is a safe and proven dosage?
Last night there was a news story on CNBC
News that scientists had discovered that dosages of vitamin C above 500
mg per day might cause DNA damage, so vitamin C might cause cancer [I
D Podmore, H R Griffiths, K E Herbert, N Mistry, P Mistry & J Lunec,
"Vitamin C exhibits pro-oxidant properties ", Nature 392: 559 (9 April
1998)]! Anyone who follows the news, especially about nutrition, realizes
that one day the media tells you butter is bad for you, the next day they
say it's good for you, and you'll worry yourself to death trying to avoid
all the dangers reported on the news to grab your attention. Given the
hype by companies trying to sell you blue green algae and diet pills,
and the scare tactics of the media, how does one decide what to do?
First, we must distinguish between epidemiological
studies, biochemical research, and clinical trials. Most promising micronutrients
are first identified by epidemiological studies. The Nurses' Health Study
has recorded the diets and health of about 50,000 nurses, while the Physicians'
Health Study has done the same for men for many years. The result is a
database that can be tested. Are those with the highest vitamin C intake
more or less likely to get cancer? This is an epidemiological study. It
shows correlation - not cause and effect. Beta-carotene was very promising
in epidemiological studies - those who ate fruits and vegetables rich
in beta-carotene were healthier than those who did not.
Biochemical research helps us to understand
the underlying physiological mechanisms by which micronutrients act. For
example, vitamin B6, pyridoxine, functions as a co-enzyme, a small molecule
that helps an enzyme do its job. An enzyme is a protein that regulates
the rate of a chemical reaction in the body. Excess vitamin B6 is metabolized
to harmless byproducts and excreted. In contrast, DHEA, another popular
micronutrient these days, has a hormone-like structure that is converted
into estrogen and testosterone. Although these hormones have beneficial
effects at the properly regulated natural levels, we do not understand
completely what artificially altered levels do, though we know that they
can cause serious side-effects, for instance estrogen increases the risk
of breast cancer, and testosterone contributes to prostate hyperplasia.
Thus the biochemistry of vitamin B6 indicates it will be safe at high
dosages, while the evidence is that DHEA may be hazardous.
The third line of evidence is placebo-controlled,
double-blind clinical trials. In these studies, two matched groups of
people are given either the micronutrient being studied or a placebo (an
identical tablet without the micronutrient), and their health is monitored
regularly to see whether they develop a particular condition. These may
be short-term, indicating whether the substance is safe for short periods,
or long term, lasting many years, to determine long-term effects. It is
also important to note whether the substance has been tested on women
during pregnancy, as many compounds that do not cause noticeable harm
in adults may cause birth defects.
The last caveat is that any one trial or study
is unreliable, like a single flip of a coin. A study must be repeated
by an independent group of investigators, and all three of the above lines
of evidence must converge on a common conclusion. Then, it is reasonable
to assume that we have a good understanding of the effect of the compound.
At this point, can we conclude that the compound
is absolutely safe? Definitely not. If we test a compound on 10,000 people
for 10 years, that does not mean that it will be safe for 100 million
people for a lifetime. If studies show that a compound has reduced the
risk of cancer by 50%, some people who take the compound will still get
cancer. A study that examines the risk for cancer tells us little about
the risk for diabetes. There will always be questions.
So what can we conclude? We may conclude that,
based on the existing evidence, the compound is much more likely to maintain
the health of the average person than it is to cause harm. We may conclude
that you are more likely to suffer if you do not take the compound than
if you do.
Let us return to the vitamin C story I began
with. There have been approximately 5,000 papers published each year for
many years, and almost all demonstrate that vitamin C is safe! The epidemiological,
biochemical, and clinical evidence about vitamin C is overwhelmingly clear
that it is both safe and likely to reduce the risk of cancer, heart disease,
and other age-associated diseases. Because of the enormous popular interest
in vitamin C, the media is delighted to run a story on a single study
indicating risk - it will draw a lot of attention and cause a lot of fear
and get a lot of people to watch the news - but the one study will not
change the overwhelming evidence that vitamin C is safe and proven likely
to reduce the risk for age-associated diseases.
Another useful true story will illustrate
the strong feelings which many respected scientists have about nutrition
and safety , taken from Nutrient Interactions (edited by C.E. Bodwell
and J. W. Erdman, Jr., Marcel Dekker, Inc., New York, 1988, pg. 297).
Dr. Herbert of Mt. Sinai Medical Center has written often about the dangers
of supplemental vitamin C. One article he wrote in 1974 reported that
substantial losses of vitamin B12 occurred when meals were incubated with
added ascorbic acid to simulate the effect of taking vitamin C after a
meal. They advised that vitamin C supplements might be hazardous and cause
vitamin B12 deficiency. After more than two decades, the only evidence
to support this "hazard" is Dr. Herbert's own study in four paraplegics.
It was later demonstrated that a technical error in Dr. Herbert's procedure
led to the erroneous conclusion that vitamin B12 is destroyed when heated
in the presence of vitamin C.
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