Yen Nien (Jason) Hou, PharmD, DiplOM, LAc

Jyothirmai Gubili, MS

The ASCO Post’s Integrative Oncology series is intended to facilitate the availability of evidence-based information on integrative and complementary therapies sometimes used by patients with cancer. In this installment, Yen Nien (Jason) Hou, PharmD, DiplOM, LAc, and Jyothirmai Gubili, MS, focus on the mixed findings regarding the use of the natural supplement creatine in oncology as well as the need for further research on both its benefits and risks.

Common Names: Several including creatine monohydrate, creatine malate, creatine phosphate, creatine pyruvate

Overview

A nonessential nutrient, creatine is present in the skeletal muscles as well as in the brain and heart. It is produced in the body from the amino acids glycine, arginine, and methionine, and it plays an important role in energy production.

The International Society of Sports Nutrition, the American College of Sports Nutrition, and the Academy of Nutrition and Dietetics all state that creatine is an effective ergogenic nutrient for athletes and for individuals starting a health and fitness program.^1-3

The Science

Substantial data indicate that creatine has a positive impact on muscle mass, strength, and acute exercise capacity.⁴However, in older individuals, such improvements have been seen only when resistance training was added to creatine supplementation.^5,6 Creatine may also help to improve atherosclerosis and arterial stiffness,⁷ memory,⁸ and depression.⁹However, thus far, studies in patients with cancer have failed to find a benefit with creatine supplementation.

Guest Editor

Jun J. Mao, MD, MSCE

Dr. Mao is the Laurance S. Rockefeller Chair in Integrative Medicine and Chief of Integrative Medicine Service at Memorial Sloan Kettering Cancer Center, New York.

In a randomized trial, 263 patients with incurable disease were assigned to receive placebo or 20 g/day of creatine for 5 days followed by 2 g/day indefinitely, provided that no adverse events were observed. The primary endpoint was 10% or greater weight gain compared with baseline during the first month. Study authors found that only two patients in the creatine group gained the desired weight (P = 1.00). Other measures such as appetite and quality of life also did not show statistically significant differences between the groups.¹⁰

In another study involving 31 patients with colorectal cancer, 8-week creatine supplementation (20 g/day for the first week followed by 5 g/day) was found to be ineffective in improving muscle mass, function, or quality of life. However, there was improvement in phase angle, a marker of body cell mass and cell integrity.¹¹

Similarly, supplementation (20 g/day for 5 days followed by 5 g/day for 12 weeks) did not confer any additional benefits when added to resistance training (36 resistance exercise sessions, performed three times per week) in a trial of 55 men with prostate cancer undergoing androgen-deprivation therapy (P = .078–0.951).¹² Researchers also failed to find any impact of creatine on muscular performance (measured by sit-to-stand power, isometric/isokinetic peak torque, and upper/lower body strength) in a study of 19 breast cancer survivors who were randomly assigned to 20 g/day of creatine or placebo for 7 days.¹³

Of note, preclinical findings suggest that creatine may have a direct impact on cancer: It suppressed tumor growth¹⁴ but also promoted metastasis of colorectal and breast cancers.¹⁵ Further research is needed to resolve the ambiguity.

Proposed mechanisms underlying the physiologic effects of creatine include increasing anaerobic energy capacity and decreasing protein breakdown, which led to increased muscle mass and physical performance.⁴ Creatine also regulates reactive oxygen species formation by preventing electron transport chain stalling via its involvement in mitochondrial creatine kinase function.⁷

Adverse Reactions

Reported adverse effects associated with the use of creatine include gastrointestinal irritation, muscle cramps, headache,¹⁶and weight gain (due to water retention).^17,18

Herb-Drug Interactions

Chronic intake of caffeine during creatine loading may interfere with the beneficial effects of creatine.¹⁹

Summary

Creatine supplementation is well supported in athletic contexts for improving muscle strength and mass; however, evidence in oncology is limited and has not shown meaningful clinical benefit. Furthermore, preclinical studies yielded mixed findings ranging from tumor suppression to increased risk of metastasis, warranting further research in cancer populations. Trials of interventions that enhance strength, energy, and quality of life—while avoiding tumor growth—are critical to identify and validate nutrition or supplement strategies that target cancer-related muscle loss (cachexia), cognitive impairment (“chemo brain” or brain fog), and treatment-related fatigue.

For additional information, visit the “About Herbs” website at https://www.mskcc.org/cancer-care/integrative-medicine/herbs/creatine-01.

DISCLOSURE:Dr. Hou and Ms. Gubili reported no conflicts of interest.

REFERENCES

1. Kreider RB, Kalman DS, Antonio J, et al: International Society of Sports Nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr 14:18, 2017.
2. Rodriguez NR, DiMarco NM, Langley S: Position of the American Dietetic Association, Dietitians of Canada, and the American College of Sports Medicine: Nutrition and athletic performance. J Am Diet Assoc 109:509-527, 2009.
3. Thomas DT, Erdman KA, Burke LM: Position of the Academy of Nutrition and Dietetics, Dietitians of Canada, and the American College of Sports Medicine: Nutrition and athletic performance. J Acad Nutr Diet 116:501-528, 2016.
4. Kreider RB, Stout JR: Creatine in health and disease. Nutrients 13:447, 2021.
5. Devries MC, Phillips SM: Creatine supplementation during resistance training in older adults—A meta-analysis. Med Sci Sports Exerc 46:1194-1203, 2014.
6. Candow DG, Chilibeck PD, Forbes SC: Creatine supplementation and aging musculoskeletal health. Endocrine 45:354-361, 2014.
7. Aron A, Landrum EJ, Schneider AD, et al: Effects of acute creatine supplementation on cardiac and vascular responses in older men: A randomized controlled trial. Clin Nutr ESPEN 63:557-563, 2024.
8. Prokopidis K, Giannos P, Triantafyllidis KK, et al: Effects of creatine supplementation on memory in healthy individuals: A systematic review and meta-analysis of randomized controlled trials. Nutr Rev 81:416-427, 2023.
9. Kious BM, Kondo DG, Renshaw PF: Creatine for the treatment of depression. Biomolecules 9:406, 2019.
10. Jatoi A, Steen PD, Atherton PJ, et al: A double-blind, placebo-controlled randomized trial of creatine for the cancer anorexia/weight loss syndrome (N02C4): An Alliance trial. Ann Oncol 28:1957-1963, 2017.
11. Norman K, Stübler D, Baier P, et al: Effects of creatine supplementation on nutritional status, muscle function and quality of life in patients with colorectal cancer: A double blind randomised controlled trial. Clin Nutr 25:596-605, 2006.
12. Fairman CM, Kendall KL, Newton RU, et al: Creatine supplementation does not add to resistance training effects in prostate cancer patients under androgen deprivation therapy: A double-blind randomized trial. J Sci Med Sport 28:118-124, 2025.
13. Parsowith EJ, Stock MS, Kocuba O, et al: Impact of short-term creatine supplementation on muscular performance among breast cancer survivors. Nutrients 16:979, 2024.
14. Di Biase S, Ma X, Wang X, et al: Creatine uptake regulates CD8 T cell antitumor immunity. J Exp Med 216:2869-2882, 2019.
15. Zhang L, Zhu Z, Yan H, et al: Creatine promotes cancer metastasis through activation of Smad2/3. Cell Metab33:1111-1123.e4, 2021.
16. de Guingand DL, Palmer KR, Snow RJ, et al: Risk of adverse outcomes in females taking oral creatine monohydrate: A systematic review and meta-analysis. Nutrients 12:1780, 2020.
17. Kutz MR, Gunter MJ: Creatine monohydrate supplementation on body weight and percent body fat. J Strength Cond Res 17:817-821, 2003.
18. Powers ME, Arnold BL, Weltman AL, et al: Creatine supplementation increases total body water without altering fluid distribution. J Athl Train 38:44-50, 2003.
19. Elosegui S, López-Seoane J, Martínez-Ferrán M, et al: Interaction between caffeine and creatine when used as concurrent ergogenic supplements: A systematic review. Int J Sport Nutr Exerc Metab 32:285-295, 2022.

Dr. Hou is Manager of the “About Herbs” website, maintained by Memorial Sloan Kettering Cancer Center’s Integrative Medicine Service. Ms. Gubili is Editor, also at the Integrative Medicine Service, Memorial Sloan Kettering Cancer Center, New York.