Muscle Protein Synthesis

Editors’ Note: This will be our first deep-dive post where we focus on only one topic. Let us know what you think!

Words in blue will be defined in Today’s Dictionary below!

TLDR

Muscle protein synthesis (MPS) is your body’s muscle-building switch. Resistance training and protein intake turn it on. If you are trying to maximize muscle growth, aim for at least 20g of high-quality protein every 3-5 hours, which usually provides about 2.5-3g of leucine. If your goal is long-term health, focus on resistance training a few times per week and try to include protein at each meal when you can. Even small improvements keep MPS working in your favor.

Your muscles are always under construction

Your muscles are not built in the gym. They are built when your body activates muscle protein synthesis (MPS), the process of assembling amino acids into new muscle proteins to repair and strengthen fibers after stress. To gain muscle, MPS needs to outpace muscle protein breakdown (MPB). Think of it as a race between a construction crew and a demolition team. If the builders stay ahead, your muscle mass increases over time.

MPS is constantly happening alongside MPB. In healthy, weight-stable adults, these processes are roughly balanced over 24 hours. Muscle is constantly being broken down and rebuilt. 

Problems arise when the balance tips the wrong way. Illness, inactivity, aging, or low protein intake can shift the resting state toward breakdown, leading to gradual muscle loss (sarcopenia). Nutrition and training push the balance back in your favor.

Two levers: training and protein

Resistance training: The tension and micro-damage from lifting weights lights up anabolic pathways (e.g., mTOR pathway), signaling your body to start building. For beginners, a single workout can elevate MPS for up to 48 hours, and the spike is large. For trained lifters, the spike is smaller and often back to baseline within 24 hours, which is why consistency is key.

Dietary protein: Eating protein floods your bloodstream with amino acids, which stimulate MPS. Among them, leucine is the “trigger” amino acid: it flips the mTOR switch to turn on synthesis. Research suggests you need enough leucine per meal for a strong response in younger adults, and older adults may need more because of anabolic resistance (reduced sensitivity to protein with age).

The ignition switch vs. the building blocks

Leucine acts as the trigger for MPS, but the rest of the essential amino acids (EAAs) are the fuel that keeps the engine running. Without enough total protein, you can trigger the process but won’t sustain it.

The common recommendation of 20-40g of high-quality protein per meal works because it usually provides both enough leucine to turn the switch on and enough EAAs to build new muscle. For larger or older individuals, the upper end of this range is more effective. 

We are coining our first Stacked Health term, 📚Minimum Protein Threshold (MPT): 20-40g of high-quality protein required to maximize the MPS response.

Stack the spikes: timing and frequency

The signal from protein or training is temporary. After a protein-rich meal, MPS rises, peaks, and then falls back to baseline within a few hours. Resistance training also creates a spike in MPS that lasts 24-48 hours.

To maximize growth, it helps to “stack” multiple MPS spikes across the day. Research shows that eating protein every 3-5 hours stimulates more muscle building than concentrating the same amount into one or two large meals. In practice, that means three meals and a snack, each with 20-40g protein (MPT), is an incredible routine but sustainable habits matter too.

Minimums over maximums

There’s a difference between what’s optimal and what’s enough.

Why you should care

We’re dedicating an entire post to muscle protein synthesis because it’s so fundamental to muscle health and healthspan.

Whether your goal is maximizing muscle growth or maintaining the muscle that you have, hitting MPT and resistance training consistently are essential. The only thing that changes is the frequency of these two behaviors. 

Atherton PJ, Smith K. Muscle protein synthesis in response to nutrition and exercise. J Physiol. 2012;590(5):1049-1057. doi:10.1113/jphysiol.2011.225003
(Mechanisms of MPS/MPB balance)

Damas F, Phillips SM, Libardi CA, Vechin FC, Lixandrão ME, Jannig PR, Costa LA, Bacurau AVN, Snijders T, Parise G, Tricoli V, Roschel H, Ugrinowitsch C. Resistance training-induced changes in myofibrillar protein synthesis are related to hypertrophy only after attenuation of muscle damage. J Physiol. 2016;594(18):5209-5222. doi:10.1113/JP272472
(Training-induced MPS response and duration)

Witard OC, Jackman SR, Breen L, Smith K, Selby A, Tipton KD. Myofibrillar muscle protein synthesis rates after increasing doses of whey protein at rest and after resistance exercise in young men. Am J Clin Nutr. 2014;99(1):86-95. doi:10.3945/ajcn.112.055517
(20–40 g protein dose response)

Moore DR, Churchward-Venne TA, Witard O, Breen L, Burd NA, Tipton KD, Phillips SM. Protein ingestion to stimulate myofibrillar protein synthesis requires greater relative protein intakes in older versus younger men. J Gerontol A Biol Sci Med Sci. 2015;70(1):57-62. doi:10.1093/gerona/glu103
(Anabolic resistance in older adults)

Areta JL, Burke LM, Ross ML, Camera DM, West DWD, Broad EM, Jeacocke NA, Moore DR, Stellingwerff T, Phillips SM, Hawley JA, Coffey VG. Timing and distribution of protein ingestion during prolonged recovery from resistance exercise alters myofibrillar protein synthesis. J Physiol. 2013;591(9):2319-2331. doi:10.1113/jphysiol.2012.244897
(Spacing meals every 3–5 hours)

Schoenfeld BJ, Aragon AA, Krieger JW. The effect of protein timing on muscle strength and hypertrophy: a meta-analysis. J Int Soc Sports Nutr. 2013;10:53. doi:10.1186/1550-2783-10-53
(Debunking the 30-min anabolic window)

Morton RW, Murphy KT, McKellar SR, Schoenfeld BJ, Henselmans M, Helms E, Aragon AA, Devries MC, Banfield L, Krieger JW, Phillips SM. 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. Br J Sports Med. 2018;52(6):376-384. doi:10.1136/bjsports-2017-097608
(Daily target: ~1.6–2.2 g/kg)

Celis-Morales CA, Welsh P, Lyall DM, Steell L, Petermann F, Anderson J, Iliodromiti S, Sillars A, Graham N, Mackay DF, Pell JP, Gill JMR, Sattar N, Gray SR. Associations of grip strength with mortality and disease outcomes in UK Biobank participants. BMJ. 2018;361:k1651. doi:10.1136/bmj.k1651
(Muscle strength linked to longevity)

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