Is creatine effective as a treatment for dementia?

Creatine for Dementia: Current Evidence and Recommendations

Creatine supplementation is not currently recommended as a treatment for dementia based on insufficient clinical evidence, though preliminary research suggests it may warrant further investigation.

Current Evidence on Creatine for Dementia

Guideline Recommendations

Current clinical practice guidelines do not recommend creatine supplementation for treating dementia. The American College of Physicians and American Academy of Family Physicians guidelines focus on FDA-approved pharmacologic therapies, specifically cholinesterase inhibitors and memantine, as the primary treatment options for dementia 1. These guidelines make no mention of creatine as a potential therapeutic agent.

Similarly, the ESPEN guidelines on nutrition in dementia do not recommend creatine or other nutritional supplements for correcting cognitive impairment or preventing cognitive decline in persons with dementia 1. The guidelines specifically state: "We do not recommend any other nutritional product for persons with dementia to correct cognitive impairment or prevent further cognitive decline" with a very low grade of evidence.

Recent Research on Creatine and Cognition

The most recent and promising evidence comes from a 2025 single-arm pilot trial that investigated the feasibility of creatine monohydrate supplementation in Alzheimer's disease 2. This study found:

• 20g/day of creatine monohydrate for 8 weeks was feasible in patients with Alzheimer's disease
• Brain total creatine increased by 11%
• Cognitive improvements were observed on global and fluid composites, List Sorting, Oral Reading, and Flanker tests

However, this was a small, single-arm pilot study without a control group, limiting the strength of its conclusions.

A 2023 randomized controlled trial examined creatine supplementation (5g daily for 6 weeks) on cognitive performance in healthy adults 3. The study found:

• A small beneficial effect of creatine that bordered significance for Backward Digit Span (p = 0.064)
• No significant improvement on Raven's Advanced Progressive Matrices or other exploratory cognitive tasks
• Side effects were reported significantly more often with creatine than placebo

Earlier research from 2011 suggested that creatine supplementation might improve cognitive processing that is either experimentally impaired (following sleep deprivation) or naturally impaired due to aging 4. This review highlighted creatine's potential benefits for older adults, including increased lean body mass, enhanced fatigue resistance, and improved muscle strength.

Pathophysiological Relevance

A 2009 study found that conversion from mild cognitive impairment to Alzheimer's dementia was associated with a decline in brain creatine levels 5. This suggests a potential pathophysiological role of creatine in dementia progression, though it doesn't necessarily mean supplementation would reverse this process.

An older study from 1987 reported decreased creatine kinase activity in brain structures of patients with Alzheimer's disease and senile dementia 6, further suggesting disrupted creatine metabolism in dementia.

Clinical Approach to Dementia Treatment

Current Standard of Care

The standard pharmacological approach for dementia includes:

1. Cholinesterase inhibitors (donepezil, galantamine, rivastigmine) which increase acetylcholine levels 1
2. Memantine, which blocks NMDA receptors and prevents excess glutamate stimulation 1

These medications have demonstrated statistically significant but clinically marginal improvements in cognition and global assessment of dementia 1.

Non-Pharmacological Approaches

Non-pharmacological treatments (NPTs) are also important in dementia management and may include cognitive training, physical exercise, and dietary interventions 1. These approaches have the potential to improve meaningful outcomes for people with dementia, though research quality varies.

Practical Recommendations

1. Primary treatment approach: Focus on FDA-approved medications (cholinesterase inhibitors and memantine) as first-line pharmacological treatments for dementia 1

2. Individualized assessment: Base decisions to initiate pharmacological therapy on individual patient factors, considering tolerability, adverse effect profile, ease of use, and cost 1

3. Regarding creatine supplementation:

   • Do not recommend creatine as a primary treatment for dementia
   • Consider discussing creatine supplementation only in the context of clinical trials or as an adjunctive approach in patients who:
     • Have shown inadequate response to standard therapies
     • Are interested in experimental approaches
     • Have no contraindications to creatine use

4. Monitor for adverse effects: If a patient chooses to try creatine supplementation, monitor for common side effects, which may include gastrointestinal distress, water retention, and potential kidney stress with long-term use 3

Limitations and Future Directions

The current evidence for creatine in dementia is preliminary and limited. Major limitations include:

• Small sample sizes in existing studies
• Limited long-term data on efficacy and safety
• Lack of large randomized controlled trials specifically in dementia populations
• Uncertainty about optimal dosing regimens

More research is needed to determine if creatine supplementation could be a viable treatment option for dementia. Future studies should focus on larger randomized controlled trials with longer follow-up periods to establish efficacy, safety, and optimal dosing strategies.