{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T19:48:13Z","timestamp":1782935293486,"version":"3.54.5"},"reference-count":69,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Ministry of Health and Welfare, Republic of Korea","doi-asserted-by":"publisher","award":["HF23C0181"],"award-info":[{"award-number":["HF23C0181"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Frailty is a major geriatric syndrome with a multifactorial etiology that induces a decline in multiple physiological and psychological functions. In traditional East Asian medicine (TEAM), qi and blood deficiency clinically represent as fatigue, anemia, anorexia, decreased strength after illness, and weakness, commonly interpretated as frailty. An herbal prescription of Insamyangyeongtang (IYT, Ninjin\u2019yoeito in Japanese, Ren-Shen-Yang-Rong-Tang in Chinese) tonifies qi and blood and has the potential to treat multiple targets caused by qi and blood deficiency. As the population ages and frailty increases, there is an increase in the potential effectiveness of IYT in frailty. This study reviewed relevant clinical trials to provide an updated view on the effect of IYT on frailty. IYT has therapeutic effects on frailty associated with chronic respiratory diseases (e.g., chronic obstructive pulmonary disease) and cognitive impairments (e.g., Alzheimer\u2019s disease) and improves respiratory symptoms and cognition. IYT also has therapeutic effects on weight gain, muscle mass, and strength, and improves nutritional status in frail elderly individuals who have decreased muscle mass and strength, loss of appetite, and weight loss. The same effect has been shown in frailty in elderly individuals with rehabilitation treatment and chronic diseases. IYT also improves frailty associated with symptoms such as intractable dizziness and genitourinary symptoms. The beneficial effects of IYT in several diseases could be important for medication replacement, reduction, and prevention of polypharmacy. Based on the results of this review, we suggest that IYT has the potential to be a therapeutic agent against frailty.<\/jats:p>","DOI":"10.3390\/nu16050721","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T11:19:24Z","timestamp":1709291964000},"page":"721","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Herbal Prescription of Insamyangyeongtang as a Therapeutic Agent for Frailty in Elderly: A Narrative Review"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7355-5638","authenticated-orcid":false,"given":"Han-Gyul","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Cardiology and Neurology, Kyung Hee University College of Korean Medicine, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9711-0449","authenticated-orcid":false,"given":"Ichiro","family":"Arai","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Nihon Pharmaceutical University, Tokyo 113-0034, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1857-3515","authenticated-orcid":false,"given":"Seungwon","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Neurology, Kyung Hee University College of Korean Medicine, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,1]]},"reference":[{"key":"ref_1","first-page":"433","article-title":"Frailty syndrome: An overview","volume":"9","author":"Chen","year":"2014","journal-title":"Clin. Interv. Aging"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.jamda.2015.12.016","article-title":"Frailty: An Emerging Public Health Priority","volume":"17","author":"Cesari","year":"2016","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/S0140-6736(12)62167-9","article-title":"Frailty in elderly people","volume":"381","author":"Clegg","year":"2013","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1111\/j.1728-4457.2008.00249.x","article-title":"Continued Reductions in Mortality at Advanced Ages","volume":"34","author":"Rau","year":"2008","journal-title":"Popul. Dev. Rev."},{"key":"ref_5","first-page":"383","article-title":"Interventions to prevent or reduce the level of frailty in community-dwelling older adults: A scoping review of the literature and international policies","volume":"46","author":"Puts","year":"2017","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1056\/NEJMoa1000485","article-title":"Adverse Events Associated with Testosterone Administration","volume":"363","author":"Basaria","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1001\/jama.288.3.321","article-title":"Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results from the Women\u2019s Health Initiative Randomized Controlled Trial","volume":"288","author":"Rossouw","year":"2002","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/j.2055-2335.2009.tb00440.x","article-title":"Pharmacological treatment of frailty in the elderly","volume":"39","author":"Campbell","year":"2009","journal-title":"J. Pharm. Pract. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s11655-013-1350-9","article-title":"Integration of Chinese medicine and Western medicine in clinical practice (Patient Care): Past, present, and a proposed model for the future","volume":"19","author":"Tsang","year":"2013","journal-title":"Chin. J. Integr. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1017\/S106279870300022X","article-title":"The integration of traditional Chinese medicine and Western medicine","volume":"11","author":"Keji","year":"2003","journal-title":"Eur. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41430-020-00737-w","article-title":"Nutrition and traditional Chinese medicine (TCM): A system\u2019s theoretical perspective","volume":"75","author":"Zhao","year":"2020","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_12","first-page":"173","article-title":"Symptom characteristics and prevalence of qi deficiency syndrome in people of varied health status and ages: A multicenter cross-sectional study","volume":"2","author":"Zhang","year":"2015","journal-title":"J. Tradit. Chin. Med. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"He, Y., Gao, T., Li, J., Chen, Z., Wang, L., Zhang, J., Gao, F., and Fu, C. (2019). Metabonomics study on the effect of Siwu Decoction for blood deficiency syndrome in rats using UPLC\u2013Q\/TOF\u2013MS analysis. Biomed. Chromatogr., 33.","DOI":"10.1002\/bmc.4617"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.tjog.2013.06.013","article-title":"On the qi deficiency in traditional Chinese medicine","volume":"53","author":"Chiang","year":"2014","journal-title":"Taiwan. J. Obstet. Gynecol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3389\/fnut.2018.00031","article-title":"Kampo Medicines for Frailty in Locomotor Disease","volume":"5","author":"Nakae","year":"2018","journal-title":"Front. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"00150","DOI":"10.3389\/fphar.2015.00150","article-title":"The translational aspect of complementary and alternative medicine for cancer with particular emphasis on Kampo","volume":"6","author":"Amitani","year":"2015","journal-title":"Front. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3389\/fnut.2018.00093","article-title":"Multifunctional Actions of Ninjinyoeito, a Japanese Kampo Medicine: Accumulated Scientific Evidence Based on Experiments with Cells and Animal Models, and Clinical Studies","volume":"5","author":"Miyano","year":"2018","journal-title":"Front. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9590260","DOI":"10.1155\/2019\/9590260","article-title":"Perspectives on the Use of Ninjin\u2019yoeito in Modern Medicine: A Review of Randomized Controlled Trials","volume":"2019","author":"Takayama","year":"2019","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_19","unstructured":"Japan Kampo Medicines Manufacturers Association (2023, November 01). Kampo Formulations for Prescription 2022\u2014Information in Package Inserts of 148 Formulation. Available online: https:\/\/www.nikkankyo.org\/seihin\/info_pi_english\/introduction.pdf."},{"key":"ref_20","first-page":"e2021031","article-title":"Frailty and chronic respiratory disease: The need for a multidisciplinary care model","volume":"38","author":"Symvoulakis","year":"2021","journal-title":"Sarcoidosis Vasc. Diffuse Lung Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13601-016-0116-9","article-title":"Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)","volume":"6","author":"Bousquet","year":"2016","journal-title":"Clin. Transl. Allergy"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.chest.2018.02.014","article-title":"The Relationship Between COPD and Frailty","volume":"154","author":"Marengoni","year":"2018","journal-title":"Chest"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.rmed.2019.01.008","article-title":"Frailty and geriatric conditions in older patients with idiopathic pulmonary fibrosis","volume":"148","author":"Sheth","year":"2019","journal-title":"Respir. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1164\/rccm.2009-040GL","article-title":"An Official ATS\/ERS\/JRS\/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management","volume":"183","author":"Raghu","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jep.2008.04.020","article-title":"Pharmacology of Schisandra chinensis Bail.: An overview of Russian research and uses in medicine","volume":"118","author":"Panossian","year":"2008","journal-title":"J. Ethnopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1089\/acm.2020.0083","article-title":"Usefulness of Ninjin\u2019yoeito for Chronic Obstructive Pulmonary Disease Patients with Frailty","volume":"26","author":"Hirai","year":"2020","journal-title":"J. Altern. Complement. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"102178","DOI":"10.1016\/j.npep.2021.102178","article-title":"A retrospective study on the efficacy of Ninjin\u2019yoeito on fatigue in patients with interstitial pneumonia","volume":"89","author":"Kushima","year":"2021","journal-title":"Neuropeptides"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3389\/fnut.2018.00071","article-title":"Improvement in Frailty in a Patient with Severe Chronic Obstructive Pulmonary Disease after Ninjin\u2019yoeito Therapy: A Case Report","volume":"5","author":"Hirai","year":"2018","journal-title":"Front. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"547512","DOI":"10.3389\/fnut.2021.547512","article-title":"Case Report: Ninjin\u2019yoeito May Improve Quality of Life After Hospitalization for Acute Illness in Patients with Frailty","volume":"8","author":"Kashima","year":"2021","journal-title":"Front. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"548076","DOI":"10.3389\/fnut.2021.548076","article-title":"Case Report: Efficacy of Ninjin\u2019yoeito Treatment for Idiopathic Pulmonary Fibrosis","volume":"8","author":"Kushima","year":"2021","journal-title":"Front. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"793","DOI":"10.3233\/JAD-150358","article-title":"Targeting Cognitive Frailty: Clinical and Neurobiological Roadmap for a Single Complex Phenotype","volume":"47","author":"Panza","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1089\/rej.2014.1637","article-title":"Cognitive Frailty: A Systematic Review of Epidemiological and Neurobiological Evidence of an Age-Related Clinical Condition","volume":"18","author":"Panza","year":"2015","journal-title":"Rejuvenation Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.arr.2013.06.004","article-title":"Frailty and cognitive impairment\u2014A review of the evidence and causal mechanisms","volume":"12","author":"Robertson","year":"2013","journal-title":"Ageing Res. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1136\/bjsports-2016-096587","article-title":"Exercise interventions for cognitive function in adults older than 50: A systematic review with meta-analysis","volume":"52","author":"Northey","year":"2018","journal-title":"Br. J. Sports Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Liu, Z., Hsu, F.-C., Trombetti, A., King, A.C., Liu, C.K., Manini, T.M., Fielding, R.A., Pahor, M., Newman, A.B., and Kritchevsky, S. (2018). Effect of 24-month physical activity on cognitive frailty and the role of inflammation: The LIFE randomized clinical trial. BMC Med., 16.","DOI":"10.1186\/s12916-018-1174-8"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/ggi.14322","article-title":"An update on cognitive frailty: Its definition, impact, associated factors and underlying mechanisms, and interventions","volume":"22","author":"Sugimoto","year":"2021","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1002\/jnr.21196","article-title":"Restoration of FcR\u03b3\/Fyn signaling repairs central nervous system demyelination","volume":"85","author":"Seiwa","year":"2007","journal-title":"J. Neurosci. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/psyg.12125","article-title":"Effect of ninjin\u2019yoeito, a Kampo (traditional Japanese) medicine, on cognitive impairment and depression in patients with Alzheimer\u2019s disease: 2 years of observation","volume":"16","author":"Kudoh","year":"2015","journal-title":"Psychogeriatrics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1080\/13880209.2020.1758732","article-title":"Polygala tenuifolia: A source for anti-Alzheimer\u2019s disease drugs","volume":"58","author":"Deng","year":"2020","journal-title":"Pharm. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.neulet.2009.08.033","article-title":"BT-11 is effective for enhancing cognitive functions in the elderly humans","volume":"465","author":"Shin","year":"2009","journal-title":"Neurosci. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.neulet.2009.03.024","article-title":"Effects of BT-11 on memory in healthy humans","volume":"454","author":"Lee","year":"2009","journal-title":"Neurosci. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0944-7113(97)80068-2","article-title":"Enhancements of choline acetyltransferase activity and nerve growth factor secretion by Polygalae radix-extract containing active ingredients in Kami-untan-to","volume":"4","author":"Yabe","year":"1997","journal-title":"Phytomedicine"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3233\/ADR-170026","article-title":"A Possibility of Simultaneous Treatment with the Multicomponent Drug, Ninjin\u2019yoeito, for Anorexia, Apathy, and Cognitive Dysfunction in Frail Alzheimer\u2019s Disease Patients: An Open-Label Pilot Study","volume":"1","author":"Ohsawa","year":"2017","journal-title":"J. Alzheimer\u2019s Dis. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3233\/ADR-220074","article-title":"Frailty Improvement by Multicomponent Drug, Ninjin\u2019Yoeito, in Mild Cognitive Impairment and Mild Alzheimer\u2019s Disease Patients: An Open-Label Exploratory Study (FRAMINGO)","volume":"7","author":"Okahara","year":"2023","journal-title":"J. Alzheimer\u2019s Dis. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"551373","DOI":"10.3389\/fnut.2021.551373","article-title":"Case Report: Nutritional Examination of Weight Loss Treatment Using Kampo","volume":"8","author":"Matsui","year":"2021","journal-title":"Front. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3389\/fnut.2019.00014","article-title":"Safety and Effectiveness of Ninjin\u2019yoeito: A Utilization Study in Elderly Patients","volume":"6","author":"Suzuki","year":"2019","journal-title":"Front. Nutr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1093\/gerona\/63.9.984","article-title":"Initial Manifestations of Frailty Criteria and the Development of Frailty Phenotype in the Women\u2019s Health and Aging Study II","volume":"63","author":"Xue","year":"2008","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/gerona\/61.6.589","article-title":"Low Nutrient Intake Is an Essential Component of Frailty in Older Persons","volume":"61","author":"Bartali","year":"2006","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1079\/BJN2003836","article-title":"The effects of exercise and protein\u2013energy supplements on body composition and muscle function in frail elderly individuals: A long-term controlled randomised study","volume":"89","author":"Bonnefoy","year":"2003","journal-title":"Br. J. Nutr."},{"key":"ref_50","first-page":"17","article-title":"Frailty and ninjin\u2019yoeito","volume":"64","author":"Sakisaka","year":"2017","journal-title":"Phil Kampo"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3389\/fnut.2018.00073","article-title":"A Clinical Study of Ninjin\u2019yoeito with Regard to Frailty","volume":"5","author":"Sakisaka","year":"2018","journal-title":"Front. Nutr."},{"key":"ref_52","first-page":"497","article-title":"Implication of frailty in elderly care","volume":"51","author":"Arai","year":"2014","journal-title":"Nihon Ronen Igakkai Zasshi"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1002\/jgf2.52","article-title":"Evaluation by the Basic Checklist and the risk of 3 years incident long-term care insurance certification","volume":"18","author":"Kamegaya","year":"2017","journal-title":"J. Gen. Fam. Med."},{"key":"ref_54","first-page":"280","article-title":"Maintaining Weight and Nutritional Status with Ninjinyoueito in Elderly Patients with Chronic Wasting Diseases","volume":"22","author":"Nakagawa","year":"2021","journal-title":"Sultan Qaboos Univ. Med. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3389\/fnut.2020.00085","article-title":"Good Rehabilitation Outcomes and Improved Nutritional Status After Treatment with the Japanese Herbal Medicine Ninjin\u2019yoeito in an Elderly Patient with Hip Fracture and Sarcopenia: A Case Report","volume":"7","author":"Morinaga","year":"2020","journal-title":"Front. Nutr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"102244","DOI":"10.1016\/j.npep.2022.102244","article-title":"Long-term administration of ninjin\u2019yoeito to treat frailty in older adults: A case series","volume":"93","author":"Sakisaka","year":"2022","journal-title":"Neuropeptides"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"102189","DOI":"10.1016\/j.npep.2021.102189","article-title":"Evaluating the usefulness of Ninjin\u2019yoeito Kampo medicine in combination with rehabilitation therapy in patients with frailty complicated by intractable dizziness","volume":"90","author":"Arai","year":"2021","journal-title":"Neuropeptides"},{"key":"ref_58","first-page":"e20210025","article-title":"Frailty syndrome and risks for falling in the elderly community","volume":"34","author":"Taguchi","year":"2022","journal-title":"CoDAS"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1007\/s00192-019-04052-2","article-title":"The association of vulvar pain and urological urgency and frequency: Findings from a community-based case\u2013control study","volume":"30","author":"Sun","year":"2019","journal-title":"Int. Urogynecol. J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1080\/13697137.2023.2194527","article-title":"Pelvic floor muscle rehabilitation for genitourinary syndrome of menopause: Why, how and when?","volume":"26","author":"Mercier","year":"2023","journal-title":"Climacteric"},{"key":"ref_61","first-page":"e40767","article-title":"Ninjin\u2019yoeito Improves Genitourinary Symptoms in Patients with Frailty","volume":"15","author":"Okui","year":"2023","journal-title":"Cureus"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"535.e1","DOI":"10.1016\/j.jamda.2015.03.003","article-title":"Prevalence and factors associated with polypharmacy in long-term care facilities: A systematic review","volume":"16","author":"Jokanovic","year":"2015","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1111\/j.1532-5415.2004.52367.x","article-title":"Risk Factors for Adverse Drug Events Among Older Adults in the Ambulatory Setting","volume":"52","author":"Field","year":"2004","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_64","first-page":"301","article-title":"Polypharmacy in the Elderly: A Marker of Increased Risk of Mortality in a Population-Based Prospective Study (NEDICES)","volume":"61","author":"Medrano","year":"2014","journal-title":"Gerontology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1517\/14740338.2013.827660","article-title":"Clinical consequences of polypharmacy in elderly","volume":"13","author":"Maher","year":"2013","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_66","first-page":"102","article-title":"Frailty and drug use","volume":"38","author":"Palmer","year":"2016","journal-title":"Frailty"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1177\/10998004231179485","article-title":"Frailty and Polypharmacy in Primary Care","volume":"25","author":"Derhem","year":"2023","journal-title":"Biol. Res. Nurs."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1111\/bcp.13590","article-title":"The relationship between frailty and polypharmacy in older people: A systematic review","volume":"84","author":"Izquierdo","year":"2018","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0140-6736(12)60240-2","article-title":"Epidemiology of multimorbidity and implications for health care, research, and medical education: A cross-sectional study","volume":"380","author":"Barnett","year":"2012","journal-title":"Lancet"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/5\/721\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:08:07Z","timestamp":1760105287000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/5\/721"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,1]]},"references-count":69,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["nu16050721"],"URL":"https:\/\/doi.org\/10.3390\/nu16050721","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,1]]}}}