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Use of anabolic signaling data to inform nutrition and training recommendations

Nutrition influences the adaptive response of training on muscle mass and function. Thus, it is important to determine the nutrition and training stimuli for optimal training adaptations. Certainly, an evidence-based approach is crucial for generating the best nutrition and training recommendations. However, interpretation of the scientific literature can be problematic. Recently, the response of anabolic signaling pathways to various nutrition and exercise interventions has been investigated. More and more, practitioners are encouraged to consider this type of information to inform recommendations for athletes and other exercisers.

Mechanisms underpinning adaptation

The primary molecular anabolic pathway that has been investigated is the mTORC1 signalling pathway. For over 20 years, the response of this pathway to nutrition and exercise has been studied in cell culture and animal models. It is quite clear that the activity of this anabolic-signaling pathway is critical for optimal stimulation of muscle protein synthesis (MPS) and thus muscle adaptation.

More recently, studies in humans have contributed more information. In fact, there are data showing a relationship between the response of the mTORC1 pathway and muscle hypertrophy. However, I would argue that use of data on the response of anabolic signaling pathways to nutrition and exercise interventions should not be the primary basis upon which practical recommendations should be made. There are a number of limitations to the measurement of the response of anabolic signaling that must be considered before using these data for anything more than interesting mechanistic information.

The mTORC1 signaling pathway is critical for optimal stimulation of MPS and thus muscle adaptation.

Here are some findings

  • Recent studies have clearly shown that blocking the mTORC1 pathway inhibits the response of MPS to resistance exercise and protein.

  • We also know that protein (essential amino acids) and resistance exercise both independently stimulate the mTORC1 signalling pathways.

  • Moreover, measuring the response of these pathways is cheaper and easier than measuring MPS or doing a long-term training study.

Thus, it is quite tempting to use this information alone to inform practical recommendations.

A big however!

However, recent studies from our laboratory (and others) have shown that there is often a mismatch between the responses of the anabolic signaling pathways and muscle protein synthesis. There are a number of methodological reasons why we see this mismatch. Measurements of signalling proteins are made in small biopsies from the muscle. Because of its invasive nature, investigators have to make decisions when to take the biopsies because for obvious reasons they cannot take biopsies every 5 min. If you can only take a few biopsies, the timing of the muscle biopsies in any given study may be an issue. Each measurement must be considered as a snapshot at the time the biopsy was taken.

Issue 1:

If we see that a particular intervention, say whey protein ingestion, results in a greater molecular response at 2h after ingestion, how do we know that the response may not be greater with ingestion of another protein at 1h and that is sufficient for maximal stimulation of muscle protein synthesis?

Issue 2:

Another issue is a potential threshold effect. Typically, the activity of the mTORC1 pathway is assessed by measuring phosphorylation of the proteins in the pathway. So, if a particular intervention (A) results in greater phosphorylation than intervention B, we would suggest that A results in greater muscle protein synthesis and is thus superior to B. however, there is evidence that phosphorylation only has to hit a certain threshold and the system in maximally stimulated. So, the response of MPS to A and B will be no different.

Issue 3:

Finally, the measurement of phosphorylation as an indication of pathway activity can be problematic. Measurement of phosphorylation is, at best, semi-quantitative so the precision often leads much to be desired. Dr. Lee Hamilton, in our research group here in Stirling, has recently validated a quantitative method for measuring molecular activity in human muscle. However, despite the improved precision that this method provides, the previous two issues, snapshot information and the threshold effect still apply. So, the information gleaned from measuring anabolic signaling in humans in vivo is important to provide mechanistic understanding. However, the unavoidable limitations of the measurements prevent use of this information for informing practical recommendations.

There is often a mismatch between the responses of the anabolic signaling pathways and muscle protein synthesis, which can be attributed to a number of methodological reasons.

Thus, nutrition or exercise interventions can not be based solely on information about anabolic signaling pathways and should not be utilized by practitioners.


  1. Macnaughton, L., Wardle, S., Witard, O., McGlory, C., Hamilton, D., Jeromson, S., Lawrence, C., Wallis, G. and Tipton, K., 2016. The response of muscle protein synthesis following whole-body resistance exercise is greater following 40 g than 20 g of ingested whey protein. Physiological Reports, 4(15), p.e12893.


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