New Service for
TodaysSeniorsNetwork.com readers...roll mouse over, click on
highlighted links in stories to review items from Amazon
Vitamin E's lack of heart
benefit linked to dosage
Nashville (Tenn.) - The reported failure of vitamin E to prevent heart
attacks may be due to underdosing, according
to a new study by investigators at
Vanderbilt University Medical Center.
The findings, published early online in Free
Radical Biology and Medicine, suggest that
these earlier studies all had a fundamental
flaw – the doses used weren’t high enough to
have a significant antioxidant effect. In
fact, no studies have ever conclusively
demonstrated the dose at which vitamin E can
be considered an antioxidant drug, the
researchers report.
Oxidant injury, or oxidative stress, occurs when
highly reactive molecules called free
radicals attack and damage cellular
proteins, lipids (fats) and DNA. Free
radicals, which are byproducts of normal
metabolism, are produced in excess in
certain disease states, including heart
disease.
Epidemiological data and animal studies suggested
that antioxidant compounds like vitamin E,
vitamin C and beta-carotene might offer some
protection against heart attack in
individuals at risk.
But subsequent controlled clinical trials of
vitamin E – which showed little to no
benefit from the vitamin – stymied that
hope.
“Multiple human trials looking at the effect of
vitamin E supplementation on coronary events
and atherosclerosis have all failed,” said
Jack Roberts, M.D., the T. Edwin Rogers
Professor of Pharmacology, professor of
Medicine, and lead author on the study.
“We’re talking about trials that examined quite
high doses,” added Jason Morrow, M.D., F.
Tremaine Billings Professor of Medicine &
Pharmacology and chief of the Division of
Clinical Pharmacology. “Short of a couple of
studies, there was no benefit in terms of
prevention of cardiovascular events and
deaths.”
These results caused many to discount vitamin E
supplementation as a cardioprotective
treatment, but Morrow and Roberts suspected
that the studies had been poorly designed.
All of the trials simply gave a dose of
vitamin E and looked for end points such as
heart attack occurrence. But Morrow and
Roberts found a critical piece of
information missing.
“All of these studies were designed in a way that
they never assessed the ability of the dose
of vitamin E tested to effectively reduce
oxidant stress,” Morrow said.
Without determining whether the dose of vitamin E
given was exerting sufficient antioxidant
effects, the previous clinical trial results
were flawed, the researchers said.
In the new study, Morrow and Roberts determined
the optimum antioxidant dose of vitamin E
using an assay they developed to measure
compounds formed by oxidative stress
processes, called F2-isoprostanes. This
measure, said Roberts, “has been
independently validated as the best measure
of oxidative stress status in vivo.”
The researchers first determined how long it took
for a very high dose of vitamin E – 3200 IU/day
– to suppress oxidative stress in
individuals at risk for cardiovascular
disease.
To their surprise, it took 16 weeks for this dose
– which is more than 100 times the
recommended daily intake and about four
times higher than doses used in most
previous clinical studies – to maximally
suppress F2-isoprostane formation.
In another group with similar cardiovascular risk
factors, the researchers administered
varying doses (0, 100, 200, 400, 800, 1600,
and 3200 IU/day) over the 16-week period to
find the minimum effective dose.
They found that it was necessary to give at least
1600 IU per day to cause a significant
reduction in oxidative stress – twice that
used in some of the previous clinical
trials.
“It was clear that large doses – and doses in
excess of what all clinical studies had used
– were necessary,” Morrow said.
“Even with this massive dose of vitamin E, you
only observe a 50 percent reduction in F2-
isoprostanes,” added Roberts. “So in my
opinion, vitamin E is not the spiffy
antioxidant everybody thinks it is – it’s a
pretty poor antioxidant.”
Because the long-term safety of such high doses
is unknown, “we are not touting taking
vitamin E in large doses,” Morrow said. “We
are saying that, in the design of clinical
trials, one needs to have good surrogate
biochemical markers.”
Based on their findings, the investigators
suggest that measures like F2-isoprostane
measurement should be incorporated into any
future studies of antioxidants in
atherosclerosis prevention.
And since oxidative stress has been linked to
numerous other diseases, including
Alzheimer’s disease, Morrow suggests that
F2-isoprostane measurement “really ought to
be incorporated into studies assessing
disease prevention by antioxidants in
general.”
...
...
...