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      The neuropsychiatric effects of vitamin C deficiency: a systematic review

      research-article
      1 , 2 , 3 , , 2 , 4
      BMC Psychiatry
      BioMed Central
      Vitamin C deficiency, Scurvy, Neuropsychiatry, Depression, Cognition

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          Abstract

          Background

          Vitamin C deficiency may be more common than is generally assumed, and the association between vitamin C deficiency and adverse psychiatric effects has been known for centuries. This paper aims to systematically review the evidence base for the neuropsychiatric effects of vitamin C deficiency.

          Methods

          Relevant studies were identified via systematic literature review.

          Results

          Nine studies of vitamin C deficiency, including subjects both with and without the associated physical manifestations of scurvy, were included in this review. Vitamin C deficiency, including scurvy, has been linked to depression and cognitive impairment. No effect on affective or non-affective psychosis was identified.

          Conclusions

          Disparate measurement techniques for vitamin C, and differing definitions of vitamin C deficiency were apparent, complicating comparisons between studies. However, there is evidence suggesting that vitamin C deficiency is related to adverse mood and cognitive effects. The vitamin C blood levels associated with depression and cognitive impairment are higher than those implicated in clinical manifestations of scurvy. While laboratory testing for ascorbic acid can be practically difficult, these findings nonetheless suggest that mental health clinicians should be alerted to the possibility of vitamin C deficiency in patients with depression or cognitive impairment. Vitamin C replacement is inexpensive and easy to deliver, although as of yet there are no outcome studies investigating the neuropsychiatric impact of vitamin C replacement in those who are deficient.

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          Most cited references25

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          The epigenetic role of vitamin C in health and disease.

          Recent advances have uncovered a previously unknown function of vitamin C in epigenetic regulation. Vitamin C exists predominantly as an ascorbate anion under physiological pH conditions. Ascorbate was discovered as a cofactor for methylcytosine dioxygenases that are responsible for DNA demethylation, and also as a likely cofactor for some JmjC domain-containing histone demethylases that catalyze histone demethylation. Variation in ascorbate bioavailability thus can influence the demethylation of both DNA and histone, further leading to different phenotypic presentations. Ascorbate deficiency can be presented systematically, spatially and temporally in different tissues at the different stages of development and aging. Here, we review how ascorbate deficiency could potentially be involved in embryonic and postnatal development, and plays a role in various diseases such as neurodegeneration and cancer through epigenetic dysregulation.
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            Nutritional comparison of fresh, frozen and canned fruits and vegetables. Part 1. Vitamins C and B and phenolic compounds

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              Vitamin C Status and Cognitive Function: A Systematic Review

              Vitamin C plays a role in neuronal differentiation, maturation, myelin formation and modulation of the cholinergic, catecholinergic, and glutaminergic systems. This review evaluates the link between vitamin C status and cognitive performance, in both cognitively intact and impaired individuals. We searched the PUBMED, SCOPUS, SciSearch and the Cochrane Library from 1980 to January 2017, finding 50 studies, with randomised controlled trials (RCTs, n = 5), prospective (n = 24), cross-sectional (n = 17) and case-control (n = 4) studies. Of these, 36 studies were conducted in healthy participants and 14 on cognitively impaired individuals (including Alzheimer’s and dementia). Vitamin C status was measured using food frequency questionnaires or plasma vitamin C. Cognition was assessed using a variety of tests, mostly the Mini-Mental-State-Examination (MMSE). In summary, studies demonstrated higher mean vitamin C concentrations in the cognitively intact groups of participants compared to cognitively impaired groups. No correlation between vitamin C concentrations and MMSE cognitive function was apparent in the cognitively impaired individuals. The MMSE was not suitable to detect a variance in cognition in the healthy group. Analysis of the studies that used a variety of cognitive assessments in the cognitively intact was beyond the scope of this review; however, qualitative assessment revealed a potential association between plasma vitamin C concentrations and cognition. Due to a number of limitations in these studies, further research is needed, utilizing plasma vitamin C concentrations and sensitive cognitive assessments that are suitable for cognitively intact adults.
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                Author and article information

                Contributors
                david.plevin@sa.gov.au
                Journal
                BMC Psychiatry
                BMC Psychiatry
                BMC Psychiatry
                BioMed Central (London )
                1471-244X
                18 June 2020
                18 June 2020
                2020
                : 20
                : 315
                Affiliations
                [1 ]GRID grid.467022.5, ISNI 0000 0004 0540 1022, Central Adelaide Local Health Network, ; Adelaide, SA Australia
                [2 ]GRID grid.1010.0, ISNI 0000 0004 1936 7304, Discipline of Psychiatry, , The University of Adelaide, ; Adelaide, SA Australia
                [3 ]Ramsay Health Care Mental Health, Gilberton, SA Australia
                [4 ]Northern Adelaide Local Health Network, Adelaide, SA Australia
                Author information
                http://orcid.org/0000-0003-3088-7434
                Article
                2730
                10.1186/s12888-020-02730-w
                7302360
                32552785
                9742db18-80d1-4d20-a219-ced088d0c497
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 9 September 2019
                : 12 June 2020
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Clinical Psychology & Psychiatry
                vitamin c deficiency,scurvy,neuropsychiatry,depression,cognition
                Clinical Psychology & Psychiatry
                vitamin c deficiency, scurvy, neuropsychiatry, depression, cognition

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