Protein Breakdown Key Points:

  • An even and skewed protein over the course of the day with similar total protein resulted in similar protein synthesis. However, an even distribution of protein resulted in lower protein breakdown.
  • An even distribution of protein resulted in a greater whole-body protein net balance driven by lower protein breakdown.
  • This could be of concern to those who practice intermittent fasting and time-restricted eating and its effect on long-term muscle gains.

Protein Synthesis and Protein Breakdown

Intermittent fasting to lose body fat is very popular in fitness circles. However, one of the main criticisms of intermittent fasting is reduced meal frequency and its effect on long-term muscle gain. A recent article on Evidence Based Muscle found that Ramadan fasting (i.e., an average fast of 14 hours) did not reduce muscle growth.  However, what about muscle gains? Will this impact long-term muscle protein synthesis if you have all your protein in one or two meals? Will this affect long-term muscle protein synthesis? This article delves into the intriguing relationship between meal frequency, protein distribution, and protein synthesis. By understanding the impact of these factors, we can unlock valuable insights into how to best support muscle gains. 

Nutrition and protein breakdown

To optimize muscle growth, you need to ensure that your body receives a consistent supply of amino acids through protein synthesis. Protein breakdown is a natural process where the body breaks down proteins into amino acids, which serve as the building blocks for new proteins. However, excessive protein breakdown can hinder muscle growth and recovery. To minimize excessive protein breakdown, it’s essential to consume a balanced diet with adequate amounts of protein and engage in resistance training. 

The Link Between Meal Frequency and Protein Synthesis:

The typical American gets most of their protein at dinner, with breakfast and lunch contributing to lesser amounts. In recent studies, it has been observed that older adults tend to have a skewed protein intake (i.e., an uneven amount of protein with each meal), with a higher proportion of protein consumed during the evening meal. (Tieland et al., 2015)

This skewed protein distribution has been associated with muscle loss and increased frailty in elderly individuals. (Bollwein et al., 2013) An equal distribution of protein throughout the day results in a balanced distribution of essential amino acids contributing to better protein kinetics over 24 hours. Some studies have found a positive effect of greater meal frequency on resistance training adaptations in resistance-trained men. (Schoenfeld et al., 2015)

Studies

Jespersen & Agergaard’s 2021 research shows that older adults who maintain an even protein intake throughout the day have greater muscle mass. Another study discovered that people with an even distribution of protein intake have greater lean mass and strength. (Johnson et al., 2022)

Areta et al. investigated the impact of daily protein distribution on muscle protein synthesis in resistance-trained young men. The study found multiple doses of whey protein (i.e., 4 times x 20 grams x every 3 hours) resulted in better muscle protein synthesis than 2 times x 40 grams x every 6 hours). (Areta et al., 2013) These findings suggest that the timing and distribution of protein intake may play a crucial role in muscle health.

muscle protein synthesismeal frequency protein breakdown
Some studies have found a positive effect of greater meal frequency on resistance training adaptations in resistance-trained men. (Schoenfeld et al., 2015)

Consuming moderate protein, around 20-30g, at each meal better stimulates 24-hour muscle protein synthesis. (Mamerow et al., 2014) Proper protein distribution throughout the day is important to maximize muscle protein synthesis. Protein intake >0.24 g/kg of body weight at a single meal is necessary to maximize muscle protein synthesis in young men. (Yasuda et al., 2019) Maintaining this protein intake rate in all three meals of a day is critical in muscle mass maintenance in young populations.

New Study on the Effects of Protein Distribution, Meal Frequency, and Amino Acid Utilization:

To further explore the impact of protein distribution, a study was conducted involving healthy elderly participants. (Agergaard et al., 2023) The participants were divided into two groups: EVEN protein distribution and SKEWED protein distribution.

The EVEN distribution of protein intake (1/3 of the day’s protein ingested at breakfast, lunch, and dinner, whereas the skewed distribution had most of their protein at dinner (1/6, 1/6, and 4/6, at breakfast, lunch, and dinner, respectively) in healthy older adults. The study provided each group with three main meals and two snacks at specific time points throughout the day.

The study divided the total protein intake of 1.5 g/kg of lean body mass into 30% at each main meal in the EVEN group, 15% at breakfast and lunch, and 60% at dinner in the SKEWED group. Snacks with 5% of the protein intake were served between meals.

Results: Greater Protein Breakdown with Skewed Protein Distribution:

However, there was no difference in muscle protein synthesis between the EVEN and SKEWED groups. However, the SKEWED protein groups had increased muscle protein breakdown. The study’s results revealed that the EVEN distribution of dietary protein intake over the day resulted in a more positive whole-body protein net balance than the SKEWED meal distribution pattern. A lower whole-body protein breakdown rate primarily drove the difference in net balance in the EVEN group compared to the SKEWED group. These findings suggest that an even protein distribution throughout the day may promote a state of amino acid sufficiency and support positive whole-body protein balance.

muscle protein synthesismeal frequency protein breakdown
A lower whole-body protein breakdown rate primarily drove the difference in net balance in the EVEN group compared to the SKEWED group.

Literature Review: Meal Frequency, Protein Synthesis, and Muscle Protein Breakdown:

Examining the literature on meal frequency and protein synthesis provides further insights. While the Agergaard study found no significant difference in muscle protein synthesis (MPS) between the EVEN and SKEWED groups, other studies have reported contrary results. For instance, a study involving young subjects found a greater MPS with an EVEN protein distribution than a SKEWED distribution. (Mamerow et al., 2014) These differences may be due to the exercise and daily protein differences between the studies. The Agergaard study used a fairly low protein intake, and the older adults were not in a resistance exercise program, so the results are difficult to extrapolate to athletes.

Exploring the Mechanisms Behind Protein Distribution’s Impact on Protein Synthesis:

To understand the underlying mechanisms behind the impact of protein distribution on protein synthesis, it’s important to consider the role of amino acid appearance and concentration. The Agergaard study observed greater amino acid appearance and concentrations throughout the day in the EVEN group compared to the SKEWED group. This prolonged exposure to amino acids may spare the efflux of amino acids from the muscle protein pool, thereby reducing protein breakdown.

A study on adult subjects found that a higher protein intake (i.e., 70 grams) led to a greater whole-body net-protein balance, primarily driven by lower protein breakdown rates compared to a lower protein intake (i.e., 40 grams). (Kim et al., 2016) This aligns with the findings of the Agergaard study, where the EVEN distribution pattern resulted in lower whole-body protein breakdown.

Research has indicated that whole-body protein net balance fluctuations occur throughout the day in response to protein intake at each main meal. The EVEN distribution pattern, with its higher amino acid appearance and concentration, may contribute to maintaining muscle mass and support an even intake of dietary protein.(Jespersen & Agergaard, 2021)

muscle protein synthesismeal frequency protein breakdown
While the Agergaard study found no significant difference in muscle protein synthesis (MPS) between the EVEN and SKEWED groups, other studies have reported contrary results. For instance, a study involving young subjects found a greater MPS with an EVEN protein distribution than a SKEWED distribution. (Mamerow et al., 2014)

Considering Recent Studies on Time-Restricted Feeding (TRF):

A recent study published in Obesity found TRE did not affect muscle protein synthesis. Researchers assigned subjects to an 8-hour TRE group (i.e., 3 meals eaten between 10 am and 8 pm) or a 12-hour eating window (i.e., 3 meals eaten between 8 am and 8 p) for 10 days. At first glance, the group that TRE is consuming protein later should result in lower protein synthesis with longer periods of not eating. The calories, protein, fats, and carbohydrates were evenly matched (56% carbohydrate, 30% Fat, and 14% Protein). The only difference was that the TRE group had longer periods of not consuming food. The researchers measured protein synthesis and continuous glucose monitoring along with body composition.

At the end of the study, there was no difference in protein synthesis between the TRE and the control groups. (Parr et al., 2022) Both groups tended to lose muscle mass, but the researchers acknowledge that they failed to set calories high enough (i.e., subjects had a higher activity level than calculated) to maintain their muscle mass.

However, it’s worth noting that the subjects in the TRF studies involved subjects with optimal daily protein targets of 1.6-1.9 g/kg, which may have influenced the results. (Parr et al., 2022) Future research is needed to explore the interplay between meal frequency, protein distribution, and TRF in different populations and protein intake scenarios.

Conclusion:

In conclusion, optimizing meal frequency and protein distribution may hold significant potential in supporting healthy aging and preserving muscle mass in older adults. The evidence with young adults who exercise is a little more complex.

Evidence suggests that an even protein distribution throughout the day promotes positive whole-body protein net balance, primarily driven by lower protein breakdown rates. While the impact on muscle protein synthesis may vary, maintaining an even dietary protein intake appears beneficial for muscle health.

What happens in protein breakdown?

Protein breakdown, also known as protein catabolism, breaks proteins into their constituent amino acids.  During protein breakdown, enzymes sever the peptide bonds, releasing the amino acids from the protein molecule.

The bloodstream then carries these individual amino acids to various tissues throughout the body, where they either help synthesize new proteins or fuel cellular processes. Maintaining overall health and wellness necessitates protein breakdown because it enables the body to repurpose old or damaged proteins, supporting crucial biological functions.

References:

Agergaard, J., Justesen, T. E. H., Jespersen, S. E., Tagmose Thomsen, T., Holm, L., & van Hall, G. (2023). Even or skewed dietary protein distribution is reflected in the whole-body protein net-balance in healthy older adults: A randomized controlled trial. Clin Nutr, 42(6), 899-908. https://doi.org/10.1016/j.clnu.2023.04.004

Areta, J. L., Burke, L. M., Ross, M. L., Camera, D. M., West, D. W., Broad, E. M., Jeacocke, N. A., Moore, D. R., Stellingwerff, T., Phillips, S. M., Hawley, J. A., & Coffey, V. G. (2013). Timing and distribution of protein ingestion during prolonged recovery from resistance exercise alters myofibrillar protein synthesis. J Physiol, 591(9), 2319-2331. https://doi.org/10.1113/jphysiol.2012.244897

Bollwein, J., Diekmann, R., Kaiser, M. J., Bauer, J. M., Uter, W., Sieber, C. C., & Volkert, D. (2013). Distribution but not amount of protein intake is associated with frailty: a cross-sectional investigation in the region of Nürnberg. Nutrition Journal, 12(1), 109. https://doi.org/10.1186/1475-2891-12-109

Jespersen, S. E., & Agergaard, J. (2021). Evenness of dietary protein distribution is associated with higher muscle mass but not muscle strength or protein turnover in healthy adults: a systematic review. European Journal of Nutrition, 60(6), 3185-3202. https://doi.org/10.1007/s00394-021-02487-2

References:

Johnson, N. R., Kotarsky, C. J., Mahoney, S. J., Sawyer, B. C., Stone, K. A., Byun, W., Hackney, K. J., Mitchell, S., & Stastny, S. N. (2022). Evenness of Dietary Protein Intake Is Positively Associated with Lean Mass and Strength in Healthy Women. Nutrition and metabolic insights, 15, 11786388221101829. https://doi.org/10.1177/11786388221101829

Kim, I.-Y., Schutzler, S., Schrader, A., Spencer, H. J., Azhar, G., Ferrando, A. A., & Wolfe, R. R. (2016). The anabolic response to a meal containing different amounts of protein is not limited by the maximal stimulation of protein synthesis in healthy young adults. American Journal of Physiology-Endocrinology and Metabolism, 310(1), E73-E80. https://doi.org/10.1152/ajpendo.00365.2015

Mamerow, M. M., Mettler, J. A., English, K. L., Casperson, S. L., Arentson-Lantz, E., Sheffield-Moore, M., Layman, D. K., & Paddon-Jones, D. (2014). Dietary Protein Distribution Positively Influences 24-h Muscle Protein Synthesis in Healthy Adults. The Journal of Nutrition, 144(6), 876-880. https://doi.org/https://doi.org/10.3945/jn.113.185280

Parr, E. B., Kouw, I. W. K., Wheeler, M. J., Radford, B. E., Hall, R. C., Senden, J. M., Goessens, J. P. B., van Loon, L. J. C., & Hawley, J. A. (2022). Eight-hour time-restricted eating does not lower daily myofibrillar protein synthesis rates: A randomized control trial. Obesity (Silver Spring). https://doi.org/10.1002/oby.23637

Schoenfeld, B. J., Aragon, A. A., & Krieger, J. W. (2015). Effects of meal frequency on weight loss and body composition: a meta-analysis. Nutr Rev, 73(2), 69-82. https://doi.org/10.1093/nutrit/nuu017

References:

Tieland, M., Borgonjen-Van den Berg, K. J., Van Loon, L. J. C., & De Groot, L. C. P. G. M. (2015). Dietary Protein Intake in Dutch Elderly People: A Focus on Protein Sources. Nutrients, 7(12), 9697-9706. https://www.mdpi.com/2072-6643/7/12/5496

Yasuda, J., Asako, M., Arimitsu, T., & Fujita, S. (2019). Association of Protein Intake in Three Meals with Muscle Mass in Healthy Young Subjects: A Cross-Sectional Study. Nutrients, 11(3), 612. https://www.mdpi.com/2072-6643/11/3/612

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