{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T05:17:33Z","timestamp":1788671853757,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018696","name":"Normandy Region","doi-asserted-by":"publisher","award":["17P03672"],"award-info":[{"award-number":["17P03672"]}],"id":[{"id":"10.13039\/501100018696","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Laboratoire Dielen\u00ae","award":["17P03672"],"award-info":[{"award-number":["17P03672"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Anxiety is a high frequency disorder in the general population. It is usually treated with benzodiazepines, which cause side effects and a dependence that could make withdrawal difficult. Alternative treatments are therefore needed to reduce the use of anxiolytics, particularly for adjustment disorder with anxiety. An observational, multicentre, prospective, longitudinal study has been conducted by general practitioners and one gynaecologist to evaluate the efficacy of a dietary supplement on adjustment disorder with anxiety (Stress 2 study). Patients diagnosed as anxious with a score of \u226520 on the Hamilton Anxiety Rating Scale (Ham-A, first visit on Day 0 (V0)) were offered a 28-day treatment with a dietary supplement formulated with bioactive peptides from a fish protein hydrolysate (Gabolysat\u00ae), magnesium and vitamin B6. At the second visit (V1), the Ham-A Rating Scale, the Patient Global Impression scale (PGI) and the Clinical Global Impressions scale (CGI) were administered. A 50% reduction in the Ham-A score, was achieved for 41.9% of the patients. The mean Ham-A score decreased by 12.1 \u00b1 5.7 points (p &lt; 0.001) between V0 (25.6 \u00b1 3.8) and V1 (13.6 \u00b1 6.0). Furthermore, according to the CGI scale, the anxiety of 75.3% of patients improved significantly and very significantly, with limited side effects and a negligible rebound effect. In conclusion, adjustment disorder with anxiety seems to be effectively managed by an alternative and safer solution than benzodiazepines.<\/jats:p>","DOI":"10.3390\/nu14122425","type":"journal-article","created":{"date-parts":[[2022,6,12]],"date-time":"2022-06-12T23:55:24Z","timestamp":1655078124000},"page":"2425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effect of a Dietary Supplement Combining Bioactive Peptides and Magnesium on Adjustment Disorder with Anxiety: A Clinical Trial in General Practice"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2888-8430","authenticated-orcid":false,"given":"Sarah","family":"Oddoux","sequence":"first","affiliation":[{"name":"Laboratoire Dielen, 50110 Cherbourg-en-Cotentin, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Violette","sequence":"additional","affiliation":[{"name":"Laboratoire Dielen, 50110 Cherbourg-en-Cotentin, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne","family":"Cornet","sequence":"additional","affiliation":[{"name":"Euraxi Pharma, 37300 Jou\u00e9-l\u00e8s-Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5392-6331","authenticated-orcid":false,"given":"Julie","family":"Akkoyun-Farinez","sequence":"additional","affiliation":[{"name":"Euraxi Pharma, 37300 Jou\u00e9-l\u00e8s-Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Besnier","sequence":"additional","affiliation":[{"name":"Centre M\u00e9dical Th\u00e9mis, 50100 Cherbourg-en-Cotentin, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"No\u00ebl","sequence":"additional","affiliation":[{"name":"Laboratoire Dielen, 50110 Cherbourg-en-Cotentin, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Rouillon","sequence":"additional","affiliation":[{"name":"H\u00f4pital Ste Anne, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association. [5th ed.].","DOI":"10.1176\/appi.books.9780890425596"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1745-0179-5-15","article-title":"Adjustment Disorder: Epidemiology, Diagnosis and Treatment","volume":"5","author":"Carta","year":"2009","journal-title":"Clin. Pract. Epidemiol. Ment. Health"},{"key":"ref_3","first-page":"CD006389","article-title":"Interventions to Facilitate Return to Work in Adults with Adjustment Disorders","volume":"12","author":"Arends","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s12325-015-0176-6","article-title":"Etifoxine Versus Alprazolam for the Treatment of Adjustment Disorder with Anxiety: A Randomized Controlled Trial","volume":"32","author":"Stein","year":"2015","journal-title":"Adv. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3109\/13651501.2012.667114","article-title":"WFSBP Task Force on Mental Disorders in Primary Care; WFSBP Task Force on Anxiety Disorders, OCD and PTSD Guidelines for the Pharmacological Treatment of Anxiety Disorders, Obsessive\u2013Compulsive Disorder and Posttraumatic Stress Disorder in Primary Care","volume":"16","author":"Bandelow","year":"2012","journal-title":"Int. J. Psychiatry Clin. Pract."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1177\/0269881113503509","article-title":"Benzodiazepines: Risks and Benefits. A Reconsideration","volume":"27","author":"Baldwin","year":"2013","journal-title":"J. Psychopharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/bs.afnr.2016.10.003","article-title":"Protein Hydrolysates and Biopeptides","volume":"Volume 81","author":"Nasri","year":"2017","journal-title":"Advances in Food and Nutrition Research"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.biotechadv.2014.12.003","article-title":"Recent Advances in Food Biopeptides: Production, Biological Functionalities and Therapeutic Applications","volume":"33","author":"Saadi","year":"2015","journal-title":"Biotechnol. Adv."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s002139900338","article-title":"Diazepam-like Effects of a Fish Protein Hydrolysate (Gabolysat PC60) on Stress Responsiveness of the Rat Pituitary-Adrenal System and Sympathoadrenal Activity","volume":"149","author":"Bernet","year":"2000","journal-title":"Psychopharmacology"},{"key":"ref_10","first-page":"115","article-title":"Anxiolytic And Antidepressant-Like Effects Of Garum Armoricum\u00ae (GA), A Blue Ling Fish Protein Autolysate In Male Wistar Rats","volume":"6","author":"Messaoudi","year":"2008","journal-title":"Curr. Top. Nutraceutical Res."},{"key":"ref_11","first-page":"41","article-title":"The Effects Of Garum Armoricum\u00ae (GA) On Elevated-Plus Maze And Conditioned Light Extinction Tests In Rats","volume":"6","author":"Messaoudi","year":"2008","journal-title":"Curr. Top. Nutraceutical Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.jveb.2015.05.007","article-title":"Assessment of Noise-Induced Fear and Anxiety in Dogs: Modification by a Novel Fish Hydrolysate Supplemented Diet","volume":"10","author":"Landsberg","year":"2015","journal-title":"J. Vet. Behav."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A Simple Practice Guide for Dose Conversion between Animals and Human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"ref_14","first-page":"193","article-title":"The Effectiveness of Garum Armoricum (Stabilium) in Reducing Anxiety in College Students","volume":"8","author":"Dorman","year":"1995","journal-title":"J. Adv. Med."},{"key":"ref_15","unstructured":"(2022, May 09). Arr\u00eat\u00e9 du 3 D\u00e9cembre 1993 Portant Application du D\u00e9cret N\u00b0 93-1130 du 27 Septembre 1993 Concernant L\u2019\u00e9tiquetage Relatif Aux Qualit\u00e9s Nutritionnelles des Denr\u00e9es Alimentaires, Available online: https:\/\/www.legifrance.gouv.fr\/loda\/id\/JORFTEXT000000484070\/."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1085\/jgp.117.3.275","article-title":"Na+ Occupancy and Mg2+ Block of the N-Methyl-d-Aspartate Receptor Channel","volume":"117","author":"Zhu","year":"2001","journal-title":"J. Gen. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1046\/j.1471-4159.1994.62030916.x","article-title":"Bidirectional Modulation of GABA-Gated Chloride Channels by Divalent Cations: Inhibition by Ca2+ and Enhancement by Mg2+","volume":"62","author":"Schwartz","year":"1994","journal-title":"J. Neurochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.pbb.2004.01.006","article-title":"Antidepressant- and Anxiolytic-like Activity of Magnesium in Mice","volume":"78","author":"Poleszak","year":"2004","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_19","first-page":"655","article-title":"NMDA\/Glutamate Mechanism of Magnesium-Induced Anxiolytic-like Behavior in Mice","volume":"60","author":"Poleszak","year":"2008","journal-title":"Pharmacol. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1089\/152460900318623","article-title":"A Synergistic Effect of a Daily Supplement for 1 Month of 200 Mg Magnesium plus 50 Mg Vitamin B6 for the Relief of Anxiety-Related Premenstrual Symptoms: A Randomized, Double-Blind, Crossover Study","volume":"9","author":"Walker","year":"2000","journal-title":"J. Womens Health Gend. Based Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1185\/030079903125002603","article-title":"Double-Blind, Randomised, Placebo-Controlled Study to Evaluate the Efficacy and Safety of a Fixed Combination Containing Two Plant Extracts (Crataegus Oxyacantha and Eschscholtzia Californica) and Magnesium in Mild-to-Moderate Anxiety Disorders","volume":"20","author":"Hanus","year":"2004","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Tarleton, E.K., Littenberg, B., MacLean, C.D., Kennedy, A.G., and Daley, C. (2017). Role of Magnesium Supplementation in the Treatment of Depression: A Randomized Clinical Trial. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180067"},{"key":"ref_23","unstructured":"Nightingale, J.M.D. (2001). Intestinal Failure, Greenwich Medical Media."},{"key":"ref_24","first-page":"23","article-title":"Higher Absorption and Lower Urinary Elimination of a New Magnesium Rice Complex Compared to Two Other Organic Forms of Magnesium: A Pilot Study in Rats","volume":"1","author":"Bangratz","year":"2016","journal-title":"Gavin J. Food Nutrit. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1177\/0148607194018005430","article-title":"Bioavailability of Magnesium Diglycinate vs Magnesium Oxide in Patients with Ileal Resection","volume":"18","author":"Schuette","year":"1994","journal-title":"J. Parenter. Enter. Nutr."},{"key":"ref_26","first-page":"1","article-title":"Magnesium Bisglycinate as Safe Form for MIneral Supplementation in Human Nutrition","volume":"144","author":"Siebrecht","year":"2013","journal-title":"Int. J. Orthomol. Relat. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/j.1749-6632.1990.tb28049.x","article-title":"Neurobiology of Pyridoxine","volume":"585","author":"Dakshinamurti","year":"1990","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_28","first-page":"333","article-title":"Effect of Vitamin B-6 on Plasma and Red Blood Cell Magnesium Levels in Premenopausal Women","volume":"11","author":"Abraham","year":"1981","journal-title":"Ann. Clin. Lab. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1024\/0300-9831\/a000589","article-title":"Higher Vitamin B6 Intake Is Associated with Lower Depression and Anxiety Risk in Women but Not in Men: A Large Cross-Sectional Study","volume":"90","author":"Kafeshani","year":"2020","journal-title":"Int. J. Vitam. Nutr. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Pouteau, E., Kabir-Ahmadi, M., Noah, L., Mazur, A., Dye, L., Hellhammer, J., Pickering, G., and Dubray, C. (2018). Superiority of Magnesium and Vitamin B6 over Magnesium Alone on Severe Stress in Healthy Adults with Low Magnesemia: A Randomized, Single-Blind Clinical Trial. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0208454"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Boyle, N., Lawton, C., and Dye, L. (2017). The Effects of Magnesium Supplementation on Subjective Anxiety and Stress\u2014A Systematic Review. Nutrients, 9.","DOI":"10.3390\/nu9050429"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/0924-977X(95)90645-T","article-title":"A Double-Blind Controlled Study of PCR 7060 vs. Buspirone in the Treatment of Generalised Anxiety Disorder","volume":"5","author":"Rouillon","year":"1995","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.2044-8341.1959.tb00467.x","article-title":"The Assessment of Anxiety States by Rating","volume":"32","author":"Hamilton","year":"1959","journal-title":"Br. J. Med. Psychol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/S0013-7006(05)82386-3","article-title":"Pr\u00e9valence et comorbidit\u00e9 des troubles psychiatriques dans la population g\u00e9n\u00e9rale fran\u00e7aise: R\u00e9sultats de l\u2019\u00e9tude \u00e9pid\u00e9miologique ESEMeD\/MHEDEA 2000\/(ESEMeD)","volume":"31","author":"Gasquet","year":"2005","journal-title":"L\u2019Enc\u00e9phale"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/hup.757","article-title":"Efficacy of Etifoxine Compared to Lorazepam Monotherapy in the Treatment of Patients with Adjustment Disorders with Anxiety: A Double-Blind Controlled Study in General Practice","volume":"21","author":"Nguyen","year":"2006","journal-title":"Hum. Psychopharmacol. Clin. Exp."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Freret, T., Largilliere, S., Nee, G., Coolzaet, M., Corvaisier, S., and Boulouard, M. (2021). Fast Anxiolytic-Like Effect Observed in the Rat Conditioned Defensive Burying Test, after a Single Oral Dose of Natural Protein Extract Products. Nutrients, 13.","DOI":"10.3390\/nu13072445"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Vink, R., and Nechifor, M. (2011). Magnesium in Neuroses and Neuroticism. Magnesium in the Central Nervous System, University of Adelaide Press.","DOI":"10.1017\/UPO9780987073051"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/S0021-9258(19)77353-0","article-title":"The Gamma-Aminobutyric Acid-Alpha-Ketoglutaric Acid Transaminase of Beef Brain","volume":"233","author":"Baxter","year":"1958","journal-title":"J. Biol. Chem."},{"key":"ref_39","unstructured":"B\u00e9netier, C., Bertin, M., Calamassi-Tran, G., Dubuisson, C., Dufour, A., Gauchard, F., Lafay, L., Lioret, S., and Touvier, M. (2009). \u00c9tude Individuelle Nationale des Consommations Alimentaires 2 (INCA 2) 2006\u20132007, AFSSA."},{"key":"ref_40","unstructured":"(2015). Avis de l\u2019Agence Nationale de S\u00e9curit\u00e9 Sanitaire de L\u2019alimentation, de L\u2019environnement et du Travail Relatif \u00e0 L\u2019\u00e9valuation des Apports en Vitamines et Min\u00e9raux Issus de L\u2019alimentation Non Enrichie, de L\u2019alimentation Enrichie et des Compl\u00e9ments Alimentaires Dans la Population Fran\u00e7aise: Estimation des Apports Usuels, des Pr\u00e9valences D\u2019inad\u00e9quation et des Risques de D\u00e9passement des Limites de S\u00e9curit\u00e9, Scientific Opinion; Saisine n\u00b02012-SA-0142."},{"key":"ref_41","first-page":"69","article-title":"Guidelines for the Clinical Use of Benzodiazepines: Pharmacokinetics, Dependency, Rebound and Withdrawal. Canadian Society for Clinical Pharmacology","volume":"6","author":"Nelson","year":"1999","journal-title":"Can. J. Clin. Pharmacol. J. Can. Pharmacol. Clin."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/12\/2425\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:27:58Z","timestamp":1760138878000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/12\/2425"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,10]]},"references-count":41,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["nu14122425"],"URL":"https:\/\/doi.org\/10.3390\/nu14122425","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,10]]}}}