Creatine is an amino acid-derived compound synthesised endogenously in the liver, kidneys and pancreas, playing a fundamental role in cellular bioenergetics(Reference Wyss and Kaddurah-Daouk1). By serving as a phosphate donor in the phosphocreatine system, creatine facilitates the rapid regeneration of ATP, particularly in tissues with high energy demands such as skeletal muscle, brain and heart(Reference Wallimann, Tokarska-Schlattner and Schlattner2). It is important to distinguish creatine from creatinine, a breakdown product of creatine catabolism that is excreted in urine and commonly used as a biomarker of renal function; unlike creatine, creatinine does not contribute to energy metabolism. Although the human body produces a portion of its daily creatine needs, approximately 50 % must be obtained through the diet – predominantly from animal-based foods like red meat and fish(Reference Brosnan, da Silva and Brosnan3). While creatine is widely recognised for its use as a dietary supplement and ergogenic aid, its broader role within food systems remains underappreciated. In the current landscape of nutrition science, where functional foods, plant-based diets and personalised nutrition are gaining momentum, there is a pressing need to reconsider how creatine can be integrated into mainstream food policy and practice. This paper examines the evolving role of creatine across four domains: its natural occurrence in food, incorporation into fortified food products, use as a dietary supplement and potential future classification as a pharmaceutical agent. Emphasis is placed on differences in regulatory status, intended use, dosage, labelling and public health implications – particularly regarding strategies to address insufficient creatine intake through food-based approaches.
Creatine requirements and population-level insufficiency
Creatine is considered a conditionally essential compound, with a daily requirement of approximately 1 g to maintain optimal physiological function (for a detailed review, see ref.no 4). Approximately half of this amount is synthesised endogenously, with the remainder expected from dietary intake. Animal-source foods are the primary contributors to exogenous creatine intake, making individuals who follow vegetarian, vegan or low-protein diets especially vulnerable to insufficient intake. Other at-risk populations include older adults, individuals with chronic disease, pregnant women and those with elevated energy demands, such as athletes.
Although severe creatine deficiency is rare and typically associated with inborn errors of metabolism(Reference Mercimek-Andrews and Salomons5), a growing body of evidence suggests that nutritional creatine insufficiency – characterised by suboptimal but non-clinical levels – may be widespread(Reference Ostojic6). Insufficiency can be assessed indirectly through circulating or urinary creatine concentrations, or more directly by measuring intramuscular creatine stores using magnetic resonance spectroscopy or biopsy-based assays(Reference Nedeljkovic and Ostojic7). In healthy young adults, plasma creatine concentrations typically range between 30 and 50 µmol/l, while intramuscular total creatine (free creatine plus phosphocreatine) averages 120–140 mmol/kg dry muscle(Reference Nedeljkovic and Ostojic7,Reference Hultman, Söderlund and Timmons8) . Suboptimal levels are often defined as values that fall below these normative ranges, though no universally accepted clinical cut-off has been established. Vegetarians and vegans, for instance, often exhibit plasma creatine levels that are 20–30 % lower and intramuscular concentrations reduced by ∼10–20 % compared with omnivores(Reference Burke, Chilibeck and Parise9).
Population-level data suggest that creatine status tends to decline with advancing age(Reference Nedeljkovic and Ostojic7). Compared with younger individuals, older adults may have muscle creatine concentrations that are 15–20 % lower(Reference Candow, Ostojic and Chilibeck10), a reduction linked to impaired muscle strength, diminished cognitive performance and reduced resilience to stressors(Reference Hong, Wang and Jin11). While some studies indicate that ageing may impair creatine synthesis and transporter function(Reference Sumien, Shetty and Gonzales12), other age-related factors – such as decreased consumption of animal-source foods, reduced physical activity and the presence of chronic disease – likely contribute to modest reductions in creatine availability(Reference Gualano, Rawson and Candow13). These combined behavioural and physiological influences may help explain why older adults often present with lower creatine stores and reduced responsiveness to supplementation, even though a consistent age-related decline has not been demonstrated across all studies. Importantly, such subclinical reductions are rarely detected in clinical practice, as creatine is not included in standard biochemical panels, and creatinine – the primary breakdown product of creatine – does not accurately reflect whole-body creatine status.
This emerging recognition of creatine insufficiency has important public health implications. It has been associated with higher risk of depression(Reference Bakian, Huber and Scholl14), cognitive decline in the elderly(Reference Ostojic, Korovljev and Stajer15), cancer(Reference Jiang, Zhao and Chen16), liver conditions(Reference Todorovic, Korovljev and Stajer17) and all-cause mortality(Reference Ostojic18). Despite its biological significance, creatine is not currently included in nutrient intake recommendations, national dietary guidelines or food composition databases. Addressing this gap will require food system-oriented interventions, including targeted nutrition education, the development of creatine-fortified food products and the responsible use of dietary supplements. Such measures offer scalable and sustainable pathways to improve creatine status and support health across diverse population groups.
Creatine as a food-derived nutrient
In its natural dietary form, creatine is found almost exclusively in animal-based products such as meat, poultry and fish(19). In omnivorous diets, food-derived creatine contributes ∼1 g per d(Reference Brosnan, da Silva and Brosnan3), which, combined with endogenous synthesis, is generally sufficient to maintain tissue saturation in healthy individuals. Creatine’s function in this context is primarily to facilitate ATP regeneration through the creatine kinase system, enabling rapid energy buffering in high-demand tissues. Despite its importance, creatine is largely absent from current food system frameworks. Regulatory agencies do not require creatine content labelling, and it is rarely included in food composition databases or nutritional surveys. This oversight limits consumer awareness and hinders the development of public health policies aimed at optimising creatine intake through diet(Reference Ostojic6). Moreover, while creatine from food is highly bioavailable, cooking and food processing can degrade its content, further reducing intake in some dietary contexts(Reference Persky, Brazeau and Hochhaus20). For individuals who consume limited animal products, this gap reinforces the need for food-based alternatives that can ensure adequate creatine status through accessible, culturally appropriate means.
Creatine-fortified foods: a food system innovation
Creatine-fortified foods offer a novel strategy for addressing dietary insufficiency within the broader framework of functional nutrition. These products involve the targeted addition of synthetic creatine to plant-based or processed food matrices, such as meat alternatives, ready-to-drink beverages, protein bars and dairy substitutes. The aim is to increase creatine intake in populations that may not consume sufficient animal-source foods and to offer an accessible alternative to supplementation(Reference Ostojic21). Fortification levels typically range from 0·5 to 3 g per serving, which is likely sufficient to support measurable increases in tissue creatine stores over time. From a regulatory perspective, these products often occupy a grey area. In regions such as the European Union, the addition of creatine to conventional foods may fall under Novel Food Regulation, requiring safety assessments and pre-market approval. While therapeutic claims are not permitted, general structure/function or nutrient content claims (e.g. ‘supports normal energy metabolism’) may be allowed. Importantly, creatine-fortified foods align with modern food system goals, including support for plant-based diets, preventive health strategies and personalised nutrition. They also provide an avenue for reducing reliance on supplements and increasing creatine intake in a format that is familiar, acceptable and integrated into everyday dietary practices. As such, creatine fortification represents a promising public health strategy that complements traditional dietary approaches.
Creatine as a dietary supplement
Creatine’s most widely recognised application is as a dietary supplement, particularly in the form of creatine monohydrate. These products are extensively used to enhance muscular performance, cognitive function and support healthy ageing and are available in various formats including powders, capsules and functional drinks (for a detailed review, see ref.no 22). In many jurisdictions, including the USA, creatine supplements are regulated under food law (e.g. DSHEA) and do not require pre-market approval as long as they are not marketed with disease-related claims. Standard dosing involves an initial loading phase of 20 g per d for 5–7 d, followed by a maintenance dose of 3–5 g daily. This regimen has been consistently shown to increase muscle creatine content and improve performance in athletic, clinical and general populations. While creatine supplements are generally safe and well tolerated(Reference Kreider, Gonzalez and Hines23), gastrointestinal discomfort may occur at high doses, and absorption efficiency diminishes with excessive intake. Despite their popularity, creatine supplements remain separate from core food systems and are often excluded from dietary policies and public health frameworks. In addition, public scepticism toward supplements – particularly among older adults and individuals seeking food-first approaches – can limit their reach. This highlights the need for complementary, food-based strategies, such as fortification, to promote broader adoption and ensure creatine sufficiency through accessible, regulated channels.
Creatine as a pharmaceutical agent: a distinct pathway
Although creatine has not been approved as a pharmaceutical drug in any country, it has been investigated in clinical trials targeting a variety of health conditions, including amyotrophic lateral sclerosis, Parkinson’s disease, heart failure and depression. These trials, often conducted under Investigational New Drug (IND) frameworks or equivalent protocols, allow for scientific exploration of therapeutic efficacy without permitting commercial marketing as a drug. If creatine were to be developed as a pharmaceutical product, it would fall outside the domain of food systems entirely. Regulatory approval would require preclinical toxicology studies, Phases I–III clinical trials, GMP manufacturing standards and formal market authorisation via regulatory bodies such as the FDA or EMA(24). Therapeutic formulations may involve higher doses than those used in supplementation – sometimes exceeding 50 g per d – and could be administered orally or intravenously. While the pharmaceutical pathway may be suitable for specific clinical populations, it introduces barriers such as increased cost, limited accessibility and dependency on healthcare systems. In contrast, food-based approaches – whether through natural intake, fortification, or supplementation – offer broader reach and align more effectively with public health objectives focused on prevention, equity and sustainability (Table 1).
Table 1. Creatine as food-derived nutrient, fortified food, supplement and pharmaceutical agent
ALS, amyotrophic lateral sclerosis.
Conclusion
Creatine occupies a unique and underutilised position within contemporary food systems. While traditionally associated with sports performance supplements, its biological importance and broad range of health benefits call for expanded integration into food policy and nutrition practice. Populations at risk of creatine insufficiency – including vegetarians, older adults and individuals with high energy demands – stand to benefit from targeted interventions that go beyond supplementation alone. Creatine-fortified foods, improved public guidance and the incorporation of creatine into national nutrition strategies represent viable pathways to improve health outcomes at scale. As interest grows in sustainable diets and food-first approaches to health, leveraging creatine as a functional nutrient within food systems offers a timely and impactful opportunity. Future research, regulation and innovation should focus on embedding creatine into the evolving landscape of food-based health solutions – bridging gaps in intake, reducing disparities and supporting health across the lifespan.
Acknowledgements
SMO expresses gratitude to Shūsaku Endō for his transformative initiatives.
Financial support
None received.
Competing interests
S.M.O. serves as a member of the Scientific Advisory Board on Creatine in Health and Medicine (AlzChem LLC). S.M.O. is a co-owner of the patent ‘Supplements Based on Liquid Creatine’ (European Patent Office, WO2019150323 A1) and of the patent application ‘Composition Comprising Creatine for Use in Telomere Lengthening’ (U.S. Patent and Trademark Office, Application No. 18/934,264). Over the past 36 months, S.M.O. has received research support related to creatine from the Ministry of Science, Technological Development and Innovation; the Provincial Secretariat for Higher Education and Scientific Research; AlzChem Group AG; Kaneka Nutrients; ThermoLife International; and Vireo Systems Inc. S.M.O. is the co-founder of KRE-ALL, a company developing creatine-enriched food products, and the founder of INOVA Nutrition, a biotechnology startup focused on innovative nutraceuticals.
Authorship
S.M.O: Conceptualisation, Investigation, Writing – original draft, and Writing – review and editing.
Ethics of human subject participation
Not applicable.
Open access
