Long
known for promoting bone health, vitamin D has also been linked to brain
health. Our experts assess the evidence and explain how to overcome a
deficiency.
Paturel, Amy
April/May 2016
In the popular press, vitamin D is
hyped as a panacea for everything from overall health and well-being to protecting
the brain from disease. With nearly 3,000 articles in the medical literature,
it's also a compelling research topic.
Amid the
hype, however, experts such as David S. Knopman, MD, FAAN, a professor of
neurology at the Mayo Clinic in Rochester, MN, caution that the rush to embrace
vitamin D has outpaced available evidence, especially regarding the vitamin's
role in neurologic conditions.
To find
the middle ground, we spoke to researchers about what the evidence says about
vitamin D and brain health—and how much vitamin D is enough.
VITAMIN
D BASICS
By
definition, the body cannot manufacture vitamins; they must be ingested. But
the body can make vitamin D when sunlight shines on the skin's top layer.
Whether it's ingested in food, obtained from the sun, or taken as a supplement,
vitamin D must still be processed by the liver and kidneys before it becomes
“active,” says Tinatin Chabrashvili, MD, PhD, an associate professor of
neurology at Tufts University School of Medicine in Boston.
“The
active form of vitamin D is not a pure vitamin. It's a hormone that has the
ability to turn genes on and off,” says Dr. Chabrashvili. A variety of tissues,
including the heart, brain, and immune cells, have vitamin D receptors. Think
of vitamin D receptors as your car's gas tank and the active form of vitamin D
as the fuel. When you put active vitamin D—also called 25-hydroxyvitamin D, or
25(OH)D—into the tank (and it binds to those receptors), it regulates the
expression of at least 900 genes.
“Vitamin
D also may protect the brain through its anti-inflammatory and immune-boosting
properties,” says Majid Fotuhi, MD, PhD, a neurologist at Johns Hopkins
Medicine in Baltimore. In a 2012 study in the Journal of Immunology,
researchers at National Jewish Health incubated human white blood cells with
varying levels of vitamin D, then exposed them to a molecule known to trigger
inflammation. Cells with adequate levels of the nutrient (30 ng/mL) inhibited
inflammation better than cells incubated at 15 ng/mL. At even higher levels (50
ng/mL), vitamin D's inhibitory effects on inflammation were more pronounced.
A
DEFICIENCY TREND
The sun
has proven to be a powerful source for vitamin D. The body can make 10,000
International Units (IU) of vitamin D in just 15 to 30 minutes of unprotected
exposure to sunshine. Today, most people spend their time indoors, slather on
sunscreen when they're outside, and wear protective clothing such as
broad-brimmed hats to reduce skin cancer risk. Plus, a one-time dose of
sunshine disappears within a few weeks and likely isn't replenished during
winter months. So, perhaps not surprisingly, researchers have noticed a trend
toward vitamin D deficiency in recent decades. In fact, according to a 2008 study
in the American Journal of Clinical Nutrition, as many as 1 billion
people worldwide have a deficiency—and not just in cloudy, rainy places far
from the equator. People in California and Florida, for example, may also be
vulnerable.
Most
experts agree that the optimal blood level of vitamin D (meaning the amount of
active vitamin D circulating in the bloodstream) is between 20 and 40 ng/mL.
Yet, according to some estimates, nearly 70 percent of Americans fall short of
the 30 ng/mL threshold, and up to 15 percent are severely deficient (less than
10 ng/mL). Those numbers skyrocket among people with brain disorders. An
estimated 80 percent of people with multiple sclerosis (MS) and 90 percent of
people with dementia have vitamin D levels of less than 20 ng/mL. Researchers
suspect people with Parkinson's or Alzheimer's disease and the elderly are
similarly deficient.
“Aging
reduces skin thickness, which inhibits the body's ability to make vitamin D
from sun exposure,” says David Llewellyn, PhD, a senior research fellow in
clinical epidemiology at the University of Exeter in the United Kingdom.
Coupled with reduced dietary intake of vitamin D and the impaired intestinal
absorption that also accompanies aging, deficiency is almost inevitable.
A
MULTIPLE SCLEROSIS LINK
Over the
past several years, vitamin D deficiency has been associated with an increased
risk of such brain-related disorders as Parkinson's disease, dementia, and,
most compellingly, MS. In a 2004 analysis of data on more than 187,000 women
enrolled in the Nurses' Health Study published in Neurology, a team of
Harvard researchers reported that those who ingested more vitamin D from food
(approximately 700 IU/day) had a 41 percent lower risk of MS compared to women
with lower intakes; those who took vitamin D supplements (400 IU/day or more)
had a 33 percent reduced risk of developing the disease compared to those who
did not.
In a 2006
study published in the Journal of the American Medical Association,
Harvard researchers discovered that people, specifically white people, whose
blood levels of vitamin D were above 40 ng/mL had a 62 percent lower risk of
developing MS. More recently, researchers have linked higher blood levels of
vitamin D with reduced risk of relapse, less active lesions on MRI, and
possible neuroprotective effects. Although it's not clear what vitamin D's role
is in relation to MS, one hypothesis is that the vitamin has an impact on the
immune system and that people with MS may have faulty vitamin D receptors.
PRELIMINARY
ASSOCIATION WITH PD
Most
evidence on the link between vitamin D and Parkinson's disease (PD) has been
from animal studies, but recent human trials have also uncovered a connection.
In a July 2010 study published in Archives of Neurology, for example,
Finnish researchers suggested that chronically deficient levels of vitamin D
may play a role in the development of PD. Based on the Mini-Finland Health
Survey, the researchers followed up with 3,173 men and women without PD and
found that those with higher blood levels of vitamin D showed a reduced risk of
the disease. A 2008 study by Emory University researchers also published in Archives
of Neurology found that more people with PD (55 percent) had a vitamin D
deficiency than a control group (36 percent). Scientists don't know how or even
if vitamin D levels affect Parkinson's risk, but the findings are generating
interest in more research.
Low
vitamin D concentrations have also been associated with the development of
dementia and Alzheimer's disease. In a 2014 Neurology study of more than
1,600 people enrolled in the Cardiovascular Health Study, for example, those
who were deficient in vitamin D had double the risk of developing dementia.
“Studies
suggest that vitamin D protects against dementia by helping to break down and
sweep out Alzheimer's disease-related proteins and by enhancing blood flow to
the brain,” says Dr. Llewellyn.
Dr.
Llewellyn's own research, published in Neurology in 2014, revealed that
compared to people with “optimum” vitamin D levels (above 20 ng/mL), those with
the lowest levels (less than 10 ng/mL) not only performed more poorly on a
battery of mental tests, they also had more than double the risk of developing
Alzheimer's disease and other types of dementia. Even a moderate deficiency (10
to 20 ng/mL) was associated with a 53 percent increased risk of developing
dementia and a 69 percent increased risk of developing Alzheimer's disease
compared to those who had adequate levels (more than 20 ng/mL).
Still,
Dr. Knopman questions the link between vitamin D deficiency and age-related
diseases. “Alzheimer's and dementia increase with advancing age and vitamin D
deficiency increases with advancing age, so you have to wonder if the
relationship is incidental or if there's a causal mechanism at play,” he says.
Scientists are trying to tease out the findings.
SUNSHINE
AND SUPPLEMENTS
Popping a
vitamin D supplement may seem like a quick and easy fix, but it's not clear
that supplements make a difference. “Many studies show a strong connection
between low levels of vitamin D and neurologic disease, but not many show that
if you increase vitamin D levels you reverse those deficits,” says Dr. Fotuhi.
Part of
the problem is that countless processes affect vitamin D levels, including
sunlight exposure, dietary habits, and functioning vitamin D receptors. “If patients
have a problem at the receptor level, giving them more vitamin D isn't going to
change their blood level,” says Dr. Chabrashvili. Similarly, the benefits of
supplements also depend on having sufficient levels of other nutrients,
including calcium, magnesium, and zinc. A deficiency in any one of these can
render vitamin D ineffective. In the same way calcium needs vitamin D for
absorption, vitamin D needs these nutrients to bind to vitamin D receptors.
Still,
experts agree that most Americans would do well to maintain a healthy, balanced
diet; get sufficient “safe” sunshine; and recognize that no vitamin or
supplement is a magic bullet for a healthy brain.
What's
Your Vitamin D Status?
Many
Americans aren't getting enough vitamin D. Here's how to make sure you aren't
one of them.
Get
tested. A simple
blood test can measure levels of vitamin D. Based on your results, you and your
physician can decide whether you need to take supplements.
Don't
shun the sun.
For
most people, sitting in the sun for 15 to 20 minutes without using sunscreen is
sufficient to achieve blood levels of vitamin D that hover around 30 ng/mL. (If
you stay in the sun longer than 20 minutes, be sure to apply sunscreen.) But
several factors determine how much vitamin D your body produces from the sun,
including the time of year, the time of day, where you live, and what type of
skin you have. According to a study published in The American Journal of
Clinical Nutrition in 2004, people with lightly pigmented skin, for
example, are approximately five times more efficient than those with darker
skin at synthesizing vitamin D from the sun.
Choose
vitamin D-rich foods.
Natural food sources of vitamin D include fatty fish, egg yolks, and certain
mushrooms, but you have to eat a lot of them to overcome a deficiency. Coupled
with adequate sunshine, fortified foods (including milk, yogurt, cereal, and
orange juice) can also help you achieve your daily quota.
Take a
supplement.
Opt for
vitamin D3 (cholecalciferol), an active form that's more readily absorbed than
its vitamin D2 (ergocalciferol) counterpart. Depending on your level of
deficiency, experts recommend taking 600 to 4,000 IU daily for a target range
of 30 to 50 ng/mL. “If you're significantly deficient, go to a higher dose, but
remember that absorption may be an issue,” says Dr. Chabrashvili. “If I give
you more, that doesn't mean you will absorb it. There may also be toxicity
concerns.”
Reassess
regularly.
If your
initial blood test indicates you have a deficiency, your doctor may want to
monitor your blood levels every three to six months until you reach the target
zone. Those who test at appropriate levels (usually above 30 ng/mL) may repeat
testing every two years. Experts recommend using the same lab every time you
get tested.
People
absorb vitamin D differently, so taking more isn't always more effective.
As the
research rolls in, experts continue to refine their dosage recommendations for
vitamin D supplements. In 2010, the nonprofit Institute of Medicine (IOM)
doubled the upper tolerable intake for adults from 2,000 to 4,000 IU per day.
Research suggests that taking substantially larger doses for a short time or
periodically (for example, 50,000 IU/week for 8 weeks) does not cause toxicity.
In a 2010 study of 75 patients with multiple sclerosis published in Neurology,
for instance, daily doses of 10,000 to 14,000 IU of vitamin D per day did not
negatively affect blood calcium levels or produce adverse events.
But while
some vitamin D is good, more is not necessarily better. There's limited
long-term data on intakes above 2,000 IU daily. Even if 3,000 to 4,000 IU daily
hasn't been linked with adverse events, scientists don't know if the benefits
outweigh the risks because the research hasn't been done yet. And extremely
high doses (over 50,000 IU) can cause nausea, vomiting, weakness, and fatigue.
More seriously, according to the IOM, it can also raise blood levels of
calcium, causing confusion, kidney problems, and heart rhythm abnormalities.
How the
Body Converts Vitamin D
Once
vitamin D enters the body, either from the sun, food, or supplements, it is
processed by both the liver and the kidneys before it becomes active. The liver
converts it into 25-hydroxyvitamin D, or 25(OH)D; the kidneys into
1,25-dihydroxyvitamin D, or 1,25(OH)2D. Since 1,25(OH)2D remains in the body
for only 15 hours and levels don't drop until there's a severe deficiency,
scientists measure levels of 25(OH)D, which stays in the body for 15 days, to
assess vitamin D stores. Nevertheless, it's not clear to what extent, if any,
25(OH)D levels reflect health outcomes. Another caveat: Blood levels of 25(OH)D
do not account for the amount of vitamin D stored in body tissues.
Scientists
continue to study how the nutrient influences brain function. Here's a sampling
of some ongoing clinical trials.
Vitamin
D Assessment Study (ViDA): University of Auckland researchers followed 5,000 New Zealanders
between the ages 50 and 84 to determine why vitamin D levels are low, how those
levels impact their risk of disease, and whether taking supplements offers any
protection. Results are expected in 2016. http://bit.ly/ViDA-study
Vitamin
D and Omega-3 Trial (VITAL): Researchers from Brigham and Women's Hospital are
investigating whether taking daily doses of 2,000 IU of vitamin D or a 1 gram
supplement of omega-3 fatty acids can reduce the risk of cancer, heart disease,
and stroke among healthy people with no history of these diseases. So far, more
than 25,874 people have been enrolled. http://vitalstudy.org
The
International Polycap Study-3 (TIPS-3): This five-year study is testing whether a combination pill
of a low dose of aspirin and vitamin D helps protect against cardiovascular
disease, cancers, and fractures among 5,000 men and women from 10 countries
with no known heart disease or prior stroke. The study will be conducted by an
international group of scientists and physicians and coordinated by the
Population Health Research Institute at Hamilton Health Sciences in Ontario,
Canada. http://bit.ly/TIPS-3
Finnish
Vitamin D Trial (FIND): Finnish researchers are investigating whether a vitamin D supplement
(1,600 IU or 3,200 IU) can be the primary prevention of cancers and
cardiovascular disease, including stroke, among 18,000 men and women over age
60 and 65, respectively. Recruitment began in 2012 and is ongoing. http://bit.ly/FIND-trial
Vitamin
D3-Omega3-Home Exercise-Healthy Ageing and Longevity Trial (DO-HEALTH): This multicenter international
research effort involving more than 2,000 men and women over age 70 spans five
countries (Switzerland, France, Germany, Portugal, and Austria) and will follow
subjects for a total of three years. The goal is to investigate whether a combination
of 2,000 IU per day of vitamin D, omega-3, and physical exercise can prevent
disease in five primary endpoints, including cognitive decline. Enrollment has
ended and results are expected in 2017. http://bit.ly/DO-HEALTH
D-Health: Funded by a research grant from the
National Health and Medical Research Council of Australia, this study of 25,000
Australians between the ages of 60 and 84 looks at whether taking a vitamin D
tablet changes the risk of a person being diagnosed with heart disease, stroke,
cancer, or infections such as the flu. http://bit.ly/D-Health
© 2016
American Academy of Neurology
http://journals.lww.com/neurologynow/Fulltext/2016/12020/Vitamin_D_Download__Long_known_for_promoting_bone.21.aspx
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