Creatine: One of the Most Studied Supplements in Sports and Health

By Dr. Steven Long, DO, MHA, CPT
Beyond Health | Precision Medicine for High-Performance Living

Author's note:  Even though I originally wrote an article on creatine only a few months ago, the evidence and expert opinions on certain areas of medicine change so rapidly that I had to revise this to provide a more accurate picture.  We will always do our best to make sure the information we share is the most up to date and pertinent for our audience.

Creatine monohydrate has long been a cornerstone supplement in the world of strength and conditioning — often associated with bodybuilders, athletes, and gym enthusiasts. But emerging evidence over the past decade has reframed creatine as something far more comprehensive: a neuroprotective, metabolic, and longevity-supporting compound.

Once dismissed as a “muscle supplement,” creatine is now being studied for its potential to support brain health, cognitive performance, and even mood regulation, particularly under conditions of stress, sleep deprivation, or aging.

And despite decades of concern and misinformation, high-quality research continues to affirm a key fact: in healthy individuals, creatine has never been shown to cause harm.

At Beyond Health, we view creatine not as a “performance enhancer,” but as a cellular energy optimizer — supporting both body and brain function for long-term healthspan.

1. What Is Creatine and How Does It Work?

Creatine is a naturally occurring compound synthesized from arginine, glycine, and methionine in the liver and kidneys. It’s stored primarily in skeletal muscle (≈95%) and the brain (≈5%) as phosphocreatine, a high-energy molecule used to rapidly regenerate ATP — the body’s primary energy currency.

During high-demand states — such as intense exercise, sleep deprivation, or mental exertion — phosphocreatine donates phosphate groups to ADP, allowing for faster ATP resynthesis and sustained cellular function.

In other words, creatine helps cells — especially neurons and muscle fibers — keep producing energy when demand outpaces supply.

2. What Does the Research Say About Physical Benefits?

Creatine remains the most extensively studied ergogenic aid in history, with over 1,000 peer-reviewed human trials.

Strength and Performance

• Creatine supplementation increases strength, power, and lean body mass by 5–15% in trained and untrained populations (Kreider et al., J Int Soc Sports Nutr, 2017).
• It enhances high-intensity exercise capacity, allowing greater total training volume and adaptation over time.
• Benefits are consistent across age groups — from young athletes to older adults combating sarcopenia.

Bone and Muscle Health

• Creatine combined with resistance training improves bone mineral density and muscle function in older adults (Candow et al., Med Sci Sports Exerc, 2019).
• It enhances myosin cross-bridge cycling and cellular hydration, both of which stimulate muscle protein synthesis.

Metabolic Health

• Some studies suggest creatine supports glucose uptake and glycogen storage, improving insulin sensitivity and mitochondrial function (Op’t Eijnde et al., Diabetes Care, 2001).

These data make creatine one of the rare supplements that truly bridges performance enhancement and metabolic health.

3. The New Frontier: Brain and Mental Health

Emerging research has expanded creatine’s benefits beyond the gym — into the realm of cognitive resilience, mood regulation, and neuroprotection.

Cognitive Function

• The brain, like muscle, relies on rapid ATP regeneration. Supplementation increases brain creatine and phosphocreatine levels by ~10%, improving mental endurance during sleep deprivation, hypoxia, or cognitive overload (Allen et al., Proc R Soc B, 2012).
• Studies show improved working memory, reaction time, and reasoning during stress or fatigue, particularly in vegetarians and older adults (Avgerinos et al., Exp Gerontol, 2018).

Mood and Mental Health

• A growing number of clinical trials have explored creatine as an adjunctive treatment for depression, with some showing enhanced antidepressant response when added to SSRIs (Rooney et al., J Affect Disord, 2012).
• Mechanisms may include improved neuronal energy metabolism, increased synaptic signaling, and modulation of brain-derived neurotrophic factor (BDNF).

Neurodegenerative Protection

• Preliminary data suggest creatine may help preserve neuronal integrity in Parkinson’s and Alzheimer’s disease, although large trials have shown mixed results (Bender et al., Front Aging Neurosci, 2021).
• Ongoing studies are exploring whether higher dosing (10 g/day) may yield more consistent central nervous system and mental clarity benefits.

4. Latest Dosing Recommendations

The traditional athletic dose remains 3–5 g per day of creatine monohydrate, ideally taken with a carbohydrate-containing meal to enhance uptake.

However, newer studies exploring neurocognitive outcomes suggest benefits may occur at higher doses (10 g daily or more):

• A 2023 meta-analysis found cognitive improvements and mood resilience in participants supplementing 10 g/day for 4–8 weeks (Avgerinos et al., Nutrients, 2023).
• Importantly, even at this higher dose, no renal, hepatic, or cardiovascular adverse effects were reported in healthy adults.

For most patients:

• 3–5 g/day is sufficient for physical and metabolic support.
• 10 g/day may be reasonable for targeted cognitive enhancement or during high-demand periods (e.g., sleep deprivation, mental fatigue, neurodegenerative risk).

5. The Myth of “Creatine Damage”

Despite decades of use, no high-quality evidence supports claims that creatine damages the kidneys, liver, or heart in healthy individuals.

• Multiple long-term trials (up to 5 years) show no change in renal biomarkers (serum creatinine, BUN, GFR) with 3–10 g/day dosing (Poortmans & Francaux, Med Sci Sports Exerc, 1999; Kreider et al., J Int Soc Sports Nutr, 2017).
• Creatinine (the breakdown product of creatine) may appear elevated on lab testing, but this reflects increased production — not reduced kidney function.
• Individuals with preexisting renal disease should be evaluated before supplementing, but otherwise, creatine remains one of the safest, most studied compounds in all of nutrition science.

6. Beyond Health Implementation: How to Use Creatine Safely and Effectively

At Beyond Health, we integrate creatine supplementation as part of a broader metabolic and performance strategy, not as a standalone fix.

1. Dose Consistently:

• 3–5 g/day for most, up to 10 g/day for cognitive benefit trials.
• No loading phase necessary; saturation occurs after ~3–4 weeks of consistent use.

2. Combine with Resistance Training:

• Synergistic effects enhance lean mass retention, muscle performance, and metabolic rate.

3. Maintain Hydration:

• Creatine draws water into muscle cells; ensure 2.5–3 L fluid daily to maintain balance.

4. Track Labs Smartly:

• Expect mild creatinine elevation — interpret in clinical context, not as renal dysfunction.
• Monitor eGFR, creatinine, and cystatin C annually in long-term users.

5. Pair with Lifestyle Foundations:

• Adequate protein, sleep, and micronutrients (magnesium, B-vitamins) further support ATP and phosphocreatine metabolism.

7. Beyond Health’s Perspective

Creatine exemplifies what we value most at Beyond Health: simple, evidence-based interventions that improve function and longevity.
 It’s inexpensive, well-studied, and safe — yet offers wide-ranging benefits for muscle, metabolism, and mind.

Used correctly, it supports both performance and protection — helping maintain strength, cognitive clarity, and resilience well into older age.

Conclusion

Creatine is far more than a gym supplement. It’s a foundational molecule for energy metabolism, neural function, and cellular health.

When combined with smart training, nutrition, and recovery, it becomes a cornerstone in the pursuit of strength and longevity.
 There’s no credible evidence that creatine harms healthy individuals — but overwhelming evidence that it can enhance quality of life and protect against age-related decline.

At Beyond Health, we see creatine as a model of modern preventive medicine: safe, affordable, and profoundly effective when paired with disciplined lifestyle practice.

References

1. Kreider RB, 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. 2017;14(1):18.
2. Candow DG, et al. Creatine Supplementation Combined with Resistance Training in Older Adults: A Systematic Review and Meta-analysis. Med Sci Sports Exerc. 2019;51(1):128–138.
3. Op’t Eijnde B, et al. Creatine Supplementation Improves Muscle Glycogen Accumulation During Recovery from Exercise in Humans. Diabetes Care. 2001;24(4):728–733.
4. Allen PJ, et al. Creatine Supplementation Improves Cognitive Performance in Sleep-Deprived Adults. Proc R Soc B. 2012;279(1749):1775–1781.
5. Avgerinos KI, et al. Effects of Creatine Supplementation on Cognitive Function in Humans: A Systematic Review and Meta-analysis. Exp Gerontol. 2018;108:166–173.
6. Rooney K, et al. Adjunctive Creatine for the Treatment of Depression: A Randomized Double-Blind Placebo-Controlled Trial. J Affect Disord. 2012;136(3):1179–1184.
7. Bender A, et al. Creatine in Neurodegenerative Diseases: Mechanistic Insights and Clinical Update. Front Aging Neurosci. 2021;13:738662.
8. Avgerinos KI, et al. Creatine Supplementation for Mental and Physical Fatigue: A Meta-analysis. Nutrients. 2023;15(3):565.
9. Poortmans JR, Francaux M. Long-Term Oral Creatine Supplementation Does Not Impair Renal Function in Healthy Athletes. Med Sci Sports Exerc. 1999;31(8):1108–1110.