muscle hypertrophy

{{short description|Enlargement or overgrowth of a muscle organ}}

File:Hairy chest - Foto Giovanni Dall'Orto, 25 luglio 2010a.jpg

Muscle hypertrophy or muscle building involves a hypertrophy or increase in size of skeletal muscle through a growth in size of its component cells. Two factors contribute to hypertrophy: sarcoplasmic hypertrophy, which focuses more on increased muscle glycogen storage; and myofibrillar hypertrophy, which focuses more on increased myofibril size.{{cite book |editor1-first=Thomas R. |editor1-last=Baechle |editor2-first=Roger W. |editor2-last=Earle | name-list-style = vanc |title=Essentials of strength training and conditioning |date=2008 |publisher=Human Kinetics |location=Champaign, IL |isbn=978-0-7360-5803-2 |edition=3rd}}{{page needed|date=October 2016}} It is the primary focus of bodybuilding-related activities.

Hypertrophy stimulation

A range of stimuli can increase the volume of muscle cells. These changes occur as an adaptive response that serves to increase the ability to generate force or resist fatigue in anaerobic conditions.

=Strength training=

File:Small group fitness sessions bundall.jpg

Strength training (resistance training) causes neural and muscular adaptations which increase the capacity of an athlete to exert force through voluntary muscular contraction: After an initial period of neuro-muscular adaptation, the muscle tissue expands by creating sarcomeres (contractile elements) and increasing non-contractile elements like sarcoplasmic fluid.{{cite book |last1=Schoenfeld |first1=Brad | name-list-style = vanc |title=Science and Development of Muscle Hypertrophy | publisher = Human Kinetics | date = 2016 |pages=1–15 | isbn = 978-1-4925-1960-7 }}

Muscular hypertrophy can be induced by progressive overload (a strategy of progressively increasing resistance or repetitions over successive bouts of exercise to maintain a high level of effort).{{cite journal | vauthors = Seynnes OR, de Boer M, Narici MV | title = Early skeletal muscle hypertrophy and architectural changes in response to high-intensity resistance training | journal = Journal of Applied Physiology | volume = 102 | issue = 1 | pages = 368–73 | date = January 2007 | pmid = 17053104 | doi = 10.1152/japplphysiol.00789.2006 | s2cid = 28981041 }} However, the precise mechanisms are not clearly understood; the current accepted theory is mechanical tension.{{Cite journal |last1=Bernárdez-Vázquez |first1=Roberto |last2=Raya-González |first2=Javier |last3=Castillo |first3=Daniel |last4=Beato |first4=Marco |date=2022 |title=Resistance Training Variables for Optimization of Muscle Hypertrophy: An Umbrella Review |journal=Frontiers in Sports and Active Living |volume=4 |pages=949021 |doi=10.3389/fspor.2022.949021 |doi-access=free |issn=2624-9367 |pmc=9302196 |pmid=35873210}}

Muscular hypertrophy plays an important role in competitive bodybuilding and strength sports like powerlifting, American football, and Olympic weightlifting.

= Blood flow restriction (BFR) training =

Another form of training that has been researched in terms of inducing muscle hypertrophy is blood flow restriction training (BFR). {{Cite journal |last1=Krzysztofik |first1=Michal |last2=Wilk |first2=Michal |last3=Wojdała |first3=Grzegorz |last4=Gołaś |first4=Artur |date=2019-12-04 |title=Maximizing Muscle Hypertrophy: A Systematic Review of Advanced Resistance Training Techniques and Methods |journal=International Journal of Environmental Research and Public Health |language=en |volume=16 |issue=24 |pages=4897 |doi=10.3390/ijerph16244897 |doi-access=free |issn=1660-4601 |pmc=6950543 |pmid=31817252}}BFR training involves the use of cuffs or bands to partially restrict blood flow to the working muscles during low-load resistance exercise. This method has been shown to induce hypertrophy comparable to traditional high-load training, likely due to mechanical tension and muscle fiber recruitment. BFR training is particularly useful for individuals who cannot tolerate high mechanical loads, such as those recovering from injury or older adults.

=Anaerobic training=

The best approach to specifically achieve muscle growth remains controversial (as opposed to focusing on gaining strength, power, or endurance); it was generally considered that consistent anaerobic strength training will produce hypertrophy over the long term, in addition to its effects on muscular strength and endurance. Muscular hypertrophy can be increased through strength training and other short-duration, high-intensity anaerobic exercises. Lower-intensity, longer-duration aerobic exercise generally does not result in very effective tissue hypertrophy; instead, endurance athletes enhance storage of fats and carbohydrates within the muscles,{{cite journal | vauthors = van Loon LJ, Goodpaster BH | title = Increased intramuscular lipid storage in the insulin-resistant and endurance-trained state | journal = Pflügers Archiv | volume = 451 | issue = 5 | pages = 606–16 | date = February 2006 | pmid = 16155759 | doi = 10.1007/s00424-005-1509-0 | s2cid = 6567497 }} as well as neovascularization.{{cite journal | vauthors = Soares JM | title = Effects of training on muscle capillary pattern: intermittent vs continuous exercise | journal = The Journal of Sports Medicine and Physical Fitness | volume = 32 | issue = 2 | pages = 123–7 | date = June 1992 | pmid = 1279273 }}{{cite journal | vauthors = Prior BM, Yang HT, Terjung RL | title = What makes vessels grow with exercise training? | journal = Journal of Applied Physiology | volume = 97 | issue = 3 | pages = 1119–28 | date = September 2004 | pmid = 15333630 | doi = 10.1152/japplphysiol.00035.2004 | s2cid = 36656568 }}

Temporary swelling

During a workout, increased blood flow to metabolically active areas causes muscles to temporarily increase in size. This phenomenon is referred to as transient hypertrophy, or more commonly known as being "pumped up" or getting "a pump."{{cite web| url=http://woman.thenest.com/causes-muscles-expand-work-out-6597.html |title=What Causes Your Muscles to Expand When You Work Out? | author=Joseph Eitel |access-date=May 5, 2017}} About two hours after a workout and typically for seven to eleven days, muscles swell due to an inflammation response as tissue damage is repaired.{{cite web |url=http://www.livestrong.com/article/75670-swell-after-workout/ |date=January 22, 2010 |title=Why Do You Swell After Workout? |author=Claire Lunardoni}} Longer-term hypertrophy occurs due to more permanent changes in muscle structure.

Hirono et al. explained the causes of muscle swelling:{{Cite journal |last1=Hirono |first1=Tetsuya |last2=Ikezoe |first2=Tome |last3=Taniguchi |first3=Masashi |last4=Tanaka |first4=Hiroki |last5=Saeki |first5=Junya |last6=Yagi |first6=Masahide |last7=Umehara |first7=Jun |last8=Ichihashi |first8=Noriaki |date=2022-02-01 |title=Relationship Between Muscle Swelling and Hypertrophy Induced by Resistance Training |url=https://pubmed.ncbi.nlm.nih.gov/31904714/ |journal=Journal of Strength and Conditioning Research |volume=36 |issue=2 |pages=359–364 |doi=10.1519/JSC.0000000000003478 |issn=1533-4287 |pmid=31904714|hdl=2433/267710 |hdl-access=free }}

"Muscle swelling occurs as a result of the following:

(a) resistance exercise can increase phosphocreatine and hydrogen ion accumulations due to blood lactate and growth hormone production, and

(b) the high lactate and hydrogen ion concentrations may accelerate water uptake in muscle cells according to cell permeability because the molecular weights of the lactate and hydrogen ions are smaller than that of muscle glycogen."

Factors affecting hypertrophy

Biological factors (such as DNA and sex), nutrition, and training variables can affect muscle hypertrophy.{{Cite web|url=https://www.unm.edu/~lkravitz/Article%20folder/musclesgrowLK.html|title=How do muscles grow? }}

Individual differences in genetics account for a substantial portion of the variance in existing muscle mass. A classical twin study design (similar to those of behavioral genetics) estimated that about 53% of the variance in lean body mass is heritable,Arden, N. K. and Spector, T. D. (1997), Genetic Influences on Muscle Strength, Lean Body Mass, and Bone Mineral Density: A Twin Study. J Bone Miner Res, 12: 2076-2081. doi:10.1359/jbmr.1997.12.12.2076 along with about 45% of the variance in muscle fiber proportion.{{cite journal | vauthors = Simoneau JA, Bouchard C | title = Genetic determinism of fiber type proportion in human skeletal muscle | journal = FASEB Journal | volume = 9 | issue = 11 | pages = 1091–5 | date = August 1995 | pmid = 7649409 | doi = 10.1096/fasebj.9.11.7649409 | doi-access = free | s2cid = 9613549 }}

File:Testosteron.svg

During puberty in males, hypertrophy occurs at an increased rate. Natural hypertrophy normally stops at full growth in the late teens. As testosterone is one of the body's major growth hormones, on average, males find hypertrophy much easier (on an absolute scale) to achieve than females, and, on average, have about 60% more muscle mass than women.{{cite journal | vauthors = Miller AE, MacDougall JD, Tarnopolsky MA, Sale DG | title = Gender differences in strength and muscle fiber characteristics | journal = European Journal of Applied Physiology and Occupational Physiology | volume = 66 | issue = 3 | pages = 254–62 | year = 1993 | pmid = 8477683 | doi = 10.1007/BF00235103 | hdl-access = free | hdl = 11375/22586 | s2cid = 206772211 }} Taking additional testosterone, as in anabolic steroids, will increase results. It is also considered a performance-enhancing drug, the use of which can cause competitors to be suspended or banned from competitions. Testosterone is also a medically regulated substance in most{{cite web |url=http://napra.ca/pages/Schedules/Search.aspx |title=Search National Drug Schedule - NAPRA |archive-url=https://web.archive.org/web/20140201220518/http://napra.ca/pages/Schedules/Search.aspx |archive-date=February 1, 2014 |url-status=dead }}{{cite web |url=https://www.fda.gov/RegulatoryInformation/Legislation/ucm148726.htm |archive-url=https://web.archive.org/web/20090710011338/http://www.fda.gov/RegulatoryInformation/Legislation/ucm148726.htm |url-status=dead |archive-date=July 10, 2009 |title=Controlled Substances Act |website=Food and Drug Administration }} countries, making it illegal to possess without a medical prescription. Anabolic steroid use can cause testicular atrophy, cardiac arrest,{{cite journal | vauthors = Fineschi V, Riezzo I, Centini F, Silingardi E, Licata M, Beduschi G, Karch SB | title = Sudden cardiac death during anabolic steroid abuse: morphologic and toxicologic findings in two fatal cases of bodybuilders | journal = International Journal of Legal Medicine | volume = 121 | issue = 1 | pages = 48–53 | date = January 2007 | pmid = 16292586 | doi = 10.1007/s00414-005-0055-9 | s2cid = 20004739 }} and gynecomastia.{{cite journal | vauthors = Basaria S | title = Androgen abuse in athletes: detection and consequences | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 95 | issue = 4 | pages = 1533–43 | date = April 2010 | pmid = 20139230 | doi = 10.1210/jc.2009-1579 | doi-access = free }}

In the long term, a positive energy balance, when more calories are consumed rather than burned, is helpful for anabolism and therefore muscle hypertrophy. An increased requirement for protein can help elevate protein synthesis, which is seen in athletes training for muscle hypertrophy. Protein intakes up to 1.6 grams per kilogram of body weight a day help increase gains in strength and muscle size from resistance training.{{cite journal | vauthors = Morton RW, Murphy KT, McKellar SR, Schoenfeld BJ, Henselmans M, Helms E, Aragon AA, Devries MC, Banfield L, Krieger JW, Phillips SM | title = A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults | journal = Br J Sports Med | volume = 52 | issue = 6 | pages = 376–384 | date = July 2018 | pmid = 28698222 | doi = 10.1136/bjsports-2017-097608| pmc = 5867436 }}

Training variables, in the context of strength training, such as frequency, intensity, and total volume also directly affect the increase of muscle hypertrophy. A gradual increase in all of these training variables will yield muscular hypertrophy.{{cite journal | vauthors = Wernbom M, Augustsson J, Thomeé R | title = The influence of frequency, intensity, volume and mode of strength training on whole muscle cross-sectional area in humansq | journal = Sports Medicine | volume = 37 | issue = 3 | pages = 225–64 | date = March 1, 2007 | pmid = 17326698 | doi = 10.2165/00007256-200737030-00004 | s2cid = 31127952 }} Range of motion is also seen as another possible factor to induce hypertrophy. Training through a full ROM, particularly at elongated muscle lengths, has been shown to enhance hypertrophy compared to partial ROM. For example, deep squats and full-ROM deadlifts increase mechanical tension on muscle fibers, particularly in the stretched position, which may stimulate greater muscle growth. Partial ROM training at longer muscle lengths has also been found to promote hypertrophy, potentially due to increased muscle damage. {{Cite journal |last1=Androulakis Korakakis |first1=Patroklos |last2=Wolf |first2=Milo |last3=Coleman |first3=Max |last4=Burke |first4=Ryan |last5=Piñero |first5=Alec |last6=Nippard |first6=Jeff |last7=Schoenfeld |first7=Brad J. |date=2023-12-29 |title=Optimizing Resistance Training Technique to Maximize Muscle Hypertrophy: A Narrative Review |journal=Journal of Functional Morphology and Kinesiology |language=en |volume=9 |issue=1 |pages=9 |doi=10.3390/jfmk9010009 |doi-access=free |issn=2411-5142 |pmc=10801605 |pmid=38249086}}

Changes in protein synthesis and muscle cell biology associated with stimuli

=Protein synthesis=

File:Summary of the protein biosynthesis process.png

The message filters down to alter the pattern of gene expression. The additional contractile proteins appear to be incorporated into existing myofibrils (the chains of sarcomeres within a muscle cell). There appears to be some limit to how large a myofibril can become: at some point, they split. These events appear to occur within each muscle fiber. That is hypertrophy results primarily from the growth of each muscle cell rather than an increase in the number of cells. Skeletal muscle cells are however unique in the body in that they can contain multiple nuclei, and the number of nuclei can increase.{{cite journal | vauthors = Bruusgaard JC, Johansen IB, Egner IM, Rana ZA, Gundersen K | title = Myonuclei acquired by overload exercise precede hypertrophy and are not lost on detraining | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 34 | pages = 15111–6 | date = August 2010 | pmid = 20713720 | pmc = 2930527 | doi = 10.1073/pnas.0913935107 | bibcode = 2010PNAS..10715111B | doi-access = free }}

Cortisol decreases amino acid uptake by muscle tissue, and inhibits protein synthesis.{{cite book | author = Manchester KL | title = Mammalian Protein Metabolism | page = 229 | year = 1970 | doi = 10.1016/B978-0-12-510604-7.50011-6 | chapter = 33 – Sites of Hormonal Regulation of Protein Metabolism | publisher = Academic Press, New York | isbn = 978-0-12-510604-7 | chapter-url-access = registration | chapter-url = https://archive.org/details/mammalianprotein0000munr }} The short-term increase in protein synthesis that occurs subsequent to resistance training returns to normal after approximately 28 hours in adequately fed male youths.{{cite journal | vauthors = Tang JE, Perco JG, Moore DR, Wilkinson SB, Phillips SM | title = Resistance training alters the response of fed state mixed muscle protein synthesis in young men | journal = American Journal of Physiology. Regulatory, Integrative and Comparative Physiology | volume = 294 | issue = 1 | pages = R172-8 | date = January 2008 | pmid = 18032468 | doi = 10.1152/ajpregu.00636.2007 | s2cid = 9743221 }} Another study determined that muscle protein synthesis was elevated even 72 hours following training.{{cite journal | vauthors = Miller BF, Olesen JL, Hansen M, Døssing S, Crameri RM, Welling RJ, Langberg H, Flyvbjerg A, Kjaer M, Babraj JA, Smith K, Rennie MJ | display-authors = 6 | title = Coordinated collagen and muscle protein synthesis in human patella tendon and quadriceps muscle after exercise | journal = The Journal of Physiology | volume = 567 | issue = Pt 3 | pages = 1021–33 | date = September 2005 | pmid = 16002437 | pmc = 1474228 | doi = 10.1113/jphysiol.2005.093690 }}

A small study performed on young and elderly found that ingestion of 340 grams of lean beef (90 g protein) did not increase muscle protein synthesis any more than ingestion of 113 grams of lean beef (30 g protein). In both groups, muscle protein synthesis increased by 50%. The study concluded that more than 30 g protein in a single meal did not further enhance the stimulation of muscle protein synthesis in young and elderly.{{cite journal | vauthors = Symons TB, Sheffield-Moore M, Wolfe RR, Paddon-Jones D | title = A moderate serving of high-quality protein maximally stimulates skeletal muscle protein synthesis in young and elderly subjects | journal = Journal of the American Dietetic Association | volume = 109 | issue = 9 | pages = 1582–6 | date = September 2009 | pmid = 19699838 | pmc = 3197704 | doi = 10.1016/j.jada.2009.06.369 }} However, this study didn't check protein synthesis in relation to training; therefore conclusions from this research are controversial. A 2018 review of the scientific literature{{cite journal | vauthors = Schoenfeld BJ, Aragon AA | title = How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution | journal = Journal of the International Society of Sports Nutrition | volume = 15 | issue = 1 | pages = 10 | date = February 27, 2018 | pmid = 29497353 | pmc = 5828430 | doi = 10.1186/s12970-018-0215-1 | doi-access = free }} concluded that for the purpose of building lean muscle tissue, a minimum of 1.6 g protein per kilogram of body weight is required, which can for example be divided over 4 meals or snacks and spread out over the day.{{citation needed|date=July 2022}}

It is not uncommon for bodybuilders to advise a protein intake as high as 2–4 g per kilogram of bodyweight per day.{{cite web | url = http://www.leehayward.com/protein_part2.htm |title=Bodybuilders and Protein – Part 2 | work = Leehayward.com | access-date=June 19, 2011}} However, scientific literature has suggested this is higher than necessary, as protein intakes greater than 1.8 g per kilogram of body weight showed to have no greater effect on muscle hypertrophy.{{cite journal | vauthors = Tarnopolsky MA, Atkinson SA, MacDougall JD, Chesley A, Phillips S, Schwarcz HP | title = Evaluation of protein requirements for trained strength athletes | journal = Journal of Applied Physiology | volume = 73 | issue = 5 | pages = 1986–95 | date = November 1992 | pmid = 1474076 | doi = 10.1152/jappl.1992.73.5.1986 | s2cid = 46188182 }} A study carried out by American College of Sports Medicine (2002) put the recommended daily protein intake for athletes at 1.2–1.8 g per kilogram of body weight.{{cite journal | vauthors = Rankin JW | title = Weight loss and gain in athletes | journal = Current Sports Medicine Reports | volume = 1 | issue = 4 | pages = 208–13 | date = August 2002 | pmid = 12831697 | doi = 10.1249/00149619-200208000-00004 | doi-access = free }}{{cite journal | vauthors = Lemon PW | title = Effect of exercise on protein requirements | journal = Journal of Sports Sciences | volume = 9 Spec No | pages = 53–70 | year = 1991 | pmid = 1895363 | doi = 10.1080/02640419108729866 }} Conversely, Di Pasquale (2008), citing recent studies, recommends a minimum protein intake of 2.2 g/kg "for anyone involved in competitive or intense recreational sports who wants to maximize lean body mass but does not wish to gain weight. However athletes involved in strength events (..) may need even more to maximize body composition and athletic performance. In those attempting to minimize body fat and thus maximize body composition, for example in sports with weight classes and in bodybuilding, it's possible that protein may well make up over 50% of their daily caloric intake."{{cite book|last=Di Pasquale|first=Mauro G. | name-list-style = vanc |title=Sports Nutrition: Energy metabolism and exercise|editor=Ira Wolinsky, Judy A. Driskell|publisher=CRC Press|year=2008|page=79|chapter=Use of Proteins in Energy Metabolism|author-link=Mauro Di Pasquale|isbn=978-0-8493-7950-5}}

=Microtrauma=

Image:Skeletal muscle.png fibres may be "microtorn" during microtrauma]]

Microtrauma is tiny damage to the muscle fibers. The precise relation between microtrauma and muscle growth is not entirely understood yet.{{citation needed|date=July 2022}}

One theory is that microtrauma plays a significant role in muscle growth.{{cite journal | vauthors = Chargé SB, Rudnicki MA | title = Cellular and molecular regulation of muscle regeneration | journal = Physiological Reviews | volume = 84 | issue = 1 | pages = 209–38 | date = January 2004 | pmid = 14715915 | doi = 10.1152/physrev.00019.2003 | s2cid = 9556386 }}{{cite web | title=How Do Muscles Grow? | website=The University of New Mexico | url=http://www.unm.edu/~lkravitz/Article%20folder/musclesgrowLK.html | ref={{sfnref | New Mexico's Flagship University | The University of New Mexico }}}} When microtrauma occurs (from weight training or other strenuous activities), the body responds by overcompensating, replacing the damaged tissue and adding more, so that the risk of repeat damage is reduced. Damage to these fibers has been theorized as the possible cause for the symptoms of delayed onset muscle soreness (DOMS), and is why progressive overload is essential to continued improvement, as the body adapts and becomes more resistant to stress.

However, other work examining the time course of changes in muscle protein synthesis and their relationship to hypertrophy showed that damage was unrelated to hypertrophy.{{cite journal | vauthors = Damas F, Phillips SM, Libardi CA, Vechin FC, Lixandrão ME, Jannig PR, Costa LA, Bacurau AV, Snijders T, Parise G, Tricoli V, Roschel H, Ugrinowitsch C | display-authors = 6 | title = Resistance training-induced changes in integrated myofibrillar protein synthesis are related to hypertrophy only after attenuation of muscle damage | journal = The Journal of Physiology | volume = 594 | issue = 18 | pages = 5209–22 | date = September 2016 | pmid = 27219125 | pmc = 5023708 | doi = 10.1113/JP272472 }} In fact, in one study the authors showed that it was not until the damage subsided that protein synthesis was directed to muscle growth.

Myofibrillar vs. sarcoplasmic hypertrophy

File:Hyperplasia vs Hypertrophy.svg

In the bodybuilding and fitness community and even in some academic books skeletal muscle hypertrophy is described as being either sarcoplasmic or myofibrillar.{{qualify evidence}} According to this hypothesis, during sarcoplasmic hypertrophy, the volume of sarcoplasmic fluid in the muscle cell increases with no accompanying increase in muscular strength, whereas during myofibrillar hypertrophy, actin and myosin contractile proteins increase in number and add to muscular strength as well as a small increase in the size of the muscle. Sarcoplasmic hypertrophy is greater in the muscles of bodybuilders because studies suggest sarcoplasmic hypertrophy shows a greater increase in muscle size while myofibrillar hypertrophy proves to increase overall muscular strength making it more dominant in Olympic weightlifters.{{cite book|url=https://books.google.com/books?id=QWSn4iKgNo8C&pg=PA50|title=Science and practice of strength training| last1 = Kraemer | first1 = William J. | last2 = Zatsiorsky | first2 = Vladimir M. | name-list-style = vanc |publisher=Human Kinetics|year=2006|isbn=978-0-7360-5628-1|location=Champaign, IL|page=50}} These two forms of adaptations rarely occur completely independently of one another; one can experience a large increase in fluid with a slight increase in proteins, a large increase in proteins with a small increase in fluid, or a relatively balanced combination of the two.

In sports

Examples of increased muscle hypertrophy are seen in various professional sports, mainly strength related sports such as boxing, olympic weightlifting, mixed martial arts, rugby, professional wrestling and various forms of gymnastics. Athletes in other more skill-based sports such as basketball, baseball, ice hockey, and football may also train for increased muscle hypertrophy to better suit their position of play. For example, a center (basketball) may want to be bigger and more muscular to better overpower their opponents in the low post.{{Cite news|url=http://www.slamonline.com/nba/chris-bosh-gaining-weight-to-play-center/#5LUvmeqjg2V5wykA.97|title=Chris Bosh Gaining Weight to Play Center|last=Khorshidi|first=Eldon| name-list-style = vanc |date=September 10, 2012|work=SLAM|access-date=April 7, 2017}} Athletes training for these sports train extensively not only in strength but also in cardiovascular and muscular endurance training.{{Citation needed|date=June 2021}}

Pathology

Some neuromuscular diseases result in true hypertrophy of one or more skeletal muscles, confirmed by MRI or muscle biopsy. As this muscle hypertrophy is not the result of resistance training nor heavy manual labour, this is why the muscle hypertrophy is described as a pseudoathletic appearance.

As muscle hypertrophy is a response to strenuous anaerobic activity, ordinary everyday activity would become strenuous in diseases that result in premature muscle fatigue (neural or metabolic), or disrupt the excitation-contraction coupling in muscle, or cause repetitive or sustained involuntary muscle contractions (fasciculations, myotonia, or spasticity).{{Cite journal |last=Walters |first=Jon |date=October 2017 |title=Muscle hypertrophy and pseudohypertrophy |journal=Practical Neurology |volume=17 |issue=5 |pages=369–379 |doi=10.1136/practneurol-2017-001695 |issn=1474-7766 |pmid=28778933|doi-access=free }}{{Cite journal |last=Nadaj-Pakleza |first=Aleksandra |date=2022-07-01 |title=Muscle hypertrophy: indicative of good health or disease? / Hypertrophie musculaire: signe de bonne santé ou de maladie ? |url=https://www.cahiers-myologie.org/articles/myolog/abs/2022/01/myolog202225p10/myolog202225p10.html |journal=Les Cahiers de Myologie |language=fr, en |issue=25 |pages=10–15 |doi=10.1051/myolog/202225004 |issn=2108-2219|doi-access=free }} In lipodystrophy, an abnormal deficit of subcutaneous fat accentuates the appearance of the muscles, though the muscles are quantifiably hypertrophic (possibly due to a metabolic abnormality).{{Cite journal |last1=Ji |first1=Hongzhao |last2=Weatherall |first2=Paul |last3=Adams-Huet |first3=Beverley |last4=Garg |first4=Abhimanyu |date=August 2013 |title=Increased skeletal muscle volume in women with familial partial lipodystrophy, Dunnigan variety |journal=The Journal of Clinical Endocrinology and Metabolism |volume=98 |issue=8 |pages=E1410–1413 |doi=10.1210/jc.2013-1297 |issn=1945-7197 |pmc=3733861 |pmid=23783098}}{{Citation |last1=El-Darouti |first1=Mohammad Ali |title=Loss of Subcutaneous Fat, Muscle Hypertrophy, Diabetes and Hyperlipidemia |date=2019 |url=https://doi.org/10.1007/978-3-030-21855-3_2 |work=Challenging Cases in Dermatology Volume 2: Advanced Diagnoses and Management Tactics |pages=7–11 |editor-last=El-Darouti |editor-first=Mohammad Ali |access-date=2023-10-12 |place=Cham |publisher=Springer International Publishing |language=en |doi=10.1007/978-3-030-21855-3_2 |isbn=978-3-030-21855-3 |last2=Al-Ali |first2=Faiza Mohamed |s2cid=202826748 |editor2-last=Al-Ali |editor2-first=Faiza Mohamed|url-access=subscription }}

Diseases that result in true muscle hypertrophy include, but not limited to, select: muscular dystrophies, metabolic myopathies, endocrine myopathies, congenital myopathies, non-dystrophic myotonias and pseudomyotonias, denervation, spasticity, and lipodystrophy. The muscle hypertrophy may persist throughout the course of the disease, or may later atrophy, or become pseudohypertrophic (muscle atrophy with infiltration of fat or other tissue). For instance, Duchenne and Becker muscular dystrophy may start as true muscle hypertrophy, but later develop into pseudohypertrophy.{{Cite journal |last1=Kornegay |first1=Joe N. |last2=Childers |first2=Martin K. |last3=Bogan |first3=Daniel J. |last4=Bogan |first4=Janet R. |last5=Nghiem |first5=Peter |last6=Wang |first6=Jiahui |last7=Fan |first7=Zheng |last8=Howard |first8=James F. |last9=Schatzberg |first9=Scott J. |last10=Dow |first10=Jennifer L. |last11=Grange |first11=Robert W. |last12=Styner |first12=Martin A. |last13=Hoffman |first13=Eric P. |last14=Wagner |first14=Kathryn R. |date=February 2012 |title=The paradox of muscle hypertrophy in muscular dystrophy |journal=Physical Medicine and Rehabilitation Clinics of North America |volume=23 |issue=1 |pages=149–172, xii |doi=10.1016/j.pmr.2011.11.014 |issn=1558-1381 |pmc=5951392 |pmid=22239881}}