The concept of training with reduced muscle glycogen (i.e. “train-low” paradigm) is recognised as a nutritional strategy to modulate acute cell signalling to drive muscle endurance adaptations. This article discusses whether carbohydrate restriction is optimal to augment these changes.
How can I apply this?
Training intensity across the session workload appears to be the greatest driver of muscular endurance adaptations. This could also be achieved by long-duration lower-intensity workload to muscular fatigue. The key is creating a disturbance in local cellular energy status—working the muscles to fatigue. For this reason it is thought that restricting carbohydrate and thus lowering glycogen achieves this better. However it appears that starting levels of glycogen matter less than the amount of glycogen that is used during the session. I.e., how hard you worked that muscle. More so it appears that starting sessions with lower glycogen may reduce intensity across the workload, and perhaps total work completed.
Therefore, though it would seem “right” to undertake training sessions with lower glycogen—lower local energy stores, this may impact how hard you can actually push yourself, and it appears it is the duration of intensity you can maintain, the use of those energy stores, that primarily drives muscular endurance adaptations.
Focus on maximising your ability to train your greatest intensity of workload. This will be starting your sessions well recovered (glycogen and creatine replete), and using carbohydrates (and optionally caffeine) during the session to maintain your highest intensity throughout.
The harder you are able to train, the more efficient you are able to perform — Tom Herbert
Overall, athletes looking to increase fat oxidation during exercise should focus more on daily fat and carbohydrate intake, and to a lesser degree, pre-exercise carbohydrate intake, while being less concerned with carbohydrate ingestion during exercise, particularly as exercise duration extends.
AMP-activated Protein Kinase (AMPK)
- AMPK (5’ Adenosine Monophosphate-activated Protein Kinase) is a cellular energy sensor that induces phosphorylation of metabolic enzymes, and the transcription of metabolic genes.
- Repeated AMPK activation contributes to chronic adaptations to endurance exercise by enhanced expression of metabolic enzymes and proteins involved in glucose transport, fat oxidation, and mitochondrial biogenesis.
- AMPK activation during exercise is influenced by changes in cellular energy charge (e.g., decreased glycogen, increased free AMP/ADP, decreased PCr:total Cr ratio), which are affected by exercise intensity, duration, individual fitness, and carbohydrate intake.
- AMPK activation is most commonly seen at exercise intensities above 60% VO2Max, but also long duration low-intensity exercise. The disturbance in muscular homeostasis that activates AMPK, occurs in response to all forms of aerobic exercise performed beyond a certain intensity.
- Elevated AMPK without subsequent inhibition of mTOR (mammalian Target Of Rapamycin) has been shown in concurrent training—endurance exercise and strength training in the same session, evidence that these two signalling pathways are not antagonistic to one another during exercise.
- Although AMPK activity increases by 8–10-fold during ∼120 min of exercise at ∼65% VO2peak in untrained individuals, there is no increase in these individuals after only 10 days of exercise training. There is also a lack of activation of skeletal muscle AMPK during 120 min of cycling exercise at 65% VO2peak in endurance-trained individuals. AMPK is not an important regulator of exercise metabolism during 120 min of exercise at 65% VO2peak in endurance trained men.
- The precise role of AMPK for training-induced adaptations is still unclear, and more research is needed to understand the relationship between acute AMPK activation and longer-term training adaptation. Research has also mainly been performed with young (~27 years) males.
Carbohydrate consumption and glycogen concentrations
Muscle glycogen concentrations before, during, and after exercise can influence AMPK signalling.
Although undertaking exercise with reduced muscle glycogen concentrations can increase AMPK activity relative to exercise undertaken with higher muscle glycogen, there is no observed relationship between starting muscle glycogen concentrations and any markers of AMPK signalling. Significant correlations are found between both ending glycogen concentration and glycogen reduction during exercise. Lines of evidence indicate undertaking exercise with low, compared to high muscle glycogen can increase AMPK activation during low- to moderate-intensity exercise, and ending glycogen levels appear more influential than starting levels, but are not the primary driver of AMPK activity.
Muscle glycogen breakdown is similar (although not always) between fed- and fasted-state exercise with similar starting glycogen concentrations, and therefore show similar AMPK activation. AMPK activity is potentially increased during exercise in the fasted state, as ingestion of carbohydrate can increase muscle glycogen within 3 hours, altering starting, and therefore ending muscle glycogen. However available evidence for fasted-state exercise increasing AMPK is weak.
Carbohydrate ingested during exercise does not appear to influence AMPK, but is possibly attenuated if glycogen breakdown is reduced, influencing ending glycogen concentrations. Carbohydrate ingested during exercise can attenuate musle AMP concentration and ATP:ADP ratio, but AMPfree levels are sufficient to activate AMPK. Carbohydrate ingestion during exercise does not affect changes in ADP and PCr.
Carbohydrate ingestion before and/or during exercise is unlikely to alter muscle AMPK signalling during exercise.
Irrespective of muscle glycogen, the use of high intensity exercise is known to iduce signifcantly greater metabolic stress that augments the phosphorylation and activation of AMPK when compared with low-intensity exercise. Since this metabolic disturbance ultimately regulates AMPK signalling, and reducing pre-exercise muscle glycogen induces negligible further modulatory effects on muscle, it appears completion of high-intensity exercise is the key driver of local musclular endurance adaptations.
Although augmented signalling has been shown in high intensity exercise commenced with low muscle glycogen, recent data suggests this may be explained by the metabolic stres of training twice per day, rather than low pre-exercise glycogen concentrations.
Compared to a post-exercise energy-deficit-low-fat meal (EDLF) [9kcal/kg FFM]; restoring the energy expended after a glycogen-depleting exercise session with an energy-balance-low-carbohydrate-high-fat meal (EBHF) [30kcal/kg FFM] has no positive effect on training adaption, and impairs glucose regulation and insulin response to a post-exercise carbohydrate meal the following day.
There is also no meaningful difference in markers of muscle adaptation to endurance exercise between the EDLF and EBHF meals, however the EDLF meal improved glucose control in the morning. The EDLF meal did not further up-regulate AMPK, suggesting no interference, synergistic or additive effect between muscle glycogen and energy status in the phosphorylation status of key proteins in this pathway.
Individual fitness levels, sex differences, exercise duration and intensity
Overall evidence indicates exercise intensity, not duration, is the driving factor for AMPK activation during exercise. This is related to the greater disturbance in cellular energy homeostasis.
Fitter individuals have reduced AMPK activation during low- to moderate-intensity exercise, likely due to improved maintenance of cellular energy homeostasis, but these differences may be minimised with higher-intensity exercise.
Although there are no sex difference observed in response to high-intensity exercise or submaximal cycling, AMPfree, and Cr concentrations have increased during submaximal cycling in men but not women.
In summary, the present study found that, unlike untrained individuals, endurance trained men have no increase in skeletal muscle AMPK activity, AMPK phosphorylation or ACC phosphorylation during 120 min of cycling exercise at ∼65% VO2peak. This finding is consistent with results following short-term exercise training where no increase in AMPK activation during moderate intensity exercise is also observed.[2:1]
- The most influential factor for AMPK activation is disruption in cellular energy charge (e.g., decreased glycogen, increased free AMP/ADP, decreased PCr:total Cr ratio)
- Exercise intensity, not duration, is correlated with markers of AMPK activation. Disruption in cellular energy charge is best achieved via short-duration high intensity interval exercise (HIIE), or long-duration continuous training performed to exhaustion.
- Commencing high-intensity exercise with reduced pre-exercise muscle glycogen confers no additional benefit to the early signalling responses that regulate mitochondrial biogenesis.
- Ending levels of glycogen appear more important than starting levels, and carbohydrate ingestion before or during exercise have minimal influence on AMPK activation.
Carbohydrate consumption prior to and/or during training has minimal impact on muscular endurance adaptation. Rather the acute disruption of cellular energy homeostasis is key. This is likely best achieved by short high-intensity training sessions, and/or longer low-intensity sessions taken to muscular fatigue.
Since long-term overall energy status (“high energy availability”) is important for athletic health and development, those who restrict carbohydrate before and during training sessions for the sake of enhancing endurance adaptations, are likely not benefiting significantly, and may be potentially increasing their risk of chronic low-level “low energy availability”. It also appears that replacing that carbohydrate energy with fat, not only does not enhance endurance adaptations, but unfavourably impacts glucose regulation and insulin response to subsequent carbohydrate meals.
There may be a small benefiting of restricting carbohydrate (and/or energy) post-training (e.g., “sleep low”). However this has to be taken into consideration with overall energy status. Acute periods of “low energy availability”, may augment training adaptations, but care must be taken.
What may be a more sensible approach is using carbohydrate leading up to and/or within training sessions to support maximal training effort and intensity—working to muscular fatigue, and then consuming a post-session low-carbohydrate lower-fat high-protein meal. Protein replacing a proportion of energy normally provided by carbohydrates.
This could be a meal replete with fresh colourful low-carbohydrate vegetables, and a large portion (~25-50g total protein content) of omega3-rich fish, or pasture raised lean meat. This meal would provide essential amino acids, vitamins, minerals, and molecules involved with the pro/anti-inflammation recovery pathways. Protein is key in supporting tissue growth and remodelling, and will have a lower impact on overnight fat-metabolism than a carbohydrate-rich evening meal.
For those who do not consume animal products, carbohydrate intake will always be moderately higher. But again this is not a problem, as the key driver of endurance training adaptation is work done during the training session, not the nutrition before, within, or after the session.
Muscle glycogen, fitness level, exercise intensity, and exercise duration each influence AMPK activity during exercise when all other factors are held constant. However, disrupting cellular energy charge (e.g., decreased glycogen, increased free AMP/ADP, and decreased PCr:total Cr ratio) is the most influential factor for AMPK activation during endur- ance exercise. This could be achieved via short-duration HIIE or lower-intensity continuous training performed to exhaustion. Ending levels of muscle glycogen appear more important than starting levels to increase AMPK activation, whereas carbohydrate ingestion before or during exercise has minimal influence on AMPK activation. Exercise inten- sity, but not duration, is correlated with indices of AMPK activity.
Aside from an exercise performance perspective, our data provide greater insights into how athletes can implement nutritional strategies that promote training quality without sacrificing cellular adaptation. Indeed, there is often a belief that nutritional strategies to promote training intensity (i.e. promotion of adequate CHO availability) are mutually exclusive to those promoting training adaptation (i.e. CHO restriction). However, the present data demonstrate that trained male athletes can still achieve these fundamental adaptive goals of training even in the presence of high CHO availability before and during training. Our data clearly demonstrate that high CHO availability (i.e. high glycogen availability, pre-exercise feeding and CHO intake during exercise) does not impair the activation of cell signalling pathways with regulatory roles in stimulating hallmark adaptations to endurance training such as mitochondrial biogenesis. Importantly, these findings were observed during an exercise challenge that adopted an exercise duration (i.e. > 3 h) and intensity (i.e. above lactate threshold) that is of ‘real world’ physiological relevance to ‘elite’ endurance athletes.
In summary, we provide novel data by demonstrating that graded pre-exercise muscle glycogen (within a range of 600–200 mmol (kg dw)−1) does not modulate the exercise-induced nuclear abundance of AMPK or PGC-1α nor does it affect the expression of genes with regulatory roles in mitochondrial biogenesis and substrate utilization. Practically, these data suggest that the additional stress of low pre-exercise muscle glycogen may not be required when performing high-intensity exercise that already subjects skeletal muscle to a sufficient metabolic challenge and may be better suited during conditions that do not elicit such cellular perturbations (e.g. prolonged low-intensity exercise completed below lactate threshold).
Moreover, these results suggest that replenishing energy expended during exercise with a high-fat meal is more likely to impair than enhance the adaptive response to training with low skeletal muscle glycogen. … As such, our findings indicate that when training with low carbohydrate availability, transient energy deficit may be more beneficial than replacing the expended energy with ingested fat and supports and extends previous findings using isoenergetic low-CHO high-protein versus low-CHO high-fat diets.
AMPK Predictor App
Rothschild, J.A., Kilding, A.E., Stewart, T. et al. Factors Influencing Substrate Oxidation During Submaximal Cycling: A Modelling Analysis. Sports Med (2022). https://doi.org/10.1007/s40279-022-01727-7 ↩︎
McConell, G. K., Wadley, G. D., Le Plastrier, K., & Linden, K. C. (2020). Skeletal muscle AMPK is not activated during 2 h of moderate intensity exercise at∼ 65% in endurance trained men. The Journal of Physiology, 598(18), 3859-3870. ↩︎ ↩︎
Rothschild, J. A., et al. (2021). Factors Influencing AMPK Activation During Cycling Exercise: A Pooled Analysis and Meta-Regression. Sports Medicine. https://doi.org/10.1007/s40279-021-01610-x ↩︎
Fell, J. M., et al. (2021). Carbohydrate improves exercise capacity but does not affect subcellular lipid droplet morphology, AMPK and p53 signalling in human skeletal muscle. The Journal of Physiology, 599(11), 2823–2849. https://doi.org/10.1113/JP281127 ↩︎
Areta, J. L., et al. (2020). Achieving energy balance with a high‐fat meal does not enhance skeletal muscle adaptation and impairs glycaemic response in a sleep‐low training model. Experimental Physiology, 105(10), 1778-1791. ↩︎