Cystine and Theanine as Stress-Reducing Amino Acids—Perioperative Use for Early Recovery after Surgical Stress
Abstract
:1. Introduction
Stress and Biological Reaction
2. Trial of Stress Reduction
2.1. Surgical Procedure
2.2. Nutritional Management (Early Enteral Feeding: Animal Model)
2.3. Nutritional Management (Perioperative Management: Enhanced Recovery after Surgery)
3. Amino Acids Cystine and Theanine
3.1. Influence of Cystine/Theanine Administration on Exercise Load in Athletes
3.2. Application of Cystine/Theanine to Patients Undergoing Surgery
3.3. Supportive Data of Animal Experiment for Cystine/Theanine
4. Conclusions and Perspective
Author Contributions
Funding
Conflicts of Interest
References
- Moore, F.D. Metabolic Care of the Surgical Patients; WB Saunders: Philadelphia, PA, USA, 1956. [Google Scholar]
- Harris, J.A.; Benedict, F.G. A Biometric Study of Human Basal Metabolism. Proc. Natl. Acad. Sci. USA 1918, 4, 370–373. [Google Scholar] [CrossRef] [Green Version]
- Long, C.L.; Schaffel, N.; Geiger, J.W.; Schiller, W.R.; Blakemore, W.S. Metabolic response to injury and illness: Estimation of energy and protein needs from indirect calorimetry and nitrogen balance. JPEN J. Parenter. Enter. Nutr. 1979, 3, 452–456. [Google Scholar] [CrossRef] [PubMed]
- Mackiewics, A.; Kushner, I.; Baumann, H. Acute Phase Protein; CRC Press: Boca Raton, FL, USA, 1993. [Google Scholar]
- Biolo, G.; Toigo, G.; Ciocchi, B.; Situlin, R.; Iscra, F.; Gullo, A.; Guarnieri, G. Metabolic response to injury and sepsis: Changes in protein metabolism. Nutrition 1997, 13, 52S–57S. [Google Scholar] [CrossRef]
- Sobotka, L.; Soeters, P.B. Basics in clinical nutrition: Metabolic response to injury and sepsis. e-ESPEN 2009, 4, e1–e3. [Google Scholar] [CrossRef] [Green Version]
- Bistrian, B.R. A simple technique to estimate severity of stress. Surg. Gynecol. Obstet. 1979, 148, 675–678. [Google Scholar]
- Cerra, F.; Blackburn, G.; Hirsch, J.; Mullen, K.; Luther, W. The effect of stress level, amino acid formula, and nitrogen dose on nitrogen retention in traumatic and septic stress. Ann. Surg. 1987, 205, 282–287. [Google Scholar] [CrossRef] [PubMed]
- Riegel, C.; Koop, C.E.; Drew, J.; Stevens, L.W.; Rhoads, J.E.; Bullitt, L.; Barrus, D.; Grigger, R.P.; Barnes, M.; Barnhart, A.; et al. The nutritional requirements for nitrogen balance in surgical patients during the early postoperative period. J. Clin. Investig. 1947, 26, 18–23. [Google Scholar] [CrossRef] [Green Version]
- Terarshima, H. The rights and wrongs of early PN after stress: Real truth of the argumentation. JJSMN 2016, 50, 111–126. [Google Scholar]
- Himal, H.S. Minimally invasive (laparoscopic) surgery. Surg. Endosc. 2002, 16, 1647–1652. [Google Scholar] [CrossRef] [PubMed]
- Clinical Outcomes of Surgical Therapy Study, G.; Nelson, H.; Sargent, D.J.; Wieand, H.S.; Fleshman, J.; Anvari, M.; Stryker, S.J.; Beart, R.W., Jr.; Hellinger, M.; Flanagan, R., Jr.; et al. A comparison of laparoscopically assisted and open colectomy for colon cancer. N. Engl. J. Med. 2004, 350, 2050–2059. [Google Scholar] [CrossRef] [Green Version]
- Kaiser, A.M.; Kang, J.C.; Chan, L.S.; Vukasin, P.; Beart, R.W., Jr. Laparoscopic-assisted vs. open colectomy for colon cancer: A prospective randomized trial. J. Laparoendosc. Adv. Surg. Techniques. Part A 2004, 14, 329–334. [Google Scholar] [CrossRef] [PubMed]
- Ordemann, J.; Jacobi, C.A.; Schwenk, W.; Stosslein, R.; Muller, J.M. Cellular and humoral inflammatory response after laparoscopic and conventional colorectal resections. Surg. Endosc. 2001, 15, 600–608. [Google Scholar] [CrossRef]
- Mochizuki, H.; Trocki, O.; Dominioni, L.; Brackett, K.A.; Joffe, S.N.; Alexander, J.W. Mechanism of prevention of postburn hypermetabolism and catabolism by early enteral feeding. Ann. Surg. 1984, 200, 297–310. [Google Scholar] [CrossRef] [PubMed]
- Fearon, K.C.; Ljungqvist, O.; Von Meyenfeldt, M.; Revhaug, A.; Dejong, C.H.; Lassen, K.; Nygren, J.; Hausel, J.; Soop, M.; Andersen, J.; et al. Enhanced recovery after surgery: A consensus review of clinical care for patients undergoing colonic resection. Clin. Nutr. 2005, 24, 466–477. [Google Scholar] [CrossRef]
- Weimann, A.; Braga, M.; Carli, F.; Higashiguchi, T.; Hubner, M.; Klek, S.; Laviano, A.; Ljungqvist, O.; Lobo, D.N.; Martindale, R.; et al. ESPEN guideline: Clinical nutrition in surgery. Clin. Nutr. 2017, 36, 623–650. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Barlow, R.; Price, P.; Reid, T.D.; Hunt, S.; Clark, G.W.; Havard, T.J.; Puntis, M.C.; Lewis, W.G. Prospective multicentre randomised controlled trial of early enteral nutrition for patients undergoing major upper gastrointestinal surgical resection. Clin. Nutr. 2011, 30, 560–566. [Google Scholar] [CrossRef] [PubMed]
- Kurihara, S.; Shibakusa, T.; Tanaka, K.A. Cystine and theanine: Amino acids as oral immunomodulative nutrients. SpringerPlus 2013, 2, 635. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Miyachi, T.; Tsuchiya, T.; Oyama, A.; Tsuchiya, T.; Abe, N.; Sato, A.; Chiba, Y.; Kurihara, S.; Shibakusa, T.; Mikami, T. Perioperative oral administration of cystine and theanine enhances recovery after distal gastrectomy: A prospective randomized trial. JPEN J. Parenter. Enter. Nutr. 2013, 37, 384–391. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- U.S. Department of Agriculture Food Data Central. Available online: https://fdc.nal.usda.gov/ (accessed on 15 November 2021).
- Buchanan, J.H. A cystine-rich protein fraction from oxidized alpha-keratin. Biochem. J. 1977, 167, 489–491. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rosenberg, L.E.; Crawhall, J.C.; Segal, S. Intestinal transport of cystine and cysteine in man: Evidence for separate mechanisms. J. Clin. Investig. 1967, 46, 30–34. [Google Scholar] [CrossRef] [PubMed]
- Juneja, L.R.; Chu, D.C.; Okubo, T.; Nagato, Y.; Yokogoshi, H. L-Theanine-a unique amino acid of green tea and its relaxation effect in humans. Trens Food Sci. Technol. 1999, 10, 199–204. [Google Scholar] [CrossRef]
- Asatoor, A.M. Tea as a source of urinary ethylamine. Nature 1966, 210, 1358–1360. [Google Scholar] [CrossRef] [PubMed]
- Lu, S.C. Glutathione synthesis. Biochim. Biophys. Acta 2013, 1830, 3143–3153. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rimaniol, A.C.; Mialocq, P.; Clayette, P.; Dormont, D.; Gras, G. Role of glutamate transporters in the regulation of glutathione levels in human macrophages. Am. J. Physiology. Cell Physiol. 2001, 281, C1964–C1970. [Google Scholar] [CrossRef] [PubMed]
- Margonis, K.; Fatouros, I.G.; Jamurtas, A.Z.; Nikolaidis, M.G.; Douroudos, I.; Chatzinikolaou, A.; Mitrakou, A.; Mastorakos, G.; Papassotiriou, I.; Taxildaris, K.; et al. Oxidative stress biomarkers responses to physical overtraining: Implications for diagnosis. Free Radic. Biol. Med. 2007, 43, 901–910. [Google Scholar] [CrossRef] [PubMed]
- Rahman, I.; MacNee, W. Oxidative stress and regulation of glutathione in lung inflammation. Eur. Respir. J. 2000, 16, 534–554. [Google Scholar] [CrossRef]
- Murakami, S.; Kurihara, S.; Titchenal, C.A.; Ohtani, M. Suppression of exercise-induced neutrophilia and lymphopenia in athletes by cystine/theanine intake: A randomized, double-blind, placebo-controlled trial. J. Int. Soc. Sports Nutr. 2010, 7, 23. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Murakami, S.; Kurihara, S.; Koikawa, N.; Nakamura, A.; Aoki, K.; Yosigi, H.; Sawaki, K.; Ohtani, M. Effects of oral supplementation with cystine and theanine on the immune function of athletes in endurance exercise: Randomized, double-blind, placebo-controlled trial. Biosci. Biotechnol. Biochem. 2009, 73, 817–821. [Google Scholar] [CrossRef] [PubMed]
- Kawada, S.; Kobayashi, K.; Ohtani, M.; Fukusaki, C. Cystine and theanine supplementation restores high-intensity resistance exercise-induced attenuation of natural killer cell activity in well-trained men. J. Strength Cond. Res. 2010, 24, 846–851. [Google Scholar] [CrossRef] [PubMed]
- Shibakusa, T.; Mikami, T.; Kurihara, S.; Chiba, Y.; Tsuchiya, T.; Miyachi, T.; Oyama, A.; Tanaka, K.A.; Koyama, N. Enhancement of postoperative recovery by preoperative oral co-administration of the amino acids, cystine and theanine, in a mouse surgical model. Clin. Nutr. 2012, 31, 555–561. [Google Scholar] [CrossRef]
- Luo, J.L.; Hammarqvist, F.; Andersson, K.; Wernerman, J. Skeletal muscle glutathione after surgical trauma. Ann. Surg. 1996, 223, 420–427. [Google Scholar] [CrossRef]
- Tanaka, K.A.; Kurihara, S.; Shibakusa, T.; Chiba, Y.; Mikami, T. Cystine improves survival rates in a LPS-induced sepsis mouse model. Clin. Nutr. 2015, 34, 1159–1165. [Google Scholar] [CrossRef] [PubMed]
- Miyakuni, T.; Fukatsu, K.; Ri, M.; Murakoshi, S.; Inoue, Y.; Kurihara, S.; Takayama, T.; Yasuhara, H. Cystine and Theanine Improve Survival after Gut Ischemia-Reperfusion. Ann. Nutr. Metab. 2018, 73, 131–137. [Google Scholar] [CrossRef] [PubMed]
- Ljungqvist, O.; Scott, M.; Fearon, K.C. Enhanced Recovery After Surgery: A Review. JAMA Surg. 2017, 152, 292–298. [Google Scholar] [CrossRef] [PubMed]
- Paton, F.; Chambers, D.; Wilson, P.; Eastwood, A.; Craig, D.; Fox, D.; Jayne, D.; McGinnes, E. Effectiveness and implementation of enhanced recovery after surgery programmes: A rapid evidence synthesis. BMJ Open 2014, 4, e005015. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kurihara, S.; Yoshida, S.; Sukegawa, E.; Yoshimura, S.; Uchida, H.; Maeda, K.; Yamamoto, T. Evaluation of safety of long-term excessive intake of L-cystine and L-theanine in healthy adult subjects. Seikatsu Eisei 2008, 52, 229–236. [Google Scholar]
- Matsuu-Matsuyama, M.; Shichijo, K.; Tsuchiya, T.; Kondo, H.; Miura, S.; Matsuda, K.; Sekine, I.; Nakashima, M. Protective effects of a cystine and theanine mixture against acute radiation injury in rats. Environ. Toxicol. Pharmacol. 2020, 78, 103395. [Google Scholar] [CrossRef] [PubMed]
- Hamaguchi, R.; Tsuchiya, T.; Miyata, G.; Sato, T.; Takahashi, K.; Miura, K.; Oshio, H.; Ohori, H.; Ariyoshi, K.; Oyamada, S.; et al. 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). Support. Care Cancer 2020, 28, 3649–3657. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kawashiri, T.; Kobayashi, D.; Egashira, N.; Tsuchiya, T.; Shimazoe, T. Oral administration of Cystine and Theanine ameliorates oxaliplatin-induced chronic peripheral neuropathy in rodents. Sci. Rep. 2020, 10, 12665. [Google Scholar] [CrossRef]
- Kobayashi, M.; Sato, R.; Komura, T.; Ichikawa, H.; Hirashima, T.; Otake, S.; Akazawa, N.; Yazawa, T.; Abe, T.; Okada, T.; et al. Protective effect of the oral administration of cystine and theanine on oxaliplatin-induced peripheral neuropathy: A pilot randomized trial. Int. J. Clin. Oncol. 2020, 25, 1814–1821. [Google Scholar] [CrossRef]
- Tsuchiya, T.; Honda, H.; Oikawa, M.; Kakita, T.; Oyama, A.; Oishi, H.; Tochikubo, K.; Hashimoto, T.; Kurihara, S.; Shibakusa, T.; et al. Oral administration of the amino acids cystine and theanine attenuates the adverse events of S-1 adjuvant chemotherapy in gastrointestinal cancer patients. Int. J. Clin. Oncol. 2016, 21, 1085–1090. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yoneda, J.; Nishikawa, S.; Kurihara, S. 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 2021, 21, 1343. [Google Scholar] [CrossRef]
Author and Year | Study Design | Number of Patients | Study Results | Conclusions |
---|---|---|---|---|
Miyachi, et al. (2013) [20] | RCT | C/T group: 15 placebo group: 18 | Significant decrease in C/T group: IL-6, CRP, body temperature and REE. | C/T reduces excessive inflammation after surgery and enhances recovery. |
Author and Year | Study Model in Mice/Cells | Study Results | Conclusions |
---|---|---|---|
Shibakusa, et al. (2012) [33] | Small intestine manipulation model in mice | Significant decrease in C/T group: IL-6. Significant increase in C/T group: GSH level, food intake and locomotor activity. | C/T reduces excessive inflammation after surgery and enhances recovery. |
Tanaka, et al. (2015) [35] | LPS-induced sepsis model in mice/LPS-treated THP-1 cells | Significant decrease in C(/T) group: IL-6. Significant increase in C(/T) group: survival rate and IL-10 production. | C(/T) reduces excessive inflammation after LPS treatment through enhancing IL-10 production and recovers survival rate. |
Miyakuni, et al. (2018) [36] | Intestinal ischemia reperfusion model in mice | Rapidly decrease in C/T group: IL-6 and TNF-α. Significant increase in C/T group: survival rate. | C/T reduces excessive inflammation after an intestinal ischemia reperfusion and recovers survival rate. |
Author and Year | Study Design | Number of Patients | Study Results | Conclusions |
---|---|---|---|---|
Tsuchiya, et al. (2016) [44] | RCT | C/T group: 32 Placebo group: 31 | C/T improved the completion rate, alleviated the adverse events, especially diarrhea in colon and gastric cancer patients. | C/T reduces adverse event of S-1 adjuvant chemotherapy. |
Hamaguchi, et al. (2019) [41] | RCT | C/T group: 52 Placebo group: 48 | C/T reduced diarrhea and hand foot syndrome in colon cancer patients, but it was not significantly different | C/T has a possibility to reduce diarrhea and hand foot syndrome of capecitabine. |
Kobayashi, et al. (2020) [43] | RCT | C/T group: 14 Control group: 14 | C/T reduced neuropathy grading score during mFOLFOX chemotherapy in colon cancer patients. | C/T has a protective effect against peripheral neuropathy induced by oxaliplatin. |
Author and Year | Study Model in Rats/Mice | Study Results | Conclusions |
---|---|---|---|
Kawashiri, et al. (2020) [42] | Oxaliplatin-induced peripheral neuropathy model in rats | Significant increase in C/T group: GSH level. Significant suppress in C/T group: axonal degeneration. | C/T enhances GSH level and suppresses peripheral neuropathy induced by oxaliplatin. |
Yoneda, et al. (2021) [45] | 5-FU-induced diarrhea model in mice | Significant improvement in C/T group: GSH level, villus destruction, diarrhea, food intake and body weight. | C/T enhances GSH level and suppresses diarrhea induced by 5-FU. |
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Tsuchiya, T.; Kurihara, S. Cystine and Theanine as Stress-Reducing Amino Acids—Perioperative Use for Early Recovery after Surgical Stress. Nutrients 2022, 14, 129. https://doi.org/10.3390/nu14010129
Tsuchiya T, Kurihara S. Cystine and Theanine as Stress-Reducing Amino Acids—Perioperative Use for Early Recovery after Surgical Stress. Nutrients. 2022; 14(1):129. https://doi.org/10.3390/nu14010129
Chicago/Turabian StyleTsuchiya, Takashi, and Shigekazu Kurihara. 2022. "Cystine and Theanine as Stress-Reducing Amino Acids—Perioperative Use for Early Recovery after Surgical Stress" Nutrients 14, no. 1: 129. https://doi.org/10.3390/nu14010129
APA StyleTsuchiya, T., & Kurihara, S. (2022). Cystine and Theanine as Stress-Reducing Amino Acids—Perioperative Use for Early Recovery after Surgical Stress. Nutrients, 14(1), 129. https://doi.org/10.3390/nu14010129