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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    • "Finally, the rate of vitamin D deficiency in our control group (15.9%) was consistent with the rate of 16% shown in a large nationwide birth cohort study of adults in the United Kingdom (Hypponen and Power, 2007). There is a growing body of evidence that vitamin D is neuroprotective and experimental evidence from animal studies linking a lack of vitamin D to behavioural and cognitive dysfunction (McCann and Ames, 2008; Groves et al., 2013). The high rates of vitamin D deficiency in our FEP patients, given the postulated neuroprotective role of vitamin D, raise the possibility that the judicious treatment of low serum vitamin D in FEP may have potential benefit. "
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    ABSTRACT: Vitamin D deficiency is seen in a high proportion of people with established psychotic disorders, but it is not known if this is present at onset of the illness. We set out to examine vitamin D levels in people with their first episode of psychosis (FEP). We conducted a matched case-control study to examine vitamin D levels and rates of vitamin D deficiency in sixty nine patients presenting with their FEP and sixty nine controls matched for age, sex and ethnicity. Differences between groups were tested using student's-t tests, paired t-tests and odds ratios for further analysis. Vitamin D levels were significantly lower in cases than in controls (p<0.001). The odds ratio of being vitamin D deficient was 2.99 in the FEP group relative to the control group. There was no correlation between vitamin D levels and length of hospitalisation in the patient group (r=-0.027, p=0.827). We found higher rates of vitamin D deficiency in people with FEP compared to matched controls. Given that vitamin D is neuroprotective; that developmental vitamin D deficiency may be a risk factor for psychosis, and that incipient psychosis may affect lifestyle factors and diet, future studies are required to examine this association further. In the meantime, there is a need for more widespread testing of vitamin D levels in FEP and for the development of appropriate management strategies.
    Schizophrenia Research 09/2013; 150(2-3). DOI:10.1016/j.schres.2013.08.036 · 4.43 Impact Factor
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    • "The importance of vitamin D to the CNS in both healthy and psychiatric populations is less well appreciated and is vastly under-studied compared to its known impact on bone health. Vitamin D receptors are present throughout the brain, and D-deficiency is associated with negative CNS effects in animal studies [79]. "
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    ABSTRACT: Background: In majority of the lower middle income countries, adolescence is associated with a double burden of diseases related to either under-nutrition or over-nutrition. In countries with rapid economic development, proatherogenic risk factors are also developing concurrently, although diseases related to under-nutrition, such as infections are not fully controlled. In this review, we describe both problems. Methods: Internet searches using different data bases and discussion with experts. Results: Approximately, 19% of the global population which is about 1 in 5 persons in the world is comprised of adolescents. This represents roughly 1.2 billion people between the ages of 10–19 years, out of which 85% live in developing countries. Nearly two thirds of premature deaths and one third of the total disease burden in adults are associated with conditions or behaviors that began in youth, including tobacco use, lack of physical activity, unprotected sex or exposure to violence. Promoting healthy practices during adolescence, and efforts that better protect this age group from risks will ensure longer lives and would protect from non-communicable diseases (NCDs) in adult life. Reports from India, Bangladesh, Nepal and Myanmar indicated that 32%, 48%, 47% and 39% adolescents, respectively, are stunted in growth, whereas 53%, 67%, 36%, and 32% adolescents from these countries are thin and underweight. Diets of adolescents were deficient in all the essential nutrients, especially in caloric energy, iron, magnesium, potassium, vitamin A, vitamin D and calcium. Chronic dietary deficiency of magnesium, potassium, selenium, chromium, zinc, and antioxidants may predispose to obesity and insulin resistance during transition from under-nutrition to over-nutrition, resulting into metabolic syndrome which is a risk factor for cardiovascular diseases (CVDs) and other chronic diseases. Eating the same amount of calories in the morning and in the evening causes less increase in body weight than eating in the evening. Hence breakfast may have greater impact than dinner for theprevention of obesity. However, a functional food with smaller breakfast appears to be an important driver for the prevention of circadian rhythms of cardiovascular events among people predisposed to CVDs, as gauged by circadian patterns of adverse cardiovascular events. Conclusions: South East Asian countries with lower income as well as upper and lower middle income countries are in a rapid transitional phase from poverty to affluence. Increase in carbohydrate and fat energy intake via chronotherapy, in the presence of micronutrient deficiency and sedentary behavior may prevent or cause obesity and the metabolic syndrome. Keywords: South Asian adolescents, obesity, metabolic syndrome, fast food energy intake, over nutrition, micronutrient deficiency, chronotherapy, lifestyle
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    • "The role of vitamin D in adult brain function has attracted considerable attention in recent years [1]. Apart from the wellestablished role in calcium homeostasis, key features of the vitamin D system have been identified in the central nervous system. "
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    ABSTRACT: Epidemiological evidence suggests that low levels of vitamin D may predispose people to develop depression and cognitive impairment. While rodent studies have demonstrated that prenatal vitamin D deficiency is associated with altered brain development, there is a lack of research examining adult vitamin D (AVD) deficiency. The aim of this study was to examine the impact of AVD deficiency on behaviour and brain function in the mouse. Ten-week old male C57BL/6J and BALB/c mice were fed a control or vitamin D deficient diet for 10 weeks prior to, and during behavioural testing. We assessed a broad range of behavioural domains, excitatory and inhibitory neurotransmission in brain tissue, and, in separate groups of mice, locomotor response to D-amphetamine and MK-801. Overall, AVD deficiency resulted in hyperlocomotion in a novel open field and reduced GAD65/67 levels in brain tissue. AVD-deficient BALB/c mice had altered behaviour on the elevated plus maze, altered responses to heat, sound and shock, and decreased levels of glutamate and glutamine, and increased levels of GABA and glycine. By contrast C57BL/6 mice had a more subtle phenotype with no further behavioural changes but significant elevations in serine, homovanillic acid and 5-hydroxyindoleacetic acid. Although the behavioural phenotype of AVD did not seem to model a specific disorder, the overall reduction in GAD65/67 levels associated with AVD deficiency may be relevant to a number of neuropsychiatric conditions. This is the first study to show an association between AVD deficiency and prominent changes in behaviour and brain neurochemistry in the mouse.
    Behavioural brain research 12/2012; 241. DOI:10.1016/j.bbr.2012.12.001 · 3.39 Impact Factor
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