Your lifestyle choices decide how well a medication works for you, findings of a new study reveal. Researchers have found that unhealthy lifestyle choices such as smoking, alcohol use, and obesity can affect the way the body metabolizes a drug.

Researchers have known the potential impact of unhealthy lifestyle choices on enzyme levels, which in turn may influence drug metabolism.

Seeking a deeper understanding of this connection, researchers from Aarhus University's Department of Forensic Medicine conducted tests on liver samples from 116 deceased individuals with mental illness. The objective was to understand the impact of lifestyle factors on the production of drug-metabolizing enzymes, with a notable portion of their study subjects being smokers, alcoholics, or obese.

"People suffering from severe mental illness have a life expectancy of about 20 years lower than the rest of the population. There are several reasons for this, for example, the mentally ill commit suicide more often. They also have an increased incidence of lifestyle-related factors such as diabetes, obesity, smoking, and alcohol or drug use," said Kata Wolff Pedersen, the study author, in a news release.

"It's exciting to see how lifestyle affects the amount of drug-metabolizing enzymes in the body, because a change in the amount of enzyme can reduce the efficacy of the drugs used by this group of patients," she said.

The researchers found that smokers have double the levels of a specific drug-metabolizing enzyme CYP1A2 compared to non-smokers. Consequently, they metabolize drugs, including antipsychotic medications, at a faster rate, posing a higher risk of receiving incorrect treatment.

In the case of participants who used alcohol, the levels of the drug-metabolizing enzyme CYP2E1 were approximately 30% higher compared with people without known alcohol consumption.

"This means that standard doses of a drug may have a lower effect on a significant part of the group of people we've studied," Pedersen said.

However, upon analyzing liver samples from obese individuals, researchers observed an opposite effect on a distinct drug-metabolizing enzyme, CYP3A4. A higher BMI was associated with a decrease in the production of this enzyme.

"The study shows that people with a very high BMI produce significantly smaller amounts of the CYP3A4 enzyme – in fact, they only have half as much enzyme in their body as people of normal weight. This can cause them to metabolize their medicine too slowly, thus increasing the risk of side effects. CYP3A4 is involved in the metabolism of a large number of important drugs, and therefore this may be significant for overweight individuals not receiving the right doses, and potentially receiving incorrect treatment," the news release stated.

"We're the first to show that tissue from deceased people can be used to examine the level of drug-metabolizing enzymes. This makes it significantly easier to obtain material in a field in which it is otherwise virtually impossible to obtain a high number of liver biopsies," Pederson said.

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