Creatine: A Supplement for Longevity?

Long relegated to the image of a supplement for bodybuilders, creatine is now recognized as a universal molecule of cellular energy . More than 500 clinical studies confirm its efficacy and safety [1], and its benefits extend well beyond athletic performance: muscle support, neuroprotection, metabolic regulation, reduction of oxidative stress and prevention of aging .

1. Biochemistry: the backup battery of our cells

Creatine is produced by the liver, kidneys, and pancreas from three amino acids (arginine, glycine, and methionine), at a rate of 1–2 g/day. A meat-based diet provides approximately 1 g/day more, but vegetarians have on average 20–30% less muscle creatine [2]. Total creatine stores in the human body vary between 120 and 160 g , with 95% located in skeletal muscles [3]. Its role is to replenish ATP (cellular energy). During intense exercise, ATP stores are depleted in 8–10 seconds . Phosphorylated creatine (phosphocreatine) triples the rate of ATP regeneration, acting as a backup battery [4].

2. Strength, muscle mass and aging

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

• Strength gain of approximately 8–10% and power gain of up to 15% in high-intensity sports [5].
• After 12 weeks of training, the 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 exercises (negative movements), and faster recovery [7].

These benefits extend beyond sport. In seniors: a meta-analysis in those over 50 years old 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].

3. The brain: energy, cognition, and mood

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/day 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 an effect lasting up to 9 h [10].
• Alzheimer's and neuroprotection : pilot trials indicate that creatine could slow cognitive decline in early stages by improving neuronal energy metabolism [11].
• Depression : Several small trials have shown that adding 5 g/day of creatine to antidepressant treatment could accelerate symptom improvement in 30 to 40% of patients [12].

These results, although sometimes preliminary, place creatine among the nutraceuticals with the greatest potential for brain health.

4. Metabolism, glucose and insulin

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

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

• 25 patients, supplemented with 5 g/day for 12 weeks, combined with an exercise program.
• Results: reduction in HbA1c from 7.4 to 6.4%, decrease in 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: improved glucose tolerance (OGTT test), without 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.

5. The Hidden Cellular Benefits

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/day + training): 30% improvement in glucose tolerance (OGTT test), without change in fasting insulin [14].

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

6. Creatine and cellular health: beyond muscles

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 the expression of IGF-1 and myogenic genes essential for muscle repair by 15 to 20% [16].

This data reinforces the idea that creatine acts as a multifunctional longevity molecule.

7. Creatine in women

Studies show that women derive as many benefits as men:

• Muscle contraction: +10% quadriceps strength 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: preserving lean mass and autonomy.

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

8. Myth: Does creatine damage the kidneys?

This is probably the most frequent 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 alteration in renal function.

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

9. How to use it?

Recommended form: creatine monohydrate (standard or micronized). Dosage: 3–5 g/day for maintenance. Optional: loading phase (20 g/day for 5–7 days) to reach saturation more quickly. Hydration: stay well hydrated, as creatine draws water into the muscles. Timing: consistency is more important than the time of day. Taking it post-workout with carbohydrates may improve absorption.

10. Conclusion: a universal molecule of longevity

Creatine isn't just a supplement for athletes. It's a universal molecule that acts as an energy and protective key: it supports muscle strength, nourishes the brain, regulates glucose, and stabilizes cells. Far from the stereotypes, creatine is now established as a cornerstone of longevity medicine—safe, accessible, and validated by decades of research.

References

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• 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
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• 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