Coffee, the love of modern society, the elixir that many crave for, the guilty pleasure that gives us that well-deserved boost. Despite our fondness for coffee, this popular beverage has never made it to the menu of a healthy diet plan. Have you ever thought to yourself, why is this so? Is coffee our friend or foe? Imagine yourself sitting in the audience in a debate hall where the coffee lovers and coffee haters vehemently argue their cases. Let the debate resume! (If you haven’t read Part 1 of this debate, please stop here and read Part 1 (here) before continuing.) Judge: Welcome back everyone. Team For-Coffee, please state your case. Team For-Coffee: Yours Honour, let me present one of my strongest pieces of evidence. In 2012, Freedman et all published a large study in the prestigious New England Journal of Medicine <1>, in which they assessed the amount of coffee consumption for the participants at the beginning then followed them up for 14 years. The study found that coffee consumption is associated with a lower rate of death from major diseases such as heart disease, stroke, diabetes and lung conditions. This was after considering other factors such as smoking. This association of coffee with lower rate of death seem to be the strongest in people who do not smoke are in relatively good health. Team Against-Coffee: Let me stop there! I appreciate the findings from this study but after all, it merely shows an association but does not prove that coffee can reduce rate of death. Judge: That is a fair point, but unfortunately the majority of the studies out there on coffee are observation-only studies. There are very few well-designed clinical trials. Team Against-Coffee: Can you tell me what would be the reason for coffee reducing the risk of these chronic diseases? Judge: There is currently no real prove in what exactly in coffee might be associated with these health benefits. But we know that coffee contains more than 1000 bioactive compounds which might be affecting health. One plausible explanation is that compounds such s antioxidants and polyphenols may be at play here<2>. These molecules might be playing a role in reducing the chronic inflammation associated with these chronic diseases. Team For-Coffee: I read your article recently about the importance of gut microbiota. Could coffee affect our microbiota? Judge: Yes. There is evidence from cellular, animal and even human studies that coffee induces changes in the gut microbiota composition in favour of organisms that are associated with anti-obesity and anti-inflammatory effects<3>. Importantly, there are also some evidence that coffee consumption is associated with decreased risks of breast, bowel, womb and prostate cancer <2>. A variety of mechanisms for such association has been proposed. Antioxidant properties of certain compounds are thought to contribute. Furthermore, coffee may be doing more than just playing the antioxidant card. A high intake of caffeine has been associated with increase in the sex hormone binding protein (SHBP), a protein which binds hormones such as testosterone, reducing the freely-roaming testosterone. This reduction of free testosterone may account for the association with reduced risk of breast and womb cancers. Different non-caffeine compounds in coffee may be also acting directly in the bowel by changing gut flora, increasing bowel movement and metabolising cancer-inducing compounds<4><5>. Team Against-Coffee: Enough with the body, let’s move on to the mind. When I have a cup of coffee, I can’t even sleep. How is that good for mental health?
Judge: It is true that caffeine in coffee can increase alertness and in sensitive individuals such as yourself, it can affect sleep. In a small number of people, it could lead to increased anxiety. However, there are many beneficial effects of coffee on mental health. It has been found to increase concentration and improve mood. Long-term consumption of coffee has been found to be associated with reduced risk of developing stroke, cognitive decline, Parkinson’s disease and Alzheimer’s disease<6>. Team Against-Coffee: Right, seems that I’m not winning here. Surely it is not healthy to drink 10 cups of coffee a day! Judge: That is a valid point. How many cups of coffee a day is considered healthy? Well, the trouble is, many studies we talked about didn’t really look at this. Neither did they distinguish between different preparations of coffee. However, amongst the studies that did look into this, some found that the more coffee you drink, the stronger the benefit, whereas others found that the benefit peaks at 4-5 cups of coffee a day. Team For-Coffee: Your Honour, I think it’s time for the verdict! Judge: Before a conclusion to be drawn, I need to reiterate that most of the evidence we looked at are observational studies, albeit with a large number of participants. The few randomized controlled studies (the strongest clinical evidence to prove causality) only looked at simple outcomes such as blood pressure and cholesterol level. Therefore, the health benefit we have examined today are not proven. It is important to bear in mind that coffee, particularly caffeine, is certainly a substance not without risks, particularly in pregnancy. However, given the evidence available to us so far, I am in favour of coffee. So, my dear jury, what do you think? <1> Freedman et al. Association of Coffee Drinking with Total and Cause-Specific Mortality. NEJM <2> Grosso et al. Coffee, Caffeine, and Health Outcomes: An Umbrella Review. Annu. Rev. Nutr. 2017. 37:131–56 <3>Pan et al. Molecular mechanisms of the anti-obesity effect of bioactive compounds in tea and coffee. Food Funct., 2016, 7, 4481 <4> Vitaglione P, Fogliano V, Pellegrini N. 2012. Coffee, colon function and colorectal cancer. Food Funct. 3:916–22 <5> Huber WW, Parzefall W. 2005. Modification of N-acetyltransferases and glutathione S-transferases by coffee components: possible relevance for cancer risk. Methods Enzymol. 401:307–41 <6> Nehlig A. 2016. Effects of coffee/caffeine on brain health and disease: What should I tell my patients? Pract. Neurol. 16:89–95
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For many people, there is nothing that makes a cloudy gloomy winter morning more satisfying than having a steamy cup of coffee in hand. There is something about coffee that captivates people. Its strong, bitter and acidic aroma seems to paradoxically bring content and excitement to the start of the day. It creates an unconscious and abstract picture of the wonderful day ahead of us. It’s an addiction that most people would happily admit with no reserve. The earliest credible evidence of coffee-drinking appears in in the middle of the 15th century, in the Sufi shrines of modern-day Yemen in Southern Arabia<1>. Nowadays, coffee plants are cultivated in over 70 countries worldwide. Coffee has quickly become one of the most popular beverages in the world. The stimulant component of coffee was traditionally seen as unhealthy. Various sources have pointed fingers at coffee over its apparent effects on the cardiovascular system. However, what is the true face of coffee? Is it really the villain that we have previously thought? Or, is it actually the unsung hero who is making us healthier? Let the debate begin! Team Against-Coffee: If coffee is good for you, why are women advised to reduce coffee intake during pregnancy? Judge: You are right. One meta-analysis (a systematic analysis of all relevant individual studies to date) in 2014 has found that increased coffee consumption in pregnancy may be associated with an increased risk of childhood acute leukaemia<2>. However, the studies included in the analysis are limited. Some case-control and cohort studies also found that increased caffeine consumption might increase pregnancy loss<3>. Nevertheless, it is important to understand that case-control and cohort studies are relatively low in quality of evidence. Another meta-analysis found that increased caffeine intake in pregnancy is associated with increased risk of low birth weight in the baby<4>. Interestingly, it seems that some studies mainly attributed the effects on pregnancy to caffeine, not coffee per se. Some studies also didn’t properly account for smoking in mothers. Smoking, as we all know, is known to cause pregnancy loss and low birth weight. All in all, it is reasonable to conclude that it is possible that increased caffeine intake in pregnancy could lead to undesired outcomes in the baby. Team For-Coffee: Ok, I acknowledge the point of Team Against-Coffee. As long as you are not pregnant, coffee is good for you, right? Judge: Well, let’s see. Some studies have found that coffee consumption may be associated with lung and stomach cancer<5>. However, looking at these studies with a critical eye, it seems that the ones with statistically significant findings didn’t adjust for the biggest confounding factor - smoking. We know that smoking is the biggest risk factor for lung and stomach cancer. Interestingly, a sub-analysis for non-smokers didn’t find any association between coffee and these cancers. Team Against-Coffee: So that is inconclusive. What about the effect of coffee on the increase in cholesterol? Judge: A 2012 systematic review<6> looked at the relationship between coffee and body lipid level. By lipid, I mean different types of fat molecules within the body, including cholesterol. It did find an association between increased coffee consumption and increased level of total cholesterol, triglycerides and the bad cholesterol (LDL-C). This effect seems to be stronger in people who already have high cholesterol. Interestingly, this association seems to be stronger with unfiltered coffee. Why is that? Perhaps the culprit is the significant quantity of a molecule, called diterpenes, present in unfiltered coffee. Diterpenes may affect the function of the bad cholesterol receptors which may lead to a consequential accumulation of cholesterol. Despite this systematic review, it has to be said that there is no evidence that long term coffee consumption leads to increased cholesterol. Team Against-Coffee: Cholesterol-aside, what do you have to say about the effect of coffee on blood pressure? Coffee is a stimulant, surely it causes high blood pressure. That is bad for you, right? Judge: That is not an unreasonable question. Caffeine in coffee is certainly a stimulant. Caffeine has been associated with acute rises in blood pressure<7,8>. By acute, I mean an immediate rise. However, it seems that long-term habitual consumption of coffee is not associated with increased risk of high blood pressure<9>. It certainly seems that the longer you drink coffee, the stimulating effect on blood pressure diminishes over time. An interesting phenomenon. What could explain this phenomenon? It could be plausible that our blood vessels are developing tolerance to long-term exposure to coffee. It may also be due to the counteracting effects of antioxidants in coffee. So far, the jury’s out on this. Judge: Now everyone, take a break! Get some coffee and let us continue in Part 2 of this debate… References
In my clinical practice, countless people are tormented by the stresses around them. As doctors, we tell our patients to have a healthy diet if their cholesterol is high or has high blood sugar. But when somebody walks through the clinic doctor presenting with low mood, a healthy diet is never emphasised to the extent of the other physical health conditions such as diabetes. All this may be changing. Our gut is one of the most important organs in the body. Over the last few years, it has been increasingly clear that a healthy gut is not just good for absorption of nutrients, it is also having a surprisingly enormous impact on our mental health. The gut is a unique organ because it has its own neural network called the enteric plexus. Enteric means gut. Plexus means a small network of interconnecting neurons. Enteric plexus acts as a mini-brain, in the sense that it has its own network of neurons without direct relations with the brain. However, it does connect with the brain via a variety of mechanisms. The connection between the gut and the brain is the gut-brain-axis. Regulation of the gut-brain-axis function is associated with changes in the stress response and overall behaviour in both animal models and in humans <1>. Irritable bowel syndrome (IBS), a common stress-related gut problem is an excellent example of how the health of the gut may be influencing the functioning of the brain and vice versa. Over half of patients with IBS also suffer from anxiety or depression. What, then, maintains the health of the gut? We all know there are good bacteria living in the gut. It is old knowledge that digestion is closely regulated by the health of the good resident bacteria in the gut, the so-called microbiota. The new knowledge is the crucial roles a healthy microbiota plays on the rest of the body, outside the digestive system. Gut microbiota is not just regulating the health of the gut but are also involved in the manufacturing of several important brain chemicals, the neurotransmitters, which are essential components of efficient brain functioning. Moreover, the microbiota interacts with the host through a variety of pathways involving the immune molecules, hormones and the nerve connections, as part of the brain-gut-microbiota axis<1>. Animal studies have demonstrated evidence which suggest that they are actively involved in the regulation of brain development, function and behaviour. What is the evidence for the link between gut microbiota and mental health? In recent years, there have been some very interesting new animal studies which put gut microbiota in the spotlight of the field of mental health and neuroscience. Preliminary studies have shown that the composition of gut microbiota is different in people with depression, compared to that in healthy people without depression<1>. They literally have different types of bacteria. How does this translate in clinic research? Perhaps you have heard of faecal transplantation. This is a clinical treatment essentially involving harvesting a healthy volunteer’s poo and put it in a patient’s gut, in the hope that the good bacteria in the donor poo will populate the gut of the patient, restoring the healthy gut microbiota in the patient. This is no longer a novel treatment and is currently being used to in the treatment of certain gut disorders. It is yet to be applied to treat mental health disorders such as depression but as you will see in the studies described below, this method may help us elucidate the relationship between gut microbiota and mental health. So far, majority of the studies have been done in mice<1>. Genetically modified mice that were born without any bacteria in their gut, so-called germ-free mice, underwent transplantation of faeces pooled from several humans with depression. As a result, they developed what could be perceived as ‘depressive behaviour’, such as reduced swimming activity when put in a pool of water. On the other hand, the behaviours of germ-free mice were unchanged after they had faecal transplantation from healthy people. In another older study, germ-free mice have been found to have an overactive stress response. This hyper-response was reverse by introduction of Bifidobacterium infantis, bacteria normally found in infant gut and commonly used in probiotics<2>. Some critics may argue, what if germ-free mice are just more susceptible to the germs unknown to them? Well, that is certainly a valid point. In fact, it was found that germ-free mice do have abnormal development of the brain and immune system<1>. This supports the hypothesis that gut microbiota is involved in regulation of the brain development and immune system maturation. Luckily, this issue with the germ-free mice was addressed in another study by using adult mice that were developed normally but had their gut microbiota stripped in adult life. This eliminated the confounding factor of possible abnormal brain development. Guess what, these mice also developed characteristics of ‘depression’, after receiving the faeces transplant from depressed patients<1>. You may ask, can we improve the mood of these ‘depressed’ mice by improving their gut microbiota? One study has done just that<3>. It found that the ingestion of a bacteria, called Lactobacillus rhamnosus, reduced anxiety and despair-like behaviour and reduced the stress hormones in mice. This finding begs the question: can our anxiety and depression also be alleviated by ingesting such bacteria? What could we conclude from these studies?
As a scientist, I’m sorry to say that despite the interesting findings these studies have shown, they do not in any way prove that gut microbiota regulates mood. Mice are obviously not humans. How these findings can be translated into humans is still questionable. There are many questions that are still unanswered. Does depression lead to change in gut microbiota? Or perhaps it is the other way around? Is it a chicken and egg thing? We don’t know yet. However, our doors of curiosity are certainly wide open. Now comes the most relevant question: what can we do to improve the health of gut microbiota? In investment, diversification is key. In gut microbiota, diversification is key. A healthy diet is certainly the most important step to increase the biodiversity of gut microbiota. You may have heard of the term prebiotic and probiotic. Prebiotics are compounds in food that induce the growth of good bacteria. These are foods such as leeks, artichokes, onion and garlic. Sounds healthy right? If eating plenty of prebiotic-rich foods are difficult for you, perhaps you could consider a reasonable intake of probiotic. Probiotics are live bacteria that help restore the diversification and health of gut microbiota. However, just be aware that in very rare cases, some people may develop intolerance to probiotics. So, what is the verdict? A healthy diet can certainly improve the health of gut microbiota. Can healthy gut improve our mood? Maybe. Animal studies have been promising so far, but let’s watch this space. References <1> Dinan et al. Brain-gut-microbiota axis - mood, metabolism and behaviour. Nature Reviews Gastroenterology & Hepatology 14, 69-70 (2017) <2> Sudo, N. et al. Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice. J. Physiol. 558, 263–275 (2004). <3> Cryan et al. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nature Reviews Neuroscience 13, 701-712 (2012) |
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