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.”
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.”
