Caffeine affects boys and girls differently after puberty

Caffeine intake by children and adolescents has been rising for decades, due in large part to the popularity of caffeinated sodas and energy drinks, which now are marketed to children as young as four. Despite this, there is little research on the effects of caffeine on young people.

One researcher who is conducting such investigations is Jennifer Temple, PhD, associate professor in the Department of Exercise and Nutrition Sciences, University at Buffalo School of Public Health and Health Professions.

Her new study finds that after puberty, boys and girls experience different heart rate and blood pressure changes after consuming caffeine. Girls also experience some differences in caffeine effect during their menstrual cycles.

The study, “Cardiovascular Responses to Caffeine by Gender and Pubertal Stage,” will be published online June 16 in the July 2014 edition of the journal Pediatrics.

Past studies, including those by this research team, have shown that caffeine increases blood pressure and decreases heart rate in children, teens and adults, including pre-adolescent boys and girls. The purpose here was to learn whether gender differences in cardiovascular responses to caffeine emerge after puberty and if those responses differ across phases of the menstrual cycle.

Temple says, “We found an interaction between gender and caffeine dose, with boys having a greater response to caffeine than girls, as well as interactions between pubertal phase, gender and caffeine dose, with gender differences present in post-pubertal, but not in pre-pubertal, participants.

“Finally,” she says, “we found differences in responses to caffeine across the menstrual cycle in post-pubertal girls, with decreases in heart rate that were greater in the mid-luteal phase and blood pressure increases that were greater in the mid-follicular phase of the menstrual cycle.

“In this study, we were looking exclusively into the physical results of caffeine ingestion,” she says.

Phases of the menstrual cycle, marked by changing levels of hormones, are the follicular phase, which begins on the first day of menstruation and ends with ovulation, and the luteal phase, which follows ovulation and is marked by significantly higher levels of progesterone than the previous phase.

Future research in this area will determine the extent to which gender differences are mediated by physiological factors such as steroid hormone level or by differences in patterns of caffeine use, caffeine use by peers or more autonomy and control over beverage purchases, Temple says.

This double-blind, placebo-controlled, dose-response study was funded by a grant from the National Institute on Drug Abuse of the National Institutes of Health. 

It examined heart rate and blood pressure before and after administration of placebo and two doses of caffeine (1 and 2 mg/kg) in pre-pubertal (8- to 9-year-old; n = 52) and post-pubertal (15- to 17-year-old; n = 49) boys (n = 54) and girls (n = 47).

Caffeine against Alzheimer’s disease

A team of researchers working with Prof. Dr. Christa E. Müller from the University of Bonn demonstrates a positive effect on tau deposits

As part of a German-French research project, a team led by  Dr. Christa E. Müller from the University of Bonn and Dr. David Blum from the University of Lille was able to demonstrate for the first time that caffeine has a positive effect on tau deposits in Alzheimer’s disease. The two-years project was supported with 30,000 Euro from the non-profit Alzheimer Forschung Initiative e.V. (AFI) and with 50,000 Euro from the French Partner organization LECMA. The initial results were published in the online edition of the journal “Neurobiology of Aging”

Tau deposits, along with beta-amyloid plaques, are among the characteristic features of Alzheimer’s disease. These protein deposits disrupt the communication of the nerve cells in the brain and contribute to their degeneration. Despite intensive research there is no drug available to date  which can prevent this detrimental process. Based on  the results of Prof. Dr. Christa Müller from the University of Bonn, Dr. David Blum and their team, a new class of drugs may now be developed for the treatment of Alzheimer’s disease.

Caffeine, an adenosine receptor antagonist, blocks various receptors in the brain which are activated by adenosine. Initial results of the team of researchers had already indicated that the blockade of the adenosine receptor subtype A2A in particular could play an important role. Initially, Prof. Müller and her colleagues developed an A2A antagonist in ultrapure and water-soluble form (designated MSX-3). This compound had fewer adverse effects than caffeine since it only blocks only the A2A adenosine receptor subtype, and at the same time it is significantly more effective. Over several weeks, the researchers then treated genetically altered mice with the A2A antagonist. The mice had an altered tau protein which, without therapy, leads to the early development of Alzheimer’s symptoms.

In comparison to a control group which only received a placebo, the treated animals achieved significantly better results on memory tests. The A2A antagonist displayed positive effects in particular on spatial memory. Also, an amelioration of the pathogenic processes was demonstrated in the hippocampus, which is the site of memory in rodents.

"We have taken a good step forward," says Prof. Müller. "The results of the study are truly promising, since we were able to show for the first time that A2A adenosine receptor antagonists actually have very positive effects in an animal model simulating hallmark characteristics and progression of  the disease. And the adverse effects are minor."

The researchers now want to test the A2A antagonist in additional animal models. If the results are positive, a clinical study may follow. “Patience is required until A2A adenosine receptor antagonists are approved as new therapeutic agents for Alzheimer’s disease. But I am optimistic that clinical studies will be performed,” says Prof. Müller.

(Image: Shutterstock)

Caffeine has positive effect on memory

Whether it’s a mug full of fresh-brewed coffee, a cup of hot tea, or a can of soda, consuming caffeine is the energy boost of choice for millions who want to wake up or stay up.

Now, researchers at Johns Hopkins University have found another use for the popular stimulant: memory enhancer.

Michael Yassa, an assistant professor of psychological and brain sciences at Johns Hopkins, and his team of scientists found that caffeine has a positive effect on our long-term memory. Their research, published by the journal Nature Neuroscience, shows that caffeine enhances certain memories at least up to 24 hours after it is consumed.

"We’ve always known that caffeine has cognitive-enhancing effects, but its particular effects on strengthening memories and making them resistant to forgetting has never been examined in detail in humans," said Yassa, senior author of the paper. "We report for the first time a specific effect of caffeine on reducing forgetting over 24 hours."

The Johns Hopkins researchers conducted a double-blind trial in which participants who did not regularly eat or drink caffeinated products received either a placebo or a 200-milligram caffeine tablet five minutes after studying a series of images. Salivary samples were taken from the participants before they took the tablets to measure their caffeine levels. Samples were taken again one, three, and 24 hours afterwards.

The next day, both groups were tested on their ability to recognize images from the previous day’s study session. On the test, some of the visuals were the same as those from the day before, some were new additions, and some were similar but not the same.

More members of the caffeine group were able to correctly identify the new images as “similar” to previously viewed images rather than erroneously citing them as the same.

The brain’s ability to recognize the difference between two similar but not identical items, called pattern separation, reflects a deeper level of memory retention, the researchers said.

"If we used a standard recognition memory task without these tricky similar items, we would have found no effect of caffeine," Yassa said. "However, using these items requires the brain to make a more difficult discrimination—what we call pattern separation, which seems to be the process that is enhanced by caffeine in our case."

The memory center in the human brain is the hippocampus, a seahorse-shaped area in the medial temporal lobe of the brain. The hippocampus is the switchbox for all short- and long-term memories. Most research done on memory—the effects of concussions in athletes, of war-related head injuries, and of dementia in the aging population—focuses on this area of the brain.

Until now, caffeine’s effects on long-term memory had not been examined in detail. Of the few studies done, the general consensus was that caffeine has little or no effect on long-term memory retention.

The research is different from prior experiments because the subjects took the caffeine tablets only after they had viewed and attempted to memorize the images.

"Almost all prior studies administered caffeine before the study session, so if there is an enhancement, it’s not clear if it’s due to caffeine’s effects on attention, vigilance, focus, or other factors," Yassa said. "By administering caffeine after the experiment, we rule out all of these effects and make sure that if there is an enhancement, it’s due to memory and nothing else."

According to the U.S. Food and Drug Administration, 90 percent of people worldwide consume caffeine in one form or another. In the United States, 80 percent of adults consume caffeine every day. The average adult has an intake of about 200 milligrams—the same amount used in the Yassa study—or roughly one cup of strong coffee per day.

Yassa’s team completed the research at Johns Hopkins before his lab moved to the University of California, Irvine, at the start of this year.

"The next step for us is to figure out the brain mechanisms underlying this enhancement," Yassa said. "We can use brain-imaging techniques to address these questions. We also know that caffeine is associated with healthy longevity and may have some protective effects from cognitive decline like Alzheimer’s disease. These are certainly important questions for the future."

Caffeine Consumption Within Six Hours Of Bedtime May Disrupt Sleep

Consumption of caffeine, even six hours before bedtime, can have significant, disruptive effects on sleep. The study, from the American Academy of Sleep Medicine, was published in the Journal of Clinical Sleep Medicine.

“Sleep specialists have always suspected that caffeine can disrupt sleep long after it is consumed,” said American Academy of Sleep Medicine President M. Safwan Badr, MD. “This study provides objective evidence supporting the general recommendation that avoiding caffeine in the late afternoon and at night is beneficial for sleep.”

The researchers found that 400 mg of caffeine (about 2-3 cups of coffee) taken at bedtime, or three to six hours before bedtime, significantly impacts sleep. Objectively measured total sleep time was reduced by more than an hour even when the caffeine was consumed six hours before going to bed. Subjective reports, however, suggest that the study participants were unaware of this sleep disturbance.

“Drinking a big cup of coffee on the way home from work can lead to negative effects on sleep just as if someone were to consume caffeine closer to bedtime,” said Christopher Drake, PhD, investigator at the Henry Ford Sleep Disorders and Research Center and associate professor of psychiatry and behavioral neurosciences at Wayne State University.

People tend to be less likely to detect the disruptive effects of caffeine on sleep when taken in the afternoon,” noted Drake, who is also on the board of directors of the Sleep Research Society.

The researchers recruited 12 healthy normal sleepers, as determined by a physical examination and clinical interview. Subjects were instructed to maintain their normal sleep schedule, but were given three pills a day for four days to be taken at six, three and zero hours before scheduled bedtime. Two of the pills were placebos, and one was 400 mg of caffeine. On one of the four days, all three of the participants’ pills were a placebo. The researchers measured sleep disturbance subjectively using a standard sleep diary and objectively using an in-home sleep monitor.

This is the first study to investigate the effects of a given dose of caffeine taken at different times before sleep. The findings suggest that, in order to allow healthy sleep, individuals should avoid caffeine after 5pm.

This Is How Your Brain Becomes Addicted to Caffeine

Within 24 hours of quitting the drug, your withdrawal symptoms begin. Initially, they’re subtle: The first thing you notice is that you feel mentally foggy, and lack alertness. Your muscles are fatigued, even when you haven’t done anything strenuous, and you suspect that you’re more irritable than usual.

Over time, an unmistakable throbbing headache sets in, making it difficult to concentrate on anything. Eventually, as your body protests having the drug taken away, you might even feel dull muscle pains, nausea and other flu-like symptoms.

This isn’t heroin, tobacco or even alcohol withdrawl. We’re talking about quitting caffeine, a substance consumed so widely (the FDA reports thatmore than 80 percent of American adults drink it daily) and in such mundane settings (say, at an office meeting or in your car) that we often forget it’s a drug—and by far the world’s most popular psychoactive one.

Like many drugs, caffeine is chemically addictive, a fact that scientists established back in 1994. This past May, with the publication of the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM), caffeine withdrawal was finally included as a mental disorder for the first time—even though its merits for inclusion are symptoms that regular coffee-drinkers have long known well from the times they’ve gone off it for a day or more.

Why, exactly, is caffeine addictive? The reason stems from the way the drug affects the human brain, producing the alert feeling that caffeine drinkers crave.

Soon after you drink (or eat) something containing caffeine, it’s absorbed through the small intestine and dissolved into the bloodstream. Because the chemical is both water- and fat-soluble (meaning that it can dissolve in water-based solutions—think blood—as well as fat-based substances, such as our cell membranes), it’s able to penetrate the blood-brain barrier and enter the brain.

Structurally, caffeine closely resembles a molecule that’s naturally present in our brain, called adenosine (which is a byproduct of many cellular processes, including cellular respiration)—so much so, in fact, that caffeine can fit neatly into our brain cells’ receptors for adenosine, effectively blocking them off. Normally, the adenosine produced over time locks into these receptors and produces a feeling of tiredness.

When caffeine molecules are blocking those receptors, they prevent this from occurring, thereby generating a sense of alertness and energy for a few hours. Additionally, some of the brain’s own natural stimulants (such as dopamine) work more effectively when the adenosine receptors are blocked, and all the surplus adenosine floating around in the brain cues the adrenal glands to secrete adrenaline, another stimulant.

For this reason, caffeine isn’t technically a stimulant on its own, says Stephen R. Braun, the author or Buzzed: the Science and Lore of Caffeine and Alcohol, but a stimulant enabler: a substance that lets our natural stimulants run wild. Ingesting caffeine, he writes, is akin to “putting a block of wood under one of the brain’s primary brake pedals.” This block stays in place for anywhere from four to six hours, depending on the person’s age, size and other factors, until the caffeine is eventually metabolized by the body.

In people who take advantage of this process on a daily basis (i.e. coffee/tea, soda or energy drink addicts), the brain’s chemistry and physical characteristics actually change over time as a result. The most notable change is that brain cells grow more adenosine receptors, which is the brain’s attempt to maintain equilibrium in the face of a constant onslaught of caffeine, with its adenosine receptors so regularly plugged (studies indicate that the brain also responds by decreasing the number of receptors for norepinephrine, a stimulant). This explains why regular coffee drinkers build up a tolerance over time—because you have more adenosine receptors, it takes more caffeine to block a significant proportion of them and achieve the desired effect.

This also explains why suddenly giving up caffeine entirely can trigger a range of withdrawal effects. The underlying chemistry is complex and not fully understood, but the principle is that your brain is used to operating in one set of conditions (with an artificially-inflated number of adenosine receptors, and a decreased number of norepinephrine receptors) that depend upon regular ingestion of caffeine. Suddenly, without the drug, the altered brain chemistry causes all sorts of problems, including the dreaded caffeine withdrawal headache.

The good news is that, compared to many drug addictions, the effects are relatively short-term. To kick the thing, you only need to get through about 7-12 days of symptoms without drinking any caffeine. During that period, your brain will naturally decrease the number of adenosine receptors on each cell, responding to the sudden lack of caffeine ingestion. If you can make it that long without a cup of joe or a spot of tea, the levels of adenosine receptors in your brain reset to their baseline levels, and your addiction will be broken.

Researchers find caffeine during pregnancy negatively impacts mice brains

A team of European researchers has found that mice who consume caffeine while pregnant give birth to pups with negative changes to their brains. In their paper published in the journal Science Translational Medicine, the team reports on their findings after examining the brains of mice pups whose mothers were given caffeine during pregnancy.

Medical researchers have shown that drugs such as cocaine, heroin or even marijuana can have a negative impact on fetal development—in contrast most believe that moderate amounts of caffeine consumption during pregnancy is “safe” meaning it has little or no adverse impact on fetal development. This new study doesn’t change that view, but it does suggest that perhaps more research needs to be done.

In their study, the researchers administered the equivalent of 4 or 5 cups of coffee a day to pregnant mice—afterwards they studied the brains of the pups that were born. In so doing, they found that GABA neurons didn’t migrate during brain development to their proper location in the Hippocampus at the same rate as untreated mice. GABA neurons are responsible for controlling the flow of information in the brain. Subsequent tests found the treated pups to be more susceptible to seizures.

The team also found that if they allowed the treated pups to grow to adulthood, they tended to demonstrate problems with memory—instead of playing with new objects placed in their cages, for example, they were satisfied with playing with objects they already knew—a trait that is uncommon for mice. Autopsies of adult brains also showed fewer neurons in the Hippocampus.

The researchers point out that their results in mice are not necessarily applicable to humans and to reinforce that point another team of researchers also published a Focus piece in the same journal pointing out that there are significant differences in the developmental process of humans and mice fetuses and thus the study with mice has no real bearing on whether caffeine may or may not cause developmental problems with human babies.

Still, the results do indicate that perhaps more research should be done to find out if caffeine does indeed have an unknown negative impact on human fetal development.

Bees get a buzz from caffeine

You may need a cup of coffee to kick start the day but it seems honeybees also get their buzz from drinking flower nectar containing caffeine.

Publishing in Science, researchers have shown that caffeine improves a honeybee’s memory and could help the plant recruit more bees to spread its pollen.

In tests honeybees feeding on a sugar solution containing caffeine, which occurs naturally in the nectar of coffee and citrus flowers, were three times more likely to remember a flower’s scent than those feeding on just sugar.

Study leader Dr Geraldine Wright, Reader in Neuroethology at Newcastle University, explained that the effect of caffeine benefits both the honeybee and the plant: “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.

“In turn, bees that have fed on caffeine-laced nectar are laden with coffee pollen and these bees search for other coffee plants to find more nectar, leading to better pollination.

“So, caffeine in nectar is likely to improve the bee’s foraging prowess while providing the plant with a more faithful pollinator.”

In the study, researchers found that the nectar of Citrus and Coffea species often contained low doses of caffeine. They included ‘robusta’ coffee species mainly used to produce freeze-dried coffee and ‘arabica’ used for espresso and filter coffee. Grapefruit, lemons, pomelo and oranges were also sampled and all contained caffeine.

Co-author Professor Phil Stevenson from the Royal Botanic Gardens, Kew and the University of Greenwich’s Natural Resources Institute said: “Caffeine is a defence chemical in plants and tastes bitter to many insects including bees so we were surprised to find it in the nectar.  However, it occurs at a dose that’s too low for the bees to taste but high enough to affect bee behaviour.”

The effect of caffeine on the bees’ long-term memory was profound with three times as many bees remembering the floral scent 24 hours later and twice as many bees remembering the scent after three days.

Typically, the nectar in the flower of a coffee plant contains almost as much caffeine as a cup of instant coffee. Just as black coffee has a strong bitter taste to us, high concentrations of caffeine are repellent to honeybees.

Dr Wright added: “This work helps us understand the basic mechanisms of how caffeine affects our brains. What we see in bees could explain why people prefer to drink coffee when studying.”

Dr Julie Mustard, a contributor to the study from Arizona State University, explains further: “Although human and honeybee brains obviously have lots of differences, when you look at the level of cells, proteins and genes, human and bee brains function very similarly. Thus, we can use the honeybee to investigate how caffeine affects our own brains and behaviours.”

This project was funded in part by the Insect Pollinators Initiative which supports projects aimed at researching the causes and consequences of threats to insect pollinators and to inform the development of appropriate mitigation strategies.

Population declines among bees have serious consequences for natural ecosystems and agriculture since bees are essential pollinators for many crops and wild flowering species. If declines are allowed to continue there is a risk to our natural biodiversity and on some crop production.

Professor Stevenson said: “Understanding how bees choose to forage and return to some flowers over others will help inform how landscapes could be better managed. Understanding a honeybee’s habits and preferences could help find ways to reinvigorate the species to protect our farming industry and countryside.”

The Case for Drinking as Much Coffee as You Like

"What I tell patients is, if you like coffee, go ahead and drink as much as you want and can," says Dr. Peter Martin, director of the Institute for Coffee Studies at Vanderbilt University. He’s even developed a metric for monitoring your dosage: If you are having trouble sleeping, cut back on your last cup of the day. From there, he says, "If you drink that much, it’s not going to do you any harm, and it might actually help you. A lot."

Officially, the American Medical Association recommends conservatively that “moderate tea or coffee drinking likely has no negative effect on health, as long as you live an otherwise healthy lifestyle.” That is a lackluster endorsement in light of so much recent glowing research. Not only have most of coffee’s purported ill effects been disproven — the most recent review fails to link it the development of hypertension — but we have so, so much information about its benefits. We believe they extend from preventing Alzheimer’s disease to protecting the liver. What we know goes beyond small-scale studies or limited observations. The past couple of years have seen findings, that, taken together, suggest that we should embrace coffee for reasons beyond the benefits of caffeine, and that we might go so far as to consider it a nutrient.

The most recent findings that support coffee as a panacea will make their premiere this December in the American Journal of Clinical Nutrition. Coffee, researchers found, appears to reduce the risk of type 2 diabetes.

Caffeine Improves Left Hemisphere Processing of Positive Words

A positivity advantage is known in emotional word recognition in that positive words are consistently processed faster and with fewer errors compared to emotionally neutral words. A similar advantage is not evident for negative words. Results of divided visual field studies, where stimuli are presented in either the left or right visual field and are initially processed by the contra-lateral brain hemisphere, point to a specificity of the language-dominant left hemisphere. The present study examined this effect by showing that the intake of caffeine further enhanced the recognition performance of positive, but not negative or neutral stimuli compared to a placebo control group. Because this effect was only present in the right visual field/left hemisphere condition, and based on the close link between caffeine intake and dopaminergic transmission, this result points to a dopaminergic explanation of the positivity advantage in emotional word recognition.