Relationship Between Vitamin D During Perinatal Development and Health

Vitamin D Effects on Brain Development

In vitro, animal and human data have provided evidence linking vitamin D to brain development. VDR and 1α-hydroxylase, the enzyme that produces 1,25(OH)₂D, have been identified in the fetal^[30,31] and adult^[32–34] brain. The distribution of VDR in the embryonic brain depends on gestational age. In rats, VDR expression increases from the twelfth day of gestation until birth and is most prominent in the neuroepithelium and proliferating zones of the central nervous system.^[30] In the human fetus, the pattern of VDR expression has not been well characterized. It is known that serum 25(OH)D and 1,25(OH)₂D can cross the blood–brain barrier,^[34] bind to VDR, and stimulate a wide range of genomic and nongenomic responses.^[35,36]

Low concentrations of 25(OH)D during critical windows of development have the potential to reprogram brain tissue structure and function. At birth, the brains of rat pups born to vitamin D–depleted mothers had more mitotic cells and fewer apoptotic cells, suggesting that low 25(OH)D concentrations can cause transcriptional deregulation in the brain.^[37] Over time, this transcriptional deregulation may promote tumor growth and lead to brain cancer. Epidemiologic evidence suggests a possible link between brain cancer and vitamin D deficiency; but whether this link is caused by the deregulation of cell cycle arrest is yet to be determined. According to work by Eyles et al.,^[37] maternal deprivation of vitamin D can cause profound alterations in the infant's brain on a cellular, molecular, and tissue level,^[37] as expanded upon below.

On a molecular level, maternal vitamin D depletion can impair the expression of neurotrophins and growth factors in the developing brain tissue of rat pups.^[37] Neurotrophins and growth factors are a family of proteins that regulate neuron production, myelination, cell growth, and the formation of synaptic connections. During fetal development, brain cells multiply at an astonishing rate. At birth, 100 billion brain cells have been established that communicate with each other by sending electrochemical impulses through nerve cells. Each impulse that a brain cell receives creates a neuronal connection inside the nerve cell that helps to strengthen the brain's overall networking system. Each cell in the brain can connect with up to 15,000 other cells, but if these connections are impaired, neurologic disorders, such as multiple sclerosis (MS), can develop.

There is emerging evidence that vitamin D may be a risk modifying factor for MS (Table 1). In a large prospective study,^[38] the probability of developing MS was significantly higher for individuals with serum 25(OH)D concentrations in the bottom quintile (6–25 ng/mL) than the top quintile (40–60 ng/mL). Importantly, the risk of developing MS for individuals in the bottom quintile decreased by 41% with a 20-ng/mL increase in serum 25(OH)D concentrations.

Early development is a crucial exposure period for MS. Individuals who are vitamin D deficient during early life may have a greater susceptibility to MS or greater severity of MS symptoms.^[39] The pathology underlying MS involves disruption of the blood–brain barrier, which allows white blood cells called T lymphocytes to cross over and damage the myelin sheaths of the central nervous system.^[40] The cause of MS remains unknown, but findings from a cell culture study indicate that, by interacting with VDR on T lymphocytes, the biologically active 1,25(OH)₂D hormone can downregulate T cell activity that damages the myelin of the central nervous system.^[41] Therefore, supplemental vitamin D may be protective when sun exposure is low for preventing myelin sheet damage and reducing the risk of MS.

On a tissue level, maternal vitamin D depletion alters the brain morphology of the developing offspring.^[42] Rat pups born to vitamin D–deprived mothers had enlarged lateral ventricles and longer cortices that were proportionally thinner. Changes in brain morphology have been associated with psychological disorders. Thinning of neocortex and ventricle overgrowth are two changes commonly observed in brains of children with schizophrenia,^[43] suggesting that vitamin D may be a risk modifying factor for schizophrenia. There is some epidemiologic evidence supporting the association between vitamin D exposure in early life and schizophrenia (Table 1).

Animal models designed to limit the organism's ability to use vitamin D during brain development have been used to investigate how vitamin D affects both cognitive and behavioral functions. Many of these observational findings are consistent with behavioral patterns of patients with schizophrenia and MS,^[44,45] and may in part be explained by deregulation of brain protein expression. Adult rats that were vitamin D–deprived during gestation had deregulation of 36 brain proteins,^[46] many of which are misexpressed in either schizophrenia or MS. If this is also true in humans, vitamin D supplementation in pregnancy and childhood may prove to be a simple yet cost-effective strategy to help to prevent or alleviate debilitating disorders in later life.

J Midwifery Womens Health. 2010;55(6):550-560. © 2010  Elsevier Science, Inc.

Cite this: Relationship Between Vitamin D During Perinatal Development and Health - Medscape - Nov 01, 2010.