Creatine Supplementation for Muscle Strength

Overseen By Darren Candow

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Regina

Disqualifiers: Pregnant, Nursing, Creatine use, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

52 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you should avoid creatine supplements for 30 days before the study.

What data supports the effectiveness of the treatment Creatine Monohydrate for increasing muscle strength?

Research shows that creatine monohydrate can increase muscle strength in patients with neuromuscular disease, as demonstrated by improvements in body weight, handgrip, dorsiflexion, and knee extensor strength. However, in patients with myotonic dystrophy type 2, creatine showed only mild improvement trends, and in myotonic dystrophy type 1, it did not significantly increase muscle strength or other outcomes. ^{1 2 3 4 5}

Is creatine supplementation safe for humans?

Creatine monohydrate is generally considered safe for healthy adults at a daily intake of 3 grams, with no serious adverse effects reported. Some mild side effects like stomach upset and muscle cramps may occur, and certain forms of creatine may have limited safety data. ^{5 6 7 8 9}

How does creatine monohydrate differ from other treatments for muscle strength?

Creatine monohydrate is unique because it has been shown to increase muscle strength in patients with neuromuscular disease and healthy individuals by enhancing muscle creatine content, which is not observed with other forms like creatyl-L-leucine. It is generally considered safe at a daily intake of 3 grams, although some forms may have safety concerns. ^{2 3 5 10 11}

What is the purpose of this trial?

Creatine supplementation improves measures of muscle accretion and performance compared to placebo during a resistance training program. However, the optimal creatine supplementation protocol for maximizing these improvements is unknown.

Research Team

Darren Candow

Principal Investigator

University of Regina

Eligibility Criteria

This trial is for young adults aged 18-39 who are physically active, doing structured resistance training at least twice a week for the past month. It's not suitable for those pregnant, nursing, or with recent creatine use.

Inclusion Criteria

Physically active (performing structured resistance training > 2x/week for ≥ 4 weeks)

Exclusion Criteria

Pregnant or nursing

I have taken creatine monohydrate in the last 30 days.

Pre-existing allergies to the placebo

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo resistance training with creatine supplementation or placebo for 16 weeks

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Creatine Monohydrate

Trial Overview The study tests whether taking creatine monohydrate improves muscle strength and growth more than a placebo during resistance training. The goal is to find the best way to take creatine for maximum benefits.

Participant Groups

Group I: Creatine Non-Training Experimental Treatment 2 Interventions

5 grams of creatine monohydrate + 3 grams of placebo on non-training days; 8 grams of placebo immediately before training sessions; 8 grams of placebo immediately after training sessions.

Group II: Creatine Before Training Experimental Treatment 2 Interventions

5 grams of creatine monohydrate + 3 grams of placebo immediately before training sessions; 8 grams of placebo immediately after training sessions; 8 grams of placebo on non-training days.

Group III: Creatine After Training Experimental Treatment 2 Interventions

5 grams of creatine monohydrate + 3 grams of placebo immediately after training sessions; 8 grams of placebo immediately before training sessions; 8 grams of placebo on non-training days.

Group IV: Placebo Placebo Group 1 Intervention

8 grams of placebo immediately before training sessions; 8 grams of placebo immediately after training sessions; 8 grams of placebo on non-training days

Creatine Monohydrate is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Creatine Monohydrate for:

• Dietary supplement for general health and wellness

Approved in European Union as Creatine Monohydrate for:

• Dietary supplement for general health and wellness

Approved in Canada as Creatine Monohydrate for:

• Dietary supplement for general health and wellness

Who Is Running the Clinical Trial?

University of Regina

Lead Sponsor

Trials

59

Recruited

9,100+

Findings from Research

Creatine monohydrate is effective for enhancing performance in high-intensity, short-duration activities, supported by a large body of research involving both acute (20 g/d) and chronic (3-5 g/d) supplementation studies.

The Observed Safe Level (OSL) for chronic creatine supplementation is established at 5 g/d, indicating strong safety evidence at this dosage, while higher intakes lack sufficient long-term safety data despite being tested without adverse effects in acute studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk assessment for creatine monohydrate. Shao, A., Hathcock, JN.[2013]

In a pilot study with 81 patients and a follow-up study with 21 patients, creatine monohydrate supplementation significantly increased strength measures, including handgrip and knee extensor strength.

The treatment involved administering 10 g daily for 5 days, followed by 5 g daily for another 5 days, demonstrating that short-term creatine use can effectively enhance high-intensity strength in individuals with neuromuscular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Creatine monohydrate increases strength in patients with neuromuscular disease. Tarnopolsky, M., Martin, J.[2019]

In a study involving 34 adult patients with myotonic muscular dystrophy type 1 (DM1), creatine monohydrate (CrM) supplementation at 5 g daily did not improve muscle strength, body composition, or daily activities over a 4-month period.

The lack of effectiveness may be due to CrM not increasing muscle phosphocreatine (PCr) levels, which are important for muscle energy, as no significant changes were observed in muscle PCr/beta-ATP ratios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Creatine monohydrate supplementation does not increase muscle strength, lean body mass, or muscle phosphocreatine in patients with myotonic dystrophy type 1. Tarnopolsky, M., Mahoney, D., Thompson, T., et al.[2013]

In a 3-month double-blind trial involving 20 patients with myotonic dystrophy type 2, creatine monohydrate did not show significant improvements in muscle strength compared to placebo, as measured by various strength assessments.

However, there were some trends suggesting mild improvements with creatine, and two patients reported relief from myalgia, indicating potential benefits that may warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Creatine monohydrate in DM2/PROMM: a double-blind placebo-controlled clinical study. Proximal myotonic myopathy. Schneider-Gold, C., Beck, M., Wessig, C., et al.[2019]

Creatine monohydrate is generally considered safe for healthy adults at a daily intake of 3 grams, with some minor side effects like gastrointestinal issues and muscle cramps reported.

While most creatine forms are unlikely to pose safety concerns, there are specific safety concerns associated with creatine orotate, creatine phosphate, and magnesium creatine chelate, indicating that not all creatine supplements are equally safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Creatine and creatine forms intended for sports nutrition. Andres, S., Ziegenhagen, R., Trefflich, I., et al.[2018]

Creatine monohydrate (CrM) remains the only form of creatine with substantial evidence supporting its bioavailability, efficacy, and safety, as confirmed by a review of various marketed creatine forms.

Despite ongoing claims about other 'novel forms' of creatine, many lack sufficient evidence for effectiveness and safety, and CrM is still the recommended source by professional organizations and regulatory authorities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability, Efficacy, Safety, and Regulatory Status of Creatine and Related Compounds: A Critical Review. Kreider, RB., Jäger, R., Purpura, M.[2022]

Oral creatine supplementation can lead to weight gain due to water retention, which might negatively affect performance in activities that rely on body mass, like running and swimming.

Short-term use of creatine (less than 28 days) at recommended doses appears safe based on limited studies, but these studies had small sample sizes and did not adequately explore potential effects on key organs like the heart and brain, highlighting the need for larger, more comprehensive trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential side effects of oral creatine supplementation: a critical review. Juhn, MS., Tarnopolsky, M.[2019]

Creatine supplementation can enhance performance in high-intensity, short-duration exercises, but it is not effective for endurance sports, based on a review of various studies.

While generally well tolerated in short-term use, creatine may cause side effects like weight gain, cramping, and potential renal function decrease, highlighting the need for caution due to variability in product quality and dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Creatine: a review of efficacy and safety. Graham, AS., Hatton, RC.[2013]

A systematic review of 29 studies involving 951 female participants found no serious adverse outcomes or deaths associated with creatine monohydrate (CrM) supplementation, indicating it is safe for use in women.

There were no significant differences in total adverse events, gastrointestinal issues, or weight gain between those taking CrM and those not, suggesting that CrM does not increase the risk of these complications in females.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Adverse Outcomes in Females Taking Oral Creatine Monohydrate: A Systematic Review and Meta-Analysis. de Guingand, DL., Palmer, KR., Snow, RJ., et al.[2021]

A study involving six healthy males showed that after a single oral dose of creatine (71 mg/kg), the clearance rate was 0.20 L/h/kg, with peak concentration reached at about 1.9 hours.

After six days of repeated dosing, the clearance rate decreased to 0.12 L/h/kg, indicating that the body may become saturated with creatine in the muscles, which could affect how the body processes it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single- and multiple-dose pharmacokinetics of oral creatine. Persky, AM., Müller, M., Derendorf, H., et al.[2019]

In a study involving 29 healthy participants over 14 days, creatine monohydrate supplementation significantly increased muscle creatine content, demonstrating its effectiveness in enhancing muscle performance.

Conversely, creatyl-L-leucine (CLL) did not result in any changes in muscle creatine levels, indicating that it may not be an effective alternative to creatine monohydrate for improving muscle performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Creatine Monohydrate Supplementation, but not Creatyl-L-Leucine, Increased Muscle Creatine Content in Healthy Young Adults: A Double-Blind Randomized Controlled Trial. Askow, AT., Paulussen, KJM., McKenna, CF., et al.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Risk assessment for creatine monohydrate. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Creatine monohydrate increases strength in patients with neuromuscular disease. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Creatine monohydrate supplementation does not increase muscle strength, lean body mass, or muscle phosphocreatine in patients with myotonic dystrophy type 1. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Creatine monohydrate in DM2/PROMM: a double-blind placebo-controlled clinical study. Proximal myotonic myopathy. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Creatine and creatine forms intended for sports nutrition. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Bioavailability, Efficacy, Safety, and Regulatory Status of Creatine and Related Compounds: A Critical Review. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Potential side effects of oral creatine supplementation: a critical review. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Creatine: a review of efficacy and safety. [2013]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Risk of Adverse Outcomes in Females Taking Oral Creatine Monohydrate: A Systematic Review and Meta-Analysis. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Single- and multiple-dose pharmacokinetics of oral creatine. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Creatine Monohydrate Supplementation, but not Creatyl-L-Leucine, Increased Muscle Creatine Content in Healthy Young Adults: A Double-Blind Randomized Controlled Trial. [2023]