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Coffee: A Most Enigmatic, Ubiquitous Beverage

Legend has it that coffee was discovered by a goat herder around 850 AD in what is now Ethiopia. It soon spread around the globe and is currently consumed by billions of people every day. But as the drink gained in popularity, it also gained a bad rap. From claims that coffee led to illegal sex in the 1500s, or that it caused impotence in the 1600s, to the more recent belief that it stunted your growth, history has not been kind to coffee.

In recent years, rumors have been replaced by scores of scientific studies. But reading through the research can be dizzying, as you’ll often come across a conclusion that directly opposes another you just read. In fact, it’s unlikely that any single study would yield enough evidence to convince us about the health effects of coffee one way or another. So some scientists instead focus compiling these disparate findings into mega-studies called meta-analyses. Eventually, the meta-analyses became so numerous that scientists started aggregating those into what are known as umbrella reviews to see if they could glean any general wisdom about coffee’s effects.

Two umbrella reviews were published last year (here and here), and their findings flew in the face of centuries of coffee gossip. The verdict was that coffee drinking is linked to lowered risk of myriad diseases like type 2 diabetes, heart disease, a few types of cancer, liver disease, Parkinson’s, Alzheimer’s and depression—not too shabby. Above all, coffee drinkers were less likely to die early from any cause. And with the possible exception of drinking it while pregnant, there were no negative effects to speak of.

“The key message is that with the evidence that we have up to date, we can say that coffee can be part of a healthy diet,” says nutritional epidemiologist Giuseppe Grosse at the University of Catania in Italy and lead author of one of the umbrella reviews.

Grosso also notes that the verdict could change. That’s because, for all of the studies out there, there’s still a whole lot we don’t know about the effects of coffee on our health. Here are some of the lingering questions that researchers are digging into.

What have genes got to do with it?


Although studies are beginning to converge on the benefits of coffee, it’s hard to ignore the often-opposing findings. A major culprit has been that pesky variable of genetic diversity among study participants, which surprisingly, is rarely considered.

Take the gene CYP1A2, which encodes an enzyme of the same name that breaks down caffeine. One variant of this gene produces an enzyme that does the job quickly—at least for those who inherit two copies of it from their parents. People who inherit the other form of the gene are slower to process caffeine, so it hangs around in their bloodstream for longer. It turns out that whether you’re a fast or slow metabolizer helps to determine the toll that glugging coffee will take on your body.

Heart attacks are a prime example. For a long time, drinking coffee was thought to raise the risk of heart attack. But when researchers sequenced the CYP1A2 genes of coffee drinkers, they found that the risk was only heightened for those with the slow caffeine metabolism version of the gene.

Marilyn Cornelis, a geneticist at Northwestern University who led the study, has since searched far and wide across the genome, and zeroed in on additional genes that, like CYP1A2, help govern how the body processes caffeine. She’s still on the hunt for more.

“Very few studies have actually accounted for genetic variation,” says Cornelis. This omission may explain many of the inconsistent findings reported both in scientific journals and in the news. “What’s kind of cool now is that you look at these more recent studies they finally at least note the limitation of not including that variation.”

What makes coffee good for you?


Although coffee is often equated with caffeine, the two are not synonymous. A seemingly simple cup of coffee is actually a complex blend of more than a thousand chemical compounds, including caffeine, chlorogenic acids and diterpenes.

Peter Martin, the founder of the Vanderbilt University Institute for Coffee Studies, says now that people are starting to accept that coffee has health benefits, the next logical question for scientists to ask is: How?

“Mechanistically, we don’t quite know how increased rates of coffee consumption can reduce rates of things like Alzheimer’s disease, various forms of cancer, depression, and Parkinson’s disease,” he says.

The answers may be as numerous as the diseases in question. Caffeine seems to be responsible for protecting coffee drinkers against Parkinson’s, for instance, but when it comes to guarding against type 2 diabetes, you’re just as well off if you prefer decaf. Clearly, there’s more to it than caffeine alone.

Many of the compounds found in coffee are antioxidants. That means they protect our cells by disarming dangerous molecules called reactive oxygen species (ROS), which can damage our DNA and proteins. “It’s easy to assume it’s a general mechanism, such as antioxidants, that works for practically every disease,” says Martin, but these antioxidant effects are probably just one piece of the puzzle.

How much coffee should you drink?


Coffee may have health benefits, but how many cups should you be knocking back on a daily basis?

Once again, part of the answer may lie in your genes. Those stretches of DNA that control how your body processes caffeine may explain why some people feel fine after six cups, whereas others will get jittery and anxious after just one. “I think it’s important to find out what subgroups of the population should not be consuming coffee or limit their caffeine intake,” says Marilyn Cornelis.

Fortunately, we are naturally equipped to regulate our coffee consumption to some extent, according to Cornelis’ research. She discovered that people tend to adapt their coffee-drinking habits to reach their own caffeine sweet spot—the point at which they feel good but not jittery.

Nonetheless, recent headlines have touted 3 to 4 cups per day as optimal. That number was linked to the best outcomes for multiple diseases in one of the big review articles published last year.

Taking that number as a one-size-fits-all guideline is problematic because, aside from ignoring genetic differences, there is also the issue of what ‘a cup of coffee’ means chemically. It could mean a big cup or a small cup, instant coffee or fresh brewed, and a light, medium, or dark roast. Each version of a cup contains different levels of biologically important chemicals like caffeine, yet most of what we know about coffee and health still comes from studies that measure coffee consumption in terms of cups.

How does coffee impact pregnancy?


Just about every aspect of health impacted by coffee-drinking deserves deeper study, but one in particular stands out.

“I would nominate the effect of caffeine on pregnancy as probably the most serious and tough problem to figure out,” says David Schardt, a senior scientist at the Center for Science in the Public Interest.

March of Dimes recommends that pregnant women limit themselves to 200 mg of caffeine per day, which is roughly the amount in one big cup of coffee. But they preface that number with an admission: “We don’t know a lot about the effects of caffeine during pregnancy on you and your baby. So it’s best to limit the amount you get each day.”

It’s true that little is known on the topic, and for good reason. When it comes to pregnancy, researchers rely on observational studies, which are often plagued by hidden factors that are not part of the study but still sway the results. That’s because randomized controlled studies—considered the gold standard of medicine—are out of the question for pregnant women, says Schardt.

“You would never randomly assign pregnant women to consume caffeine or not because if it turns out to be harmful, that would be unethical,” he says.

Saddled with lower-quality data, scientists have found that drinking coffee while pregnant may be linked to low birth weight, preterm birth, and pregnancy loss. Caffeine can pass through the placenta, where it gets broken down slowly because the fetus’ version of the caffeine-processing enzyme CYP1A2 doesn’t work as hard. That means when a pregnant mother drinks caffeine, the fetus gets prolonged exposure to the chemical. Still, with mainly observational data to go on, it’s hard to pin down if and how caffeine ultimately affects pregnancy.

(All images by Tevs Iuliia/Shutterstock)

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A Functioning Fake Womb

In a potential breakthrough for human babies born prematurely, scientists announced this year they’d successfully removed lamb fetuses from their mother’s wombs and raised them into healthy sheep. Their survival comes thanks to an artificial placenta — called a BioBag — created by researchers at the Children’s Hospital of Philadelphia.

The fake womb consists of a clear plastic bag filled with electrolytes. The lamb’s umbilical cord pulls in nutrients, and its heart pumps blood through an external oxygenator. The success caps a decades-long effort toward a working artificial placenta.

The BioBag could improve human infant mortality rates and lower the chances of a premature baby developing lung problems or cognitive disorders. But there are still challenges to scaling the device for human babies, which are much smaller than lambs. The scientists are also refining the electrolyte mix and studying how to connect human umbilical cords. They expect human trials in three to five years.

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Are Airplanes Really a Microbial Playground?

(credit: Matej Kastelic/Shutterstock)

Crying babies, chronic snorers — they’re the usual targets of our displeasure when we fly. But, the real villains of the sky might be germs.

Flyers are packed into a cramped metal tube for hours on end where movement is limited. It seems like a microbe’s playground. But research on the topic is a bit inconclusive, despite worrying cases involving SARS and an aggressive type of influenza. Studies suggest that caution is warranted, but researchers have so far had trouble saying exactly how air travel affects disease transmission. At the moment, public health guidelines state that anyone within two rows of an infected individual could be at risk, although other studies suggest otherwise.

Fly the Germy Skies?

Most recently, a team of researchers from Emory University and the Georgia Institute of Technology—funded by Boeing—conducted their own boots-on-the-plane study of infectious disease transmission aboard commercial aircraft. On 10 flights from Atlanta to the West Coast and back, they took swabbed samples of various surfaces and recorded how often passengers and crew members moved around. Pairing the data with models of air movement and microbe dispersion gave them an idea of just how far a potential pathogen might travel.

Their findings, published Monday in the Proceedings of the National Academy of Sciences, indicate that a sick neighbor is certainly something to worry about when flying. Those within a row of a sick person and within two seats to either side had an 80 percent chance of getting sick in their model, which used a fairly high assumed rate of transmission. The risk of infection drops off sharply after that, though. Those more than a few seats away had little to worry about. That’s even closer than the two row-minimum suggested by public health agencies.

A sick crew member, however, posed a little more danger. They move around the cabin more and have more contact with passengers, so the risk of transmission increases. Just one sick flight attendant infected almost five people on average in the researcher’s model. That’s a big number, but it does make some assumptions, the biggest of which is that sick crew members even come in to work. It’s more likely that they would just stay home.

Back Down to Earth

There are difficulties in modeling disease transmission rates on such a small scale like this, and this particular study wasn’t very big. They looked at just ten flights and the longest was only a bit over five hours. International flights can go for fifteen hours or longer, and involve much more movement on the part of passengers, something that could increase the risk of infection.

Their model also only looked at microbes that could be carried by droplets, which don’t travel very far. Viruses spread by smaller aerosol particles could circulate much longer and farther. This includes diseases like tuberculosis and measles. Air travel also involves extended periods of contact with other passengers at boarding gates, security checkpoints and elsewhere, and this could affect rates of transmission as well.

It’s also worth pointing out that we encounter similarly confined, crowded spaces during the course of our daily lives. Buses, movie theaters, workplaces and more pose the same sort of risks, though the authors don’t provide any measure of comparison here. Airplanes, do, however, travel long distances very quickly, something that can turn a local epidemic into a pandemic within days. That hasn’t happened yet, though scattered cases involving SARS and Ebola, among other diseases, have stoked worry.

Ultimately, a review of the scientific literature on the topic found moderate evidence that airplane cabins helped to spread influenza. This latest study doesn’t really change that, though it does reveal the danger that an infected crew member poses.

So, for flight attendants — and for all of us, really — if you’re sick, just stay home.

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This Optical Illusion Could Help to Diagnose Autism

(Credit: Turi et al., eLife, 7:e32399, 2018)

You probably see a cylinder when you look at the illusion above. But how our brains translate two intersecting sheets of moving dots into a 3D image reveals telling differences in visual perception that could perhaps help diagnose autism spectrum disorder.

It’s been shown that people with autism are better at picking out the details of complex images, at the cost of understanding what all those details mean when put together. This can mean seeing the trees, but not the forest, or the strokes of a paintbrush but not the subject of a painting. It’s a trait that’s supported by years of research, but it can be difficult to assess exactly how an individual perceives an image just by asking them questions. The cylinder illusion, applied here by a group of researchers from Italy and Australia, offers a more reliable way of telling what a subject is seeing.

Grow and Shrink

It comes down to the pupils. Our pupils are responsive to light, but they also widen and constrict in response to the notion of brightness or darkness, even if light levels remains the same. Here, the white dots are perceived as brighter, and the black dots as darker, and our pupils respond accordingly. It’s a way for the researchers to tell what parts of the illusion study participants are focusing on. They published their findings in March in the journal eLife.

The illusion itself relies on our brain’s assumptions of how a rotating cylinder behaves. The dots cross over each other just as marks on a transparent cylinder would, they even slow down at the edges to give the impression of curvature. The two colors give imply depth, though a closer look reveals that neither actually seems to be in front — some white dots cross over black dots, and some black over white. It allows us to reverse the cylinder’s apparent direction by focusing on one color over the other. Importantly for the researchers, the illusion is composed of both discrete details in the form of the dots, and a holistic image, in the form of the cylinder. Having both allows them to see which component their study participants favor.

They asked 50 adults, none of whom had autism, to watch the illusion, and while they were doing so, the researchers were watching them — their pupils at least. They wanted to see whether their pupils changed size rapidly throughout the experiment or stayed the same. If they changed size, it indicated that the participants were switching focus back and forth between the white and the black dots — i.e. they were focused on the details of the images. If their pupils stayed about the same, they were likely focused on both at once, meaning they saw the image as a whole. Crucially, both methods of perception produce the same cylinder illusion. But how they do so differs.


Before taking the test, the subjects all took the autism spectrum quotient, a self-reported questionnaire that measures various behaviors associated with autism. Higher scores indicate more correlation with autistic traits. When they paired scores on the test with measurements of pupil dilation and contraction, they saw that they were clearly related. Those whose pupils changed with greater frequency also reported more autistic traits. It was another validation of the theory that those with autism tend to focus on specific details as opposed to entire images.

Remember, none of the subjects had been formally diagnosed with autism, and none of their scores on the test indicated that they should be. In fact, the mean value of the test scores was about average. But, autism is a spectrum, and we all lie on it somewhere. Even in nominally average individuals, a tendency toward autistic traits was associated with a propensity to focus on details over holistic images. It adds further evidence that autism alters how we process visual information, and hints that it extends beyond those diagnosed with the disorder. The researchers say measuring changes in pupil size could potentially serve as another means of diagnosing autism.

The results are still a bit preliminary, so it’s too soon to draw definite conclusions based on their work. The surveys were all self-reported, for one thing, which can skew results a bit. And the study involved participants without autism, meaning that we’d need to see similar work in those with autism spectrum disorder to back up their findings.

But, with more research, the authors think their research could be used to perform assessments of those with autism who are non-verbal, which can happen in children. It would give doctors and teachers a way to get information from those who may not be able to communicate it themselves.

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