Your skin color may influence how safe and effective a given drug is for you, a new analysis suggests.
In a recent think piece, published Oct. 9 in the journal Human Genomics, scientists examined a plethora of studies, revealing that melanin — the pigment that gives our skin, hair and eyes their color — can absorb certain drugs that are either applied to the skin or taken orally, thus affecting how much of a dose makes it to the tissues that need treatment.
This means that people's responses to a standard dose of a given drug may vary depending on their skin tone. For instance, research has shown that nicotine binds to melanin and that variations in skin pigmentation may influence how much people smoke. This may be because, once nicotine is inhaled, it travels through the bloodstream and is absorbed by melanin-containing cells in the skin, therefore reducing how much of the drug reaches the brain. However, the exact reason is not yet fully understood.
Toxic chemicals, such as those found in fertilizers and pesticides, may also accumulate in higher concentrations in darker skin than in lighter skin, the researchers found. This could reframe what a standard safe-exposure level might be for certain demographics.
In the think piece, Sophie Zaaijer, a consultant and researcher affiliated with the University of California, Riverside, and Simon Groen, an assistant professor of evolutionary systems biology at UC Riverside, noted that melanin's ability to interact with specific drugs was flagged back in the 1960s. However, they argued that its effects have not been properly considered in preclinical research or in clinical trials of new drugs.
So what can be done to tackle this persistent issue?
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Use more diverse cellular models
Drugs go through many rounds of testing as they're developed. First, after identifying a potential drug, scientists assess how it works in animal and human cells in the lab. If it appears to have the desired effect, the drug is tested in living animals, such as rats, which should help flag potential safety issues before the drug is tested in human patients. Then, the drug enters clinical trials in humans, confirming it really works as expected and is safe in people.
Initial drug tests in the lab have mainly been done in cell lines from people of European descent. However, in the past few years, technological advancements have allowed scientists to create more complex cellular models in the lab that include varying degrees of pigmentation.
"This is a super exciting time," Zaaijer said. "Innovations in cell biology are going at light speed."
It's now possible to grow 3D cell models that accurately mimic different shades of human skin, and these models can be ordered easily online. The researchers say these models, which are fairly new, could be used in preclinical experiments to show how potential drugs interact with melanin, long before the medicines are given to people.
Scientists have also developed credit-card-sized devices that mimic different cells and organs and can be hooked together into a complex system. These are known as "organ-on-a-chip" models. Skin cells can be kept in one chamber of a given device and liver cells in another, allowing researchers to simultaneously study how drugs interact with melanin in the skin and with detoxifying enzymes in the liver.
These devices could be useful for predicting how people with different skin tones may respond to drugs in clinical trials, Zaaijer said.
Implement regulatory guidelines
For these technologies to be used widely, there needs to be input from regulatory bodies, Zaaijer and Groen argued. Otherwise, pharmaceutical companies may be less inclined to employ them, they said.
Another burgeoning issue is to address the lack of diversity in clinical trials. For some patients in minority groups, clinical trials may be geographically inaccessible or too expensive in terms of travel costs or the need to take time off work to participate in them, Zaaijer said.
New legislation aims to improve this situation. In 2022, the Food and Drug Omnibus Reform Act was signed into law. This legislation stipulates that plans should be developed to increase the diversity of participants in clinical trials.
In 2024, the U.S. Food and Drug Administration (FDA) also published a draft guidance document to aid drug manufacturers in developing "Diversity Action Plans," which aim to make clinical trials more diverse. These plans must include information on a company's goals for enrolling people of different ages, ethnicities, races and sexes into clinical trials, as well as how they intend to achieve these objectives.
Researchers can also be more transparent about the types of cell models they have used to test particular drugs in preclinical research, Zaaijer said. Most studies, for instance, report the code names of cell lines that they used but not their ancestry, she added. This is something that the FDA could easily enforce, she said. The agency could state that data must note whether experiments are done with cell models of European descent or African descent.
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Regain patients' trust
Patients should also feel empowered to ask questions during clinical trial recruitment, Zaaijer said. If you're being invited to enroll in a clinical trial, ask the researchers, "Has this drug been tested in a variety of ancestral models in preclinical research?" she said. In other words, has the company that developed it considered your needs as an individual of your race and ethnicity?
Taking into account differences in skin tone during preclinical research could help encourage more people from diverse backgrounds to participate in clinical trials, Groen said. This is important because research has shown that members of racial and ethnic minority groups are less likely to sign up for trials than their white peers. Research staff are also likely to display bias toward recruiting people from minority groups, according to other analyses.
"There's a distinct lack of trust — for example, in the African American community — towards 'Big Pharma' companies," Groen said. If these companies can show people more representative preclinical data before they sign up for a trial, they're going to be more likely to trust that these drugs are not going to harm them, he suggested.
"Representation in clinical trials is a critical issue for the clinical trial community, and fortunately, representation and diversity in clinical research has been improving over time," said Jakub Hlávka, a research assistant professor in health policy and management at the University of Southern California who was not involved in the new think piece.
"However, less is known about representation with respect to skin pigmentation, which may have an effect on the bioavailability of drugs," he told Live Science in an email.
In a 2022 study, Hlávka and colleagues concluded that a lack of representation in clinical trials compromises how well the trial findings generalize to the whole U.S. population, which may hinder innovation, among other negative effects.
"Further analysis may include the study of representation of populations with different skin tones in clinical trials, particularly in areas where there may be implications for the clinical effectiveness of investigational drugs," Hlávka said.
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