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Comparison of Creatine Supplementation Before Versus After Supervised Resistance Training in Healthy Older Adults a
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Darren G. Candow , Gordon A. Zello , Binbing Ling , Jonathan P. c
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Farthing , Philip D. Chilibeck , Katherine McLeod , Jonathan Harris & Shanthi Johnson
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Faculty of Kinesiology and Health Studies, University of Regina, Regina, Saskatchewan, Canada
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College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada c
College of Kinesiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Published online: 06 Jan 2014.
To cite this article: Darren G. Candow, Gordon A. Zello, Binbing Ling, Jonathan P. Farthing, Philip D. Chilibeck, Katherine McLeod, Jonathan Harris & Shanthi Johnson (2014) Comparison of Creatine Supplementation Before Versus After Supervised Resistance Training in Healthy Older Adults, Research in Sports Medicine: An International Journal, 22:1, 61-74, DOI: 10.1080/15438627.2013.852088 To link to this article: http://dx.doi.org/10.1080/15438627.2013.852088
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Research in Sports Medicine, 22:61–74, 2014 Copyright © Taylor & Francis Group, LLC ISSN: 1543-8627 print/1543-8635 online DOI: 10.1080/15438627.2013.852088
Comparison of Creatine Supplementation Before Versus After Supervised Resistance Training in Healthy Older Adults Downloaded by [Florida International University] at 11:38 28 December 2014
DARREN G. CANDOW Faculty of Kinesiology and Health Studies, University of Regina, Regina, Saskatchewan, Canada
GORDON A. ZELLO and BINBING LING College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
JONATHAN P. FARTHING and PHILIP D. CHILIBECK College of Kinesiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
KATHERINE McLEOD, JONATHAN HARRIS, and SHANTHI JOHNSON Faculty of Kinesiology and Health Studies, University of Regina, Regina, Saskatchewan, Canada
This study was performed to compare the effects of creatine supplementation (CR) before vs. after supervised resistance training (RT) in healthy older adults. Participants were randomized to one of two groups: CR-Before (0.1g•kg−1 creatine before + 0.1g•kg−1 placebo [rice flour] after RT, n = 11) or CR-After (placebo before + creatine after RT, n = 11). Resistance training (RT) was performed 3 days/week, on nonconsecutive days, for 12 weeks. Prior to and following the study, measures were taken for body composition, maximum strength, muscle protein catabolism, and kidney function. Over the 12-week training period, both groups experienced a significant increase in whole-body lean tissue mass, limb muscle thickness, and upper and lower body strength and a decrease in muscle protein catabolism ( p < 0.001), with no differences
Received 28 June 2012; accepted 30 November 2012. Address correspondence to Darren G. Candow, Ph.D., Associate Professor, Faculty of Kinesiology and Health Studies, Centre on Aging and Health, University of Regina, Regina, SK, S4S 0A2, Canada. E-mail: [email protected] 61
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between groups. There was no change in kidney function over time. Changes in muscle mass or strength are similar when creatine is ingested before or after supervised resistance training in older adults. KEYWORDS aging, timing, lean tissue mass, strength, muscle protein catabolism
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INTRODUCTION Sarcopenia is defined as the age-related loss of muscle mass (i.e., 1%–2% per year after 50 years of age; (Abellan van Kan, 2009), which has a negative effect on strength (i.e., 1.5% decline between the ages of 50 and 60, and 3% per year thereafter; von Haehling, Morley, & Anker, 2010) and the ability to perform tasks of daily living (Short & Nair, 2001). It is well established that resistance training has a positive effect on aging muscle biology (Forbes, Little, & Candow, 2012). Furthermore, there is a growing body of evidence suggesting that creatine supplementation, when consumed in conjunction with resistance training, can further augment aging muscle accretion and strength (for reviews see Candow, 2011; Candow & Chilibeck, 2008; Forbes et al., 2012). Creatine is a nitrogen-containing compound synthesized in the body from glycine, arginine, and methionine and is also found in the diet, primarily in red meat and seafood (Wyss & Kaddurah-Daouk, 2000). Creatine ingestion, in close proximity to resistance training sessions, may be an important and unique strategy for increasing muscle mass and strength (Candow & Chilibeck, 2008). For example, healthy older men who consumed creatine immediately before and immediately after resistance training sessions for 10 weeks experienced a greater increase in lean tissue mass and muscle thickness and a decrease in muscle protein catabolism compared with placebo (Candow et al., 2008). Creatine immediately before and after resistance training sessions for 6 weeks also led to a significant increase in upperlimb muscle accretion in young adults compared with placebo (Candow et al., 2011). Furthermore, in trained athletes, creatine before and after resistance training sessions for 10 weeks increased lean tissue mass and muscle cross-sectional areas of type II fibers compared with consuming creatine in the morning and evening on exercise training days (Cribb & Hayes, 2006). Results across studies suggest that the strategic ingestion of creatine before and after resistance training sessions is important for improving muscle mass and strength possibly because of exercise-induced blood flow and greater delivery of creatine to exercising muscles (Harris, Soderlund, & Hultman, 1992). Accelerated creatine uptake may subsequently enhance hypertrophy of aging muscle through an increase in satellite cell activity (Dangott, Schultz, & Mozdziak, 2000; Olsen et al., 2006), pathways involved in muscle protein
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synthesis (Safdar, Yardley, Snow, Melov, & Tarnopolsky, 2008), anabolic hormone secretion (i.e., insulin-like growth factor 1; Burke et al., 2008), myogenic transcription factors (Willoughby & Rosene, 2003), or by reducing protein catabolism (Candow et al., 2008). A key deficit in the literature, however, is that no study has directly examined whether creatine supplementation before vs. after resistance training sessions is more beneficial for stimulating muscle accretion and strength in older adults. It was hypothesized that creatine supplementation before resistance training would lead to greater physiological adaptations compared with creatine after exercise based on the findings of Louis et al. (2003), who showed that 5 days of creatine supplementation before performing an acute bout of resistance training in young males resulted in a 21% increase in total muscle creatine content (23 ± 3.1 to 27.9 ± 4.7 umol/g) and that creatine ingestion before training sessions helped improve muscle mass and strength (Candow et al., 2008, 2011; Cribb & Hayes, 2006). Creatine supplementation leads to greater gains in muscle mass and strength compared with placebo during resistance training in older adults (Brose, Parise, & Tarnopolsky, 2003; Candow et al., 2008; Chrusch, Chilibeck, Chad, Davison, & Burke, 2001). Therefore, the purpose of this study was to directly compare the effects of creatine supplementation before vs. after resistance training in healthy older adults.
METHODS Participants Twenty-two healthy adults (50–64 yrs of age, 9 male, 13 female) who were not engaged in resistance training for 6 weeks prior to the start of the study were recruited to participate. We chose to use non-resistance trained participants as they have been shown to respond more favorably to creatine supplementation and resistance training (Candow et al., 2011). Participants were required to fill out a leisure time exercise questionnaire where the number of times on average per week strenuous (i.e., heart beats rapidly), moderate (i.e., not exhausting), and mild exercise (i.e., minimal effort) were performed (Godin & Shephard, 1985). Participants were also required to fill out a Physical Activity Readiness Questionnaire, which assesses an individual’s readiness for participation in exercise training programs and includes questions related to heart conditions, angina at rest or during physical exercise, balance, and bone or joint problems that may affect exercise performance (Thomas, Reading, & Shephard, 1992). Participants were excluded if they had supplemented with creatine within the past 6 weeks, if they were vegetarians, if they consumed more than 200 mg of caffeine daily as this dosage of caffeine may impair creatine metabolism (Vandenberghe et al., 1996), and if they had preexisting kidney abnormalities. Participants were instructed not to change their diet or engage in additional physical activity that was not part of their normal daily routine. The study was approved
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by the university ethics review board for research in human subjects at the University of Regina. Participants were informed of any risks and purpose of the study before their written consents were obtained.
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Experimental Procedures The study was a double-blind, repeated measures design in which all participants participated in resistance training and were randomized to supplement with creatine, only on training days (3 days per week), for 12 weeks. Prior to the first visit to the laboratory for initial testing and data collection, participants were instructed to refrain from physical activity for 48 hours, alcohol for 24 hours, and food and drink for 2 hours. The dependent variables measured before and after 12 weeks follow: (1) lean tissue mass, (2) muscle thickness of the elbow and knee flexors and extensors, (3) strength (leg press and chest press one repetition maximum; 1-RM), (4) urinary 3-methylhistidine excretion (an index of muscle protein catabolism), and (5) urinary microalbumin (an indicator of kidney function). In addition, participants completed dietary records for 3 days during the first and final week of resistance training and supplementation to assess nutrient differences between groups. At the end of the study, participants were asked whether they perceived to be on the creatine supplement or placebo. Detailed procedures for lean tissue mass, muscle strength, dietary analysis, and muscle protein catabolism (Candow, Chilibeck, Facci, Abeysekara, & Zello, 2006), muscle thickness (Candow & Chilibeck, 2005), and kidney function (Cornish et al., 2009) are described in detail elsewhere; therefore, only a brief description of these procedures is provided.
Randomization and Supplementation A research assistant, who was not involved in any other part of the study, was responsible for randomizing the participants and coding the supplements to ensure all participants and investigators remained blinded throughout the study. Using a computer generated allocation schedule, participants were randomly assigned to one of two groups: CR-Before (0.1g•kg−1 creatine before + 0.1g•kg−1 placebo [rice flour] after resistance training, n = 11, 4 male, 7 female) and CR-After (placebo before + creatine after resistance training, n = 11, 5 male, 6 female). The creatine dosage (0.1g•kg−1 or ∼8 grams) was chosen because this amount has been shown to increase muscle mass and strength, without resulting in adverse effects, in young and older adults (Candow et al., 2008, 2011). Creatine and placebo were identical in taste, texture, color, and appearance. Participants consumed creatine or placebo, with water, immediately before (i.e., 5 minutes) and immediately after (i.e., 5 minutes) each resistance training session as the purpose of the study was to directly compare the effects of creatine before vs. after
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resistance training. Responders to creatine supplementation were classified as having a net gain in whole-body lean tissue mass over the training period, whereas nonresponders were classified as having no change or a net loss in whole-body lean tissue mass.
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Resistance Training Program Prior to the start of the study, each participant familiarized him or herself with the resistance training equipment for 1 week. Participants followed the same supervised whole-body resistance training program combined with creatine or placebo for 12 weeks. Prior to training sessions, but after the supplement was consumed, each participant performed a 5-minute aerobic warm-up at a self-selected intensity. Participants completed 3 sets of 10 repetitions to muscle fatigue with a 2-minute rest between sets for each exercise at an intensity corresponding to their 10 repetition maximum for each exercise. Resistance exercises included leg press, chest press, lat pull-down, shoulder press, leg (knee) extension, leg curl (knee flexion), triceps extension, biceps curl, and calf press. Participants maintained daily training logs where the load, number of sets, and repetitions were recorded. Resistance was increased by 2–5 kg once a subject could complete 3 sets of 10 repetitions to muscle fatigue for an exercise. Once the resistance was increased, participants maintained this load until a subsequent 3 sets of 10 repetitions to fatigue were completed.
Lean Tissue Mass Whole-body lean tissue mass was assessed by air-displacement plethysmography (BOD POD, Life Measurement Inc., Concord, CA). The coefficient of variation for lean tissue mass was 0.84% (Candow et al., 2006).
Muscle Thickness Elbow and knee flexor and extensor muscle thickness was measured using B-Mode ultrasound (Aloka SSD-500 Tokyo, Japan). The coefficients of variation for muscle thickness measurements were 2.6% for elbow flexors, 1.7% for elbow extensors, 3.1% for knee flexors, and 0.9% for knee extensors (Candow & Chilibeck, 2005).
Muscle Strength Leg press and chest press strength was assessed using a 1-repetition maximum (1-RM) standard testing procedure. Following 5 minutes of cycling on a stationary cycle ergometer, participants performed two warm-up sets in order: 1 set of 10 repetitions using a weight determined by each subject
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to be comfortable and 1 set of 5 repetitions using increased weight. Two minutes following the warm-up sets, weight was progressively increased for each subsequent 1-RM attempt with a 2-minute rest interval. The 1-RM was reached in 4–6 trials, independent of the 2 warm-up sets. The leg press and chest press strength measures had coefficients of variation of 3.8% and 3.1%, respectively (Candow et al., 2006).
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Muscle Protein Catabolism and Kidney Function For the measurement of 3-methylhistidine, an index of muscle protein catabolism, urine was collected during the last 24 hours of a 72-hour meat-free diet immediately before and immediately after the study. A meatfree diet was implemented because meat consumption increases urinary 3-methylhistidine values and may falsely represent an increase in muscle protein catabolism (Lukaski, Mendez, Buskirk, & Cohn, 1981). Three days of a meat-free diet are required to return 3-methylhistidine levels to baseline (Lukaski et al., 1981). The designated urine collection procedure was to discard the first urination upon waking in the morning and then collect all urine samples for 24 hours, including the first urination upon waking the following morning. The concentration of 3-methylhistidine was measured using high-performance liquid chromatography (HPLC, Agilent 1200, Agilent Technologies, Palo Alto, CA, USA) following precolumn derivations with fluorescamine with slight modifications of a previously described method (Wassner, Schlitzer, & Li, 1980). The daily amount of 3-methylhistidine excreted by each participant was determined by multiplying the concentration by the 24-hour urine volume. The intra-assay coefficient of variation for 3-methylhistidine is 5.1% (Candow et al., 2006). To measure microalbumin, an indicator of kidney function, 24-hour urine samples were obtained prior to and following supplementation and resistance training. Microalbumin was measured using immunochromatographic lateral flow membrane test strips containing specific monoclonal antibody against human albumin (Genzyme Diagnostics, Charlottetown, PEI, Canada). The test gives one of three results: microalbumin less than 18 mg·L−1 , equal to 18 mg·L−1 , or greater than 18 mg·L−1 . A test greater than 18 mg·L−1 indicates compromised kidney function.
Dietary Assessment Dietary intake was recorded during the first and final week of supplementation and resistance training (outside of the meat-free diet period that was required for the 3-methylhistidine assessment) to assess differences in total energy and macronutrient composition between the CR-Before and CR-After groups. Participants used a 3-day food booklet to record what they ate for 2 weekdays and 1 weekend day. Participants were instructed to record all
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food items, including portion sizes consumed for the 3 designated days. The Interactive Healthy Eating Index (Center for Nutrition Policy and Promotion, United States Department of Agriculture; http://www.usda.gov/cnpp/) was used to analyze 3-day food records.
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Statistical Analyses A 2 (CR-Before vs. CR-After) × 2 (pre- and post-test periods) ANOVA with repeated measures on the second factor was used to determine differences between groups over time for each of the dependent variables of lean tissue mass, muscle thickness, strength, 3-methylhistidine, microalbumin, and diet. A one-factor ANOVA was used to determine whether there were differences in baseline measurements between groups and to determine differences between males and females on creatine. Statistical analyses were carried out using SPSS version 11.0 for Windows XP (SPSS, Chicago, IL, USA). Significance was set at p < 0.05. All results are expressed as mean ± SD.
RESULTS Participant characteristics and physical activity performed at baseline are found in Table 1. Dietary intakes (i.e., total calories, carbohydrates, fats, proteins; Table 2) and body mass at baseline and after the intervention were not different between groups. There were no differences in the volume of resistance training performed between groups over time (CR-Before: 14911 ± 5460 kg; Cr-After: 13537 ± 6481 kg). Thirteen participants did not know whether they were supplementing with creatine or placebo, while 9 participants correctly guessed which supplement they were ingesting. There were no adverse effects from creatine supplementation or placebo reported. Over the 12 weeks of training, both groups experienced a significant increase in lean tissue mass (CR-Before: 1.4 ± 0.4 kg, CR-After: 1.9 ± 0.7 kg, p < 0.001; Figure 1), muscle thickness (elbow and knee flexor and extensors combined: CR-Before: 1.8 ± 0.7 cm, CR-After: 1.9 ± 0.8 cm, p < 0.001; Table 3), muscle strength (leg press: CR-Before: 51.8 ± 27.8 kg, CR-After: 45.0 ± 30.0 kg, Figure 2; chest press: CR-Before: 24.1 ± 21.1 kg CR-After: 21.2 ± 16.0 kg, p < 0.001; Figure 3), and a decrease in muscle protein catabolism (CR-Before: -119.5 ± 132.2 mmol 3-MH/24 hr, CR-After: -167.2 ± 5.4 mmol 3-MH/24 hr, p < 0.001; Figure 4), with no differences between groups. All measures for urinary microalbumin before and after training and supplementation were less than 18 mg·L−1 .
68 56 (4) 55 (2)
Age (years)
Values are expressed as mean (standard deviation).
CR-Before (4 male, 7 female) CR-After (5 male, 6 female)
Group 77 (19) 79 (14)
Body mass (kg) 167 (7) 170 (10)
Height (cm)
TABLE 1 Participant Characteristics and Physical Activity Performed at Baseline
2 (2) 3 (2)
Strenuous activity (times per week)
3 (2) 2 (1)
Moderate activity (time per week)
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4 (3) 4 (2)
Mild activity (times per week)
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TABLE 2 Total Calories (Kcal/Day) and Macronutrient (Grams/Day) Content of Creatine Groups for 3 Days During the First and Final Week of Supplementation and Training CR-Before (n = 9) Week 1 1715.0 241.2 86.1 133.6
Week 12
(320.0) (79.3) (32.9) (51.6)
1922.6 201.4 94.6 108.7
(771.2)∗ (54.2)∗ (45.3) (36.5)∗
Week 1 1999.8 238.2 75.4 91.9
Week 12
(750.0) (81.5) (29.8) (38.8)
1795.3 201.0 73.6 82.1
(664.0)∗ (63.8)∗ (30.1) (34.4)∗
Values are means (standard deviation). Data are based on the average for one day from 3-day food records. ∗ Indicates significantly different over time (p < 0.05).
Pre
100 Lean Tissue Mass (kg)
Post 80
*
*
60 40 20 0 CR-Before
CR-After
FIGURE 1 Change in lean tissue mass after 12 weeks of supplementation and resistance training for CR-Before (n = 11) and Cr-After (n = 11) groups. Values are expressed as mean ± standard deviation. ∗ Significant increase over time (p < 0.05). Pre
300 Leg Press Strength (kg)
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Kilocalories Carbohydrates Fat Protein
CR-After (n = 7)
*
*
250
Post
200 150 100 50 0 CR-Before
CR-After
FIGURE 2 Change in leg press strength after 12 weeks of supplementation and resistance training for CR-Before (n = 11) and Cr-After (n = 11) groups. Values are expressed as mean ± standard deviation. ∗ Significant increase over time (p < 0.05).
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Pre Post
150
*
120
*
90 60 30 0 CR-Before
CR-After
FIGURE 3 Change in chest press strength after 12 weeks of supplementation and resistance training for CR-Before (n = 11) and Cr-After (n = 11) groups. Values are expressed as mean ± standard deviation. ∗ Significant increase over time (p < 0.05). Pre
1000 3-MH (mmol 3-MH/24 hr)
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Chest Press Strength (kg)
D. G. Candow et al.
Post 800 600 *
*
400 200 0 CR-Before
CR-After
FIGURE 4 Change in 3-methylhistidine after 12 weeks of supplementation and resistance training for CR-Before (n = 11) and Cr-After (n = 11) groups. 3MH = 3-methylhisditine. Values are expressed as mean ± standard deviation. ∗ Significant decrease over time (p < 0.05).
Females supplementing with creatine (n = 13) experienced a greater relative increase (postmean – premean / premean × 100%) in leg press (30 ± 10%) and chest press strength (87 ± 57%) compared with males on creatine (n = 9; leg press: 19 ± 13%; chest press: 36 ± 35%; p < 0.05). Males supplementing with creatine experienced a greater relative increase in knee extensor muscle thickness (15 ± 8%) compared with females on creatine (4 ± 4%; p < 0.05). There were no other gender differences. Three participants (1 female in the creatine before group; 1 male and 1 female in the creatine after group) did not respond to creatine supplementation.
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DISCUSSION This was the first study to directly compare the effects of creatine supplementation immediately before versus after resistance training in healthy older adults. Results showed similar gains in muscle accretion and strength from creatine, independent of the timing of ingestion. Unfortunately, without a placebo control for comparison, we cannot conclude that creatine supplementation had a greater effect over resistance training alone. We have previously demonstrated, however, that creatine supplementation before and after resistance training (6–12 weeks) led to greater gains in muscle mass and strength compared with placebo (Candow et al., 2008, 2011; Chilibeck, Stride, Farthing, & Burke, 2004; Chrusch et al., 2001). Older men who ingested creatine (0.1g•kg−1 ) immediately before and after resistance training sessions for 10 weeks experienced greater muscle accretion compared with the placebo group (Candow et al., 2008). In young adults, creatine (0.1–0.15g•kg−1 ) immediately before and after resistance training for 6 weeks resulted in greater elbow flexor muscle thickness compared with placebo (Candow et al., 2011). Mechanistically, creatine supplementation may improve aging muscle mass and strength by increasing satellite cell activity (Dangott, et al., 2000; Olsen et al., 2006), pathways involved in muscle protein synthesis (Safdar et al., 2008), anabolic hormone secretion (Burke et al., 2008), myogenic transcription factors (Willoughby & Rosene, 2003), or by reducing protein catabolism (Candow et al., 2008). We previously showed that creatine supplementation in older adults reduced urinary excretion of 3-methylhistidine, an indicator of muscle protein catabolism, by 40% compared with an increase of 29% for placebo (Candow et al., 2008). In the present study, we found a reduction (23%–43%) in 3-methylhistidine between creatine groups over time. Although speculative, the lack of differences between the two creatine supplementation protocols may be related to creatine absorption kinetics (Preen et al., 2002). Lower-dose creatine supplementation (1–10 grams) TABLE 3 Muscle Thickness Measurements (cm) for the Elbow and Knee Flexors and Extensors Before and After 12 Weeks of Creatine Supplementation and Resistance Training CR-Before (n = 11) Muscle group Elbow flexors Elbow extensors Knee flexors Knee extensors Ave. total change
Pre 3.7 3.8 5.0 4.5
(0.8) (0.6) (0.6) (0.6)
Post 4.0 4.4 5.5 4.9
CR-After (n = 11) %
∗
(1.0) (1.0)∗ (0.6)∗ (0.8)∗
8.0 13.0 10.8 8.6 10.1
(13.1) (9.0) (8.9) (8.9) (10.0)
Pre 3.8 3.6 5.0 4.4
(0.9) (0.6) (0.7) (0.6)
Post 4.4 4.1 5.4 4.8
% ∗
(1.0) (0.7)∗ (0.6)∗ (0.6)∗
Values are expressed as mean (standard deviation). % = percent change over time. ∗ Significant increase with training (p < 0.05).
18 (18.8) 9.8 (13.0) 10.4 (16.9) 8.7 (6.6) 11.7 (13.8)
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reaches peak maximal plasma concentration (T max) at ≤ 2 hours (Harris et al., 1992; Schedel, Tanaka, Kiyonaga, Shindo, & Schutz, 1999). In the present study, we administered a creatine dosage of approximately 8 grams immediately before or after each training session, which lasted approximately 1 hour, for 12 weeks. Therefore, creatine concentrations may not have reached maximum until 1–2 hours postexercise, resulting in reduced intramuscular creatine uptake from dissipating blood flow after exercise, which could have influenced our ability to detect significant differences between the creatine interventions. A limitation in our study design, as noted earlier, is that we did not include a placebo control group for comparison to creatine supplementation. Although not the primary objective of this study, the lack of a placebo eliminates our ability to determine whether creatine supplementation, independent of the timing of ingestion, was more effective than resistance training alone. Furthermore, muscle biopsies were not performed, which diminishes our ability to assess intramuscular creatine concentrations at baseline and after creatine supplementation. In addition, blood flow kinetics, muscle fiber type composition, muscle cross-sectional area, myogenic transcription factors, or hormonal properties were not measured in this study.
CONCLUSIONS Healthy older adults supplementing with creatine before and after resistance training sessions experienced similar gains in muscle mass and strength after 12 weeks of training. The timing of creatine ingestion did not influence the adaptations from resistance training. Future research should directly compare the longer-term (>12 weeks), mechanistic actions of creatine supplementation before, during, and after resistance training with a placebo control to determine the optimal creatine dosing and frequency strategies for older adults.
ACKNOWLEDGMENTS Creatine and placebo were donated by Rivalus Inc.
REFERENCES Abellan van Kan, G. (2009). Epidemiology and consequences of sarcopenia. Journal of Nutrition, Health and Aging, 13(8), 708–712. Brose, A., Parise, G., & Tarnopolsky, M. A. (2003). Creatine supplementation enhances isometric strength and body composition improvements following
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strength exercise training in older adults. Journal of Gerontology and Biological and Medical Sciences, 58, 11–19. Burke, D. G., Candow, D. G., Chilibeck, P. D., MacNeil, L. G., Roy, B. D., Tarnopolsky, M. A., & Ziegenfuss, T. (2008). Effect of creatine supplementation and resistance-exercise training on muscle insulin-like growth factor in young adults. International Journal of Sport Nutrition and Exercise Metabolism, 18(4), 389–398. Candow, D. G. (2011). Sarcopenia: Current theories and the potential beneficial effect of creatine application strategies. Biogerontology, 12(4), 273–281. Candow, D. G., Burke, D. G., Chilibeck, P. D., Mueller, K., Lewis, J., & Lazorko, J. (2011). Effect of different frequencies of creatine supplementation on muscle size and strength in young adults. Journal of Strength and Conditioning Research, 25(7), 1831–1838. Candow, D. G., & Chilibeck, P. D. (2005). Differences in size, strength, and power of upper and lower body muscle groups in young and older men. Journal of Gerontololgy and Biological and Medical Sciences, 60(2), 148–156. Candow, D. G., & Chilibeck, P. D. (2008). Timing of creatine or protein supplementation and resistance training in the elderly. Applied Physiology, Nutrition and Metabolism, 33(1), 184–190. Candow, D. G., Chilibeck, P. D., Facci, M., Abeysekara, S., & Zello, G. A. (2006). Protein supplementation before and after resistance training in older men. European Journal of Applied Physiology, 97(5), 548–556. Candow, D. G., Little, J. P., Chilibeck, P. D., Abeysekara, S., Zello, G., Kazachhov, M. . . . Yu, P. H. (2008). Low-dose creatine combined with protein during resistance training in older men. Medicine and Science in Sports and Exercise, 40, 1645–1652. Chilibeck, P. D., Stride, D., Farthing, J. P., & Burke, D. G. (2004). Effect of creatine ingestion after exercise on muscle thickness in males and females. Medicine and Science in Sports and Exercise, 36(10), 1781–1788. Chrusch, M. J., Chilibeck, P. D., Chad, K. E., Davison, K. S., & Burke, D. G. (2001). Creatine supplementation combined with resistance training in older men. Medicine and Science in Sports and Exercise, 33(12), 2111–2117. Cornish, S. M., Candow, D. G., Jantz, N. T., Chilibeck, P. D., Little, J. P., Forbes, S., . . . Zello, G. A. (2009). Conjugated linoleic acid combined with creatine monohydrate and whey protein supplementation during strength training. International Journal of Sport Nutrition and Exercise Metabolism, 19(1), 79–96. Cribb, P. J., & Hayes, A. (2006). Effects of supplement timing and resistance exercise on skeletal muscle hypertrophy. Medicine and Science in Sports and Exercise, 38(11), 1918–1925. Dangott, B., Schultz, E., & Mozdziak, P. E. (2000). Dietary creatine monohydrate supplementation increases satellite cell mitotic activity during compensatory hypertrophy. International Journal of Sports Medicine, 21(1), 13–16. Forbes, S. C., Little, J. P., & Candow, D. G. (2012). Exercise and nutritional interventions for improving aging muscle health. Endocrine, 42(1), 29–38. Godin, G., & Shephard, R. J. (1985). A simple method to assess exercise behavior in the community. Canadian Journal of Applied Sport Science, 10(3), 141–146.
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Harris, R. C., Soderlund, K., & Hultman, E. (1992). Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clinical Science (London), 83(3), 367–374. Louis, M., Poortmans, J. R., Francaux, M., Berré, J., Boisseau, N., Brassine, E. . . . Rennie, M. J. (2003). No effect of creatine supplementation on human myofibrillar and sarcoplasmic protein synthesis after resistance exercise. American Journal of Physiology-Endocrinology and Metabolism, 285(5), E1089–E1094. Lukaski, H. C., Mendez, J., Buskirk, E. R., & Cohn, S. H. (1981). Relationship between endogenous 3-methylhistidine excretion and body composition. Americal Journal of Physiology, 240(3), E302–307. Olsen, S., Aagaard, P., Kadi, F., Tufekovic, G., Verney, J. . . . & Kjaer, M. (2006). Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training. Journal of Physiology, 573(Pt 2), 525–534. Preen, D., Dawson, B., Goodman, C., Lawrence, S., Beilby, J., & Ching, S. (2002). Pre-exercise oral creatine ingestion does not improve prolonged intermittent sprint exercise in humans. The Journal of Sports Medicne and Physical Fitness, 42(3), 320–329. Safdar, A., Yardley, N. J., Snow, R., Melov, S., & Tarnopolsky, M. A. (2008). Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation. Physiological Genomics, 32, 219–228. Schedel, J. M., Tanaka, H., Kiyonaga, A., Shindo, M., & Schutz, Y. (1999). Acute creatine ingestion in human: Consequences on serum creatine and creatinine concentrations. Life Sciences, 65(23), 2463–2470. Short, K. R., & Nair, K. S. (2001). Muscle protein metabolism and the sarcopenia of aging. International Journal of Sport Nutrition and Exercise Metabolism, 11(Suppl.), S119–127. Thomas, S., Reading, J., & Shephard, R. J. (1992). Revision of the Physical Activity Readiness Questionnaire (PAR-Q). Canadian Journal of Sport Science, 17(4), 338–345. Vandenberghe, K., Gillis, N., Van Leemputte, M., Van Hecke, P., Vanstapel, F., & Hespel, P. (1996). Caffeine counteracts the ergogenic action of muscle creatine loading. Journal of Applied Physiology, 80(2), 452–457. von Haehling, S., Morley, J. E., & Anker, S. D. (2010). An overview of sarcopenia: Facts and numbers on prevalence and clinical impact. Journal of Cachexia Sarcopenia and Muscle, 1(2), 129–133. Wassner, S. J., Schlitzer, J. L., & Li, J. B. (1980). A rapid, sensitive method for the determination of 3-methylhistidine levels in urine and plasma using high-pressure liquid chromatography. Analytical Biochemistry, 104(2), 284–289. Willoughby, D. S., & Rosene, J. M. (2003). Effects of oral creatine and resistance training on myogenic regulatory factor expression. Medicine and Science in Sports and Exercise, 35(6), 923–929. Wyss, M., & Kaddurah-Daouk, R. (2000). Creatine and creatinine metabolism. Physiological Reviews, 80(3), 1107–1213.
Research in Sports Medicine: An International Journal Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/gspm20
Comparison of Creatine Supplementation Before Versus After Supervised Resistance Training in Healthy Older Adults a
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Darren G. Candow , Gordon A. Zello , Binbing Ling , Jonathan P. c
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Farthing , Philip D. Chilibeck , Katherine McLeod , Jonathan Harris & Shanthi Johnson
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Faculty of Kinesiology and Health Studies, University of Regina, Regina, Saskatchewan, Canada
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College of Kinesiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Published online: 06 Jan 2014.
To cite this article: Darren G. Candow, Gordon A. Zello, Binbing Ling, Jonathan P. Farthing, Philip D. Chilibeck, Katherine McLeod, Jonathan Harris & Shanthi Johnson (2014) Comparison of Creatine Supplementation Before Versus After Supervised Resistance Training in Healthy Older Adults, Research in Sports Medicine: An International Journal, 22:1, 61-74, DOI: 10.1080/15438627.2013.852088 To link to this article: http://dx.doi.org/10.1080/15438627.2013.852088
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Research in Sports Medicine, 22:61–74, 2014 Copyright © Taylor & Francis Group, LLC ISSN: 1543-8627 print/1543-8635 online DOI: 10.1080/15438627.2013.852088
Comparison of Creatine Supplementation Before Versus After Supervised Resistance Training in Healthy Older Adults Downloaded by [Florida International University] at 11:38 28 December 2014
DARREN G. CANDOW Faculty of Kinesiology and Health Studies, University of Regina, Regina, Saskatchewan, Canada
GORDON A. ZELLO and BINBING LING College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
JONATHAN P. FARTHING and PHILIP D. CHILIBECK College of Kinesiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
KATHERINE McLEOD, JONATHAN HARRIS, and SHANTHI JOHNSON Faculty of Kinesiology and Health Studies, University of Regina, Regina, Saskatchewan, Canada
This study was performed to compare the effects of creatine supplementation (CR) before vs. after supervised resistance training (RT) in healthy older adults. Participants were randomized to one of two groups: CR-Before (0.1g•kg−1 creatine before + 0.1g•kg−1 placebo [rice flour] after RT, n = 11) or CR-After (placebo before + creatine after RT, n = 11). Resistance training (RT) was performed 3 days/week, on nonconsecutive days, for 12 weeks. Prior to and following the study, measures were taken for body composition, maximum strength, muscle protein catabolism, and kidney function. Over the 12-week training period, both groups experienced a significant increase in whole-body lean tissue mass, limb muscle thickness, and upper and lower body strength and a decrease in muscle protein catabolism ( p < 0.001), with no differences
Received 28 June 2012; accepted 30 November 2012. Address correspondence to Darren G. Candow, Ph.D., Associate Professor, Faculty of Kinesiology and Health Studies, Centre on Aging and Health, University of Regina, Regina, SK, S4S 0A2, Canada. E-mail: [email protected] 61
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between groups. There was no change in kidney function over time. Changes in muscle mass or strength are similar when creatine is ingested before or after supervised resistance training in older adults. KEYWORDS aging, timing, lean tissue mass, strength, muscle protein catabolism
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INTRODUCTION Sarcopenia is defined as the age-related loss of muscle mass (i.e., 1%–2% per year after 50 years of age; (Abellan van Kan, 2009), which has a negative effect on strength (i.e., 1.5% decline between the ages of 50 and 60, and 3% per year thereafter; von Haehling, Morley, & Anker, 2010) and the ability to perform tasks of daily living (Short & Nair, 2001). It is well established that resistance training has a positive effect on aging muscle biology (Forbes, Little, & Candow, 2012). Furthermore, there is a growing body of evidence suggesting that creatine supplementation, when consumed in conjunction with resistance training, can further augment aging muscle accretion and strength (for reviews see Candow, 2011; Candow & Chilibeck, 2008; Forbes et al., 2012). Creatine is a nitrogen-containing compound synthesized in the body from glycine, arginine, and methionine and is also found in the diet, primarily in red meat and seafood (Wyss & Kaddurah-Daouk, 2000). Creatine ingestion, in close proximity to resistance training sessions, may be an important and unique strategy for increasing muscle mass and strength (Candow & Chilibeck, 2008). For example, healthy older men who consumed creatine immediately before and immediately after resistance training sessions for 10 weeks experienced a greater increase in lean tissue mass and muscle thickness and a decrease in muscle protein catabolism compared with placebo (Candow et al., 2008). Creatine immediately before and after resistance training sessions for 6 weeks also led to a significant increase in upperlimb muscle accretion in young adults compared with placebo (Candow et al., 2011). Furthermore, in trained athletes, creatine before and after resistance training sessions for 10 weeks increased lean tissue mass and muscle cross-sectional areas of type II fibers compared with consuming creatine in the morning and evening on exercise training days (Cribb & Hayes, 2006). Results across studies suggest that the strategic ingestion of creatine before and after resistance training sessions is important for improving muscle mass and strength possibly because of exercise-induced blood flow and greater delivery of creatine to exercising muscles (Harris, Soderlund, & Hultman, 1992). Accelerated creatine uptake may subsequently enhance hypertrophy of aging muscle through an increase in satellite cell activity (Dangott, Schultz, & Mozdziak, 2000; Olsen et al., 2006), pathways involved in muscle protein
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synthesis (Safdar, Yardley, Snow, Melov, & Tarnopolsky, 2008), anabolic hormone secretion (i.e., insulin-like growth factor 1; Burke et al., 2008), myogenic transcription factors (Willoughby & Rosene, 2003), or by reducing protein catabolism (Candow et al., 2008). A key deficit in the literature, however, is that no study has directly examined whether creatine supplementation before vs. after resistance training sessions is more beneficial for stimulating muscle accretion and strength in older adults. It was hypothesized that creatine supplementation before resistance training would lead to greater physiological adaptations compared with creatine after exercise based on the findings of Louis et al. (2003), who showed that 5 days of creatine supplementation before performing an acute bout of resistance training in young males resulted in a 21% increase in total muscle creatine content (23 ± 3.1 to 27.9 ± 4.7 umol/g) and that creatine ingestion before training sessions helped improve muscle mass and strength (Candow et al., 2008, 2011; Cribb & Hayes, 2006). Creatine supplementation leads to greater gains in muscle mass and strength compared with placebo during resistance training in older adults (Brose, Parise, & Tarnopolsky, 2003; Candow et al., 2008; Chrusch, Chilibeck, Chad, Davison, & Burke, 2001). Therefore, the purpose of this study was to directly compare the effects of creatine supplementation before vs. after resistance training in healthy older adults.
METHODS Participants Twenty-two healthy adults (50–64 yrs of age, 9 male, 13 female) who were not engaged in resistance training for 6 weeks prior to the start of the study were recruited to participate. We chose to use non-resistance trained participants as they have been shown to respond more favorably to creatine supplementation and resistance training (Candow et al., 2011). Participants were required to fill out a leisure time exercise questionnaire where the number of times on average per week strenuous (i.e., heart beats rapidly), moderate (i.e., not exhausting), and mild exercise (i.e., minimal effort) were performed (Godin & Shephard, 1985). Participants were also required to fill out a Physical Activity Readiness Questionnaire, which assesses an individual’s readiness for participation in exercise training programs and includes questions related to heart conditions, angina at rest or during physical exercise, balance, and bone or joint problems that may affect exercise performance (Thomas, Reading, & Shephard, 1992). Participants were excluded if they had supplemented with creatine within the past 6 weeks, if they were vegetarians, if they consumed more than 200 mg of caffeine daily as this dosage of caffeine may impair creatine metabolism (Vandenberghe et al., 1996), and if they had preexisting kidney abnormalities. Participants were instructed not to change their diet or engage in additional physical activity that was not part of their normal daily routine. The study was approved
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by the university ethics review board for research in human subjects at the University of Regina. Participants were informed of any risks and purpose of the study before their written consents were obtained.
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Experimental Procedures The study was a double-blind, repeated measures design in which all participants participated in resistance training and were randomized to supplement with creatine, only on training days (3 days per week), for 12 weeks. Prior to the first visit to the laboratory for initial testing and data collection, participants were instructed to refrain from physical activity for 48 hours, alcohol for 24 hours, and food and drink for 2 hours. The dependent variables measured before and after 12 weeks follow: (1) lean tissue mass, (2) muscle thickness of the elbow and knee flexors and extensors, (3) strength (leg press and chest press one repetition maximum; 1-RM), (4) urinary 3-methylhistidine excretion (an index of muscle protein catabolism), and (5) urinary microalbumin (an indicator of kidney function). In addition, participants completed dietary records for 3 days during the first and final week of resistance training and supplementation to assess nutrient differences between groups. At the end of the study, participants were asked whether they perceived to be on the creatine supplement or placebo. Detailed procedures for lean tissue mass, muscle strength, dietary analysis, and muscle protein catabolism (Candow, Chilibeck, Facci, Abeysekara, & Zello, 2006), muscle thickness (Candow & Chilibeck, 2005), and kidney function (Cornish et al., 2009) are described in detail elsewhere; therefore, only a brief description of these procedures is provided.
Randomization and Supplementation A research assistant, who was not involved in any other part of the study, was responsible for randomizing the participants and coding the supplements to ensure all participants and investigators remained blinded throughout the study. Using a computer generated allocation schedule, participants were randomly assigned to one of two groups: CR-Before (0.1g•kg−1 creatine before + 0.1g•kg−1 placebo [rice flour] after resistance training, n = 11, 4 male, 7 female) and CR-After (placebo before + creatine after resistance training, n = 11, 5 male, 6 female). The creatine dosage (0.1g•kg−1 or ∼8 grams) was chosen because this amount has been shown to increase muscle mass and strength, without resulting in adverse effects, in young and older adults (Candow et al., 2008, 2011). Creatine and placebo were identical in taste, texture, color, and appearance. Participants consumed creatine or placebo, with water, immediately before (i.e., 5 minutes) and immediately after (i.e., 5 minutes) each resistance training session as the purpose of the study was to directly compare the effects of creatine before vs. after
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resistance training. Responders to creatine supplementation were classified as having a net gain in whole-body lean tissue mass over the training period, whereas nonresponders were classified as having no change or a net loss in whole-body lean tissue mass.
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Resistance Training Program Prior to the start of the study, each participant familiarized him or herself with the resistance training equipment for 1 week. Participants followed the same supervised whole-body resistance training program combined with creatine or placebo for 12 weeks. Prior to training sessions, but after the supplement was consumed, each participant performed a 5-minute aerobic warm-up at a self-selected intensity. Participants completed 3 sets of 10 repetitions to muscle fatigue with a 2-minute rest between sets for each exercise at an intensity corresponding to their 10 repetition maximum for each exercise. Resistance exercises included leg press, chest press, lat pull-down, shoulder press, leg (knee) extension, leg curl (knee flexion), triceps extension, biceps curl, and calf press. Participants maintained daily training logs where the load, number of sets, and repetitions were recorded. Resistance was increased by 2–5 kg once a subject could complete 3 sets of 10 repetitions to muscle fatigue for an exercise. Once the resistance was increased, participants maintained this load until a subsequent 3 sets of 10 repetitions to fatigue were completed.
Lean Tissue Mass Whole-body lean tissue mass was assessed by air-displacement plethysmography (BOD POD, Life Measurement Inc., Concord, CA). The coefficient of variation for lean tissue mass was 0.84% (Candow et al., 2006).
Muscle Thickness Elbow and knee flexor and extensor muscle thickness was measured using B-Mode ultrasound (Aloka SSD-500 Tokyo, Japan). The coefficients of variation for muscle thickness measurements were 2.6% for elbow flexors, 1.7% for elbow extensors, 3.1% for knee flexors, and 0.9% for knee extensors (Candow & Chilibeck, 2005).
Muscle Strength Leg press and chest press strength was assessed using a 1-repetition maximum (1-RM) standard testing procedure. Following 5 minutes of cycling on a stationary cycle ergometer, participants performed two warm-up sets in order: 1 set of 10 repetitions using a weight determined by each subject
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to be comfortable and 1 set of 5 repetitions using increased weight. Two minutes following the warm-up sets, weight was progressively increased for each subsequent 1-RM attempt with a 2-minute rest interval. The 1-RM was reached in 4–6 trials, independent of the 2 warm-up sets. The leg press and chest press strength measures had coefficients of variation of 3.8% and 3.1%, respectively (Candow et al., 2006).
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Muscle Protein Catabolism and Kidney Function For the measurement of 3-methylhistidine, an index of muscle protein catabolism, urine was collected during the last 24 hours of a 72-hour meat-free diet immediately before and immediately after the study. A meatfree diet was implemented because meat consumption increases urinary 3-methylhistidine values and may falsely represent an increase in muscle protein catabolism (Lukaski, Mendez, Buskirk, & Cohn, 1981). Three days of a meat-free diet are required to return 3-methylhistidine levels to baseline (Lukaski et al., 1981). The designated urine collection procedure was to discard the first urination upon waking in the morning and then collect all urine samples for 24 hours, including the first urination upon waking the following morning. The concentration of 3-methylhistidine was measured using high-performance liquid chromatography (HPLC, Agilent 1200, Agilent Technologies, Palo Alto, CA, USA) following precolumn derivations with fluorescamine with slight modifications of a previously described method (Wassner, Schlitzer, & Li, 1980). The daily amount of 3-methylhistidine excreted by each participant was determined by multiplying the concentration by the 24-hour urine volume. The intra-assay coefficient of variation for 3-methylhistidine is 5.1% (Candow et al., 2006). To measure microalbumin, an indicator of kidney function, 24-hour urine samples were obtained prior to and following supplementation and resistance training. Microalbumin was measured using immunochromatographic lateral flow membrane test strips containing specific monoclonal antibody against human albumin (Genzyme Diagnostics, Charlottetown, PEI, Canada). The test gives one of three results: microalbumin less than 18 mg·L−1 , equal to 18 mg·L−1 , or greater than 18 mg·L−1 . A test greater than 18 mg·L−1 indicates compromised kidney function.
Dietary Assessment Dietary intake was recorded during the first and final week of supplementation and resistance training (outside of the meat-free diet period that was required for the 3-methylhistidine assessment) to assess differences in total energy and macronutrient composition between the CR-Before and CR-After groups. Participants used a 3-day food booklet to record what they ate for 2 weekdays and 1 weekend day. Participants were instructed to record all
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food items, including portion sizes consumed for the 3 designated days. The Interactive Healthy Eating Index (Center for Nutrition Policy and Promotion, United States Department of Agriculture; http://www.usda.gov/cnpp/) was used to analyze 3-day food records.
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Statistical Analyses A 2 (CR-Before vs. CR-After) × 2 (pre- and post-test periods) ANOVA with repeated measures on the second factor was used to determine differences between groups over time for each of the dependent variables of lean tissue mass, muscle thickness, strength, 3-methylhistidine, microalbumin, and diet. A one-factor ANOVA was used to determine whether there were differences in baseline measurements between groups and to determine differences between males and females on creatine. Statistical analyses were carried out using SPSS version 11.0 for Windows XP (SPSS, Chicago, IL, USA). Significance was set at p < 0.05. All results are expressed as mean ± SD.
RESULTS Participant characteristics and physical activity performed at baseline are found in Table 1. Dietary intakes (i.e., total calories, carbohydrates, fats, proteins; Table 2) and body mass at baseline and after the intervention were not different between groups. There were no differences in the volume of resistance training performed between groups over time (CR-Before: 14911 ± 5460 kg; Cr-After: 13537 ± 6481 kg). Thirteen participants did not know whether they were supplementing with creatine or placebo, while 9 participants correctly guessed which supplement they were ingesting. There were no adverse effects from creatine supplementation or placebo reported. Over the 12 weeks of training, both groups experienced a significant increase in lean tissue mass (CR-Before: 1.4 ± 0.4 kg, CR-After: 1.9 ± 0.7 kg, p < 0.001; Figure 1), muscle thickness (elbow and knee flexor and extensors combined: CR-Before: 1.8 ± 0.7 cm, CR-After: 1.9 ± 0.8 cm, p < 0.001; Table 3), muscle strength (leg press: CR-Before: 51.8 ± 27.8 kg, CR-After: 45.0 ± 30.0 kg, Figure 2; chest press: CR-Before: 24.1 ± 21.1 kg CR-After: 21.2 ± 16.0 kg, p < 0.001; Figure 3), and a decrease in muscle protein catabolism (CR-Before: -119.5 ± 132.2 mmol 3-MH/24 hr, CR-After: -167.2 ± 5.4 mmol 3-MH/24 hr, p < 0.001; Figure 4), with no differences between groups. All measures for urinary microalbumin before and after training and supplementation were less than 18 mg·L−1 .
68 56 (4) 55 (2)
Age (years)
Values are expressed as mean (standard deviation).
CR-Before (4 male, 7 female) CR-After (5 male, 6 female)
Group 77 (19) 79 (14)
Body mass (kg) 167 (7) 170 (10)
Height (cm)
TABLE 1 Participant Characteristics and Physical Activity Performed at Baseline
2 (2) 3 (2)
Strenuous activity (times per week)
3 (2) 2 (1)
Moderate activity (time per week)
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4 (3) 4 (2)
Mild activity (times per week)
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TABLE 2 Total Calories (Kcal/Day) and Macronutrient (Grams/Day) Content of Creatine Groups for 3 Days During the First and Final Week of Supplementation and Training CR-Before (n = 9) Week 1 1715.0 241.2 86.1 133.6
Week 12
(320.0) (79.3) (32.9) (51.6)
1922.6 201.4 94.6 108.7
(771.2)∗ (54.2)∗ (45.3) (36.5)∗
Week 1 1999.8 238.2 75.4 91.9
Week 12
(750.0) (81.5) (29.8) (38.8)
1795.3 201.0 73.6 82.1
(664.0)∗ (63.8)∗ (30.1) (34.4)∗
Values are means (standard deviation). Data are based on the average for one day from 3-day food records. ∗ Indicates significantly different over time (p < 0.05).
Pre
100 Lean Tissue Mass (kg)
Post 80
*
*
60 40 20 0 CR-Before
CR-After
FIGURE 1 Change in lean tissue mass after 12 weeks of supplementation and resistance training for CR-Before (n = 11) and Cr-After (n = 11) groups. Values are expressed as mean ± standard deviation. ∗ Significant increase over time (p < 0.05). Pre
300 Leg Press Strength (kg)
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Kilocalories Carbohydrates Fat Protein
CR-After (n = 7)
*
*
250
Post
200 150 100 50 0 CR-Before
CR-After
FIGURE 2 Change in leg press strength after 12 weeks of supplementation and resistance training for CR-Before (n = 11) and Cr-After (n = 11) groups. Values are expressed as mean ± standard deviation. ∗ Significant increase over time (p < 0.05).
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Pre Post
150
*
120
*
90 60 30 0 CR-Before
CR-After
FIGURE 3 Change in chest press strength after 12 weeks of supplementation and resistance training for CR-Before (n = 11) and Cr-After (n = 11) groups. Values are expressed as mean ± standard deviation. ∗ Significant increase over time (p < 0.05). Pre
1000 3-MH (mmol 3-MH/24 hr)
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Chest Press Strength (kg)
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Post 800 600 *
*
400 200 0 CR-Before
CR-After
FIGURE 4 Change in 3-methylhistidine after 12 weeks of supplementation and resistance training for CR-Before (n = 11) and Cr-After (n = 11) groups. 3MH = 3-methylhisditine. Values are expressed as mean ± standard deviation. ∗ Significant decrease over time (p < 0.05).
Females supplementing with creatine (n = 13) experienced a greater relative increase (postmean – premean / premean × 100%) in leg press (30 ± 10%) and chest press strength (87 ± 57%) compared with males on creatine (n = 9; leg press: 19 ± 13%; chest press: 36 ± 35%; p < 0.05). Males supplementing with creatine experienced a greater relative increase in knee extensor muscle thickness (15 ± 8%) compared with females on creatine (4 ± 4%; p < 0.05). There were no other gender differences. Three participants (1 female in the creatine before group; 1 male and 1 female in the creatine after group) did not respond to creatine supplementation.
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Creatine Before and After Exercise
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DISCUSSION This was the first study to directly compare the effects of creatine supplementation immediately before versus after resistance training in healthy older adults. Results showed similar gains in muscle accretion and strength from creatine, independent of the timing of ingestion. Unfortunately, without a placebo control for comparison, we cannot conclude that creatine supplementation had a greater effect over resistance training alone. We have previously demonstrated, however, that creatine supplementation before and after resistance training (6–12 weeks) led to greater gains in muscle mass and strength compared with placebo (Candow et al., 2008, 2011; Chilibeck, Stride, Farthing, & Burke, 2004; Chrusch et al., 2001). Older men who ingested creatine (0.1g•kg−1 ) immediately before and after resistance training sessions for 10 weeks experienced greater muscle accretion compared with the placebo group (Candow et al., 2008). In young adults, creatine (0.1–0.15g•kg−1 ) immediately before and after resistance training for 6 weeks resulted in greater elbow flexor muscle thickness compared with placebo (Candow et al., 2011). Mechanistically, creatine supplementation may improve aging muscle mass and strength by increasing satellite cell activity (Dangott, et al., 2000; Olsen et al., 2006), pathways involved in muscle protein synthesis (Safdar et al., 2008), anabolic hormone secretion (Burke et al., 2008), myogenic transcription factors (Willoughby & Rosene, 2003), or by reducing protein catabolism (Candow et al., 2008). We previously showed that creatine supplementation in older adults reduced urinary excretion of 3-methylhistidine, an indicator of muscle protein catabolism, by 40% compared with an increase of 29% for placebo (Candow et al., 2008). In the present study, we found a reduction (23%–43%) in 3-methylhistidine between creatine groups over time. Although speculative, the lack of differences between the two creatine supplementation protocols may be related to creatine absorption kinetics (Preen et al., 2002). Lower-dose creatine supplementation (1–10 grams) TABLE 3 Muscle Thickness Measurements (cm) for the Elbow and Knee Flexors and Extensors Before and After 12 Weeks of Creatine Supplementation and Resistance Training CR-Before (n = 11) Muscle group Elbow flexors Elbow extensors Knee flexors Knee extensors Ave. total change
Pre 3.7 3.8 5.0 4.5
(0.8) (0.6) (0.6) (0.6)
Post 4.0 4.4 5.5 4.9
CR-After (n = 11) %
∗
(1.0) (1.0)∗ (0.6)∗ (0.8)∗
8.0 13.0 10.8 8.6 10.1
(13.1) (9.0) (8.9) (8.9) (10.0)
Pre 3.8 3.6 5.0 4.4
(0.9) (0.6) (0.7) (0.6)
Post 4.4 4.1 5.4 4.8
% ∗
(1.0) (0.7)∗ (0.6)∗ (0.6)∗
Values are expressed as mean (standard deviation). % = percent change over time. ∗ Significant increase with training (p < 0.05).
18 (18.8) 9.8 (13.0) 10.4 (16.9) 8.7 (6.6) 11.7 (13.8)
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reaches peak maximal plasma concentration (T max) at ≤ 2 hours (Harris et al., 1992; Schedel, Tanaka, Kiyonaga, Shindo, & Schutz, 1999). In the present study, we administered a creatine dosage of approximately 8 grams immediately before or after each training session, which lasted approximately 1 hour, for 12 weeks. Therefore, creatine concentrations may not have reached maximum until 1–2 hours postexercise, resulting in reduced intramuscular creatine uptake from dissipating blood flow after exercise, which could have influenced our ability to detect significant differences between the creatine interventions. A limitation in our study design, as noted earlier, is that we did not include a placebo control group for comparison to creatine supplementation. Although not the primary objective of this study, the lack of a placebo eliminates our ability to determine whether creatine supplementation, independent of the timing of ingestion, was more effective than resistance training alone. Furthermore, muscle biopsies were not performed, which diminishes our ability to assess intramuscular creatine concentrations at baseline and after creatine supplementation. In addition, blood flow kinetics, muscle fiber type composition, muscle cross-sectional area, myogenic transcription factors, or hormonal properties were not measured in this study.
CONCLUSIONS Healthy older adults supplementing with creatine before and after resistance training sessions experienced similar gains in muscle mass and strength after 12 weeks of training. The timing of creatine ingestion did not influence the adaptations from resistance training. Future research should directly compare the longer-term (>12 weeks), mechanistic actions of creatine supplementation before, during, and after resistance training with a placebo control to determine the optimal creatine dosing and frequency strategies for older adults.
ACKNOWLEDGMENTS Creatine and placebo were donated by Rivalus Inc.
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