Vitamins and Minerals: Vitamin D for Thought

Increasingly, research conducted over the last several years has focused on the potential benefits of vitamin D for the prevention and treatment of several chronic disease conditions. Vitamin D controls the expression of hundreds-and probably thousands-of genes. It is now recognized to play a crucial role in bone, cardiovascular, and colon and digestive-tract health; regulating blood pressure; guarding against cancer; and supporting healthy blood sugar levels in the human body.

Recently, several researchers have discovered the profound influence of vitamin D on brain development. This discovery has opened up an exciting new paradigm leading to interesting theories regarding how ensuring optimal concentrations of vitamin D may prevent or drastically reduce the occurrence of several developmental disorders and mental illnesses in humans.

An article on the subject published in December 2009 by Darryl Eyles and his research group from the University of Queensland in Australia details the potential effects of vitamin D on brain development based on their own studies and published research. The results of studies in animals and cell-culture models clearly suggest that vitamin D has neurotrophic activity (maintaining the health of the nerves and nervous system) by promoting production of several nerve-growth factors.

Vitamin D also shows neuroprotective activity, as studies have found that it protects brain cells against free radical damage and prevents damage to cells as a result of autoimmune conditions. Vitamin D may also have potent anti-inflammatory properties, as some evidence points to its ability to suppress the production of pro-inflammatory cytokines in brain tissue.

Vitamin D has further been shown to impact brain structure and gene expression, as has been found in the offspring of rats who were deficient in vitamin D. These offspring were shown to have structural anomalies not seen in rats with sufficient vitamin D concentrations, as well as altered rates of nerve and brain tissue development. Further research on these rats has found alterations in the expression of genes involved in calcium processing and nerve-signal transmission.

Studies conducted by the group also reveal behavior abnormalities in offspring of vitamin D–deficient rats, including adverse effects on motor function and impaired attention.

In addition to this evidence, research by the same group conducted over the last four years suggests that the receptor for vitamin D is expressed in various areas of the brain at different times during the course of the developmental process. This indicates vitamin D’s significant role in neural development and nerve-cell proliferation. It also suggests the ability of vitamin D to modulate the differentiation and development of different regions of the brain.

Eyles and colleagues further elaborate on the vitamin D link to brain development by summarizing several studies on schizophrenia. Epidemiological investigations have shown positive associations between low prenatal concentrations of vitamin D and increased risk of developing schizophrenia. For example, researchers looked at maternal vitamin D supplementation in the first year of life and the risk of schizophrenia in male offspring of a northern Finnish cohort. They found a direct association between maternal vitamin D supplementation and reduced risk of schizophrenia in male offspring.

In another investigation, serum measurements of 25-hydroxyvitamin D concentrations (a commonly used laboratory indicator of vitamin D status) in mothers were taken in the third trimester of pregnancy and banked over three decades. There was a greater rate of vitamin D deficiency in mothers of children who developed schizophrenia compared to mothers of children who did not.

Similar epidemiological evidence exists for the relationship between multiple sclerosis (MS) and vitamin D. The incidence of MS decreases in areas that are nearer to the equator with higher sun exposure and higher vitamin D concentrations. Experimental animal models of MS also indicate that vitamin D administration is protective against development of this condition. While more research is needed to assess vitamin D’s potential for this condition, the epidemiological evidence for low vitamin D concentrations playing a role in the development of MS is strong.

Earlier work published in 2007 by Lionel Almeras, Darryl Eyles, and colleagues in France and Australia in the realm of proteomics found that prenatal vitamin D deficiency in rats led to the altered expression of 36 different brain proteins in the offspring of these animals. Interestingly, the researchers focused on regions of the brain known to be implicated in symptoms of schizophrenia and MS, namely the prefrontal cortex and hippocampus. It was found that vitamin D deficiency caused long-term dysregulation in several proteins involved in such critical areas as mitochondrial function, nerve transmission, antioxidant balance, and energy production. These findings correlated well with proteins found to be defective in those with schizophrenia and MS, providing further evidence of vitamin D’s importance for healthy brain development.

Highlighting vitamin D’s continued importance to brain function throughout life, several studies have correlated vitamin D status with measures of cognitive function and health in adults. While not all studies examining this correlation have yielded clearly positive findings, several others have demonstrated that those with higher vitamin D concentrations have enhanced cognitive function.

A paper published this year in the European Journal of Clinical Nutrition summarized research conducted by Kelly Seamans, Kevin Cashman, and others from University College Cork in Ireland, which analyzed the vitamin D status and cognitive capacity of healthy older European adults. Their results suggest that vitamin D insufficiency is widespread throughout many European countries, and that lower vitamin D status is associated with lower spatial working-memory capacity.

An earlier study by David Llewellyn and colleagues from the UK looked at the Healthy Survey for England 2000 and data on 1766 adults ages 65 and older, of which 212 participants were found to be cognitively impaired. Assessments of serum 25-hydroxyvitamin D revealed that those with the lowest levels had significantly increased odds of cognitive impairment.

Furthermore, a paper published in January 2010 in Neurology assessed 25-hydroxyvitamin D concentrations in 752 women, which were a randomized subset of participants from the EPIDOS study, a French cohort study designed to evaluate risk of hip fractures in community-dwelling women ages 75 and older. A standardized mental-state questionnaire was used to determine cognitive function. The researchers found that those women with deficient vitamin D concentrations had significantly lower scores on the mental-state questionnaire compared to those with sufficient vitamin D concentrations.

Taking into account the entirety of the evidence linking vitamin D to brain development and cognitive function, John Cannell, MD, of the Vitamin D Council has proposed an interesting theory linking the increased prevalence of autism with the epidemic of vitamin D deficiency that has been seen over the last 20 years.

In a 2008 paper published in the journal Medical Hypotheses, Cannell points out that this epidemic of vitamin D deficiency correlates with medical advice over the last few decades to avoid the sun. During this same period, the rise in autism rates has been astronomical.

Data from animal studies has shown that vitamin D deficiency leads to the defective production of several brain proteins, as discussed above. As with schizophrenia and MS, a number of the abnormalities seen in autism can be linked to the defective nature of these brain proteins. The adverse consequences of vitamin D deficiency can plausibly impact brain development in autistic children, leading to increased inflammation, decreased mitochondrial function, and other deficits.

Furthermore, epidemiological data suggest that autism is more common in areas with less sun exposure, and also more common in dark-skinned individuals. Dark-skinned individuals require extended sun exposure to produce levels of vitamin D comparable to those with lighter skin. It has also been noted that autism is more common in children of dark-skinned immigrants that have settled in countries in more northern latitudes compared to those remaining in native populations.

Lending further support to the theory that vitamin D deficiency may be a factor in autism is an Egyptian study published earlier this year in which 70 children diagnosed as autistic were compared to 42 healthy age-matched controls of the same socioeconomic status. Serum levels of 25-hydroxyvitamin D and 1,25-hydroxyvitamin D were measured and found to be significantly lower in autistic children than controls. While the cause of autism remains elusive, and there are likely multiple contributing factors, the theory that maternal vitamin D deficiency could play a part is certainly not far-fetched and merits strong consideration.

While research into this theory is ongoing, and more research is needed to confirm it, ensuring adequate vitamin D concentrations in expecting mothers may make sense. Given the low toxicity of vitamin D, and given what is now known about the influence of vitamin D on brain development and on other critical organs and systems, implementing this simple and inexpensive intervention could help ensure that the rate of development of several debilitating conditions is drastically reduced.

Also: Read our sidebar on the benefits of magnesium.