{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T09:53:25Z","timestamp":1770285205682,"version":"3.49.0"},"reference-count":51,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012107","name":"The Waterloo Foundation","doi-asserted-by":"publisher","award":["E6798"],"award-info":[{"award-number":["E6798"]}],"id":[{"id":"10.13039\/100012107","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Elevated inflammation has been associated with adverse mood states, such as depression and anxiety, and antioxidant nutrients, such as vitamin C, have been associated with decreased inflammation and improved mood. In the current study comprising a cohort of pregnant women with depression and anxiety, we hypothesised that elevated inflammation would be associated with adverse mood states and inversely associated with vitamin C status and that multinutrient supplementation would optimise vitamin concentrations and attenuate inflammation. Sixty-one participants from the NUTRIMUM trial had blood samples collected between 12 and 24 weeks gestation (baseline) and following 12 weeks of daily supplementation with a multinutrient formula containing 600 mg of vitamin C or active placebo. The samples were analysed for inflammatory biomarkers (C-reactive protein (CRP) and cytokines) and vitamin C content and were related to scales of depression and anxiety. Positive correlations were observed between interleukin-6 (IL-6) and all of the mood scales administered (p &lt; 0.05), including the Edinburgh Postnatal Depression Scale, the Clinical Global Impressions\u2014Severity Scale, the Montgomery and \u00c5sberg Depression Rating Scale, the Depression Anxiety Stress Scale 21, and the Generalized Anxiety Disorder-7 (GAD-7). CRP correlated weakly with GAD-7 (p = 0.05). There was an inverse correlation between CRP and the vitamin C status of the cohort (p = 0.045), although there was no association of the latter with the mood scales (p &gt; 0.05). Supplementation with the multinutrient formula resulted in a significant increase in the vitamin C status of the cohort (p = 0.007) but did not affect the inflammatory biomarker concentrations (p &gt; 0.05). In conclusion, greater systemic inflammation was associated with worse mood states; however, 12-week multinutrient supplementation did not alter inflammatory biomarker concentrations. Nevertheless, the vitamin C status of the cohort was improved with supplementation, which may aid pregnancy and infant outcomes.<\/jats:p>","DOI":"10.3390\/antiox12040941","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T04:45:32Z","timestamp":1681706732000},"page":"941","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Inflammation and Vitamin C in Women with Prenatal Depression and Anxiety: Effect of Multinutrient Supplementation"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5890-2977","authenticated-orcid":false,"given":"Anitra C.","family":"Carr","sequence":"first","affiliation":[{"name":"Nutrition in Medicine Research Group, Department of Pathology and Biomedical Science, University of Otago, Christchurch 8011, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hayley A.","family":"Bradley","sequence":"additional","affiliation":[{"name":"School of Psychology, Speech and Hearing, University of Canterbury, Christchurch 8041, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Vlasiuk","sequence":"additional","affiliation":[{"name":"Nutrition in Medicine Research Group, Department of Pathology and Biomedical Science, University of Otago, Christchurch 8011, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hayley","family":"Pierard","sequence":"additional","affiliation":[{"name":"Centre for Postgraduate Nursing Studies, University of Otago, Christchurch 8011, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Beddow","sequence":"additional","affiliation":[{"name":"Centre for Postgraduate Nursing Studies, University of Otago, Christchurch 8011, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3793-7342","authenticated-orcid":false,"given":"Julia J.","family":"Rucklidge","sequence":"additional","affiliation":[{"name":"School of Psychology, Speech and Hearing, University of Canterbury, Christchurch 8041, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mathers, C.D., and Loncar, D. (2006). Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med., 3.","DOI":"10.1371\/journal.pmed.0030442"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association. [5th ed.]. DSM-5.","DOI":"10.1176\/appi.books.9780890425596"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1177\/0004867415622406","article-title":"The prevalence of symptoms of depression and anxiety, and the level of life stress and worry in New Zealand M\u0101ori and non-M\u0101ori women in late pregnancy","volume":"51","author":"Signal","year":"2017","journal-title":"Aust. N. Z. J. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/da.22687","article-title":"The effect of perinatal depression treatment for mothers on parenting and child development: A systematic review","volume":"34","author":"Letourneau","year":"2017","journal-title":"Depress. Anxiety"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.bbi.2020.02.010","article-title":"Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls","volume":"87","author":"Osimo","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jri.2012.01.007","article-title":"Association of depressive symptoms with inflammatory biomarkers among pregnant African-American women","volume":"94","author":"Peters","year":"2012","journal-title":"J. Reprod. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.bbi.2009.02.012","article-title":"Depressive symptoms are associated with elevated serum proinflammatory cytokines among pregnant women","volume":"23","author":"Christian","year":"2009","journal-title":"Brain Behav. Immun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1016\/j.psyneuen.2013.03.019","article-title":"Perinatal depression\u2014The fourth inflammatory morbidity of pregnancy?: Theory and literature review","volume":"38","author":"Osborne","year":"2013","journal-title":"Psychoneuroendocrinology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"868936","DOI":"10.3389\/fpsyt.2022.868936","article-title":"Stress-related mental health disorders and inflammation in pregnancy: The current landscape and the need for further investigation","volume":"13","author":"Ravi","year":"2022","journal-title":"Front. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.appet.2015.03.017","article-title":"The association between diet quality and mental health during the perinatal period. A systematic review","volume":"91","author":"Baskin","year":"2015","journal-title":"Appetite"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Singh, A., Trumpff, C., Genkinger, J., Davis, A., Spann, M., Werner, E., and Monk, C. (2017). Micronutrient dietary intake in Latina pregnant adolescents and its association with level of depression, stress, and social support. Nutrients, 9.","DOI":"10.3390\/nu9111212"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1749-6632.1975.tb29271.x","article-title":"Distribution of ascorbic acid, metabolites and analogues in man and animals","volume":"258","author":"Hornig","year":"1975","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1146\/annurev.nu.06.070186.002053","article-title":"The biochemical functions of ascorbic acid","volume":"6","author":"Englard","year":"1986","journal-title":"Annu. Rev. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/978-94-007-2199-9_6","article-title":"Vitamin C transport and its role in the central nervous system","volume":"56","author":"May","year":"2012","journal-title":"Subcell. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1079\/BJN20051718","article-title":"Maternal intake of antioxidant vitamins in pregnancy in relation to maternal and fetal plasma levels at delivery","volume":"95","author":"Scaife","year":"2006","journal-title":"Br. J. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1093\/ajcn\/28.9.1000","article-title":"Comparison of the nutritional status of pregnant adolescents with adult pregnant women. I. Biochemical findings","volume":"28","author":"Morse","year":"1975","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3704","DOI":"10.1073\/pnas.93.8.3704","article-title":"Vitamin C pharmacokinetics in healthy volunteers: Evidence for a recommended dietary allowance","volume":"93","author":"Levine","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/ajcn\/24.4.455","article-title":"Some behavioral effects of ascorbic acid deficiency","volume":"24","author":"Kinsman","year":"1971","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"108459","DOI":"10.1016\/j.jnutbio.2020.108459","article-title":"The role of vitamin C in stress-related disorders","volume":"85","author":"Moritz","year":"2020","journal-title":"J. Nutr. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.genhosppsych.2021.04.006","article-title":"The effect of vitamin C supplementation on mood status in adults: A systematic review and meta-analysis of randomized controlled clinical trials","volume":"71","author":"Yosaee","year":"2021","journal-title":"Gen. Hosp. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3520","DOI":"10.2174\/1381612824666181017101810","article-title":"A meta-analysis of randomized control trials: The impact of vitamin C supplementation on serum CRP and serum hs-CRP concentrations","volume":"24","author":"Jafarnejad","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3405","DOI":"10.2147\/DDDT.S83144","article-title":"Effect of vitamin C on inflammation and metabolic markers in hypertensive and\/or diabetic obese adults: A randomized controlled trial","volume":"9","author":"Ellulu","year":"2015","journal-title":"Drug. Des. Devel. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.neubiorev.2011.12.005","article-title":"Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression","volume":"36","author":"Leonard","year":"2012","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Bradley, H.A., Campbell, S.A., Mulder, R.T., Henderson, J.M.T., Dixon, L., Boden, J.M., and Rucklidge, J.J. (2020). Can broad-spectrum multinutrients treat symptoms of antenatal depression and anxiety and improve infant development? Study protocol of a double blind, randomized, controlled trial (the \u2018NUTRIMUM\u2019 trial). BMC Pregnancy Childbirth, 20.","DOI":"10.1186\/s12884-020-03143-z"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.chc.2014.04.001","article-title":"Single-micronutrient and broad-spectrum micronutrient approaches for treating mood disorders in youth and adults","volume":"23","author":"Popper","year":"2014","journal-title":"Child. Adolesc. Psychiatr. Clin. N. Am."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3945\/ajcn.2008.27268","article-title":"Dietary screening tool identifies nutritional risk in older adults","volume":"90","author":"Bailey","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1192\/bjp.150.6.782","article-title":"Detection of postnatal depression. Development of the 10-item Edinburgh Postnatal Depression Scale","volume":"150","author":"Cox","year":"1987","journal-title":"Br. J. Psychiatry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1111\/j.1365-2753.2007.00921.x","article-title":"The validity of the CGI severity and improvement scales as measures of clinical effectiveness suitable for routine clinical use","volume":"14","author":"Berk","year":"2008","journal-title":"J. Eval. Clin. Pract."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1192\/bjp.bp.106.032532","article-title":"Development and reliability of a structured interview guide for the Montgomery Asberg Depression Rating Scale (SIGMA)","volume":"192","author":"Williams","year":"2008","journal-title":"Br. J. Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/0005-7967(94)00075-U","article-title":"The structure of negative emotional states: Comparison of the Depression Anxiety Stress Scales (DASS) with the Beck Depression and Anxiety Inventories","volume":"33","author":"Lovibond","year":"1995","journal-title":"Behav. Res. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lovibond, S.H., and Lovibond, P.F. (1995). Manual for the Depression Anxiety Stress Scales, Psychology Foundation. [2nd ed.].","DOI":"10.1037\/t01004-000"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1001\/archinte.166.10.1092","article-title":"A brief measure for assessing generalized anxiety disorder: The GAD-7","volume":"166","author":"Spitzer","year":"2006","journal-title":"Arch. Intern. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Pullar, J.M., Bayer, S., and Carr, A.C. (2018). Appropriate handling, processing and analysis of blood samples is essential to avoid oxidation of vitamin C to dehydroascorbic acid. Antioxidants, 7.","DOI":"10.3390\/antiox7020029"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.1017\/jns.2012.15","article-title":"Bioavailability of vitamin C from kiwifruit in non-smoking males: Determination of \u2018healthy\u2019 and \u2018optimal\u2019 intakes","volume":"1","author":"Carr","year":"2012","journal-title":"J. Nutr. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1097\/MCO.0b013e32833cf3bc","article-title":"Conceptual and methodological issues relevant to cytokine and inflammatory marker measurements in clinical research","volume":"13","author":"Zhou","year":"2010","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Rowe, S., and Carr, A.C. (2020). Global vitamin C status and prevalence of deficiency: A cause for concern?. Nutrients, 12.","DOI":"10.3390\/nu12072008"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Carr, A.C., and Rowe, S. (2020). Factors affecting vitamin C status and prevalence of deficiency: A global health perspective. Nutrients, 12.","DOI":"10.3390\/nu12071963"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Carr, A.C., Block, G., and Lykkesfeldt, J. (2022). Estimation of vitamin C intake requirements based on body weight: Implications for obesity. Nutrients, 14.","DOI":"10.20944\/preprints202203.0203.v1"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e13215","DOI":"10.1111\/mcn.13215","article-title":"Vitamin C levels in a Central-African mother-infant cohort: Does hypovitaminosis C increase the risk of enteric infections?","volume":"17","author":"Koyembi","year":"2021","journal-title":"Matern. Child. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Coker, S.J., Smith-D\u00edaz, C.C., Dyson, R.M., Vissers, M.C.M., and Berry, M.J. (2022). The epigenetic role of vitamin C in neurodevelopment. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031208"},{"key":"ref_41","first-page":"Cd004072","article-title":"Vitamin C supplementation in pregnancy","volume":"2015","author":"Rumbold","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1097\/00001648-200207000-00008","article-title":"Vitamin C and the risk of preeclampsia\u2014Results from dietary questionnaire and plasma assay","volume":"13","author":"Zhang","year":"2002","journal-title":"Epidemiology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1080\/10408398.2020.1744513","article-title":"Discrepancies in global vitamin C recommendations: A review of RDA criteria and underlying health perspectives","volume":"61","author":"Carr","year":"2021","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/j.1468-1293.2007.00454.x","article-title":"Multivitamin supplementation in HIV-positive pregnant women: Impact on depression and quality of life in a resource-poor setting","volume":"8","author":"Kaaya","year":"2007","journal-title":"HIV Med."},{"key":"ref_45","first-page":"517","article-title":"Analysis of serum and supplemented vitamin C and oxidative stress in HIV-infected children and adolescents","volume":"87","author":"Oliveira","year":"2011","journal-title":"J. Pediatr. (Rio J.)"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"S283","DOI":"10.1016\/j.jaac.2022.07.579","article-title":"Vitamins and minerals treat antenatal depression and improve birth and infant development: Results of the double-blind NutriMum RCT [Abstract]","volume":"61","author":"Rucklidge","year":"2022","journal-title":"J. Am. Acad. Child. Adolesc. Psychiatry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1096\/fj.02-1167fje","article-title":"Impaired adrenal catecholamine system function in mice with deficiency of the ascorbic acid transporter (SVCT2)","volume":"17","author":"Bornstein","year":"2003","journal-title":"FASEB J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1093\/ajcn\/86.1.145","article-title":"Human adrenal glands secrete vitamin C in response to adrenocorticotrophic hormone","volume":"86","author":"Padayatty","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13054-019-2332-x","article-title":"The adrenal-vitamin C axis: From fish to guinea pigs and primates","volume":"23","author":"Hooper","year":"2019","journal-title":"Crit. Care"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"S84","DOI":"10.21037\/jtd.2019.12.64","article-title":"Vitamin C: An essential \u201cstress hormone\u201d during sepsis","volume":"12","author":"Marik","year":"2020","journal-title":"J. Thorac. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1086\/421997","article-title":"Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: A systematic review and meta-analysis","volume":"39","author":"Simon","year":"2004","journal-title":"Clin. Infect. Dis."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/4\/941\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:17:06Z","timestamp":1760123826000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/4\/941"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,17]]},"references-count":51,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["antiox12040941"],"URL":"https:\/\/doi.org\/10.3390\/antiox12040941","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,17]]}}}