Creatine and Resistance Training for Mild Cognitive Impairment

Overseen By Lindsay Nagamatsu, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Western University, Canada

Must not be taking: NSAIDs

Disqualifiers: Neurological disorders, Kidney disease, Heart disease, Liver abnormalities, Uncontrolled chronic conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 26 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if creatine supplements (creatine monohydrate) and resistance training can enhance memory and physical health in older adults with mild memory problems. Participants will be divided into four groups: one group will take creatine and engage in resistance training, another will take a placebo (a harmless sugar pill) and perform resistance training, while the remaining groups will either take creatine or a placebo while doing lighter exercises like balance and stretching. The focus is to discover if these treatments can boost brain and body health, especially when combined. This trial might suit those who have noticed memory decline over the last five years and can commit to exercising three times a week. As an unphased trial, this study offers a unique opportunity to contribute to scientific understanding and potentially improve health.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking medication that may impact kidney function, like ibuprofen or naproxen.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that taking creatine monohydrate orally in the right amounts is likely safe for up to five years. Studies have found that creatine can help increase muscle mass and bone strength in older adults. Some research also suggests it might benefit brain health and cognitive skills, but more studies are needed to fully understand its effects on the aging brain.

For weightlifting, studies support its safety for older adults, even those with mild memory or cognitive issues. Research indicates that weightlifting can improve brain health and protect certain brain areas from deterioration. It is generally well-tolerated and enhances physical health.

Overall, these findings suggest that both creatine supplements and weightlifting are safe for older adults, including those with mild memory issues. However, as with any new treatment, monitoring for possible side effects is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for mild cognitive impairment because they combine creatine monohydrate supplementation with structured physical activity, which is a fresh approach compared to existing options like medications and cognitive training. Creatine is a naturally occurring compound known to enhance energy production in the brain, potentially offering cognitive benefits. The incorporation of resistance training is also significant, as it not only helps with physical health but may also boost brain function through increased blood flow and neuroplasticity. By combining these elements, this approach aims to tackle cognitive decline from both metabolic and physical angles, offering a comprehensive strategy that could complement or enhance current treatment options.

What evidence suggests that this trial's treatments could be effective for mild cognitive impairment?

Research suggests that creatine monohydrate might improve thinking and memory in adults. Some studies have found that creatine can strengthen and enlarge muscles, particularly in older adults and those with Alzheimer's disease. Resistance training, or exercise with weights, has also benefited brain health and thinking skills in older adults. This trial will evaluate the effects of combining creatine with resistance training, as well as creatine with an active control group, to determine if these combinations enhance brain and muscle health more than either approach alone. Although more research is needed to confirm these effects for individuals with mild memory problems, early results are encouraging. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for older adults with mild cognitive impairment. Participants should be interested in taking creatine supplements or doing resistance training, like weightlifting. They must not have any health conditions that would make it unsafe to take part in the study.

Inclusion Criteria

Participants must be able to exercise at a moderate pace using resistance training for 60 minutes 3x/week

Participants must be right-handed

Participants must have subjective feelings of memory decline in the past 5 years

Exclusion Criteria

Participants cannot partake or commit to exercise training 3x/week for 26 weeks or have regularly (>1x/week) engaged in exercise training over the past 3 months

Participants cannot partake or commit to consuming a daily supplement for 26 weeks or consumed nutritional supplements containing creatine monohydrate over the past 3 months

I am allergic to creatine monohydrate or dextrose.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Participants complete baseline assessments including consent, questionnaires, and optional MRI

1 week

1-2 visits (in-person)

Treatment

Participants undergo 26 weeks of creatine supplementation and/or resistance training or active control exercises

26 weeks

3 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Creatine monohydrate
• Resistance training

Trial Overview The study tests if creatine and resistance training can improve brain health, cognition, and physical function over 26 weeks. Participants will be randomly placed into one of four groups: creatine with exercise, placebo with exercise, creatine without exercise, or placebo without exercise.

How Is the Trial Designed?

Group I: Placebo supplementation and resistance training Experimental Treatment 1 Intervention

Placebo supplementation: Participants in the placebo group will follow the same protocol as the creatine supplementation groups but will consume dextrose powder instead of creatine. Resistance training: All participants will attend three 60-minute exercise classes per week. Classes will consist of a 10-minute warm-up on a treadmill or stationary bike followed up 40 minutes of core-content and ending with a 10-minute cool down and stretch. Resistance training classes will be completed using HUR machines which will target each major muscle group. Progression will follow the 7RM method where load will increase after two sets of 6-8 repetitions can be completed with proper form and range of motion.

Group II: Creatine monohydrate supplementation and resistance training Experimental Treatment 2 Interventions

Creatine supplementation: Participants will consume one serving (0.10g of creatine/kg/day) of creatine monohydrate mixed into at least eight ounces of a beverage of their choice daily. Participants will choose what meal they will take the supplement and will be asked to keep timing consistent throughout the 26 weeks. Resistance training: All participants will attend three 60-minute exercise classes per week. Classes will consist of a 10-minute warm-up on a treadmill or stationary bike followed up 40 minutes of core-content and ending with a 10-minute cool down and stretch. Resistance training classes will be completed using HUR machines which will target each major muscle group. Progression will follow the 7RM method where load will increase after two sets of 6-8 repetitions can be completed with proper form and range of motion.

Group III: Creatine monohydrate supplementation and active control group Experimental Treatment 1 Intervention

Creatine supplementation: Participants will consume one serving (0.10g of creatine/kg/day) of creatine monohydrate mixed into at least eight ounces of a beverage of their choice daily. Participants will choose what meal they will take the supplement and will be asked to keep timing consistent throughout the 26 weeks. Active control group: This group will follow the same protocol as the resistance training group, however, the core-content will consist of balance, stretching, and range of motion exercises. This serves as our active control group to control for socialization and commitment to an exercise program that may influence our outcome measures. This protocol has been used in previous exercise studies and there is no evidence that the balance and tone classes result in cognitive benefits.

Group IV: Placebo supplementation and active control group Active Control 1 Intervention

Placebo supplementation: Participants in the placebo group will follow the same protocol as the creatine supplementation groups but will consume dextrose powder instead of creatine. Active control group: This group will follow the same protocol as the resistance training group, however, the core-content will consist of balance, stretching, and range of motion exercises. This serves as our active control group to control for socialization and commitment to an exercise program that may influence our outcome measures. This protocol has been used in previous exercise studies and there is no evidence that the balance and tone classes result in cognitive benefits.

Who Is Running the Clinical Trial?

Western University, Canada

Lead Sponsor

Trials

270

Recruited

62,500+

Alzheimer Society of Canada

Collaborator

Trials

10

Recruited

2,900+

Published Research Related to This Trial

The BRAIN Training Trial is investigating the effects of high-intensity aerobic interval training (HIIT) and high-intensity power training (POWER) on cognitive function in 160 older adults (≥ 60 years) with mild cognitive impairment (MCI) over 12 months, aiming to provide clearer insights into effective exercise interventions for cognitive health.

The primary outcome will be assessed through a cognitive composite score at baseline, 6 months, and 12 months, which will help determine if these high-intensity exercise programs can significantly improve cognitive performance compared to a sham exercise control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol for the BRAIN Training Trial: a randomised controlled trial of Balance, Resistance, And INterval training on cognitive function in older adults with mild cognitive impairment. Valenzuela, T., Coombes, JS., Liu-Ambrose, T., et al.[2023]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06948149

Creatine and Resistance Training in Older Adults With Mild ... Some research has suggested that creatine may also improve cognition and brain health. However, little is known about how creatine supplementation affects the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11275561/

The effects of creatine supplementation on cognitive function ... Current evidence suggests that creatine monohydrate supplementation may confer beneficial effects on cognitive function in adults.

3. frontiersin.org frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1670641/full

Eight weeks of creatine monohydrate supplementation is ... Eight weeks of creatine monohydrate supplementation is associated with increased muscle strength and size in Alzheimer's disease: data from a ...

4. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc2.70101

Creatine monohydrate pilot in Alzheimer's: Feasibility, brain ... Our data suggest that CrM supplementation is feasible in AD and provides preliminary evidence for future efficacy and mechanism studies.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06948149?term=creatine&viewType=Table&rank=4

Creatine and Resistance Training in Older Adults With Mild ... Studies have shown that creatine increases muscle mass and bone density in older adults when supplemented. Some research has suggested that creatine may also ...

6. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/Creatine_%28supplement%29_.pdf

Creatine In addition, these reports include evaluation of safety data, from clinical trials if available, and from preclinical models. Creatine. Evidence Summary.

7. mayoclinic.org mayoclinic.org/drugs-supplements-creatine/art-20347591

Creatine When used orally at appropriate doses, creatine is likely safe to take for up to five years. As with any dietary supplement, it's important to choose a product ...