The purpose of this study was to determine whether the training responses observed with low-load resistance exercise to volitional fatigue translates into significant muscle hypertrophy, and compare that response to high-load resistance training. Nine previously untrained men (aged 25 [SD 3] years at the beginning of the study, standing height 1.73 [SD 0.07] m, body mass 68.9 [SD 8.1] kg) completed 6-week of high load-resistance training (HL-RT) (75% of one repeti-tion maximal [1RM], 3-sets, 3x/wk) followed by 12 months of detraining. Following this, subjects completed 6 weeks of low load-resistance training (LL-RT) to volitional fatigue (30% 1 RM, 4 sets, 3x/wk). Increases (p < 0.05) in magnetic resonance imaging-measured triceps brachii and pectorals major muscle cross-sectional areas were similar for both HL-RT (11.9% and 17.6%, respectively) and LL-RT (9.8% and 21.1%, respectively). In addition, both groups increased (p < 0.05) 1RM and maximal elbow extension strength following training; however, the percent increases in 1RM (8.6% vs. 21.0%) and elbow extension strength (6.5% vs. 13.9%) were significantly (p < 0.05) lower with LL-RT. Both protocols elicited similar increases in muscle cross-sectional area, however differences were observed in strength. An explanation of the smaller relative increases in strength may be due to the fact that detraining after HL-RT did not cause strength values to return to baseline levels thereby producing smaller changes in strength. In addition, the results may also suggest that the consistent practice of lifting a heavy load is necessary to maximize gains in muscular strength of the trained movement. These results demonstrate that significant muscle hypertrophy can occur without high-load resistance training and suggests that the focus on percentage of external load as the important deciding factor on muscle hypertrophy is too simplistic and inappropriate.
 M. J. Drummond, C. S. Fry, E. L. Glynn, K. L. Timmer man, J. M. Dickinson, D. K. Walker, D. M. Gundermann, E. Volpi and B. B. Rasmussen, “Skeletal Muscle Amino Acid Transporter Expression Is Increased in Young and Older Adults Following Resistance Exercise,” Journal of Applied Physiology, Vol. 111, No. 1, 2011, pp. 135 142. doi:10.1152/japplphysiol.01408.2010
 N. A. Burd, R. J. Andrews, D. W. West, J. P. Little, A. J. Cochran, A. J. Hector, J. G. Cashaback, M. J. Gibala, J. R. Potvin, S. K. Baker and S. M. Phillips, “Muscle Time un der Tension during Resistance Exercise Stimulates Dif ferential Muscle Protein Sub Fractional Synthetic Re sponses in Men,” Journal of Physiology, Vol. 590, No. 2, 2012, pp. 351 362.
 J. P. Loenneke, C. A. Fahs, J. M. Wilson and M. G. Bem ben, “Blood Flow Restriction: The Metabolite/Volume Threshold Theory,” Medical Hypotheses, Vol. 77, No. 5, 2011, pp. 748 752. doi:10.1016/j.mehy.2011.07.029
 S. M. Phillips, “Physiologic and Molecular Bases of Muscle Hypertrophy and Atrophy: Impact of Resistance Exer cise on Human Skeletal Muscle (Protein and Exercise Dose Effects),” Applied Physiology, Nutrition, and Me tabolism, Vol. 34, No. 3, 2009, pp. 403 410. doi:10.1139/H09 042
 American College of Sports Medicine (ACSM) Position Stand, “Progression Models in Resistance Training for Healthy Adults,” Medicine and Science in Sports and Ex ercise, Vol. 41, No. 3, 2009, pp. 687 708. doi:10.1249/MSS.0b013e3181915670
 N. A. Burd, D. W. West, A. W. Staples, P. J. Atherton, J. M. Baker, D. R. Moore, A. M. Holwerda, G. Parise, M. J. Rennie, S. K. Baker and S. M. Phillips, “Low Load High Volume Resistance Exercise Stimulates Muscle Protein Synthesis More than High Load Low Volume Resistance Exercise in Young Men,” PLoS One, Vol. 5, No. 8, 2010, e12033. doi:10.1371/journal.pone.0012033
 J. M. Willardson, “The Application of Training to Failure in Periodized Multiple Set Resistance Exercise Pro grams,” Journal of Strength and Conditioning Research, Vol. 21, No. 2, 2007, pp. 628 631.
 G. E. Campos, T. J. Luecke, H. K. Wendeln, K. Toma, F. C. Hagerman, T. F. Murray, K. E. Ragg, N. A. Ratamess, W. J. Kraemer and R. S. Staron, “Muscular Adaptations in Response to Three Different Resistance Training Re gimens: Specificity of Repetition Maximum Training Zones,” European Journal of Applied Physiology, Vol. 88, No. 1 2, 2002, pp. 50 60. doi:10.1007/s00421 002 0681 6
 B. Leger, R. Cartoni, M. Praz, S. Lamon, O. Deriaz, A. Crettenand, C. Gobelet, P. Rohmer, M. Konzelmann, F. Luthi and A. P. Russell, “Akt Signalling through GSK 3Beta, mTOR and Foxo1 Is Involved in Human Skeletal Muscle Hypertrophy and Atrophy,” Journal of Physiol ogy, Vol. 576, No. 3, 2006, pp. 923 933. doi:10.1113/jphysiol.2006.116715
 D. W. West, N. A. Burd, J. E. Tang, D. R. Moore, A. W. Staples, A. M. Holwerda, S. K. Baker and S. M. Phillips, “Elevations in Ostensibly Anabolic Hormones with Resistance Exercise Enhance neither Training Induced Mus cle Hypertrophy nor Strength of the Elbow Flexors,” Journal of Applied Physiology, Vol. 108, No. 1, 2010, pp. 60 67. doi:10.1152/japplphysiol.01147.2009
 D. W. West and S. M. Phillips, “Associations of Exer cise Induced Hormone Profiles and Gains in Strength and Hypertrophy in a Large Cohort after Weight Training,” European Journal of Applied Physiology, Vol. 112, No. 7, 2012, pp. 2693 2702. doi:10.1007/s00421 011 2246 z
 V. G. Coffey, Z. Zhong, A. Shield, B. J. Canny, A. V. Chibalin, J. R. Zierath and J. A. Hawley, “Early Signaling Responses to Divergent Exercise Stimuli in Skeletal Mus cle from Well Trained Humans,” FASEB Journal, Vol. 20, No. 1, 2006, pp. 190 192.
 S. B. Wilkinson, M. A. Tarnopolsky, E. J. Grant, C. E. Correia and S. M. Phillips, “Hypertrophy with Unilateral Resistance Exercise Occurs without Increases in Endo genous Anabolic Hormone Concentration,” European Journal of Applied Physiology, Vol. 98, No. 6, 2006, pp. 546 555. doi:10.1007/s00421 006 0300 z
 C. J. Mitchell, T. A. Churchward Venne, D. W. West, N. A. Burd, L. Breen, S. K. Baker and S. M. Phillips, “Resis tance Exercise Load Does Not Determine Training Me diated Hypertrophic Gains in Young Men,” Journal of Applied Physiology, Vol. 113, No. 1, 2012, pp. 71 77. doi:10.1152/japplphysiol.00307.2012
 R. Ogasawara, R. S. Thiebaud, J. P. Loenneke and T. Abe, “Time Course for Arm and Chest Muscle Thickness Changes Following Bench Press Training,” Interventional Medicine and Applied Science, Vol. 4, No. 4, 2012, pp. 217 220. doi:10.1556/IMAS.4.2012.4.7
 R. Ogasawara, T. Yasuda, N. Ishii and T. Abe, “Com parison of Muscle Hypertrophy Following 6 Month of Continuous and Periodic Strength Training,” European Journal of Applied Physiology, in Press. doi:10.10007/s00421 012 2511 9
 P. Kannus, D. Alosa, L. Cook, R. J. Johnson, P. Renstrom, M. Pope, B. Beynnon, K. Yasuda, C. Nichols and M. Kaplan, “Effect of One Legged Exercise on the Strength, Power and Endurance of the Contralateral Leg. A Ran domized, Controlled Study Using Isometric and Concen tric Isokinetic Training,” European Journal of Applied Physiology and Occupational Physiology, Vol. 64, No. 2, 1992, pp. 117 126. doi:10.1007/BF00717948
 T. Abe, D. V. DeHoyos, M. L. Pollock and L. Garzarella, “Time Course for Strength and Muscle Thickness Changes Following Upper and Lower Body Resistance Training in Men and Women,” European Journal of Applied Physi ology, Vol. 81, No. 3, 2000, pp.174 180. doi:10.1007/s004210050027
 T. Yasuda, R. Ogasawara, M. Sakamaki, H. Ozaki, Y. Sato and T. Abe, “Combined Effects of Low Intensity Blood Flow Restriction Training and High Intensity Re sistance Training on Muscle Strength and Size,” Euro pean Journal of Applied Physiology, Vol. 111, No. 10, 2011, pp. 2525 2533. doi:10.1007/s00421 011 1873 8
 J. Tannerstedt, W. Apro and E. Blomstrand, “Maximal Lengthening Contractions Induce Different Signaling Re sponses in the Type I and Type II Fibers of Human Ske letal Muscle,” Journal of Applied Physiology, Vol. 106, No. 4, 2009, pp. 1412 1418. doi:10.1152/japplphysiol.91243.2008
 G. Terzis, G. Georgiadis, G. Stratakos, I. Vogiatzis, S. Kavouras, P. Manta, H. Mascher and E. Blomstrand, “Resistance Exercise Induced Increase in Muscle Mass Correlates with p70S6 Kinase Phosphorylation in Human Subjects,” European Journal of Applied Physiology, Vol. 102, No. 2, 2008, pp. 145 152. doi:10.1007/s00421 007 0564 y
 M. J. Rennie, H. Wackerhage, E. E. Spangenburg and F. W. Booth, “Control of the Size of the Human Muscle Mass,” Annual Review of Physiology, Vol. 66, 2004, pp. 799 828. doi:10.1146/annurev.physiol.66.052102.134444
 J. C. Bruusgaard, I. B. Johansen, I. M. Egner, Z. A. Rana and K. Gundersen, “Myonuclei Acquired by Overload Exercise Precede Hypertrophy and are Not Lost on De training,” Proceedings of the National Academy of Sciences in the United States of America, Vol. 107, No. 34, 2010, pp. 15111 15116. doi:10.1073/pnas.0913935107
 O. R. Seynnes, M. de Boer and M. V. Narici, “Early Skeletal Muscle Hypertrophy and Architectural Changes in Response to High Intensity Resistance Training,” Jour nal of Applied Physiology, Vol. 102, No. 1, 2007, pp. 368 373. doi:10.1152/japplphysiol.00789.2006
 R. Ogasawara, T. Yasuda, M. Sakamaki, H. Ozaki and T. Abe, “Effects of Periodic and Continued Resistance Training on Muscle CSA and Strength in Previously Untrained Men,” Clinical Physiology and Functional Imag ing, Vol. 31, No. 5, 2011, pp. 399 404. doi:10.1111/j.1475 097X.2011.01031.x
 T. Yasuda, R. Ogasawara, M. Sakamaki, M. G. Bemben and T. Abe, “Relationship between Limb and Trunk Mus cle Hypertrophy Following High Intensity Resistance Training and Blood Flow Restricted Low Intensity Resis tance Training,” Clinical Physiology and Functional Im aging, Vol. 31, No. 5, 2011, pp. 347 351. doi:10.1111/j.1475 097X.2011.01022.x
 R. S. Staron, M. J. Leonardi, D. L. Karapondo, E. S. Ma licky, J. E. Falkel, F. C. Hagerman and R. S. Hikida, “Strength and Skeletal Muscle Adaptations in Heavy Resistance Trained Women after Detraining and Retraining,” Journal of Applied Physiology, Vol. 70, No. 2, 1991, pp. 631 640.
 C. S. Bickel, J. M. Cross and M. M. Bamman, “Exercise Dosing to Retain Resistance Training Adaptations in Young and Older Adults,” Medicine and Science in Sports Exer cise, Vol. 43, No. 7, 2011, pp. 1177 1187. doi:10.1249/MSS.0b013e318207c15d
 K. Smith, K. Winegard, A. L. Hicks and N. McCartney, “Two Years of Resistance Training in Older Men and Women: The Effects of Three Years of Detraining on the Retention of Dynamic Strength,” Canadian Journal of Applied Physiology, Vol. 28, No. 3, 2003, pp. 462 474. doi:10.1139/h03 034
 C. Del Balso and E. Cafarelli, “Adaptations in the Activa tion of Human Skeletal Muscle Induced by Short Term Isometric Resistance Training,” Journal of Applied Physi ology, Vol. 103, No. 1, 2007, pp. 402 411. doi:10.1152/japplphysiol.00477.2006