Protein, Fish Oil, Glycogen, and What Limits Muscle Growth (Episode 53)

Meta-analyses pool data from many studies with varied characteristics (e.g., intervention length, age, training programs). While covariates are used to adjust for some variation, they do not equate experimental conditions. This makes precise, universal interpretation challenging, suggesting the need for a 'ballpark estimate' rather than an exact number.

Yes, higher protein intake (around 2.3 to 3.1 grams per kilogram of fat-free mass) might be warranted for individuals who are already quite lean and in a significant caloric deficit, particularly when aiming to get 'shredded' for physique competitions. However, for most lifters at energy balance or in a mild surplus, the 1.6-2.2 g/kg range is sufficient.

A 2019 meta-analysis by Hu and colleagues found marine-derived omega-3 supplementation was associated with a modest (3-8%) reduction in the risk of certain cardiovascular outcomes like myocardial infarction and coronary heart disease, but not stroke. The effects are statistically significant but small, and the topic remains debated among experts.

For lifters and athletes, fish oil, particularly EPA and DHA, may offer modest positive effects on muscle recovery, cognition, nitric oxide metabolism, mental health, inflammation, immune function, muscle protein balance, and neuromuscular function. At typical doses (1-2 grams of combined EPA/DHA), the downside risks like bleeding problems or lipid peroxidation are minimal with quality products.

A study by Hawking and colleagues found that while total muscle glycogen depletion after a resistance workout might only be 24-40%, specific localized compartments, particularly intramyofibrillar glycogen in type 2 fibers, can deplete by a much larger extent (e.g., 54%). This localized depletion is crucial for sustaining muscle force.

Most lifters eating at maintenance or surplus with a moderate carb diet (at least 40% of calories from carbs) and resting 24+ hours between intense workouts for the same muscle group probably don't need to worry much. However, those in a large energy deficit, on a very low-carb diet, or performing multiple glycolytic bouts within 24 hours should carefully consider their carbohydrate strategy for effective glycogen replenishment.

Research suggests myonuclear content scales linearly with muscle fiber surface area, not volume. As fibers grow, volume increases faster than surface area, leading to fewer myonuclei per unit of fiber volume. This could cause fibers to hit a 'myonuclear domain limit,' where each myonucleus can no longer effectively oversee the increasing cytoplasmic volume, thereby constraining further growth.

Myostatin is a protein that limits muscle growth. In genetically engineered myostatin-deficient animals (mutants), muscles become exceptionally large with larger myonuclear domains, meaning fiber volume increases disproportionately to myonuclear number. However, these muscles often exhibit functional limitations, being less strong per unit of size.

Studies on genetically engineered mice show an inverse relationship between nuclear numbers and reserve capacity. As myonuclear numbers increase, the transcriptional capacity per nucleus diminishes, possibly due to competition for finite transcription factors or increased diffusion distance. This suggests that higher myonuclear density can itself limit further growth by reducing the efficiency of each nucleus.

While controversial, some evidence, including observations in animals and in humans (e.g., more muscle fibers in the non-dominant tibialis anterior), suggests hyperplasia (increase in muscle fiber number) might occur. If myonuclear limits constrain individual fiber size, then hyperplasia could explain the gradual but continuous muscle growth observed in some individuals over decades of training.

Anabolic steroids (exogenous anabolics) could promote muscle growth by allowing for larger myonuclear domains, enhancing the transcriptional capacity of each myonucleus, increasing rates of myonuclear accretion (as shown by Katy Kadi's research with testosterone), or potentially promoting hyperplasia. They might also help individuals reach their theoretical upper limit of fiber size.