KEY LEARNING POINTS
Understand how creatine impacts the effectiveness of resistance training.
Understand the value of creatine timing
Understand the benefits of pre and post-exercise creatine ingestion.
Understand how protein impacts creatine effectiveness.
Be able to ascertain if there are any adverse effects to creatine ingestion.
Creatine is a nitrogen-containing compound consumed in the diet primarily from red meat and seafood (i.e., 2-3 grams per day) or produced in the body from reactions involving the amino acids glycine, arginine, and methionine in the liver and kidney 33
. Typically, dietary creatine matches endogenous creatine degradation, resulting in the formation of creatinine 30
. Based on a 70 kg human with a total creatine pool of 120 grams, creatinine excretion typically amounts to 2 grams per day 26, 30
. Dietary creatine enters circulation and is transported to skeletal muscle, liver, kidney, and the brain 21
. The majority of creatine is transported from areas of synthesis (i.e., liver, kidney) to areas of storage and utilisation (i.e. skeletal muscle) 26
. Skeletal muscle accounts for approximately 95% of all creatine stores in the body 20
. Skeletal muscle creatine content is dependent on muscle fiber composition 26. Type II muscle fibers have high levels of free creatine (Cr) and phosphocreatine (PCr). Intramuscular creatine stores range from 120-160 mmol/ kg dry muscle 12
with approximately 60% being PCr 12, 22
. An increase in intramuscular creatine from creatine supplementation should theoretically increase PCr resynthesis during muscle contraction leading to greater muscle mass and strength.
Potential Mechanistic Actions of Creatine Supplementation
The potential mechanistic actions of creatine on skeletal muscle are multifactorial. Creatine increases intracellular osmolarity 3
which may in turn activate genes and signalling pathways 27
involved in muscle protein synthesis. Creatine supplementation during resistance exercise training significantly increases the mRNA and protein expression of myogenic transcription factors 32
and mRNA expression of myosin heavy chain (MHC I and IIa) in young adults18
. Creatine supplementation increases satellite cell number and myonuclei concentration in muscle fibers following resistance exercise 23
and the content of Akt/protein kinase B in humans 27
. Akt/Protein kinase B activates p70s6k
downstream in the mammalian target of rapamycin (mTOR) muscle protein synthetic pathway 19
. Insulin-like growth factor 1 (IGF-1) stimulates the mTOR muscle protein synthetic pathway28
and satellite cell proliferation and differentiation2
. Creatine supplementation (21 g·day-1
for 5 days) augments IGF-1 mRNA in resting muscle and phosphorylation of eukaryotic initiation factor-4e binding protein-1 (4E-BP1) one day following an acute bout of resistance exercise in young adults 17
. Over longer durations of training (i.e. 8 weeks), creatine supplementation increases intramuscular protein levels of IGF-1 7. Creatine may also have anti-catabolic properties. Creatine decreases urinary excretion of 3-methylhistidine, an indicator of muscle protein catabolism, in older men during resistance exercise training10
and whole body protein breakdown (e.g., plasma leucine rate of appearance) in younger men 24
Strategic creatine ingestion
Muscle hypertrophy following resistance training requires net synthesis of myofibrillar proteins and therefore, maximal stimulation of muscle protein synthesis is required for the development of muscle mass 9
. It is well established that the mechanical stimulus from resistance training results in increased protein catabolism and subsequent protein synthesis 25
. Although the machinery for stimulating the synthetic rate of muscle proteins is increased after exercise 31
, it appears that this response may not be increased until some time after the resistance training session 29
. Recent evidence suggests that creatine ingestion, in close proximity to resistance training sessions (i.e., before and after exercise), may be more beneficial than ingesting creatine at other times of the day. For example, in the most recent study, creatine ingestion immediately before (0.1g∙kg-1
) and immediately after (0.1g∙kg-1
) resistance training sessions for 32 weeks in older adults increased lower and upper body strength compared to placebo 11
. While the mechanisms explaining the greater increase in maximal muscle strength from creatine remain to be elucidated, high-energy phosphate metabolism and actin-myosin cross-bridge cycling may be involved. Creatine is a component of phosphocreatine which rapidly rephosphorylates adenosine diphosphate to help maintain adenosine triphosphate during resistance training. Regarding actin-myosin cross bridge cycling, creatine may increase calcium re-uptake into the sarcoplasmic reticulum which would result in faster detachment of the actin-myosin cross-bridge and potentially augment force generating capacity 4
. Interestingly, post-exercise creatine resulted in greater gains in lean tissue mass compared to placebo 11
. In comparing the effects of creatine (5 grams) immediately before and immediately after resistance training (20 sessions) in young males, Antonio and Ciccone 1
found slightly greater increases in muscle mass and strength from post-exercise creatine ingestion. Potentially, the greater muscle benefits from post-exercise creatine may be due to an increase in skeletal muscle blood flow during resistance training which would result in greater creatine transport and accumulation in exercising muscles. With repeated training sessions, elevated intramuscular creatine stores may effectively influence genes, signalling pathways 27
, transcription factors 32
, satellite cells 23
and anabolic hormones (i.e. insulin-like growth factor 1; 7, 17) involved in skeletal muscle hypertrophy. Furthermore, creatine immediately before (0.05g•kg-1
) and immediately after (0.05g•kg-1
) resistance training sessions (3 days/week, 10 weeks) resulted in greater whole-body muscle hypertrophy (2.0 ± 0.3cm) compared to placebo (0.8 ± 0.3cm) and resistance training in healthy older males (59-77 years; 10). Older adults supplementing with creatine also had a reduction in urinary excretion of 3- methylhistidine, an indicator of muscle protein catabolism, by 40% compared to an increase of 29% for the placebo group; suggesting that creatine exhibits muscle anti-catabolic properties. These results support previous findings of a significant increase in lean tissue mass (6%), type II muscle fiber area (29%), and insulin growth-factor I (78%) in adults (19-55 years) who ingested creatine before (0.03g•kg-1
) and after (0.03g•kg-1
) resistance training (6 days/week, 8 weeks; 7). Interestingly, in comparing the effects of creatine ingestion before (0.5g•kg-1
) and after (0.5g•kg-1
) resistance training (10 weeks) to creatine ingestion in the morning and evening of training days, Cribb & Hayes 14
showed that creatine ingestion before and after exercise resulted in significantly greater intramuscular creatine content, lean tissue mass, and muscle cross sectional-area of type II fibers.
Results across studies suggest that the timing of creatine ingestion is important. Pre- and post-exercise creatine supplementation produce similar beneficial effects with slightly greater adaptations from post-exercise creatine. Independent of the timing of ingestion, creatine is superior to placebo for augmenting the physiological gains from resistance training in young and older adults.
The combination of creatine and whey protein may further enhance the physiological adaptations from resistance exercise. For example, healthy older males (n=10) who ingested creatine (0.1 g∙kg-1
) and whey protein (0.3 g∙kg-1
) during 10 weeks of supervised whole-body resistance training (3 sets of 10 repetitions to muscle fatigue, 3 days per week; exercises: leg press, chest press, lat pull-down, shoulder press, leg extension, leg curl, triceps extension, biceps curls, calf press) experienced a greater increase in lean tissue mass compared to older men who consumed creatine alone (n=12) or an iso-caloric carbohydrate placebo (n=13) 10
. In younger men, the co-ingestion of creatine (0.1 g∙kg-1
) and whey protein (1.2 g∙kg-1
) during 6 weeks of heavy resistance training produced greater gains in lean tissue mass and bench press strength compared to men who consumed whey protein alone or placebo during training 8
. Furthermore, trained bodybuilders who consumed creatine (0.1 g∙kg-1
) and whey protein (1.5 g∙kg-1
) during resistance exercise experienced greater gains in lean body mass, and maximum strength compared to bodybuilders who consumed protein or carbohydrate alone 14, 15
. Whey protein (a component of milk) has a high essential amino acid profile and is rapidly absorbed upon digestion 5
and increases the rates of muscle protein synthesis following resistance exercise 13
. Therefore, the greater increase in muscle accretion from the co-ingestion of creatine and whey protein may be the result of a synergistic anabolic effect from these dietary compounds.
Practical Application and Take Home Points
1. Creatine increases muscle mass and muscle performance in young and older adults
2. A daily dosage of 8-10 grams appears optimal
3. Pre- and post-exercise creatine supplementation is important
4. Post-exercise creatine appears to be an optimal strategy
5. Combining creatine (8-10 grams) and whey protein (30-40grams) post-exercise is an effective strategy to maximise muscle mass and muscular performance.
Written by ACA Contributor Dr Darren Candow
Dr. Darren Candow, PhD, CSEP-CEP, is Professor and Associate Dean-Graduate Studies and Research in the Faculty of Kinesiology & Health Studies. Dr. Candow supervises the Aging Muscle and Bone Health Laboratory, and serves on the editorial board for the Journal of Aging and Physical Activity, Journal of the International Society of Sports Nutrition, and Biogerontology. Dr. Candow's research program involves the development of effective resistance training and nutritional intervention strategies for improving properties of muscle and bone health. Dr. Candow's research is funded by the Canadian Institutes of Health Research (CIHR), Canada Foundation for Innovation (CFI), the Saskatchewan Health Research Foundation (SHRF), and the Nutricia Research Foundation.
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