How Melanin Can Change How Medicines Work

Many medicines were tested on light-skinned people - yet the amount of pigment in your skin can help determine whether they work for you or mainly leave you with side effects.

Medicine is often treated as objective and neutral. However, researchers are increasingly showing that something as basic as skin colour can affect how much of a drug actually reaches its target in the body, how long it stays there, and whether today’s recommended dose is truly right. The reason lies in the pigment cells themselves: melanin.

Melanin: More than just skin colour

Melanin is the pigment that gives skin, hair and eyes their colour. People with darker skin generally have far more melanin than those with very fair skin. Crucially, this pigment can bind to certain active substances - and in doing so, it can change how those substances are distributed around the body.

"Melanin acts like a sponge for some medicines and chemicals. It traps them, stores them, and in doing so changes their effect."

Evidence from studies suggests that nicotine, for example, can bind to melanin. In people with darker skin, that may mean less freely available nicotine reaches the blood and the brain. That, in turn, could help explain why some people smoke more to feel the same effect - a vicious cycle with serious health consequences.

A similarly worrying issue involves toxins: certain pesticides may accumulate more strongly in pigment-rich tissues. In that case, general limit values for “safe exposure” may fall short, because they rely on averages that barely take melanin’s influence into account.

A warning sign since the 1960s - and largely ignored

Specialists have been finding indications for decades that melanin and medicines can interact. Even so, these insights still tend to play only a minor role in modern drug development. Standard dosing commonly assumes that bodies absorb, distribute and break down medicines in broadly the same way.

In pharmacology, this is described as pharmacokinetics: how an active substance enters the bloodstream, reaches target organs, is stored, and is ultimately eliminated. If melanin “locks away” some of a drug, less of it reaches where it is meant to work - for instance in the brain, the lungs, or tumour tissue.

• high melanin levels: more binding of certain active substances
• low melanin levels: more freely available drug, often a stronger effect
• unequal baseline data: doses are still based largely on light-skinned participants

This one-sided evidence base is increasingly becoming a real problem - especially in a globalised medical landscape where treatments are expected to work for everyone.

New technologies bring real-world variation into the lab

To close this gap, research teams are turning more and more to advanced cell models. Instead of relying on a single standard cell line, scientists are developing three-dimensional cell cultures that recreate different degrees of skin pigmentation.

These 3D models mimic real layers of skin, including pigment cells with variable melanin levels. That allows researchers to observe directly how strongly an active substance binds to the pigment, how long it remains in cells, and how much of it ultimately “gets through” into the body.

Organ-on-a-chip: Mini organs in the laboratory

A particularly important step forward is the rise of so-called organ-on-a-chip systems. These are tiny, perfused plastic chips on which different cell types can grow together - for example, skin cells alongside liver cells.

A nutrient solution flows through microchannels, mimicking circulation. This makes it possible to track in real time what happens when a medicine:

• first comes into contact with pigment-rich skin cells,
• is then broken down by liver enzymes,
• and how much active substance is still active in the end.

Such systems could reveal early in development whether a drug works more weakly or more strongly in people with high melanin levels, whether it stays in the body longer, or whether it accumulates in particular tissues. For pharmaceutical companies, that would provide a way to plan dosing with greater nuance.

"With organ-on-a-chip, you can test in the laboratory what previously only becomes apparent in late-stage studies - or, in the worst case, in patients’ everyday lives."

For this technology to be adopted widely, regulatory requirements are still needed. Without clear rules on what must be reported about skin pigmentation and the origin of cell material, the more complex models often remain an option rather than the default.

Who is included in trials - and who is missing?

Another blind spot sits within clinical trials themselves. In the past, many large drug studies recruited predominantly people of European ancestry. That may reduce costs, but it distorts the overall picture: effects and side effects in people with darker skin or different genetic backgrounds are then captured inadequately.

Policy and regulators are responding - slowly. New requirements in the US ask manufacturers to submit concrete plans for reaching more diverse participant groups, in terms of ancestry, ethnicity and skin colour.

This may sound technocratic, but it has direct consequences for patients. When reading a patient information leaflet, people increasingly want to know not only the ages of participants, but also whether individuals with similar skin colour, similar genetic background and similar pre-existing conditions were included.

Barriers: Mistrust and access

Communities that have historically had bad experiences with medical research often have limited trust in pharmaceutical companies. Practical obstacles add to that: trial sites are frequently far away, the time burden is unpaid, and travel costs are not always reimbursed.

If research is meant to represent everyone, trial organisers need to:

• bring study locations closer to underserved areas,
• compensate travel costs and time commitments,
• explain clearly - in plain language - what data are collected, including information on skin pigmentation.

Only then will people feel less like “guinea pigs” and more like respected partners in a study.

Transparency: Who knows how testing was done?

One point experts repeatedly stress is disclosure: where cell models come from, and who makes up trial populations. At present, many publications include little more than average age and the split between men and women. Whether a medicine was tested on heavily pigmented skin often goes unreported.

"Anyone taking medicines should be able to find out whether people with similar skin colour, similar background and a similar daily life were represented in the studies."

Especially for drugs whose effects depend heavily on blood concentration - such as cancer treatments, psychiatric medicines, or strong painkillers - a melanin-related shift in distribution can, in extreme cases, determine whether treatment succeeds or leads to severe side effects.

What patients can do in practice

The responsibility does not rest solely with companies and regulators. Patients can also ask targeted questions during appointments, for example:

• “Is there data on how this medicine works in people with darker/lighter skin?”
• “Was the active substance tested in different population groups?”
• “With my skin colour, is there a higher risk of over- or under-dosing?”

Doctors will not know every study in detail, but these questions make the issue visible and increase pressure to demand more differentiated evidence.

Key terms explained briefly

Term	Meaning
Melanin	Pigment in skin, hair and eyes; protects against UV radiation and binds certain active substances.
Bioavailability	The proportion of an active substance that actually reaches the body and can become active.
Pharmacokinetics	The study of how the body absorbs, distributes, metabolises and excretes a medicine.
Organ-on-a-chip	A mini laboratory system that recreates organ functions using living cells on a chip.

Why this topic will not go away any time soon

The more precise medicine becomes, the more clearly differences between individuals come into focus: genes, diet, environment - and, importantly, skin pigmentation. Melanin does not influence every medicine, but for certain classes of active substance the effect is likely to be substantial.

That also creates opportunities. In future, doses could be tailored more accurately so treatments become safer and more effective for everyone. At the same time, pressure is growing on researchers and industry to share data more openly and to design studies more fairly.

Anyone taking medicines should therefore feel able to raise individual factors. Skin colour is not a minor detail; in many cases it is a central element of personal pharmacology - and science is only just beginning to incorporate that element systematically into its calculations.

---