Metabolic Response to Coffee Consumption

The Challenge: What Are the Underlying Mechanisms of Coffee Metabolism and its Beneficial and Adverse Effects?

There are both pros and cons of drinking coffee, beyond the impact caffeine can have on energy levels. One of the most widely consumed drinks in the world, coffee has been linked to both disease prevention, as well as adverse effects in humans.¹ Research suggests that coffee consumption may play a role in preventing chronic diseases such as Parkinson’s disease, liver disease, and type 2 diabetes.² Other studies have revealed adverse effects including increases in cardiovascular disease risk factors, which can be exacerbated in certain patient populations.³ Understanding the underlying mechanisms that could be regulating these various outcomes of coffee consumption is increasing in importance. Coffee contains hundreds of compounds, each capable of eliciting changes in the metabolome of the individuals who consume it.⁴ Researchers sought to systemically profile the changes in metabolic signature following coffee drinking in a number of individuals.⁵

Metabolon Insight: Utilizing Metabolomics to Investigate Changes In Response to Caffeine Consumption

To investigate this, a three-stage clinical trial was conducted (ISRCTN12547806). Habitual coffee drinkers under the age of 65 who had an elevated risk of type II diabetes were selected, all residing in Finland. In the first month they were restricted from drinking coffee, followed by consumption of 4 cups of coffee a day (1 cup=150 mL) during the second month, and finally 8 cups of coffee a day in the third month. Fasting serum samples were collected for 47 participants after each month. Each sample underwent global metabolomics profiling using UPLC-ESI-MS/MS, and 733 metabolites were identified across all samples. From these, 115 total metabolites were significantly associated with changes in coffee consumption. Out of those 115, 81 were increased and 34 decreased following the 3-month trial.

The Solution: Metabolomics Reveals Changes in Key Metabolomic Pathways Following Persistent Coffee Consumption

Through pathway analysis, the researchers identified the following significantly enriched pathways that were altered with coffee intake: xanthine metabolism, fatty acid metabolism, endo-cannabinoid, benzoate metabolism, steroid, kynurenine, indoleacetate and 5-bromotryptophan. Xanthine metabolism includes caffeine and caffeine derivates that were expected to be higher following coffee consumption. These metabolites were further removed from other statistical analysis. The researchers identified a small subset of increased coffee-derived metabolites which were a product of microbial metabolism, likely from gut microbiota. Furthermore, they found that metabolites that were parts of endocannabinoid and fatty acid acylcholine pathway decreased following persistent coffee consumption. In fact, a subset of these metabolites was able to significantly discriminate the non-coffee drinking period from the coffee drinking period. In addition, the predictive power to identify these biomarkers was high across models, as demonstrated by similar results between the secondary Random Forest (RF) analysis and MPLSDA. Altogether, the identification of these novel metabolites and their pathways open up new research questions that could be the target of future studies.

The Outcome: Future Directions of Study Illuminated as a Result of Metabolomic Differences Identified Following Persistent Coffee Consumption

From this study, several key metabolites and pathways excited the researchers due to links to other studies of coffee consumption and its role in health and disease. The finding that coffee consumption increased metabolite production from gut microbiota is exciting because numerous studies have reported that gut microbiota changes impact diseases that are associated with persistent coffee consumption.^6,7 For example, it has been hypothesized that coffee-induced changes in the microbiota mitigates inflammation in Parkinson’s disease.⁸ Ultimately this study provided the first profiling of metabolomic changes in response to persistent coffee consumption. Due to the high number of metabolites and metabolic pathways identified, this provides many research questions for investigation. These future studies will further reveal the mechanism and role that coffee exerts on human health, both positively and negatively.