Vitamin D: Is It the Best Thing
Under the Sun?
Robert
Finn; Deborah Flapan; Darbe Rotach Contributor Information
February 7, 2013
Vitamin
D and Bone
Vitamin
D has long been known to play an important role in bone health, and several
recent studies provided additional confirmation. One study[1]
suggested that low levels of vitamin D increase the risk for forearm fracture
in children, and another[2] showed that girls who consumed the most
vitamin D had the lowest risk for stress fractures. It's not just children who
are at risk: 44% of postmenopausal women treated for distal radius fracture
were vitamin D deficient or insufficient. And a meta-analysis[3]
showed that high doses of vitamin D lower the risk for fracture by 14% to 30%
in people age 65 years or older.
Vitamin
D and Respiratory Infections?
If
Linus Pauling were alive today, perhaps he would turn his attention away from
vitamin C and write "Vitamin D and the Common Cold."
One
randomized controlled trial[4] suggested that vitamin D
supplementation reduced acute respiratory tract infections in children during
the long, cold, and dark Mongolian winter. Another randomized controlled trial[5]
showed that vitamin D reduced symptoms and antibiotic use in a group of
patients with an increased frequency of respiratory infections. On the other
hand, a third randomized controlled trial[6] showed no effect of
vitamin D on reducing the incidence or severity of respiratory infection in
healthy adults.
Links
to Diabetes
Low
levels of vitamin D have been linked to several types of diabetes. A study[7]
conducted in Australia found that children with type1 diabetes are more likely
to have low levels of vitamin D. It's unclear, however, whether low levels of
vitamin D caused the diabetes or vice versa. A larger study,[8] in
active-duty military personnel in the United States, found that those with low
levels of vitamin D were more likely to develop insulin-requiring diabetes
within 1 year. And women who have low vitamin D levels during their first
trimester of pregnancy were more likely to develop gestational diabetes.
Vitamin
D and Cardiovascular Disease
Numerous
epidemiologic studies, including the largest one to date,[9] suggest
that a low vitamin D level increases the risk for cardiovascular disease. But
there may be a threshold effect,[10] with heart health improving as
circulating vitamin D levels increase from 20 to 60 nmol/L, followed by a
plateau or perhaps even an increase in risk at higher levels. Unfortunately, a
randomized controlled trial among older women failed to find evidence that
vitamin D supplementation[11] improved markers of heart
health.
Obesity
Women
with low levels of vitamin D during pregnancy[12] may have children
that are more prone to excess body fat at age 6 years. Furthermore, children
ages 6 to 18 years[13] who are overweight are more likely to have
low vitamin D levels. Adequate levels of vitamin D are associated with less
weight gain among women age 65 and older.[14]
Vitamin
D and Cancer
Less
information has been published about connections between vitamin D and cancer,
but some developments have occurred in the past year. In a result the
researchers termed "unexpected," women with breast cancer who were
being treated with zoledronic acid for bone complications had a lower risk for
bone recurrence if they had sufficient vitamin D levels. Vitamin D
supplementation may help breast cancer survivors adhere to adjuvant treatment
with aromatase inhibitors. And differences in vitamin D–related genes may
contribute to increased susceptibility to colon cancer among black Americans. Photo
Neurologic
Function
Vitamin
D has been tied to several higher neurologic functions. Studies have linked
autism to low vitamin D during pregnancy, a connection that was strengthened by
a map showing that autism rates were highest among children living in states
with the lowest levels of ultraviolet B radiation.[15] People with
Alzheimer's disease tend to have low levels of vitamin D, and better cognitive
test results are linked to higher vitamin D levels.[16] Vitamin D3
may help clear the brain of amyloid-β.[17] And low vitamin D levels
in pregnant women have been associated with poor language development in their
offspring.[18]
Stroke
and Multiple Sclerosis
Data
from the Honolulu Heart Program show that people with low dietary vitamin D at
baseline were about 25% more likely to sustain thromboembolic stroke, but not
hemorrhagic stroke, during the ensuing 34 years.[19]
The
last year has seen a flurry of studies linking vitamin D to multiple sclerosis
(MS), and all of them tie low levels of vitamin D to the disease. Three of
these studies were published in a single issue of the journal Neurology.
Another study linked low levels of vitamin D plus exposure to the Epstein-Barr
virus to the development of MS.[20] Low vitamin D levels predict a
near-term conversion of clinically isolated syndromes to definite MS. And the
risk of developing MS has been linked to lower sun exposure in early life.
Pain
About
half of women prescribed aromatase inhibitors for metastatic breast cancer
suffer intense musculoskeletal pain,[21] but high-dose vitamin D2
supplements appear to help. A single oral dose of 300,000 IU of vitamin D
appears to help with dysmenorrhea.[22] And a low level of vitamin D
in black Americans increases the risk for knee osteoarthritis pain.[23]
Lung
Disorders
High-dose
vitamin D may speed tuberculosis recovery.[24] And low vitamin D
levels appear to be linked to the need for steroids in asthma and may also
blunt the effectiveness of asthma treatment.[25]
For
chronic obstructive pulmonary disease, however, the story isn't as clear cut.
According to one study, high-dose vitamin D supplementation improves exercise
capacity and respiratory muscle strength during rehabilitation. But according
to another, high-dose supplements failed to prevent exacerbations or secondary
outcomes.[26]
Gastrointestinal
Disorders
Women
with sufficient vitamin D levels at baseline are 62% less likely to develop
Crohn's disease over 22 years than those with vitamin D insufficiency.[27]
Women
living at southern latitudes in the United States are 52% less likely to have
inflammatory bowel disease than those living in the north.[28]
Kidney
Disease
Vitamin
D deficiency is almost universal among patients with chronic kidney disease
(CKD).[29] Two recent studies independently concluded that high-dose
cholecalciferol (vitamin D3) supplementation safely prevents[30]
and corrects this in patients undergoing dialysis. Vitamin D supplementation
also lowers hepcidin levels in patients with CKD.
But
Wait, There's More
Within
the past year, studies have shown that vitamin D may reduce risk for dental
caries,[31] low vitamin D may be a result of depression,[32]
vitamin D deficiency increases risk for perforated eardrums, and low vitamin D
is linked to food allergy. And the list goes on.
How
Much Is Enough?
There's
little consensus about what blood levels of vitamin D are adequate, and even
less on how much supplementation is enough. The Institute of Medicine says
blood levels should be 20 ng/mL, but the Endocrine Society sets the level at 30
ng/mL. The US Recommended Dietary Allowance is 600 IU for people ages 1 to 70
years and 800 IU for those who are older. Some authorities recommend that
people who are deficient should receive supplements of 1000 to 2000 IU daily,
but others have recommended single-bolus doses of up to 500,000 IU.
How
to Measure?
If
there's little agreement on how much vitamin D we need, there's even less on
how to measure blood levels. You can choose an old, slow, but accurate method,
or you can choose one of several new and fast but wildly inaccurate methods.
According to one study, these rapid tests may be inaccurate as much as 40% of
the time, most often characterizing patients as vitamin D deficient when
they're not.
Elixir
of Life?
While
vitamin D appears to be involved in almost every body system, some researchers
are looking at the big picture — overall mortality. Oral active vitamin D is
associated with reduced all-cause mortality in patients undergoing peritoneal
dialysis. Vitamin D has also been linked to lower mortality in patients with
pneumonia.[33] And a large meta-analysis found that increased intake
of vitamin D plus calcium, but not vitamin D alone, is linked to a decrease in
all-cause mortality among elderly patients.[34]
And
Now for Something Completely Different
So
if you've been paying attention to the previous slides, they nearly all seem to
point in one direction: Lower levels of vitamin D bad, higher levels good or
neutral. Case closed? Maybe not. A recent study suggests that some people with
a genetic predisposition to longevity have a reduced frequency of a gene
variant that predisposes people to high vitamin D levels. They also have lower
levels of vitamin D.[35] If only science gave us simple, unambiguous
answers!
******************************
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Vitamin D: More may not be better
Benefits in healthy adults wear off at higher doses, research suggests
In recent years, healthy people have been bombarded by stories in the media and on health websites warning about the dangers of too-low vitamin D levels, and urging high doses of supplements to protect against everything from hypertension to hardening of the arteries to diabetes.
But new research from Johns Hopkins finds that blood levels of the so-called "sunshine vitamin" higher than the top of the range suggested by the Institute of Medicine confer no additional benefit. This finding, combined with results of a previous study by the same group noting potential harm from higher vitamin D levels in healthy people, has urged investigators to prescribe caution.
"Healthy people have been popping these pills, but they should not continue taking vitamin D supplements unchecked," says study leader Muhammad Amer, M.D., M.H.S., an assistant professor in the Division of General Internal Medicine at the Johns Hopkins University School of Medicine. "At a certain point, more vitamin D no longer confers any survival benefit, so taking these expensive supplements is at best a waste of money."
Amer stresses that there are some groups of people — elderly, postmenopausal women, and people with kidney disease — who do benefit from higher blood levels of a vitamin vital to bone health. Such groups may need to take supplements.
In an article published online in the American Journal of Medicine, Amer and Rehan Qayyum, M.D., M.H.S., also of Johns Hopkins, describe their review of data from more than 10,000 participants in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2004. They matched those data with mortality data from the National Death Index through Dec. 2006.
When they looked at deaths from all causes and cardiovascular disease specifically, those with blood levels of 21 nanograms per milliliter of 25-Hydroxyvitamin D — at the top of the range that the IOM considers "adequate" and at the low end of "normal" — cut their risk of death in half. Above 21 nanograms per milliliters, the data suggest that the protective effect appears to wear off.
The primary source of vitamin D is the sun, and although it is found naturally in very few foods, commercially sold milk is usually fortified with it. Amer says as people spend more and more time indoors and slather their bodies with sunscreen when outdoors, concern is rising that many are vitamin D-deficient. But he says there is no set amount of supplementation that can bring someone up to 21 nanograms per milliliter because the way people process vitamins varies.
In research published in January 2012 in the American Journal of Cardiology, Amer and Qayyum found that increasing levels of vitamin D in the blood are linked with lower levels of a popular marker for cardiovascular inflammation — c-reactive protein (also known as CRP). Beyond blood levels of 21 nanograms per milliliter, any additional increase in vitamin D was associated with an increase in CRP, a factor linked to stiffening of the blood vessels and an increased risk of cardiovascular problems. The team's unpublished research also suggests a link between excess vitamin D and elevated homocysteine levels, another danger sign for cardiovascular disease.
People should consult with their doctors, Amer says, before starting vitamin D supplements and should have their blood levels checked. Still, he says, "most healthy people are unlikely to find that supplementation prevents cardiovascular diseases or extends their lives," and there is no consensus among doctors on what is the right level of vitamin D in the blood for healthy people.
"There are a lot of myths out there and not enough data," he concludes.
Qayyum's work is supported by a grant from the National Heart, Lung, and Blood Institute (1K23HL105897-01).
Media Contacts:
Stephanie Desmon
410-955-8665; sdesmon1@jhmi.edu
Helen Jones
410-502-9422; hjones49@jhmi.edu
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