Is there convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction?

Nutrition and Metabolism Center, Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA.
The FASEB Journal (Impact Factor: 5.48). 05/2008; 22(4):982-1001. DOI: 10.1096/fj.07-9326rev
Source: PubMed

ABSTRACT Vitamin D insufficiency is common in the United States; the elderly and African-Americans are at particularly high risk of deficiency. This review, written for a broad scientific readership, presents a critical overview of scientific evidence relevant to a possible causal relationship between vitamin D deficiency and adverse cognitive or behavioral effects. Topics discussed are 1) biological functions of vitamin D relevant to cognition and behavior; 2) studies in humans and rodents that directly examine effects of vitamin D inadequacy on cognition or behavior; and 3) immunomodulatory activity of vitamin D relative to the proinflammatory cytokine theory of cognitive/behavioral dysfunction. We conclude there is ample biological evidence to suggest an important role for vitamin D in brain development and function. However, direct effects of vitamin D inadequacy on cognition/behavior in human or rodent systems appear to be subtle, and in our opinion, the current experimental evidence base does not yet fully satisfy causal criteria. Possible explanations for the apparent inconsistency between results of biological and cognitive/behavioral experiments, as well as suggested areas for further research are discussed. Despite residual uncertainty, recommendations for vitamin D supplementation of at-risk groups, including nursing infants, the elderly, and African-Americans appear warranted to ensure adequacy.

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    ABSTRACT: To determine whether supplementation with vitamin D improves resilience to the adverse effects of earthquakes. Opportunistic addition to an established randomised double blind placebo controlled trial. Christchurch, New Zealand, where a prolonged series of catastrophic earthquakes beginning on 4 September 2010 occurred, which caused widespread destruction, fatalities, and extensive psychological damage. 322 healthy adults (241 women; 81 men) aged 18-67 who were already participating in the vitamin D and acute respiratory infections study (VIDARIS) between February 2010 and November 2011. Participants were randomised to receive an oral dose of either 200 000 IU vitamin D3 monthly for two months then 100 000 IU monthly (n=161) or placebo (n=161) for a total of 18 months. This is a post hoc analysis from the previously published VIDARIS trial. The primary endpoint in the current analysis was the self reported effects and overall adverse impact of the Christchurch earthquakes as assessed by questionnaire four months after the most destructive earthquake on 22 February 2011, which was used as the index event. The secondary end point was the number of "psychological" adverse events that participants reported at their usual monthly appointments as part of the original VIDARIS trial. 308 participants completed the earthquake impact questionnaire (n=152 in the vitamin D group and 156 in the placebo group). There was no significant difference in the number of self reported adverse effects between those receiving vitamin D supplementation and those receiving placebo. There was also no difference in the overall adverse impact score between treatment groups (χ(2) P=0.44). The exception was that those in the vitamin D group experienced more adverse effects on family relationships (22% v 13%; χ(2) P=0.03). The number of psychological adverse events-such as fatigue, stress, anxiety, and insomnia-that participants reported at their usual monthly appointments was significantly higher after the earthquake (χ(2) P=0.007) but did not differ between treatment groups. In this trial, vitamin D supplementation did not reduce the adverse impact of earthquakes in healthy adults. Trial registration Australian New Zealand Clinical Trials Registry ( ACTRN12609000486224. © Slow et al 2014.
    BMJ Clinical Research 12/2014; 349:g7260. DOI:10.1136/bmj.g7260 · 14.09 Impact Factor
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    ABSTRACT: Over the last decade a convergent body of evidence has emerged from epidemiology, animal experiments and clinical trials which links low vitamin D status with a range of adverse neuropsychiatric outcomes. This research demonstrates that the timing of exposure to low vitamin D influences the nature of brain phenotypes, as exposures during gestation versus adulthood result in different phenotypes. With respect to early life exposures, there is robust evidence from rodent experiments indicating that transient developmental vitamin D (DVD) deficiency is associated with changes in brain structure, neurochemistry, gene and protein expression and behavior. In particular, DVD deficiency is associated with alterations in the dopaminergic neurotransmitter systems. In contrast, recently published animal experiments indicate that adult vitamin D (AVD) deficiency is associated with more subtle neurochemical and behavioral phenotypes. This paper explores key issues that need to be addressed in future research. There is a need to define the timing and duration of the ‘critical window’ during which low vitamin D status is associated with differential and adverse brain outcomes. We discuss the role for ‘two-hit hypotheses’, which propose that adult vitamin D deficiency leaves the brain more vulnerable to secondary adverse exposures, and thus may exacerbate disease progression. Finally, we explore the evidence implicating a role for vitamin D in rapid, non-genomic mechanisms that may involve L-type calcium channels and brain function.
    The Journal of Steroid Biochemistry and Molecular Biology 11/2014; 148. DOI:10.1016/j.jsbmb.2014.11.004 · 4.05 Impact Factor
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    ABSTRACT: Background: Schizophrenia is one of the most disabling psychiatric disorders, with serious consequences on families and society. Although a genetic component in its aetiology is indisputable, environmental factors also play an important role. Vitamin D (VD) has been implicated in central nervous system development and some evidence points to its role on schizophrenia aetiology. We aim to summarize brain alterations occurring in schizophrenia and how VD is relevant to them. Methods: Literature review up to 30th September 2014, using MeSH terms schizophrenia, vitamin D, brain, and central nervous system. Results: We summarize alterations occurring at anatomical and histological levels. Moreover, we describe biological pathways in which VD is involved that are proven to be disrupted in schizophrenia: neurotrophic factors, neurotransmission, synaptic and cytoskeleton anomalies, calcium homeostasis, energy metabolism and redox balance. Finally, we give some emphasis to cognitive disturbances. Conclusions: The heterogeneity of some studies does not allow to definitely affirm that VD deficit plays a role on schizophrenia aetiology. Studies on different populations and animal models should be conducted in order to achieve reproducible results. Therefore, this paper should be regarded as a guide to the pathways and anatomical structures disrupted by VD deficit in schizophrenia, and warrant further investigation. Although we cannot definitely affirm that VD deficiency is essential for schizophrenia aetiology, literature currently points to this hypothesis.


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