Caffeine, Energy Drinks, and Everything Else

It's the everything else that adds up.

A couple of years ago, coffee drinkers were buoyed by the release of a massive study in the New England Journal of Medicine that “did not support a positive association between coffee drinking and mortality.” In fact, the analysis by Neal D. Freedman and associates showed that even at the level of 6 or more cups per day, coffee consumption appeared to be mildly protective against diabetes, stroke, and death due to inflammatory diseases. Men who drank that much coffee had a 10% lower risk of death, and women in this category show a 15% lower death risk. Coffee, it seemed, was good for you.

Hooray for coffee—but lost in the general joy over the findings was the constant association of coffee with unhealthy behaviors like smoking, heavy alcohol, use, and consumption of red meat. And the happy coffee findings did not consider the consumption of caffeine in other forms, such as energy drinks, stay-awake pills, various foodstuffs, and even shampoos.

One of the earliest battles over “energy drinks” was an action taken in 1911 under the new Pure Food and Drug Act—the seizure by government agents of 40 kegs and 20 barrels of Coca-Cola syrup in Chattanooga. Led by chemist Harvey Wiley, the first administrator of the Food and Drug Administration (FDA), agents of the fledgling organization acted on the belief that the soft drink contained enough caffeine to pose a significant public health hazard. The court case went on forever. Eventually Coca-Cola cut back on caffeine content, and the charges were dropped.

Jump cut to 2012, and watch the FDA grapple with the same question a hundred years later, citing concerns about undocumented caffeine levels in so-called energy drinks in the wake of an alleged link between the caffeinated soft drinks and the death of several young people. According to Dr. Kent Sepkowitz, writing in the Journal of the American Medical Association, while only 6% of young American men consume the drinks, “in a recent survey of U.S. overseas troops, 45% reported daily use.” In 2006, more than 500 new energy drinks hit the market. By 2011, sales of energy drinks in the U.S. climbed by more than 15% to almost $9 billion.

Death by caffeine has long been a subject of morbid interest, and an article in the Journal of Caffeine Research  by Jack E. James of Iceland’s Reykjavik University questions these prevailing assumptions, and brings together the latest research on this perennial question, including, yes, a consideration of whether the time has come to regulate caffeine as some sort of controlled substance.

In 2013, the FDA released reports that attributed a total of 18 deaths to energy drinks. Somewhere between 3 and 10 grams of caffeine will kill you, especially if you are young, old, or suffer from various health problems. The generally accepted lethal dose is 10 g. The wide gap in estimates and mortality reports reflects the wide variation in caffeine’s effects.  Half the lethal dose can kill a child, and some adults have survived 10 times that amount. As I wrote in an earlier post (“Energy Drinks: What’s the Big Deal?”): “Energy drinks are safe—if you don’t guzzle several of them in a row or substitute them for dinner, or have diabetes, or an ulcer, or happen to be pregnant, or are suffering from hearth disease or hypertension. And if you do OD on high caffeine intake, it will not be pleasant: Severe cardiac arrhythmias, palpitations, panic, mania, muscle spasms, and seizures.”

Warning signs include racing heart, abdominal pain, vomiting, and agitation. Since the average cup of coffee weighs in at about 100 milligrams, there doesn’t seem to be much to worry about in that regard. Nonetheless, the American National Poison Data System (NPDS) has more than 6,000 “case mentions” related to caffeine. One of these cases generated considerable press coverage: the death of a 14 year-old girl with an inherited connective tissue disorder.

In his article for the Journal of Caffeine Research, James starts by noting other fatalities, including two confirmed caffeine-related deaths in New Mexico, and four in Sweden, among other long-standing historical reports. Still, not much there to wring your hands over—but James insists that data on poisonings “do not show what contributory role caffeine may have had in cases where fatal and near-fatal outcomes were deemed to have been due to other compounds also present.”

Fair enough. But here is where the argument gets interesting. “Considerably smaller amounts of caffeine,” writes James, "may be fatal under a variety of atypical though not necessarily rare circumstances.” Among these, he singles out: 1) Prior medical conditions predisposing patients toward unusual caffeine metabolism. 2) Unknown interactions and synergies with prescription, over-the-counter, and illegal drugs. 3) Physical stress and high-intensity sports. 4) Children, for whom caffeine is easily available.

James claims we don’t know enough to insist caffeine is essentially harmless, let along good for us in large doses. He compiled this eye-opening list of foods and other products that sometimes contain caffeine: ice cream, chewing gum, yogurt, breakfast cereal, cookies, flavored milk, beef jerky, cold and flu medications, weight-loss compounds, breath-freshener sprays and mints, skin lotion, lip balm, soap, shampoo, and, most notably, as a contaminant in illegal drugs. James says that the largest category of incidents with over-caffeinated young people involve “miscellaneous stimulants and street drugs…”

As for energy drinks themselves: “As a nonselective adenosine receptor antagonist, caffeine counteracts the somnogenic effects of acute alcohol intoxication, and alcohol may in turn ameliorate the anxiogenic effects of caffeine.” It’s an age-old practice: caffeine doesn’t sober up drunks, but it does keep them awake. James believes the evidence shows that the combination of caffeine and alcohol increases the risks of unprotected sex, sexual assault, drunk driving, violence, and emergency room visits.

Furthermore, “the ubiquity of caffeine is such that it has become a biologically significant contaminant of freshwater and marine systems….”

Finally, James offers a vision of a caffeine-regulated future, noting that Denmark, France, and Norway have already introduced sales restrictions on energy drinks. Restrictions on the sale of powdered caffeine may follow, as a valid public health measure. “Canada requires labeling in relation to the same product, advising that it should not be mixed with alcohol.” Other countries have labeled energy drinks as “high caffeine content” beverages. And Sweden regulates the number of caffeine tablets that can be purchased at one time from a drugstore.  Meanwhile, in the U.S., makers of energy drinks, unlike makers of soft drinks, do not even have to print the amount of caffeine on the label as dietary information, although this is in the process of changing. Major energy drink makers are moving to put caffeine content labels on their products, in part to shift their relationship with the FDA. Last year, The Food and Drug Administration advised consumers to avoid powdered caffeine due to health risks.

Originally published March 13, 2013

Graphics: http://www.runnersworld.com

From “The Pleasures and Pains of Coffee”

By Honore de Balzac, translated by Robert Onopa.

Coffee is a great power in my life; I have observed its effects on an epic scale….

Coffee affects the diaphragm and the plexus of the stomach, from which it reaches the brain by barely perceptible radiations that escape complete analysis; that aside, we may surmise that our primary nervous flux conducts an electricity emitted by coffee when we drink it. Coffee's power changes over time. [Italian composer Gioacchino] Rossini has personally experienced some of these effects as, of course, have I. "Coffee," Rossini told me, "is an affair of fifteen or twenty days; just the right amount of time, fortunately, to write an opera." This is true. But the length of time during which one can enjoy the benefits of coffee can be extended.

For a while - for a week or two at most - you can obtain the right amount of stimulation with one, then two cups of coffee brewed from beans that have been crushed with gradually increasing force and infused with hot water.

For another week, by decreasing the amount of water used, by pulverizing the coffee even more finely, and by infusing the grounds with cold water, you can continue to obtain the same cerebral power.

When you have produced the finest grind with the least water possible, you double the dose by drinking two cups at a time; particularly vigorous constitutions can tolerate three cups. In this manner one can continue working for several more days....

Finally, I have discovered a horrible, rather brutal method that I recommend only to men of excessive vigor... It is a question of using finely pulverized, dense coffee, cold and anhydrous, consumed on an empty stomach. This coffee falls into your stomach, a sack whose velvety interior is lined with tapestries of suckers and papillae. The coffee finds nothing else in the sack, and so it attacks these delicate and voluptuous linings; it acts like a food and demands digestive juices; it wrings and twists the stomach for these juices, appealing as a pythoness appeals to her god; it brutalizes these beautiful stomach linings as a wagon master abuses ponies; the plexus becomes inflamed; sparks shoot all the way up to the brain. From that moment on, everything becomes agitated. Ideas quick-march into motion like battalions of a grand army to its legendary fighting ground, and the battle rages. Memories charge in, bright flags on high; the cavalry of metaphor deploys with a magnificent gallop; the artillery of logic rushes up with clattering wagons and cartridges; on imagination's orders, sharpshooters sight and fire; forms and shapes and characters rear up; the paper is spread with ink - for the nightly labor begins and ends with torrents of this black water, as a battle opens and concludes with black powder.

I recommended this way of drinking coffee to a friend of mine, who absolutely wanted to finish a job promised for the next day: he thought he'd been poisoned and took to his bed, which he guarded like a married man. He was tall, blond, slender and had thinning hair; he apparently had a stomach of papier-mache. There has been, on my part, a failure of observation…."

Dying For Caffeine

It’s not the coffee, it’s everything else.

Late last year, coffee drinkers were buoyed by the release of a massive study in the New England Journal of Medicine that “did not support a positive association between coffee drinking and mortality.” In fact, the analysis by Neal D. Freedman and associates showed that even at the level of 6 or more cups per day, coffee consumption appeared to be mildly protective against diabetes, stroke, and death due to inflammatory diseases. Men who drank that much coffee had a 10% lower risk of death, and women in this category show a 15% lower death risk. Coffee, it seemed, was good for you.

Hooray for coffee—but lost in the general joy over the findings was the constant association of coffee with unhealthy behaviors like smoking, heavy alcohol, use, and consumption of red meat. And the happy coffee findings did not consider the consumption of caffeine in other forms, such as energy drinks, stay-awake pills, various foodstuffs, and even shampoos. 

One of the earliest battles over “energy drinks” was an action taken in 1911 under the new Pure Food and Drug Act—the seizure  by government agents of 40 kegs and 20 barrels of Coca-Cola syrup in Chattanooga. Led by chemist Harvey Wiley, the first administrator of the Food and Drug Administration (FDA), agents of the fledgling organization acted on the belief that the soft drink contained enough caffeine to pose a significant public health hazard. The court case went on forever. Eventually Coca-Cola cut back on caffeine content, and the charges were dropped.

Jump cut to 2012, and watch the FDA grapple with the same question a hundred years later, citing concerns about undocumented caffeine levels in so-called energy drinks in the wake of an alleged link between the caffeinated soft drinks and the death of several young people. According to Dr. Kent Sepkowitz, writing in the Journal of the American Medical Association, while only 6% of young American men consume the drinks, “in a recent survey of U.S. overseas troops, 45% reported daily use.” In 2006, more than 500 new energy drinks hit the market. By 2011, sales of energy drinks in the U.S. climbed by more than 15% to almost $9 billion.

Death by caffeine has long been a subject of morbid interest, and a recent article in the Journal of Caffeine Research  by Jack E. James of Iceland’s Reykjavik University questions these prevailing assumptions, and brings together the latest research on this perennial question, including, yes, a consideration of whether the time has come to regulate caffeine as some sort of controlled substance.

Last month, the FDA released reports that attributed a total of 18 deaths to energy drinks. Somewhere between 3 and 10 grams of coffee will kill you, especially if you are young, old, or suffer from various health problems. The generally accepted lethal dose is 10 g. The wide gap in estimates and mortality reports reflects the wide variation in caffeine’s effects.  Half the lethal dose can kill a child, and some adults have survived 10 times that amount. As I wrote in an earlier post (“Energy Drinks: What’s the Big Deal?”): “Energy drinks are safe—if you don’t guzzle several of them in a row or substitute them for dinner, or have diabetes, or an ulcer, or happen to be pregnant, or are suffering from hearth disease or hypertension. And if you do OD on high caffeine intake, it will not be pleasant: Severe cardiac arrhythmias, palpitations, panic, mania, muscle spasms, and seizures.”

Warning signs include racing heart, abdominal pain, vomiting, and agitation. Since the average cup of coffee weighs in at about 100 milligrams, there doesn’t seem to be much to worry about in that regard. Nonetheless, the American National Poison Data System (NPDS) has more than 6,000 “case mentions” related to caffeine. One of these cases generated considerable press coverage: the death of a 14 year-old girl with an inherited connective tissue disorder. 

In his article for the Journal of Caffeine Research, James starts by noting other fatalities, including two confirmed caffeine-related deaths in New Mexico, and four in Sweden, among other long-standing historical reports. Still, not much there to wring your hands over—but James insists that data on poisonings “do not show what contributory role caffeine may have had in cases where fatal and near-fatal outcomes were deemed to have been due to other compounds also present.”

Fair enough. But here is where the argument gets interesting. “Considerably smaller amounts of caffeine,” writes James, "may be fatal under a variety of atypical though not necessarily rare circumstances.” Among these, he singles out: 1) Prior medical conditions predisposing patients toward unusual caffeine metabolism. 2) Unknown interactions and synergies with prescription, over-the-counter, and illegal drugs. 3) Physical stress and high-intensity sports. 4) Children, for whom caffeine is easily available.

James claims we don’t know enough to insist caffeine is essentially harmless, let along good for us in large doses. He compiled this eye-opening list of foods and other products that sometimes contain caffeine: ice cream, chewing gum, yogurt, breakfast cereal, cookies, flavored milk, beef jerky, cold and flu medications, weight-loss compounds, breath-freshener sprays and mints, skin lotion, lip balm, soap, shampoo, and, most notably, as a contaminant in illegal drugs. James says that the largest category of incidents with over-caffeinated young people involve “miscellaneous stimulants and street drugs…”

As for energy drinks themselves: “As a nonselective adenosine receptor antagonist, caffeine counteracts the somnogenic effects of acute alcohol intoxication, and alcohol may in turn ameliorate the anxiogenic effects of caffeine.” It’s an age-old practice: caffeine doesn’t sober up drunks, but it does keep them awake. James believes the evidence shows that the combination of caffeine and alcohol increases the risks of unprotected sex, sexual assault, drunk driving, violence, and emergency room visits.

Furthermore, “the ubiquity of caffeine is such that it has become a biologically significant contaminant of freshwater and marine systems….”

Finally, James offers a vision of a caffeine-regulated future, noting that Denmark, France, and Norway have already introduced sales restrictions on energy drinks. “Canada requires labeling in relation to the same product, advising that it should not be mixed with alcohol.” Other countries have labeled energy drinks as “high caffeine content” beverages. And Sweden regulates the number of caffeine tablets that can be purchased at one time from a drugstore.  Meanwhile, in the U.S., makers of energy drinks, unlike makers of soft drinks, do not even have to print the amount of caffeine on the label as dietary information, although this is in the process of changing. Major energy drink makers are moving to put caffeine content labels on their products, in part to shift their relationship with the FDA.

Bonus: Check HERE for the 15 most caffeinated cities in America. Sure, Seattle is first, but can you guess the others?

Graphics credit: Wikipedia

Bees Benefit From Caffeine

Caffeinated plants provide an unforgettable experience.

Honeybees rewarded with caffeine remember the smell of specific flowers longer than bees given only sucrose, according to a study published in Science. “By using a drug to enhance memories of reward,” the study says, “plants secure pollinator fidelity and improve reproductive success.”

Many drugs used by humans come from plants. But what role do the drugs play for the plants themselves? Frequently, they play the role of toxic avenger, providing a chemical defense against attacks by herbivores. But in smaller doses, they often have pharmacological effects on mammals. The researchers looked at two genera of caffeine-producing plants—Coffea and Citrus. “If caffeine confers a selective advantage when these pants interact with pollinators,” the investigators reasoned, “we might expect it to be commonly encountered in nectar.” And it was. Caffeine at very low doses was measured in the nectar of several of the caffeine-producing plant species, including several Coffea species, as well as some citrus nectars—grapefruit, lemons, and oranges among them.

Next, the researchers wanted to find out if the caffeine-laced nectar could affect learning and memory in pollinating bees. They trained individual honeybees to associate various floral scents with sucrose containing various concentrations of caffeine. This pairing of odor and reward, with high-concentration sucrose as the control, demonstrated that low doses of caffeine had almost no effect on the rate of honeybee learning—but a profound effect on long-term memory. Three times as many caffeinated bees remembered the conditioned floral scent 24 hours later, “and responded as if it predicted reward.” Twice as many bees remembered the scent at the 72-hour mark.

What’s the trick? Caffeine’s ability to influence mammalian behavior is due to its action as an adenosine receptor antagonist. “In the hippocampal region,” the authors write, “inhibition of adenosine receptors by caffeine induces long-term potentiation, a key mechanism of memory formation." The Kenyon cells in mushroom bodies of the insect brain, which showed “increased excitability” under the influence of caffeine, are similar in function to hippocampal neurons, they write. “Remembering floral traits is difficult for bees to perform at a fast pace as they fly from flower to flower and we have found that caffeine helps the bee remember where the flowers are,” said Geraldine Wright of the UK’s Newcastle University, who was lead author on the study. “So, caffeine in nectar is likely to improve the bee’s foraging prowess while providing the plant with a more faithful pollinator.”

It is an interesting balancing act by nature: Too much caffeine makes the nectar toxic and repellent to honeybees. Too little, and there is no behavioral effect on bee memory. “This implies that pollinators drive selection toward concentrations of caffeine that are not repellent but still pharmacologically active,” says the report.  Humans have selected for a not-too-much, not-too-little dose of caffeine in the form of soda drinks and coffee. Is it possible that the humble coffee bean is pharmacologically manipulating us into taking good care of it? And do we drink it when we read or study because, for one thing, it enhances long-term memory? And speaking of memory, people often forget where they tucked the oregano, but they usually have little difficulty remembering where they stashed the coffee.

More pragmatically, honeybees on caffeine may lead researchers toward a better understanding of the foraging strategies of pollinator insects, and allow for improved management of crops and landscapes.

Wright G.A., Baker D.D., Palmer M.J., Stabler D., Mustard J.A., Power E.F., Borland A.M. & Stevenson P.C. (2013). Caffeine in Floral Nectar Enhances a Pollinator's Memory of Reward, Science, 339 (6124) 1202-1204. DOI: 10.1126/science.1228806

Photo credit: http://www.coorgblog.orangecounty.in

Energy Drinks: What’s the Big Deal?

The sons of Red Bull are sporting record concentrations of caffeine.

Are energy drinks capable of pushing some people into caffeine-induced psychotic states? Some medical researchers think so, under the right set of conditions.

Red Bull, for all its iconic ferocity, is pretty tame, weighing in at approximately half a cup of coffee. Drinks like Monster Energy and Full Throttle push it up to 100-150, or the equivalent of a full cuppa joe, according to USDA figures at Talk About Coffee. That doesn’t sound so bad—unless you’re ten years old. A little caffeine might put you on task, but an overdose can leave you scattered and anxious—or worse. If you cut your teeth on Coke and Pepsi, then two or three energy drinks can deliver an order-of-magnitude overdose by comparison.

Readers are entitled to ask: Are you serious? Can’t we just ignore the inevitable view-this-with-alarm development in normal kid culture, and move on? 

My interest began when I ran across a 2009 case report in CNS Spectrums, describing an apparent example of “caffeine-induced delusions and paranoia” in a very heavy coffee drinking farmer. “Convinced of a plot against him,” the psychologists write, “he installed surveillance cameras in his house and on his farm…. He became so preoccupied with the alleged plot that he neglected the business of the farm…. and he had his children taken from him because of unsanitary living conditions.”

The patient was not known to be a drinker, reporting less than a case of beer annually. He had shown no prior history of psychotic behaviors. But for the past seven years, he had been consuming about 36 cups of coffee per day, according to his account. Take that number of cups times 125 milligrams, let’s say, for a daily total of 4500 milligrams. At that level, he should be suffering from panic and anxiety disorders, according to caffeine toxicity reports, and he would be advised to call the Poison Control Center. And that certainly seems to have been the case. “At presentation,” the authors write, “the patient reported drinking 1 gallon of coffee/day.”

On the one hand, the idea of caffeine causing a state resembling chronic psychosis is the stuff of sitcoms. On the other hand, metabolisms do vary, and the precise manner in which coffee stimulates adenosine receptors can lead to anxiety, aggression, agitation, and other conditions. Could caffeine, in an aberrant metabolism, break over into full-blown psychosis? At the Caffeine Web, where psychiatrists and toxicologists duke it out over all things caffeinated, Sidney Kay of the Institute of Legal Medicine writes: “Coffee overindulgence is overlooked many times because the bizarre symptoms may resemble and masquerade as an organic or mental disease.” Symptoms, he explains, can include "restlessness, silliness, elation, euphoria, confusion, disorientation, excitation, and even violent behavior with wild, manic screaming, kicking and biting, progressing to semi-stupor.”

That doesn’t sound so good. In “Energy drinks: What is all the hype?” Mandy Rath examines the question in a recent issue of the Journal of the American Academy of Health Practitioners.

Selling energy drinks to kids from 6 to 19 years old is a $3.5 billion annual industry,Rath asserts. And while “most energy drinks consumed in moderation do not pose a huge health risk,” more and more youngsters are putting away higher and higher doses of caffeine. At the level of several cans of Coke, or a few cups of strong coffee or, an energy drink or three, students can expect to experience improved reaction times, increased aerobic endurance, and less sleepiness behind the wheel. Most people can handle up to 300 mg of caffeine in a concentrated blast. Certainly a better bargain, overall, than three or four beers.

But first of all, you don’t need high-priced, caffeine-packed superdrinks to achieve that effect. A milligram of caffeine is a milligram of caffeine. But wait, what about the nifty additives in Full Throttle and Monster and Rockstar? The taurine and… stuff. Taurine is an amino acid found in lots of foods. Good for you in the abstract. Manufacturers also commonly add sugar (excess calories), ginseng (at very low levels), and bitter orange (structurally similar to norepinephrine). However, the truly interesting addition is guarana, a botanical product from South America. When guarana breaks down, it’s principal byproduct is, yes, caffeine. Guarana seeds contain twice the caffeine found in coffee beans. Three to five grams of guarana provide 250 mg of caffeine. Energy drink manufacturers don’t add that caffeine to the total on the label because—oh wait, that’s right, because makers of energy drinks, unlike makers of soft drinks, don’t have to print the amount of caffeine as dietary information. And on an ounce-for-pound basis, kids are getting a lot more caffeine with the new drinks than the older, labeled ones.

All of this increases the chances of caffeine intoxication. Rath writes that researchers have identified caffeine-related increases among children in hypertension, insomnia, motor tics, irritability, and headaches. Chronic caffeine intoxication results in “anxiety, emotional disturbances, and chronic abdominal pain.” Not to mention cardiac arrhythmia, seizures, and mania.

So what have we learned, kids? Energy drinks are safe—if you don’t guzzle several of them in a row, or substitute them for dinner, or have diabetes, or an ulcer, or happen to be pregnant, or are suffering from heart disease or hypertension. And if you do OD on high-caffeine drinks, it will not be pleasant: Severe palpitations, panic, mania, muscle spasms, etc. Somebody might even want to take you to the emergency room. Coaches and teachers need to keep a better eye out for caffeine intoxication.

Note: There is a “caffeine calculator” available at the Caffeine Awareness website, designed to determined whether you are a coffee addict. I can by no means swear to its scientific accuracy, but, based on my own, distinctly non-young person daily intake, the test told me that my consumption was likely to manifest itself as “high irritability, moodiness & personality disorders.” Can I blame it all on those endless cokes we had as kids? Growing up in the Baby Boom suburbs, we all drank carbonated caffeine beverages instead of water. Nothing much has changed except the caffeine levels.

Rath, M. (2012). Energy drinks: What is all the hype? The dangers of energy drink consumption Journal of the American Academy of Nurse Practitioners, 24 (2), 70-76 DOI: 10.1111/j.1745-7599.2011.00689.x

Graphics Credit: http://urlybits.com/

Night Owls Get a Coffee Break

“Morning people” have more caffeine-related sleep problems.

Let me start by saying that I love this caffeine study for personal reasons. As a lifelong night owl, I have been chastised by wife, family, and friends over the years for my regular habit of drinking coffee after 10 pm. (And falling easily asleep two or three hours later, if I choose to.) Other coffee drinkers have told me how rare and weird this is. If we have a cup, they tell me, or even an afternoon sip, we toss and turn all night.

As it turns out, I was talking to the wrong kind of coffee drinkers. I needed to consult my crowd, and that’s what I did. I checked in with a few confirmed fellow night owls, and yes, a few of them reported that they had no problems going to sleep after a late night cup or two.

Anecdotal, of course—but a recent clinical study published in Sleep Medicine backs me up. The study, “Modeling caffeine concentrations with the Stanford Caffeine Questionnaire: Preliminary evidence for an interaction of chronotype with the effects of caffeine on sleep,” sets out to examine the effects of caffeine on the sleep patterns of college students. Researchers at Stanford told the students to keep sleep logs and to wear an actigraphy wristband to record rest/activity cycles. The students filled out daily questionnaires about their caffeine intake at different times of the day, and gave saliva samples for caffeine assessments.

 The scientists were able to accurately predict salivary caffeine concentrations based on the questionnaires, which was the primary intent of the study. But in the process, they discovered what they believe to be “a novel relationship between the effects of caffeine on sleep and genotype and chronotype.” What the researchers ended up with was some seriously suggestive evidence about the relationship of caffeine and natural sleep rhythms. (Here’s a nifty little test to determine whether you are a lark or an owl, i.e., your chronotype.)

Typically, clinical trials with caffeine are limited to the basic question: How much coffee did you drink today? But the Stanford researchers wanted to include the many variables that modulate caffeine intake—things like the timing of ingestion, the variations in the amount of caffeine among beverages, individual variations in caffeine metabolism, and the wide differences in half-life that caffeine can exhibit under various circumstances. They attempted to establish the students’ genotypes for adenosine receptors, where caffeine does most of its work, and to select volunteers who had “statistically indistinguishable” differences in adenosine receptor gene frequencies.

As you might expect, even among students, caffeine intake progressively decreased throughout the day in the study group. However, a small number of participants continued their intake of caffeine well into the night. The metric known as “wake after sleep onset,” or WASO, was used as the primary measurement of sleep disruption. “Our data indicate caffeine strongly influences WASO in those who self-identify as morning-type,” the researchers found. “It affects WASO less so in those who are neither type, and does not appear to affect WASO in those who are evening-type. To our knowledge, there have been no previous reports linking the effects of caffeine and chronotype.”

Some warnings on the study: It involved only 50 college students. And they were students, meaning their schedules were highly erratic by definition, and they were chronically sleep-deprived by habit. The study authors attempted to turn this defect into a virtue, noting that “the students were under such homeostatic pressure that their mood had little effect on their sleep.” Nonetheless, we will need to see if the findings hold up using less, er, unpredictable subjects.

If they do hold up, it will make it easier for people to understand the homily delivered by the coffee-drinking grandmother of a friend of mine: “The only time coffee ever kept me awake was when I knew there was another cup in the pot.”

Photo credit: http://www.facebook.com/

Nova, P., Hernandez, B., Ptolemy, A., & Zeitzer, J. (2012). Modeling caffeine concentrations with the Stanford Caffeine Questionnaire: Preliminary evidence for an interaction of chronotype with the effects of caffeine on sleep Sleep Medicine DOI: 10.1016/j.sleep.2011.11.011

The Black Bag: Odds and Ends

Drug news from the world of science and medicine.


--How Marijuana Impairs Memory

Mo Costandi at the UK Guardian expands on his Nature article about the mechanisms that result in memory impairment when people smoke marijuana. Memory formation depends on the neurotransmitter glutamate. What goes wrong when you smoke pot? Enter the astrocyte…

--Coffee Will Disrupt Your Sleep—Unless You’re a Night Owl

From Scientific American comes the news that your “chronotype”—the chronological patterns you naturally favor—may determine whether or not caffeine keeps you tossing and turning and night. Morning people, or “larks,” had more periods of wakefulness during sleep hours than night people, or “owls.” The findings, published in the journal Sleep Medicine, show that “for the early risers, the more caffeine in their bodies, the more time they spent awake during the night after initially falling asleep. This was not seen in the night owls.”

--Brain Scans Get Better

You wouldn’t know it from all the bad press about moving heads and specious interpretations, but fMRI technology continues to improve. Time Healthland reports that new machines will be able to do a better job spotting traumatic brain injury in military personnel, athletes, and accident victims. High-definition fiber tracking, as this article in the Journal of Neurosurgery explains, will allow medical staff to better assess damage to nerve fibers deep in the brain, due to technological improvements in “assessing white matter injuries that are not apparent in standard anatomical imaging.”

--Cig Makers Trump FDA on Free Speech Grounds

The FDA maybe didn’t think this one through quite as thoroughly as they should have. Reuters reports  that a U.S. judge “sided with tobacco companies on Wednesday, ruling that regulations requiring large graphic health warnings on cigarette packaging and advertising violate free-speech rights under the U.S. Constitution.” Evidently, FDA officials didn’t see the 1st Amendment argument coming. By mandating grisly pictures of diseased lungs, rotting teeth, and dying smokers on cigarette packs, “the government has failed to carry both its burden of demonstrating a compelling interest and its burden of demonstrating that the rule is narrowly tailored to achieve a constitutionally permissible form of compelled commercial speech," U.S. District Judge Richard Leon said.

--Meth Head Burns Down Tree Older Than Jesus

And finally, as if we needed any more evidence, here’s a story about bad decision-making among the meth head crowd: WFTV reports that a female meth addict in Seminole County, Florida, burned down a historic cypress believed to have been the world’s 5th oldest tree. Authorities learned that the woman and a friend had been cooking methamphetamine under the 3,500 year-old tree. Officials said the woman took pictures of the disaster with her cell phone, and was quoted saying: "I can't believe I burned down a tree older then Jesus."

Photo Credit: http://www.squidoo.com 

Coffee and Your Heart

Recent research shows that coffee drinkers come in two flavors: “fast” metabolizers and “slow” metabolizers. People with a particular gene variant are more vulnerable to it’s effects. The gene in question controls the production of a key enzyme, known as CYP1A2, responsible for metabolizing coffee in the liver. People who inherit the slow version face a greater risk of non-fatal heart attacks at high levels of caffeine intake.

“The association between coffee and myocardial infarction [heart attack] was found only among individuals with the slow CYP1A2 allele [gene variant], which impairs caffeine metabolismm, suggesting that caffeine plays a role in the association,” the authors wrote in the Journal of the American Medical Association (JAMA).

The University of Toronto’s Ahmed El-Sohemy, a co-author of the published study, told the Associated Press that metabolic differences might help to explain why previous studies of caffeine’s cardiovascular effects have proven to be contradictory and inconclusive.*

Unfortunately, at present only an expensive lab test will reveal which variant a given coffee drinker has inherited.

Sources:

--Cornelis, Marilyn, C., et al. “Coffee, CYP1A2 Genotype, and Risk of Myocardial Infarction.” Journal of the American Medical Association. 295 10: 1135 March 8, 2006.

--”Coffee May Spell Heart Trouble for Some.” Associated Press. March 7, 2006.
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*Drugs are broken down into their constituent waste products by specific sets of enzymes. A subset of the human population, variously estimated at 3% to 7%, are categorized as “poor metabolizers.” For them, a drug’s recommended dosage is often far too high.

The culprit is a genetic variant that codes for a liver enzyme called cytochrome P450 isoenzyme 2D6, known in shorthand as CYP2D6. Poor metabolizers produce less of this crucial enzyme, which means that drugs are broken down and excreted at a much slower pace. In these people, the recommended dose results in higher drug concentrations. This obviously can make a crucial difference in how a person reacts to the drugs.

About one out of 20 people has a mutation in the 2D6 gene that causes a lack of the enzyme, according to UC-San Francisco biochemist Ira Herskowitz. “Those people are really getting a whopping dose.” In addition, if a person with normal CYP2D6 levels is taking several drugs that are broken down by CYP2D6, then the enzyme’s ability to degrade one drug can greatly inhibit its ability to degrade the others. This increases the possibility of adverse drug interactions, particularly among the elderly, who may already be suffering from liver disease or impaired renal function. Drugs of abuse severely complicate these enzymatic issues, since addicts and alcoholics are not known for volunteering information about their condition to medical or hospital personnel. Poor metabolizers often have little or no reaction to codeine-based medications. Screening tests for CYP2D6 variations are becoming cheaper and more widely available.

Enzyme interactions can work the other way, too. St. John’s Wort, for example, is suspected of activating another drug breakdown enzyme, CPY3A, thereby accelerating, rather than retarding, the destruction of other drugs. The herb can alter the metabolization of Phenobarbital, tamoxifen, oral contraceptives, and antiviral medications. Drugs must be combined with caution, and people need to monitor dosages, because of the tremendous degree of metabolic variation that exists.

“Start low and go slow” is still the best advice.

--The Chemical Carousel: What Science Tells Us About Beating Addiction © Dirk Hanson 2008, 2009.