Vitamin D in Brain Function

In a definitive critical review, scientists at Children’s Hospital &
Research Center Oakland ask whether there is convincing biological or
behavioral evidence linking vitamin D deficiency to brain dysfunction.
Joyce C. McCann, Ph.D., assistant staff scientist and Bruce N. Ames,
Ph.D., senior scientist at Children’s Hospital Oakland Research
Institute (CHORI) conclude that there is ample biological evidence to
suggest an important role for vitamin D in brain development and
function, and that supplementation for groups chronically low in vitamin
D is warranted. Their conclusions will be published on April 22, 2008 in
the Federation of American Societies for Experimental Biology (FASEB)

“This critical analysis of vitamin D function and the brain is a model
of careful thinking about nutrition and behavior”, says Gerald
Weissmann, MD, Editor-in-Chief of the FASEB Journal “One wishes that all
studies of nutritional supplements or requirements were this thoughtful.
Drs. McCann and Ames deftly show that while vitamin D has an important
role in the development and function of the brain, its exact effects on
behavior remain unclear. Pointing to the need for further study, the
authors argue for vitamin D supplementation in groups at risk.”

Vitamin D has long been known to promote healthy bones by regulating
calcium levels in the body. Lack of sufficient vitamin D in very young
children results in rickets, which can be easily prevented by vitamin D
supplements. Only recently the scientific community has become aware of
a much broader role for vitamin D. For example, we now know that, in
addition to its role in maintaining bone health, vitamin D is involved
in differentiation of tissues during development and in proper
functioning of the immune system. In fact, over 900 different genes are
now known to be able to bind the vitamin D receptor, through which
vitamin D mediates its effects. In addition to protecting against
rickets, evidence now strongly indicates that a plentiful supply of
vitamin D helps to protect against bone fractures in the elderly.
Evidence also continues to accumulate suggesting a beneficial role for
vitamin D in protecting against autoimmune diseases, including multiple
sclerosis and type I diabetes, as well as some forms of cancer,
particularly colorectal and breast.

Vitamin D is present in only a few foods (e.g., fatty fish), and is also
added to fortified milk, but our supply typically comes mostly from
exposure to ultraviolet rays (UV) in sunlight. UV from the sun converts
a biochemical in the skin to vitamin D, which is then metabolized to
calcitriol, its active form and an important hormone. Formation of
vitamin D by UV can be 6 times more efficient in light skin than dark
skin, which is an important cause of the known widespread vitamin D
deficiency among African Americans living in northern latitudes. Dark
skin has been selected during evolution because it protects against the
burning UV rays of the sun in the tropics. White skin has been selected
for allowing as much UV exposure to make sufficient vitamin D in
Northern (high) latitudes. Thus, fair-skinned northerners are at risk in
Australia or Arizona for sunburns and UV-induced cancer, while
dark-skinned people in the Northern U.S. or European latitudes with
little exposure to the sun are at risk for rickets, bone fractures and
possibly other diseases including several types of cancer due to a lack
of vitamin D. Fortunately sun-screens and vitamin D supplements are

McCann & Ames point out that evidence for vitamin D’s involvement in
brain function includes the wide distribution of vitamin D receptors
throughout the brain. They also discuss vitamin D’s ability to affect
proteins in the brain known to be directly involved in learning and
memory, motor control, and possibly even maternal and social behavior.
The review also discusses studies in both humans and animals that
present suggestive though not definitive evidence of cognitive or
behavioral consequences of vitamin D inadequacy. The authors discuss
possible reasons for the apparent discrepancy between the biological and
behavioral evidence, and suggest new, possibly clarifying avenues of

Many vitamin D experts advise that the currently recommended level of
vitamin D intake is much too low and should be raised to protect against
bone fractures and possibly cancer in addition to rickets (2). Indeed,
even using present guidelines, too many Americans have low vitamin D
blood levels. McCann & Ames propose that, despite uncertainty regarding
all of the deleterious effects of vitamin D inadequacy, the evidence
overall indicates that supplementation, which is both inexpensive and
prudent, is warranted for groups whose vitamin D status is exceptionally
low, particularly nursing infants, the elderly, and African Americans.

This review is the fourth in a series by McCann & Ames that critically
evaluate scientific evidence linking deficiencies in micronutrients (the
approximately 40 vitamins, minerals, amino acids, and fatty acids
required for the body to function) to brain function. Other reviews in
the series discuss the long-chain polyunsaturated fatty acid
docosahexaenoic acid (DHA), choline, and iron.


1. McCann, JC, Ames BN (2008) Review Article: Is there convincing
biological or behavioral evidence linking vitamin D deficiency to brain
dysfunction" FASEB J. 22: 982-1001.
2. Vieth R, Bischoff-Ferrari H, Boucher BJ, et al. The urgent need to
recommend an intake of vitamin D that is effective. Am J Clin Nutr
3. Bodnar LM, Simhan HN, Powers RW, Frank MP, Cooperstein E, Roberts JM.
High prevalence of vitamin D insufficiency in black and white pregnant
women residing in the northern United States and their neonates. J Nutr
4. McCann JC, Ames BN. Is docosahexaenoic acid, an n-3 long chain
polyunsaturated fatty acid, required for the development of normal brain
function" An overview of evidence from cognitive and behavioral tests in
humans and animals. Am J Clin Nutr 2005;82:281-95.
5. McCann JC, Ames BN. DHA and cognitive development: an update on the
science. Pediatric Basics 2007;April.
6. McCann JC, Hudes M, Ames BN. An overview of evidence for a causal
relationship between dietary availability of choline during development
and cognitive function in offspring. Neurosci Biobehav Rev
7. McCann JC, Ames BN. An overview of evidence for a causal relationship
between iron deficiency during development and cognitive or behavioral
function in children. Am J Clin Nutr 2007;85:931-45.

Research at Children’s Hospital & Research Center Oakland, CA