Caffeine cravings: Specific genes may influence coffee consumption

Globally, coffee is one of the most commonly consumed drinks, and caffeine is the most widely consumed psychoactive drug.

Yet, despite decades of research, links between coffee and health are still being examined.

There is some evidence that moderate coffee intake is linked to a reduced risk of liver disease, cardiovascular disease, certain cancers, and neurodegenerative conditions.

On the other hand, coffee may also be associated with the use and misuse of other substances and some cancers. It is a complex situation, likely involving genetics, how much someone drinks, and a wide range of other factors.

As the authors of the new paper write, “Addressing the full spectrum of coffee’s correlations with health and disease is therefore an important but challenging task.”

As strange as it seems, how much coffee or caffeine an individual drinks might be partly inherited from their parents. Previous research on twins has suggested that caffeine-related traits are 36–58% heritable.

To investigate these relationships, scientists use so-called genome-wide association studies (GWAS). In short, these studies analyze participants’ whole genomes to identify gene variants associated with a given trait.

In particular, they focus on single nucleotide polymorphisms (SNPs). These are the most common form of genetic variants and involve change in a single nucleotide — the building blocks of DNA.

Researchers then look for links between particular SNPs and the trait of interest. In this case, coffee consumption.

The latest study used genetic data from two large datasets:

1. 23andMe from the United States: 130,153 people.
2. UK Biobank from the United Kingdom: 334,659 people.

Alongside genetic information, these datasets have information from questionnaires, including how much coffee they drink. They also distinguished between caffeinated and decaffeinated coffee.

“We used this data to identify regions on the genome associated with whether somebody is more or less likely to consume coffee. And then identify the genes and biology that could underlie coffee intake,” explains lead author Hayley H. A. Thorpe, Ph.D., from the Schulich School of Medicine and Dentistry at Western University in Ontario, Canada.

As expected, in both datasets, the scientists found evidence of a genetic disposition to coffee consumption.

“We were also able to confidently identify specific genes that influenced coffee consumption, including some that influence how quickly caffeine is metabolized,” Thorpe told Medical News Today.

In both the U.K. and U.S. datasets, the scientists noted positive associations between coffee consumption and health outcomes, including substance use and obesity.

MNT spoke with Michael Foti, PhD., an assistant professor of internal medicine at Touro College of Osteopathic Medicine in New York who was not involved in the study. We asked what a “positive association” between coffee and obesity means:

“This study found that certain genes were found consistently among enough participants to say the two may be linked.”

In agreement, Thorpe told MNT that “the genetics of coffee intake positively overlapped with the genetics of obesity and related traits.” She also added an important caveat:

“This does not mean that coffee intake promotes obesity. Rather, it means that the genetic differences among individuals that influence coffee intake also influence obesity.”

Foti also adds an important caveat: “The development of obesity is multifactorial and unlikely the product of genetics alone.”

In another part of the study, the scientists carried out a phenome-wide association study (PheWAS).

In this type of study, Thorpe explained, they use genetic data to train a model to predict the genetic tendency to consume coffee. Then, using another population, they “explored whether people who carry those coffee intake-associated genetic variants are more or less likely to have different health outcomes.”

“We found that those who carry genetic variants related to coffee intake had greater odds of an obesity diagnosis.”

Again, she explained that this only tells us that the genetics of coffee consumption are associated with obesity odds, not that they cause obesity.

When the scientists looked at psychiatric conditions, the results were less clear-cut. Thorpe explains:

“Look at the genetics of anxiety, for instance, or bipolar and depression: In the 23andMe data set, they tend to be positively genetically correlated with coffee intake genetics. But then, in the UK Biobank, you see the opposite pattern, where they’re negatively genetically correlated. This is not what we expected.”

One of the reasons for this discrepancy might be how the questionnaires asked about coffee intake.

The 23andMe questionnaire asked, “How many 5-ounce (cup-sized) servings of caffeinated coffee do you consume each day?” The UK Biobank questionnaire, however, asks, “How many cups of coffee do you drink each day? (Include decaffeinated coffee).”

Also, the questionnaires did not capture how the coffee was consumed. In the U.K. for instance, people are more likely to drink instant coffee, while ground coffee and frappuccinos with added sugar are more common in the U.S.

In other words, if two people had identical coffee consumption genes, their coffee-drinking habits might be different if they were born in the U.K. versus the U.S. Our environment can have a powerful effect on how we act out our genetic influences.

“GWAS provide important information on potential associations between certain genes and traits and diseases,” Foti explained to MNT.

“However, they are limited in how you can apply these findings to the general population as the GWAS findings in one population may not apply to others,” he said.

He also said that some diseases and traits are “likely the product of many factors, including environmental and other associated diseases. Moreover, it is likely that more than one gene likely affects a single trait or disease.”

On a positive note, “GWAS can allow researchers to explore the biology of complex traits,” Thorpe told MNT. They also help scientists “examine how the genetics of one trait relates to the genetics of another trait, or how the genetics of a trait associate with different outcomes.”

On the downside, she also told MNT that these studies “are disproportionately conducted using populations most resembling a European genetic background.” This means that the results are not necessarily generalizable to a diverse population.

Coffee drinkers worldwide are keen to know whether their coffee habits are healthy or not. As is increasingly clear, this is not a simple question.

MNT contacted Emily Leeming, Ph.D., a registered dietician, scientist, and author of Genius Gut: The Life-Changing Science of Eating for Your Second Brain.

“A lot of the confusion around coffee seems to be from differences in how we all drink coffee — different amounts, and whether cream or sugar is used.”

“For most people,” Leeming continues, “drinking a moderate amount of coffee is safe and healthy. Drinking about 1–2 cups a day is linked to better brain health and function.”

However, more does not mean better: “6 or more cups of coffee daily is associated with a smaller brain volume and 53% greater odds of dementia,” she explained.

Beyond brain health, Leeming told us that “Coffee contains polyphenols that feed your gut microbiome. People who regularly drink coffee tend to have a more diverse, ‘healthy’ gut microbiome than those who don’t.”

We also asked Thorpe what she thinks about coffee and health based on the latest evidence:

“Our study tells us that the health outcomes of coffee intake could vary widely across different populations and contexts. How someone drinks coffee and the habits surrounding its intake are likely key to its health outcomes, which this study did not explore.”

“Our study also supported that the genetics of coffee intake may be simultaneously associated with health benefits and adversities, depending on what health trait is being looked at.”

“Whether coffee intake is ‘good’ or ‘bad’ for someone is likely very dependent on the individual, the context, and the health domain in question,” she concluded.

Foti believes more research is necessary and suggested “checking in with your healthcare provider because many factors, including medical history, influence how much caffeine intake is safe for an individual.”

Leeming also adds a note of caution: “If you have a sensitive stomach or gut issues like irritable bowel syndrome, then coffee might not be the best drink for you.”

“For some people,” she continued, “coffee can speed up how quickly food moves through their gut, making them urgently dash to the bathroom. And some are caffeine sensitive, so coffee can make them uncomfortably jittery.”

Overall, the health benefits and risks of coffee are still under scrutiny. As with many health questions, the pros and cons probably vary from person to person. Thanks to coffee’s near ubiquity, more research is sure to follow.