August 17, 2022

Muscle Hyperplasia: Process and Protocol

Arguably the most important questions in exercise physiology scientific research have always centered around understanding the mechanisms that can drive muscle adaptation to increase force production capacity, or more simply stated, ways for people to get stronger. The most accepted science dictates that muscles grow in size due to the growth of existing muscle fibers.

The Stretch Effect for Extra Growth

Some studies, however, have demonstrated that under extreme conditions of muscle size, lengthening, and workload, there is evidence that muscles can take advantage of an even more powerful mechanism. Muscle cells/fibers can split to form additional new fibers, a process called hyperplasia. Dr. Jose Antonio has been at the center of this controversial research and did his doctoral dissertation on the subject. The following covers his findings and supporting research, as well as a practical approach to using X3 to both trigger and amplify this effect to the maximum degree.

Hypertrophy refers to an increase in the size of the muscle cell/fiber while hyperplasia refers to an increase in the number of cells/fibers. Since this adaptation has been identified and confirmed, destruction of muscle cells/fibers has also been observed with endurance athletes when compared to individuals who have never trained for athletic adaptation in any way.1 2

When the body begins adapting to higher levels of force being put through a muscle, the adaptation is specific to help improve the tolerance of the imposed demand. So for example, the elements within a cell that aid in aerobic metabolism like mitochondria, do not increase in volume or performance with strength type exercise. Only the amount of contractile proteins is important in the context of maximum force production, and that is what grows. Single muscle cell/fiber hypertrophy does happen in two ways, sarcoplasmic and myofibrillar hypertrophy, but the instantaneous force production is only influenced by the amount of contractile proteins available, which is the myofibrillar effect.

Back in the 1970s, researchers began testing a stretching type stimulus with animals for extended periods in order to see how the muscle would adapt. While the parameters of this research made it impractical and unethical to perform with human test subjects, much was learned. For example, with a thirty-day stretching-type protocol, researchers observed a 172 percent increase in muscle mass and a 52–75 percent increase in muscle-fiber count.3 This study was then replicated in 1991 with very similar results.4

Can We Induce This Effect In Humans

Throughout the natural growth progression from childhood to adolescence to adulthood, it has been shown that the continual passive mechanical stretch imposed by growing bone on muscle is responsible for f in length and size, including general mass adaptation.5 Studies have been conducted that show that adolescents undergoing their growth spurt increase in lean body mass in a manner directly proportional to the growth of the skeleton.6 This literature led to something called “bag theory.”

Bag theory speaks to the constraints of the tissue that surrounds the muscle, called muscle fascia. Muscle does not exist in a vacuum, but rather it exists with a substantial connective tissue membrane surrounding it, which may be one of the major determinants of growth for that muscle. As referenced above, through natural growth, this connective tissue membrane stretches in humans, and muscle growth shortly follows. Also, proven through animal models, pressure applied to stretching of the muscle can facilitate growth. This argument is key in the “muscle memory” discussion. Since athletes who experience muscle mass loss through detraining can regain the lost mass very easily, scientists have theorized that they benefit during retraining because the muscle fascia had previously been stretched or expanded and allowed a greater level of flexibility based on the extra mass that previously existed. This larger “container” for muscle tissue may then facilitate more rapid regrowth when the individual begins training again.

Can We Induce This Effect In Humans

When looking at the physical mechanics of bag theory, the stretching of the fascia allows for more space inside of the muscle for hydration and for nutrients to be utilized by the muscle so that both sarcoplasmic and myofibril hypertrophy can be amplified. When this happens, another phenomenon has been shown to occur in the animal models of research. Hyperplasia occurs. So how do we know that hyperplasia can occur in humans just like in the animal models?

We know hyperplasia occurs in humans because of one particular study done with elite bodybuilders and powerlifters that had upper arm circumferences 27 percent greater than the normal non-exerciser control group yet the cross-sectional size of the athlete’s muscle fibers in the triceps were not different than the controls, meaning there were more cells in the triceps.7 Nygaard and Neilsen performed a similar study and showed similar results, so we know that humans can induce hyperplasia.8 But based on what we have learned with the animal models, the biggest question is how do we create the largest stretch on the muscle without doing what was done to the animals, which was basically multi-day constant stretching of the muscle?

Creating An Extended Stretch Effect for Extra Growth

One of the problems with flexibility work via stretching singular muscles is that the extended flexibility of the target muscle is extremely temporary. A 2001 study took rapid measurements of flexibility adaptations after stretching sessions of specific muscles and determined that the effect begins to diminish after six minutes.9 So how do we keep the effect of the stretch in place for extended periods of time? This is obviously needed for the more aggressive level of muscle protein synthesis and hyperplasia.

As you perform your X3 session, especially with the hypoxia inducing constant tension technique, you will see a muscle blood flow increasing effect in the target muscle that is most likely beyond anything you have ever experienced. This effect can last for thirty minutes. So when an individual does a set, a thirty-second stretch of the target muscles will amplify this process and allow more blood flow into the muscle. Now, within (AND ONLY WITHIN) this thirty-minute window, you have the opportunity to do something that runs very contrary to almost everything else we say nutritionally. In that thirty minute window, you could eat simple carbohydrates.

Don’t let this confuse you. Carbohydrates play absolutely NO role in muscle protein synthesis and are not needed in any way to grow muscle, and more than ten studies have demonstrated this, including some that demonstrate that no organ in the body needs carbohydrates.10 11 12 13 14 15 16 17 18 19 20

HOWEVER, carbohydrates play a role in the hydration of muscle cells and, not surprisingly, in the hydration of most other cells in the body. You retain two to three grams of water per gram of carbohydrates you intake.21 This is part of the reason why so many suffer from high blood pressure. They are constantly overconsuming carbohydrates and driving their blood pressure up because of water retention. However, in our case, we first deplete muscle glycogen, then replenish it immediately using carbohydrates, and after stretching the entire muscle and creating more room within the cells and within the entire muscle fascia, we create a hyper-hydration environment which enables accelerated muscle protein synthesis.

In 2004, one of the most important studies to support the hypothesis of muscle fascia stretching delivering better cellular hydration and accelerated muscle growth was published. This study concluded, “Thus the pressurization of L6 cells (mammal skeletal muscle) stimulated lactate utilization and glucose uptake. These findings suggest that mechanical pressure enhanced aerobic metabolism in skeletal muscle cells and may provide valuable clues toward elucidating the nervous system-independent mechanism(s) for metabolic activation and/or adaptation by skeletal muscle contraction.” This means that by increasing the pressures within the cell, more muscle growth can occur.22

It seems 2004 was a popular year for research around the immediate post-workout replenishment of glycogen in musculature, because another case study came out then. This one concluded, “For rapid recovery from prolonged exercise, it is important to replenish muscle glycogen stores and initiate muscle tissue repair and adaptation… To maximize muscle glycogen replenishment, it is important to consume a carbohydrate supplement as soon after exercise as possible.”23 Low and researchers demonstrated earlier that this environment could better transport amino acids to facilitate greater muscle protein synthesis, concluding “Hyper-hydration also may have a direct effect on amino acid transport systems.”24 Most recently in 2014 another study has confirmed these same findings, concluding: “Cellular swelling, often referred to as “the pump,” has been shown to mediate increase in muscle protein synthesis and decrease protein degradation.”25

What Is The Best Protocol For Hyperhydration Of Muscle?

Now, this may just sound like the opportunity to have an incredible “cheat meal.” Not the case. In fact, a relatively small amount of carbohydrates are required to replenish muscle glycogen even in a stretched muscle. Consuming 0.5–0.7 grams of carbs per pound (1.1–1.5 grams/kg) of body weight within thirty minutes after training results in proper glycogen resynthesis.26 27

So for a 200-pound male lifter for example, this would, on the higher side, be 140g of carbohydrates. That would be approximately three cups of rice. White rice absorbs rather quickly, therefore it is a good choice for this endeavor. There is insulin secretion with this process, but it’s lower than if there was no workout because the insulin and glucose should be matched, thus absorbing into muscle quickly. This keeps users of this practice from having the sugar cravings normally associated with carbohydrate intake.

Jaquish Biomedical recently launched FortagenHP, a supplement combining essential amino acids with glucose to rapidly replenish muscle glycogen and enhance cellular hydration, promoting muscle hyperplasia.

  • Unique and precisely balanced amino acid formula
  • 5x more efficient than standard protein sources
  • Perfect protein for the Hyperplasia Protocol

What Is The Best Protocol For Hyperhydration Of Muscle?

Amplification of this process can come from vasodilation or other methods of encouraging extracellular hydration. There are four possibilities that we are aware of:

Creatine monohydrate.** Our least favorite cellular hydration amplifier

Creatine occurs naturally in animal proteins and has no side effects, but in its isolated form, it has been seen to exacerbate bipolar disorder, kidney dysfunctions, and Parkinson’s disease. It has also been extensively tested as a weightlifting supplement, with unimpressive results.


Once on the banned substance list for some strange reason, this supplement will attract water and in effect increase blood flow into muscle with a vasodilatory (opening of blood vessels) effect. If you choose this option, use the Hydromax versions. The straight glycerol powder will likely give you diarrhea and compromise digestion of all nutrients you consume later that day.


This is a vasodilation agent that will increase blood flow all over the body. Many fake Viagra-type products are made of this, as it has a similar, albeit far weaker, effect.

Viagra/Levitra/Cialis (prescription vasodilator)

Probably the most powerful way to amplify muscular cellular hydration beyond carbohydrate consumption alone. Obviously, you would need a prescription for these medications. We do not advise walking into your physician’s office and talking about a prescription vasodilator for the purposes of muscle building. Many physicians would not understand this as a need and will deny you the prescription. You may consider going down this path if you have other legitimate reasons for qualifying for the prescription, as determined by you and your physician. This has been specifically demonstrated in clinical literature to increase the amount of muscle protein synthesis.28

Steps to amplified growth and hyperplasia are as follows:

  1. Approximately one hour before your workout time, you will take whatever it is you decided to amplify cellular hydration and blood flow, meaning creatine/glycerol/epimedium/prescription vasodilator. Then, 15 minutes before your workout, consume FortagenHP. This supplement combines EAAs with glucose to enhance cellular hydration and replenish muscle glycogen, promoting hyperplasia.
  2. Do your normal workout, assuming X3, and keep constant tension so that your hypoxia and blood flow are at their absolute maximum and never do less than fifteen reps. The “pump” from this workout will be one of the largest you have ever felt.
  3. After the workout, stretch all the target muscles for thirty seconds each. We aren’t going to recommend any particular types of stretch for individual muscles because throughout life we all have slight joint pain and dysfunctions (this is an example of where many people are different). We want you to pick the stretches that feel the most comfortable. This takes the already present “pump” extra blood flow and amplifies it based on the fascia stretching described earlier. So here the stretch and the extra blood flow are working together in a synergistic manner.
  4. As soon as possible, and definitely before thirty minutes have passed since the end of your workout, consume between 0.5–0.7 grams of carbs per pound (1.1–1.5 grams/kg) of body weight. This replenishes the spent glycogen stores and can amplify the stretch effect within the muscle to increase muscle protein synthesis and trigger hyperplasia.
  5. (Optional for those doing fasting) Eat your one meal for the day, or enter your eating window, where you may have two meals. You want to make sure that when your appetite is stimulated from carbohydrates, you take advantage of that fact and get as much high-quality protein as possible. As stated earlier, one gram per pound of body weight, or 2.2g/kg of body weight.
An Amino Acid Supplement Engineered to Build Muscle


  1. Costill, D. L., E. F. Coyle, W. F. Fink, G. R. Lesmes, and F. A. Witzmann. (1979). Adaptations in skeletal muscle following strength training. J. Appl. Physiol. 46(1): 96-99. ↩︎

  2. Tesch, P. A. and L. Larsson. (1982). Muscle hypertrophy in bodybuilders. Eur. J. Appl. Physiol. 49: 301-306. ↩︎

  3. Sola, O. M., D. L. Christensen, and A. W. Martin. (1973). Hypertrophy and hyperplasia of adult chicken anterior latissimus dorsi muscles following stretch with and without denervation. Exp. Neurol. 41: 76-100. ↩︎

  4. Winchester, P. K., M. E. Davis, S. E. Alway, and W. J. Gonyea. (1991). Satellite cell activation of the stretchenlarged anterior latissimus dorsi muscle of the adult quail. Am. J. Physiol. 260: C206-C212. ↩︎

  5. Gajdosik, R. L. 2001, “Passive extensibility of skeletal muscle: review of the literature with clinical implications,” Clin.Biomech.(Bristol., Avon.), vol. 16, no. 2, pp. 87–101 ↩︎

  6. Gajdosik, R. L. 2001, “Passive extensibility of skeletal muscle: review of the literature with clinical implications,” Clin.Biomech.(Bristol., Avon.), vol. 16, no. 2, pp. 87–101 ↩︎

  7. Yamada, S., N. Buffinger, J. Dimario, and R. C. Strohman. (1989). Fibroblast growth factor is stored in fiber extracellular matrix and plays a role in regulating muscle hypertrophy. Med. Sci. Sports Exerc. 21(5): S173-S180. ↩︎

  8. Nygaard, E. and E. Nielsen. (1978). Skeletal muscle fiber capillarisation with extreme endurance training in man. Swimming Medicine IV(vol. 6, pp. 282-293). University Park Press, Baltimore. ↩︎

  9. Spernoga, S. G., Uhl, T. L., Arnold, B. L., & Gansneder, B. M. (2001). Duration of maintained hamstring flexibility after a one-time, modified hold-relax stretching protocol. Journal of Athletic Training, 36(1), 44. ↩︎

  10. Staples AW, Burd NA, West DW, Currie KD, Atherton PJ, Moore DR, Rennie MJ, Macdonald MJ, Baker SK, Phillips SM. (2011). Carbohydrate does not augment exercise-induced protein accretion versus protein alone. Med Sci Sports Exerc.;43(7):1154–1161. ↩︎

  11. Koopman R, Beelen M, Stellingwerff T, Pennings B, Saris WH, Kies AK, Kuipers H, Van Loon LJ. (2007). Coingestion of carbohydrate with protein does not further augment postexercise muscle protein synthesis. Am J Physiol Endocrinol Metab.;293(3):E833–842. ↩︎

  12. Koopman R, Beelen M, Stellingwerff T, Pennings B, Saris WH, Kies AK, Kuipers H, Van Loon LJ. (2007). Coingestion of carbohydrate with protein does not further augment postexercise muscle protein synthesis. Am J Physiol Endocrinol Metab.;293(3):E833–842. ↩︎

  13. Glynn EL, Fry CS, Timmerman KL, Drummond MJ, Volpi E, Rasmussen BB. (2013). Addition of carbohydrate or alanine to an essential amino acid mixture does not enhance human skeletal muscle protein anabolism. J Nutr.;143(3):307–314. ↩︎

  14. Hamer HM, Wall BT, Kiskini A, De Lange A, Groen BBL, Bakker JA, Gijsen AP, Verdijk LB, Van Loon LJC. (2013). Carbohydrate co-ingestion with protein does not further augment post-prandial muscle protein accretion in older men. _Nutr Metab;10(1):15. ↩︎

  15. Cuthbertson D Smith K Babraj J et al. (2005). Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB Journal;19:422–424. ↩︎

  16. Greenhaff, P. L., Karagounis, L. G., Peirce, N., Simpson, E. J., Hazell, M., Layfield, R., ……& Rennie, M. J. (2008). Disassociation between the effects of amino acids and insulin on signaling, ubiquitin ligases, and protein turnover in human muscle. American Journal of Physiology-Endocrinology and Metabolism, 295(3), E595-E604. ↩︎

  17. Volpi, E., Kobayashi, H., Sheffield-Moore, M., Mittendorfer, B., & Wolfe, R. R. (2003). Essential amino acids are primarily responsible for the amino acid stimulation of muscle protein anabolism in healthy elderly adults. The American Journal of Clinical Nutrition, 78(2), 250-258. ↩︎

  18. Moore, D. R., Churchward-Venne, T. A., Witard, O., Breen, L., Burd, N. A., Tipton, K. D., & Phillips, S. M. (2014). Protein ingestion to stimulate myofibrillar protein synthesis requires greater relative protein intakes in healthy older versus younger men. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 70(1), 57-62. ↩︎

  19. Paddon-Jones, D., Campbell, W. W., Jacques, P. F., Kritchevsky, S. B., Moore, L. L., Rodriguez, N. R., & van Loon, L. J. (2015). Protein and healthy aging. The American Journal of Clinical Nutrition, 101(6), 1339S-1345S. ↩︎

  20. US Food and Nutrition Board’s 2005 textbook. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. 275-277. ↩︎

  21. Figueiredo, V. C., & Cameron-Smith, D. (2013). Is carbohydrate needed to further stimulate muscle protein synthesis/hypertrophy following resistance exercise? Journal of the International Society of Sports Nutrition, 10(1), 42. ↩︎

  22. Steen, J. (2017, November 6). We Found Out If Carbs Really Make You Look ‘Puffy’ And Retain Water. Retrieved March 7, 2020, from ↩︎

  23. Morita, N., Iizuka, K., Okita, K., Oikawa, T., Yonezawa, K., Nagai, T., …& Kawaguchi, H. (2004). Exposure to pressure stimulus enhances succinate dehydrogenase activity in L6 myoblasts. American Journal of Physiology-Endocrinology and Metabolism, 287(6), E1064-E1069. ↩︎

  24. Ivy, J. L. (2004). Regulation of muscle glycogen repletion, muscle protein synthesis and repair following exercise. Journal of Sports Science & Medicine, 3(3), 131. 231 Low SY, Rennie MJ, and Taylor PM. (1997). Signaling elements involved in amino acid transport responses to altered muscle cell volume. FA SEB J 11: 1111–1117. ↩︎

  25. Schoenfeld, B. J., & Contreras, B. (2014). The muscle pump: potential mechanisms and applications for enhancing hypertrophic adaptations. _Strength & Conditioning Journal, 36(3), 21-25. ↩︎

  26. Kerksick, C. M., Arent, S., Schoenfeld, B. J., Stout, J. R., Campbell, B., Wilborn, C. D., …& Willoughby, D. (2017). International society of sports nutrition position stand: nutrient timing. Journal of the International Society of Sports Nutrition, 14(1), 33. ↩︎

  27. Haff, G. G., Koch, A. J., Potteiger, J. A., Kuphal, K. E., Magee, L. M., Green, S. B., & Jakicic, J. J. (2000). Carbohydrate supplementation attenuates muscle glycogen loss during acute bouts of resistance exercise. International Journal of Sport Nutrition and Exercise Metabolism, 10(3), 326-339. ↩︎

  28. Sheffield-Moore, M., Wiktorowicz, J. E., Soman, K. V., Danesi, C. P., Kinsky, M. P., Dillon, E. L., …& Lynch, J. P. (2013). Sildenafil increases muscle protein synthesis and reduces muscle fatigue. Clinical and Translational Science, 6(6), 463-468. ↩︎

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