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[Definitie:] "An ergogenic aid is any substance or phenomenon that enhances performance."
(Wilmore and Costill) 
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1 0 - 1 1 - 2 0 0 4 Vitamin E Linked to Higher Death Rates
By Janice Billingsley
WEDNESDAY, Nov. 10 (HealthDayNews) -- High doses of the antioxidant vitamin E could increase the risk of death, Johns Hopkins researchers have found.
By re-analyzing the data from 19 vitamin E studies over the past decade, the scientists found that a daily dose of 400 IUs or more was linked to a 6 percent increased risk of death.
"People take significant amounts of vitamin E because they have a perception that it will provide some health benefit and that this will help them live longer, but just the opposite could be the case," said study author Dr. Edgar R. Miller, an associate professor of medicine at Johns Hopkins University.
The finding was presented Wednesday at the American Heart Association's scientific sessions in New Orleans, and will be simultaneously published online in the Nov. 10 issue of the Annals of Internal Medicine. Miller said this study is similar to recent findings that high doses of another antioxidant, beta carotene -- which has been touted as a cancer preventive -- can do more harm than good.
"This is not new. In several large studies, high doses of beta carotene have been shown to increase the risk for lung cancer and death compared to risk in those who took placeboes, but vitamin E has been given a pass," Miller said.
The Hopkins' researchers noted one caveat: Most of the patients in the trials were over age 60 and were not well, so the study's relevance for younger, healthy adults might be limited.
Dean Jones, a professor of medicine at Emory University Hospital in Atlanta, said the new study warrants reconsideration of the amount of vitamin E people should take.
"When I lecture on this, which I have done for years, the textbook standard is that vitamin E is relatively non-toxic in excess, and I have never distinguished between the amounts of 200 IUs, 400 IUs or even 800 IUs, but in the future I will," he said.
However, the Council for Responsible Nutrition (CRN), a Washington, D.C.-based trade association representing the dietary-supplement industry, was sharply critical of the new study.
The study "inappropriately tries to draw conclusions for the whole population based on a combination of studies of people who were already at grave risk with existing diseases, including cancer, heart disease, Alzheimer's, Parkinson's and kidney failure," the council said in a prepared statement.
John Hathcock, the council's vice president for scientific and international affairs, added, "In reviewing the totality of evidence on vitamin E, including all clinical trial data and several large observational studies, CRN agrees with the Institute of Medicine in finding vitamin E supplements safe at levels of at least up to 1,000 mg (1,600 IU) for normal, healthy adults. This meta-analysis provides no convincing evidence to the contrary."
Hopkins' Miller said the reason for the increase in mortality risk needs to be studied further. But it could be that high doses of vitamin E disrupt the natural balance of antioxidants in the body and increase vulnerability to oxidative damage. Previous research has suggested that antioxidants may protect cells from damage to their DNA caused by oxygen molecules called free radicals. Another possibility is that the vitamin's anticoagulant properties interfere with clotting mechanisms, he said.
For the study, Miller and his colleagues used a process called meta-analysis to reevaluate the data from the 19 studies, which involved 135,967 people, sorting information by whether they were taking high or low doses of the vitamin. Nine of the trials tested vitamin E alone and 10 tested it in combination with other vitamins.
Eleven trials involved intake of 400 IUs or more daily, and nine of those trials showed a 6 percent higher death rate among those who took the vitamin, compared to those who took placeboes. The other eight trials involved low-dose use, 200 IUs daily or less, and it was unclear whether the low doses increased a person's risk of death, Miller said.
Jones explained that the antioxidants vitamin E, vitamin C and beta carotene are different from other vitamins. Most vitamins have specific recommended doses based on the function they perform in the body. For instance, the B vitamin folate interacts with certain proteins in the body, so it's known how much folate is needed to saturate these proteins, he said.
But the antioxidant vitamins react chemically to the free radicals in the body. Because doctors can't accurately measure free radicals, a recommended dose of antioxidants is difficult.
Further, while vitamin C is water-soluble and any excess leaves the body via urine, beta carotene and vitamin E are both fat-soluble so any excess accumulates in the fat cell membranes, Jones said.
There is no recommended dose for vitamin E, although current guidelines set a tolerable limit of up to 1,500 IUs per day. On average, Miller said, daily intake of vitamin E through foods is 10 IUs, and multivitamin pills usually contain 30 to 60 IUs of vitamin E. Vitamin E is found in nuts, leafy green vegetables and wheat germ oil.
1 1 - 1 1 – 2 0 0 4 Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality
Edgar R. Miller III, MD, PhD; Roberto Pastor-Barriuso, PhD; Darshan Dalal, MD, MPH; Rudolph A. Riemersma, PhD, FRCPE; Lawrence J. Appel, MD, MPH; and Eliseo Guallar, MD, DrPH.
4 January 2005 Annals of Internal Medicine Volume 142 • Number 1
Hieronder een paar tekstfragmenten en figuren uit het hierboven genoemde onderzoek.
Search Strategy and Inclusion Criteria We searched for all reports of clinical trials (with no language restrictions) that tested the effect of vitamin E supplementation in humans. We performed a MEDLINE search by using the Medical Subject Heading (MeSH) terms vitamin E, antioxidant vitamins, alpha tocopherol, tocopherol, and clinical trials. The search period was 1966 through August 2004. We complemented the MEDLINE search by searching the Cochrane database of randomized, controlled trials; reviewing the reference lists from original research, review articles, and previous meta-analyses; and reviewing the files of the investigators.
Trials Nine of 19 trials used vitamin E alone, while the other 10 trials combined vitamin E with other vitamins or minerals. All but 3 trials (42, 43, 51) were placebo-controlled and double-blind. Average follow-up ranged from 1.4 to 8.2 years. Vitamin E dosage varied between 16.5 and 2000 IU/d, with a median dosage of 400 IU/d.
Combined Effect of Vitamin E on All-Cause Mortality
Overall, vitamin E
supplementation did not affect all-cause mortality. The
pooled risk difference comparing vitamin E with control
was 10 per 10 000 persons. However, there was significant
heterogeneity of study results that was explained
by differences in results between low-dosage
(>400 IU/d) and high-dosage (<400 IU/d) vitamin E trials.
[Overzicht studies - figuur]
‘Many adverse effects’ A recent meta-analysis that examined the effects of antioxidants, not specifically vitamin E, in preventing cancer noted a possible increase in all-cause mortality. [ErGs] However, in an accompanying comment, Forman and Altman [ErGs] cautioned that these mortality analyses were exploratory and incomplete. A strength of our paper is the systematic search for trials that presented mortality data.
Although vitamin E is considered relatively safe compared to other fat-soluble vitamins (56), an increase in mortality at high dosages of vitamin E is biologically plausible. In fact, some researchers warned against the longterm administration of mega-dosages of vitamin E because it could be associated with many adverse effects (57). In vitro studies have shown that vitamin E may have prooxidant effects at high doses (58, 59). In in vitro models, the pro-oxidant effect of vitamin E on low-density lipoproteins is related to the production of the tocopheroxyl radical, which can be inhibited by co-antioxidants such as vitamin C (60).
However, the trials that combined highdosage vitamin E with vitamin C (48, 49, 51) showed increased mortality in the vitamin E groups, with the exception of the small Polyp Prevention Study (PPS) (46). High dosages of vitamin E may displace other fat-soluble Antioxidants, disrupting the natural balance of antioxidant systems and increasing vulnerability to oxidative damage. Vitamin E may also inhibit human cytosolic glutathione S-transferases, which help detoxify drugs and endogenous toxins (62).
Vitamin E also has anticoagulant properties, possibly by interfering with vitamin K–dependent clotting mechanisms (63). In fact, the Alpha-Tocopherol, Beta Carotene (ATBC) Cancer Prevention Study (38) showed a statistically significant increased risk for hemorrhagic stroke among participants assigned to vitamin E. (Over een andere studie, met soortgelijke resultaten, vind je [hier] meer.)
Conclusion On the basis of our study, high-dosage vitamin E supplementation is clearly unjustified. Policymaking bodies, which currently do not recommend antioxidant vitamin supplement use to the general population (1–3), should also caution the public against the use of high-dosage vitamin E supplementation. Current practice guidelines, however, recommend the use of vitamin E supplementation to delay the progression of Alzheimer disease (69, 70). This recommendation may be premature until larger randomized, controlled clinical trials evaluate the efficacy and safety of high-dosage vitamin E supplementation in patients with Alzheimer disease.
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