Rebuttal to Vitamins Are Bad Editorial

By Rhonda Patrick, Ph.D.

In this article I will discuss a recent headline-grabbing editorial that was published in the Annals
of Internal Medicine that reviewed three studies on the topic of multivitamins and chronic
disease prevention. The editorial, is titled: Enough is Enough: Stop Wasting Money on Vitamin
and Mineral Supplements,

and its purpose was to serve as a direct call to action for medical
professionals to advise against the daily use of vitamin and mineral supplements and for scientists
to stop further research into the potential benefits of supplements.
Watch the video here: http://youtu.be/o0u8UdZeOhc
This editorial ignored decades of well-done nutrition research that has shown that supplementing
appropriate levels of micronutrients (such as vitamin D, B vitamins, and omega-3s) are
extremely helpful in preventing disease and decreasing all-cause mortality primarily due to
widespread dietary inadequacy of essential vitamins, minerals, and fatty acids.
According to a NHANES and CDC report published in 2012, the percentage of adults in the
US that do not take vitamin and mineral supplements and fall below the estimated average
requirement for vitamin and minerals are the following:
96% for vitamin D (1)
48% for vitamin C (1)
96% for vitamin E (1)
58% for vitamin A (1)
Now compare this to the percentage of Adults in the US who do routinely use multivitamin
supplements, in these cases:
25% for vitamin D (1)
3% for vitamin C (1)
5% for vitamin E (1)
2% for vitamin A (1)
These data demonstrate that many US adults are not getting adequate levels of important
vitamins from their diet and vitamin/mineral supplements help to fill these nutritional gaps at a low
cost.
The misleading editorial was broken down into three specific categories:
Effects on cancer incidence and other age-related diseases
Effects on cognition and cognitive decline
Effects on cardiovascular disease
The final conclusion of the editorial was that vitamin/mineral supplements were functionally
ineffective or, worse yet, deleterious in their effects in all three categories.
This editorial covered one meta-analysis including multiple studies and two other studies. I
identified a few common methodological problems with these studies, which the authors relied
upon as their supporting evidence. These problems were the following:
Lack of any objective biochemical analyses on vitamin and mineral levels in plasma or
blood cells either at baseline (before treatment) or at the follow-up (after the treatment).
In many cases, the study population was severely deficient in a particular micronutrient
and at the end of the trial they were still deficient, meaning the vitamin/mineral dose in
the treatment group was inadequate.
Dose being often extremely inadequate or conversely, excessively high.
Study participants being already in an advanced diseased state (which is funny, since the
editorial emphasized multivitamins had no effect on prevention)
Some of these studies included meta-analyses, which consisted of multiple studies some
of which had positive findings, which were left out and not mentioned in the editorial. I
feel that this point, in particular, demonstrates overt bias by the editorial's authors.
Lets begin with the effects on cancer incidence:
Out of eleven studies analyzed, two studies showed a protective effect of multivitamin or
calcium supplementation on cancer incidence, of course the positive effects were not mentioned
in the attention-grabbing editorial. One study began with a severely vitamin D deficient
population of women (12ng/ml) and at the end of the study women had only raised their vitamin
D levels (23ng/ml) from severely deficient to just deficient (2). If you are designing a clinical trial
with vitamin D and your population is severely deficient then you should aim at giving the
treatment group a dose high enough that will get them up to adequate serum levels of vitamin D,
which is generally considered to be above 30ng/ml.
Several of the studies did not measure the vitamin and mineral levels at baseline or at follow-up;
therefore, negative data (meaning no effect on cancer incidence) is meaningless and no
conclusions can be made. While the majority of studies included in this particular meta-analysis
involved diseased individuals the editorial claimed that vitamins and minerals have no effect on
cancer prevention. This is misleading as a very small percentage of these studies looked at
cancer prevention and actually had biochemical evidence that treatment worked and those
studies found that multivitamin protected against cancer incidence in men but not women
(2).When we examine the data we see the reason there was no effect in women is because the
plasma levels of vitamins and minerals were the same in the placebo compared to the treatment
group, so of course supplementation did not show an effect compared to placebo if their levels
of the micronutrient were the same between the two groups. If there were no biochemical data
in this study it would not have been possible to understand why there was a protective effect in
men but not women. This really highlights the importance of biochemical endpoints to quantify
the effectiveness of treatment as well as compliance. For those studies with no quantification of
any biochemical data, there can be no conclusions made. I cannot emphasize this enough.
Some of studies included in this meta-analysis also started with a population of individuals that
were in an early or late stage of cancer and found that giving them a high dose of particular
vitamins namely folate or vitamin A actually accelerated the cancer (2).
This is a really important point that I want to emphasize. You need to understand the potential
mechanism before designing a clinical trial in which the treatment may actually harm people. For
example, folate is an essential B vitamin because it is required for DNA replication and DNA
repair among other things. Folate is required for the incorporation of a specific nucleotide,
thymine into DNA. This is important because your body synthesizes new DNA as it makes new
cells, meaning folate is required to make DNA for newly made cells. However, if you already
have cancer, taking high doses of folic acid is not a good thing because cancer (among other
things) is a disease of rapid and excessive cellular proliferation. This means that cancer cells
require a continuous supply of nucleotides, amino acids, and energy to flourish. Since folate it
necessary to make new DNA, cancer cells may use this to their advantage because they are
continuously making new DNA. The results of the study are very specific to folate, and not
something that should be generalized to other vitamins and minerals. The fact of the matter is
that inhibition of folate metabolism is a well-established chemotherapeutic target for many types
of cancer. This does not mean, however, that folate is bad if you do not have cancer, having
adequate levels of folate is very important to prevent cancer. In fact, inadequate folate levels
actually damage your DNA -- which is itself known to cause cancer -- in a manner not unlike
irradiation (3).
One other vitamin that has shown similar paradoxical effects is vitamin A. Vitamin A ultimately
gets converted into a steroid hormone, retinoic acid, which regulates the transcription of many
different genes. For example, Retinoic acid plays an important role in the function of the immune
system, which is important to fight off cancer.
With that said, it has been shown that individuals at high risk for lung cancer due to smoking
cigarettes or asbestos exposure should avoid high doses of vitamin A because it can accelerate
carcinogenesis (3). The same dose of vitamin A given to non-smokers does not affect cancer
incidence. It has been shown that the lungs of smokers have a highly oxidative environment in
addition to low levels of anti-oxidants such as vitamins C and E (3). Under these highly
oxidative conditions caratenoids can be cleaved into products that can damage DNA (which is
known to cause carcinogenesis) and these cleaved products also interfere with caratenoids
forming active vitamin A hormone (3).
As for the negative effects of high doses of particular vitamins, it is important to differentiate
between the effects on someone in a healthy versus diseased state. In the case of folate,
inadequate levels in a healthy person can cause cancer but for someone that already has cancer,
high doses of folate is fuel to feed the cancer cells. In the case of vitamin A, people that are
smokers or have been exposed to asbestos, need to be cautious about supplementing with high
doses of vitamin A and this does not appear to be the case for non-smokers. Well, everyone
should be cautious about high doses of vitamin A since it is fat-soluble it can be toxic at high
levels to anyone. Too much of a good this can sometimes be a bad thing.
There are also multitude of well-done studies that have shown the protective effects of vitamin D
on cancer incidence and metastasis. Theses studies have shown that people with adequate levels
of vitamin D have a decreased cancer incidence and all-cause mortality. Additionally, the same
has been shown for individuals that have already had cancer: adequate levels of vitamin D were
associated with decreased metastasis and relapse.
I also want to point out that many micronutrients are important for immune function, which is a
critical line of defense against cancer. You need your immune cells to be functioning at their best
so having micronutrient inadequacies is one way to ensure that will not happen.
Now lets take a look at the two studies that investigated the effect of V/M
supplementation on cognitive function:
The first study looked at the effects of vitamin D on cognition and while this study actually used
adequate doses of vitamin D (5,000 IU/day), the serum levels of vitamin D after treatment were
39ng/ml compared to the placebo, which was 30ng/nl (2). Both the placebo and treatment
groups were in the adequate range so it is difficult to make any conclusions about the effect of
vitamin D on cognitive function. If you want to investigate the effects of vitamin D on cognitive
function then I suggest comparing populations that have different serum levels of vitamin D. The
second study looked at the effects of a multivitamin similar to centrum silver on cognitive
function in men over 65 but did not measure any serum levels of V/M at baseline or after
treatment (4). Therefore, with no biochemical analysis, no conclusions can be made. An
additional drawback of this study was that cognitive function was assessed by a phone call
instead of any substantive, quantitative metric.
Lets look at the effects on cardiovascular disease:
Two studies looked at the effect of long-term multivitamin supplementation on cardiovascular
diseases. In both studies, no biochemical data on serum levels of vitamins or minerals were
provided either at baseline or at the followup. Also, one study required taking 6 pills a day for
4.5 years and with no biochemical data, there is no real way to no if people were compliant (5).
Therefore, the conclusions are questionable. Again to highlight the importance of biochemical
data, one study demonstrated that vitamins C and E supplementation significantly reduced
incidence of athleroslerotic lesions (2). They showed that plasma vitamin E levels increased by
90% and the vitamin C levels increased by 72% after supplementation (2). Why was this
positive effect not mentioned in the editorial? Could it be that the positive effects will not grab
the attention of the press?
In summary:
If you are going to take time to attempt to compile data collected from nutritional clinical trials, I
suggest you understand how to critically analyze the data. Clinical trials in nutrition are extremely
difficult to do right. It is imperative to measure vitamin/mineral concentrations in the plasma both
BEFORE and AFTER treatment.
The failures of this editorial are the following:
Failures to critically analyze the data in the studies and over generalizing the results.
Lumping all vitamins and minerals together when effects depend on dose and even
individual disease status.
Failure to quantitate any vitamin/mineral concentrations at baseline or follow-up.
The answer is not to end all research and stop supplementation of vitamins and minerals s
Instead, the answer is quite the opposite. It is to do MORE research and establish what those
very specific edge cases are and for healthcare providers to make recommendations based on
knowledge of the positive and negative effects and not to make poorly-informed
recommendations caused by lack of knowledge or from having read too many highly misleading
editorials.
References
1. Bailey RL, Fulgoni VL, 3rd, Keast DR, & Dwyer JT (2012) Examination of
vitamin intakes among US adults by dietary supplement use. Journal of the
Academy of Nutrition and Dietetics 112(5):657-663 e654.
2. Fortmann SP, Burda BU, Senger CA, Lin JS, & Whitlock EP (2013) Vitamin
and Mineral Supplements in the Primary Prevention of Cardiovascular
Disease and Cancer: An Updated Systematic Evidence Review for the U.S.
Preventive Services Task Force. Annals of internal medicine.
3. Russell RM (2004) The Enigma of -Carotene in Carcinogenesis: What Can
Be Learned from Animal Studies. The Jpurnal of Nutrition 134:262-268.
4. Grodstein F OBJ, Kang JH, Dushkes R, Cook NR, Okereke O (2013) Long-term
multivitamin supplementation and cognitive function in men. A
randomized trial. Ann Intern Med. 159:601-612.
5. Lamas GA BR, Goertz C, Mark DB, Rosenberg Y, Stylianou M. (2013) Oral
high-dose multivitamins and minerals after myocardial infarction. A
randomized trial. Ann Intern Med. 159:797-804.