Creatine Supplementation in Palliative and Hospice Care: A Supportive Strategy for Muscle Preservation and Quality of Life

Palliative and hospice care medicine has always centered around enhancing quality of life, prioritizing symptom control, preserving function, and supporting dignity in the face of serious, often terminal illnesses. While pharmacologic interventions are widely employed to manage pain, dyspnea, nausea, and agitation, nutritional and metabolic interventions have received comparatively less attention. Among these, creatine supplementation—a well-known ergogenic aid in sports medicine—has begun to attract interest for its potential role in supportive care for individuals with life-limiting disease.

Although data specific to end-of-life populations remain limited, the known pharmacologic and physiologic actions of creatine suggest a valuable, underutilized tool to mitigate common symptoms encountered in palliative care, particularly in the setting of cachexia, weakness, and fatigue.

The Physiology of Creatine

Creatine is a naturally occurring compound found predominantly in skeletal muscle, where it plays a central role in maintaining cellular energy homeostasis. It is converted to phosphocreatine and stored in muscle tissue, where it functions as a rapid reserve of high-energy phosphate groups to regenerate ATP during periods of high demand. Supplemental creatine, usually in the form of creatine monohydrate, has been extensively studied and shown to enhance muscle mass, strength, and performance across a wide range of populations—from athletes to older adults with sarcopenia.

Its appeal in palliative medicine lies not in improving athletic performance, but in preserving function and mitigating decline in patients vulnerable to profound metabolic and musculoskeletal depletion.

Creatine and Cachexia: A Supportive Intervention

Cancer cachexia is a multifactorial syndrome marked by progressive loss of skeletal muscle mass, metabolic alterations, weight loss, and functional impairment. While common in cancer, similar patterns of wasting are also observed in advanced cardiac, pulmonary, hepatic, and neurologic disease. Patients affected often experience marked fatigue, loss of independence, and social withdrawal—compounding both physical and emotional suffering.

Emerging evidence from clinical trials in cancer rehabilitation and chronic disease populations suggests creatine supplementation may modestly improve lean body mass and muscle strength, particularly when paired with resistance activity or physical therapy. In earlier stages of illness, such gains may help patients remain ambulatory, delay transitions to bed-bound status, and maintain the ability to perform basic ADLs—all of which directly translate to improvements in quality of life and autonomy.

A randomized trial conducted by Tarnopolsky et al. in patients with neuromuscular disease demonstrated improved muscle strength and endurance with creatine supplementation. While not specific to cancer or hospice populations, these findings support the notion that creatine’s cellular energy-enhancing properties may have broad application in diseases marked by muscle loss and mitochondrial dysfunction. Tarnopolsky has also proposed that creatine’s anti-inflammatory and antioxidant properties could provide additional benefit in systemic wasting syndromes such as cachexia.

Addressing Fatigue in Serious Illness

Fatigue is a leading complaint among patients with life-limiting disease and one of the most difficult symptoms to treat. It is often multifactorial, arising from disease burden, anemia, poor nutritional intake, deconditioning, or polypharmacy. Unlike stimulants such as methylphenidate or modafinil, which are sometimes employed but carry risks of anxiety or insomnia, creatine offers a gentler approach through metabolic support.

By replenishing phosphocreatine reserves and promoting more efficient ATP turnover, creatine may improve subjective and objective energy levels in debilitated patients. Small studies in chronic heart failure and multiple sclerosis patients—two populations with high fatigue burden—have shown improved exercise tolerance and reduced perceived fatigue. These findings support further investigation in palliative populations, where even minor improvements in energy can enable greater interaction with family or participation in meaningful activities.

Neurocognitive Support: A Possible Additional Benefit

Cognitive decline—whether due to dementia, delirium, or underlying neurodegeneration—is common in hospice and palliative care. Interestingly, creatine has been shown to cross the blood-brain barrier and may enhance neuronal energy metabolism. Some pilot studies suggest creatine supplementation may improve working memory and mental clarity in older adults, although results are mixed and limited by sample size. Still, in patients with early cognitive decline, especially when related to fatigue or systemic disease, creatine may support cerebral energetics in a way that contributes to better cognition and mood.

Safety, Practicality, and Limitations

Creatine is generally well-tolerated and inexpensive. Side effects are rare and usually limited to minor gastrointestinal upset or bloating. A potential increase in serum creatinine levels may be observed, but this reflects increased creatine metabolism and is not necessarily indicative of renal dysfunction. Nonetheless, caution is advised in patients with advanced kidney disease, as creatine is renally excreted and safety data in this population is sparse.

In hospice patients with very limited life expectancy, the benefits of creatine may be negligible given the time required (several days to weeks) for physiologic effects to manifest. However, in palliative care patients with a prognosis of months, those participating in rehabilitation efforts, or patients with neurodegenerative conditions experiencing progressive functional decline, creatine may offer a valuable adjunct.

 Integrating Creatine Into Palliative Care Plans

From a clinical standpoint, creatine supplementation could be considered for:

- Patients with cancer cachexia and a prognosis exceeding several weeks;

- Individuals with advanced neuromuscular disease (e.g., ALS, Parkinson’s) experiencing progressive motor decline;

- Debilitated patients undergoing palliative rehabilitation who remain motivated to maintain function;

- Patients suffering from fatigue not responsive to traditional interventions.

A typical dosage of creatine monohydrate is 3–5 grams daily. Unlike loading strategies used in athletic populations, a consistent daily maintenance dose is sufficient in medical settings.

Dr. Mark Tarnopolsky's Contributions

Dr. Mark Tarnopolsky, a profession at McMaster University in Canada, specializing in neuromuscular and neurometabolic disorders, has conducted extensive research on creatine supplementation. In a randomized controlled trial, Dr. Tarnopolsky and colleagues investigated the effects of creatine monohydrate in patients with mitochondrial cytopathies, finding improvements in muscle strength and function.  While this study did not focus on cancer cachexia, it highlights creatine's potential benefits in muscle-related conditions.

Conclusion

As palliative medicine continues to evolve beyond symptom control toward enhancing function, dignity, and quality of life, safe and practical interventions such as creatine deserve greater consideration. While more targeted studies are needed to establish creatine's efficacy in end-of-life populations, its known physiologic effects—supporting muscle mass, reducing fatigue, and possibly aiding cognition—align with many of the goals of palliative care.

In the right patient, creatine supplementation may represent a small but meaningful step in preserving autonomy, reducing suffering, and enhancing the final chapter of life.

References:

• Tarnopolsky MA, Parise G, Fu MH, et al. Creatine monohydrate increases strength in patients with neuromuscular disease. Neurology. 1999;52(4):854-857.
• Johannsmeyer S. The effects of 'high-low' resistance training and creatine supplementation in aging adults [dissertation]. Regina, Saskatchewan, Canada: University of Regina; 2016. Available from: ProQuest Dissertations & Theses Global. Publication No. 28140829.
• Gala K, Desai V, Liu N, et al. How to increase muscle mass in critically ill patients: Lessons learned from athletes and bodybuilders. Curr Nutr Rep. 2020;9:369-380. doi:10.1007/s13668-020-00334-0
• Persky AM, Brazeau GA. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacol Rev. 2001;53(2):161-176.
• Writing Group for the NINDS Exploratory Trials in Parkinson Disease (NET-PD) Investigators. Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: A randomized clinical trial. JAMA. 2015;313(6):584-593. doi:10.1001/jama.2015.12
• Karam CY, Paganoni S, Joyce N, Carter GT, Bedlack R. Palliative care issues in amyotrophic lateral sclerosis: An evidence-based review. Am J Hosp Palliat Med. 2014;33(1):84-92. doi:10.1177/1049909114548719