Anabolic effects of leucine-rich whey protein, carbohydrate, and soy protein with and without β-hydroxy-β-methylbutyrate (HMB) during fasting-induced catabolism: A human randomized crossover trial

Clinical Nutrition

Volumn 36, Issue 3, 2017, Pages 697-705

  Rittig, Nikolaj ^a   Bach, Ermina ^a   Thomsen, Henrik H ^a   Møller, Andreas B ^a   Hansen, Jakob ^b   Johannsen, Mogens ^b   Jensen, Erik ^c   Serena, Anja ^c   Jørgensen, Jens O ^a   Richelsen, Bjørn ^a   Jessen, Niels ^a   Møller, Niels ^a  

^a AARHUS UNIVERSITY HOSPITAL   (Denmark)

^b AARHUS UNIVERSITY   (Denmark)

^c Arla Foods   (Denmark)

Author keywords

Fasting; HMB; Leucine; Protein; Soy; Whey

Indexed keywords

BETA HYDROXY BETA METHYLBUTYRATE; CARBOHYDRATE; GLUCOSE; INITIATION FACTOR 4E BINDING PROTEIN 1; INSULIN; LEUCINE RICH WHEY PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN; MICROTUBULE ASSOCIATED PROTEIN; MUSCLE PROTEIN; NUTRITION SUPPLEMENT; PHENYLALANINE; PROTEIN LC3I; PROTEIN LC3II; S6 KINASE; SOYBEAN PROTEIN; UNCLASSIFIED DRUG; WHEY PROTEIN; ANABOLIC AGENT; BETA-HYDROXYISOVALERIC ACID; EIF4EBP1 PROTEIN, HUMAN; GLUCAGON; LEUCINE; MTOR PROTEIN, HUMAN; PHOSPHOPROTEIN; RIBOSOMAL PROTEIN S6 KINASE 1, HUMAN; SIGNAL TRANSDUCING ADAPTOR PROTEIN; TARGET OF RAPAMYCIN KINASE; VALERIC ACID DERIVATIVE;

ADULT; ARTICLE; AUTOPHAGY; BEVERAGE; CARBOHYDRATE INTAKE; CATABOLISM; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIET RESTRICTION; GLUCOSE BLOOD LEVEL; HUMAN; HUMAN EXPERIMENT; HUMAN TISSUE; INSULIN BLOOD LEVEL; MALE; NORMAL HUMAN; PROTEIN INTAKE; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS; RANDOMIZED CONTROLLED TRIAL; SIGNAL TRANSDUCTION; ADMINISTRATION AND DOSAGE; BLOOD; BODY MASS; CARBOHYDRATE DIET; DRUG EFFECTS; GENETICS; METABOLISM; PHOSPHORYLATION; SKELETAL MUSCLE; YOUNG ADULT;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ADULT; ANABOLIC AGENTS; BODY MASS INDEX; CROSS-OVER STUDIES; DIETARY CARBOHYDRATES; FASTING; GLUCAGON; HUMANS; LEUCINE; MALE; MUSCLE, SKELETAL; PHOSPHOPROTEINS; PHOSPHORYLATION; RIBOSOMAL PROTEIN S6 KINASES, 90-KDA; SIGNAL TRANSDUCTION; SOYBEAN PROTEINS; TOR SERINE-THREONINE KINASES; VALERATES; WHEY PROTEINS; YOUNG ADULT;

EID: 84971664003     PISSN: 02615614     EISSN: 15321983     Source Type: Journal    
DOI: 10.1016/j.clnu.2016.05.004     Document Type: Article

References (48)

1. [1] Puthucheary, Z.A., Rawal, J., McPhail, M., Connolly, B., Ratnayake, G., Chan, P., et al. Acute skeletal muscle wasting in critical illness. JAMA J Am Med Assoc 310:15 (2013), 1591–1600, 10.1001/jama.2013.278481.
2. [2] Wray, C.J., Mammen, J.M., Hasselgren, P.O., Catabolic response to stress and potential benefits of nutrition support. Nutrition 18:11–12 (2002), 971–977.
3. [3] Vendelbo, M.H., Moller, A.B., Christensen, B., Nellemann, B., Clasen, B.F., Nair, K.S., et al. Fasting increases human skeletal muscle net phenylalanine release and this is associated with decreased mTOR signaling. PLoS One, 9(7), 2014, e102031, 10.1371/journal.pone.0102031.
4. [4] Nielsen, T.S., Vendelbo, M.H., Jessen, N., Pedersen, S.B., Jorgensen, J.O., Lund, S., et al. Fasting, but not exercise, increases adipose triglyceride lipase (ATGL) protein and reduces G(0)/G(1) switch gene 2 (G0S2) protein and mRNA content in human adipose tissue. J Clin Endocrinol Metab 96:8 (2011), E1293–E1297, 10.1210/jc.2011-0149.
5. [5] Browning, J.D., Baxter, J., Satapati, S., Burgess, S.C., The effect of short-term fasting on liver and skeletal muscle lipid, glucose, and energy metabolism in healthy women and men. J Lipid Res 53:3 (2012), 577–586, 10.1194/jlr.P020867.
6. [6] Tang, J.E., Moore, D.R., Kujbida, G.W., Tarnopolsky, M.A., Phillips, S.M., Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men. J Appl Physiol (1985) 107:3 (2009), 987–992, 10.1152/japplphysiol.00076.2009.
7. [7] Pennings, B., Groen, B., de Lange, A., Gijsen, A.P., Zorenc, A.H., Senden, J.M., et al. Amino acid absorption and subsequent muscle protein accretion following graded intakes of whey protein in elderly men. Am J Physiol Endocrinol Metab 302:8 (2012), E992–E999, 10.1152/ajpendo.00517.2011.
8. [8] Anthony, J.C., Yoshizawa, F., Anthony, T.G., Vary, T.C., Jefferson, L.S., Kimball, S.R., Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway. J Nutr 130:10 (2000), 2413–2419.
9. [9] Abumrad, N.N., Nissen, S.L., Nutritional role of the leucine metabolite β-hydroxy β-methylbutyrate (HMB). J Nutr Biochem, 8, 1997, 12.
10. [10] Nissen, S., Sharp, R., Ray, M., Rathmacher, J.A., Rice, D., Fuller, J.C. Jr., et al. Effect of leucine metabolite beta-hydroxy-beta-methylbutyrate on muscle metabolism during resistance-exercise training. J Appl Physiol (1985) 81:5 (1996), 2095–2104.
11. [11] Decombaz, J., Bury, A., Hager, C., HMB meta-analysis and the clustering of data sources. J Appl Physiol (1985) 95:5 (2003), 2180–2182, 10.1152/japplphysiol.00563.2003 author reply 2.
12. [12] Drummond, M.J., Rasmussen, B.B., Leucine-enriched nutrients and the regulation of mammalian target of rapamycin signalling and human skeletal muscle protein synthesis. Curr Opin Clin Nutr Metab Care 11:3 (2008), 222–226, 10.1097/MCO.0b013e3282fa17fb.
13. [13] Pimentel, G.D., Rosa, J.C., Lira, F.S., Zanchi, N.E., Ropelle, E.R., Oyama, L.M., et al. beta-Hydroxy-beta-methylbutyrate (HMbeta) supplementation stimulates skeletal muscle hypertrophy in rats via the mTOR pathway. Nutr Metab, 8(1), 2011, 11, 10.1186/1743-7075-8-11.
14. [14] Smith, H.J., Mukerji, P., Tisdale, M.J., Attenuation of proteasome-induced proteolysis in skeletal muscle by {beta}-hydroxy-{beta}-methylbutyrate in cancer-induced muscle loss. Cancer Res 65:1 (2005), 277–283.
15. [15] Wilkinson, D.J., Hossain, T., Hill, D.S., Phillips, B.E., Crossland, H., Williams, J., et al. Effects of leucine and its metabolite beta-hydroxy-beta-methylbutyrate on human skeletal muscle protein metabolism. J Physiol 591:Pt 11 (2013), 2911–2923, 10.1113/jphysiol.2013.253203.
16. [16] Rasmussen, B.B., Wolfe, R.R., Volpi, E., Oral and intravenously administered amino acids produce similar effects on muscle protein synthesis in the elderly. J Nutr Health Aging 6:6 (2002), 358–362.
17. [17] Paddon-Jones, D., Sheffield-Moore, M., Zhang, X.J., Volpi, E., Wolf, S.E., Aarsland, A., et al. Amino acid ingestion improves muscle protein synthesis in the young and elderly. Am J Physiol Endocrinol Metab 286:3 (2004), E321–E328, 10.1152/ajpendo.00368.2003.
18. [18] Pennings, B., Boirie, Y., Senden, J.M., Gijsen, A.P., Kuipers, H., van Loon, L.J., Whey protein stimulates postprandial muscle protein accretion more effectively than do casein and casein hydrolysate in older men. Am J Clin Nutr 93:5 (2011), 997–1005, 10.3945/ajcn.110.008102.
19. [19] Cooke, M.B., Rybalka, E., Stathis, C.G., Cribb, P.J., Hayes, A., Whey protein isolate attenuates strength decline after eccentrically-induced muscle damage in healthy individuals. J Int Soc Sports Nutr, 7, 2010, 30, 10.1186/1550-2783-7-30.
20. [20] Reitelseder, S., Agergaard, J., Doessing, S., Helmark, I.C., Lund, P., Kristensen, N.B., et al. Whey and casein labeled with L-[1-13C]leucine and muscle protein synthesis: effect of resistance exercise and protein ingestion. Am J Physiol Endocrinol Metab 300:1 (2011), E231–E242, 10.1152/ajpendo.00513.2010.
21. [21] Sapir, D.G., Walser, M., Nitrogen sparing induced early in starvation by infusion of branched-chain ketoacids. Metab Clin Exp 26:3 (1977), 301–308.
22. [22] Sherwin, R.S., Effect of starvation on the turnover and metabolic response to leucine. J Clin Investig 61:6 (1978), 1471–1481, 10.1172/JCI109067.
23. [23] Mitch, W.E., Walser, M., Sapir, D.G., Nitrogen sparing induced by leucine compared with that induced by its keto analogue, alpha-ketoisocaproate, in fasting obese man. J Clin Investig 67:2 (1981), 553–562, 10.1172/JCI110066.
24. [24] Abumrad, N.N., Rabin, D., Diamond, M.P., Lacy, W.W., Use of a heated superficial hand vein as an alternative site for the measurement of amino acid concentrations and for the study of glucose and alanine kinetics in man. Metab Clin Exp 30:9 (1981), 936–940.
25. [25] Fujita, S., Dreyer, H.C., Drummond, M.J., Glynn, E.L., Cadenas, J.G., Yoshizawa, F., et al. Nutrient signalling in the regulation of human muscle protein synthesis. J Physiol 582:Pt 2 (2007), 813–823, 10.1113/jphysiol.2007.134593.
26. [26] Cooper, K.E., Edholm, O.G., Mottram, R.F., The blood flow in skin and muscle of the human forearm. J Physiol 128:2 (1955), 258–267.
27. [27] Whitney, R.J., The measurement of volume changes in human limbs. J Physiol 121:1 (1953), 1–27.
28. [28] Thompson, G.N., Pacy, P.J., Merritt, H., Ford, G.C., Read, M.A., Cheng, K.N., et al. Rapid measurement of whole body and forearm protein turnover using a [2H5]phenylalanine model. Am J Physiol 256:5 Pt 1 (1989), E631–E639.
29. [29] Gurtler, A., Kunz, N., Gomolka, M., Hornhardt, S., Friedl, A.A., McDonald, K., et al. Stain-Free technology as a normalization tool in Western blot analysis. Anal Biochem 433:2 (2013), 105–111, 10.1016/j.ab.2012.10.010.
30. [30] Sorensen, L.K., Rittig, N.F., Holmquist, E.F., Jorgensen, K.A., Jorgensen, J.O., Moller, N., et al. Simultaneous determination of beta-hydroxybutyrate and beta-hydroxy-beta-methylbutyrate in human whole blood using hydrophilic interaction liquid chromatography electrospray tandem mass spectrometry. Clin Biochem 46:18 (2013), 1877–1883, 10.1016/j.clinbiochem.2013.08.011.
31. [31] Ferrannini, E., The theoretical bases of indirect calorimetry: a review. Metab Clin Exp 37:3 (1988), 287–301.
32. [32] Bohe, J., Low, J.F., Wolfe, R.R., Rennie, M.J., Latency and duration of stimulation of human muscle protein synthesis during continuous infusion of amino acids. J Physiol 532:Pt 2 (2001), 575–579.
33. [33] Rennie, M.J., Bohe, J., Smith, K., Wackerhage, H., Greenhaff, P., Branched-chain amino acids as fuels and anabolic signals in human muscle. J Nutr 136:1 Suppl (2006), 264S–268S.
34. [34] Vesali, R.F., Klaude, M., Rooyackers, O., Wernerman, J., Amino acid metabolism in leg muscle after an endotoxin injection in healthy volunteers. Am J Physiol Endocrinol Metab 288:2 (2005), E360–E364, 10.1152/ajpendo.00248.2004.
35. [35] Bach, E., Nielsen, R.R., Vendelbo, M.H., Moller, A.B., Jessen, N., Buhl, M., et al. Direct effects of TNF-alpha on local fuel metabolism and cytokine levels in the placebo-controlled, bilaterally infused human leg: increased insulin sensitivity, increased net protein breakdown, and increased IL-6 release. Diabetes 62:12 (2013), 4023–4029, 10.2337/db13-0138.
36. [36] Farnfield, M.M., Carey, K.A., Gran, P., Trenerry, M.K., Cameron-Smith, D., Whey protein ingestion activates mTOR-dependent signalling after resistance exercise in young men: a double-blinded randomized controlled trial. Nutrients 1:2 (2009), 263–275, 10.3390/nu1020263.
37. [37] Yamamoto, D., Maki, T., Herningtyas, E.H., Ikeshita, N., Shibahara, H., Sugiyama, Y., et al. Branched-chain amino acids protect against dexamethasone-induced soleus muscle atrophy in rats. MuscleNerve 41:6 (2010), 819–827, 10.1002/mus.21621.
38. [38] Maki, T., Yamamoto, D., Nakanishi, S., Iida, K., Iguchi, G., Takahashi, Y., et al. Branched-chain amino acids reduce hindlimb suspension-induced muscle atrophy and protein levels of atrogin-1 and MuRF1 in rats. Nutr Res 32:9 (2012), 676–683, 10.1016/j.nutres.2012.07.005.
39. [39] Naito, T., Kuma, A., Mizushima, N., Differential contribution of insulin and amino acids to the mTORC1-autophagy pathway in the liver and muscle. J Biol Chem 288:29 (2013), 21074–21081, 10.1074/jbc.M113.456228.
40. [40] Noh, K.K., Chung, K.W., Choi, Y.J., Park, M.H., Jang, E.J., Park, C.H., et al. beta-Hydroxy beta-methylbutyrate improves dexamethasone-induced muscle atrophy by modulating the muscle degradation pathway in SD rat. PLoS One, 9(7), 2014, e102947, 10.1371/journal.pone.0102947.
41. [41] Baptista, I.L., Silva, W.J., Artioli, G.G., Guilherme, J.P., Leal, M.L., Aoki, M.S., et al. Leucine and HMB differentially modulate proteasome system in skeletal muscle under different sarcopenic conditions. PLoS One, 8(10), 2013, e76752, 10.1371/journal.pone.0076752.
42. [42] Secor, S.M., Specific dynamic action: a review of the postprandial metabolic response. J Comp Physiol B, Biochem Syst Environ Physiol 179:1 (2009), 1–56, 10.1007/s00360-008-0283-7.
43. [43] Duan, Y., Li, F., Li, Y., Tang, Y., Kong, X., Feng, Z., et al. The role of leucine and its metabolites in protein and energy metabolism. Amino Acids 48:1 (2016), 41–51, 10.1007/s00726-015-2067-1.
44. [44] Jakubowicz, D., Froy, O., Ahren, B., Boaz, M., Landau, Z., Bar-Dayan, Y., et al. Incretin, insulinotropic and glucose-lowering effects of whey protein pre-load in type 2 diabetes: a randomised clinical trial. Diabetologia 57:9 (2014), 1807–1811, 10.1007/s00125-014-3305-x.
45. [45] Gaudel, C., Nongonierma, A.B., Maher, S., Flynn, S., Krause, M., Murray, B.A., et al. A whey protein hydrolysate promotes insulinotropic activity in a clonal pancreatic beta-cell line and enhances glycemic function in ob/ob mice. J Nutr 143:7 (2013), 1109–1114, 10.3945/jn.113.174912.
46. [46] Tessari, P., Kiwanuka, E., Zanetti, M., Barazzoni, R., Postprandial body protein synthesis and amino acid catabolism measured with leucine and phenylalanine-tyrosine tracers. Am J Physiol Endocrinol Metab 284:5 (2003), E1037–E1042, 10.1152/ajpendo.00416.2002.
47. [47] Gallagher, P.M., Carrithers, J.A., Godard, M.P., Schulze, K.E., Trappe, S.W., Beta-hydroxy-beta-methylbutyrate ingestion, Part I: effects on strength and fat free mass. Med Sci Sports Exerc 32:12 (2000), 2109–2115.
48. [48] Crozier, S.J., Kimball, S.R., Emmert, S.W., Anthony, J.C., Jefferson, L.S., Oral leucine administration stimulates protein synthesis in rat skeletal muscle. J Nutr 135:3 (2005), 376–382.