Beyond Performance: Why We Tested a Longevity Creatine Formula in Zebrafish

Beyond Performance: Why We Tested a Longevity Creatine Formula in Zebrafish

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Sep 1, 2026 |5 mins to read

Most creatine products are designed for performance over longevity. They are a staple for gym goers, supporting muscle strength and aiding recovery. However, creatine’s main benefit is its ability to quickly recycle cellular energy, crucial for supporting longevity. 

As we age, multiple biological systems begin to change simultaneously. Cellular energy production in the mitochondria becomes less efficient, oxidative stress accumulates, inflammation increases, and mechanisms that maintain DNA integrity begin to decline. These interconnected processes may seem small, but combined over time, they influence how we move, feel, and age. 

This understanding led us to develop MitoQ Longevity Creatine Complex, a formulation designed not just for performance, but for healthy aging rooted in cellular energy. To better understand how our ingredient combination worked at a cellular level, we conducted a preclinical zebrafish study that examined several biological markers associated with aging.  

What you’ll learn: 

  • What makes MitoQ Longevity Creatine Complex different from traditional creatine supplements. 
  • Why we studied the formula in a zebrafish model of accelerated ageing. 
  • How creatine, L-carnitine and AKG worked better together than alone. 
  • What the findings tell us about cellular energy, resilience and healthy ageing. 
  • Why We Created MitoQ Longevity Creatine Complex 

 

Creatine monohydrate is one of the most researched nutritional ingredients available with over 600 clinical studies. Decades of research have demonstrated benefits for muscle performance, strength, recovery, and increasingly, cognitive function.  

However, healthy aging is a multi-system challenge. Maintaining muscle function is important, but so are mitochondrial health, metabolic flexibility, cellular resilience, immune balance, and brain function. 

We wanted to build upon the foundation of creatine by combining it with ingredients that support complementary biological pathways involved in healthy aging. The result was a formulation that supports: 

  • Muscle strength and performance 
  • Cognitive function and focus 
  • Cellular energy production 
  • Healthy aging pathways 
  • Cellular resilience and recovery 

What's Inside the Formula? 

Creatine Monohydrate 

Creatine acts as a rapid energy recycling system. It helps replenish ATP, the body's primary energy currency, supporting muscles, the brain, and other high-energy tissues.  

Citicoline 

A highly bioavailable form of choline, citicoline is a precursor to building phospholipids and neurotransmitters for healthy brain function. Citicoline has been clinically shown to support cognition, attention, and focus, which are often affected by aging. 

L-Carnitine 

L-carnitine is used by the body to transport fatty acids into mitochondria where they can be converted into energy. This supports metabolic flexibility and mitochondrial function, helping cells access a broader range of fuel sources.  

Alpha-Ketoglutarate (AKG) 

AKG is a naturally occurring intermediate in the Krebs cycle, the central pathway that produces cellular energy. Beyond its role in metabolism, AKG has attracted growing interest for its potential role in healthy aging and cellular resilience and is known to activate key healthy aging pathways. 

Glycine 

Glycine is an amino acid that serves several important functions in healthy ageing. It is a building block for creatine synthesis and is also required for the production of glutathione, one of the body's most important antioxidants. Through its role in cellular repair, antioxidant defence and energy metabolism, glycine helps support the systems that protect cells from age-related stress. 

CreaSpanTM 

Of these ingredients, we wanted to test the three that were most closely tied to cellular energy – Creatine, L-Carnitine, and AKG. Together, these three ingredients form CreaSpan™, our Cell Longevity Complex. 

Why Combine These Ingredients? 

In order for creatine to work, it relies on energy production in the mitochondria. Remember, creatine does not make energy (ATP), it recycles it, so that energy first has to come from somewhere. Each ingredient we chose for the study contributes to cellular energy production from a different angle. 

Ingredient Primary function
Creatine Rapid ATP recycling
L-Carnitine Fat transport into mitochondria
 AKG Supports mitochondrial energy metabolism

 

Rather than targeting a single pathway, the combination was designed to support how cells create, utilize, and maintain energy over time. 

The hypothesis was simple: if these ingredients support complementary energy and resilience pathways, could they produce greater benefits together than individually?  

We used the same ratio of creatine: AKG : L-carnitine as is found in our formulation, but at a much smaller, appropriate, dose. 

Why Synergy Matters: Testing the Combination vs Individual Ingredients 

When developing MitoQ Longevity Creatine Complex, we weren't simply looking for a way to add more ingredients to creatine. The goal was to determine whether combining ingredients that support complementary aspects of cellular energy and healthy aging could produce a greater effect than any single ingredient alone.  

Creatine, L-carnitine and alpha-ketoglutarate (AKG) each contribute to cellular health through different biological pathways: 

  • Creatine helps rapidly recycle ATP, providing immediate energy for muscles, the brain and other high-demand tissues.  
  • L-carnitine helps transport fatty acids into mitochondria, where they can be converted into energy.  
  • AKG is a key component of mitochondrial energy metabolism and has been investigated for its potential role in cellular resilience and healthy aging pathways.  

Rather than acting through the same mechanism, these ingredients support different parts of the cellular energy network. We hypothesized that targeting multiple interconnected pathways simultaneously could have a greater impact on cellular health than targeting any one pathway alone. 

Why Use a Zebrafish Model? 

Zebrafish are widely used in aging research because many of the biological processes involved in aging are conserved across species. 

For this study, a team of external researchers used an oxidative stress-induced aging model designed to reproduce several hallmarks associated with aging, including: 

  • Oxidative stress 
  • Mitochondrial dysfunction 
  • Reduced cellular energy 
  • Inflammation 
  • Neurotransmitter changes 
  • Alterations in telomere biology 

The model allowed us to rapidly evaluate whether the ingredient combination influenced multiple markers of healthy aging simultaneously.  

What Did We Measure? 

Researchers evaluated biomarkers associated with five key areas of healthy aging: 

  • Cellular Energy 
  • Measured through ATP production. 
  • Oxidative Stress 
  • Measured through reactive oxygen species (ROS). 
  • Immune Response 
  • Measured through IL-6, a marker associated with inflammatory signalling. 
  • DNA Integrity 
  • Measured through telomerase activity and telomere length. 
  • Brain Health and Signalling 

Measured through dopamine and acetylcholinesterase activity. Acetylcholinesterase is an enzyme that breaks down acetylcholine, and important neurotransmitter.  

The Results 

Compared with the ageing model, the combination of creatine, L-carnitine and AKG demonstrated improvements across every biomarker measured.* Researchers also compared the effects of creatine monohydrate alone with the complete Longevity Creatine Complex to determine whether the ingredients worked better in combination than individually. 

The results showed a consistent pattern: the ingredient combination produced stronger effects than creatine alone across all markers of healthy ageing. This included greater improvements in cellular energy production, oxidative stress, inflammation, brain signalling and DNA integrity. 

Most notably, the Longevity Creatine Complex reduced reactive oxygen species (ROS), a key driver of oxidative stress, by 16%, compared with an 8% reduction from creatine alone. Similarly, the combination increased telomere length by 253%, more than double the improvement observed with creatine monohydrate (121%). 

Across all biomarkers, the combined formulation delivered improvements that were approximately 1.5 to 2 times greater than creatine alone, providing evidence that these ingredients may work synergistically to support multiple hallmarks of healthy ageing. 

 Marker Creatine improvement vs aging model  Longevity complex improvement vs aging model  MitoQ Mix effect vs Creatine Monohydrate alone. 
Telomere length  121% increase  253% increase  2.1× greater 
Telomerase  31% increase  45% increase 1.5x greater
AChE 18% reduction 29% reduction 1.6x greater
IL-6 13% reduction 23% reduction 1.8x greater
ATP 11% increase 19% increase 1.8x greater
ROS 8% reduction 16% reduction 2.0x greater

 

*Results are from a preclinical model of aging. Results may not be reflected in humans.  

What Do These Results Mean? 

The findings suggest that combining creatine, L-carnitine and AKG may influence multiple biological systems involved in healthy aging simultaneously. 

Several observations are particularly interesting: 

  • Increased ATP production suggests improved cellular energy availability. 
  • Reduced ROS indicates support against oxidative stress. 
  • Lower IL-6 suggests improved immune balance. 
  • Improvements in telomere biology may indicate enhanced cellular resilience. 
  • Changes in dopamine and acetylcholinesterase suggest support for neurological signalling pathways. 

Collectively, the results support the concept that healthy aging is driven by interconnected systems, and that addressing multiple pathways may be more effective than targeting a single mechanism.  

Important Considerations 

While these findings are exciting, they come from a preclinical zebrafish model, not a human clinical trial. 

Preclinical studies help researchers understand biological mechanisms and explore whether ingredient combinations behave differently from individual ingredients. However, results observed in zebrafish cannot be assumed to occur to the same extent in humans. 

What the study does provide is evidence supporting the scientific rationale behind the formulation and demonstrating that the ingredient combination produced stronger responses than individual ingredients across several aging-related biomarkers.  

Final Takeaway 

Creatine has long been viewed as a performance ingredient. Our goal was to explore what happens when creatine is combined with ingredients that support mitochondrial function, metabolic flexibility, and cellular resilience. 

The zebrafish study suggests that combining creatine, L-carnitine and AKG may support multiple markers associated with healthy aging more effectively than the ingredients alone. While further human research is needed, these findings helped validate the scientific rationale behind MitoQ Longevity Creatine Complex and its focus on strength, cognition, cellular energy, and healthy aging.  

Disclaimer: This blog contains promotional content about our products. The information provided in this blog is for educational and informational purposes only and should not be construed as medical advice. Always consult your healthcare provider with any questions you may have regarding a medical condition or health objectives.
Georgia Truman is the Scientific Affairs Manager at MitoQ, based in Hamilton, New Zealand. She leads the Mitochondrial Collaborative Research Programme (MCRP) and oversees science communications, helping bring the latest research on mitoquinol, mitochondrial health, and longevity to life for the MitoQ community. Georgia also hosts The MitoPod, MitoQ’s podcast dedicated to mitochondrial health and longevity science