For many, the day doesn’t start until the first sip of coffee. As one of the most cherished beverages globally, coffee’s rich aroma and invigorating taste are not its only benefits. A deeper dive into its biochemistry reveals that coffee may play a protective role against chronic liver disease, hepatocellular carcinoma, and diabetes. But what’s behind coffee’s health-protective profile? The answer may lie in its epigenetic effects, particularly how it regulates UGT1A genes.
Understanding UGT1A Genes
UGT1A genes encode for a group of proteins known as UDP glucuronosyltransferases. These proteins are crucial in our body’s defense system, contributing indirect antioxidant, cytoprotective, and genoprotective functions. Intriguingly, recent research shows that coffee consumption can upregulate these genes in both cultured cells and living organisms.
The Study Breakdown
Kalthoff et al exposed HepG2 and CaCo2 cells to various coffee types, including regular, metal- or paper-filtered, decaffeinated, and instant coffee. They also compared these effects with other beverages like green and black tea and cocoa. Remarkably, all coffee types, regardless of caffeine content or filtering method, induced significant transcription of UGT1A genes.
The Role of Coffee in Epigenetic Regulation:
The induction of UGT1A was found to be independent of caffeine, suggesting other compounds in coffee are at play. Through meticulous experimentation, scientists discovered that this regulation is orchestrated by the aryl hydrocarbon receptor (AhR) and the nuclear factor erythroid-related factor 2 (Nrf2). These receptors bind to specific sequences in DNA, leading to increased expression of UGT1A genes.
In Vivo Evidence
The study’s credibility is further solidified by its in vivo component. Humanized transgenic mice expressing human UGT1A genes were given coffee, which resulted in a substantial increase in UGT1A transcription in the liver and stomach—by 10 and 14 times, respectively.
Implications for Health
The research suggests that the health benefits of coffee, particularly its role in preventing certain chronic diseases, may be due to its ability to enhance the glucuronidation process. This is a detoxification pathway where harmful substances are made water-soluble and excreted from the body. By up-regulating UGT1A genes through AhR signaling and Nrf2 binding, coffee helps maintain the body’s cellular integrity.
Conclusions: UGT1A genes are induced in vitro and in vivo by coffee, independent of caffeine content, cafestol, or kahweol. Coffee up-regulates glucuronidation by AhR signaling and Nrf2 binding to the ARE/XRE. Glucuronidation could mediate the protective and antioxidant effects of coffee.
Kalthoff 2010
Since that aritcle was written a number of other studies have confirmed the positive effects of coffee intake.
In 2023 Safe et al conducted a review of the literature, particularly the more recent studies. This was their conclusion:
Coffee is not only the most consumed beverage worldwide, but it joins the Mediterranean diet as being among those dietary components that extend life, protect against neurological and liver diseases, and protect against the diseases of other organs. There is also an association between higher coffee consumption and overall anti-inflammatory effects and protection against some cancers, whereby coffee acts as both a chemopreventive and chemotherapeutic agent. The mechanisms of action of coffee are dependent on the effects of its constituents, including chlorogenic acids, polyphenolics, terpenoids, alkaloids, and other phytochemicals. Caffeine may contribute to some coffee-induced responses, but there are studies showing similar health benefits in individuals consuming caffeinated or decaffeinated coffee. There is evidence that the antioxidant activity of coffee, which activates Nrf2, may be an important mechanism of action. However, since Nrf2 exhibits both health-protective and drug-resistant activities, other cell context-dependent factors may also be important. There is also evidence that the protective effects of coffee in the gut and decreased colon cancer risk may be due to its activity as an AhR ligand. Moreover, some of the components of coffee bind the orphan nuclear receptor NR4A1 to the interactions with this receptor, and as of yet, unidentified receptors may also be important. Overall, these mechanisms, in concert with possible epigenetic pathways and the modulation of gut microbiota/microbial metabolites, contribute to the health benefits of higher coffee consumption, and this suggests that clinical applications of coffee extracts, particularly for treating some cancers, should be considered.
(Safe et al 2022)
and theres more!
Data from the current review similarly indicates that coffee consumption, potentially due to its abundant antioxidants, is associated with the improved biomarkers of oxidative stress and inflammation in healthy individuals (Table 1 and Table 2). With some studies even showing that coffee consumption can reduce biomarkers of oxidative stress and inflammation to alleviate CVD risk in individuals with metabolic complications (Figure 3). This is consistent with preclinical evidence [42,97,98] on the proposed mechanisms by which coffee alleviates the toxic effects of oxidative stress and inflammation within diverse tissues to enhance its potential benefits. Enhancement of intracellular antioxidants via activation of nuclear factor erythroid 2-related factor-2 (Nrf2) is likely the leading mechanism that explains enhanced therapeutic effects of coffee or its bioactive compounds [99,100,101], as previously reviewed with other active ingredient found in other natural beverages [102,103].
Next time you enjoy your cup of coffee, remember that it’s more than a comforting routine or energy booster. It’s a complex beverage with the potential to influence your health at the genetic level. As research continues to unravel the mysteries of coffee’s health benefits, we’re reminded of the intricate ways our diet influences our well-being—down to our very genes.
(Dludla 2023)
Disclaimer: This blog is for information purposes only. Before making significant dietary changes, it’s wise to consult a healthcare professional or a registered dietitian to ensure that your choices align with your health goals.
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