Many of us, especially the current or former graduate students among us, are addicted to our breakfast caffeinated beverage of choice. Mine is tea, but if I had to guess, I’d wager that the most popular option is coffee. We chug it down in the morning to get ready for our day, we sip it thoughtfully at work, and we seek it out in the wee hours when we should be sleeping but instead we’re at the lab or at our desks, telling ourselves that we’ll run just one more gel or write just one more page. The ritual of coffee (or tea!) is deeply ingrained in our daily lives for many of us, but aside from keeping us alert, what else does it do for us? A recent study suggests that certain polyphenolic compounds in tea and coffee may offer protective effects against type 2 diabetes mellitus (T2 diabetes) by interfering with the formation of amyloid fibrils in the pancreas. Wow, that sounds great, doesn’t it? Another excuse to drink more of the stuff! But what the heck does it mean? In order to understand how this might work, we first need to understand some concepts. Specifically, what is an amyloid fibril, and what does it have to do with T2 diabetes?
Amyloids are deposits of proteins that have been folded in a specifically incorrect way (proteins must be folded properly in order to function properly). These misfolded proteins form aggregates (i.e., they clump together) that build up in tissues and cells, similar to the way that calcium deposits might build up in your pipes, for instance. You can see what this looks like in the photo to the left, which shows amyloid deposits (brown) of Abeta protein in the cerebral cortex. Amyloids tend to be associated with diseases such as Parkinson’s and Alzheimer’s disease in addition to T2 diabetes. The exact way that these protein deposits contribute to these diseases is unclear, but it is thought that their presence causes the tissues around them to be deformed, thus interfering with their ability to do their job. They may also cause cell death by interfering with the mitochondria, which are the organelles that supply cells with energy. In the case of T2 diabetes, the presence of amyloid fibrils in the pancreas is thought to kill the beta-cells that produce insulin. The amyloid fibrils in this case are made of a protein called human islet amyloid polypeptide (hIAPP, or amylin), which normally functions as an endocrine (i.e., hormone) that is released along with insulin from the beta-cells. Therefore, one way we can think about treating T2 diabetes is to stop hIAPP amyloid fibrils from forming in the first place.
Previous studies (in people of European and Asian descent) have reported that regular coffee-drinkers have up to a 50% lower risk of developing T2 diabetes than non-drinkers, but how might this work? One polyphenolic compound commonly found in tea, (-)-epigallocatechin 3-gallate (or EGCG), has been shown to have inhibitory effects on the amyloid formation of Abeta, alpha-synuclein, and hIAPP proteins, which are known to be associated with Alzheimer’s, Parkinson’s, and T2 diabetes, respectively. Coffee, like tea, has a host of polyphenolic compounds, such as caffeic acid (CA), chlorogenic acid (CGA), and their metabolites. It serves to reason that these polyphenols and related compounds in coffee may offer similar protective effects against amyloid formation and aggregation.
Caffeine, CA, and CGA are the three most abundant chemical compounds in coffee, so researchers from Huazhong University of Science and Technology, Wuhan University, and Wuhan Institute of Biotechnology (China) investigated whether they exhibited similar protective effects against amyloid formation as the tea polyphenol EGCG (published in the Journal of Agricultural and Food Chemistry). They exposed the amyloid-forming protein hIAPP to the tea polyphenol EGCG, caffeine, and the coffee polyphenols CA and CGA, and then they measured, among other things, the amount of amyloid fibrils that formed and the survival rate of exposed beta-cells from a rat cell line.
To the left are transmission electron microscopy images of hIAPP incubated with the compounds listed above (click to enlarge). I have edited the figure slightly to include labels. In part A, which had hIAPP alone, and parts C and D, which had hIAPP incubated with caffeine, you can see the fibrous amyloid protein bundles, which look a little bit like hairs or threads. Caffeine clearly was ineffective at stopping amyloid formation. In part B, EGCG appeared to stop amyloids from forming, as there were no fibrils detected, which is consistent with the existing research leading up to this study. In addition, both CA and CGA also inhibited amyloid fibrils from forming, with greater concentrations causing more complete inhibition. Small aggregates of hIAPP were detected, but they did not form mature bundles. So the coffee polyphenols do seem to stop amyloid fibrils from forming, similar to the tea polyphenol.
Does this inhibition result in less cell death? In fact, that does seem to be the case! The graph to the right shows the percentage of cells that survived when exposed to hIAPP alone or in combination with the study compounds relative to an untreated group of cells (the untreated group = 100% viability; click to enlarge). hIAPP alone caused the survival rate of beta-cells to drop by almost two-thirds, presumably because of the cytotoxic (i.e., cell-killing) effects of amyloid fibrils. In contrast, all four of the study compounds increased the survival rate to various degrees. EGCG (in a 1:1 ratio with hIAPP) and CA (in a 1:5 ratio with hIAPP) seemed to be the most effective at protecting the beta-cells at 75 and 96%, respectively. Perhaps the most interesting thing is that although caffeine did not stop the amyloid fibrils from forming, it still offered some protection against cell death! It could be that caffeine somehow alters the structure of the amyloid fibrils in a way that makes them less deadly to the beta-cells, even though it doesn’t stop them from forming entirely. It is also possible that caffeine interferes with the receipt of some of the chemical messengers involved in the cell death process.
These results show one potential way that drinking coffee may provide some beneficial effects against the symptoms of T2 diabetes. Polyphenols in the coffee probably slow or stop the formation of the amyloid fibrils, with caffeine itself also contributing to some degree. Slowing the aggregation of amyloid fibrils results in less beta-cell death, which means that the pancreas is less hindered in its ability to secrete insulin into the bloodstream after a meal. While the results weren’t shown in the paper, the authors also noted that the metabolites (i.e., the breakdown products) of CA and CGA showed similar anti-amyloid effects, meaning that even after CA and CGA are broken down chemically, the protective effects could still continue for some time.
Personally, I would be interested to know if ingesting significant amounts of sugar or cream with your coffee or tea would mitigate the benefits of these protective polyphenols. It may also be worthwhile to test the protective effect of coffee across a broader set of ethnicities, since some populations are more prone to developing T2 diabetes than others. Finally, it is worth pointing out that the cell viability study was conducted with rat cells, and therefore may or may not be indicative of what may happen with human beta-cells.
This doesn’t mean that your doctor will some day be prescribing you two extra cups of coffee per day to treat your diabetes, but it does mean that some of the compounds in your daily cuppa may wind up in diabetes medications in the future. All of that being said, drinking coffee should not be used as an alternative to seeking professional medical care for T2 diabetes or any other medical condition. The title of this post is somewhat tongue-in-cheek, because while many of us enjoy a cup or two (or five) of coffee or tea on a daily basis, it is not intended to cure or prevent any disease!
Cheng, B., Liu, X., Gong, H., Huang, L., Chen, H., Zhang, X., Li, C., Yang, M., Ma, B., Jiao, L., Zheng, L., & Huang, K. (2011). Coffee Components Inhibit Amyloid Formation of Human Islet Amyloid Polypeptide in Vitro: Possible Link between Coffee Consumption and Diabetes Mellitus Journal of Agricultural and Food Chemistry, 59 (24), 13147-13155 DOI: 10.1021/jf201702h