{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T19:44:30Z","timestamp":1788551070206,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:00:00Z","timestamp":1693353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Veterans Affairs"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Many veterans deployed to Gulf War areas suffer from persistent chronic diarrhea that is disabling and affects their quality of life. The causes for this condition have eluded investigators until recently and recent literature has shed light on the effect of vitamin D on the brain\u2013gut axis. This study focused on determining clinical causes contributing to diarrhea and assessed whether reversing the identified causes, specifically vitamin D deficiency (VDD), could reduce the incidence of diarrhea in Gulf War veterans (GWVs). All patients completed a workup that included serologies (IBD, celiac), routine laboratory tests (CBC, chemistry panels, TSH, T4, CRP), cultures for enteric pathogens (C diff, bacteria, viruses, small intestinal bacterial overgrowth (SIBO)), and upper and lower endoscopies with histology and a trial of cholestyramine to exclude choleretic diarrhea and rifaximin for dysbiosis. A total of 4221 veterans were screened for chronic diarrhea, yielding 105 GWVs, of which 69 GWVs had irritable bowel syndrome with diarrhea (IBS-D). Paired t-tests demonstrated that all GWVs had VDD (t-11.62, df68 and sig(2-tailed) 0.0001) (defined as a vitamin D level less than 30 ng\/mL with normal ranges of 30\u2013100 ng\/mL) but no positive serologies, inflammatory markers, abnormal endoscopies, cultures, or histology to explain their persistent diarrhea. There was no correlation with age, BMI, or inflammation. Some zip codes had a higher frequency of GWVs with VDD, but the number of deployments had no impact. Treatment with vitamin D supplementation (3000\u20135000 units), given in the morning, based on weight, reduced the number of bowel movements per day (p &lt; 0.0001) without causing hypercalcemia. We suggest that VDD is important in the etiology of IBS-D in GWVs and that vitamin D supplementation significantly reduces diarrhea.<\/jats:p>","DOI":"10.3390\/diagnostics13172807","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T09:48:15Z","timestamp":1693388895000},"page":"2807","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Vitamin D Deficiency (VDD) and Benefits of Supplementation in Veterans with IBS-D"],"prefix":"10.3390","volume":"13","author":[{"given":"Chandrasekhar","family":"Kesavan","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, VA Loma Linda Healthcare System, Loma Linda, CA 92357, USA"},{"name":"Department of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"},{"name":"Musculoskeletal Disease Center, VA Loma Linda Healthcare System, Loma Linda, CA 92357, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, VA Loma Linda Healthcare System, Loma Linda, CA 92357, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preeya","family":"Goyal","sequence":"additional","affiliation":[{"name":"Department of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"},{"name":"Presbyterian Intercommunity Hospital, Los Angeles, CA 90602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian S.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, VA Loma Linda Healthcare System, Loma Linda, CA 92357, USA"},{"name":"Department of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna D.","family":"Strong","sequence":"additional","affiliation":[{"name":"Department of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"},{"name":"Musculoskeletal Disease Center, VA Loma Linda Healthcare System, Loma Linda, CA 92357, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Strong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, VA Loma Linda Healthcare System, Loma Linda, CA 92357, USA"},{"name":"Department of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1093\/clind\/16.4.580","article-title":"Infectious Diseases During the Civil War: The Triumph of the \u201cThird Army\u201d","volume":"16","author":"Sartin","year":"1993","journal-title":"Clin. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e13533","DOI":"10.1111\/nmo.13533","article-title":"Risk factors for upper and lower functional gastrointestinal disorders in Persian Gulf War Veterans during and post-deployment","volume":"31","author":"Tuteja","year":"2019","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1136\/jim-2021-002291","article-title":"Autonomic dysfunction and gastroparesis in Gulf War veterans","volume":"71","author":"Verne","year":"2023","journal-title":"J. Investig. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1111\/j.1365-2036.2010.04387.x","article-title":"Trauma history and risk of the irritable bowel syndrome in women veterans","volume":"32","author":"White","year":"2010","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/ajg.2015.386","article-title":"The Epidemiology of Irritable Bowel Syndrome in the US Military: Findings from the Millennium Cohort Study","volume":"111","author":"Riddle","year":"2016","journal-title":"Am. J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1080\/1028415X.2022.2031494","article-title":"Efficacy of B-vitamins and vitamin D therapy in improving depressive and anxiety disorders: A systematic review of randomized controlled trials","volume":"26","author":"Cardoso","year":"2023","journal-title":"Nutr. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s40263-019-00640-4","article-title":"Potential Role of Vitamin D for the Management of Depression and Anxiety","volume":"33","author":"Casseb","year":"2019","journal-title":"CNS Drugs"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jad.2020.03.029","article-title":"Effects of vitamin D supplementation on depression and some involved neurotransmitters","volume":"269","author":"Kaviani","year":"2020","journal-title":"J. Affect. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kouba, B.R., Camargo, A., Gil-Mohapel, J., and Rodrigues, A.L.S. (2022). Molecular Basis Underlying the Therapeutic Potential of Vitamin D for the Treatment of Depression and Anxiety. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137077"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Rajkumar, R.P. (2023). Biomarkers of Neurodegeneration in Post-Traumatic Stress Disorder: An Integrative Review. Biomedicines, 11.","DOI":"10.20944\/preprints202303.0533.v1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"109760","DOI":"10.1016\/j.pnpbp.2019.109760","article-title":"Posttraumatic stress disorder is associated with reduced vitamin D levels and functional polymorphisms of the vitamin D binding-protein in a population-based sample","volume":"96","author":"Terock","year":"2020","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_12","first-page":"50","article-title":"Gastrointestinal problems, mechanisms and possible therapeutic directions in Gulf war illness: A mini review","volume":"8","author":"Kimono","year":"2021","journal-title":"Mil. Med. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"59","DOI":"10.4269\/ajtmh.2011.10-0093","article-title":"A Prospective Study of Acute Diarrhea in a Cohort of United States Military Personnel on Deployment to the Multinational Force and Observers, Sinai, Egypt","volume":"84","author":"Riddle","year":"2011","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_14","first-page":"2095","article-title":"Traveler\u2019s diarrhea","volume":"71","author":"Yates","year":"2005","journal-title":"Am. Fam. Physician"},{"key":"ref_15","first-page":"15","article-title":"Gastrointestinal problems in modern wars: Clinical features and possible mechanisms","volume":"2","author":"Wang","year":"2015","journal-title":"Mil. Med. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1097\/00042737-200501000-00002","article-title":"Intestinal infection and irritable bowel syndrome","volume":"17","author":"Parry","year":"2005","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/j.1365-2036.2007.03399.x","article-title":"Systematic review and meta-analysis: The incidence and prognosis of post-infectious irritable bowel syndrome","volume":"26","author":"Thabane","year":"2007","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1093\/infdis\/167.4.986","article-title":"Norwalk Virus Infection among Desert Storm Troops","volume":"167","author":"Hyams","year":"1993","journal-title":"J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3262","DOI":"10.1007\/s10620-011-1762-3","article-title":"Risk of Functional Gastrointestinal Disorders in U.S. Military Following Self-Reported Diarrhea and Vomiting During Deployment","volume":"56","author":"Porter","year":"2011","journal-title":"Dig. Dis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1093\/jnci\/djj101","article-title":"Prospective Study of Predictors of Vitamin D Status and Cancer Incidence and Mortality in Men","volume":"98","author":"Giovannucci","year":"2006","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1001\/archinte.168.12.1340","article-title":"Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality","volume":"168","author":"Dobnig","year":"2008","journal-title":"Arch. Intern. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/j.1440-1746.2011.06643.x","article-title":"Post-infectious irritable bowel syndrome: The past, the present and the future","volume":"26","author":"Ghoshal","year":"2011","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"497585","DOI":"10.1155\/2013\/497585","article-title":"The Prevalence of Functional Gastrointestinal Disorders in the Chinese Air Force Population","volume":"2013","author":"Wu","year":"2013","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/milmed\/166.3.223","article-title":"Functional Gastrointestinal Disorders among Soldiers in Peacetime Versus Out-of-Area Missions","volume":"166","author":"Fallen","year":"2001","journal-title":"Mil. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"696","DOI":"10.7205\/MILMED.170.8.696","article-title":"Evaluation of Chronic Gastrointestinal Symptoms following Persian Gulf War Exposure","volume":"170","author":"Koch","year":"2005","journal-title":"Mil. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1136\/gutjnl-2022-328515","article-title":"Irritable bowel syndrome: Treatment based on pathophysiology and biomarkers","volume":"72","author":"Camilleri","year":"2023","journal-title":"Gut"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Altomare, A., Di Rosa, C., Imperia, E., Emerenziani, S., Cicala, M., and Guarino, M.P.L. (2021). Diarrhea Predominant-Irritable Bowel Syndrome (IBS-D): Effects of Different Nutritional Patterns on Intestinal Dysbiosis and Symptoms. Nutrients, 13.","DOI":"10.3390\/nu13051506"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17","DOI":"10.14309\/ajg.0000000000001036","article-title":"ACG Clinical Guideline: Management of Irritable Bowel Syndrome","volume":"116","author":"Lacy","year":"2020","journal-title":"Am. J. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"709","DOI":"10.20452\/pamw.16067","article-title":"Recent advances in the treatment of irritable bowel syndrome","volume":"131","author":"Bonetto","year":"2021","journal-title":"Pol. Arch. Intern. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s12325-019-01116-z","article-title":"Current US Food and Drug Administration-Approved Pharmacologic Therapies for the Treatment of Irritable Bowel Syndrome with Diarrhea","volume":"37","author":"Brenner","year":"2020","journal-title":"Adv. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1053\/j.gastro.2022.04.017","article-title":"AGA Clinical Practice Guideline on the Pharmacological Management of Irritable Bowel Syndrome With Diarrhea","volume":"163","author":"Lembo","year":"2022","journal-title":"Gastroenterology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1111\/j.1365-2036.2005.02463.x","article-title":"Irritable bowel syndrome in the United States: Prevalence, symptom patterns and impact","volume":"21","author":"Hungin","year":"2005","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_33","first-page":"755","article-title":"A Systematic Review of the Economic and Humanistic Burden of Illness in Irritable Bowel Syndrome and Chronic Constipation","volume":"19","author":"Nellesen","year":"2013","journal-title":"J. Manag. Care Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1053\/gast.2000.16484","article-title":"The impact of irritable bowel syndrome on health-related quality of life","volume":"119","author":"Gralnek","year":"2000","journal-title":"Gastroenterology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1093\/fampra\/cmg608","article-title":"Family practitioners\u2019 attitudes and knowledge about irritable bowel syndrome: Effect of a trial of physician education","volume":"20","author":"Longstreth","year":"2003","journal-title":"Fam. Pract."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1097\/00042737-199707000-00008","article-title":"Irritable bowel syndrome: The view from general practice","volume":"9","author":"Thompson","year":"1997","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_37","first-page":"495","article-title":"Prevalence of irritable bowel syndrome: A community survey","volume":"54","author":"Wilson","year":"2004","journal-title":"Br. J. Gen. Pract."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1097\/00004836-199912000-00009","article-title":"A National Survey of Practice Patterns of Gastroenterologists With Comparison to the Past Two Decades","volume":"29","author":"Russo","year":"1999","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1002\/ueg2.12259","article-title":"Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility","volume":"10","author":"Savarino","year":"2022","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Roffe-Vazquez, D.N., Huerta-Delgado, A.S., Castillo, E.C., Villarreal-Calder\u00f3n, J.R., Gonzalez-Gil, A.M., Enriquez, C., Garcia-Rivas, G., and Elizondo-Montemayor, L. (2019). Correlation of Vitamin D with Inflammatory Cytokines, Atherosclerotic Parameters, and Lifestyle Factors in the Setting of Heart Failure: A 12-Month Follow-Up Study. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225811"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s11154-019-09532-w","article-title":"Consensus statement from 2nd International Conference on Controversies in Vitamin D","volume":"21","author":"Giustina","year":"2020","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1089\/neu.2022.0053","article-title":"Vitamin D Deficiency and Prognosis after Traumatic Brain Injury with Intracranial Injury: A Multi-Center Observational Study","volume":"39","author":"Jung","year":"2022","journal-title":"J. Neurotrauma"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1007\/s11914-022-00732-z","article-title":"Vitamin D Regulation of Immune Function","volume":"20","author":"Bikle","year":"2022","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1080\/07315724.2018.1510349","article-title":"Association of Serum Vitamin D Concentration With Clinical Symptoms and Quality of Life in Patients With Irritable Bowel Syndrome","volume":"38","author":"Abbasnezhad","year":"2019","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e43","DOI":"10.1017\/SJP.2020.40","article-title":"Meta-analysis and Scientific Mapping of Well-being and Job Performance","volume":"23","author":"Polo","year":"2020","journal-title":"Span. J. Psychol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"115","DOI":"10.5001\/omj.2015.25","article-title":"Vitamin D Deficiency in Patients with Irritable Bowel Syndrome: Does it Exist?","volume":"30","author":"Khayyat","year":"2015","journal-title":"Oman Med. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1007\/s11154-021-09693-7","article-title":"Vitamin D: Dosing, levels, form, and route of administration: Does one approach fit all?","volume":"22","author":"Bilezikian","year":"2021","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e832","DOI":"10.1542\/peds.2012-3986","article-title":"Vitamin D3 Supplementation and Childhood Diarrhea: A Randomized Controlled Trial","volume":"132","author":"Aluisio","year":"2013","journal-title":"Pediatrics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s12937-022-00777-x","article-title":"The efficacy of vitamin D supplementation for irritable bowel syndrome: A systematic review with meta-analysis","volume":"21","author":"Huang","year":"2022","journal-title":"Nutr. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"894","DOI":"10.31729\/jnma.7070","article-title":"Low Vitamin D Levels in Patients with Irritable Bowel Syndrome of a Tertiary Care Hospital: A Descriptive Cross-sectional Study","volume":"59","author":"Bhandari","year":"2021","journal-title":"J. Nepal Med. Assoc."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1111\/jgh.15166","article-title":"Diarrhea and altered inflammatory cytokine pattern in severe coronavirus disease 2019: Impact on disease course and in-hospital mortality","volume":"36","author":"Zhang","year":"2021","journal-title":"J. Gastroenterol. Hepatol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/17\/2807\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:42:49Z","timestamp":1760128969000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/17\/2807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,30]]},"references-count":51,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["diagnostics13172807"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics13172807","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,30]]}}}