McCann JC, Ames BN. Is there convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction? FASEB J 22, 982-1001

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: 5.04). 05/2008; 22(4):982-1001. DOI: 10.1096/fj.07-9326rev
Source: PubMed


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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    • "However, there is evidence that high doses of vitamin D are not necessarily protective; in 424 matched pairs from a population-based cohort, a bi-modal relationship appeared in which the participants with the lowest and highest levels of vitamin D had increased risk of schizophrenia. Therefore, the relationship between vitamin D and schizophrenia needs further investigation, even though a recent review of the evidence concluded that adequate levels of vitamin D are needed for normal brain development and function and furthermore that at-risk groups should be offered supplementation [112]. "
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    ABSTRACT: Schizophrenia is a chronic condition that impacts significantly not only on the individual and family, but the disorder also has wider consequences for society in terms of significant costs to the economy. This highly prevalent condition affects approximately 1% of the worldwide population, yet there are few therapeutic options. The predominant treatment strategy for schizophrenia is anti-psychotic medication (with or without additional talking therapy) even though this approach lacks efficacy in managing the negative symptoms of the condition, is not effective in one-third of the patient group and the side effects of the medication can be severe and debilitating. In recent years, a number of pathophysiological processes have been identified in groups of people with schizophrenia including oxidative stress, one-carbon metabolism and immune-mediated responses. A number of studies have shown that these altered physiological mechanisms can be ameliorated by nutritional interventions in some individuals with schizophrenia. This review briefly describes the aforementioned processes and outlines research that has investigated the utility of nutritional approaches as an adjunct to anti-psychotic medication including antioxidant and vitamin B supplementation, neuroprotective and anti-inflammatory nutrients and exclusion diets. Whilst none of these interventions provides a ‘one-size-fits-all’ therapeutic solution, we suggest that a personalised approach warrants research attention as there is growing agreement that schizophrenia is a spectrum disorder that develops from the interplay between environmental and genetic factors. Electronic supplementary material The online version of this article (doi:10.1186/1475-2891-13-91) contains supplementary material, which is available to authorized users.
    Nutrition Journal 09/2014; 13(1):91. DOI:10.1186/1475-2891-13-91 · 2.60 Impact Factor
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    • "A large body of research suggests that an inadequate dietary supply of any of a number of essential micronutrients such as vitamin D can adversely affect brain function (Bryan et al., 2004). Some studies also suggest positive effects of Vitamin D, multivitamin and mineral supplementation on cognitive function (Holick, 2012; Holick et al., 2011; McCann & Ames, 2007; Bener et al., 2008; TheNemoGroup, 2007; Polívka et al., 2012). "
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    ABSTRACT: Attention deficit hyperactivity disorder (ADHD) is the most common behavioral disorders in children and recent studies reported a relationship between low levels of Vitamin D and incidence of ADHD. The aim of this study was to investigate the association between vitamin D deficiency and attention deficit hyperactivity disorder (ADHD). Also, to study the impact and role of vitamin D on the development of ADH in children. This is a case-control study which was conducted in children below 18 years of age from June 2011 to May 2013 at the School Health and Primary Health care Clinics, Qatar. The study was based on 1,331 cases and 1,331 controls. The data collection instrument included socio-demographic & clinical data, physician diagnosis family history, BMI, and serum 25(OH) vitamin D, calcium, albumin, billirubin, magnesium, calcium, cholesterol, urea, triglyceride and phosphorus. Descriptive and univariate statistical analysis were performed. Of the total number of 3470 children surveyed, 1331 of ADHD and 1,331 of healthy children gave their consent to participate in this study. The mean age (± SD, in years) for ADHD versus control children was 10.63±3.4 vs. 10.77±3.4. Overweight (7.7% vs 9.4%) and obesity (4.6% vs 7.7%) were significantly lower in ADHD children compared to their counterparts (P=0.001). Vitamin D deficiency was considerably higher in ADHD children compared to healthy children. The mean value of vitamin D in ADHD children was much lower than the normal value and there was a significant difference found in the mean values of vitamin D between ADHD (16.6±7.8 with median 16) and control children (23.5±9.9) (p<0.0001) and with median 23 (p = 0.006). Mean values of Calcium and phosphorous were significantly higher in control compared to ADHD children (p<0.001). 1331 of all ADHD children had 19.1% had severe vitamin D deficiency (< 10 ng/ml), 44.9% has moderate insufficient levels (between 10-20 ng/ml), 27.3% has mild insufficient levels (between 20-30 ng/ml) and only 8.1% of ADHD had sufficient serum vitamin D levels (>30 ng/ml). Multivariate logistic regression analysis revealed that household income, poor relationship between parents, mothers' occupation, consanguinity, BMI in percentiles, low duration of time under sun light, physical activity, low serum calcium level and low vitamin D level were considered as the main risk factors associated with the ADHD after adjusting for age, gender and other variables. The study showed that vitamin D deficiency was higher in ADHD children compared to healthy children. Supplementing infants with vitamin D might be a safe and effective strategy for reducing the risk of ADHD, but, further genomic and some other test and relevant studies need to be done.
    Global journal of health science 02/2014; 6(2):47-57. DOI:10.5539/gjhs.v6n2p47
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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 · 3.92 Impact Factor
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