Jon's Health Tips - Vitamins B, C and E

I have gradually stopped using I wide variety of vitamins and supplements in the last few years, although I have picked up some new ones. The ones I will address today are Vitamins B, C, and E. They were all touted at one time or another as absolutely the best thing around. Vitamin E in particular was the Vitamin D of 2 years ago. One form of Vitamin D was praised so highly on the front page of the Wall Street Journal that I went out and bought a year’s supply. Then came new research that said while it appeared to prevent cancer formation, if you had any cancer at all in your system it actually promoted cancerous growth.

I’m still not convinced that some of these are beneficial against some diseases not specifically addressed in the recent studies, but I feel I can take only so many supplements, and there are better ones out there I now believe – more on these in future letters.

Here is a summary of the recent research that discouraged me from continuing to use these supplements (despite all the earlier research about how efficacious they were.)

Heavy multivitamin use = advanced prostate cancer?

While regular multivitamin use is not linked with early or localized prostate cancer, taking too many multivitamins may be associated with an increased risk for advanced or fatal prostate cancers, according to a study in the May 16 issue of the Journal of the National Cancer Institute.__
Millions of Americans take multivitamins because of a belief in their potential health benefits, even though there is limited scientific evidence that they prevent chronic disease. Researchers have wondered what impact multivitamin use might have on cancer risk.__
Karla Lawson, Ph.D., of the National Cancer Institute in Bethesda, Md., and colleagues followed 295,344 men enrolled in the National Institutes of Health-AARP Diet and Health Study to determine the association between multivitamin use and prostate cancer risk. After five years of follow-up, 10,241 men were diagnosed with prostate cancer, including 8,765 with localized cancers and 1,476 with advanced cancers._
The researchers found no association between multivitamin use and the risk of localized prostate cancer. But they did find an increased risk of advanced and fatal prostate cancer among men who used multivitamins more than seven times a week, compared with men who did not use multivitamins. The association was strongest in men with a family history of prostate cancer and men who also took selenium, beta-carotene, or zinc supplements.__
“Because multivitamin supplements consist of a combination of several vitamins and men using high levels of multivitamins were also more likely to take a variety of individual supplements, we were unable to identify or quantify individual components responsible for the associations that we observed,” the authors write.
It’s Time to Reassess the Value, Safety of Multivitamin Use
Although physician-scientists and supplement manufacturers are often at odds, they don’t spend much time sparring over multivitamins. In fact, half the physicians on the Harvard Men’s Health Watch advisory board report taking a multivitamin themselves. In recent years, Harvard Men’s Health Watch has also endorsed these popular supplements, reasoning that even if they don’t help, they won’t hurt. However, the March 2008 issue of the newsletter states that a reappraisal of that advice is in order.
Harvard Men’s Health Watch notes that some recent studies have linked multivitamin use to prostate cancer. More convincingly, studies have linked high intakes of folic acid to colon polyps, the precursors of colorectal cancer. Researchers speculate that high intakes of folic acid, which was first added to grain products in the 1990s, may have contributed to an increase in colorectal cancers in the mid-1990s.
What does all of this have to do with multivitamins? Now that folic acid is added to so many grain products, it’s easy to see how a healthy diet, combined with a multivitamin, could boost a person’s daily intake to 1,000 mcg or more, potentially increasing the risk of colorectal and possibly prostate and breast cancers.
In light of this research, Harvard Men’s Health Watch suggests that the average man give up the multivitamin, at least until scientists solve the puzzle of folic acid and cancer. However, if you stop taking a multivitamin, consider taking a vitamin D supplement, the newsletter says. The typical diet for most men and women doesn’t supply enough of this crucial vitamin, and while sun exposure boosts vitamin D production, it has health risks of its own.


High doses in supplements could be unhealthy

Those phytochemicals — natural plant-based compounds that give fruits and vegetables a reputation as healthy food — could be unhealthy if consumed in high doses in dietary supplements, teas or other preparations, scientists in New Jersey have concluded after a review of studies on the topic.
In their article, scheduled for the current issue of ACS's Chemical Research in Toxicology, a monthly journal, Chung S. Yang and colleagues analyze available data on the toxic potential of polyphenols. That group of dietary phytochemicals includes flavonoids, whose suggested beneficial effects in fruits and vegetables include prevention of heart disease and cancer. The data was from studies done in humans and laboratory animals.
The report cites specific examples of toxic effects, including reports of liver, kidney, and intestinal toxicity related to consumption of high doses of green tea-based dietary supplements. The risk of such toxicity may be greater in individuals taking certain medications, or with genetic traits, that increase the bioavailability of phytochemicals, the researchers said. Citing the need for new studies on the topic, the report concludes: "Only when such data are compared to the evidence for beneficial health effects can a balanced judgment be made regarding the potential utility of these compounds for disease prevention and treatment."

Certain vitamin supplements may increase lung cancer risk, especially in smokers

Vitamin supplements do not protect against lung cancer, according to a study of more than 77,000 vitamin users. In fact, some supplements may even increase the risk of developing it.
“Our study of supplemental multivitamins, vitamin C, vitamin E and folate did not show any evidence for a decreased risk of lung cancer,” wrote the study’s author, Christopher G. Slatore, M.D., of the University of Washington, in Seattle. “Indeed, increasing intake of supplemental vitamin E was associated with a slightly increased risk of lung cancer.”
The findings were published in the first issue for March of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.
Dr. Slatore and colleagues selected a prospective cohort of 77,126 men and women between 50 and 76 years of age in the Washington state VITAL (VITamins And Lifestyle) study, and determined their rate of developing lung cancer over four years with respect to their current and past vitamin usage, smoking, and other demographic and medical characteristics.
Of the original cohort, 521 developed lung cancer, the expected rate for a low-risk cohort such as VITAL. But among those who developed lung cancer, in addition to the unsurprising associations with smoking history, family history, and age, there was a slight but significant association between use of supplemental vitamin E and lung cancer.
“In contrast to the often assumed benefits or at least lack of harm, supplemental vitamin E was associated with a small increased risk of lung cancer,” said Dr. Slatore.
When modeled continuously, the increased risk was equivalent to a seven percent rise for every 100 mg/day. “This risk translates into a 28 percent increased risk of lung cancer at a dose of 400 mg/day for ten years,” wrote Dr. Slatore. The increased risk was most prominent in current smokers.
The idea that vitamin supplements are healthy, or at the very least, do no harm, comes from the desire of many people to mimic the benefits of a healthy diet with a convenient pill says Tim Byers, M.D., M.P.H., of the University of Colorado School of Medicine in an editorial in the same issue of the journal. However, he points out, “fruits contain not only vitamins but also many hundreds of other phytochemical compounds whose functions are not well understood.”
The World Cancer Research Fund and the American Cancer Society recommend two servings of fruit each day, based on a study that previously found a 20 percent increase in cancer risk among people who ate the least amount of fruit. This recommendation “would likely lead to a reduced risk for lung cancer, as well as reduced risk of several other cancers and cardiovascular disease,” writes Dr. Byers. “However, any benefit to the population of smokers from increasing fruit intake to reduce cancer risk by 20 percent would be more than offset if even a small proportion of smokers decided to continue tobacco use in favor of such a diet change.”
These findings have broad public health implications, given the large population of current and former smokers and the widespread use of vitamin supplements. “Future studies may focus on other components of fruits and vegetables that may explain the decreased risk [of cancer] that has been associated with fruits and vegetables,” writes Dr. Slatore. “Meanwhile,” he says, “our results should prompt clinicians to counsel patients that these supplements are unlikely to reduce the risk of lung cancer and may be detrimental.”
Antioxidants show no clear benefit against cardiovascular events, death in high-risk women

Vitamins C and E and beta carotene, either individually or in combination, do not appear to reduce the risk of cardiovascular events or death among women at high risk for heart disease, according to a report in the August 13/27 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.
Oxidative damage—harm to cells caused by exposure to oxygen—may contribute to the development of cardiovascular disease, according to background information in the article. In addition, compounds known as free radicals may damage artery linings, encourage blood clots and alter the function of blood vessels. “Antioxidants scavenge free radicals and limit the damage they can cause,” the authors write. “Diets high in fruit and vegetable intake, and thus rich in such antioxidants, have been associated with reduced rates of coronary heart disease and stroke. Vitamins C and E and beta carotene are potential mediators of the apparent protective effect of a plant-based diet on cardiovascular disease.”
Nancy R. Cook, Sc.D., of Brigham & Women’s Hospital and Harvard Medical School, Boston, and colleagues tested the effects of these compounds in the Women’s Antioxidant Cardiovascular Study, which followed 8,171 women 40 years or older (average age 60.6) beginning in 1995 to 1996. The women, who either had a history of cardiovascular disease or three or more risk factors, were randomly assigned to take 500 milligrams of ascorbic acid (vitamin C) or placebo every day; 600 international units of vitamin E or placebo every other day; and 50 milligrams of beta carotene or placebo every other day. Participants were followed up for the occurrence of heart events (including stroke, heart attack and bypass surgery) or death through 2005.
During the average study period of 9.4 years, 1,450 women had one or more cardiovascular events, including 274 heart attacks, 298 strokes, 889 coronary revascularization procedures (bypass surgery or angioplasty) and 395 cardiovascular deaths (out of a total 995 deaths). “There was no overall effect of ascorbic acid, vitamin E or beta carotene on the primary combined end point or on the individual secondary outcomes of myocardial infarction, stroke, coronary revascularization or cardiovascular disease death,” the authors write. “There were no significant interactions between agents for the primary end point, but those randomized to both active ascorbic acid and vitamin E experienced fewer strokes.”
No additional adverse effects were observed for those taking active pills vs. placebo, with the exception of a small increase in reports of upset stomach among those taking active beta carotene.
“Overall, we found no benefit on the primary combined end point for any of the antioxidant agents tested, alone or in combination,” the authors conclude. “We also found no evidence for harm. While additional research into combinations of agents, particularly for stroke, may be of interest, widespread use of these individual agents for cardiovascular protection does not appear warranted.”
Supplements can't protect you against cancer or heart disease,
Most experts agree that supplements add little, if anything, to a well-balanced diet. Exercise, however, is proven to achieve the benefits claimed for vitamins, even for people who eat properly, reports the November 2007 issue of Harvard Men’s Health Watch.
One leading reason people take vitamin supplements is to protect against cancer. But sadly, this strategy has been a flop. While studies continue on whether vitamin E and selenium can help reduce prostate cancer risk, data already show that beta carotene actually boosts the risk of lung cancer in smokers. And zinc, as well as high doses of folic acid, may also do more harm than good for men seeking to ward off prostate cancer. The bottom line: Supplements do not reduce cancer risk.
In addition, vitamins are not recommended for heart disease prevention. Trials of B vitamins have failed to demonstrate protection against heart disease. But people who eat fish twice a week enjoy a reduced risk of heart attack and sudden cardiac death. Leafy, green vegetables and whole grains also help protect against heart disease.
If supplements can't protect you against cancer or heart disease, what can? Current evidence suggests that exercise may be a crucial weapon in reducing the risk of some cancers. Studies show that active people are less likely to develop colon cancer than sedentary individuals, and that women who exercise can reduce their breast cancer risk. Exercise’s effect on prostate cancer, however, is less clear; studies have produced varying results. Evidence is also incomplete for lung and pancreatic cancers. But when it comes to reducing the risk of heart disease, regular exercise is associated with a sharp reduction in heart attacks and cardiac deaths.
Some Antioxidants May Increase Mortality Risk

Contradicting claims of disease prevention, an analysis of previous studies indicates that the antioxidant supplements beta carotene, vitamin A, and vitamin E may increase the risk of death, according to a meta-analysis and review article in the February 28 issue of JAMA.__Many people take antioxidant supplements, believing they improve their health and prevent diseases. Whether these supplements are beneficial or harmful is uncertain, according to background information in the article.__Goran Bjelakovic, M.D., Dr.Med.Sci., of the Center for Clinical Intervention Research, Copenhagen University Hospital, Copenhagen, Denmark, and colleagues conducted an analysis of previous studies to examine the effects of antioxidant supplements (beta carotene, vitamins A and E, vitamin C [ascorbic acid], and selenium) on all-cause death of adults included in primary and secondary prevention trials. Using electronic databases and bibliographies, the researchers identified and included 68 randomized trials with 232,606 participants in the review and meta-analysis. The authors also classified the trials according to the risk of bias based on the quality of the methods used in the study, and stratified trials as "low-bias risk" (high quality) or "high-bias risk" (low quality).__In an analysis that pooled all low-bias risk and high bias risk trials, there was no significant association between antioxidant use and mortality. In 47 low-bias trials involving 180,938 participants, the antioxidant supplements were associated with a 5 percent increased risk of mortality. Among low-bias trials, use of beta carotene, vitamin A, and vitamin E was associated with 7 percent, 16 percent and 4 percent, respectively, increased risk of mortality, whereas there was no increased mortality risk associated with vitamin C or selenium use.__"Our systematic review contains a number of findings. Beta carotene, vitamin A, and vitamin E given singly or combined with other antioxidant supplements significantly increase mortality. There is no evidence that vitamin C may increase longevity. We lack evidence to refute a potential negative effect of vitamin C on survival. Selenium tended to reduce mortality, but we need more research on this question," the authors write.__"Our findings contradict the findings of observational studies, claiming that antioxidants improve health. Considering that 10 percent to 20 percent of the adult population (80-160 million people) in North America and Europe may consume the assessed supplements, the public health consequences may be substantial. We are exposed to intense marketing with a contrary statement, which is also reflected by the high number of publications per included randomized trial found in the present review."__"There are several possible explanations for the negative effect of antioxidant supplements on mortality. Although oxidative stress has a hypothesized role in the pathogenesis of many chronic diseases, it may be the consequence of pathological conditions. By eliminating free radicals from our organism, we interfere with some essential defensive mechanisms . Antioxidant supplements are synthetic and not subjected to the same rigorous toxicity studies as other pharmaceutical agents. Better understanding of mechanisms and actions of antioxidants in relation to a potential disease is needed," the researchers conclude.

Folic acid, B vitamins do not appear to affect cancer risk

A daily supplementation combination that included folic acid and vitamin B6 and B12 had no significant effect on the overall risk of cancer, including breast cancer, among women at high risk of cardiovascular disease, according to a study in the November 5 issue of JAMA.
Folate, vitamin B6, and vitamin B12 (water-soluble, essential B vitamins) are thought to play an important role in cancer prevention. "Background fortification of the food supply with folic acid (a synthetic form of folate), a policy that began in the United States in 1998 to reduce risk of neural tube defects, has improved folate status in the general population. Approximately one-third of U.S. adults currently take multivitamin supplements containing folic acid, vitamin B6, and vitamin B12," the authors write. Data from randomized trials of folic acid alone or in combination with B vitamins and cancer risk are limited, not entirely consistent, and one trial has even raised concerns about harmful effects.
Shumin M. Zhang, M.D., Sc.D., of Brigham and Women's Hospital and Harvard Medical School, Boston, and colleagues conducted a trial to evaluate the effect of combined folic acid, vitamin B6, and vitamin B12 treatment on cancer risk in women at high risk for cardiovascular disease. The Women's Antioxidant and Folic Acid Cardiovascular Study included 5,442 U.S. female health professionals age 42 years or older, with pre-existing cardiovascular disease or three or more coronary risk factors, who were randomly assigned to receive either a daily combination (n = 2,721) of folic acid (2.5 mg.), vitamin B6 (50 mg.), and vitamin B12 (1 mg.) or a matching placebo (n = 2,721). They were treated for 7.3 years, from April 1998 through July 2005.
"A total of 379 women developed invasive cancer (187 in the active treatment group and 192 in the placebo group)," the authors write. "Compared with placebo, women receiving the active treatment had similar risk of developing total invasive cancer, breast cancer, or any cancer death." There were no differences according to current use of multivitamin supplements, intakes of total folate, vitamin B6, and vitamin B12, or history of cancer at baseline. Lack of effect for total invasive cancer did not vary over time.
Age significantly modified the effect of combined B vitamin treatment on risk of total invasive cancer and breast cancer. A significantly reduced risk was observed for total invasive cancer and breast cancer among women age 65 years or older at study entry, but no reductions in risk were observed among younger women (40-54 years or 55-64 years).
"If the finding is real and substantiated, the results may have public health significance because the incidence rates of cancer are high in elderly persons. The finding is biologically plausible because elderly individuals have increased requirements for these B vitamins," the authors write.
"In conclusion, treatment with combined folic acid, vitamin B6, and vitamin B12 provided neither beneficial nor harmful effects on overall risk of total cancer, breast cancer, or deaths from cancer among women at high risk for CVD."

No protective effect on cancer from long-term vitamin E or vitamin C supplementation

The Physicians' Health Study II is a large-scale, long-term, randomized clinical trial that included 14,641 physicians who were at least 50 years old at enrollment. These physicians were given 400 IU of vitamin E every other day or its placebo, or 500 mg of vitamin C daily or its placebo.
Researchers followed these patients for up to 10 years for the development of cancer with high rates of completion of annual questionnaires, and the confirmation of reported cancer endpoints.
Analyses indicate that randomization to vitamin E did not have a significant effect on prostate cancer. This lack of effect for vitamin E also extended to total cancer. Vitamin C had a similar lack of effect on total cancer.
"After nearly 10 years of supplementation with either vitamin E or vitamin C, we found no evidence supporting the use of either supplement in the prevention of cancer," said Howard D. Sesso, Sc.D., M.P.H., an assistant professor of medicine at Brigham and Women's Hospital. "While vitamin E and C supplement use did not produce any protective benefits, they also did not cause any harm," he added.
Previous laboratory research and observational studies in which people who reported eating a diet rich in vitamins E and C were found to have a lower risk of cancer, had suggested that taking these vitamins as individual supplements may offer some protective benefits.
Study co-author and principal investigator J. Michael Gaziano, M.D., M.P.H., associate professor of medicine at Brigham and Women's Hospital and VA Boston, adds, "Individual vitamin supplements such as vitamin E and C do not appear to provide the same potential advantages as vitamins included as part of a healthy, balanced diet."
Finally, Sesso said that these results provide clinically meaningful new information. "Our results represent one of only a few clinical trials that have tested this idea. The final component of the Physicians' Health Study II, testing daily multivitamin supplementation, remains ongoing."

Vitamins C and E and beta carotene again fail to reduce cancer risk in randomized controlled trial

Women who took beta carotene or vitamin C or E or a combination of the supplements had a similar risk of cancer as women who did not take the supplements, according to data from a randomized controlled trial in the December 30 online issue of the Journal of the National Cancer Institute.
Epidemiological studies have suggested that people whose diets are high in fruits and vegetables, and thus antioxidants, may have a lower risk of cancer. Results from randomized trials that address the issue, however, have been inconsistent and have rarely supported that observation.
In the current study, Jennifer Lin, Ph.D., of the Brigham and Women's Hospital and Harvard Medical School in Boston, and colleagues tested the impact of antioxidant supplements on cancer incidence in a randomized controlled trial. A total of 7,627 women who were at high risk of cardiovascular disease were randomly assigned to take vitamin C, vitamin E, or beta-carotene.
With an average of 9.4 years of follow-up time, there was no statistically significant benefit from antioxidant use compared with placebo in terms of disease risk or mortality due to cancer. Overall, 624 women developed cancer and 176 died from cancer during the follow-up time. Compared with placebo, the relative risk of a new cancer diagnosis was 1.11 for women who took vitamin C, 0.93 for women who took vitamin E, and 1.00 for women who took beta carotene. None of these relative risks was statistically significantly different from 1.
"Supplementation with vitamin C, vitamin E, or beta carotene offers no overall benefits in the primary prevention of total cancer incidence or cancer mortality," the authors conclude. "In our trial, neither duration of treatment nor combination of the three antioxidant supplements had effects on overall fatal or nonfatal cancer events. Thus, our results are in agreement with a recent review of randomized trials indicating that total mortality was not affected by duration of supplementation and single or combined antioxidant regimens."
In an accompanying editorial, Demetrius Albanes, M.D., of the National Cancer Institute, reviewed data from previous randomized controlled trials that examined supplement use and cancer incidence. He noted that while the trial data reported by Lin are negative with respect to lowering cancer risk, there is valuable information uncovered that should not be overlooked. There was a trend for a reduction in colon cancer with vitamin E supplementation, which has been observed in other studies. Additionally, beta carotene use was associated with a modest excess of lung cancer, which is consistent with previous reports.
"Null trials or those with unexpected outcomes should not, however, be viewed as failures; they have and will con¬tinue to shed light on the causes of cancer and help us discover the means for its prevention," the editorialist concludes.

Study finds selenium, vitamin E do not prevent prostate cancer
Findings from one of the largest cancer chemoprevention trials ever conducted have concluded that selenium and vitamin E taken alone or in combination for an average of five and a half years did not prevent prostate cancer, according to a team of researchers coordinated by the Southwest Oncology Group (SWOG) and led by scientists at The University of Texas M. D. Anderson Cancer Center and Cleveland Clinic.
Data and analysis gathered through Oct. 23, 2008, from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) were published in the Dec. 9 issue of the Journal of the American Medical Association (JAMA) by Scott M. Lippman, M.D., professor and chair of Thoracic/Head and Neck Medical Oncology at M. D. Anderson, Eric A. Klein, M.D., of the Cleveland Clinic Lerner College of Medicine, and 30 coauthors from the United States, Puerto Rico and Canada.
Funded by the National Cancer Institute (NCI) with some additional contribution from the National Center for Complementary and Alternative Medicine, the Phase III trial began recruitment in August 2001 and aimed to determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases in relatively healthy men. The study followed 35,533 participants from 427 sites in the United States, Canada and Puerto Rico. The randomized, placebo-controlled and double-blind trial divided the participants into four intervention groups: selenium, vitamin E, both selenium and vitamin E, and placebos.
Supplement Cases 5-year prostate cancer diagnosis
Placebo 416 4.43 percent
Selenium 432 4.56 percent
Vitamin E 473 4.93 percent
Selenium + Vitamin E 437 4.56 percent
The study found no evidence of benefit from selenium, vitamin E, or both. Additionally, the data showed two statistically non-significant findings of concern: slightly increased risks of prostate cancer in the vitamin E group and type two diabetes mellitus in the selenium group. Both trends may be due to chance and were not observed in the group taking selenium and vitamin E together.
An independent data and safety monitoring committee reached the same conclusion and recommended supplementation be discontinued Oct. 23 for lack of evidence of benefit.
"SELECT presented a unique opportunity to improve the lives of men from every social and ethnic background through chemoprevention," said Lippman, who serves as a national study coordinator. "Although supplementation has been discontinued, we will continue to follow these men and monitor their health for approximately three more years, conducting regular prostate screening tests and questioning them about diabetes and other health issues. Doing so is critical not only to determine any possible long-term effects of the selenium and vitamin E, but also in order to gain a better understanding of prostate and other cancers and age-related disease."
Prostate cancer is the most common male cancer in the U.S. and the second leading cause of cancer deaths overall. The American Cancer Society estimates that more than 180,000 American men will be diagnosed with prostate cancer this year and nearly 29,000 will die from the disease. African-American men have a 60 percent higher incidence rate of prostate cancer and are two times more likely to die from the disease compared with Caucasian men.
Elise Cook, M.D., an associate professor in M. D. Anderson's Department of Clinical Cancer Prevention and the location's principal investigator, served as the chair of SELECT's Minority and Medically Underserved Subcommittee. "Our site has placed a strong emphasis on recruiting African-American men to participate. Of the 387 men we follow, 101 of those are African-American. It is important we continue to follow these men to determine long-term effects and complete the ancillary studies in which many participate," said Cook.
SELECT was based upon the secondary outcomes from two previous cancer prevention trials. The first, a 1996 study of selenium versus placebo to prevent non-melanoma skin cancer, showed that although the supplement did not reduce the risk of skin cancer, selenium did reduce prostate cancer by two-thirds; and in the second, a 1998 study conducted by Finnish researchers determined that although vitamin E did not prevent lung cancer in more than 29,000 male smokers, it did result in 32 percent fewer prostate cancers in men taking the supplement.
"Preliminary data suggesting benefits - no matter how promising - cannot reliably result in new clinical recommendations until they've been tested in definitive trials," said Ernest T. Hawk, M.D., vice president and division head of M. D. Anderson's Cancer Prevention and Population Sciences.
Although the SELECT trial did not turn out as we'd hoped - identifying a new way to reduce men's risk of prostate cancer - it was nevertheless extremely valuable by generating definitive evidence. Cancer prevention advances by rigorous science."
Identity of SELECT participants will remain blinded to prevent the introduction of any unintentional bias, however, they may be unblinded upon request. The sub-studies, funded and conducted by the National Institutes of Health's National Heart, Lung and Blood Institute, the National Institute of Aging, the National Eye Institute and the NCI, will continue without the participants taking any supplementation. These ancillary studies were evaluating the effects of selenium and vitamin E on chronic obstructive pulmonary disease, the development of Alzheimer's disease, the development of age-related macular degeneration and cataracts, and the development of colon polyps.
Neither vitamin C or E associated with reduced risk of prostate cancer, or other cancers

In a major cancer prevention study, long-term supplementation with vitamin E or C did not reduce the risk of prostate or other cancers for nearly 15,000 male physicians. This study, along with another cancer prevention study, will be published in the January 7 issue of JAMA, and both reports are being released early online because of public health implications.
In some observational studies, intake or blood levels of vitamins E and C have been associated with reduced risk of certain cancers. "However, definitive proof that vitamins E and C can reduce the risk of overall or site-specific cancers must rely on large-scale randomized trials," the authors write. "A number of trials have addressed the potential role of vitamins in the prevention of cancer; however, the results from these trials have not been consistent." Despite uncertainty about the long-term health effects or benefits, more than half of U.S. adults take vitamin supplements, and vitamins E and C are among the most popular individual supplements, according to background information in the article.
J. Michael Gaziano, M.D., M.P.H., of Brigham and Women's Hospital and VA Boston Healthcare System, Boston, and colleagues conducted the Physicians' Health Study II, a randomized, placebo-controlled trial to examine the effects of vitamin E and vitamin C on prostate cancer and total cancer. The study included 14,641 male physicians in the United States, age 50 years or older at the time of entering the trial, of whom 1,307 had a prior history of cancer. Participants were randomized to receive individual supplements of 400 IU of vitamin E every other day and 500 mg. of vitamin C daily.
During an average follow-up of 8.0 years, there were 1,943 confirmed total cancer cases and 1,008 prostate cancer cases. Compared with placebo, vitamin E had no effect on the incidence of prostate cancer or total cancer. The researchers also found no significant effect of vitamin C on total cancer or prostate cancer. Neither vitamin E nor vitamin C had a significant effect on site-specific cancers, including colorectal, lung, bladder and pancreatic. Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk.
"These data provide no support for the use of these supplements in the prevention of cancer in middle-aged and older men," the authors conclude.
Preventing colds: Washing your hands is more effective than taking vitamins
Vitamin C cannot prevent colds / Benefit of vitamins and dietary supplements is often overestimated

The days are getting shorter, temperatures are dropping, and the cold and flu season is beginning. Many people have started taking vitamin C tablets as a precautionary measure. But research has shown that vitamin supplements do not provide nearly as much protection as other measures, like frequently washing your hands - and that high doses can even be harmful. The German Institute for Quality and Efficiency in Health Care (IQWiG) has published information and a quiz on the subject of prevention, helping to separate widespread myths from facts.

Promising news is quickly assumed to be true

Many people overestimate the benefits of vitamin C and other antioxidants. For years it was believed that taking vitamin C supplements not only provided protection against colds, but also against cancer, thereby helping people to live longer. An easy-to-understand summary of the research in this area, refuting these beliefs, has now been published on IQWiG's website www.informedhealthonline.org. "Not only is there no proof that some antioxidants prolong life, but there is some evidence that certain products may even lead to earlier death", says Professor Peter Sawicki, the Institute's Director.

"Positive" news gives people hope, which can quickly spread, become deeply held beliefs. Professor Sawicki: "It can be very difficult to accept that these beliefs are myths, but they are not true if further research does not confirm them or the research points to the opposite conclusion."

Simple strategies can prevent respiratory infections

Whether it is caused by a mild cold or the flu, a runny nose and sore throat are signs of a viral infection. Many people are absolutely convinced that vitamin C provides protection against respiratory infections. Yet research has shown that vitamin C does not prevent infection, and that high doses can even be harmful.

There are many simple but effective ways to lower the risk of respiratory infections. These include frequently washing your hands with normal soap and water, and not touching your face with your hands. People who already have a respiratory infection can stop it from spreading by throwing away tissues immediately after using them and not shaking hands with other people.

In a quiz published on www.informedhealthonline.org today, you can test how much you know about preventing illness and find out some facts which may surprise you.

The Institute's website, www.informedhealthonline.org, provides the public with easy-to-understand information about current medical developments and research on important health issues. If you would like to be kept up-to-date with the latest publications on the independent health information website, you can subscribe to the informedhealthonline.org newsletter.

More information: http://www.informedhealthonline.org/dietary-supplements-and-complementary-medicine.483.56.en.html

Surgeons Discover that Vitamin C and Other Antioxidants Reduce Infections, Pulmonary Failure, and Abdominal Wall Complications in Trauma Patients

Despite continuing improvements in overall delivery of care to critically injured patients, many trauma victims who survive their initial injury will often die of multiple-organ failure following an operation. In a study presented at the 2008 Clinical Congress of the American College of Surgeons (ACS), Bryan A. Cotton, MD, FACS, reported that “implementation of high-dose antioxidant protocol (vitamins C, E, and selenium) resulted in a reduction of pulmonary complications, in general, as well as infectious complications, including central line and catheter-related infections.”
Dr. Cotton, who is assistant professor of surgery at Vanderbilt University Medical Center, Nashville, TN, also observed a remarkable decrease in abdominal wall complications—including abdominal compartment syndrome and surgical site infections. When an abdominal wound opens up, the result is not just an infection to be treated with antibiotics, he explained. The wounds need packing and some of them open up to the point where they have to be reconstructed with expensive agents.
“This is a high mortality, high morbidity, may-never-return-to-work-again problem _in a young healthy patient,” he said. “Abdominal wall complications are enormous, yet we noted a reduction in some of these complications with implementation of antioxidants. Importantly, the biggest difference was in those patients who had a predicted mortality exceeding 50 percent.”
Immediately prior to completing this study, Dr. Cotton and his colleagues at Vanderbilt demonstrated that this same high-dose antioxidant protocol resulted in a stunning 28 percent reduction in mortality in acutely injured patients. In addition, patients’ length-of-stay in both the hospital and intensive care unit (ICU) were reduced. After the team observed the reduction in mortality after initiating the protocol, they wanted to learn exactly how antioxidants might work. It is all related to addressing the overwhelming oxidative stress, Dr. Cotton said.
He explained that any time a patient has an acute injury, an operation, or some kind of infection, it places a huge stress on the body. This stress can result in injured oxygen molecules called free radicals being released in the body. These molecules roam around, causing considerable damage at the cellular level. This damage is called oxidative stress.
Dr. Cotton said that past research by some renowned scientists in this field has shown a depletion in the store of antioxidants in critically stressed, critically injured patients. Essentially, it appears that antioxidants work as a team in mopping up some of the oxidative stress waste byproducts, reducing the stressors that cause harm.
As Dr. Cotton explains it, antioxidants are like an army of molecular warriors that _rush to the site of an injury to fight infection. In the course of doing battle on the front lines, however, most troops are lost early on. When infectious insurgents rise up later on, patients are highly vulnerable to infections. Depletion of antioxidants is one of the mechanisms that explains why we are vulnerable. Antioxidant therapy replenishes those troops to help keep us safe.
“Antioxidant therapy is so simple and that’s what throws people off,” Dr. Cotton _said, confessing that he had some doubts about it at first as well. Then he saw an impressive randomized prospective trial conducted by Avery B. Nathens, MD, MPH, which showed that some inflammatory states and responses were remarkably improved in patients who had received antioxidants versus those who did not. Dr. Nathens’ trial did not have enough patients in each arm of the study, though, so they were limited in their mortality conclusions.
“Based on these results, we were inspired to initiate a study with vitamins C and E. When we looked at the literature, however, there were some concurrent studies showing that selenium had an impact too, especially on sepsis and other infectious complications. So we combined all the existing research and did a cost analysis. When we learned it would cost only $11 a patient for a seven-day course of antioxidants, we decided to give it a try.”
This retrospective study followed a total of 4,279 patients admitted to the Vanderbilt University Medical Center trauma unit during the study period. High-dose antioxidant protocol was administered to all acutely injured patients (2,258 individuals) admitted to the center between October 1, 2005, and September 30, 2006. This treatment included 1,000 mg. vitamin C (ascorbic acid) and 1,000 IU vitamin E (DL-_-tocopherol acetate), each routinely given every eight hours by mouth, if the patient could take it that way. In addition, 200 mcg. selenium was given once daily intravenously. Patients received these supplements upon arrival, and they were continued for seven days or until discharge, whichever happened first. Patients who were pregnant or had serum creatinine levels >2.5mg/dL did not receive antioxidants.
A comparison cohort was made up of all patients (2,021 individuals) admitted to the trauma center between October 1, 2004, and September 30, 2005—prior to implementation of the antioxidant protocol. While pneumonia and renal failure were similar between the groups, the incidence of abdominal compartment syndrome was significantly less (90 versus 31), as were catheter-related infections (75 versus 50) and surgical site infections (101 versus 44). Pulmonary failure—meaning the patient could not get off the ventilator—was less as well (721 versus 528).
Dr. Cotton is now prescribing high-dose antioxidants only to the most seriously ill patients in the ICU, as they seem to derive the greatest benefit. He and his colleagues will now focus on dose adjustments and length of administration to see if the doses and duration they are currently using are optimal. They have been approached by several groups that are interested in collaborating and investigating these agents as part of multiinstitutional trials and expanding their use to critically ill nontrauma patients.
“While we are all looking for that magic bullet to cure some of the horrible things that can happen after someone is injured or has an operation, we have something at our disposal,” Dr. Cotton said. “It might not be that magic bullet, but it is a very inexpensive and safe way to reduce complications and mortality in the sickest patients.”

Optimal Dose of Vitamin E Maximizes Benefits, Minimizes Risk

Vitamin E has been heralded for its ability to reduce the risk of blood clots, heart attack, and sudden death. Yet in some people, vitamin E causes bleeding. Scientists have known for more than 50 years that excess vitamin E promotes bleeding by interfering with vitamin K, which is essential in blood clotting. However, they haven’t been able to pinpoint how the two vitamins interact. Nutrition researcher Maret Traber of Oregon State University reviews studies of possible explanations of the interaction in an article published recently in Nutrition Reviews.

One of the most compelling studies of the benefits of vitamin E is the Women’s Health Study, in which 40,000 healthy women, 45 and older, took 600 IU vitamin E supplements or a placebo every other day for 10 years. Women taking the supplements had 24 percent fewer deaths from heart disease. Vitamin E’s protective effect appeared even stronger in women 65 and older. Those taking the vitamin experienced a 26 percent reduction in cardiovascular events and a 49 percent reduction in cardiovascular deaths.

“That’s a significant benefit,” Traber said. Yet, she added, “In some people high doses of vitamin E increase the tendency to bleed. Women enrolled in the study had an increase in nose bleeds.”

To lessen the bleeding risk, the U.S.-based Food and Nutrition Board in 2000 set the upper tolerable limit for daily vitamin E intake at 1500 I.U.

Research Traber reviewed suggests that a shared metabolic pathway in the liver causes vitamins E and K to interact. Vitamin K in the liver appears to diminish as vitamin E increases.

“Several different explanations could account for the interaction between the two vitamins,” Traber said. “We need more research to understand the delicate balance between vitamins E and K.”

Vitamins E and C supplements not effective for prevention of cardiovascular disease in men

Neither vitamin E nor vitamin C supplements reduced the risk of major cardiovascular events in a large, long-term study of male physicians, according to a study in the November 12 issue of JAMA. The article is being released early online November 9 to coincide with the scientific presentation of the study findings at the American Heart Association meeting.
Most adults in the United States have taken vitamin supplements in the past year, according to background information provided by the authors. "Basic research studies suggest that vitamin E, vitamin C, and other antioxidants reduce cardiovascular disease by trapping organic free radicals, by deactivating excited oxygen molecules, or both, to prevent tissue damage." Some previous observational studies have supported a role for vitamin E in cardiovascular disease prevention. Some previous observational studies have also shown a role for vitamin C in reducing coronary heart disease risk.
In this study, known as the Physicians' Health Study II, Howard D. Sesso, Sc.D, M.P.H., and colleagues from Brigham and Women's Hospital, Harvard Medical School and School of Public Health and VA Boston Healthcare System, Boston, assessed the effects of vitamin E and vitamin C supplements on the risk of major cardiovascular disease events among 14,641 male physicians. These physicians were 50 years or older and at low risk of cardiovascular disease at the beginning of the study in 1997, and 754 (5.1 percent) had prevalent cardiovascular disease. The study participants were randomized to receive 400 IU of vitamin E every other day or a placebo and 500 mg of vitamin C daily or a placebo.
"During a mean (average) follow-up of 8 years, there were 1,245 confirmed major cardiovascular events," the researchers report. There were 511 total myocardial infarctions (heart attacks), 464 total strokes, and 509 cardiovascular deaths, with some men experiencing multiple events. A total of 1,661 men died during follow-up. Compared with placebo, neither vitamin E nor vitamin C had an effect on the prevention of major cardiovascular events. "Neither vitamin E nor vitamin C had a significant effect on total mortality, but vitamin E was associated with an increased risk of hemorrhagic stroke."
In conclusion the authors write: "In this large, long-term trial of male physicians, neither vitamin E nor vitamin C supplementation reduced the risk of major cardiovascular events. These data provide no support for the use of these supplements for the prevention of cardiovascular disease in middle-aged and older men."

Vitamin E shows possible promise in easing chronic inflammation

With up to half of a person’s body mass consisting of skeletal muscle, chronic inflammation of those muscles – which include those found in the limbs – can result in significant physical impairment.

According to University of Illinois kinesiology and community health professor Kimberly Huey, past research has demonstrated that the antioxidant properties of Vitamin E may be associated with reduced expression of certain pro-inflammatory cytokines, in vitro, in various types of cells. Cytokines are regulatory proteins that function as intercellular communicators that assist the immune system in generating a response.

To consider whether the administration of Vitamin E, in vivo, might have similar effects on skeletal and cardiac muscle, Huey and a team of Illinois researchers put Vitamin E to the test in mice. The team included study designer Rodney Johnson, a U. of I. professor of animal sciences, whose previous work has suggested a possible link, in mice, between short-term Vitamin E supplementation and reduced inflammation in the brain.

The study represents the first time researchers have looked at in vivo effects of Vitamin E administration on local inflammatory responses in skeletal and cardiac muscle.

In this study, the researchers investigated the effects of prior administration of Vitamin E in mice that were then injected with a low dose of E. coli lipopolysaccharide (LPS) to induce acute systemic inflammation. The effects were compared with those found in placebo control groups.

The research team examined the impact the Vitamin E or placebo treatment had on the mRNA and protein levels of three cytokines – interleukin (IL-6), tumor necrosis factor-alpha (TNF-alpha) and IL-1beta.

“The mice were administered Vitamin E for three days prior to giving them what amounts to a minor systemic bacterial infection,” Huey said. “One thing we did – in addition to (looking at) the cytokines – was to look, in the muscle, at the amount of oxidized proteins.

“Oxidation can be detrimental, and in muscle has been associated with reduced muscle strength,” Huey said.

Among the team’s major findings, in terms of function, Huey said, was that “there was a significant reduction in the amount of LPS-induced oxidized proteins with Vitamin E compared to placebo.”

“So that’s a good thing,” she said. “Potentially, if you reduce the oxidized proteins, that may correlate to increased muscle strength.”

Additionally, the researchers’ experiments yielded a significant decrease in two cytokines – IL-6 and IL-1beta – with Vitamin E, compared with the placebo.

That finding translates to somewhat mixed reviews.

“It’s hard to say functionally what those cytokine changes might mean,” Huey said. “IL-1beta is primarily a pro-inflammatory cytokine, so that could be a good thing – especially in terms of cardiac function.”

However, she said, “IL-6 can have both pro- or anti-inflammatory actions.” She said that the literature has yielded some evidence pointing to the detrimental effects of chronic increases in IL-6. But the effects of acute increases in IL-6 in skeletal muscles – which occur during exercise – may be another story.

“Whether there’s a difference between exercise-induced increases versus inflammation-induced increases in IL-6 is still highly debatable,” she said.

Nonetheless, Huey said, the larger take-home message of the study, published in the December issue of the journal Experimental Physiology, is that Vitamin E “may be beneficial in individuals with chronic inflammation, such as the elderly or patients with type II diabetes or chronic heart failure.”

While the Illinois research team’s work provides a foundation for future investigations that could ultimately have positive outcomes for people afflicted with chronic skeletal or cardiac muscle inflammation, Huey cautioned that it is still far too soon to speculate on results in humans.

“This is clearly an animal model so whether it would translate to humans still requires a lot more research,” she said. “Vitamin E is a supplement that is already approved, and these results may suggest an additional benefit of taking Vitamin E beyond what’s already been shown.”

Omega-6 fatty acids

Omega-6 fatty acids: Make them a part of heart-healthy eating

Omega-6 fatty acids – found in vegetable oils, nuts and seeds – are a beneficial part of a heart-healthy eating plan, according to a science advisory published in Circulation: Journal of the American Heart Association.

View the full Omega-6 Advisory
here.


The association recommends that people aim for at least 5 percent to 10 percent of calories from omega-6 fatty acids. Most Americans actually get enough of these oils in the foods they are currently eating, such as nuts, cooking oils and salad dressings, the advisory reports. Recommended daily servings of omega-6 depend on physical activity level, age and gender, but range from 12 to 22 grams per day.

Omega-6, and the similarly-named omega-3 fatty acids (found in fattier fish such as tuna, mackerel and salmon), are called polyunsaturated fatty acids (PUFA), and can have health benefits when consumed in the recommended amounts, especially when used to replace saturated fats or trans fats in the diet. Omega-6 and omega-3 PUFA play a crucial role in heart and brain function and in normal growth and development. PUFA are “essential” fats that your body needs but can’t produce, so you must get them from food.

For more on good fats vs. bad fats, visit www.AmericanHeart.org/FacetheFats

“Of course, as with any news about a single nutrient, it’s important to remember to focus on an overall healthy dietary pattern – one nutrient or one type of food isn’t a cure-all,” said William Harris, Ph.D., lead author of the advisory. “Our goal was simply to let Americans know that foods containing omega-6 fatty acids can be part of a healthy diet, and can even help improve your cardiovascular risk profile.”

The American Heart Association’s dietary recommendations suggest a broadly defined healthy eating pattern over time – with an emphasis on fruits, vegetables, high-fiber whole grains, lean meat, poultry, and fish twice a week. Diets rich in fruits, vegetables and whole grains have been associated in a large number of studies with reduced cardiovascular risk.

Linoleic acid (LA) is the main omega-6 fatty acid in foods, accounting for 85 percent to 90 percent of the dietary omega-6 PUFA.

There has been some debate within the nutrition community regarding the benefits of omega-6 based on the belief that they may promote inflammation, thus increasing cardiovascular risk. “That idea is based more on assumptions and extrapolations than on hard data,” said Harris, a research professor for the Sanford School of Medicine at the University of South Dakota and director of the Metabolism and Nutrition Research Center at Sanford Research/USD.

The linking of omega-6 intake to inflammation stems from the fact that arachidonic acid (AA), which can be formed from LA, is involved in the early stages of inflammation. However, the advisory explains that AA and LA also give rise to anti-inflammatory molecules.

For example, in the cells that form the lining of blood vessels, omega-6 PUFA have anti-inflammatory properties, suppressing the production of adhesion molecules, chemokines and interleukins — all of which are key mediators of the atherosclerotic process. “Thus, it is incorrect to view the omega-6 fatty acids as ‘pro-inflammatory,’” Harris explained. “Eating less LA will not lower tissue levels of AA (the usual rationale for reducing LA intakes) because the body tightly regulates the synthesis of AA from LA.”

The advisory reviewed a meta-analysis of randomized, controlled trials, and more than two dozen observational, cohort, case/control and ecological reports.

Observational studies showed that people who ate the most omega-6 fatty acids usually had the least heart disease. Other studies examined blood levels of omega-6 in heart patients compared with healthy people and found that patients with heart disease had lower levels of omega-6 in their blood.

In controlled trials in which researchers randomly assigned people to consume diets containing high versus low levels of omega-6 and then recorded the number of heart attacks over several years, those assigned to the higher omega-6 diets had less heart disease.

A meta-analysis of several trials indicated that replacing saturated fats with PUFA lowered risk for heart disease events by 24 percent. “When saturated fat in the diet is replaced by omega-6 PUFA, the blood cholesterol levels go down,” Harris said. “This may be part of the reason why higher omega-6 diets are heart-healthy.”

Jon's Health Tips - Coffee and Caffeine

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.