How Melanin Affects Medicines and Side Effects

Most tablets, injections and patches are designed on the assumption that every body processes medicines in the same way. New research indicates that this is not the case. In particular, the amount of melanin in the skin may affect how much of an active substance reaches its target – and how great the risk of side effects may be.

How melanin changes the effects of medicines

Melanin is the pigment that gives skin, hair and eyes their colour. People with darker skin have more of it, while those with very fair skin have considerably less. What is less widely known is that melanin can bind certain molecules – including medicinal compounds and toxins.

This is where the difficulty begins: if a medicine becomes ‘stuck’ to melanin, less of its active ingredient reaches the place where it is meant to work, such as the brain or other organs.

“Melanin can act like a chemical sponge: it absorbs certain medicines and thereby changes their distribution in the body.”

Nicotine as an example: why smoking works differently in some bodies

This effect has been studied particularly closely in relation to nicotine. Research suggests that nicotine binds to melanin. In people with darker skin, some nicotine may therefore be ‘stored’ in pigment-rich cells rather than rapidly reaching the brain.

As a result, the intended effect – for instance, the familiar ‘kick’ sensation – may be less pronounced. Some people affected may then unconsciously smoke more in order to feel the same effect. This does not alter how harmful smoking is, but it does change the dynamics of addiction and consumption.

When toxins accumulate in the skin

Melanin interacts not only with medicines but also with environmental toxins, including certain pesticides. These substances can build up at higher concentrations in darker skin than in lighter skin.

This calls long-established threshold values into question. Many so-called ‘safe’ exposure limits were set using test participants whose pigmentation was barely considered. If toxins accumulate more readily in pigment-rich skin, some people may be exposed to substantially greater burdens even though they are formally below the limit.

“Uniform limits imply equal safety for everyone – the available evidence shows that this is not automatically true when skin pigmentation differs.”

A research gap since the 1960s – and no one has caught up

Scientists found indications as early as the 1960s that melanin interacts with certain medicinal compounds. Even so, this knowledge was barely incorporated into the pharmaceutical industry’s standard procedures. To this day, many dosage recommendations implicitly assume that all bodies absorb, distribute and break down medicines at similar rates.

This may have two consequences:

• Medicines may be too weak for some people even when they receive the ‘standard’ dose.
• Toxins or by-products may be deposited in pigment-rich tissues, increasing the long-term risk of harm.

Experts therefore argue that melanin should be treated as a fixed parameter in drug development, much like body weight, age or kidney function.

New technologies: mini-organs and chips with artificial skin

The good news is that the tools required for fairer medicines research already exist. Modern cell biology makes it possible to grow artificial tissues with different levels of pigmentation and test precisely how medicines behave within them.

3D skin models with different pigmentation

Laboratories can now grow 3D skin models that closely resemble real human skin. Researchers can deliberately produce versions containing low, medium or high levels of melanin, then examine:

• How deeply does an active substance penetrate heavily pigmented skin?
• How much remains bound to melanin, and how much enters the bloodstream?
• Does the duration of action change depending on pigmentation?

Such experiments provide data long before the first person receives a test dose. This makes it possible to fine-tune dosages and identify risks at an early stage.

Organ-on-a-chip: when skin and liver work together on a chip

Another approach involves so-called organ-on-a-chip systems. Nutrient solutions and active substances flow through tiny channels containing different cell types – skin cells and liver cells, for example, at the same time.

This enables realistic scenarios: a medicine first encounters pigmented skin cells, partly binds to melanin, and the remainder then travels to the ‘liver’ on the chip, where it is broken down. Researchers can observe in real time how much active substance reaches each location.

“Organ-on-a-chip technology shows in the laboratory what happens in the real body – while allowing skin colour to be varied deliberately.”

To ensure that these technologies do not remain confined to a small number of pilot laboratories, regulators need to establish clear guidance. Without pressure from authorities and funding programmes, many companies are reluctant to take on the additional costs.

Who is tested at all? The problem of one-sided studies

Another weakness is the selection of trial participants. For decades, many clinical studies recruited predominantly people of European heritage. This produced data that can be transferred to other groups only to a limited extent – especially where skin colour directly affects the distribution of an active substance.

Laws such as the Food and Drug Omnibus Reform Act of 2022 now require pharmaceutical companies in the United States to submit specific plans for greater diversity in their studies. These include:

• Targets for including different ethnic groups and skin tones
• Strategies for reaching population groups that are difficult to engage
• Measures to reduce mistrust of the pharmaceutical industry

Many minority groups have had negative experiences with research and healthcare. Without transparent information and genuine involvement, trust remains low – and so does participation in studies.

Everyday barriers: who can afford to take part?

Even where people are in principle willing to join a study, participation often fails because of practical issues:

• Study centres are far away, often in major cities.
• Travel costs and lost earnings are reimbursed inadequately.
• Information is not available in the target group’s first language.

Only when studies become more inclusive in organisational and financial terms will their participants better reflect reality – including different skin colours and melanin levels.

Greater transparency: which data patients should ask for

Experts are calling for far greater openness around study data. Anyone taking part in a clinical trial today could, for example, ask specifically:

• In which population groups has the active substance already been tested?
• Were analyses carried out according to skin pigmentation or melanin content?
• Which cell models did the laboratory use in the early stages – those of predominantly European or African ancestry?

“The more clearly studies disclose whom they genuinely represent, the more likely trust is to develop – particularly among population groups that have so far felt overlooked.”

If this information appeared as standard in study documentation, patients would be better able to judge whether the available data apply to them.

What this may mean in practical terms for affected people

This has several practical implications for everyday care. Doctors should recognise that characteristics such as skin colour, ancestry and pigmentation may indicate different medicine profiles – much as impaired kidney function can affect dosage.

When prescribed new medicines, patients can ask directly:

• Is there evidence that the active substance works differently in people with darker or very fair skin?
• Is study material available that includes comparable patient groups?
• Which side effects occur more often in different population groups?

There is still very little melanin-related data for many medicines. However, the more often these questions are raised, the greater the pressure on manufacturers and regulators to close this gap.

Why skin colour is more than a visual feature in medicine

In everyday life, skin colour is often reduced to aesthetics and social identity. From a pharmacological perspective, however, it is also a biological factor with tangible implications for the effectiveness and safety of medicines.

Melanin affects how long certain active substances remain in the body, where they accumulate and how strongly they work in the first place. This is not a minor detail: in borderline cases, it can determine whether a treatment works optimally or whether people receive too little or too much care.

Once medicines research, regulatory bodies and clinics consistently take melanin into account, it will be possible to develop medicine that takes every skin colour seriously – bringing it closer to the promise of being genuinely safe and effective for everyone.