various doses and subsequently identify the lowest dose that causes the greatest efficacy with the lowest toxicity.