creatine

Creatine is an organic compound made endogenously by the liver, kidneys, and pancreas from the amino acids glycine, arginine, and methionine. Although often called an amino acid or peptide, creatine is chemically distinct as N‑(aminoiminomethyl)‑N‑methylglycine and does not serve as a building block of proteins but participates in energy metabolism. The majority of creatine in the body is stored in skeletal muscle (~95%), with smaller amounts in the brain and testes. In muscle cells, creatine is phosphorylated to phosphocreatine, which acts as a high‑energy phosphate reservoir that donates phosphate to ADP to regenerate ATP, the primary cellular energy currency. This system is particularly important during short bursts of intense muscular activity such as lifting, sprinting, or jumping, where rapid ATP turnover is needed. Creatine was first identified in the 19th century and has since become one of the most studied compounds in sports nutrition and muscle physiology. Unlike essential vitamins or minerals with defined dietary requirements, the human body can synthesize creatine in sufficient amounts under normal conditions, which is why official RDAs have not been established by NIH. However, dietary intake from foods such as red meat and fish contributes to whole‑body creatine stores. Creatine’s popularity as a supplement stems from robust evidence showing its ability to increase muscle phosphocreatine content, enhancing performance in repeated high‑intensity efforts and increasing lean body mass when combined with resistance training. Beyond exercise, creatine is being investigated for potential benefits in brain health, aging, and disease states characterized by impaired energy metabolism.

Creatine’s primary biological role is to support the rapid regeneration of ATP, which fuels muscular contractions and high‑intensity activity. In the phosphocreatine system, creatine phosphate donates a phosphate group to ADP, rapidly regenerating ATP during the first seconds of intense effort. This mechanism underlies creatine’s widely documented ability to increase strength, power output, and training volume. A 2018 review in the Journal of the International Society of Sports Nutrition emphasized creatine monohydrate as the most effective supplement for increasing high‑intensity exercise capacity and training adaptations, reporting improvements in maximal power and performance metrics ranging from 5% to 15% in repeated bouts of effort. Research also supports broader benefits beyond physical performance. Clinical studies have examined creatine supplementation’s role in preserving lean muscle mass during aging and mitigating the severity of sarcopenia, the age‑associated loss of muscle. Emerging evidence suggests creatine may support cognitive function, particularly in situations where energy demand is high or endogenous synthesis is compromised. Preliminary research indicates potential improvements in memory and executive function in older adults or individuals under cognitive stress, though larger randomized trials are needed to confirm these findings. Creatine also contributes to skeletal muscle recovery and adaptation post‑exercise. By increasing intramuscular creatine stores, supplementation enhances training volume capacity, enabling greater mechanical stimulus and subsequent muscle protein synthesis. Additional non‑performance roles include support for glucose metabolism when combined with exercise and possible bone health benefits via indirect effects on muscle mass and function. While these areas are active research topics, the most consistent evidence regards creatine’s ergogenic effects in high‑intensity performance and muscle mass gains.

Unlike essential vitamins and minerals, creatine does not have an established Recommended Dietary Allowance (RDA) set by NIH because the body can synthesize it endogenously, and baseline requirements vary with muscle mass and activity level. However, research consensus and clinical guidelines provide practical intake ranges. Typical omnivorous diets supply approximately 1–2 grams of creatine per day from foods such as red meat and fish. For individuals engaging in regular high‑intensity exercise, supplemental intake of 3–5 grams per day of creatine monohydrate is commonly used to saturate creatine stores and optimize performance benefits. Sport science literature often employs a loading protocol of ~0.3 g/kg/day, split into multiple doses for 5–7 days, to rapidly increase muscle creatine stores, followed by a maintenance dose of 3–5 g/day. Alternatively, skipping the loading phase and taking a consistent 3–6 g/day results in similar saturation over a longer period (approximately 3–4 weeks). Larger or highly active individuals may require doses at the higher end of these ranges. Populations with lower baseline creatine stores, such as vegetarians and vegans, may experience greater increases in muscle creatine content with supplementation due to lower dietary intake. NIH highlights the lack of formal RDAs for creatine but acknowledges its widespread use and research supporting supplemental doses in performance and clinical contexts. Factors affecting needs include muscle mass, exercise intensity, age, and diet. Creatine synthesis declines modestly with age, making dietary or supplemental creatine potentially more relevant in older adults to support muscle maintenance and functional capacity.

Because the body synthesizes creatine and dietary deficiency is uncommon in omnivores, classical deficiency syndromes are rare. However, genetically determined creatine deficiency syndromes, such as creatine transporter defect and defects in creatine biosynthesis pathways, can lead to severe neurological symptoms due to impaired creatine delivery or synthesis. Creatine transporter deficiency (CTD), caused by mutations in the SLC6A8 gene, results in inadequate creatine uptake into brain and muscle tissues despite normal circulating levels; affected individuals exhibit intellectual disability, speech delay, and movement disorders. Standard oral creatine supplementation does not correct CTD due to the underlying transport defect. In broader clinical nutrition contexts, low creatine stores may be suspected in individuals with markedly low meat/fish intake, particularly vegans, though this rarely manifests as a clinical deficiency. Instead, low stores may present as reduced exercise capacity, prolonged recovery from high‑intensity activity, and fatigue during efforts reliant on rapid ATP turnover. Tests to assess creatine status often measure creatinine, a breakdown product excreted in urine; however, serum creatinine is a poor indicator of tissue creatine stores because it reflects a combination of dietary intake, endogenous production, and muscle mass. In clinical genetic disorders, specialized assays such as brain 1H‑MRS (magnetic resonance spectroscopy) can detect low creatine concentrations directly in affected tissues. For the general population, creatine deficiency is not widely prevalent owing to endogenous synthesis and dietary intake.

Creatine is found primarily in animal‑sourced foods, particularly in muscle tissue where it naturally accumulates. Herring and other oily fish are among the richest natural dietary sources, providing substantial creatine per serving. Red meats such as beef, pork, lamb, and venison also supply meaningful amounts of creatine alongside high‑quality protein, iron, zinc, and B vitamins. Fish varieties including salmon, tuna, and cod contribute creatine while offering heart‑healthy omega‑3 fatty acids; herring, in particular, has been d with approximately 0.75–1.1 grams of creatine per 4‑oz serving, making it one of the most potent whole food sources. Poultry such as chicken and turkey contain lower, yet still relevant, amounts of creatine relative to red meats. Shellfish like shrimp and sardines provide smaller levels. Dairy products (milk, cheese) contain trace creatine, as do eggs, though these amounts are typically low and not considered significant contributors to total creatine intake. Cooking methods influence creatine content; prolonged high heat can degrade creatine, so gentler methods such as steaming or poaching may preserve more of the compound. Plant‑based foods contain negligible creatine; individuals following vegan or vegetarian diets largely rely on endogenous synthesis and may consider supplementation to achieve levels associated with performance benefits. Overall, a combination of fish and meat sources across meals offers an effective dietary strategy to meet baseline creatine needs without supplements.

Creatine absorbed from foods and supplements enters the bloodstream where it is taken up by tissues with high energy demands, predominantly skeletal muscle. Transport into cells is mediated by a specific creatine transporter (CRT), which carries creatine across cell membranes. Once inside the cell, creatine is phosphorylated to phosphocreatine and stored; higher intramuscular levels correlate with greater availability for rapid ATP regeneration during intense activity. The bioavailability of creatine from dietary supplements, particularly creatine monohydrate, is high, with studies indicating excellent uptake into muscle tissue when dosed appropriately. Co‑ingestion with carbohydrates or carbohydrate/protein mixtures enhances creatine uptake, likely via insulin signaling that promotes creatine transporter activity. Factors such as age, muscle fiber type, and training status influence creatine uptake and storage capacity. Vegetarians and older adults often show greater relative increases in muscle creatine with supplementation due to lower baseline stores. Endogenous synthesis and regular dietary patterns also affect overall creatine status. Timing of intake relative to exercise may influence uptake; post‑exercise ingestion appears to coincide with increased muscle sensitivity to nutrient uptake. Overall, creatine monohydrate remains the most evidence‑supported form regarding absorption and effectiveness.

Supplemental creatine, particularly creatine monohydrate, represents one of the most researched dietary supplements for performance and muscle health. Evidence supports its safe and effective use to enhance high‑intensity performance, increase lean muscle mass, and improve recovery when combined with resistance training. Athletes engaged in short bursts of effort (e.g., sprinting, lifting) often derive the greatest ergogenic benefits. Older adults with sarcopenia or those seeking to preserve muscle function may also consider creatine supplementation as part of a broader nutrition and resistance training plan. Individuals on vegetarian or vegan diets, whose dietary creatine intake is minimal, frequently experience larger relative increases in muscle creatine stores when supplementing. Typical dosing strategies include a loading phase of ~0.3 g/kg/day for 5–7 days followed by maintenance at 3–5 grams daily. Alternatively, a consistent 3–6 grams daily intake without loading yields similar benefits over a longer timeframe. Creatine monohydrate is the most studied form, with strong evidence supporting its efficacy and safety; alternative forms (e.g., creatine hydrochloride) lack comparable depth of research. When choosing supplements, third‑party testing for purity and potency is recommended due to the limited regulatory oversight of dietary supplements. Consultation with a healthcare provider is advisable for individuals with underlying health conditions such as kidney disease or those taking medications affecting renal function.

Unlike essential micronutrients with defined upper limits, creatine does not have an established tolerable upper intake level from NIH. Research studies have safely administered up to 10 grams daily of creatine monohydrate for extended periods without adverse effects in healthy adults. Transient side effects during high intake, particularly during loading phases, may include water retention, mild bloating, or gastrointestinal discomfort. Creatine draws water into muscle cells, which can increase body weight due to intracellular fluid shifts; this effect is benign in most cases but may be misconstrued as fat gain. Although concerns historically centered on kidney health, evidence indicates that typical supplemental doses do not impair renal function in healthy individuals. Very high doses beyond common practice (e.g., >20 g/day for prolonged periods) may increase the likelihood of digestive issues or water balance disturbances but are not routinely studied. Individuals with existing kidney disease or compromised renal function should avoid creatine supplementation unless counseled by a healthcare provider due to the added metabolic load and potential for elevated serum creatinine levels that complicate kidney function assessment.

Creatine supplementation is generally considered safe with few well‑documented direct drug interactions. However, creatine metabolism and excretion involve the kidneys, which has implications when combined with medications affecting renal function. Drugs such as cimetidine, trimethoprim, and probenecid can interfere with creatinine handling and renal creatine excretion, potentially leading to elevated serum creatinine levels that may be misinterpreted as kidney dysfunction on lab tests. Nonsteroidal anti‑inflammatory drugs (NSAIDs) like ibuprofen and naproxen also affect kidney function; concomitant use with creatine could place cumulative stress on renal processes, particularly in individuals with underlying kidney issues. Diuretics, which alter fluid and electrolyte balance, may interact with creatine’s water‑retaining effects, potentially leading to dehydration or electrolyte imbalances if fluid intake is inadequate. Additionally, caffeine and certain stimulants may reduce creatine’s effectiveness and increase dehydration risk. While no strong interactions with common cardiovascular or diabetes medications are well established, careful monitoring is advisable if these drugs are used, especially in combination with creatine supplementation in individuals with comorbid conditions. Healthcare providers should be informed of all supplements and medications a person is taking to interpret kidney function tests accurately and ensure safe combined use.

Common Forms: Creatine monohydrate, Buffered creatine, Creatine hydrochloride, Creatine citrate

Typical Doses: 3–5 grams daily (with optional loading 20–25 g/day for 5–7 days)

When to Take: Consistent daily intake; often post‑exercise with carbs/protein

Best Form: Creatine monohydrate

⚠️ Interactions: NSAIDs (e.g., ibuprofen), Diuretics, Cimetidine, Trimethoprim, Probenecid