Hypertrophy Mechanisms [3/3]: Metabolic Stress - Training Strategies and Techniques [Part 2/2]

Training strategies

1. Repetition schemes
Moderate repetition schemes rely heavily on anaerobic glycolysis (1,2). This results in a significant buildup of metabolites. Buildup of these metabolites has been shown to have a significant impact on anabolic processes (1,3). There may be a maximum threshold for tension-induced hypertrophy, above which metabolic factors become more important than additional increases in load (1).

Moderate repetition ranges also maximize acute cellular hydration. During moderate rep training, the veins taking blood out of working muscles are compressed while arteries continue to deliver blood into the working muscles. This creates an increased concentration of intramuscular blood plasma. The buildup of fluid in the interstitial spaces causes an extracellular pressure gradient, known as the ‘‘pump’’ (1). This is augmented by the accumulation of metabolic byproducts, which function as osmolytes, drawing fluid into the cell (1,4).

2. Muscular failure

Training to failure is hypothesized to activate a greater number of MUs (5).

Henneman’s size principle (of motor unit activation) states that motor units are recruited in an orderly fashion from smallest to largest with increasing requirement for force generation (6,7). If a submaximal (below 1RM), contraction is sustained motor units that were initially recruited fatigue, thus producing less force or cease firing completely, and need the recruitment of additional motor units (8). This provides an additional stimulus for hypertrophy (9).

It follows that as the repetitions are repeated or as the set progresses to the point of failure, near maximal motor unit recruitment to sustain muscle tension is achieved (10).

3. Intensity

Lower loads (30% RM) lifted to failure result in similar hypertrophy as heavy loads (80% RM) lifted to failure (at least in recreationally active subjects) (11). Lifting lighter loads, so long as fatigue is induced, leads to roughly equivalent hypertrophy and strength gains (11,12,13,14,15).

Also, lighter loads lifted to the point of failure result in a similar amount of muscle fiber activation compared with heavier loads, and both fiber types are stimulated to a roughly equivalent extent (11,16).

4. Time under tension

Time under tension has been shown to stimulate optimal growth (17). The time under tension during lower repetition sets appears to be suboptimal for hypertrophy.

Increased time under tension may enhance the potential for microtrauma and fatigueability. This would seem to have greatest applicability for hypertrophy of slow-twitch fibers, which have greater endurance capacity than fast-twitch fibers and thus would benefit by increased time under tension (1).

5. Rest Interval

Short rest intervals (30s) tend to generate significant metabolic stress leading to metabolite buildup, which enhance anabolic processes (1,18), however this compromises mechanical tension. Moderate rest intervals (60s) appear to provide a satisfactory compromise between long and short rest periods for maximizing the muscle hypertrophy (1).

Moderate rest (60s) induces greater hypoxia, heightening the potential for increased muscular growth (1,19). Moderate rest also is associated with a greater metabolic buildup, spiking anabolic hormonal concentrations after exercise (1,20).

Training techniques

1. Drop sets

Drop sets involve performing a set to muscular failure and then immediately reducing the load for another set (21). Multiple drops can be done in this fashion. The more multiple drops the greater the fatigue for the whole muscle will be (22) and the greater the metabolic stress for slow twitch fibers. Note that fast twitch fibers (for a giving load) are all involved when failure is reached. Drops sets allow for an increased time under tension, more metabolic stress and ischemia.

2. Ascending sets

This is sort of the opposite of drop sets. Rather than dropping the weight each time, the weight is increased every time as the repetitions decrease (12+10+8+6 reps).

Ascending sets might be beneficial to delay their fatigue response (rapid with low reps) and allow them to build up lactate until muscular failure where they are maximally recruited (size-principle). Slow-twitch fibers will get optimally stimulated as well anyway with long periods under tension.

3. Supersets

Supersets are 2 exercises or more performed in succession without rest (21,27). Supersets can performed for the same muscle, or for opposing muscles such as in an agonist-antagonist paired set (APS) training.  Because there’s practically no rest between sets, this may increase muscular fatigue and metabolic stress (28), the same as with drop sets with moderate to high repetitions. Supersets should have be done to failure (every exercise).

4. Blood flow restriction

Occlusion training causes blood flow restriction and involves obstructing blood flow to the veins, but not the arteries so that they continue to deliver blood to the limb (25,26). In other words, blood gets in but struggles to get out. This is done using knee wraps for the legs, and wrist wraps for the arms (25).

Blood flow should not be completely restricted, it should be restricted at about 50-70%. A scale of perceived pressure should be used, for example from 1-10 (10-100%). During BFR, muscle cells reach become so full of fluid that they have to grow or die (29). BFR increase muscle cell swelling, the low oxygen level and accumulation of blood increase fast-twitch muscle fiber recruitment (26,29,30,31) and increase blood lactic acid levels 2 which stimulate protein synthesis (32).

Shorter rest periods (30 seconds) are optimal (32). Interestingly, the concentric action is more important than the eccentric action (33), which is the opposite of traditional training where the eccentric causes more damage and increased protein synthesis. This is because high forces can be generated at a relatively low metabolic cost in eccentric contractions compared to either isometric or concentric contractions (34).

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Also read:


1. Brad Schoenfeld. The mechanisms of muscle hypertrophy and their application to resistance training. J Strength Cond Res. 24(10): 2857–2872, 2010. 
2. Robergs, RA, Ghiasvand, F, and Parker, D. Biochemistry of exercise induced metabolic acidosis. Am J Physiol. Reg Int Comp Physiol  287: R502–R516, 2003.
3. Kraemer, WJ and Ratamess, NA. Hormonal responses and adaptations to resistance exercise and training. Sport Med 35: 339–361, 2005.
4. Sj√łgaard, G, Adams, RP, and Saltin, B. Water and ion shifts in skeletal muscle of humans with intense dynamic knee extension. Am J Physiol 248: R190–R196, 1985
5. Willardson JM. The application of training to failure in periodized multiple-set resistance exercise programs. J Strength Cond Res 21: 628–631, 2007.
6. Henneman E. Relation between size of neurons and their susceptibility to discharge. Science 126: 1345–1347, 1957.
7. Henneman E, Somjen G, Carpenter DO. Functional significance of cell size in spinal motoneurons. J Neurophysiol 28: 560–580, 1965.
8. Fallentin N, Jorgensen K, Simonsen EB. Motor unit recruitment during prolonged isometric contractions. Eur J Appl Physiol Occup Physiol 67:335–341, 1993.
9. Rooney, KJ, Herbert, RD, and Balnave, RJF. Fatigue contributes to the strength training stimulus. Med Sci Sport Exerc 26: 1160–1164, 1994.
10. Fuglevand AJ, Zackowski KM, Huey KA, Enoka RM. Impairment of neuromuscular propagation during human fatiguing contractions at submaximal forces. J Physiol 460: 549–572, 1993.
11. Mitchell CJ, Churchward-Venne TA, West DW, Burd NA, Breen L, Baker SK, Phillips SM. Resistance exercise load does not determine training-mediated hypertrophic gains in young men. J Appl Physiol 113: 71–77, 2012.
12. Leger B, Cartoni R, Praz M, Lamon S, Deriaz O, Crettenand A, Gobelet C, Rohmer P, Konzelmann M, Luthi F, Russell AP. Akt
signalling through GSK-3beta, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy. J Physiol 576: 923–933, 2006.
13. Takarada Y, Sato Y, Ishii N. Effects of resistance exercise combined with vascular occlusion on muscle function in athletes. Eur J Appl Physiol
86: 308–314, 2002.
14. Takarada Y, Takazawa H, Sato Y, Takebayashi S, Tanaka Y, Ishii N. Effects of resistance exercise combined with moderate vascular occlusion on muscular function in humans. J Appl Physiol 88: 2097–2106, 2000.
15. Tanimoto M, Ishii N. Effects of low-intensity resistance exercise with slow movement and tonic force generation on muscular function in young men. J Appl Physiol 100: 1150–1157, 2006.
16. Ogasawara R, Loenneke JP, Thiebaud RS, and Abe T. Low-load bench press training to fatigue results in muscle hypertrophy similar to high-load bench press training. International Journal of Clinical Medicine 4: 114–121, 2013.
17. Evans, W.J. The metabolic effects of exercise-induced muscle damage. Exerc. Sport Sci. Rev. 19: (-HD-). 99–125. 1991.
18. Goto, K, Nagasawa, M, Yanagisawa, O, Kizuka, T, Ishii, N, and Takamatsu, K. Muscular adaptations to combinations of high- and low-intensity resistance exercises. J Strength Cond Res 18: 730–737, 2004.
19. Bodine, SC, Stitt, TN, Gonzalez, M, Kline, WO, Stover, GL, Bauerlein, R, Zlotchenko, E, Scrimgeour, A, Lawrence, JC, Glass, DJ, and Yancopoulos, GD. Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol 3: 1014–1019, 2001
20. Kraemer, WJ, Marchitelli, L, Gordon, SE, Harman, E, Dziados, JE, Mello, R, Frykman, P, McCurry, D, and Fleck, SJ. Hormonal and growth factor responses to heavy resistance exercise protocols. J Appl Physiol 69: 1442–1450, 1990
21. Brad Schoenfeld. The Use of Specialized Training Techniques to Maximize Muscle Hypertrophy. Strength & Conditioning Journal: August 2011 - Volume 33 - Issue 4 - pp 60-65
22. Willardson JM. The application of training to failure in periodized multiple-set resistance exercise programs. J Strength Cond Res 21: 628–631, 2007.
23. Pauletto B. Choice and order of exercises. Natl Strength Cond Assoc J 8: 71–73, 1986.
24. Kelleher AR, Hackney KJ, Fairchild TJ, Keslacy S, and Ploutz-Snyder LL. The metabolic costs of reciprocal supersets vs. traditional resistance exercise in young recreationally active adults. J Strength Cond Res 24: 1043–1051, 2010.
25. Wilson JM, Lowery RP, Joy JM, Loenneke JP, & Naimo MA (2013). Practical Blood Flow Restriction Training Increases Acute Determinants of Hypertrophy Without Increasing Indices of Muscle Damage. J Strength Cond Res, epub ahead of print.
26. Loenneke JP, Abe T, Wilson JM, Ugrinowitsch C, & Bemben MG (2012) Blood flow restriction: how does it work? Front Physiol, 3, 392.
27. Pauletto B. Choice and order of exercises. Natl Strength Cond Assoc J 8: 71–73, 1986
28. Kelleher AR, Hackney KJ, Fairchild TJ, Keslacy S, and Ploutz-Snyder LL. The metabolic costs of reciprocal supersets vs. traditional resistance exercise in young recreationally active adults. J Strength Cond Res 24: 1043–1051, 2010.
29.  Loenneke JP, Fahs CA, Rossow LM, Abe T, & Bemben MG (2011). The anabolic benefits of venous blood flow restriction training may be induced by muscle cell swelling. Med Hypotheses, 78(1), 151-154.
30.  Loenneke JP, Fahs CA, Wilson JM, & Bemben MG (2011). Blood flow restriction: the metabolite/volume threshold theory. Med Hypotheses, 77(5), 748-752.
31. Loenneke JP, Wilson GJ, & Wilson JM (2010). A mechanistic approach to blood flow occlusion. Int J Sports Med, 31(1), 1-4.
32.  Loenneke JP, Wilson JM, Marin PJ, Zourdos MC, & Bemben MG (2012). Low intensity blood flow restriction training: a meta-analysis. Eur J Appl Physiol, 112(5), 1849-1859.
33. Schoenfeld, BJ (2013). Potential mechanisms for a role of metabolic stress in hypertrophic adaptations to resistance training. Sports Med, 43(3), 179-194.

34. Bigland-Ritchie B, Woods JJ (1976) Integrated electromyogram and oxygen uptake during positive and negative work. J Physiol (Lond) 260:267-277