Effects of Casein Hydrolysate Containing Val-Pro-Pro and Ile-Pro-Pro on Muscle Pump, Muscle Hypertrophy, and Motivation in Resistance-Trained Men: A Placebo-Controlled, Double-Blind, Parallel-Group Comparison Study Original Research
Main Article Content
Keywords
lactotripeptide, fatigue, strength training
Abstract
Introduction: The purpose was to investigate the effects of lactotripeptides (LTP) immediately after training.
Methods: This randomized, placebo-controlled, double-blind, parallel-group comparison study included males who undertook leg strength training every 2 weeks for ≥3 months. Thirty-six participants received placebo, low-dose (LD) (Val-Pro-Pro 0.7 mg/Ile-Pro-Pro 1.0 mg) or high-dose (HD) (Val-Pro-Pro 1.4 mg/Ile-Pro-Pro 2.0 mg) lactotripeptides daily for 4 weeks. Muscle pump, muscle hypertrophy, fatigue, and training motivation were evaluated.
Results: In the HD group, thigh circumference before exercise, lean body mass versus baseline and thigh circumference after exercise versus placebo significantly increased (p=0.002, 0.031, 0.032). In the LD group, subjective questionnaire scores related to muscle pump versus placebo significantly improved (p=0.042). Thigh circumference changes, before and after exercise, and subjective questionnaire scores, regardless of dosage, significantly correlated (p=0.026). Individuals with flow-mediated dilation (FMD) <7% showed a trend toward increased FMD in the HD group (p=0.081). Significant positive correlation occurred between FMD changes and thigh circumference, before and after exercise (p=0.021). In the HD group, fatigue scores after exercise and motivation for training scores the morning after exercise versus placebo significantly improved (p=0.020, 0.043).
Conclusions: LTP intake may be beneficial for muscle pump after training and muscle hypertrophy, reduce training-induced fatigue, and enhance strength training motivation.
Key Words: fatigue; lactotripeptide; strength training
Corresponding author: [email protected]
References
2. Takarada Y, Nakamura Y, Aruga S, Onda T, Miyazaki S, Ishii N. Rapid increase in plasma growth hormone after low-intensity resistance exercise with vascular occlusion. J Appl Physiol. 2000;88:61–65. doi: 10.1152/jappl.2000.88.1.61
3. Wackerhage H, Schoenfeld BJ, Hamilton DL, Lehti M, Hulmi JJ. Stimuli and sensors that initiate skeletal muscle hypertrophy following resistance exercise. J Appl Physiol. (1985) 2019;126:30–43. doi: 10.1152/japplphysiol.00685.2018
4. Hirono T, Ikezoe, T, Taniguchi M, et al. Relationship between muscle swelling and hypertrophy induced by resistance training. J Strength Cond Res. 2020;36:359–364. doi: 10.1519/JSC.0000000000003478
5. Monaghan L. Looking good, feeling good: The embodied pleasures of vibrant physicality. Sociol Health Illn. 2001;23:330–356. doi: 10.1111/1467-9566.00255
6. Schwarzenegger A, Dobbins, B. The New Encyclopedia of Modern Bodybuilding. Simon and Schuster; 1998:68–69.
7. Vieira A, Blazevich A, Souza N, et al. Acute changes in muscle thickness and pennation angle in response to work-matched concentric and eccentric isokinetic exercise. Appl Physiol Nutr Metab. 2018;43:1069–1074. doi: 10.1139/apnm-2018-0055
8. Trexler ET, Keith DS, Schwartz TA, et al. Effects of citrulline malate and beetroot juice supplementation on blood flow, energy metabolism, and performance during maximum effort leg extension exercise. J Strength Cond Res. 2019;33:2321–2329. doi: 10.1519/JSC.0000000000003286
9. Gonzalez AM, Spitz RW, Ghigiarelli JJ, Sell KM, Mangine GT. Acute effect of citrulline malate supplementation on upper-body resistance exercise performance in recreationally resistance-trained men. J Strength Cond Res. 2018;32:3088–3094. doi: 10.1519/JSC.0000000000002373
10. Gonzalez AM, Yang Y, Mangine GT, Pinzone AG, Ghigiarelli JJ, Sell KM. Acute effect of L-citrulline supplementation on resistance exercise performance and muscle oxygenation in recreationally resistance trained men and women. J Funct Morphol Kinesiol. 2023;8:88. doi: 10.3390/jfmk8030088
11. Bürkle F, Doll J, Neide A, Gantz S, Tsitlakidis S, Fischer C. New perspectives for investigating muscular perfusion response after dietary supplement intake: an exploratory, randomized, double-blind, placebo-controlled crossover trial in healthy young athletes using contrast-enhanced ultrasound (CEUS). J Int Soc Sports Nutr. 2022;19:397–416. doi: 10.1080/15502783.2022.2097018
12. Gonzalez AM, Townsend JR, Pinzone AG, Hoffman JR. Supplementation with nitric oxide precursors for strength performance: a review of the current literature. Nutrients 2023;15:660. doi: 10.3390/nu15030660
13. Armin MK, Marco GV. Cardioprotective peptides from milk processing and dairy products: from bioactivity to final products including commercialization and legislation. Foods 2022;11:1270–1293. doi: 10.3390/foods11091270
14. Yamaguchi N, Kawaguchi K, Yamamoto N. Study of the mechanism of antihypertensive peptides VPP and IPP in spontaneously hypertensive rats by DNA microarray analysis. Eur J Pharmacol. 2009;620:71–77. doi: 10.1016/j.ejphar.2009.08.005
15. Hirota T, Nonaka A, Matsushita A, et al. Milk casein-derived tripeptides, VPP and IPP induced NO production in cultured endothelial cells and endothelium-dependent relaxation of isolated aortic rings. Heart Vessels 2011;26:549–556. doi: 10.1007/s00380-010-0096-y
16. Hatanaka M, Kanzato H, Nadaoka I, et al. Beneficial effect of lactotripeptide on peripheral blood flow in healthy volunteers: a randomized placebo-controlled double-blind study. Jpn Pharmacol Ther. 2021;49:73–82.
17. Nakamura Y, Yamamoto N, Sakai K, Okubo A, Yamazaki S, Takano T. Purification and characterization of angiotensin I-converting enzyme inhibitors from sour milk. J Dairy Sci. 1995;78:777–783. doi: 10.3168/jds.S0022-0302(95)76689-9
18. Sano J, Ohki K, Higuchi T, et al. Effect of casein hydrolysate, prepared with protease derived from Aspergillus oryzae, on subjects with high-normal blood pressure or mild hypertension. J Med Food 2005;8:423–430. doi: 10.1089/jmf.2005.8.423
19. Nakamura T, Mizutani J, Ohki K, et al. Casein hydrolysate containing Val-Pro-Pro and Ile-Pro-Pro improves central blood pressure and arterial stiffness in hypertensive subjects: a randomized, double-blind, placebo-controlled trial. Atherosclerosis 2011;219:298–303. doi: 10.1016/j.atherosclerosis.2011.06.007
20. Uchida N, Osawa K, Oki K, et al. Effect of tablets containing lactotripeptides (VPP, IPP) on vascular endothelial function in healthy subjects -a randomized, double-blind, placebo-controlled trial. Jpn Pharmacol Ther. 2016;44:1025–1034.
21. Tagawa K, Ra SG, Choi Y, Maeda S. Lactotripeptides supplementations alleviate the decrease in maximal isometric force following high-intensity eccentric exercise: a randomized, placebo-controlled, double-blinded clinical trial. Am J Phys Med Rehabil. 2018;97:370–374. doi: 10.1097/PHM.0000000000000867
22. Iwasa M, Aoi W, Nakayama A, et al. Milk casein hydrolysate alleviates muscle soreness and fatigue after downhill walking exercise in middle-aged to elderly men. Ann Sports Med Res. 2015;2:1045. doi: 10.47739/2379-0571/1045
23. Mizuno S, Nishimura S, Matsuura K, Gotou T, Yamamoto N. Release of short and proline-rich antihypertensive peptides from casein hydrolysate with an Aspergillus oryzae protease. J Dairy Sci. 2004;87:3183–3188. doi: 10.3168/jds.S0022-0302(04)73453-0
24. Steele J, Butler A, Comerford Z, et al. Similar acute physiological responses from effort and duration matched leg press and recumbent cycling tasks. Peer J. 2018;28;6:e4403. doi: 10.7717/peerj.4403
25. Freitas ED, Poole C, Miller RM, et al. Time course change in muscle swelling: high-intensity vs. blood flow restriction exercise. Int J Sports Med. 2017;38:1009–1016. doi: 10.1055/s-0043-118342
26. Wilson JM, Lowery RP, Joy JM, Loenneke JP, Naimo MA. Practical blood flow restriction training increases acute determinants of hypertrophy without increasing indices of muscle damage. J Strength Cond Res. 2013;27:3068–3075. doi: 10.1519/JSC.0b013e31828a1ffa
27. Greenberg D, Emerson, K, Ojalvo SP, Sylla S, Komorowski J. Inositol-stabilized arginine silicate reduces exercise induced muscle damage and increases perceived energy. J Exerc Nutr. 2023;6:5. doi: 10.53520/jen2023.103141
28. Hamasaki A, Akazawa N, Yoshikawa T, et al. Combined effects of lactotripeptide and aerobic exercise on cognitive function and cerebral oxygenation in middle-aged and older adults. Am J Clin Nutr. 2019;109:353–360. doi: 10.1093/ajcn/nqy235
29. Iwasa M, Aoi W, Mune K, et al. Fermented milk improves glucose metabolism in exercise-induced muscle damage in young healthy men. Nutr J. 2013:12:83. doi: 10.1186/1475-2891-12-83
30. Akazawa N, Hamasaki A, Tanahashi K, et al. Lactotripeptide ingestion increases cerebral blood flow velocity in middle-aged and older adults. Nutr Res. 2018;53:61–66. doi: 10.1016/j.nutres.2018.03.009
31. John S, Schlaich M, Langenfeld M, et al. Increased bioavailability of nitric oxide after lipid-lowering therapy in hypercholesterolemic patients. Circulation 1998;98:211–216. doi: 10.1161/01.cir.98.3.211
32. Ishida Y, Shibata Y, Fukuhara I, Yano Y, Takehara I, Kaneko K. Effect of an excess intake of casein hydrolysate containing Val-Pro-Pro and Ile-Pro-Pro in subjects with normal blood pressure, high-normal blood pressure, or mild hypertension. Biosci Biotechnol Biochem. 2011;75:427–433. doi: 10.1271/bbb.100560.
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