Creatine

What is creatine?

Creatine is a naturally occurring compound your body synthesizes from three amino acids: arginine, glycine, and methionine, primarily in the liver and kidneys. About 95% of the body's creatine is stored in skeletal muscle as phosphocreatine, where it functions as a rapid-access energy reserve. During high-intensity muscle contractions, ATP is consumed and creatine phosphate donates its phosphate group to regenerate ATP within seconds, faster than any other metabolic pathway ^[1].

What makes creatine particularly interesting from a longevity perspective is that endogenous creatine synthesis declines with age, and this decline appears to correlate with DNA methylation patterns that predict biological aging and mortality risk ^[2].

Creatine for muscle strength and body composition

Decades of research confirm that creatine monohydrate increases intramuscular phosphocreatine stores by 20-40%, producing measurable gains in strength, power, and high-intensity exercise capacity. A 2024 meta-analysis found that creatine combined with resistance training increased upper-body strength by 4.4 kg and lower-body strength by 11.4 kg versus placebo ^[3].

For aging adults, the benefits go beyond the gym. Sarcopenia, the age-related loss of muscle mass, is one of the strongest predictors of frailty and mortality. A 2025 systematic review of over 1,000 older adults showed that creatine combined with exercise training significantly improved maximal strength, with effects becoming clear after 12 weeks ^[4]. A 2025 JISSN position paper recommended creatine as a viable intervention for sarcopenia, osteoporosis, and frailty ^[5].

Brain health and cognitive benefits

The brain consumes roughly 20% of the body's total energy despite being only 2% of body mass. A 2024 meta-analysis of 16 RCTs found that creatine significantly improves memory, attention, and processing speed in adults ^[6]. These benefits are strongest during sleep deprivation, mental fatigue, or chronic stress, when the brain's energy demands outstrip supply.

A 2025 review focused on older adults found that five of six studies reported positive effects of creatine on cognition in aging populations, particularly for memory and attention ^[7]. Preclinical evidence also points to neuroprotective properties: creatine may buffer against excitotoxicity and mitochondrial dysfunction.

Creatine, methylation, and biological aging

Your body's synthesis of creatine consumes approximately 40% of all methyl groups donated by S-adenosylmethionine (SAMe), the universal methyl donor. Supplementing with exogenous creatine reduces this burden, freeing up SAMe methyl groups for other functions including DNA methylation, neurotransmitter synthesis, and detoxification ^[2]. A 2025 study of nearly 5,000 adults aged 50 and older found that higher dietary creatine intake was inversely correlated with epigenetic mortality risk scores, even after adjusting for demographic and dietary factors. In practical terms: people who consumed more creatine showed younger biological age markers ^[2].

Creatine for women

Women have 70-80% lower endogenous creatine stores compared to men, which means they may benefit even more from supplementation. A 2025 review in the Journal of the International Society of Sports Nutrition examined creatine across the female lifespan and found that hormonal fluctuations during menstruation, pregnancy, and menopause all affect creatine metabolism ^[8]. Population data from NHANES showed that women consuming adequate dietary creatine had a 25% lower risk of irregular periods. For postmenopausal women, creatine combined with resistance training improved bone geometric properties at the femoral neck, a common fracture site ^[9].

Mood and mental health

Emerging research connects creatine to mental health, likely through its effects on brain energy metabolism. A 2024 randomized controlled pilot trial found that creatine added to cognitive behavioral therapy reduced depression scores (PHQ-9) by 5.12 points more than placebo plus CBT over 8 weeks ^[10]. Population-level data from a study published in Translational Psychiatry showed an inverse, stepwise association between dietary creatine consumption and depression risk ^[11]. The proposed mechanism: creatine restores brain energy levels and modulates neurotransmitter systems that regulate mood.

Safety and kidney health

Creatine monohydrate has an excellent safety record. A 2025 meta-analysis of 21 studies confirmed that creatine does not adversely affect kidney function in healthy individuals ^[12]. While serum creatinine may rise slightly, this reflects natural conversion of creatine to creatinine, not kidney damage. Long-term studies of up to five years report no serious adverse effects ^[13]. The FDA classified creatine as GRAS (generally recognized as safe) in 2020.

Dosing and practical recommendations

Take 3-5 grams of creatine monohydrate daily, consistently. Loading phases (20 g/day for 5-7 days) saturate stores faster but aren't necessary; daily dosing reaches full saturation within 3-4 weeks ^[14]. Creatine monohydrate remains the gold standard. Newer forms like creatine HCl have no proven advantage despite higher cost.

• Take with a meal or post-workout for optimal absorption
• Stay well hydrated, as creatine increases intracellular water retention
• No cycling is required. Long-term daily use has been studied with an excellent safety profile
• Vegetarians, vegans, and women often see larger benefits due to lower baseline creatine stores
• Look for third-party tested products (NSF Certified for Sport or Informed Choice)