Creatine: A Supplement for Longevity?

Clinical trials confirm that creatine is the gold standard supplement for muscle performance:

• Strength gain of about 8–10% and power gain of up to 15% in high-intensity sports [5].
• After 12 weeks of training, supplemented participants gained 2 to 4 lbs more lean mass than those on placebo [6].

A 2004 trial showed a 20–40% reduction in muscle damage markers after eccentric exercise (negative movements), and faster recovery [7].

These benefits go beyond sport. In seniors: a meta-analysis in those over 50 shows an average gain of +1.4 kg of muscle mass and +14% of strength over 12 weeks , slowing sarcopenia and reducing the risk of falls [8].

The brain uses nearly 20% of our total energy, and relies heavily on creatine phosphate to rapidly regenerate neuronal ATP.

• Cognition and memory : In a randomized trial (Rae et al., 2003), vegetarians supplemented with 5 g/d for 6 weeks improved working memory by +45% and reasoning by +15% [9].
• Sleep deprivation : In 2024, a study published in Scientific Reports showed that a single dose of 0.35 g/kg (≈20–30 g) improved memory and cognitive processing speed by 20–25%, with the effect lasting up to 9 h [10].
• Alzheimer's and neuroprotection : Pilot trials indicate that creatine may slow cognitive decline in early stages by improving neuronal energy metabolism [11].
• Depression : Several small trials have shown that adding 5 g/d of creatine to antidepressant treatment could accelerate the improvement of symptoms in 30 to 40% of patients [12].

These results, although sometimes preliminary, place creatine among the promising nutraceuticals for brain health.

Creatine also plays a little-known role in blood glucose regulation. It enhances the expression and translocation of GLUT-4, the transporter that allows glucose to enter muscle cells.

Clinical trial in type 2 diabetic patients (Gualano et al., 2011) [11]:

• 25 patients, supplemented with 5 g/day for 12 weeks, combined with an exercise program.
• Results: Reduction of HbA1c from 7.4 to 6.4%, lower postprandial blood glucose, improved glucose tolerance.
• Safety: no negative impact on renal function (stable glomerular clearance).

Trial in healthy sedentary men (2023, Nutrients) [12]:

• 30 participants, supplemented with 10 g/day + aerobic training for 3 months.
• Results: Improvement in glucose tolerance (OGTT test), with no change in fasting insulin or HOMA-IR.👉 These data suggest that creatine could be a preventive tool against insulin resistance and diabetes, especially when combined with exercise.

Creatine improves glucose uptake into muscles by stimulating the GLUT-4 transporter.

Type 2 diabetes (25 patients, 12 weeks, 5 g/day): decrease in HbA1c from 7.4% to 6.4%, reduction in postprandial blood glucose and improved glucose tolerance [13].

Sedentary men (30 participants, 3 months, 10 g/d + training): 30% improvement in glucose tolerance (OGTT test), with no change in fasting insulin [14].

👉 Creatine appears to be a preventative tool against insulin resistance and diabetes, especially when combined with exercise.

Creatine acts at the cellular level through more subtle mechanisms:

• Membrane stabilization: improves the integrity of phospholipids.
• Oxidative stress: reduces oxidative markers by 25% and stimulates antioxidant enzymes such as superoxide dismutase [15].
• Growth factors: increases by 15 to 20% the expression of IGF-1 and myogenic genes essential for muscle repair [16].

These data reinforce the idea that creatine acts as a multifunctional longevity molecule.

Trials show that women benefit as much as men:

• Muscle contraction: +10% strength in the quadriceps after short supplementation [17].
• Bone health: In postmenopausal women, creatine + resistance increased bone mineral density by +2 to 3% after 12 months [18].
• Muscle aging: preservation of lean mass and autonomy.

👉 Contrary to popular belief, creatine does not cause masculinization or excessive weight gain. The slight weight gain observed corresponds to beneficial intracellular hydration.

This is probably the most common criticism. The reality is simple: creatine increases blood creatinine, a natural byproduct of its metabolism, but this does not reflect kidney damage.

• Trial in type 2 diabetics (Gualano et al., 2011) [13]: despite the expected increase in creatinine, glomerular clearance (measured with 51Cr-EDTA) remained stable, without proteinuria or albuminuria.
• Long-term study (Poortmans et al., 1999) [19]: athletes consuming up to 20 g/day for several years showed no impairment of renal function.

These results converge: in healthy people, creatine is safe, even in the long term and at high doses.

• Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM. Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the 'phosphocreatine circuit' for cellular energy homeostasis. Physiol Rev. 2000;80(3):1107–1171. PMID: 10893433
• Burke DG, Chilibeck PD, Parise G, Candow DG, Mahoney D, Tarnopolsky M. Effect of creatine and weight training on muscle creatine and performance in vegetarians. Med Sci Sports Exercise 2003;35(11):1946–55. PMID: 14600563
• Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev. 2000;80(3):1107–1213. PMID: 10893433
• Sestili P, Martinelli C, Colombo E, Barbieri E, Potenza L. Creatine as an antioxidant. Amino Acids. 2011;40(5):1385–96. PMID: 20809238
• Rawson ES, Volek JS. Effects of creatine supplementation and resistance training on muscle strength and weightlifting performance. J Strength Cond Res. 2003;17(4):822–31. PMID: 14636102
• Vandenberghe K, et al. Long-term creatine intake in humans is safe and effective. J Appl Physiol. 1997;83(1):205–213. PMID: 9390970
• Cooke MB, et al. Creatine supplementation reduces markers of muscle damage and inflammation after eccentric exercise. J Sports Sci. 2009;27(9):956–62. PMID: 19253048
• Devries MC, Phillips SM. Creatine supplementation during resistance training in older adults—a meta-analysis. J Gerontol A Biol Sci Med Sci. 2014;69(11):1429–36. PMID: 24787146
• Rae C, Digney AL, McEwan SR, Bates TC. Oral creatine monohydrate supplementation improves brain performance: a double–blind, placebo–controlled, cross–over trial. Proc Biol Sci. 2003;270(1529):2147–50. PMID: 12614580
• McMorris T, et al. Creatine supplementation and cognitive performance under sleep deprivation. SciRep. 2024. DOI: 10.1038/s41598-024-xxxxx
• Adhihetty PJ, Beal MF. Creatine and its potential therapeutic value for targeting cellular energy impairment in neurodegenerative diseases. Neurotherapeutics. 2008;5(4):616–29. PMID: 19016132
• Roitman S, Green T, Osher Y, Karni N, Levine J. Adjunctive creatine monohydrate for the treatment of major depressive disorder: a preliminary study. J Affect Disord. 2007;101(1–3):245–9. PMID: 17173982
• Gualano B, et al. Creatine supplementation improves glycemic control in type 2 diabetes patients. Med Sci Sports Exercise 2011;43(5):770–8. PMID: 20881878
• Gualano B, et al. Creatine supplementation and aerobic training improve glucose tolerance in sedentary males. Nutrients. 2023;15(2):341. PMID: 37445435
• Sestili P, et al. Creatine exerts direct antioxidant effects and enhances cellular resistance to oxidative stress. Free Radic Biol Med. 2002;33(11):1544–53. PMID: 12361800
• Willoughby DS, Rosene JM. Effects of oral creatine and resistance training on myogenic regulatory factor expression. J Strength Cond Res. 2003;17(4):793–9. PMID: 12930196
• Kambis KW, Pizzedaz SK. Short-term creatine supplementation increases maximal quadriceps contraction in women. Int J Sport Nutr Exerc Metab. 2003;13(1):87–96. PMID: 12759936
• Chilibeck PD, et al. Effect of creatine and resistance training on bone health in postmenopausal women. Med Sci Sports Exercise 2015;47(8):1587–95. PMID: 25546444
• Poortmans JR, Francaux M. Long-term creatine supplementation does not impair renal function in healthy athletes. J Sports Med Phys Fitness. 1999;39(3):178–82. PMID: 10395357