Jon's Health Tips - Coffee and Caffeine

Saturday, January 24, 2009

I drink lots of tea – mostly green tea. My wife drinks some tea and lots of diet Coke and even more coffee. It turns out that both coffee and tea are good for us, whether for their unique ingredients, and for their common ingredient, caffeine. Caffeine is very bad for pregnant women, and too much caffeine can be harmful for everyone. Here are the details:


Moderate coffee drinking reduces many risks

Recent advances in epidemiologic and experimental knowledge have transformed many of the negative health myths about coffee drinking into validated health benefits

Coffee is among the most widely consumed beverages in the world, and Dr. Coughlin says that the preponderance of scientific evidence - some by the panelists - suggests that moderate coffee consumption (3-5 cups per day) may be associated with reduced risk of certain disease conditions, such as Parkinson’s disease. Some research in neuropharamacology suggests that one cup of coffee can halve the risk of Parkinson’s disease. Other studies have found it reduces the risk of Alzheimer's disease, kidney stones, gallstones, depression and even suicide.

In recent epidemiological studies in the U.S., Europe and Japan, persons who were heavy coffee consumers had a lower risk of type 2 diabetes than persons who consumed little coffee. Interestingly, he says, associations were similar for caffeinated and decaffeinated coffee, suggesting that coffee components other than caffeine may be beneficial for glucose metabolism.

Coffee contains hundreds of components including substantial amounts of chlorogenic acid, caffeine, magnesium, potassium, vitamin B3, trigonelline, and lignans.

There are two areas in which there is some evidence of increased risk: leukemia and stomach cancer. The evidence for the former is intriguing, for the latter insubstantial.
Midlife Coffee And Tea Drinking May Protect Against Late-life Dementia

Midlife coffee drinking can decrease the risk of dementia/Alzheimer's disease (AD) later in life. This conclusion is made in a Finnish Cardiovascular Risk Factors, Aging and Dementia (CAIDE) Study published in the Journal of Alzheimer's Disease.

This study has been conducted at the University of Kuopio, Finland in collaboration with Karolinska Institutet, Stockholm, Sweden, and the National Public Health Institute, Helsinki, Finland. The study included participants from the survivors of population-based cohorts previously surveyed within the North Karelia Project and the FINMONICA study in 1972, 1977, 1982 or 1987 (midlife visit). After an average follow-up of 21 years, 1409 individuals (71%) aged 65 to 79 completed the re-examination in 1998. A total of 61 cases were identified as demented (48 with AD).

"We aimed to study the association between coffee and tea consumption at midlife and dementia/AD risk in late-life, because the long-term impact of caffeine on the central nervous system was still unknown, and as the pathologic processes leading to Alzheimer's disease may start decades before the clinical manifestation of the disease," says lead researcher, associate professor Miia Kivipelto, from the University of Kuopio, Finland and Karolinska Institutet, Stockholm, Sweden.
At the midlife examination, the consumption of coffee and tea was assessed with a previously validated semi-quantitative food-frequency questionnaire. Coffee drinking was categorized into three groups: 0-2 cups (low), 3-5 cups (moderate) and >5 cups (high) per day. Further, the question concerning tea consumption was dichotomized into those not drinking tea (0 cup/day) vs. those drinking tea (≥1 cup/day).

The study found that coffee drinkers at midlife had lower risk for dementia and AD later in life compared to those drinking no or only little coffee. The lowest risk (65% decreased) was found among moderate coffee drinkers (drinking 3-5 cups of coffee/day). Adjustments for various confounders did not change the results. Tea drinking was relatively uncommon and was not associated with dementia/AD.
Kivipelto also notes that, "Given the large amount of coffee consumption globally, the results might have important implications for the prevention of or delaying the onset of dementia/AD. The finding needs to be confirmed by other studies, but it opens the possibility that dietary interventions could modify the risk of dementia/AD. Also, identification of mechanisms of how coffee exerts its protection against dementia/AD might help in the development of new therapies for these diseases."

Caffeine experts at Johns Hopkins call for warning labels for energy drinks
Caffeinated energy drinks may present health risks

Johns Hopkins scientists who have spent decades researching the effects of caffeine report that a slew of caffeinated energy drinks now on the market should carry prominent labels that note caffeine doses and warn of potential health risks for consumers.

"The caffeine content of energy drinks varies over a 10-fold range, with some containing the equivalent of 14 cans of Coca-Cola, yet the caffeine amounts are often unlabeled and few include warnings about the potential health risks of caffeine intoxication," says Roland Griffiths, Ph.D., one of the authors of the article that appears in the journal Drug and Alcohol Dependence this month.
The market for these drinks stands at an estimated $5.4 billion in the United States and is expanding at a rate of 55 percent annually. Advertising campaigns, which principally target teens and young adults, promote the performance-enhancing and stimulant effects of energy drinks and appear to glorify drug use.
Without adequate, prominent labeling; consumers most likely won't realize whether they are getting a little or a lot of caffeine. "It's like drinking a serving of an alcoholic beverage and not knowing if its beer or scotch," says Griffiths.
Caffeine intoxication, a recognized clinical syndrome included in the Diagnostic and Statistical Manual of Mental Disorders and the World Health Organization's International Classification of Diseases, is marked by nervousness, anxiety, restlessness, insomnia, gastrointestinal upset, tremors, rapid heartbeats (tachycardia), psychomotor agitation (restlessness and pacing) and in rare cases, death.
Reports to U.S. poison control centers of caffeine abuse showed bad reactions to the energy drinks. In a 2007 survey of 496 college students, 51 percent reported consuming at least one energy drink during the last month. Of these energy drink users, 29 percent reported "weekly jolt and crash episodes," and 19 percent reported heart palpitations from drinking energy drinks. This same survey revealed that 27 percent of the students surveyed said they mixed energy drinks and alcohol at least once in the past month. "Alcohol adds another level of danger," says Griffiths, "because caffeine in high doses can give users a false sense of alertness that provides incentive to drive a car or in other ways put themselves in danger."
A regular 12-ounce cola drink has about 35 milligrams of caffeine, and a 6-ounce cup of brewed coffee has 80 to 150 milligrams of caffeine. Because many energy drinks are marketed as "dietary supplements," the limit that the Food and Drug Administration requires on the caffeine content of soft drinks (71 milligrams per 12-ounce can) does not apply. The caffeine content of energy drinks varies from 50 to more than 500 milligrams.
"It's notable that over-the-counter caffeine-containing products require warning labels, yet energy drinks do not," says Chad Reissig, Ph.D., one of the study's authors.
Griffiths notes that most of the drinks advertise their products as performance enhancers and stimulants – a marketing strategy that may put young people at risk for abusing even stronger stimulants such as the prescription drugs amphetamine and methylphenidate (Ritalin). A 2008 study of 1,253 college students found that energy drink consumption significantly predicted subsequent non-medical prescription stimulant use, raising the concern that energy drinks might serve as "gateway" products to more serious drugs of abuse. Potentially feeding that "transition" market, Griffiths says, are other energy drinks with alluring names such as the powdered energy drink additive "Blow" (which is sold in "vials" and resembles cocaine powder) and the "Cocaine" energy drink. Both of these products use the language of the illegal drug trade.

A low dose of caffeine when pregnant may damage the heart of offspring for a lifetime
New article in the FASEB Journal shows that caffeine during pregnancy affects heart development and function
A new study published online in The FASEB Journal shows that the equivalent of one dose of caffeine (just two cups of coffee) ingested during pregnancy may be enough to affect fetal heart development and then reduce heart function over the entire lifespan of the child. In addition, the researchers also found that this relatively minimal amount of exposure may lead to higher body fat among males, when compared to those who were not exposed to caffeine. Although the study was in mice, the biological cause and effect described in the research paper is plausible in humans.
According to Scott Rivkees, Yale's Associate Chair of Pediatric Research and a senior researcher on the study, "Our studies raise potential concerns about caffeine exposure during very early pregnancy, but further studies are necessary to evaluate caffeine's safety during pregnancy."
To reach their conclusion researchers studied four groups of pregnant mice under two sets of conditions for 48 hours. The first two groups were studied in "room air," with one group having been injected with caffeine and another injected with saline solution. The second two groups were studied under conditions where ambient oxygen levels were halved, with one group receiving caffeine and the other receiving saline solution. They found that under both circumstances, mice given caffeine produced embryos with a thinner layer of tissue separating some of the heart's chambers than the group that was not given caffeine.
The researchers then examined the mice born from these groups to determine what long-term effects, if any, caffeine had on the offspring. They found that all of the adult males exposed to caffeine as fetuses had an increase in body fat of about 20 percent, and decreased cardiac function of 35__ percent when compared to mice not exposed to caffeine.
"Caffeine is everywhere: in what we drink, in what we eat, in pills that we use to relieve pain, and even in candy," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "This report shows that despite popular notions of safety, there's one place it probably shouldn't be: in the diet of an expectant mother."

Consuming small amounts of caffeine when pregnant may affect the growth of an unborn child
Research paper: Human maternal caffeine intake during pregnancy and the risk of fetal growth restriction: Large prospective study
Consuming caffeine at any time during pregnancy is associated with an increased risk of fetal growth restriction (low birth weight), according to research published on bmj.com today.
Although some previous studies have also shown this, this BMJ study additionally shows that any amount and type of caffeine intake—from tea, cola, chocolate, cocoa, and some prescription drugs, as well as coffee—is linked with relatively slower fetal growth.
Dr Justin Konje and colleagues from the University of Leicester as well as collaborators from the University of Leeds, examined the association of maternal caffeine intake and individual caffeine metabolism on birth weight.
From two large teaching hospitals in the UK between September 2003 and June 2006 the authors recruited 2645 low risk pregnant women of average age 30, who were between 8-12 weeks pregnant. They used a caffeine assessment tool (CAT) to record caffeine intake from all possible dietary sources in the four weeks before and throughout pregnancy, and also used a saliva sample test to calculate individual caffeine metabolism.
The researchers report that the average caffeine intake during pregnancy was 159mg/day, much lower than the limit of 300mg/day recommended by the UK government's Food Standards Agency. Interestingly, 62% of the caffeine use reported came from tea. Other sources were coffee (14%), cola (12%), chocolate (8%), and soft drinks (2%).
Most of the babies were born at full term, with an average birth weight of 3450g (which is around the UK average), while 4% were born prematurely, 0.3% were stillborn, and 0.7% were miscarried late. Overall, the results confirmed that these were low risk pregnancies. However, the authors found a 'dose-response relationship', showing that increasing caffeine intake was associated with increasing risk of fetal growth restriction (FGR).
Compared to pregnant women consuming less than 100mg/day (the equivalent of less than one cup of coffee), the risk estimates of having a lower birth weight baby increased by 20% for intakes of 100-199mg/day, by 50% for those taking between 200-299mg/day, and by 40% for over 300mg/day.
There was no level of caffeine intake at which the increased risk of FGR stopped increasing during pregnancy. Caffeine consumption of more than 100mg/day, the equivalent of one cup of coffee, was associated with a reduction in birth weight of 34-59g in the first, 24-74g in the second, and about 66-89g in the third trimesters. This effect was significant and consistent across all trimesters with consumption of over 200mg/day. The authors also noted that the link between caffeine and FGR was stronger in women who metabolised caffeine more quickly.
The authors explain that, although these reductions in birth weight may seem small given that the average birth weight is over 3kg, a drop of 60-70 g might be important for a baby that was already small and at risk. Pregnant women should make every effort to significantly reduce their caffeine consumption before and during pregnancy, they warn.
In light of this evidence, the UK Government's Food Standards Agency are altering their guidance on the recommended daily limit of caffeine consumption and reducing it from 300mg to 200mg.
These findings will reinforce the concern that caffeine is a potential fetotoxic substance, say Professor Jørn Olsen and Professor Bodil Hammer Bech, in an accompanying editorial. But the advice offered by the authors could unnecessarily frighten women who have consumed some caffeine during pregnancy.
Pregnant women should reduce their intake of caffeine, but must not replace it with unhealthy alternatives such as alcoholic drinks or soft drinks full of sugar, they add.


Caffeine may prevent heart disease death in elderly

Habitual intake of caffeinated beverages provides protection against heart disease mortality in the elderly, say researchers at SUNY Downstate Medical Center and Brooklyn College._

Using data from the first federal National Health and Nutrition Examination Survey Epidemiologic Follow-up Study, the researchers found that survey participants 65 or more years old with higher caffeinated beverage intake exhibited lower relative risk of coronary vascular disease and heart mortality than did participants with lower caffeinated beverage intake.__

John Kassotis, MD, associate professor of medicine at SUNY Downstate, said, "The protection against death from heart disease in the elderly afforded by caffeine is likely due to caffeine's enhancement of blood pressure."_

The protective effect also was found to be dose-responsive: the higher the caffeine intake the stronger the protection. The protective effect was found only in participants who were not severely hypertensive. No significant protective effect was in patients below the age of 65.

Coffee consumption may lower blood uric acid levels

Coffee consumption may lower blood uric acid levels -- the precursor of gout
High uric acid levels in the blood are a precursor of gout, the most common inflammatory arthritis in adult men. It is believed that coffee and tea consumption may affect uric acid levels but only one study has been conducted to date. A new large-scale study published in the June 2007 issue of Arthritis Care & Research (http://www.interscience.wiley.com/journal/arthritiscare) examined the relationship between coffee, tea, caffeine intake, and uric acid levels and found that coffee consumption is associated with lower uric acid levels but that this appears to be due to components other than caffeine.__
The results showed that levels of uric acid in the blood significantly decreased with increasing coffee intake, but not with tea intake. In addition, there was no association between total caffeine intake from beverages and uric acid levels. These results were similar to those found in the only previous study on the topic, which was conducted in Japan. Interestingly, there was an association between decaffeinated coffee consumption and uric acid levels. "These findings suggest that components of coffee other than caffeine contribute to the observed inverse association between coffee intake and uric acid levels," the researchers state.
A recent study found that coffee was associated lower C peptide levels (a marker of insulin levels). The researchers in the current study suggest that because there is a strong relationship between insulin resistance and elevated uric acid levels, the decreased insulin levels associated with coffee consumption may lead to lower uric acid levels. Coffee is also a major source of chlorogenic acid, a strong antioxidant, which may improve insulin sensitivity. Chlorogenic acid also helps inhibit glucose absorption in the intestine; in another study decaffeinated coffee seemed to delay intestinal absorption of glucose and increase concentrations of glucagon-like peptide 1, which is well known for its beneficial effects on insulin secretion and action. The researchers note further that their results could be due to an effect of non-caffeine components found in coffee, which would also explain why coffee affected uric acid levels but tea did not.

Most significantly, the data revealed that the risk for developing gout decreased with increasing coffee consumption. The risk of gout was 40 percent lower for men who drank 4 to 5 cups a day and 59 percent lower for men who drank 6 or more cups a day than for men who never drank coffee. There was also a modest inverse association with decaffeinated coffee consumption. These findings were independent of all other risk factors for gout. Tea drinking and total caffeine intake were both shown to have no effect on the incidence of gout among the subjects. On the mechanism of these findings, Dr. Choi speculates that components of coffee other than caffeine may be responsible for the beverage’s gout-prevention benefits. Among the possibilities, coffee contains the phenol chlorogenic acid, a strong antioxidant.__
Caffeine prevents multiple sclerosis-like disease in mice
Mice given caffeine equivalent to a human drinking six to eight cups of coffee a day were protected from developing experimental autoimmune encephalomyelitis (EAE), the animal model for the human disease Multiple Sclerosis (MS), according to researchers at Cornell University.
Caffeine is a well-known adenosine receptor blocker, and the researchers believe results show the importance of this molecule in permitting the infiltration of immune cells into the central nervous system of patients with MS.
Dr. Jeffrey H. Mills, a postdoctoral associate in the laboratory of Dr. Margaret S. Bynoe, presented the findings at Experimental Biology 2008 on April 7. The presentation was part of the scientific programs of the American Society of Immunologists.
Multiple sclerosis is an autoimmune disease of the central nervous system (CNS) that occurs when the body’s immune system attacks and damages nerves in the brain and spinal cord. The infiltration of immune cells into brain and other CNS tissue is rarely seen in healthy individuals without MS. What allows the immune cells to infiltrate the CNS tissue of patients with MS is unknown. In earlier work, the Bynoe laboratory became convinced that the molecule adenosine is responsible for this infiltration.
Adenosine is widely present in the body and plays an important role in many biochemical processes, such as energy transfer and the promotion of sleep and suppression of arousal. The researchers’ first studies found that mice that lacked CD73, the enzyme necessary for synthesizing extracellular adenosine, were protected from developing the mouse form of MS (experimental autoimmune encephalomyelitis or EAE).
Additional studies involving immune cells from mice that lack CD73 further convinced them that normal CD73’s ability to synthesize extracellular adenosine was what was important for development and progression of the MS-like disease. That helped explain the presence of adenosine near the cells, but how did the compound get into the CNS cells? Since adenosine must bind to its receptor in order to affect a cell, the researchers reasoned that perhaps adenosine receptor activation was what allowed for entry of immune cells into the brain and spinal cord. To test that idea in the study presented at Experimental Biology 2008, they turned to caffeine.
Caffeine’s stimulatory effects on the CNS are in large part due to its ability to bind to the same receptors as adenosine, thus blocking adenosine’s ability to affect CNS cells. Mice that consumed caffeine in their drinking water were protected from development of EAE, the MS model. Dr. Bynoe concludes that these experiments show that CD73 and adenosine receptor signaling are required for the efficient entry of immune cells into the CNS during the initiation and progression of EAE in mice and, quite possibly, during the development of MS in humans.
Dr. Bynoe adds, “These results might mark the first in a series of discoveries from our lab that could spawn the impetus for the development of adenosine-based therapies for the treatment of MS.”

Caffeine and exercise can team up to prevent skin cancer
A potential dynamic duo that may help avert sun-induced skin cancer
Regular exercise and little or no caffeine has become a popular lifestyle choice for many Americans. But a new Rutgers study has found that it may not be the best formula for preventing sun-induced skin damage that could lead to cancer. Low to moderate amounts of caffeine, in fact, along with exercise can be good for your health.
According to the National Cancer Institute, sunlight-induced skin cancer is the most prevalent cancer in the United States with more than 1 million new cases each year. A research team at Rutgers, The State University of New Jersey, showed that a combination of exercise and some caffeine protected against the destructive effects of the sun’s ultraviolet-B (UVB) radiation, known to induce skin cancer. The caffeine and exercise seemingly conspire in killing off precancerous cells whose DNA has been damaged by UVB-rays.
In women, caffeine may protect memory
Caffeine may help older women protect their thinking skills, according to a study published in the August 7, 2007, issue of Neurology, the medical journal of the American Academy of Neurology.
The study found that women age 65 and older who drank more than three cups of coffee (or the equivalent in tea) per day had less decline over time on tests of memory than women who drank one cup or less of coffee or tea per day. The results held up even after researchers adjusted for other factors that could affect memory abilities, such as age, education, disability, depression, high blood pressure, medications, cardiovascular disease, and other chronic illnesses.
“Caffeine is a psychostimulant which appears to reduce cognitive decline in women,” said study author Karen Ritchie,. “While we have some ideas as to how this works biologically, we need to have a better understanding of how caffeine affects the brain before we can start promoting caffeine intake as a way to reduce cognitive decline. But the results are interesting – caffeine use is already widespread and it has fewer side effects than other treatments for cognitive decline, and it requires a relatively small amount for a beneficial effect.”
The study involved 7,000 people whose cognitive abilities and caffeine consumption were evaluated over four years. Compared to women who drank one cup or less of coffee per day, those who drank over three cups were less likely to show as much decline in memory. Moreover, the benefits increased with age – coffee drinkers being 30 percent less likely to have memory decline at age 65 and rising to 70 percent less likely over age 80.
Caffeine consumers did not seem to have lower rates of dementia. “We really need a longer study to look at whether caffeine prevents dementia; it might be that caffeine could slow the dementia process rather than preventing it,” said Ritchie.
Ritchie said researchers aren’t sure why caffeine didn’t show the same result in men. “Women may be more sensitive to the effects of caffeine,” she said. “Their bodies may react differently to the stimulant, or they may metabolize caffeine differently.”
Coffee drinking related to reduced risk of liver cancer
After lung and stomach cancer, liver cancer is the third largest cause of cancer deaths in the world. A new study on the relationship between coffee drinking and the risk of hepatocellular carcinoma (HCC) confirmed that there is an inverse association between coffee consumption and HCC, although the reasons for this relationship are still unresolved.
The results showed a 41 percent reduction of HCC risk among coffee drinkers compared to those who never drank coffee. “Moreover, the apparent favorable effect of coffee drinking was found both in studies from southern Europe, where coffee is widely consumed, and from Japan, where coffee consumption is less frequent, and in subjects with chronic liver diseases,” the researchers state.
Certain compounds found in coffee may act as blocking agents by reacting with enzymes involved in carcinogenic detoxification. Other components, including caffeine, have been shown to have favorable effects on liver enzymes. Coffee has also been related to a reduced risk of liver diseases and cirrhosis, which can lead to liver cancer.


A coffee with your doughnut could protect against Alzheimer's disease

A daily dose of caffeine blocks the disruptive effects of high cholesterol that scientists have linked to Alzheimer's disease. A study in the open access publication, Journal of Neuroinflammation revealed that caffeine equivalent to just one cup of coffee a day could protect the blood-brain barrier (BBB) from damage that occurred with a high-fat diet.
The BBB protects the central nervous system from the rest of the body's circulation, providing the brain with its own regulated microenvironment. Previous studies have shown that high levels of cholesterol break down the BBB which can then no longer protect the central nervous system from the damage caused by blood borne contamination. BBB leakage occurs in a variety of neurological disorders such as Alzheimer's disease.
In this study, researchers from the University of North Dakota School of Medicine and Health Sciences gave rabbits 3 mg caffeine each day – the equivalent of a daily cup of coffee for an average-sized person. The rabbits were fed a cholesterol-enriched diet during this time.
After 12 weeks a number of laboratory tests showed that the BBB was significantly more intact in rabbits receiving a daily dose of caffeine.
“Caffeine appears to block several of the disruptive effects of cholesterol that make the blood-brain barrier leaky,” says Jonathan Geiger, University of North Dakota School of Medicine and Health Sciences. “High levels of cholesterol are a risk factor for Alzheimer's disease, perhaps by compromising the protective nature of the blood-brain barrier. For the first time we have shown that chronic ingestion of caffeine protects the BBB from cholesterol-induced leakage.”
Caffeine appears to protect BBB breakdown by maintaining the expression levels of tight junction proteins. These proteins bind the cells of the BBB tightly to each other to stop unwanted molecules crossing into the central nervous system.
The findings confirm and extend results from other studies showing that caffeine intake protects against memory loss in aging and in Alzheimer’s disease.
“Caffeine is a safe and readily available drug and its ability to stabilise the blood-brain barrier means it could have an important part to play in therapies against neurological disorders,” says Geiger.
New study: Coffee drinkers have slightly lower death rates than people who do not drink coffee
Drinking large amounts of coffee does not increase a person's risk for dying sooner than expected and may actually be protective

A new study published today in Annals of Internal Medicine has good news for coffee drinkers: Regular coffee drinking (up to 6 cups per day) is not associated with increased deaths in either men or women. In fact, both caffeinated and decaffeinated coffee consumption is associated with a somewhat smaller rate of death from heart disease.
"Coffee consumption has been linked to various beneficial and detrimental health effects, but data on its relation with death were lacking," says Esther Lopez-Garcia, PhD, the study's lead author. "Coffee consumption was not associated with a higher risk of mortality in middle-aged men and women. The possibility of a modest benefit of coffee consumption on heart disease, cancer, and other causes of death needs to be further investigated."
Women consuming two to three cups of caffeinated coffee per day had a 25 percent lower risk of death from heart disease during the follow-up period (which lasted from 1980 to 2004 and involved 84,214 women) as compared with non-consumers, and an 18 percent lower risk of death caused by something other than cancer or heart disease as compared with non-consumers during follow-up. For men, this level of consumption was associated with neither a higher nor a lower risk of death during the follow-up period (which lasted from 1986 to 2004 and involved 41,736 men).
The researchers analyzed data of 84,214 women who had participated in the Nurses' Health Study and 41,736 men who had participated in the Health Professionals Follow-up Study. To be in the current study, participants had to have been free of cancer and heart disease at the start of those larger studies.
The study participants completed questionnaires every two to four years that included questions about how frequently they drank coffee, other diet habits, smoking, and health conditions. The researchers then compared the frequency of death from any cause, death due to heart disease, and death due to cancer among people with different coffee-drinking habits.
Among women, 2,368 deaths were due to heart disease, 5,011 were due to cancer, and 3,716 were due to another cause. Among men, 2,049 deaths were due to heart disease, 2,491 were due to cancer, and 2,348 were due to another cause.
While accounting for other risk factors, such as body size, smoking, diet, and specific diseases, the researchers found that people who drank more coffee were less likely to die during the follow-up period. This was mainly because of lower risk for heart disease deaths among coffee drinkers.
The researchers found no association between coffee drinking and cancer deaths. These relationships did not seem to be related to caffeine because people who drank decaffeinated coffee also had lower death rates than people who did not drink coffee.
The editors of Annals of Internal Medicine caution that the design of the study does not make it certain that coffee decreases the chances of dying sooner than expected. Something else about coffee drinkers might be protecting them. And some measurement error in the assessment of coffee consumption is inevitable because estimated consumption came from self-reports.

Higher Coffee Consumption Associated with Lower Liver Cancer Risk
Liver Cancer is the Third Most Common Global Cause of Cancer Death
A new large, prospective population-based study confirms an inverse relationship between coffee consumption and liver cancer risk. The study also found that higher levels of gamma-glutamyltransferase (GGT) in the blood were associated with an increased risk of developing the disease. These findings are published in the July issue of Hepatology, a journal published by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD). The article and an accompanying editorial are also available online at Wiley Interscience (www.interscience.wiley.com).

Researchers led by Gang Hu at the University of Helsinki set out to examine the associations between coffee consumption and serum GGT with the risk of liver cancer in a large prospective cohort. Residents of Finland drink more coffee per capita than the Japanese, Americans, Italians, and other Europeans, so Hu and colleagues studied 60,323 Finnish participants ages 25 to 74 who were cancer-free at baseline. The Finns were included in seven independent cross-sectional population surveys conducted between 1972 and 2002 and followed up through June 2006.

The participants completed a mail-in questionnaire about their medical history, socioeconomic factors and dietary and lifestyle habits. For a subset of participants, clinical data was available, including serum levels of GGT. Data on subsequent cancer diagnoses was collected from the country-wide Finnish Cancer Registry.

Based on their answers to the question: “How many cups of coffee do you drink daily?” the participants were divided into five categories: 0-1 cup, 2-3 cups, 4-5 cups, 6-7 cups, and 8 or more cups per day. After a median follow-up period of 19.3 years, 128 participants were diagnosed with liver cancer.

The researchers noted a significant inverse association between coffee drinking and the risk of primary liver cancer. They found that the multivariable hazards ratio of liver cancer dropped for each group that drank more coffee. It fell from 1.00, to .66, to .44, to .38 to .32 respectively. “The biological mechanisms behind the association of coffee consumption with the risk of liver cancer are not known,” the authors point out.

They also found that high levels of serum GGT were associated with an increased risk of liver cancer. The hazard ratio of liver cancer for the highest vs. lowest quartile of serum GGT was 3.13. “Nevertheless,” they report, “the inverse association between coffee consumption and the risk of liver cancer was consistent in the subjects at any level of serum GGT.”

An accompanying editorial by Carlo La Vecchia of Milan says that Hu’s new study solidly confirms the inverse relationship between coffee drinking and liver cancer risk, though we still don’t know if it is causal. “Furthermore, the study by Hu et al. provides original and important quantitative evidence that the levels of GGT are related to subsequent incidence of liver cancer, with an overall relative risk of 2.3,” he says.

La Vecchia notes, however, that, “It remains difficult, however, to translate the inverse relation between coffee drinking and liver cancer risk observed in epidemiological studies into potential implications for prevention of liver cancer by increasing coffee consumption.”

Post-exercise caffeine helps muscles refuel
Recipe to recover more quickly from exercise: Finish workout, eat pasta, and wash down with five or six cups of strong coffee.
Glycogen, the muscle's primary fuel source during exercise, is replenished more rapidly when athletes ingest both carbohydrate and caffeine following exhaustive exercise, new research from the online edition of the Journal of Applied Physiology shows. Athletes who ingested caffeine with carbohydrate had 66% more glycogen in their muscles four hours after finishing intense, glycogen-depleting exercise, compared to when they consumed carbohydrate alone, according to the study, published by The American Physiological Society.
The study, "High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is co-ingested with caffeine," is by David J. Pedersen, Sarah J. Lessard, Vernon G. Coffey, Emmanuel G. Churchley, Andrew M. Wootton, They Ng, Matthew J. Watt and John A. Hawley. Dr. Pedersen is with the Garvan Institute of Medical Research in Sydney, Australia, Dr. Watt is from St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia. All others are with the Royal Melbourne Institute of Technology University (RMIT) in Bundoora, Victoria, Australia.
A fuller audio interview with Dr. Hawley is available in Episode 11 of the APS podcast, Life Lines, at www.lifelines.tv. The show also includes an interview with Dr. Stanley Schultz, whose physiological discovery of how sugar is transported in the gut led to the development of oral rehydration therapy and sports drinks such as Gatorade.
Caffeine aids carbohydrate uptake
It is already established that consuming carbohydrate and caffeine prior to and during exercise improves a variety of athletic performances. This is the first study to show that caffeine combined with carbohydrates following exercise can help refuel the muscle faster.
"If you have 66% more fuel for the next day's training or competition, there is absolutely no question you will go farther or faster," said Dr. Hawley, the study's senior author. Caffeine is present in common foods and beverages, including coffee, tea, chocolate and cola drinks.
The study was conducted on seven well-trained endurance cyclists who participated in four sessions. The participants first rode a cycle ergometer until exhaustion, and then consumed a low-carbohydrate dinner before going home. This exercise bout was designed to reduce the athletes' muscle glycogen stores prior to the experimental trial the next day.
The athletes did not eat again until they returned to the lab the next day for the second session when they again cycled until exhaustion. They then ingested a drink that contained carbohydrate alone or carbohydrate plus caffeine and rested in the laboratory for four hours. During this post-exercise rest time, the researchers took several muscle biopsies and multiple blood samples to measure the amount of glycogen being replenished in the muscle, along with the concentrations of glucose-regulating metabolites and hormones in the blood, including glucose and insulin.
The entire two-session process was repeated 7-10 days later. The only difference was that this time, the athletes drank the beverage that they had not consumed in the previous trial. (That is, if they drank the carbohydrate alone in the first trial, they drank the carbohydrate plus caffeine in the second trial, and vice versa.)
The drinks looked, smelled and tasted the same and both contained the same amount of carbohydrate. Neither the researchers nor the cyclists knew which regimen they were receiving, making it a double-blind, placebo-controlled experiment.
Glucose and insulin levels higher with caffeine ingestion
The researchers found the following:

• one hour after exercise, muscle glycogen levels had replenished to the same extent whether or not the athlete had the drink containing carbohydrate and caffeine or carbohydrate only
• four hours after exercise, the drink containing caffeine resulted in 66% higher glycogen levels compared to the carbohydrate-only drink
• throughout the four-hour recovery period, the caffeinated drink resulted in higher levels of blood glucose and plasma insulin
• several signaling proteins believed to play a role in glucose transport into the muscle were elevated to a greater extent after the athletes ingested the carbohydrate-plus-caffeine drink, compared to the carbohydrate-only drink

Dr. Hawley said it is not yet clear how caffeine aids in facilitating glucose uptake from the blood into the muscles. However, the higher circulating blood glucose and plasma insulin levels were likely to be a factor. In addition, caffeine may increase the activity of several signaling enzymes, including the calcium-dependent protein kinase and protein kinase B (also called Akt), which have roles in muscle glucose uptake during and after exercise.
Lower dose is next step
In this study, the researchers used a high dose of caffeine to establish that it could help the muscles convert ingested carbohydrates to glycogen more rapidly. However, because caffeine can have potentially negative effects, such as disturbing sleep or causing jitteriness, the next step is to determine whether smaller doses could accomplish the same goal.
Hawley pointed out that the responses to caffeine ingestion vary widely between individuals. Indeed, while several of the athletes in the study said they had a difficult time sleeping the night after the trial in which they ingested caffeine (8 mg per kilogram of body weight, the equivalent of drinking 5-6 cups of strong coffee), several others fell asleep during the recovery period and reported no adverse effects.
Athletes who want to incorporate caffeine into their workouts should experiment during training sessions well in advance of an important competition to find out what works for them.

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