{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T22:20:25Z","timestamp":1783030825117,"version":"3.54.6"},"reference-count":31,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MARUSAN-AI Co., LTD."},{"name":"National Center for Geriatrics and Gerontology of Japan","award":["21-2"],"award-info":[{"award-number":["21-2"]}]},{"name":"National Center for Geriatrics and Gerontology of Japan","award":["24-9"],"award-info":[{"award-number":["24-9"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: The primary outcome of a 12-week randomized controlled trial studying the effects of continuous high-soy-protein (HSP) soymilk consumption in Japanese frail and pre-frail elderly individuals has previously been reported. The authors of this post hoc study aimed to conduct a statistical analysis focusing on changes in the skeletal muscle index (SMI) and evaluate the effect of HSP soymilk intake on appendicular skeletal muscle mass (ASM). Methods: A full analysis of all subjects (n = 68, HSP group: n = 34, control group: n = 34) and a subgroup analysis of only pre-frail elderly individuals (n = 58, HSP group: n = 29, control group: n = 29) were performed. The following nine subgroup analyses were conducted: frailty phenotype, basal metabolic rate, walking speed, step counts, total energy expenditure (TEE), total energy intake (TEI), estimated protein intake, age, and sex. Results: In the overall analysis (primary combined cohort), the SMI showed no significant change between the HSP and control soymilk groups (p = 0.18); however, a significant difference in the change in the SMI between the HSP and control groups was revealed for pre-frail elderly subjects (mean difference in SMI change: 0.08 kg\/m2 [95% CI 0.004, 0.15], p = 0.044). Furthermore, in four distinct subgroups restricted to the pre-frail elderly individuals\u2014step counts (\u22655000 steps\/day), TEE (\u226530 kcal\/kg BW\/day), TEI (\u226530 kcal\/kg BW\/day), and male sex\u2014the HSP group also showed significant differences in SMI change. Conclusions: In this study, no significant improvement in the SMI was observed across all subjects (frail and pre-frail elderly individuals); however, an exploratory subgroup analysis suggested that continued daily HSP soymilk intake was associated with potential benefits in pre-frail elderly individuals with high physical activity and energy intake levels. These findings are preliminary and require further research.<\/jats:p>","DOI":"10.3390\/nu17243900","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T13:32:37Z","timestamp":1765805557000},"page":"3900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Effect of Routine High-Soy-Protein Soymilk Intake on the Skeletal Muscle Index (SMI) in Japanese Pre-Frail Elderly Individuals with an Ordinary Life: A Post Hoc Analysis of a Randomized Controlled Trial"],"prefix":"10.3390","volume":"17","author":[{"given":"Daigo","family":"Sakamoto","sequence":"first","affiliation":[{"name":"Research and Development Division, MARUSAN-AI Co., Ltd., Okazaki 444-2193, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Terashima","sequence":"additional","affiliation":[{"name":"Research and Development Division, MARUSAN-AI Co., Ltd., Okazaki 444-2193, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Sugawara","sequence":"additional","affiliation":[{"name":"Research and Development Division, MARUSAN-AI Co., Ltd., Okazaki 444-2193, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoichi","family":"Unno","sequence":"additional","affiliation":[{"name":"Research and Development Division, MARUSAN-AI Co., Ltd., Okazaki 444-2193, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2627-8102","authenticated-orcid":false,"given":"Tomoyuki","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Health and Nutritional Sciences, Faculty of Health Sciences, Aichi Gakuin University, Nisshin 470-0131, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Uno","sequence":"additional","affiliation":[{"name":"Department of Health and Nutritional Sciences, Faculty of Health Sciences, Aichi Gakuin University, Nisshin 470-0131, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuo","family":"Maruyama","sequence":"additional","affiliation":[{"name":"Geroscience Research Center, Research Institute, National Center for Geriatrics and Gerontology, Obu 474-8511, Aichi, Japan"},{"name":"Department of Aging Research, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1093\/gerona\/glad167","article-title":"The Health, Aging, and Body Composition (Health ABC) Study-Ground-Breaking Science for 25 Years and Counting","volume":"78","author":"Newman","year":"2023","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e1581","DOI":"10.1093\/nutrit\/nuae200","article-title":"Effect of Plant Versus Animal Protein on Muscle Mass, Strength, Physical Performance, and Sarcopenia: A Systematic Review and Meta-analysis of Randomized Controlled Trials","volume":"83","author":"Brennan","year":"2025","journal-title":"Nutr. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"177","DOI":"10.2152\/jmi.62.177","article-title":"Effects of dietary soy protein on skeletal muscle volume and strength in humans with various physical activities","volume":"62","author":"Hashimoto","year":"2015","journal-title":"J. Med. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1007\/s40279-023-01899-w","article-title":"Effect of Soy Protein Supplementation on Muscle Adaptations, Metabolic and Antioxidant Status, Hormonal Response, and Exercise Performance of Active Individuals and Athletes: A Systematic Review of Randomised Controlled Trials","volume":"53","author":"Zare","year":"2023","journal-title":"Sports Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Govindasamy, K., Parpa, K., Katanic, B., Clark, C.C.T., Elayaraja, M., Kambitta Valappil, I.N., Dulceanu, C., Geant\u0103, V.A., Tolan, G.A., and Zouhal, H. (2025). Effect of Plant-Based Proteins on Recovery from Resistance Exercise-Induced Muscle Damage in Healthy Young Adults\u2014A Systematic Review. Nutrients, 17.","DOI":"10.3390\/nu17152571"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1056\/NEJM199406233302501","article-title":"Exercise training and nutritional supplementation for physical frailty in very elderly people","volume":"330","author":"Fiatarone","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.2147\/CIA.S46826","article-title":"Effectiveness of exercise and protein supplementation intervention on body composition, functional fitness, and oxidative stress among elderly Malays with Sarcopenia","volume":"8","author":"Shahar","year":"2013","journal-title":"Clin. Interv. Aging"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Sato, N., Terashima, Y., Sugawara, M., Unno, R., Asao, H., Iwasaki, M., Watanabe, T., Uno, T., and Maruyama, M. (2025). Continuous high-soy protein soymilk intake affects ordinary walking speed in the Japanese pre-frail and frail elderly: A randomized controlled trial. BMC Geriatr., 25.","DOI":"10.1186\/s12877-024-05539-4"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1111\/ggi.14005","article-title":"The revised Japanese version of the Cardiovascular Health Study criteria (revised J-CHS criteria)","volume":"20","author":"Satake","year":"2020","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/ki.1985.10","article-title":"A method for estimating nitrogen intake of patients with chronic renal failure","volume":"27","author":"Maroni","year":"1985","journal-title":"Kidney Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/sj.jhh.1001307","article-title":"A simple method to estimate populational 24-h urinary sodium and potassium excretion using a casual urine specimen","volume":"16","author":"Tanaka","year":"2002","journal-title":"J. Hum. Hypertens."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1017\/S1368980011000504","article-title":"Comparison of relative validity of food group intakes estimated by comprehensive and brief-type self-administered diet history questionnaires against 16 d dietary records in Japanese adults","volume":"14","author":"Kobayashi","year":"2011","journal-title":"Public Health Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2165\/00007256-200434010-00001","article-title":"How many steps\/day are enough? Preliminary pedometer indices for public health","volume":"34","author":"Tudor","year":"2004","journal-title":"Sports Med."},{"key":"ref_14","unstructured":"Ministry of Health, and Labour and Welfare (2025, January 01). Report of the Study Group on the Formulation of Dietary Intakes for Japanese (2020 Edition). (In Japanese)."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lorenzo-L\u00f3pez, L., Maseda, A., de Labra, C., Regueiro-Folgueira, L., Rodr\u00edguez-Villamil, J.L., and Mill\u00e1n-Calenti, J.C. (2017). Nutritional determinants of frailty in older adults: A systematic review. BMC Geriatr., 17.","DOI":"10.1186\/s12877-017-0496-2"},{"key":"ref_16","unstructured":"Ministry of Health, and Labour and Welfare (2025, January 01). Report of the Study Group on the Formulation of Dietary Intakes for Japanese (2015 Edition). (In Japanese)."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s12603-022-1740-9","article-title":"Adequate protein intake on comprehensive frailty in older adults: Kyoto-Kameoka study","volume":"26","author":"Nanri","year":"2022","journal-title":"J. Nutr. Health Aging"},{"key":"ref_18","first-page":"32","article-title":"Protein intake and transitions between frailty states and to death in very old adults: The Newcastle 85+ study","volume":"49","author":"Kingston","year":"2019","journal-title":"Age Ageing"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/bmt.2012.244","article-title":"Investigation of the freely available easy-to-use software \u2018EZR\u2019 for medical statistics","volume":"48","author":"Kanda","year":"2013","journal-title":"Bone Marrow Transplant."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s00394-024-03506-8","article-title":"Pea and soy fortified with leucine stimulates muscle protein synthesis comparable to whey in a murine ageing model","volume":"64","author":"Dijk","year":"2024","journal-title":"Eur. J. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"907565","DOI":"10.1155\/2013\/907565","article-title":"Soy Glycinin Contains a Functional Inhibitory Sequence against Muscle-Atrophy-Associated Ubiquitin Ligase Cbl-b","volume":"2013","author":"Abe","year":"2013","journal-title":"Int. J. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kitajima, Y., Ogawa, S., Egusa, S., and Ono, Y. (2017). Soymilk Improves Muscle Weakness in Young Ovariectomized Female Mice. Nutrients, 9.","DOI":"10.3390\/nu9080834"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1017\/S0954422420000219","article-title":"Dietary protein considerations for muscle protein synthesis and muscle mass preservation in older adults","volume":"34","author":"Olaniyan","year":"2021","journal-title":"Nutr. Res. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Morita, M., Hirano, T., Doi, K., Han, X., Matsunaga, K., and Jiang, Z. (2024). A novel method for identifying frailty and quantifying muscle strength using the six-minute walking test. Sensors, 24.","DOI":"10.3390\/s24144489"},{"key":"ref_25","first-page":"938","article-title":"Analysis of muscle synergy and muscle functional network at different walking speeds based on surface electromyographic signal","volume":"40","author":"Cui","year":"2023","journal-title":"Sheng Wu Yi Xue Gong Cheng Xue Za Zhi"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1093\/nutrit\/nuaa104","article-title":"Dose-response relationship between protein intake and muscle mass increase: A systematic review and meta-analysis of randomized controlled trials","volume":"79","author":"Tagawa","year":"2020","journal-title":"Nutr. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Stoodley, I.L., Williams, L.M., and Wood, L.G. (2023). Effects of Plant-Based Protein Interventions, with and without an Exercise Component, on Body Composition, Strength and Physical Function in Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients, 15.","DOI":"10.3390\/nu15184060"},{"key":"ref_28","first-page":"133","article-title":"Long-term longitudinal epidemiological study of frailty and sarcopenia","volume":"66","author":"Shimokata","year":"2017","journal-title":"Jpn. J. Phys. Fit. Sports Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"301","DOI":"10.7600\/jpfsm.5.301","article-title":"Epidemiology of frailty in elderly Japanese","volume":"5","author":"Yuki","year":"2016","journal-title":"J. Phys. Fit. Sports Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"852","DOI":"10.3390\/nu5030852","article-title":"Influence of amino acids, dietary protein, and physical activity on muscle mass development in humans","volume":"5","author":"Dideriksen","year":"2013","journal-title":"Nutrients"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"119","DOI":"10.7600\/jpfsm.6.119","article-title":"Regulation of muscle protein metabolism by nutrition and exercise","volume":"6","author":"Ato","year":"2017","journal-title":"J. Phys. Fit. Sports Med."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/24\/3900\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T13:39:45Z","timestamp":1765805985000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/24\/3900"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,13]]},"references-count":31,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["nu17243900"],"URL":"https:\/\/doi.org\/10.3390\/nu17243900","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,13]]}}}