How does the body make creatine?

Your body synthesises creatine in a two-step process. First, the enzyme AGAT in the kidneys combines arginine and glycine to form guanidinoacetate (GAA). Then, the enzyme GAMT in the liver methylates GAA using SAMe to produce creatine. This yields approximately 1-2g of creatine per day.

Why do we need to supplement if the body makes creatine?

Endogenous production of 1-2g/day covers basic metabolic needs but is not enough to maximise muscle creatine stores. Supplementation with 3-5g/day raises total muscle creatine by approximately 20% above what diet and endogenous synthesis alone provide.

Does supplementation suppress natural creatine production?

There is no evidence that creatine supplementation permanently suppresses endogenous synthesis. When you stop supplementing, your body resumes normal creatine production within days. The AGAT/GAMT pathway is not permanently downregulated.

Creatine Synthesis in the Body: The AGAT/GAMT Pathway Explained

TL;DR — Creatine Synthesis in the Body

Your body produces approximately 1-2g of creatine per day through a two-step enzymatic pathway involving the kidneys and liver. The enzyme AGAT in the kidneys produces an intermediate called guanidinoacetate (GAA), and the enzyme GAMT in the liver converts GAA into creatine using SAMe as a methyl donor. This endogenous production, combined with dietary creatine from meat and fish (another 1-2g/day for omnivores), maintains baseline creatine levels. However, supplementation with 3-5g/day raises total muscle creatine stores by approximately 20% above what your body can achieve on its own (RB et al., 2017) .

1-2g/day

endogenous creatine production by the kidneys and liver — not enough to maximise muscle and brain creatine stores

Kreider et al., 2017

Step 1: AGAT Reaction (Kidneys)

The first step of creatine biosynthesis occurs primarily in the kidneys (with smaller contributions from the pancreas). The enzyme AGAT (also known as GATM, glycine amidinotransferase) catalyses the transfer of an amidino group from arginine to glycine, producing guanidinoacetate (GAA) and ornithine.

This reaction requires two amino acids: arginine (a semi-essential amino acid) and glycine (a non-essential amino acid abundantly available from dietary protein). The AGAT reaction is considered the rate-limiting step of creatine biosynthesis, meaning it is the slowest step and determines the overall rate of creatine production.

AGAT activity is regulated by feedback inhibition from creatine itself — when creatine levels are high, AGAT activity decreases slightly. This is why some have raised concerns about supplementation suppressing natural production, though the effect is temporary and reversible.

Step 2: GAMT Reaction (Liver)

GAA produced in the kidneys is transported via the bloodstream to the liver, where the enzyme GAMT catalyses the final step. GAMT transfers a methyl group from S-adenosylmethionine (SAMe) to GAA, producing creatine and S-adenosylhomocysteine (SAH).

This methylation step is metabolically significant. Creatine synthesis consumes approximately 40% of all SAMe-derived methyl groups in the body, making it one of the largest consumers of methyl donors in human metabolism (T et al., 2011) . Providing exogenous creatine through supplementation spares SAMe for other critical methylation reactions including DNA methylation, neurotransmitter synthesis, and phospholipid production.

Distribution to Target Tissues

Once synthesised in the liver, creatine enters the bloodstream and is distributed to target tissues via the sodium-chloride-dependent creatine transporter (SLC6A8/CrT). This transporter actively pumps creatine into cells against a concentration gradient.

The primary destinations:

Skeletal muscle (95%): The largest creatine reservoir, storing approximately 120-140g in a 70kg adult
Brain (2-3%): Contains significant creatine concentrations reflecting the brain’s enormous energy demands
Heart, kidneys, testes (remaining 2-3%): Smaller but functionally important creatine pools

Harris et al. (1992) showed that supplementation significantly increases the amount of creatine transported into and stored in skeletal muscle, raising stores by approximately 20% (RC et al., 1992) .

~40%

of all SAMe-derived methyl groups in the body are consumed by creatine synthesis — supplementation spares this demand

Wallimann et al., 2011

Why Endogenous Production Is Not Enough

The combined creatine supply from endogenous synthesis (1-2g/day) and diet (1-2g/day from meat and fish) maintains baseline creatine levels adequate for survival. However, these levels are not sufficient to maximise performance.

Typical total muscle creatine content is approximately 60-80% of maximum storage capacity. Supplementation raises stores to approximately 90-100% of capacity. Vegetarians and vegans, who receive no dietary creatine from meat or fish, rely entirely on endogenous synthesis and typically have 20-30% lower muscle creatine stores than omnivores.

High-intensity athletes also have higher creatine turnover from increased phosphocreatine utilisation and creatinine production, potentially exceeding what endogenous synthesis and typical diet can replace.

The Methylation Connection

The fact that creatine synthesis is the body’s largest consumer of SAMe-derived methyl groups has sparked interest in creatine supplementation as a methylation-sparing strategy. By providing exogenous creatine, you reduce the liver’s need to synthesise it, freeing up SAMe for other methylation reactions including homocysteine metabolism, DNA methylation for gene regulation, and neurotransmitter production.

This methylation-sparing effect represents a biological benefit of supplementation that extends beyond athletic performance.

Malaysian Dietary Context

Malaysian dietary patterns influence creatine status in several ways. Omnivore Malaysians consuming regular nasi with ayam, ikan, or daging typically obtain 1-2g of dietary creatine daily. Chicken contains approximately 3.4g/kg, beef approximately 4.5g/kg, and fish approximately 3-4g/kg of creatine.

Vegetarian Malaysians following Buddhist or Hindu dietary practices and vegans obtain virtually zero dietary creatine, relying entirely on endogenous synthesis. These individuals are likely to have lower baseline creatine stores and may benefit most from supplementation.

Regardless of diet, supplementation with 3-5g/day raises muscle creatine stores beyond what any dietary pattern can achieve on its own.

Sources & References

This article cites the ISSN Position Stand (Kreider et al., 2017), the comprehensive creatine metabolism review by Wallimann et al. (2011), and the foundational loading study by Harris et al. (1992). Full citations with DOI links are available in our Research Library.