Research Review: Molecular Responses to Strength & Endurance Training – Are They Incompatible?

In his review Molecular Responses to Strength and Endurance Training: Are They Incompatible?, John Hawley explores the possibility of competing signaling cascades associated with strength and aerobic adaptations when these qualities are trained simultaneously. Most research describes this phenomenon as the concurrent training effect or interference effect.
Research Summary

Hawley’s paper opens by describing the molecular foundation on which strength and conditioning is based:


The signal above could be any training activity chosen for an athlete – plyometrics, heavy box squats, tempo runs, etc. At the cellular level, training will cause the upregulation of primary and secondary messengers, which constitutes a response. This response produces a cascade of molecular events (e.g., gene expression, protein synthesis) that produce transient alterations in the cellular milieu through the accumulation of proteins specific to the activity in question. Over time, the repetition of these processes through consistent training will produce long-term adaptation.

This genetics-based model takes an engineer’s approach toward strength and conditioning. At its foundation, the programming we write for athletes is turning on specific genes. As coaches, it’s our job to choose the right signals to send. And to effectively do so, we need to understand how the human body responds to different signals.

Resistance training sends a signal to athletes’ cells that tells them to be anabolic – i.e., the rate of protein synthesis exceeds the rate of protein breakdown and over time the result is skeletal muscle hypertrophy. The cell responds to resistance training by phosphorylating what’s known as the PI3-k–AKT–mTOR signaling cascade and activating ribosomal protein s6 kinase, or p70 s6k, both of which have been implicated in the anabolic molecular processes that follow acute and chronic resistance training.

Conversely, endurance training causes its own unique signaling cascade, which, according to Hawley, augments the most important aerobic adaptation we can induce in athletes – mitochondrial biogenesis, or the formation of new mitochondria in the cell. The two primary responses leading to mitochondrial biogenesis are the activation of PGC-1a and AMP-activated protein kinase, or AMPK for short.

When studied in isolation, both resistance and endurance exercise produced divergent cellular responses matching the profiles described above. Concurrent training, however, produced sub-optimal activation of both signaling pathways in question.

The party at fault appears to be the complex biochemical interplay, with one pathway activating and repressing gene expression/cell signaling with direct and potentially suppressive ramifications for the other. See Coffey & Hawley’s review The Molecular Bases of Training Adaptation for more information on this subject

Hawley concludes that for the performance-minded coach, concurrent training reduces the potential hypertrophy or mitochondrial biogenesis adaptations that can be achieved through single-mode training alone.

Implications & Limitations

The major implication of Hawley’s review concerns the timing of the training protocols we prescribe athletes.

If the goals of an athlete include adding lean muscle mass, having them perform a high-volume of aerobic work (45-90min) around his or her training session is probably not a smart idea, as this can suppress the signaling cascade that drives protein synthesis. Research has shown elevated protein synthesis for 24-48 hours post-resistance exercise; you’ll likely want to wait at least that long before introducing any dense aerobic training.

Likewise, if an athlete is trying to increase his or her aerobic performance, heavy strength work peri-workout may lead to the downregulation of PGC-1a, thus repressing potential mitochondrial biogenesis.

Following the above guidelines will maximize the athletes’ signaling pathways and stimulate the greatest response for adaptation.

Hawley’s review is not without its limitations, however.

Though the phrase “strength” is mentioned multiple times throughout the review, Hawley’s concern is with hypertrophy alone – and it is unclear whether he consistently means sarcoplasmic or myofibrillar hypertrophy.

As most agree, there is an enormous neural component that is essential to becoming stronger that may not be diminished by the concurrent training effect. In fact, if you were training an athlete whose priority was strength gain without weight gain, performing aerobic work post-workout might even prove beneficial in blunting the anabolic hormonal response.

This study by Chtara et al., however, showed the greatest aerobic adaptation occurring when endurance training was performed prior to strength training — http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1725284/pdf/v039p00555.pdf

Coupled with the fact that there is a link between mitochondrial density and fiber relaxation speed, it seems clear that strength/power adaptations and aerobic adaptations need not be mutually exclusive.

As I hope is clear, further research is necessary to decipher the complex network of signaling pathways that underlie training adaptation. Once unraveled, though, scientists and coaches alike will have the ability to amplify molecular signaling or turn pathways on or off at will, leading to a new level of performance enhancement.



  1. Just making sure you get the comment…didn’t mean to post it to Facebook like that…the link to the Hawley paper seems to be broken…..but great post!

  2. Great thought provoking article Joel, however it leaves me perplexed as how to schedule my workouts. I’ve been doing Monday and Thursday as Strength Days, LSD on Tuesdays and Fridays, HICT on weds, speed/power based off your dvd on Saturdays.

    I read on Lyle’s site that light cardio is good for recovery of the worked muscles, so I put my LSD days of 90 mins after my strength days. Now I’m confused as to how I should rearrange my workout week in light of this article. Feedback from anyone would be greatly appreciate it, and if its too much of a loaded question, I’ll post in the forum if I got no replies. Thanks!

      1. mikiemike87,

        Glad you enjoyed the piece, man.

        Without knowing your goals, it would be hard to assess the effectiveness of the training schedule you presented.

        As mentioned in the article, however, developing a strong aerobic foundation for energy production and getting stronger are not necessarily competing adaptations. While I accept that training both qualities may inhibit the ability to maximize one over the other, aerobic training is NOT the strength/power killer that some make it out to be. This is even more true of someone who is a beginner/intermediate.

        And I completely agree with Lyle – 15-20 minutes of moderately paced aerobic after a strength session can definitely help speed up recovery. Can we both agree that 90 minutes of CO development may not constitute LIGHT aerobic work? 🙂


        1. I thought if a little was good, a lot is even better! I’ll just play around with my schedule. I’m a true beginner in fitness, but have been reading up on Joel, and Lyles stuff for the past few years. Fascinating stuff, thanks Eric

  3. Joel, I’m also having difficulties downloading the article. Any other suggestions. I’m getting a compatibility error, and I’m certain my software is compatible…

  4. My biochemistry isn’t so advanced… when the article is talking about all the different adaptations are they local adaptations or general adaptations… Simple question I guess, If I go running all month do all my muscles begin to show the same aerobic adaptations or is it localized in the muscles that have done the aerobic work?

    1. Muscular adaptations are localized to the muscles that are actually doing the work because that’s where the stress is placed during the exercise. If there is no metabolic or mechanical demand placed on a muscle then there is no reason for it to adapt.

  5. Hi Joel,
    I know that this is an old post but I still love reading all of your stuff.

    I’d like to know your take on concurrently training someone specifically for CrossFit. The obvious challenge lies within the fact that CrossFit athletes need to have a good level of development in all energy systems.

    For this type of athlete if strength/structural balance and an aerobic “base” lay the foundation for the more intense/high volume of training to come later in the year, how would you schedule this appropriately into the week if the athlete trains twice per day? Thanks!

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