{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T16:48:10Z","timestamp":1780850890278,"version":"3.54.1"},"reference-count":40,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Older people are prone to frailness, present poor adherence to pharmacotherapy, and often have adverse drug effects. Therefore, it is important to develop effective and safe interventions to mitigate the burden of anxiety and depression disorders in this population. The aim of this study was to investigate the effect of vitamin D supplementation on the anxiety and depression status of elderly people with prediabetes. Participants were randomly assigned a weekly dose of vitamin D3 of 25,000 IU (n = 45, mean age 73.10 \u00b1 7.16 years) or nothing (n = 45, mean age 74.03 \u00b1 7.64 years), in addition to suggested lifestyle measures. The State-Trait Anxiety Inventory subscales (STAI-T and STAI-S) and the Patient Health Questionnaire-9 (PHQ-9) were used to evaluate anxiety and depression levels, respectively, at baseline, 6, and 12 months. A total of 92.68% of the participants in the vitamin D group and 97.14% of the controls exhibited vitamin D deficiency (&lt;20 ng\/mL) at baseline. Mean STAI-T scores were lower in supplemented individuals than in the control group at 6 (38.02 \u00b1 9.03 vs. 43.91 \u00b1 7.18, p = 0.003) and 12 months (32.35 \u00b1 7.77 vs. 44.97 \u00b1 7.78, p &lt; 0.001). The same pattern was evident for STAI-S scores at 6 (37.11 \u00b1 7.88 vs. 43.20 \u00b1 9.33, p = 0.003) and 12 months (32.59 \u00b1 6.45 vs. 44.60 \u00b1 9.53, p &lt; 0.001). Supplemented participants demonstrated lower mean PHQ-9 scores compared to controls at 6 (15.69 \u00b1 6.15 vs. 19.77 \u00b1 8.96, p = 0.021) and 12 months (13.52 \u00b1 5.01 vs. 20.20 \u00b1 8.67, p &lt; 0.001). Participants with deficiency and insufficiency at baseline experienced equal benefits of supplementation in terms of anxiety and depression scores. In conclusion, in a high-risk population, a weekly vitamin D supplementation scheme was effective in alleviating anxiety and depression symptoms. More studies are needed to elucidate the relevant mechanisms.<\/jats:p>","DOI":"10.3390\/metabo12100884","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T22:36:44Z","timestamp":1663713404000},"page":"884","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Vitamin D Alleviates Anxiety and Depression in Elderly People with Prediabetes: A Randomized Controlled Study"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0122-4391","authenticated-orcid":false,"given":"Evangelia","family":"Zaromytidou","sequence":"first","affiliation":[{"name":"Nuclear Medicine Department, Hippokration General Hospital, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5853-1352","authenticated-orcid":false,"given":"Theocharis","family":"Koufakis","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, First Department of Internal Medicine, AHEPA University Hospital, Medical School, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2351-7411","authenticated-orcid":false,"given":"Georgios","family":"Dimakopoulos","sequence":"additional","affiliation":[{"name":"BIOSTATS, Epirus Science and Technology Park Campus, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despina","family":"Drivakou","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, First Department of Internal Medicine, AHEPA University Hospital, Medical School, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stavroula","family":"Konstantinidou","sequence":"additional","affiliation":[{"name":"Theageneio Hospital, 54639 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pantelitsa","family":"Rakitzi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, First Department of Internal Medicine, AHEPA University Hospital, Medical School, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Grammatiki","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, First Department of Internal Medicine, AHEPA University Hospital, Medical School, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Manthou","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, First Department of Internal Medicine, AHEPA University Hospital, Medical School, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Notopoulos","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Department, Hippokration General Hospital, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Iakovou","sequence":"additional","affiliation":[{"name":"Second Academic Nuclear Medicine Department, Academic General Hospital of Thessaloniki \u201cAHEPA\u201d, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Gotzamani-Psarrakou","sequence":"additional","affiliation":[{"name":"Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalliopi","family":"Kotsa","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, First Department of Internal Medicine, AHEPA University Hospital, Medical School, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/2049-3258-72-32","article-title":"Effects of vitamin D in the elderly population: Current status and perspectives","volume":"72","author":"Cavalier","year":"2014","journal-title":"Arch. Public Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1530\/EJE-13-0855","article-title":"Vitamin D deficiency in elderly people in Swedish nursing homes is associated with increased mortality","volume":"170","author":"Samefors","year":"2014","journal-title":"Eur. J. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/ageing\/afh209","article-title":"Vitamin D supplementation improves neuromuscular function in older people who fall","volume":"33","author":"Dhesi","year":"2004","journal-title":"Age Ageing"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/s41574-021-00593-z","article-title":"The health effects of vitamin D supplementation: Evidence from human studies","volume":"18","author":"Bouillon","year":"2022","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"328","DOI":"10.2337\/cd19-0101","article-title":"Prediabetes Deserves More Attention: A Review","volume":"38","author":"Lawal","year":"2020","journal-title":"Clin. Diabetes"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1001\/archinternmed.2010.356","article-title":"Bidirectional Association Between Depression and Type 2 Diabetes Mellitus in Women","volume":"170","author":"Pan","year":"2010","journal-title":"Arch. Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1111\/dme.14232","article-title":"Anxiety boosts progression of prediabetes to type 2 diabetes: Findings from the prospective Cooperative Health Research in the Region of Augsburg F4 and FF4 studies","volume":"37","author":"Jiang","year":"2020","journal-title":"Diabet. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/nyas.13712","article-title":"Inflammation in psychiatric disorders: What comes first?","volume":"1437","author":"Bauer","year":"2019","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.2337\/diacare.27.9.2154","article-title":"Relationship of Depression and Diabetes Self-Care, Medication Adherence, and Preventive Care","volume":"27","author":"Lin","year":"2004","journal-title":"Diabetes Care"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.maturitas.2020.10.005","article-title":"Type 2 diabetes management in people aged over seventy-five years: Targets and treatment strategies","volume":"143","author":"Koufakis","year":"2021","journal-title":"Maturitas"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/17512433.2022.2043153","article-title":"The effect of vitamin D supplementation on glycemic status of elderly people with prediabetes: A 12-month open-label, randomized-controlled study","volume":"15","author":"Zaromytidou","year":"2022","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Professional Practice Committee (2022). 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2022. Diabetes Care, 45, S17\u2013S38.","DOI":"10.2337\/dc22-S002"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e722","DOI":"10.1161\/CIR.0000000000001040","article-title":"Comprehensive Management of Cardiovascular Risk Factors for Adults with Type 2 Diabetes: A Scientific Statement from the American Heart Association","volume":"145","author":"Joseph","year":"2022","journal-title":"Circulation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1744-859X-5-2","article-title":"Reliability and psychometric properties of the Greek translation of the State-Trait Anxiety Inventory form Y: Preliminary data","volume":"5","author":"Fountoulakis","year":"2006","journal-title":"Ann. Gen. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000478993","article-title":"State and Trait Anxiety Scores of Patients Receiving Intravitreal Injections","volume":"2","author":"Kayikcioglu","year":"2017","journal-title":"Biomed. Hub"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1046\/j.1525-1497.2001.016009606.x","article-title":"The PHQ-9: Validity of a brief depression severity measure","volume":"16","author":"Kroenke","year":"2001","journal-title":"J. Gen. Intern. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/j.comppsych.2012.05.008","article-title":"Patient Health Questionnaire: Greek language validation and subscale factor structure","volume":"53","author":"Karekla","year":"2012","journal-title":"Compr. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"E191","DOI":"10.1503\/cmaj.110829","article-title":"Optimal cut-off score for diagnosing depression with the Patient Health Questionnaire (PHQ-9): A meta-analysis","volume":"184","author":"Manea","year":"2011","journal-title":"Can. Med. Assoc. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1210\/jc.2011-0385","article-title":"Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline","volume":"96","author":"Holick","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e21506","DOI":"10.1097\/MD.0000000000021506","article-title":"Vitamin D sup-plement on prevention of fall and fracture: A Meta-analysis of Randomized Controlled Trials","volume":"99","author":"Thanapluetiwong","year":"2020","journal-title":"Medicine"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zheng, Y.T., Cui, Q.Q., Hong, Y.M., and Yao, W.G. (2015). A Meta-Analysis of High Dose, Intermittent Vitamin D Supplementation among Older Adults. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0115850"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3430","DOI":"10.1210\/jc.2008-0241","article-title":"Comparison of Daily, Weekly, and Monthly Vitamin D3 in Ethanol Dosing Protocols for Two Months in Elderly Hip Fracture Patients","volume":"93","author":"Segal","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1001\/jamainternmed.2020.8774","article-title":"Risk of Progression to Diabetes Among Older Adults with Prediabetes","volume":"181","author":"Rooney","year":"2021","journal-title":"JAMA Intern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1192\/bjp.bp.111.106666","article-title":"Vitamin D deficiency and depression in adults: Systematic review and me-ta-analysis","volume":"202","author":"Anglin","year":"2013","journal-title":"Br. J. Psychiatry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11","DOI":"10.4103\/IJPSYM.IJPSYM_160_19","article-title":"Vitamin D and Depression: A Critical Appraisal of the Evidence and Future Directions","volume":"42","author":"Menon","year":"2020","journal-title":"Indian J. Psychol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1016\/j.clnu.2018.09.011","article-title":"Effect of vitamin D supplementation on depression in elderly patients: A randomized clinical trial","volume":"38","author":"Alavi","year":"2019","journal-title":"Clin. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e2342","DOI":"10.1002\/brb3.2342","article-title":"Effect of omega-3 and vitamin D co-supplementation on psychological distress in reproductive-aged women with pre-diabetes and hypovitaminosis D: A randomized controlled trial","volume":"11","author":"Dolatian","year":"2021","journal-title":"Brain Behav."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1002\/da.23025","article-title":"The effect of vitamin D supplement on negative emotions: A systematic review and me-ta-analysis","volume":"37","author":"Cheng","year":"2020","journal-title":"Depress. Anxiety"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.1017\/jns.2018.14","article-title":"Effect of vitamin D supplementation on depressive symptoms and psychological wellbeing in healthy adult women: A double-blind randomised controlled clinical trial","volume":"7","author":"Choukri","year":"2018","journal-title":"J. Nutr. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e30","DOI":"10.1017\/jns.2018.19","article-title":"No improvement in depressive symptoms by vitamin D supplementation: Results from a randomised con-trolled trial","volume":"7","author":"Jorde","year":"2018","journal-title":"J. Nutr. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4103\/ijpvm.IJPVM_174_18","article-title":"Effect of Vitamin D supplement on mood status and inflammation in Vitamin D deficient Type 2 diabetic women with anxiety: A randomized clinical trial","volume":"10","author":"Amani","year":"2019","journal-title":"Int. J. Prev. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1124\/pr.116.013227","article-title":"Vitamin D and Depression: Cellular and Regulatory Mechanisms","volume":"69","author":"Berridge","year":"2017","journal-title":"Pharmacol. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/j.1469-1809.2010.00631.x","article-title":"Vitamin D Receptor Gene as a Candidate Gene for Parkinson Disease","volume":"75","author":"Butler","year":"2010","journal-title":"Ann. Hum. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"530","DOI":"10.2174\/157015911798376262","article-title":"Neurotrophins Role in Depression Neurobiology: A Review of Basic and Clinical Evidence","volume":"9","author":"Neto","year":"2011","journal-title":"Curr. Neuropharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"641","DOI":"10.12659\/MSM.889278","article-title":"The effect of acute administration of Vitamin D on micro vascular endothelial function in Caucasians and South Asian Indians","volume":"19","author":"Save","year":"2013","journal-title":"Med. Sci. Monit."},{"key":"ref_36","first-page":"18","article-title":"Racial Difference in Response to Vitamin D Supplementation","volume":"107","author":"Kresevic","year":"2015","journal-title":"J. Natl. Med. Assoc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1207\/S15327752JPA8001_10","article-title":"Self-Report Bias and Underreporting of Depression on the BDI-II","volume":"80","author":"Hunt","year":"2003","journal-title":"J. Pers. Assess."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1176\/appi.ajp.2021.20101479","article-title":"Incident Major Depressive Disorder Predicted by Three Measures of Insulin Resistance: A Dutch Cohort Study","volume":"178","author":"Watson","year":"2021","journal-title":"Am. J. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"300060520918411","DOI":"10.1177\/0300060520918411","article-title":"Negative emotions in community-dwelling adults with prediabetes and hyper-tension","volume":"48","author":"Zhuang","year":"2020","journal-title":"J. Int. Med. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"M210","DOI":"10.1093\/geronj\/46.6.M210","article-title":"The association of age and depression among the elderly: An epidemiologic ex-ploration","volume":"46","author":"Blazer","year":"1991","journal-title":"J. Gerontol."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/10\/884\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:35:40Z","timestamp":1760142940000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/10\/884"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,20]]},"references-count":40,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["metabo12100884"],"URL":"https:\/\/doi.org\/10.3390\/metabo12100884","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,20]]}}}