ARE VITAMIN SUPPLEMENTS SAFE
Anyone who recently
has been reading the major newspapers, surfing for news on the Internet or just
watching the news on television likely
has been surprised by the claim that “vitamins are deadly.” The Wall
Street Journal (October 25, 2011) asks, “Is This the End of Popping Vitamins?” And theArchives of Internal
Medicine just published “Dietary Supplements and Mortality Rate in
Older Women,” an article that comes to the conclusion that “in older women,
several commonly used dietary vitamin and mineral supplements may be associated
with increased total mortality risk.” A second study published in the Journal
of the American Medical Association, (JAMA) claims that men who take
vitamin E are at higher risk of developing prostate cancer. What is to be made
of such claims? Are they true, false, or something in between? How can the
non-expert decide?
Dangerous
Multivitamins?
“Dietary Supplements and Mortality Rate in Older Women: The Iowa Women’s Health Study” at first appears to be a large and well-laid out study. As the study describes its own design, “We assessed the use of vitamin and mineral supplements in relation to total mortality in 38,772 older women in the Iowa Women’s Health Study; mean age was 61.6 years at baseline in 1986. Supplement use was self-reported in 1986, 1997, and 2004.” It reports that a number of nutrients supposedly are linked to greater rates of death in vitamin users than in non-users. There was an associated increased risk of total mortality when compared with corresponding non-use for multivitamins, vitamin B6, folic acid, iron, magnesium, zinc and copper. Indeed, of 15 supplements analyzed by the researchers, only calcium was associated with a lower risk of mortality.
“Dietary Supplements and Mortality Rate in Older Women: The Iowa Women’s Health Study” at first appears to be a large and well-laid out study. As the study describes its own design, “We assessed the use of vitamin and mineral supplements in relation to total mortality in 38,772 older women in the Iowa Women’s Health Study; mean age was 61.6 years at baseline in 1986. Supplement use was self-reported in 1986, 1997, and 2004.” It reports that a number of nutrients supposedly are linked to greater rates of death in vitamin users than in non-users. There was an associated increased risk of total mortality when compared with corresponding non-use for multivitamins, vitamin B6, folic acid, iron, magnesium, zinc and copper. Indeed, of 15 supplements analyzed by the researchers, only calcium was associated with a lower risk of mortality.
How reliable is this study and its conclusions? Not very. Many
have criticized the publication vigorously as being highly misleading for
reasons easy to grasp. Here are some of the concerns that have been expressed:
·
This was only an
observational study based on self-reporting via questionnaires and not a study
establishing cause and effect.
·
No attempt was made to
assess the accuracy of self-reporting. As is well known from highly controlled
clinical trials, many individuals will recall and report usage when they in
fact are recalling and reporting their intentions. The authors cannot say
whether the recall statistics were 90 percent accurate or only 50 percent
accurate or varied by the supplement being taken.
·
No attempt was made to
independently assess the relative health of the participants or link such
information to the vitamin usage. No attempt was made and there is no
information on the actual nutrient status of the participants.
·
Those who took
vitamins at the beginning of the study reported being significantly healthier
than those who did not, i.e., less hypertension, less diabetes, etc. This means
that comparing those taking vitamins and those not taking vitamins was not
comparing apples to apples, but potentially comparing apples to oranges because
of a host of traits and conditions that might have separated these groups from
the start.
·
To assess the impact
of vitamin usage, statistical modeling was used to remove factors that
supposedly might skew the results. This modeling is highly controversial.
The statistical manipulation of the data is the worst offense of
the authors of this study and it primarily is through this manipulation that
they reached their negative conclusions. The authors adjusted all the numbers
for “age, educational level, place of residence, diabetes mellitus, high blood
pressure, body mass index (calculated as weight in kilograms divided by height
in meters squared), waist to hip ratio, hormone replacement therapy, physical
activity, smoking status, and intake of energy.” The results were further
manipulated via yet more “multivariable adjustment” to take into account
alcohol, saturated fatty acids, whole grain products, fruits, and vegetables.
It is important to
understand the impact of these adjustments. Bear in mind that the women being
surveyed who took supplements before the start of the study were healthier than
those who did not. Jacob Teitelbaum, MD, a holistic physician and coauthor of Real
Cause, Real Cure (Rodale, 2011), has provided an excellent analogy of
how the authors of the Archives of Internal Medicine study
biased the results via their statistical adjustments: “One could come to the
same conclusion about exercise not being helpful using this same statistical
approach. Take, for example a study with two control groups: those who exercise
and those who do not, but both of which are put on a new exercise program. At
the beginning of the study, those who already are exercisers are healthier than
those who are not. By canceling this fact out, and negating the prior health of
the exercisers, you can find that exercise is not beneficial.” Teitelbaum’s
point is that the better health of the already exercising group may not be
greatly improved by merely changing the exercise program, whereas the health of
the non-exercisers will be enhanced. If the benefits of the prior exercise of
the first group are subtracted from the results and then the two groups are
compared, it will make prior exercise appear to be bad for health inasmuch as
the prior exercise group’s health will not have improved during the course of
the trial compared to the newly exercising group.
So the Archives
of Internal Medicine researchers “controlled” for good health habits
and for good health at the start of the observational period. Their adjustments
subtracted the starting health status of the vitamin users just as in
Teitelbaum’s exercise analogy. As Teitelbaum astutely observes, “The hypothesis
wasn’t to state whether supplements will harm or help. It was to see if they
would harm, which gives you an idea of what their study was about.”
How powerful are these adjustments, i.e., statistical
manipulations? Very. Consider the actual raw findings reported in Table 2 of
the study:
·
Vitamin B complex was
associated with a 7 percent reduction in mortality
·
Vitamin C was
associated with a 4 percent reduction in mortality
·
Vitamin D was
associated with an 8 percent reduction in mortality
·
Magnesium was
associated with a 3 percent reduction in mortality
·
Selenium was
associated with a 3 percent reduction in mortality
·
Zinc was associated
with a 3 percent reduction in mortality
This is not to say that all nutrients were good—for instance,
copper was associated with a 31 percent increase in mortality and this negative
finding well may be accurate because of the known dangers of copper
overload—but the statistical adjustments significantly reversed most of the
findings of the non-adjusted data. This should give one serious pause in
accepting the study and its conclusions.
In short, this study would appear to be an unreliable guide to
the benefits of supplements, especially multivitamin and mineral formulas. A
large number of published studies, in fact, have found just the opposite, to
wit, multivitamin/ mineral intake and the intake of a number of individual
nutrients is associated with improved health. Here are the conclusions of just
one of these studies, a study much more rigorous than that just examined:
“These results indicate that use of supplements significantly improved the
status of several vitamins in elderly people. Due to age-related problems
concerning the intake and digestion of nutrients, a moderate, regular
supplementation might be a useful option for older people who are otherwise
unable to satisfy their micronutrient requirements.”
What About Vitamin E
and Other Antioxidants?
Do the questionable findings of the Archives of Internal Medicine study mean that other studies with negative conclusions about supplements are wrong? Not necessarily. The JAMA study is a case in point. It found that men who took vitamin E for prostate health were 17 percent more likely to develop prostate cancer than those not supplementing. The authors of this study warned that the “observed 17 percent increase in prostate cancer incidence demonstrates the potential for seemingly innocuous yet biologically active substances such as vitamins to cause harm.” In this instance, the findings most likely are accurate. Nevertheless, there are problems in drawing conclusions about supplements from this study.
This study builds upon an earlier study published in 2008, the
“Selenium and Vitamin E Cancer Prevention Trial,” which found a “statistically
non-significant” increase in prostate cancer risk in those taking 400 IU of
vitamin E daily. In the earlier study, the primary analysis included 34,887 men
who were randomly assigned to 1 of 4 treatment groups: 8,752 to receive
selenium; 8,737, vitamin E; 8,702, both agents, and 8,696, placebo. The 2011
trial included 54,464 additional person-years of follow-up and 521 additional
cases of prostate cancer since the primary report. Compared with placebo, the
absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for
vitamin E, 0.8 for selenium, and 0.4 for the combination. This led to the
conclusion: “Dietary supplementation with vitamin E significantly increased the
risk of prostate cancer among healthy men.”
The Council for Responsible Nutrition (CRN) and other observers
have admitted that this JAMA study was well done—and, indeed, it was well
performed within its stated parameters. The issue is the degree to which its
results can be generalized. The form of vitamin E studied was the synthetic
alpha-tocopherol. This likely is the real reason that the study failed. In
several other studies on control of inflammation, prevention of cancer, etc.,
gamma-tocopherol and deltatocopherol have exhibited benefits, whereas
alpha-tocopherol has not. In fact, the excessive intake of alpha-tocopherol
long has been known to be potentially harmful. Here are some reasons why:
·
Supplementation with
alpha-tocopherol clearly depresses gamma-tocopherol levels, whereas gamma-tocopherol
has little or no impact on alpha-tocopherol levels. Supplementation with
alpha-tocopherol clearly depresses delta-tocopherol levels, whereas
delta-tocopherol has little or no impact on alpha-tocopherol levels.
·
Alpha-Tocopherol also
attenuates the benefits of gamma-tocotrienol on cardiovascular disease and at
high levels may interfere with the benefits of the four tocotrienols more
generally.
·
High chronic intake of
alpha-tocopherol from any source may compromise mitochondrial ubiquinol (CoQ10)
metabolism. Excessive oxidative degradation of tocopherol can potentially
interfere with mitochondrial electron transfer.
The tocotrienols family of vitamin E and gamma- and
delta-tocopherols all seem to offer only positive results. To the contrary, alpha-tocopherol
supplementation, regardless whether the source is natural or otherwise, at this
point in time appears to be questionable.
Vitamin E is an exemplar of a more general trend in the research
regarding antioxidants. Because it is the premier example of an antioxidant
that breaks free radical chain reactions, it initially was expected to have
positive results against cancer, heart disease, and so forth and so on. For
alpha-tocopherol after numerous large and lengthy trials, this promise no
longer is supportable. The era of excessive expectations for oral antioxidants
is being tamed by the realism of clinical and other research. Inasmuch as
expectations for supplements in general were bolstered by the antioxidant
theory and the evidence apparently supporting it, the failures of large
extended clinical trials to unequivocally support vitamin E and, to a lesser
extent, additional antioxidants, such as selenium, cannot but damage the image
of other supplements. Today, it has become apparent that many of the benefits
of the tocotrienols, gammatocopherol, etc., clearly are not due to their
antioxidant and free radical trapping and chain-breaking functions and,
instead, are due to other mechanisms of action.
Vitamin E (as alpha-tocopherol), selenium and beta-carotene are
three antioxidants whose stars have been tarnished the most in recent years.
Under certain circumstances, excessive intakes of each of these have proven to
be potentially harmful. It should be noted that two of these are fat-soluble,
hence can build up in the body, and the third is a trace element. In contrast,
no realistic general concerns have been demonstrated with regard to vitamin C,
which is water soluble and easily eliminated from the body.
Conclusions
Balanced and reasonably dosed multivitamin and mineral supplements have proven track records not only for safety, but also for insuring nutritional adequacy in groups, such as the elderly and teenagers, who otherwise often experience significant shortfalls in essential nutrient intakes. Most studies on multivitamin and mineral supplements have found that these contribute to improved health. Nevertheless, expectations should be reasonable.
Very high intakes of individual supplements being taken
essentially as drugs is another issue entirely. Consuming daily the amount of
alpha-tocopherol found in several bushels of wheat or the amount of catechins
found in 30 cups of green tea is a practice that always needs to be examined
critically. With some nutrients, there are significant benefits with little
possibility of harm. However, as the case of alpha-tocopherol demonstrates,
this is not always the case.
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