Lifestyle determines drug effectiveness

By testing liver samples from 116 people who died with severe mental disorders, researchers found that smoking, obesity, and alcohol consumption are critical factors in determining how drugs work in individual patients. It has been demonstrated that it is possible.

It is already well known in the research community that an unhealthy lifestyle affects the levels of enzymes in the body and therefore the potential for drug metabolism.

However, research from the Department of Forensic Medicine at Aarhus University has shed new light on the influence of lifestyle. Liver samples from 116 deceased mentally ill people were tested, and importantly, the majority of those who died were smokers, alcoholics, and/or obese.

By looking at the amount of enzymes expressed in the livers of deceased people, researchers can show how well they metabolized important drugs.

“The life expectancy of people suffering from severe mental illness is about 20 years shorter than the rest of the population. There are several reasons for this. For example, mentally ill people often commit suicide. The incidence is also high, with associated factors such as diabetes, obesity, smoking, and alcohol and drug use,” explains Master and PhD student Kata Wolff Pedersen. Health science researchers, who are behind the research?

“It will be interesting to see how lifestyle affects the amount of drug-metabolizing enzymes in the body. Changes in the amount of enzymes may reduce the effectiveness of drugs used by this group of patients. “Because there is,” she says.

Alcohol and smoking increase drug metabolism

Research from the Department of Forensic Medicine shows that smokers have twice as much of a certain drug-metabolizing enzyme (CYP1A2) as non-smokers. This means that smokers metabolize certain drugs (such as antipsychotics) more quickly, so they are theoretically at greater risk of receiving the wrong treatment.

“We are the first to demonstrate at the protein level that smokers have increased enzyme levels simply because more enzymes are expressed in the body,” says Kata Wolf-Pedersen.

Liver tissue was collected during forensic autopsy. A full toxicological analysis was then performed based on statements in the autopsy report from the police, next of kin, or general practitioner, combined with information about the deceased's alcohol and smoking history.

Based on this, Kata Wolff Pedersen concluded that the levels of the enzyme CYP2E1 in people who use alcohol are approximately 30% higher than in people who do not use alcohol.

“Forty percent of the deaths included in our study were registered alcoholics. They are an interesting group because they have a special lifestyle. “We can prove that alcohol use increases the amount of enzymes in the body,” she explains.

“This means that a standard dose of a drug may have a lower effect on a significant portion of the group of people we studied,” says Kata Wolf-Pedersen. , this is certainly worth noting.

Obesity and overweight reduce levels of another enzyme

Researchers rarely have access to liver samples from such large groups. Studies of enzyme levels are typically performed in liver microsomes in vitro or in animal studies. The samples in this study were taken from identifiable people, allowing us to verify that lifestyle factors, including being overweight, are involved.

However, obesity and being overweight can have the opposite effect on important enzymes. This study shows that people with very high BMI produce significantly less of the CYP3A4 enzyme. In fact, the amount of enzymes in your body is only half that of a normal weight person.

This can cause the drug to be metabolized very slowly and increase the risk of side effects. Because CYP3A4 is involved in the metabolism of a number of important drugs, this can be a significant problem for overweight people who may not receive the correct dose and receive incorrect treatment. there is.

“40% of those studied died from poisoning by a mixture of legal and illegal drugs. However, since most substances are metabolized by several different enzymes, it is unlikely that the poisoning was caused by too few enzymes. It cannot be shown. They die because of changes in enzyme levels,” explains Kata Wolff Pedersen.

refrigerated pork liver

The study also included liver samples from dead pigs, and Kata Wolff Pedersen used these to confirm that enzyme levels after two days at room temperature were exactly the same as in fresh pig liver. . If the liver is kept refrigerated, the levels will remain the same for a whole week.

This is good news for researchers interested in enzyme levels.

“We have shown for the first time that tissue from deceased people can be used to test levels of drug-metabolizing enzymes. “It makes it much easier to obtain materials for liver biopsies,” she says.

The paper will be published in a magazine Drug metabolism and properties.