A new scientific review reveals the molecular networks underlying coffee’s most potent compounds, demonstrating how this everyday drink may reduce disease risks through its coordinated antioxidant, anti-inflammatory, and neuroprotective effects.
Study: Transforming coffee from an empirical beverage to a targeted nutritional intervention: health effects of coffee's core functional components on chronic diseases. Image credit: mariaeleman/Shutterstock.com
Scientists have conducted a systematic review to establish a molecular-theoretical foundation for repositioning coffee as a targeted nutritional intervention rather than an empirical beverage. The results are published in Frontiers of Nutrition.
Coffee: A highly popular global beverage
Coffee is a popular beverage derived from the processed fruits of the Coffea species. Scientists have traced the use of coffee back to 15th-century Yemeni Sufi monasteries, and highlight its relevance within the concept of “food–medicine homology,” where foods possess both nutritional and medicinal functions.
The global coffee industry continues to exhibit robust growth, with annual coffee bean production exceeding 10 million metric tons. Commercial coffee cultivation predominantly involves Coffea arabica L. (Arabica), Coffea liberica Hiern (Liberica), and Coffea canephora Pierre ex A. Froehner (Robusta). Arabica accounts for approximately 70% of the global market share, primarily because of its low bitterness and complex aromatic profile.
Multiple studies have described coffee as a chemically complex beverage rich in bioactive compounds. Raw (unroasted) coffee beans mainly contain carbohydrates, lipids, and proteins. It also includes a minimal quantity of nitrogenous compounds, minerals, and acid-ester substances.
The process of roasting coffee beans also produces several compounds, such as melanoidins, driven by Maillard reactions and pyrolysis. For instance, the content of carbohydrates and nitrogenous compounds decreases, while the lipid content increases after roasting. Notably, melanoidins formed during roasting may constitute up to one-quarter of the roasted bean mass, reflecting extensive chemical transformation.
Functional chemistry of coffee
Scientists have broadly classified the bioactive compounds of coffee into four major categories, namely, alkaloids (e.g., caffeine, trigonelline), polyphenols (e.g., chlorogenic acids), diterpenes (e.g., cafestol), and Maillard reaction products (melanoidins). These compounds interact through synergistic and antagonistic mechanisms, forming multidimensional regulatory networks that lead to diverse health benefits.
It is emphasized that understanding these network-level interactions is essential, as focusing on isolated compounds does not accurately reflect how coffee behaves under real consumption conditions.
Bioactive compounds
The mechanisms associated with the bioactive compounds in coffee and their therapeutic effects are described below.
Alkaloids:
Caffeine, a methylxanthine derivative, is a highly stable alkaloid that is primarily metabolized in the liver through P450 1A2 (CYP1A2). This alkaloid primarily derives its physiological functions from competitive antagonism of adenosine A1/A2A receptors and specific inhibition of phosphodiesterase 4/5 (PDE4/5) activity. Through these mechanisms, caffeine acts as a low-affinity benzodiazepine-site antagonist at γ-aminobutyric acid type A (GABA_A) receptors that play a crucial role in reducing seizure threshold.
Molecular studies have demonstrated caffeine's neuroprotective role. It acts as a central nervous system (CNS) stimulant, potentially enhancing cognitive function and reducing the risk of Parkinson's disease (PD) through antagonism of the adenosine A2A receptor (A2AR). However, increased caffeine intake may increase sleep disturbances and anxiety.
Multiple studies have demonstrated the anti-inflammatory, neuroprotective, anti-obesity, and anti-diabetic effects of caffeine. The review also cites human cohort evidence showing that caffeinated coffee, rather than decaffeinated coffee, is strongly associated with a reduced risk of neurodegenerative disease.
Several in vitro studies, animal models, and molecular docking analyses have demonstrated the potential of trigonelline for neurodegenerative disorders, including AD, PD, and depression, through mechanisms that include oxidative stress mitigation, acetylcholine inhibition, and neuroinflammatory suppression.
Polyphenols:
Chlorogenic acids (CGAs) are hydroxycinnamic acid derivatives, which are the most abundantly found polyphenols in coffee. These polyphenols are key contributors to coffee's antioxidant and metabolic regulatory properties. Mechanistically, 5-O-caffeoylquinic acid (5-CQA), an abundantly found CGA, activates the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to suppress oxidative stress and inhibits α-glucosidase to modulate postprandial glycemia.
A typical coffee serving contains approximately 27 to 121mg of CGAs. These bioactive compounds are associated with glycemic regulation, anti-inflammatory actions, and neuroprotection. Roasting significantly degrades CGAs, with light roasting retaining far more CGAs than dark roasting.
Diterpenes:
Cafestol and kahweol are furan diterpenes that are abundantly found in coffee oils. Their physiological effects largely depend on the brewing methods. For instance, paper-filtered techniques remove a significant amount of diterpenoids, whereas unfiltered brewing techniques, such as the French press, retain the full content.
Diterpenes exhibit paradoxical biological activities. It triggers an increase in low-density lipoprotein (LDL) cholesterol levels, potentially elevating the risk of cardiovascular disease, and induces glutathione S-transferase (GST) for anticancer activity. Diterpenes also exhibit hepatoprotective and anti-inflammatory properties.
Maillard reaction products:
During coffee roasting, the Maillard reaction produces a complex array of compounds, including melanoidins. These compounds exhibit furan and pyrrole ring-enriched molecular structures, responsible for their metal ion chelation capacity and lipid peroxidation inhibitory activity.
However, the Maillard reaction also leads to the production of harmful compounds, such as acrylamide, a Group 2A carcinogen. Higher acrylamide concentration has been found in dark-roasted coffee, which exhibits neurotoxic and carcinogenic effects.
Although acrylamide levels can be measurable, typical dietary exposure from coffee remains below most regulatory concern thresholds.
The complexity of coffee
Coffee contains a variety of chemical compounds that work together, oppose each other, or act in sequence to affect multiple molecular targets. Through these interactions, coffee helps regulate oxidative stress, inflammation, metabolism, and neuroprotection. Extensive epidemiological evidence links moderate coffee consumption with lower risks of type 2 diabetes, Alzheimer’s disease, Parkinson’s disease, and cardiovascular disorders.
Current pharmacological research on coffee is often fragmented, focusing on isolated components and overlooking interactions among multiple compounds. This results in three major research limitations: an overemphasis on isolated compounds rather than multicomponent synergy, a limited investigation of minor bioactive constituents, and an overreliance on in vitro or rodent models that lack human translational validation.
By mapping the target networks of CGAs, caffeine, and related compounds, researchers will be able to clarify the biological basis of coffee's multi-target regulation. This integrated approach would support a more holistic view of coffee as a functional food and provide a theoretical foundation for its health benefits.
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