Caffeine caution: Genetic responses to caffeine fall into three main groups, study finds

08 Jun 2018 --- Coffee drinkers fall into one of three major groups based on their caffeine sensitivity, according to a new report: Genetics, Metabolism and Individual Responses to Caffeine. The study sought to determine why some coffee drinkers are more affected by caffeine than others and how healthcare professionals can take this into account when advising patients.

The study suggests that an individual's response to caffeine is likely determined by two main genetic factors: whether their liver can metabolize caffeine quickly or slowly; and whether they carry a genetic variation that makes their central nervous system more sensitive to caffeine's stimulating effects.

“We all know someone who can drink coffee all day and then sleep at night without any problems, while others need to limit themselves to just one or two cups to avoid feeling jittery. So I knew that there were differences on an individual level in the physiological and stimulating reactions to caffeine. But I was surprised to realize the degree to which genetic variability determines the everyday experience of such a basic action as drinking coffee,” Dr. J.W Langer, Physician and study author, tells NutritionInsight.

Based on these genetic factors, Dr. Langer has proposed three descriptive levels of overall caffeine sensitivity:

• High sensitivity to caffeine: Slow-metabolism in the liver and high binding in the central nervous system. Even small amounts of caffeine will cause a stimulating effect and higher doses may cause sleep problems, as seen in a minority of people.
• Regular sensitivity to caffeine: The balance between caffeine inactivation in the liver and binding in the central nervous system means that the individual can typically drink 2-5 cups of coffee during the day without adverse reactions or sleep disturbances. Caffeine is normally not recommended in the evening, but individual differences prevail, as seen in most people.
• Low sensitivity to caffeine: Fast-metabolisers of caffeine. Higher intakes can be consumed, (although healthcare professionals should advise that they still stay within the EFSA guidelines of no more than five cups of coffee per day). Coffee drinking before bedtime does not typically disturb sleep.

“It's common for people to ask their doctor questions such as why they are kept awake by one cup of coffee, while their partner easily falls asleep after five cups. The answer is that we are all unique coffee drinkers. Our genetic make-up programs our reaction to caffeine, just as it programs our hair color and eye color,” says Langer.

An individual with low sensitivity to caffeine probably will not experience the typically desired effects of caffeine, such as wakefulness, alertness and increased concentration. It is important for healthcare professionals to stress that fast metabolizers should not exceed the recommended daily caffeine intake trying to achieve the desired effects.

“Most people will self-moderate their caffeine intake based on their personal experience of what they can tolerate. However it's important that those with a low sensitivity to caffeine stay within the recommended daily caffeine intake of up to 400mg caffeine, which is equivalent to around five cups of coffee,” he adds.

“As a lifestyle-focused physician my advice is that you should not consume coffee purely for health reasons or to prevent or treat diseases. It’s better to go for a long walk or eat a large bowl of veggies. But if you, like me, love coffee, then the research reassures us that coffee will do you no harm, and can be part of a healthy, balanced diet.” 

This report explains the genetic variations that affect individuals' responses to caffeine in more detail, as well as outlining some of the non-genetic factors such as smoking status, pregnancy, and age. The report also stresses the importance of taking individual responses into consideration when healthcare professionals are advising patients and consumers on their caffeine intake.

NutritionInsight has previously reported on the expanding research around coffee, for example, a study published in the BMJ Open journal stated that even moderate coffee consumption during pregnancy, one to two cups per day, is related to a risk of overweight or obesity in school-age children. It had not been clearly shown if caffeine was the direct cause of the overweight, but the relationship, alone, caused researchers to encourage increased caution.