Introduction
Creatine monohydrate is one of the most studied and most effective ergogenic aids available at increasing various metrics of human performance (Kreider et al., 2017). Creatine monohydrate has been shown to be overwhelmingly safe and effective for increasing anaerobic capacity, strength, and muscle mass when paired with resistance training (Buford et al., 2007) (Kreider et al., 2017). Furthermore, there are implications of its benefit in various medical and clinical applications such as neurodegenerative diseases (Kreider et al., 2017).
Many studies on creatine monohydrate focus on a dosage level and measure the outcome (Bemben et al., 2001). However, it was not until more recently that the question arose of optimal timing and or co-ingestion interactions (Antonio, Ciccone, 2013; Taylor et al., 2011). This review encompasses creatine monohydrate optimization through the lens of the independent variables ingestion timing and carbohydrate co-ingestion. In addition, it examines dependant variables such as creatine absorption and storage as well as sports performance metrics such as strength and peak power output. The purpose of this review is to examine the current literature relating to creatine ingestion timing and carbohydrate co-ingestion and make a recommendation for current best practices in athletic creatine supplementation.
Literature Review
Creatine Timing
Creatine supplementation is known to increase the stores of creatine phosphate within the muscle, where it is able to rapidly provide a phosphate molecule to dephosphorylated adenosine triphosphate (ATP), which is called adenosine diphosphate (ADP). Because creatine is stored within the muscle, the concept of timed ingestion of creatine is not immediately apparent to be vital as it imparts no acute benefits but instead acts based on increased muscle stores of creatine. Studies frequently test creatine monohydrate based on dosage to manipulate creatine stores and then measure outcomes (Bemben et al., 2001), and while this is an acceptable model, there may be potential creatine performance and storage benefits left to be examined by using timing protocols to build on this research.
Pre-Workout Creatine Timing
Several pre-workout supplements combine various acute performance-boosting ingredients, such as caffeine with creatine monohydrate (Outlaw et al., 2014). While these supplements tend to increase performance (Outlaw et al., 2014), likely by nature of their stimulants, there is a small amount of evidence to support decreases in storage and performance in the creatine loading phase when co-ingested with caffeine. Furthermore, there is a theoretical reason to be cautious of co-ingestion due to their opposing actions at the muscular level (Guest et al., 2021). As caffeine is known to be a potent performance enhancer and exerts its benefits acutely, it is likely best to supplement caffeine prior to sport or exercise (Guest et al., 2021). With the pre-workout benefits of caffeine and the potential deleterious interactions with caffeine and creatine co-ingestion, there may be a reason to consider that pre-workout is not optimal for creatine, especially if the athlete is also supplementing with caffeine. There exists a theoretical framework that creatine supplementation late in the day or prior to bed could limit this interaction as there is likely less caffeine in the body at this time. If caffeine is not a concern, there is data to support that the benefit in nutrient intake within the muscle occurs both 1-2 hours before and after a workout, meaning in theory, creatine could be taken pre-workout. Furthermore, there is a small amount of data to support that creatine taken 2 hours prior to training increases power performance and total workload (Bach, 2014). However, this may change if the subject already has elevated creatine stores from chronic supplementation.
Due to the generalized increases in nutrient receptiveness within the muscle pre-workout, creatine supplementation is potentially more effective than non-workout timed supplementation. However, there are potential contraindications with caffeine co-ingestion, which is a very effective pre-workout supplement.
Post-Workout Creatine Timing
After resistance training, the body changes from a catabolic state to an anabolic state to start the repair process, and muscle protein synthesis starts to rise. During this time, the muscles are receptive to nutrients for restoration (Reidy and Rasmussen, 2016). In theory, this anabolism plus the lack of caffeine intake post-workout makes an ideal environment for creatine uptake and storage. Independently of caffeine, a study by Antionio and Ciccone (2013). showed when examining pre-workout vs. post-workout creatine supplementation, there were significant performance increases in the bench press (P < 0.001) and body composition improvements (P < 0.001) in the post-workout supplementation group over four weeks. On top of the muscle being more receptive to nutrients and the general state of anabolism post-workout (Reidy, Rasmussen, 2016), there could also be a benefit to creatine storage and function by nature of the increase in blood flow easing creatine transport (Forbes, Waltz, Candow, 2014).
Further evidence of the value of post-workout supplementation is seen when in a study examing a group of subjects that trained one arm on one day and supplemented 2g/kg creatine post-workout, then the next day trained the other arm and supplemented a placebo. The arm that was trained with supplemented creatine post-workout increased muscle mass significantly more than the group that did not (10.3 ± 1.7%, 0.36 ± 0.06 cm) vs. (6.3 ± 1.9%, 0.24 ± 0.07 cm) (P < 0.02) (Chilibeck et al., 2004). This crossover design shows a unique perspective to creatine supplementation and shows potential added hypertrophic benefits to post-workout creatine supplementation.
Mechanistically creatine has an intracellular hyperhydration effect which is an efficacious tool in performance when stores are elevated (Beis et al., 2011) and recovery when the athlete is depleted and dehydrated (Ricci, Forbes, Candow, 2020), which is an expected effect post-workout. Creatine also increases intracellular water retention, specifically within the muscle (Antonio et al., 2021), which causes a degree of cellular swelling. Cellular swelling to a high level, as seen from muscular pumps, is hypertrophic (Schoenfeld et al., 2014), and the low levels of cellular swelling from creatine storage and water retention may stimulate anabolic pathways similarly to a lesser degree (Forbes, Candow, 2018), which makes it an excellent pairing with a post-workout need for anabolism.
There is an increased anabolic environment before and after resistance training, both of which have potential benefits for creatine uptake and storage. In addition, post-workout has specific advantages on top of the anabolic environment due to the lack of the contraindication of caffeine ingestion as well as potential combined effects with various other nutrients such as carbohydrate and protein, which will be discussed further later in the review.
Non-Workout Timing Considerations
Frequently nutrient timing is limited to the scope of pre or post-workout. For example, if a complete avoidance of the potential negative interaction between caffeine and creatine is the primary goal, a nighttime dose of creatine makes some theoretical sense. However, it appears that the anabolic window, which has since expanded to be 1-2 hours before and after a resistance training workout (Schoenfeld et al., 2016), is also a prime time for creatine uptake and storage as well. A study examining creatine, carbohydrate, and protein supplementation in either pre and post-workout doses or morning and night doses found that lean body mass, bench press, glycogen, and creatine stores all significantly elevated in the pre and post-workout group (LBM: 2.7 ± .4 vs. 1.5 ± .2kgs) (Bench:12.5 ± 2.5 vs. 8 ± 2kgs) (Glycogen: 232.9 ± 2.8 vs.294.1 ± 8mmol/kg) (Creatine: 81.6 ± 2.7 vs. 91.2 ± 1.4mmol/kg) (Cribb, Hayes, 2006). The potency of the anabolic window opens theoretical doors to high-frequency training and twice-daily resistance training to expand this added benefit as it is already a potentially significant benefactor in managing progressive overload and fatigue in very intense training protocols (Israetel et al., 2020). There are currently substantial amounts of data showing that timing creatine either before or after a workout is likely better than other times. Furthermore, robust data show that post-workout creatine supplementation is likely slightly more effective than pre-workout (Naderi et al., 2016) independent of the theoretical contraindications with caffeine which needs more research.
Creatine and Carbohydrate Co-ingestion
Carbohydrate ingestion, especially when paired with resistance training, has been shown to increase net protein balance (Borsheim et al., 2004), likely by nature of a protein-sparing effect or an insulinogenic storage effect. This potentially sets up a theoretical framework where the storage of creatine could be increased with carbohydrate co-ingestion by the nature of an insulin response. In addition, while carbohydrate and creatine mechanistically act differently within the muscle, their outcome is similar in that they increase strength, work output, and recovery (Koenig et al., 2008), so a theoretical synergistic relationship may exist and is potentially worth examining.
Creatine monohydrate, when ingested alone, has normalized effects on creatine storage within the muscle. However, when creatine monohydrate and 93g of simple carbohydrates are co-ingested, there are significant (P < 0.01) increases in total creatine storage within the muscle, which was 60 percent higher than the control group that only supplemented creatine. Interestingly, there was a significant increase in insulin (P < 0.001) concentration, which is expected with carbohydrate intake, and the storage effect of insulin is well known. Thus, theoretically, a potential added insulin-mediated creatine storage effect could exist (Green et al., 1996). While this is a somewhat large amount of simple carbohydrates, there is also data to suggest that this effect is still present with much smaller amounts of carbohydrate co-ingestion. (Greenwood et al., 2003). In a pilot study examining creatine monohydrate supplementation independently of dextrose versus a group co-ingesting 18 grams of dextrose and creatine, there were significant increases in the storage of creatine within the muscle (dextrose control =0±0; creatine monohydrate =61±15; creatine monohydrate + dextrose =80±11 % p = 0.001) (Greenwood et al., 2003). This insulinogenic response is potentially also supplemented by carbohydrate + protein co-ingestion as well which will be covered in the next section.
Carbohydrate
intake creates the potential for an anaerobic environment, which can help add
to creatine stores potentially by insulin secretion. Furthermore, like
creatine, muscle glycogen is stored in the muscle, which may somewhat explain
the synergistic storage relationship. Future research should seek to examine
dose-response relationships for creatine storage with carbohydrate intake.
Creatine and Protein Co-ingestion
Creatine and high carbohydrate co-ingestion are efficacious in increasing stores of creatine in the body and increasing performance. However, there is data to support that protein might have similar benefits. A study comparing creatine protein and carbohydrate intake vs. creatine and carbohydrate intake alone found no differences between the groups (Steenge, Simpson, Greenhaff, 2000). In addition, protein intake around the workout is already known to be beneficial for recovery and increasing muscle protein synthesis. Thus, mixing protein, creatine, and carbohydrates post-workout, in theory, may benefit recovery and performance. While the direct research of protein plus creatine co-ingestion is still limited, the data so far show it is at least comparable to creatine plus carbohydrate ingestion and creatine plus carbohydrate and protein intake. With the small amount of research showing its efficacy and all of these supplements’ long tenure for increasing its performance, it is potentially efficacious to co-ingest them.
Conclusion
Creatine monohydrate supplementation is likely stored more effectively in the muscle when supplemented within 1-2 hours pre or post-workout. There may exist a negative interaction between creatine and caffeine function when co-ingested. If pre-workout caffeine is ingested, it is potentially best practice to supplement creatine post-workout to avoid this interaction. Furthermore, independent of caffeine intake, post-workout supplementation of creatine is likely a small amount more effective than pre-workout due to the muscular depletion of resources and the temporary anabolic state needed for repair.
Creatine
monohydrate supplementation is also likely more effective when paired with
simple carbohydrate and or protein intake. This effect is likely due to the
insulin response facilitated by carbohydrate intake and gluconeogenesis of
superlative protein intake. Thus, while protein intake is not better than
carbohydrate intake for increasing creatine storage, it is likely similar and
is also similar when mixed between carbohydrate and protein. Therefore, based
on the current literature, it is likely best practice to consume creatine
monohydrate post resistance training, paired with 50-100g of simple
carbohydrates and 20-40 grams of complete protein sources. The goal of these
recommendations is to both optimize creatine storage and facilitate
post-workout recovery.
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