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JAMDA 15 (2014) 229e231

JAMDA
journal homepage: www.jamda.com

Editorial

Vitamins: The Good, the Bad, and the Ugly


John E. Morley MB, BCh *
Divisions of Geriatric Medicine and Endocrinology, Saint Louis University School of Medicine, Saint Louis, MO

The only consistent nding in the prospective studies of diet


and coronary heart disease is that higher total energy intake, is
associated with lower rates of disease.
Walter Willett
The data that a healthy diet rich in fruits and vegetables is associated with increased longevity and improved quality of life is overwhelming.1,2 In some magical way, this has been translated into the
concept that rather than eating a healthy diet, a quick x is to take
multivitamins or other supplements. Fifty-three percent of persons in
the United States take supplements, with 39% using multivitamins.
The supplement industry is worth $14 billion. In the last year, there
was a 5.7% increase in spending on supplements in the United States.

Antioxidants
A recent Cochrane Review3,4 reported on the use of antioxidants
for prevention of mortality in 296,707 adults. Overall, antioxidant
supplements had a 22.7% mortality compared with a 10.2% in placebo.
This was not signicant. In 56 trials where there were minimal risks
of bias, antioxidants had a signicant increase in mortality (relative
risk 1.04; 1.01e1.07). The evidence that Vitamin E and beta-carotene
increased mortality was strong. Higher doses of vitamin A also
increased mortality.
A 2007 satirical novel, Boomsday by Christopher Buckley5 suggested that boomers should be given nancial incentives to commit
suicide and thus reduce the burden on younger persons who were
responsible for generating the money to pay for their Social Security.
It would appear that if the data on antioxidants and the increase in
supplement purchases are to be taken at face value, the young need
not worry as Boomercide appears to already be occurring with the
older persons actually putting money back into the economy while
doing it!
The fact that antioxidant supplements fail to extend life is not
surprising. Simply put, free radicals are essential for survival. Free
radicals are essential as part of the bodys defense against infections
and cancer. In addition, free radicals play an important role as
neurotransmitters (eg, nitric oxide) and increasing blood ow (eg,
nitric oxide again) and in modulating a variety of signaling pathways.
The author declares no conicts of interest.
* Address correspondence to John E. Morley, MB, BCh, Division of Geriatric
Medicine, Saint Louis University School of Medicine, 1402 S. Grand Blvd, M238,
St. Louis, MO 63104.
E-mail address: morley@slu.edu (J.E. Morley).

A clear example of the deleterious effect of antioxidants is that when


an antioxidant is given before exercise training, it inhibits the increase in endothelial mediated vasodilation, which would normally
occur with exercise.6 Antioxidants also prevent exercise-dependent
induction of insulin sensitivity,7e9 though this may not be true for
alpha-lipoic acid10 (Figure 1).
While supplements fail to produce benet, there is emerging data
that food itself has magical properties. For example, cruciferous foods
such as broccoli decrease cancer risk, though this is only true in persons with certain genetic variants.11 This appears to be due to the fact
that sulforaphane from broccoli modulates NrF-2 leading to a decrease
in oxidative stress. There is much data that olive oil will reduce the
odds of rst myocardial infarction, mortality, and the chances of
developing Alzheimers disease.12e21 In an animal model of Alzheimers disease, extra-virgin olive oil improved memory and reduced
oxidative damage.22 Olive oil is a polyphenol and another polyphenol,
resveratrol, which is present in red wine has been suggested to
enhance health.23 Resveratrol is thought to produce these effects
through sirtuins, which increase lifespan in ies and mice. Sirtuins play
a role in enhancing mitochondrial energy metabolism, and enhancing
DNA repair. At present, there is no data supporting the use of resveratrol as a supplement or sirtuins for improving human health.
A recent article in JAMA suggested that vitamin E slowed functional deterioration in early Alzheimers disease.24 Unfortunately, the
change was miniscule and vitamin E had no effect when given with
memantine. The only value of the study was that memantine did not
work! A study of vitamin E in mild cognitive impairment failed to
show any effect.25 The Cochrane Analysis found no effect of vitamin E
in Alzheimers disease.
It has been suggested that substances that diffuse freely across the
inner mitochondrial membrane can stabilize the mitochondrial
membrane and improve electron ow to proton movement. Agents
that do this better than vitamin E are coenzyme Q10 and alpha lipoic
acid. In Alzheimers disease, it appears that elevated amyloid-beta
protein damages the mitochondrial membrane releasing excess free
radicals and producing oxidative damage.26e28 In our studies on
SAMP8 mice, an animal model of Alzheimers disease, we found that
alpha-lipoic acid decreased oxidative damage in the brain and
reversed memory decits.29,30 Unfortunately, alpha-lipoic acid also
decreased survival time.31 One poorly controlled study out of Germany in humans has suggested a positive effect of alpha-lipoic acid
on dementia in humans.32 Mitoquinone with direct mitochondrial
effects have been shown to have positive effects in animals and
appear to be safe for up to a year in humans.33

1525-8610/$ - see front matter 2014 - American Medical Directors Association, Inc. All rights reserved.
http://dx.doi.org/10.1016/j.jamda.2014.01.013

230

Editorial / JAMDA 15 (2014) 229e231

Data supports that calcium and vitamin D will reduce hip fracture.54,55 Data is less solid but does suggest that vitamin D supplement in persons who are truly vitamin D decient may decrease falls
and mortality.56e58 Vitamin D deciency may also play a role in
cognitive function.59 There is no evidence suggesting a need for more
than 1000 IU per day.
Conclusions

Fig. 1. Effect of antioxidants on exercise.

The vitamin and supplement industry is poorly regulated by the


Food and Drug Administration. It gives the right of manufacturers to
provide food extracts that are generally regarded as safe to the public
with minimal requirements. It has become clear that these supplements should be regulated to the same extent as drugs.
The question arises whether persons who are frail and/or
malnourished and are eating less than a 1000 Kcal a day should take
a multivitamin.60e68 There is some data to suggest that vitamin
deciency in these persons may increase delirium and cognitive
impairment.69 Here again food, perhaps as a fruit drink, would appear
to be a better method to give vitamins, particularly as liquid caloric
supplements between meals increase food intake.70e72
Overall, it would appear that most nursing home residents should
receive 1000 IU of vitamin D a day, and otherwise, only when clear
vitamin deciency is demonstrated (eg, vitamin B12 deciency).
References

Perhaps the most exciting data in the utility of preventing


oxidative damage comes from the studies of CisD2.34 CisD2 plays a
major role in maintaining the outer membrane of the mitochondria.
CisD2 knockout mice develop premature aging while CisD2 transgenic
mice have a 5-month increase in lifespan. CisD2 decreases with aging
in mice and humans.
Thus, data to date suggested a limited effect of antioxidants in
having positive effects and a substantial negative effect. Future
development in this eld will require a focus on reducing reactive
oxygen species leaks and preventing mitochondrial apoptosis due to
mitochondrial membrane damage.

Other Vitamins
Data from Europe has consistently suggested that reducing
elevated homocysteine levels with folate may reduce coronary artery
disease, Alzheimers disease, and osteoporosis.35e37 The data from the
United States has in general been negative.38,39 This is explained by
folate supplement of food in the United States. The most common
reason for elevated homocysteine in the United States is renal failure.
Thus, folate deciency is rare in the United States and is mostly due to
drugs such as methotrexate.
Vitamin B12 deciency is due to pernicious anemia, bacterial
overgrowth, and drugs (metformin and proton pump inhibitors).40 It
is a common treatable cause of dementia and should be replaced
when deciency is demonstrated by nding an increase in methylmalonic acid.41
Vitamin D deciency is a common problem in older persons.42e45
The interpretation of vitamin D levels are made difcult by the poor
quality of many assays and the fact that vitamin D binding protein
levels need to be measured if the true bioavailable vitamin D level is
to be determined.46 The Institute of Medicine has suggested that
25(OH) vitamin D levels should be between 20 and 25 ng/dL to return
parathormone to normal ranges.47,48 Others have suggested a higher
range but there is no good data to support this.49 In older persons,
exposure to 30 minutes of sun or ultraviolet light can restore values
to normal.50e53

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