The prospect of peak coffee raises the menace of massive caffeine withdrawal, with hordes of headachy addicts rendered into grouchy slackers. Could a cut in coffee production also cost us the many health benefits that coffee seems to provide?

For ages, the bitter black brew has been scorned as jet fuel for jittery insomniacs, providing nothing more than a momentary surge of focus and energy.

But recently, some researchers are starting to see java as the juice of the gods: In some studies, coffee appears to be protective against dementia, type 2 diabetes and even several types of cancer.

Coffee, it turns out, is loaded with polyphenols, anti-oxidant chemicals that fight damaging free radicals, which are implicated in many of the diseases of aging.

Caveat quaffer

Before we fill our cup with a discussion of the health benefits of coffee, remember these cautions:

For all these reasons, we are not prescribing coffee as medicine. But then, do we drink coffee for medicine, or for the taste, the excuse to talk things over with a friend, the acceleration physical and mental energy?

So bottoms up, and let’s check some recent studies showing how coffee affects dementia, diabetes, cardiovascular disease and cancer

Coffee: Good for your brain?

Many studies over the past decade have suggested that coffee can partly block Parkinson’s disease, a movement disorder that afflicts millions of elders. In 2006, ² researchers reported on a 22-year study of Finns – who boast Earth’s highest average coffee consumption – and found that people who drank more than 10 cups a day had about one-quarter the risk of Parkinson’s as non-drinkers. (Do Finns ever finish guzzling? While only 5 percent of the sample abstained, about 10 percent drank at least 10 cups a day!)

The researchers suggested that since Parkinson’s may be caused by oxidative attack on neurons, coffee’s protection may arise from its anti-oxidants.

Several studies – the results are inconsistent but suggestive – have linked caffeine and coffee with a reduction in Alzheimer’s disease. In 2010, after a 21-year study, researchers from Finland and Sweden³ reported that “coffee drinking of three to five cups per day at midlife was associated with a decreased risk of dementia/Alzheimer’s disease by about 65 percent at late-life.”

Research using mice with a genetic tendency to Alzheimer’s shows that coffee and caffeine improve learning and memory while reducing the beta amyloid plaques that mark Alzheimer’s. In 2011, when Gary Arendash and Chuanhai Cao of the University of South Florida compared coffee, caffeine and decaf,⁴ coffee was most effective at stimulating chemicals that apparently defend against Alzheimer’s. The researchers wrote that “coffee may be the best source of caffeine to protect against [Alzheimer's disease]” because another coffee chemical acts with caffeine to enhance protection.

Arendash did not respond to our email but said in 2009 that he’s seen “evidence that caffeine could be a viable ‘treatment’ for established Alzheimer’s disease, and not simply a protective strategy. That’s important because caffeine is a safe drug for most people, it easily enters the brain, and it appears to directly affect the disease process.”

Coffee ‘n cancer

Can coffee help protect against cancer? Sometimes.

Photo Florida Alzheimer’s Disease Research Center

Caffeine removed harmful beta amyloid plaques from the brains of mice that simulate Alzheimer’s disease.

A study of coffee and liver cancer followed 60,323 Finns for a median of 19.3 years. After adjusting for factors like age, alcohol and smoking, the hazard ratio of those who drank four to five cups was 0.44.

Hazard ratio means the probability of an outcome, compared to the reference group (non-drinkers, in this case). All other things being equal, abstainers were three times as likely to get liver cancer as those who swilled eight cups a day.⁵

To decipher conflicting or inconclusive studies, scientists can pool data using meta-analysis, a technique that sets standards for acceptable studies and then statistically groups the results.

In 2010, Mia Hashibe, in the department of family and preventive medicine at the University of Utah re-analyzed⁶ nine studies and found a 39 percent reduction in mouth and throat cancers among people who drank at least four cups. “Since coffee is so widely used and there is a relatively high incidence and low survival rate of these forms of cancers, our results have important public health implications that need to be further addressed,” said Hashibe. With such a large sample, “We had more statistical power to detect associations between cancer and coffee.”

If we shift the focus to all cancers, a new meta-analysis⁷ of 59 studies showed that each additional cup of coffee reduced the incidence of cancer by 3 percent.

The results concerning breast cancer are less encouraging. A 2008 report⁸, based on data from 85,987 women, found no significant link to coffee, decaf or tea, except for a slight reduction in breast cancer among post-menopausal women who ingested a significant amount of caffeine.

Similarly, a 2009 study in the Netherlands ⁹ found no association between coffee and breast cancer.

Ironically, coffee contains a chemical that could stimulate the many breast cancers that respond to estrogen by growing, according to Clinton Allred, an assistant professor of nutrition at Texas A&M University. Allred, who has found large amounts of a plant estrogen called trigonelline in coffee, says, “This is one of the least studied compounds I have ever been around.”

In the lab, Allred showed that trigonelline can affect cells even when it is thousands of times more dilute than the effective concentration of isoflavone, a common plant estrogen found in soy.

Allred is not worried about trigonelline, since people have been guzzling coffee for a long time, and plant chemicals consumed in a whole food or beverage act differently than they do in isolation in the lab. “People with a healthy diet that is high in plant products are exposed to these kinds of compounds all the time.”

A diabetes connection?

Could coffee slow the epidemic of type 2 diabetes, which disrupts sugar metabolism, which raises blood sugar that harms small blood vessels in the kidney, eye and heart? A 2006 study¹⁰ of 88,259 American women showed that drinking at least four cups of coffee reduced the diabetes rate to 53 percent of the rate among non-drinkers. Although both coffee and decaf (but not tea), were beneficial, diabetes prevention was most closely linked to coffee intake rather than caffeine intake.

According to a meta-analysis¹¹ based on more than 450,000 people from Asia, North American and Europe, “Every additional cup of coffee consumed in a day was associated with a 7 percent reduction in the excess risk of diabetes type 2. … Drinking three to four cups of coffee per day was associated with an approximate 25 percent lower risk of diabetes… .”

If coffee reduces diabetes, could it deter cancers associated with diabetes? A 2007 exploration¹² of the soaring rate of cancer after World War II in Japan linked coffee to reductions in liver and pancreatic cancer in men, and liver, colon and endometrial cancer in women. The authors speculated that coffee could reduce resistance to insulin, “and may thereby reduce the risk of diabetes-related cancers such as colon, liver, pancreas and endometrium.”

A matter of the heart

A 2010 study¹³ of 37,514 Dutch people found a slight benefit for coffee in heart disease: People who drank two to three cups a day had only 79 percent the rate of heart disease as abstainers, but the reduction was not statistically significant. Above 4 cups per day, the rate returned close to the no-coffee rate. Coffee did not affect the rate of strokes.

However, Swedish researchers studied¹⁴ people after a heart attack, and found that drinking one to three cups of coffee reduced the odds of dying to 68 percent of the risk for abstainers.

We put down our coffee mug with a jittery hand, wondered whether swilling coffee could harm the heart, and phoned Richard Page, a professor of medicine at the University of Wisconsin-Madison. Page, an expert in arrhythmias – the irregular heart rhythms that can cause deadly heart attacks – said, “It’s hard to demonstrate a relationship between caffeine consumption and arrhythmias, but there are case reports. I see a number of patients with arrhythmias, particularly atrial fibrillation, and occasionally we see some relationship with excessive consumption of caffeine.”

Although Page was not alarmed by coffee, he was not so sure about the mega-doses that were linked to health benefits in some studies. “I would be cautious; I have heard of a couple of adolescents developing atrial fibrillation (a hard-to-treat arrhythmia) after taking monster energy drinks; I don’t think such high doses of caffeine are good for people.”

The bottom line

If Captain C seems helpful against some cancers, dementia and diabetes, is it guaranteed to extend your life? No. A European study¹⁵, for example, found that “Neither coffee nor tea consumption was associated with stroke or all-cause mortality.”

A long American study, using data from 41,736 men (followed for 18 years), and 86, 214 women (24 years), found a slight, significant trend toward fewer deaths from all causes; those who drank at least six cups a day had a death rate just 80 percent (men) to 83 percent (women) of the non-drinkers. The main benefit was a reduction in cardiovascular disease.

However, coffee consumption did not affect cancer deaths, after adjusting for factors like obesity and smoking, and the authors concluded, ¹⁶ “The possibility of a modest benefit of coffee consumption on all-cause and cardiovascular disease mortality needs to be further investigated.”

Not exactly a ringing endorsement, but then, did we promise a simple answer?

Would you like your triple-espresso with soy milk?

Photo: Vince Panzano

A hungry fruit fly (Drosophila melanogaster) extends its proboscis to feed on a droplet of sugar water. The proboscis contains sensors that detect irritating chemicals such as the ones in wasabi. Quite similar sensors occur inside the human mouth.

Whether you are a cobra or a cocker spaniel, a raccoon or a raconteur, lots of natural, reactive chemicals will cause pain and possibly damage your cells. Even fruitflies quickly learn to shy away from sugar water that contains caffeine or chemicals found in cinnamon, cigarette smoke, onion and horseradish.

These chemicals trigger activity at receptors on cell surfaces which eventually results in an “ouch” signal being sent brain-ward.

In a study published in Nature this week, a group lead by Paul Garrity, an associate professor of biology at Brandeis University, showed that a major class of pain receptors have ancient roots. We are talking older than yesterday: the report shows that TRPA1 (transient receptor potential A1) receptor was found in the critter that spawned both vertebrates (green tree snakes, bullfrogs, dinosaurs and talk-show guests) and invertebrates (horse flies, crabs, quahog clams and talk-show hosts) at least 500 million years ago.

The investigation, spearheaded by Kyeongjin Kang in Garrity’s lab, showed that the TRPA1 receptor is so similar across the entire vert-invert realm that it must have evolved once, and then descended through countless generations without significant changes. “The fly and human proteins in this receptor appear, to a very, very high degree of significance, to be from a common ancestor,” Garrity told us.

The pain in Spain

Unlike TRPA1, many other chemical receptors, like those involved in most smell and taste, vary greatly between animals, Garrity added. “There are big families of these receptors that look quite different in different species, so there is a lot of flexibility and change, but this TRPA1 is pretty much fixed.”

When structures have remained constant over long periods, scientists conclude that the evolutionary pressures that favored them were also static. Fish retain fins because they still live in water. We retain eyes because seeing is so handy.

And the stasis of the TRPA1 receptor “suggests there has been some sort of strong evolutionary pressure in these toxic chemicals that was maintained since the receptor was invented,” says Garrity. The chemicals in question are made by plants or other organisms as self-protection, and they can damage or destroy proteins and nucleic acids, at least in high doses, and therefore are to be avoided.

Fans of horseradish and wasabi know that a nibble can be tasty but a gobble can cause an eruption of coughing.

Image: NIH

A human taste bud, shown here, contains some types of chemical receptor, but the TRPA1 receptors that first formed 500 million years ago are found elsewhere in our mouths, in structures called chemical nociceptors.

Work by study co-author Doug Theobold, also at Brandeis, suggested the original TRPA1 receptor arose after the jellyfish branched away from our lineage about 700 million years ago. The first TRPA1 receptor was apparently present in the last common ancestor of vertebrates and invertebrates, which lived between 500 million and 550 million years ago.

And that means we may have the same tastes in food as fruitflies, but not jellyfish. “It’s bad enough to think about shooing the flies away from the sushi bar, but jellyfish, well, they may be on the menu, but I don’t want to see one on the stool,” growls the resident Why Files cynic.

How they did it

To explore the responses to these reactive chemicals, Garrity and his colleagues offered sugar water to fruit flies. Some of the water was tainted with pungent chemicals derived from cinnamon or wasabi. Some of the fruit flies had genetic mutations affecting the TRPA1 receptor. In some trials, the flies touched the toxic chemical with their legs; in others, they drank it.

Flies extend their proboscis (snout) toward something they want to eat, and the scientists measured this behavior as they offered a droplet of food five times. All flies extended the proboscis at the first offering.

Curiously, when the fruitflies drank sweetened caffeine-bearing water, they turned jittery and stayed up all night, devouring junk food and cramming for a biochemistry exam. Just java jiving…

So what?

Finding such a long-term similarity in a major class of pain receptors could have broad implications, Garrity says. TRPA1 receptors exist on the aphids that spread disease to many crops and the mosquitoes that carry malaria. If compounds that trigger these receptors while sparing those of benign species can be found, they could be developed into pesticides that inflict pain and cause the nasty bugs to stay away from where they are not wanted.

A second application, which may be closer to fruition, depends on the similarity of receptors between fruit flies and mammals, Garrity says.

Compounds derived from capsaicin, the active agent in hot peppers, are already used to treat pain. Although TRPA1 receptors respond to a totally separate group of pungent compounds, drug companies are already searching for TRPA1 antagonists that might treat chronic pain, asthma, arthritis or migraine headache, Garrity says.

The TRPA1 receptor responds to oxidative stress caused by nasty compounds called free radicals. “It is a key to many aspects of pain and inflammation,” Garrity says.

- David J. Tenenbaum

Auger, who studies sex differences in the brain, agrees that women have a stronger craving for chocolate. This distinction can be found as far down the evolutionary ladder as rats, where females also have a stronger craving for the blessed bean. The difference is probably rooted in the female’s cyclic rise and fall of estrogen and progesterone, Auger says.

In June, a new study showed that chocolate also affects brains differently after it’s eaten. Magnetic resonance (MR) images of brains showed that the hypothalamus was less active in women after they consumed large amounts of chocolate. Since the hypothalamus helps regulate food intake, this could explain why chocolate is more likely to reduce a woman’s hunger, or at least her motivation to eat more chocolate.

The study also found decreased activity in the amygdala, a key emotional center in the brain. “I’m intrigued,” says Auger, “because the amygdala not only regulates positive and negative emotions, but also sexual behavior and desire. So chocolate has a potential impact on those behaviors, although there are no direct data to prove that. But biologically, these differences could be underlying mechanisms to explain why men and women have different preferences, as well as behavioral and physiological responses to chocolate.”