Common questions and misconceptions about protein supplementation: what does the scientific evidence really show?

Protein supplementation often refers to increasing the intake of this particular macronutrient through dietary supplements in the form of powders, ready-to-drink shakes, and bars. The primary purpose of protein supplementation is to augment dietary protein intake, aiding individuals in meeting their protein requirements, especially when it may be challenging to do so through regular food (i.e. chicken, beef, fish, pork, etc.) sources alone. A large body of evidence shows that protein has an important role in exercising and sedentary individuals. A PubMed search of "protein and exercise performance" reveals thousands of publications. Despite the considerable volume of evidence, it is somewhat surprising that several persistent questions and misconceptions about protein exist. The following are addressed: 1) Is protein harmful to your kidneys? 2) Does consuming "excess" protein increase fat mass? 3) Can dietary protein have a harmful effect on bone health? 4) Can vegans and vegetarians consume enough protein to support training adaptations? 5) Is cheese or peanut butter a good protein source? 6) Does consuming meat (i.e., animal protein) cause unfavorable health outcomes? 7) Do you need protein if you are not physically active? 8) Do you need to consume protein ≤ 1 hour following resistance training sessions to create an anabolic environment in skeletal muscle? 9) Do endurance athletes need additional protein? 10) Does one need protein supplements to meet the daily requirements of exercise-trained individuals? 11) Is there a limit to how much protein one can consume in a single meal? To address these questions, we have conducted a thorough scientific assessment of the literature concerning protein supplementation.

Effect of Creatine Supplementation on Body Composition and Malnutrition-Inflammation Score in Hemodialysis Patients: An Exploratory 1-Year, Balanced, Double-Blind Design.

Hemodialysis has a detrimental effect on fat-free mass (FFM) and muscle strength over time. Thus, we aimed to evaluate the effect of creatine supplementation on the body composition and Malnutrition-Inflammation Score (MIS) in patients with chronic kidney disease (CKD) undergoing hemodialysis. An exploratory 1-year balanced, placebo-controlled, and double-blind design was conducted with hemodialysis patients (≥18 years). The creatine group (CG) received 5 g of creatine monohydrate and 5 g of maltodextrin per day and the placebo group (PG) received 10 g of maltodextrin per day. MIS and body composition were analyzed at three time points: pre, intermediate (after 6 months), and post (after 12 months). After 6 months, 60% of patients on creatine experienced an increase in FFM compared to a 36.8% increase for those on placebo. Moreover, 65% of patients on creatine increased their skeletal muscle mass index (SMMI) compared to only 15.8% for those on placebo. Creatine increased intracellular water (ICW) in 60% of patients. MIS did not change after the intervention. In the CG, there was an increase in body weight (p = 0.018), FFM (p = 0.010), SMMI (p = 0.022). CG also increased total body water (pre 35.4 L, post 36.1 L; p = 0.008), mainly due to ICW (pre 20.2 L, intermediate 20.7 L, post 21.0 L; p = 0.016). Long-term creatine supplementation in hemodialysis patients did not attenuate the MIS, but enhanced FFM and SMMI, which was likely triggered by an increase in ICW.

Resistance Exercise and Creatine Supplementation on Fat Mass in Adults < 50 Years of Age: A Systematic Review and Meta-Analysis.

The combination of resistance exercise and creatine supplementation has been shown to decrease body fat percentage in adults ≥ 50 years of age. However, the effect on adults < 50 years of age is currently unknown. To address this limitation, we systematically reviewed the literature and performed several meta-analyses comparing studies that included resistance exercise and creatine supplementation to resistance exercise and placebo on fat mass and body fat percentage Twelve studies were included, involving 266 participants. Adults (<50 years of age) who supplemented with creatine and performed resistance exercise experienced a very small, yet significant reduction in body fat percentage (-1.19%, p = 0.006); however, no difference was found in absolute fat mass (-0.18 kg, p = 0.76). Collectively, in adults < 50 years of age, the combination of resistance exercise and creatine supplementation produces a very small reduction in body fat percentage without a corresponding decrease in absolute fat mass.

The Effects of Creatine Supplementation Combined with Resistance Training on Regional Measures of Muscle Hypertrophy: A Systematic Review with Meta-Analysis.

The purpose of this paper was to carry out a systematic review with a meta-analysis of randomized controlled trials that examined the combined effects of resistance training (RT) and creatine supplementation on regional changes in muscle mass, with direct imaging measures of hypertrophy. Moreover, we performed regression analyses to determine the potential influence of covariates. We included trials that had a duration of at least 6 weeks and examined the combined effects of creatine supplementation and RT on site-specific direct measures of hypertrophy (magnetic resonance imaging (MRI), computed tomography (CT), or ultrasound) in healthy adults. A total of 44 outcomes were analyzed across 10 studies that met the inclusion criteria. A univariate analysis of all the standardized outcomes showed a pooled mean estimate of 0.11 (95% Credible Interval (CrI): -0.02 to 0.25), providing evidence for a very small effect favoring creatine supplementation when combined with RT compared to RT and a placebo. Multivariate analyses found similar small benefits for the combination of creatine supplementation and RT on changes in the upper and lower body muscle thickness (0.10-0.16 cm). Analyses of the moderating effects indicated a small superior benefit for creatine supplementation in younger compared to older adults (0.17 (95%CrI: -0.09 to 0.45)). In conclusion, the results suggest that creatine supplementation combined with RT promotes a small increase in the direct measures of skeletal muscle hypertrophy in both the upper and lower body.

"Heads Up" for Creatine Supplementation and its Potential Applications for Brain Health and Function.

There is emerging interest regarding the potential beneficial effects of creatine supplementation on indices of brain health and function. Creatine supplementation can increase brain creatine stores, which may help explain some of the positive effects on measures of cognition and memory, especially in aging adults or during times of metabolic stress (i.e., sleep deprivation). Furthermore, creatine has shown promise for improving health outcome measures associated with muscular dystrophy, traumatic brain injury (including concussions in children), depression, and anxiety. However, whether any sex- or age-related differences exist in regard to creatine and indices of brain health and function is relatively unknown. The purpose of this narrative review is to: (1) provide an up-to-date summary and discussion of the current body of research focusing on creatine and indices of brain health and function and (2) discuss possible sex- and age-related differences in response to creatine supplementation on brain bioenergetics, measures of brain health and function, and neurological diseases.

A 2-yr Randomized Controlled Trial on Creatine Supplementation during Exercise for Postmenopausal Bone Health.

PURPOSE: Our purpose was to examine the effects of 2 yr of creatine monohydrate supplementation and exercise on bone health in postmenopausal women. METHODS: Two hundred and thirty-seven postmenopausal women (mean age, 59 yr) were randomized to receive creatine (0.14 g·kg -1 ·d -1 ) or placebo during a resistance training (3 d·wk -1 ) and walking (6 d·wk -1 ) program for 2 yr. Our primary outcome was the femoral neck bone mineral density (BMD), with lumbar spine BMD and proximal femur geometric properties as the secondary outcomes. RESULTS: Compared with placebo, creatine supplementation had no effect on BMD of the femoral neck (creatine: 0.725 ± 0.110 to 0.712 ± 0.100 g·cm -2 ; placebo: 0.721 ± 0.102 to 0.706 ± 0.097 g·cm -2 ), total hip (creatine: 0.879 ± 0.118 to 0.872 ± 0.114 g·cm -2 ; placebo: 0.881 ± 0.111 to 0.873 ± 0.109 g·cm -2 ), or lumbar spine (creatine: 0.932 ± 0.133 to 0.925 ± 0.131 g·cm -2 ; placebo: 0.923 ± 0.145 to 0.915 ± 0.143 g·cm -2 ). Creatine significantly maintained section modulus (1.35 ± 0.29 to 1.34 ± 0.26 vs 1.34 ± 0.25 to 1.28 ± 0.23 cm 3 (placebo), P = 0.0011), predictive of bone bending strength, and buckling ratio (10.8 ± 2.6 to 11.1 ± 2.2 vs 11.0 ± 2.6 to 11.6 ± 2.7 (placebo), P = 0.011), predictive of reduced cortical bending under compressive loads, at the narrow part of the femoral neck. Creatine reduced walking time over 80 m (48.6 ± 5.6 to 47.1 ± 5.4 vs 48.3 ± 4.5 to 48.2 ± 4.9 s (placebo), P = 0.0008) but had no effect on muscular strength (i.e., one-repetition maximum) during bench press (32.1 ± 12.7 to 42.6 ± 14.1 vs 30.6 ± 10.9 to 41.4 ± 14 kg (placebo)) and hack squat (57.6 ± 21.6 to 84.4 ± 28.1 vs 56.6 ± 24.0 to 82.7 ± 25.0 kg (placebo)). In the subanalysis of valid completers, creatine increased lean tissue mass compared with placebo (40.8 ± 5.7 to 43.1 ± 5.9 vs 40.4 ± 5.3 to 42.0 ± 5.2 kg (placebo), P = 0.046). CONCLUSIONS: Two years of creatine supplementation and exercise in postmenopausal women had no effect on BMD; yet, it improved some bone geometric properties at the proximal femur.

Creatine supplementation and endurance performance: surges and sprints to win the race.

Creatine supplementation is an effective ergogenic aid to augment resistance training and improve intense, short duration, intermittent performance. The effects on endurance performance are less known. The purpose of this brief narrative review is to discuss the potential mechanisms of how creatine can affect endurance performance, defined as large muscle mass activities that are cyclical in nature and are >~3 min in duration, and to highlight specific nuances within the literature. Mechanistically, creatine supplementation elevates skeletal muscle phosphocreatine (PCr) stores facilitating a greater capacity to rapidly resynthesize ATP and buffer hydrogen ion accumulation. When co-ingested with carbohydrates, creatine enhances glycogen resynthesis and content, an important fuel to support high-intensity aerobic exercise. In addition, creatine lowers inflammation and oxidative stress and has the potential to increase mitochondrial biogenesis. In contrast, creatine supplementation increases body mass, which may offset the potential positive effects, particularly in weight-bearing activities. Overall, creatine supplementation increases time to exhaustion during high-intensity endurance activities, likely due to increasing anaerobic work capacity. In terms of time trial performances, results are mixed; however, creatine supplementation appears to be more effective at improving performances that require multiple surges in intensity and/or during end spurts, which are often key race-defining moments. Given creatines ability to enhance anaerobic work capacity and performance through repeated surges in intensity, creatine supplementation may be beneficial for sports, such as cross-country skiing, mountain biking, cycling, triathlon, and for short-duration events where end-spurts are critical for performance, such as rowing, kayaking, and track cycling.

Creatine monohydrate supplementation changes total body water and DXA lean mass estimates in female collegiate dancers.

Collegiate dance is unique because it requires athletic and academic performance; therefore, optimizing physical and mental function is crucial. Research among athletic populations demonstrate improvements in body composition, performance, and cognition following creatine monohydrate (CR) supplementation, yet dancers have not been investigated. The purpose of this study was to determine the effects of CR supplementation on body composition, performance, and cognitive function in female collegiate dancers. Participants were randomized to CR (CR; n = 7; 0.1 g·kg -1·day -1 CM +0.1 g·kg -1·day -1 corn-starch maltodextrin) or placebo (PL; n = 6; 0.2 g·kg -1·day -1 corn-starch maltodextrin) for 42 days. Pre- and post-testing included body composition, total body water (TBW), Depression, Anxiety and Stress Scale, Diet History Questionnaire, the National Institute of Health Toolbox fluid cognition battery and isokinetic strength, vertical jump, medicine ball throw, and Wingate anaerobic power test. CR demonstrated a significant increase in TBW (pre, 32.2 ± 3.5 kg; post, 32.7 ± 3.6 kg; p = 0.024) and lean mass (LM; pre, 39.8 ± 3.6 kg; post, 41.5 ± 4.5 kg; p = 0.020). CR supplementation may be an effective strategy to increase TBW and estimates of LM in female collegiate dancers. Although this may optimize aesthetics, larger samples sizes with resistance training are needed to determine if CR supplementation increases muscle mass and translates to improved performance.

The impact of branched-chain amino acid supplementation on measures of glucose homeostasis in individuals with hepatic disorders: A systematic review of clinical studies.

BACKGROUND: Branched chain amino acid (BCAA) supplementation may influence glucose metabolism in individuals with an impaired glyceamic profile. This systematic review investigated the effects of isolated BCAA supplementation on measures of glucose homeostasis in individuals with hepatic disorders. METHODS: We searched PubMed, Web of Science, Cochrane Library and Scopus for published clinical trials that investigated the effects of isolated BCAA supplementation on measures of glucose homeostasis, including serum glucose and insulin, glycated haemoglobin (HbA1c) levels and homeostatic model assessment for insulin resistance (HOMA-IR) scores. RESULTS: Eleven trials met the inclusion criteria. Only one study revealed a decrease in serum glucose from BCAA supplementation compared to three studies that showed increases. Five studies demonstrated no significant changes in serum glucose, and two studies displayed no changes in HbA1c following BCAA supplementation. Serum levels of insulin were decreased in three studies, remained unchanged in one, and increased in the remaining three studies. BCAA supplementation reduced HOMA-IR scores in two studies, increased HOMA-IR scores in another two, or resulted in no changes in two other studies. CONCLUSIONS: BCAA supplementation in isolation had no effect on overall glucose homeostasis in individuals with hepatic disorders, although some improvements on serum insulin levels and HOMA-IR scores were observed. Overall, there is little evidence to support the utilisation of BCAA supplementation as a potential nutritional strategy for improving measures of glucose homeostasis in individuals with hepatic disorders.

Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: From an energy perspective, the brain is very metabolically demanding. It is well documented that creatine plays a key role in brain bioenergetics. There is some evidence that creatine supplementation can augment brain creatine stores, which could increase memory. OBJECTIVE: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to determine the effects of creatine supplementation on memory performance in healthy humans. DATA SOURCES: The literature was searched through the PubMed, Web of Science, Cochrane Library, and Scopus databases from inception until September 2021. DATA EXTRACTION: Twenty-three eligible RCTs were initially identified. Ten RCTs examining the effect of creatine supplementation compared with placebo on measures of memory in healthy individuals met the inclusion criteria for systematic review, 8 of which were included in the meta-analysis. DATA ANALYSIS: Overall, creatine supplementation improved measures of memory compared with placebo (standard mean difference [SMD] = 0.29, 95%CI, 0.04-0.53; I2 = 66%; P = 0.02). Subgroup analyses revealed a significant improvement in memory in older adults (66-76 years) (SMD = 0.88; 95%CI, 0.22-1.55; I2 = 83%; P = 0.009) compared with their younger counterparts (11-31 years) (SMD = 0.03; 95%CI, -0.14 to 0.20; I2 = 0%; P = 0.72). Creatine dose (≈ 2.2-20 g/d), duration of intervention (5 days to 24 weeks), sex, or geographical origin did not influence the findings. CONCLUSION: Creatine supplementation enhanced measures of memory performance in healthy individuals, especially in older adults (66-76 years). SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. 42021281027.

Medium-chain triglycerides may improve memory in non-demented older adults: a systematic review of randomized controlled trials.

BACKGROUND: Ketosis has been exploited for its neuroprotective impact and treatment of neurological conditions via ketone production. Exogenous medium-chain triglyceride (MCT) supplementation may induce nutritional ketosis. The aim of this systematic review is to explore the effects of MCTs on memory function in older adults without cognitive impairment. METHODS: A systematic literature search of PubMed, Cochrane Library, Scopus, and Web of Science was employed from inception until April 2022 for randomized controlled trials (RCTs) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, investigating the impact of MCT oils on components of memory. Risk of bias (RoB2) tool was utilized for quality assessment. RESULTS: Six trials were included for qualitative synthesis, in which two studies examined the effect of MCTs through a ketogenic meal. MCT supplementation compared to controls was associated with improved indices of memory function in 4 out of 6 studies, particularly working memory. A meta-analysis was not employed due to the low number of studies, therefore, a true effect measure of MCT supplementation was not explored. CONCLUSIONS: MCT supplementation may enhance working memory in non-demented older adults. These effects may be more prominent in individuals with lower baseline scores, from short and long-term supplementation. Further studies are warranted to confirm these findings in terms of optimal dose and MCTs composition, which may protect from memory decline during aging.

Influence of age, sex, and type of exercise on the efficacy of creatine supplementation on lean body mass: A systematic review and meta-analysis of randomized clinical trials.

Creatine supplementation has been shown to increase measures of lean body mass (LBM); however, there often is high heterogeneity across individual studies. Therefore, the aim of this study was to systematically review and meta-analyze randomized controlled trials (RCTs) investigating creatine supplementation on LBM. Subanalyses were performed based on age, sex, and type of exercise. Based on PRISMA guidelines, we searched the following databases: Pubmed, SPORTDiscus, Web of Science, and Scopus (PROSPERO register: CRD42020207122) until May 2022. RCTs for investigation of creatine supplementation on LBM were included. Animal studies and studies on individuals with specific diseases were excluded. Thirty-five studies were included, with 1192 participants. Overall (i.e., inclusion of all studies with and without exercise training interventions) revealed that creatine increased LBM by 0.68 kg (95% confidence interval [CI], 0.26-1.11). Subanalyses revealed greater gains in LBM when creatine was combined with resistance training (mean difference [MD], 1.10 kg; 95% CI, 0.56-1.65), regardless of age. There was no statistically significant effect of creatine on LBM when combined with mixed exercise (MD, 0.74 kg; 95% CI, -3.89 to 5.36) or without exercise (MD, 0.03 kg; 95% CI, -0.65 to 0.70). Further subanalyses found that males on creatine increased LBM by 1.46 kg (95% CI, 0.47-2.46), compared with a non-significant increase of 0.29 kg (95% CI, -0.43 to 1.01) for females. In conclusion, the addition of creatine supplementation to a resistance training program increases LBM. During a resistance training program, males on creatine respond more favorably than females.

Creatine supplementation for older adults: Focus on sarcopenia, osteoporosis, frailty and Cachexia.

Sarcopenia refers to the age-related reduction in strength, muscle mass and functionality which increases the risk for falls, injuries and fractures. Sarcopenia is associated with other age-related conditions such as osteoporosis, frailty and cachexia. Identifying treatments to overcome sarcopenia and associated conditions is important from a global health perspective. There is evidence that creatine monohydrate supplementation, primarily when combined with resistance training, has favorable effects on indices of aging muscle and bone. These musculoskeletal benefits provide some rationale for creatine being a potential intervention for treating frailty and cachexia. The purposes of this narrative review are to update the collective body of research pertaining to the effects of creatine supplementation on indices of aging muscle and bone (including bone turnover markers) and present possible justification and rationale for its utilization in the treatment of frailty and cachexia in older adults.

Effects of Omega-3 Supplementation Alone and Combined with Resistance Exercise on Skeletal Muscle in Older Adults: A Systematic Review and Meta-Analysis.

Sarcopenia negatively affects skeletal muscle mass and function in older adults. Omega-3 (ω-3) fatty acid supplementation, with or without resistance exercise training (RET), is suggested to play a role as a therapeutic component to prevent or treat the negative effects of sarcopenia. A systematic review and meta-analysis were conducted on the impact of ω-3 fatty acid supplementation with or without RET on measures of muscle mass and function in older adults (≥55 y). The data sources included SPORTDiscus, PubMed, and Medline. All the study types involving ω-3 fatty acid supplementation on measures of muscle mass and function in older adults (without disease) were included. The mean differences (MDs) or standardized mean differences (SMDs) with 95% confidence intervals were calculated and pooled effects assessed. Sixteen studies (1660 females, 778 males) met our inclusion criteria and were included in the meta-analysis. ω-3 fatty acid supplementation did not impact lean tissue mass (SMD 0.09 [-0.10, 0.28]). Benefits were observed for lower body strength (SMD 0.54 [0.33, 0.75]), timed-up-and-go (MD 0.29 [0.23, 0.35]s), and 30-s sit-to-stand performance (MD 1.93 [1.59, 2.26] repetitions) but not walking performance (SMD -0.01 [-0.10, 0.07]) or upper body strength (SMD 0.05 [-0.04, 0.13]). Supplementing with ω-3 fatty acids may improve the lower-body strength and functionality in older adults.

Effects of short-term betaine supplementation on muscle endurance and indices of endocrine function following acute high-intensity resistance exercise in young athletes.

Objective: This study examined the effects of short-term betaine supplementation on muscle endurance, plasma lactate, testosterone and cortisol levels, and the testosterone to cortisol (T/C) ratio in response to acute resistance exercise (RE). Method: Using a double-blind, crossover study design, 10 handball players (age ± SD = 16 ± 1 yrs) without prior-structured RE experience performed a high-intensity RE session (leg press followed by bench press; 5 sets to volitional fatigue using 80% baseline 1 repetition maximum (1RM)), before and after 14 days of either placebo (maltodextrin) or betaine (2.5 g·d-1) supplementation. A 30-day washout period separated each treatment. 48 h prior to testing sessions, participants recorded their food intake and did not perform strenuous exercise. Venous blood was sampled before supplementation, and before and after each RE session. Results: After betaine supplementation, participants performed more repetitions (p < 0.001) during the leg press (Betaine: 35.8 ± 4.3; Placebo: 24.8 ± 3.6, Cohen's d = 2.77) and bench press (Betaine: 36.3 ± 2.6; Placebo: 26.1 ± 3.5, Cohen's d = 3.34). Betaine resulted in lower post-exercise cortisol (Betaine: 7.6 ± 1.7; Placebo: 13 ± 3.4 µg.dL-1, p = 0.003, generalized eta squared ( η G 2 ) = 0.49) and lactate (Betaine: 5.2 ± 0.3; Placebo: 6 ± 0.3 mmol.L-1, p < 0.001, η G 2 = 0.96) and higher total testosterone (Betaine: 15.2 ± 2.2; Placebo: 8.7 ± 1.7 ng.mL-1, p < 0.001, η G 2 = 0.87) and T/C ratio (Betaine: 0.21 ± 0.05; Placebo: 0.07 ± 0.02, p < 0.001, = 0.82). Conclusions: Two weeks of betaine supplementation improved upper- and lower-body muscle endurance and influenced indices of endocrine function following an acute session of high-intensity RE in adolescent handball players.

Effects of Creatine Supplementation on Brain Function and Health.

While the vast majority of research involving creatine supplementation has focused on skeletal muscle, there is a small body of accumulating research that has focused on creatine and the brain. Preliminary studies indicate that creatine supplementation (and guanidinoacetic acid; GAA) has the ability to increase brain creatine content in humans. Furthermore, creatine has shown some promise for attenuating symptoms of concussion, mild traumatic brain injury and depression but its effect on neurodegenerative diseases appears to be lacking. The purpose of this narrative review is to summarize the current body of research pertaining to creatine supplementation on total creatine and phophorylcreatine (PCr) content, explore GAA as an alternative or adjunct to creatine supplementation on brain creatine uptake, assess the impact of creatine on cognition with a focus on sleep deprivation, discuss the effects of creatine supplementation on a variety of neurological and mental health conditions, and outline recent advances on creatine supplementation as a neuroprotective supplement following traumatic brain injury or concussion.

Anti-Inflammatory and Anti-Catabolic Effects of Creatine Supplementation: A Brief Review.

It is well established that creatine supplementation, primarily when combined with resistance training, significantly increases measures of muscle mass and performance (primarily strength). Emerging research also indicates that creatine supplementation may have favorable effects on measures of bone biology. These anabolic adaptations may be related to creatine influencing cellular hydration status, high-energy phosphate metabolism, growth factors, muscle protein kinetics, and the bone remodeling process. Accumulating research also suggests that creatine supplementation has anti-inflammatory and anti-catabolic properties, which may help create a favorable environment for muscle and bone accretion and recovery from exercise. Creatine supplementation has the ability to decrease markers of inflammation and possibly attenuate cancerous tumor growth progression. From a musculoskeletal perspective, there is some evidence to show that creatine supplementation reduces measures of muscle protein catabolism (primarily in males) and bone resorption when combined with resistance training. The purpose of this brief review is to summarize the current body of literature examining the potential anti-inflammatory and anti-catabolic effects of creatine supplementation across various research populations.

Effects of Creatine and Caffeine Supplementation During Resistance Training on Body Composition, Strength, Endurance, Rating of Perceived Exertion and Fatigue in Trained Young Adults.

The primary purpose was to determine the separate and combined effects of creatine and caffeine supplementation during resistance training on body composition and muscle performance in trained young adults. Twenty-eight participants were randomized to supplement with creatine and caffeine (CR-CAF; n = 9, 22 ± 4 years; 0.1 g·kg-1·d-1 of creatine monohydrate + 3 mg·kg-1·d-1 of caffeine anhydrous micronized powder); creatine (CR; n = 7, 22 ± 4 years, 0.1 g·kg-1·d-1 of creatine + 3 mg·kg-1·d-1 of micronized cellulose), caffeine (CAF; n = 6, 19 ± 1 years, 3 mg·kg-1·d-1 of caffeine + 0.1 g·kg-1·d-1 of maltodextrin) or placebo (PLA; n = 6, 23 ± 7 years, 0.1 g·kg-1·d-1 of maltodextrin + 3 mg·kg-1·d-1 micronized cellulose) one hour prior to performing resistance training for 6 weeks. Before and after training and supplementation, fat-free and fat mass (air-displacement plethysmography), muscle thickness (elbow and knee flexors and extensors; ultrasound), muscle strength (1-repetition maximum [1-RM] for the leg press and chest press), and endurance (one set of repetitions to volitional fatigue using 50% baseline 1-RM for leg press and chest press) were assessed. There was a group x time interaction (p = 0.049) for knee extensor muscle thickness with CR experiencing an increase over time with no changes in the other groups. There were no other between group differences for any variable. In conclusion, creatine supplementation and resistance training results in a small improvement in knee extensor muscle accretion in trained young adults.