{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:43:40Z","timestamp":1792205020636,"version":"4.4.0"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T00:00:00Z","timestamp":1640649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Perioperative nutritional therapy requires the consideration of metabolic changes, and it is desirable to reduce stress aiming at early metabolic normalization. Glutathione (GSH) is a tripeptide composed of glutamic acid, cysteine, and glycine. It is one of the strongest antioxidants in the body and important for adjusting immune function. Cystine and theanine (\u03b3-glutamylethylamide) provide substrates of GSH, cysteine and glutamic acid, promoting the synthesis of GSH. It has been reported that the ingestion of cystine (700 mg) and theanine (280 mg) exhibits inhibitory effects against excess inflammation after strong exercise loads in athletes, based on which its application for invasive surgery has been tried. In patients undergoing gastrectomy, ingestion of cystine (700 mg) and theanine (280 mg) for 10 days from 5 days before surgery inhibited a postoperative increase in resting energy expenditure, promoted recovery from changes in interleukin-6, C-reactive protein, lymphocyte ratio, and granulocyte ratio and inhibited an increase in body temperature. In a mouse small intestine manipulation model, preoperative 5-day administration of cystine\/theanine inhibited a postoperative decrease in GSH in the small intestine and promoted recovery from a decrease in behavior quantity. Based on the above, cystine\/theanine reduces surgical stress, being useful for perioperative management as stress-reducing amino acids.<\/jats:p>","DOI":"10.3390\/nu14010129","type":"journal-article","created":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T02:31:27Z","timestamp":1640745087000},"page":"129","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Cystine and Theanine as Stress-Reducing Amino Acids\u2014Perioperative Use for Early Recovery after Surgical Stress"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2594-1811","authenticated-orcid":false,"given":"Takashi","family":"Tsuchiya","sequence":"first","affiliation":[{"name":"Department of Surgery, Sendai City Medical Center, Sendai 983-0824, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigekazu","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Nutrition Care Group, Quick Nourishment Department, Food Products Division, Ajinomoto Co., Inc., Tokyo 104-8315, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,28]]},"reference":[{"key":"ref_1","unstructured":"Moore, F.D. (1956). Metabolic Care of the Surgical Patients, WB Saunders."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1073\/pnas.4.12.370","article-title":"A Biometric Study of Human Basal Metabolism","volume":"4","author":"Harris","year":"1918","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1177\/014860717900300609","article-title":"Metabolic response to injury and illness: Estimation of energy and protein needs from indirect calorimetry and nitrogen balance","volume":"3","author":"Long","year":"1979","journal-title":"JPEN J. Parenter. Enter. Nutr."},{"key":"ref_4","unstructured":"Mackiewics, A., Kushner, I., and Baumann, H. (1993). Acute Phase Protein, CRC Press."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"52S","DOI":"10.1016\/S0899-9007(97)00206-2","article-title":"Metabolic response to injury and sepsis: Changes in protein metabolism","volume":"13","author":"Biolo","year":"1997","journal-title":"Nutrition"},{"key":"ref_6","first-page":"e1","article-title":"Basics in clinical nutrition: Metabolic response to injury and sepsis","volume":"4","author":"Sobotka","year":"2009","journal-title":"e-ESPEN"},{"key":"ref_7","first-page":"675","article-title":"A simple technique to estimate severity of stress","volume":"148","author":"Bistrian","year":"1979","journal-title":"Surg. Gynecol. Obstet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1097\/00000658-198703000-00011","article-title":"The effect of stress level, amino acid formula, and nitrogen dose on nitrogen retention in traumatic and septic stress","volume":"205","author":"Cerra","year":"1987","journal-title":"Ann. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1172\/JCI101786","article-title":"The nutritional requirements for nitrogen balance in surgical patients during the early postoperative period","volume":"26","author":"Riegel","year":"1947","journal-title":"J. Clin. Investig."},{"key":"ref_10","first-page":"111","article-title":"The rights and wrongs of early PN after stress: Real truth of the argumentation","volume":"50","author":"Terarshima","year":"2016","journal-title":"JJSMN"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1007\/s00464-001-8275-7","article-title":"Minimally invasive (laparoscopic) surgery","volume":"16","author":"Himal","year":"2002","journal-title":"Surg. Endosc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1056\/NEJMoa032651","article-title":"A comparison of laparoscopically assisted and open colectomy for colon cancer","volume":"350","author":"Nelson","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1089\/lap.2004.14.329","article-title":"Laparoscopic-assisted vs. open colectomy for colon cancer: A prospective randomized trial","volume":"14","author":"Kaiser","year":"2004","journal-title":"J. Laparoendosc. Adv. Surg. Techniques. Part A"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1007\/s004640090032","article-title":"Cellular and humoral inflammatory response after laparoscopic and conventional colorectal resections","volume":"15","author":"Ordemann","year":"2001","journal-title":"Surg. Endosc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1097\/00000658-198409000-00007","article-title":"Mechanism of prevention of postburn hypermetabolism and catabolism by early enteral feeding","volume":"200","author":"Mochizuki","year":"1984","journal-title":"Ann. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.clnu.2005.02.002","article-title":"Enhanced recovery after surgery: A consensus review of clinical care for patients undergoing colonic resection","volume":"24","author":"Fearon","year":"2005","journal-title":"Clin. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.clnu.2017.02.013","article-title":"ESPEN guideline: Clinical nutrition in surgery","volume":"36","author":"Weimann","year":"2017","journal-title":"Clin. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.clnu.2011.02.006","article-title":"Prospective multicentre randomised controlled trial of early enteral nutrition for patients undergoing major upper gastrointestinal surgical resection","volume":"30","author":"Barlow","year":"2011","journal-title":"Clin. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1186\/2193-1801-2-635","article-title":"Cystine and theanine: Amino acids as oral immunomodulative nutrients","volume":"2","author":"Kurihara","year":"2013","journal-title":"SpringerPlus"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1177\/0148607112458798","article-title":"Perioperative oral administration of cystine and theanine enhances recovery after distal gastrectomy: A prospective randomized trial","volume":"37","author":"Miyachi","year":"2013","journal-title":"JPEN J. Parenter. Enter. Nutr."},{"key":"ref_21","unstructured":"(2021, November 15). U.S. Department of Agriculture Food Data Central, Available online: https:\/\/fdc.nal.usda.gov\/."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1042\/bj1670489","article-title":"A cystine-rich protein fraction from oxidized alpha-keratin","volume":"167","author":"Buchanan","year":"1977","journal-title":"Biochem. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1172\/JCI105508","article-title":"Intestinal transport of cystine and cysteine in man: Evidence for separate mechanisms","volume":"46","author":"Rosenberg","year":"1967","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0924-2244(99)00044-8","article-title":"L-Theanine-a unique amino acid of green tea and its relaxation effect in humans","volume":"10","author":"Juneja","year":"1999","journal-title":"Trens Food Sci. Technol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1038\/2101358b0","article-title":"Tea as a source of urinary ethylamine","volume":"210","author":"Asatoor","year":"1966","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.1016\/j.bbagen.2012.09.008","article-title":"Glutathione synthesis","volume":"1830","author":"Lu","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"C1964","DOI":"10.1152\/ajpcell.2001.281.6.C1964","article-title":"Role of glutamate transporters in the regulation of glutathione levels in human macrophages","volume":"281","author":"Rimaniol","year":"2001","journal-title":"Am. J. Physiology. Cell Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.freeradbiomed.2007.05.022","article-title":"Oxidative stress biomarkers responses to physical overtraining: Implications for diagnosis","volume":"43","author":"Margonis","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1034\/j.1399-3003.2000.016003534.x","article-title":"Oxidative stress and regulation of glutathione in lung inflammation","volume":"16","author":"Rahman","year":"2000","journal-title":"Eur. Respir. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1550-2783-7-23","article-title":"Suppression of exercise-induced neutrophilia and lymphopenia in athletes by cystine\/theanine intake: A randomized, double-blind, placebo-controlled trial","volume":"7","author":"Murakami","year":"2010","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1271\/bbb.80663","article-title":"Effects of oral supplementation with cystine and theanine on the immune function of athletes in endurance exercise: Randomized, double-blind, placebo-controlled trial","volume":"73","author":"Murakami","year":"2009","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1519\/JSC.0b013e3181c7c299","article-title":"Cystine and theanine supplementation restores high-intensity resistance exercise-induced attenuation of natural killer cell activity in well-trained men","volume":"24","author":"Kawada","year":"2010","journal-title":"J. Strength Cond. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.clnu.2012.02.001","article-title":"Enhancement of postoperative recovery by preoperative oral co-administration of the amino acids, cystine and theanine, in a mouse surgical model","volume":"31","author":"Shibakusa","year":"2012","journal-title":"Clin. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1097\/00000658-199604000-00011","article-title":"Skeletal muscle glutathione after surgical trauma","volume":"223","author":"Luo","year":"1996","journal-title":"Ann. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/j.clnu.2014.11.014","article-title":"Cystine improves survival rates in a LPS-induced sepsis mouse model","volume":"34","author":"Tanaka","year":"2015","journal-title":"Clin. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1159\/000489825","article-title":"Cystine and Theanine Improve Survival after Gut Ischemia-Reperfusion","volume":"73","author":"Miyakuni","year":"2018","journal-title":"Ann. Nutr. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1001\/jamasurg.2016.4952","article-title":"Enhanced Recovery After Surgery: A Review","volume":"152","author":"Ljungqvist","year":"2017","journal-title":"JAMA Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e005015","DOI":"10.1136\/bmjopen-2014-005015","article-title":"Effectiveness and implementation of enhanced recovery after surgery programmes: A rapid evidence synthesis","volume":"4","author":"Paton","year":"2014","journal-title":"BMJ Open"},{"key":"ref_39","first-page":"229","article-title":"Evaluation of safety of long-term excessive intake of L-cystine and L-theanine in healthy adult subjects","volume":"52","author":"Kurihara","year":"2008","journal-title":"Seikatsu Eisei"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Matsuu-Matsuyama, M., Shichijo, K., Tsuchiya, T., Kondo, H., Miura, S., Matsuda, K., Sekine, I., and Nakashima, M. (2020). Protective effects of a cystine and theanine mixture against acute radiation injury in rats. Environ. Toxicol. Pharmacol., 78.","DOI":"10.1016\/j.etap.2020.103395"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3649","DOI":"10.1007\/s00520-019-05205-1","article-title":"Efficacy of oral administration of cystine and theanine in colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery: A multi-institutional, randomized, double-blinded, placebo-controlled, phase II trial (JORTC-CAM03)","volume":"28","author":"Hamaguchi","year":"2020","journal-title":"Support. Care Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"12665","DOI":"10.1038\/s41598-020-69674-9","article-title":"Oral administration of Cystine and Theanine ameliorates oxaliplatin-induced chronic peripheral neuropathy in rodents","volume":"10","author":"Kawashiri","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1007\/s10147-020-01728-4","article-title":"Protective effect of the oral administration of cystine and theanine on oxaliplatin-induced peripheral neuropathy: A pilot randomized trial","volume":"25","author":"Kobayashi","year":"2020","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1007\/s10147-016-0996-7","article-title":"Oral administration of the amino acids cystine and theanine attenuates the adverse events of S-1 adjuvant chemotherapy in gastrointestinal cancer patients","volume":"21","author":"Tsuchiya","year":"2016","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Yoneda, J., Nishikawa, S., and Kurihara, S. (2021). Oral administration of cystine and theanine attenuates 5-fluorouracil-induced intestinal mucositis and diarrhea by suppressing both glutathione level decrease and ROS production in the small intestine of mucositis mouse model. BMC Cancer, 21.","DOI":"10.1186\/s12885-021-09057-z"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/1\/129\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:55:04Z","timestamp":1760169304000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/1\/129"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,28]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["nu14010129"],"URL":"https:\/\/doi.org\/10.3390\/nu14010129","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,28]]}}}