Written by Michael J. Rudolph, Ph.D.


The sequential implementation of strength training immediately followed by cardiovascular exercise has become standard practice to maximize muscle mass and reduce body fat. Despite the popular use of this approach, it has become evident that the body responds very differently to both modes of training, especially at the molecular and cellular levels. In fact, not only are the molecular and cellular reactions different in response to strength and cardiovascular training, they can also be antagonistic to each other— potently diminishing the positive influence that each can have on the body.

In general, resistance exercise increases muscle cell size by activating the enzyme mTOR, which stimulates muscle protein synthesis and therefore muscle growth.

1 On the other hand, endurance exercise reduces fat cell mass by triggering the enzyme AMPK, which boosts fatty acid oxidation, ultimately leading to less body fat.

2 It has also been shown that AMPK activation directly shuts down mTOR-driven muscle protein synthesis and muscle growth.

3 Consequently, performing endurance work right after weightlifting may not be the best training sequence for optimal muscle growth as the activation of AMPK from endurance training counteracts mTOR function in response to resistance work, negatively influencing muscle growth. This is especially true because mTOR function is typically maximized right after lifting weights

4,5, Meaning that the simultaneous activation of AMPK from endurance training would greatly deplete mTOR activity and muscle growth.

Fortunately, recent evidence has uncovered a seemingly straightforward, yet somewhat counterintuitive, approach to successfully resolve this potential muscle-depleting conflict between AMPK and mTOR. That solution requires the performance of cardiovascular exercise before resistance work to prevent the muscle loss caused by synchronized activation of AMPK and mTOR.

Cardio After Weightlifting Kills Muscle Growth

Contrary to popular belief, extensive cardiovascular work after weight training is not the best method to augment muscularity. While cardiovascular exercise at the end of your workout promotes the greatest weight loss, a study by Willis et al.

6 Showed that a considerable portion of this weight loss is actually muscle mass. Moreover, a second study by Mournier et al.

7 Went even further, clearly demonstrating the link between the muscle-depleting influence of cardiovascular training with its capacity to activate AMPK and directly turn off mTOR-driven muscle growth. In this study, mice exposed to mechanical overload of the muscle increased mTOR activation— while mice that had their AMPK gene removed (preventing the function of AMPK) had an even greater level of mTOR activation in response to an identical amount of mechanical stress. Overall, these results confirm that AMPK plays an important role in limiting muscle growth through inhibition of the mTOR-signaling pathway.

Endurance Training Before Weights Supports Muscle Growth

Despite the previously mentioned scientific data showing that endurance training after weightlifting clearly inhibits the capacity to build muscle, it appears that performing a standard cardiovascular workout before resistance exercise enhances the propensity to gain muscle mass. Because AMPK activation from cardiovascular training only lasts for approximately one hour after working out

8, in theory, performing resistance training for that one hour after cardiovascular work should completely prevent the simultaneous activation of AMPK and mTOR— as well as the muscle loss that results from the concomitant activation of these two enzymes.

In order to confirm this hypothesis, a study by Ogasawara et al.

9 Looked at the different mTOR-activity levels achieved when performing endurance training, either before or after weightlifting. As expected, they found endurance exercise performed after strength training resulted in increased AMPK activity, which directly attenuated mTOR function as well as muscle protein anabolism. However, the opposite exercise order resulted in the activation of AMPK for only one hour after the endurance work was finished. Since the resistance training lasted for one hour, the authors of this study concluded that AMPK activation did not coincide with mTOR activation from the resistance work. As a result, this training sequence led to a greater level of mTOR function, providing a more anabolic environment that favors muscle growth.

Endurance Work First Depletes Testosterone Without Reducing Strength

Standard resistance training provides a stimulus that increases one of the most prominent muscle-building hormones, testosterone. Conversely, extensive cardiovascular exercise typically suppresses the level of circulating testosterone, which likely depletes muscle growth.

10 What’s more, combining cardiovascular exercise with resistance training still reduces testosterone levels no matter what training order is followed.11 However, the depletion of testosterone from endurance work is short lived— and can apparently still yield considerable strength gains, especially when performing the endurance exercise before strength training.

This effect was shown in a study by Schumann et al.

11, which examined the acute response on testosterone levels from combined endurance and strength training in two independent groups performing endurance training either first or last. The results showed that the group performing the endurance exercise first had relatively lower testosterone levels than the group doing the endurance work last. However, the lower testosterone levels did not correlate with strength development, as the group that performed endurance work first actually showed greater strength gains, with a 17 percent increase of their one-repetition maximum in the leg press— compared to the group performing endurance training second, that only improved their one-repetition maximum by 13 percent.

Taken together, the above results indicate that although cardiovascular training depletes the potent muscle-building hormone testosterone, performing endurance training first is apparently better for gaining size and strength.

For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a Research Scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.