“The super-athlete mutation”
The Good: Increased fast-twitch muscle fibers provide quicker movements in elite athletes. Carriers of this mutation potentially have exceptionally well-developed fast-twitch muscles, leading to faster and stronger athletes. The mutation was discovered more frequently among elite athletes.
The reality: The ACTN3 mutation is directly associated with the absence of α-actinin-3, which leads to loss of muscle power and strength, is determined to be toxic, detrimental to force generation, and performance-enhancing isoforms (harmful to muscle function), reduced bone and muscle mass increasing susceptibility to injury. Linked to an early onset of Pompe disease, decreased muscle strength in boys with Duchenne muscular dystrophy, and a slower, more oxidative muscle profile in people carrying two copies (of the mutation). The mutation has been linked to increased muscle glycogen, usually a rare condition that causes a Glycogen Storage Disease-2. Other adverse effects include hypertension, hyperkalemia, acidosis, and expression of structural and oxidative signaling proteins associated with functional or sensory loss in neurodegenerative diseases-3. Also, an imbalanced metabolism and excess reactive oxygen species (ROS) generation end in a range of disorders such as Alzheimer’s disease, Parkinson’s disease, premature aging, and many other neural diseases are associated with this mutation, and more.-4. There has also been an association between the mutation and acute mountain sickness due to a decreased rate of acclimatization, making the mutation carriers more susceptible to the effects of hypoxia during the acclimatization process and may develop AMS symptoms due to “decreased pressure of oxygen in the arterial blood.” These result in adaptation compensations that emerge as decreased oxygen raised heart rates and cardiac output, headache, fatigue, dizziness, anorexia, and nausea.-5
“The ACTN3 gene encodes for α-actinin-3, an actin-binding protein that is specifically expressed in fast skeletal muscle fibers.” Excessive α-actinin-3 expression such as seen in this mutation have “a “toxic” effect on skeletal muscles.”
“Contrary to expectation, in vivo “doping” of ACTN3 at low to moderate doses demonstrated an absence of any change in function. At high doses, ACTN3 is toxic and detrimental to force generation…detrimental for muscle function.”
Gene transfer overexpression due to the ACTN3 mutation…”did not enhance muscle mass but highlighted the primary role of α-actinin-3 in modulating muscle metabolism with altered fatiguability.”
“Our findings demonstrate the sensitive balance of sarcomeric α-actinin expression…(the) overexpression of ACTN3 reveals insight into its metabolic role in skeletal muscle, but this is innately linked to the level of expression which can be easily disrupted causing detrimental functional effects, reminiscent of disease.”https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986729/
Summary: While the genetic mutation to the ACTN3 gene does at least anecdotally render the proclaimed benefit of an increased force generation in muscles, proof for this claim has not been identified if they exist. The ACTN3 mutation has been determined to impact the a-actinin-3 that modulates muscle metabolism directly. It appears the specific benefits claimed by this mutation are largely yet unidentified, but the clear tendencies for side effects are clear and measurable. Higher levels of a-actinin “may increase muscle mass and force-producing capacity (in one) deficient in such skeletal muscle…causing detrimental functional effects, reminiscent of disease.”-4. Contrary to expectations, doping increased levels of a-actinin are detrimental to force generation and overall muscle function.
1-The Effect of ACTN3 Gene Doping on Skeletal Muscle Performance;