Supplements

Agmatine Sulfate

Updated · 25 sources · Editorial policy

Agmatine sulfate is the sulfate salt of agmatine, a small molecule the body makes by removing a carbon dioxide group from the amino acid L-arginine. It is sold as a dietary supplement ingredient (Gilad et al., Toxicol Rep 2024), and it shows up in products marketed for exercise as well as nerve health.

The most important fact is how little human evidence exists. The only placebo-controlled trial of agmatine sulfate alone tested it for sciatica-type back pain, analyzed 61 patients and lasted 14 days. There are no controlled human trials of agmatine for muscle growth, strength, endurance or blood flow during exercise. Most of the research is in rats and mice.

This page summarizes what the clinical studies, animal data and regulators report. It is for education only and is not medical advice.

Property Detail
Class Endogenous amine made from L-arginine; dietary supplement ingredient
Chemistry Agmatine C₅H₁₄N₄, 130.19 g/mol; agmatine sulfate C₅H₁₆N₄O₄S, 228.27 g/mol (PubChem)
Route Oral (capsules or powder)
Doses in human studies 0.65–3.56 g/day agmatine sulfate; 2.67 g/day in the main pain studies
Half-life Not measured in humans; in rats, about 15–19 minutes after IV dosing and 74–117 minutes after oral dosing
Key mechanism Binds imidazoline and α2-adrenergic receptors; blocks NMDA glutamate receptors (animal and lab data)
US status Sold as a dietary supplement; no FDA-approved drug contains agmatine
WADA status Not named on the 2026 Prohibited List

What it is

Agmatine’s chemical name is 2-(4-aminobutyl)guanidine (PubChem CID 199). It was discovered in 1910 (Manole et al., Med Sci 2025). Supplements use the sulfate salt (PubChem CID 2794990). Because the salt includes sulfuric acid, a gram of agmatine sulfate contains less than a gram of agmatine itself.

Form Formula Molecular weight
Agmatine (free base) C₅H₁₄N₄ 130.19 g/mol
Agmatine sulfate C₅H₁₆N₄O₄S 228.27 g/mol

Interest in agmatine grew in 1994, when a team at Cornell identified it in bovine brain as the long-sought “clonidine-displacing substance” (Li et al., Science 1994). Clonidine is a blood-pressure drug that binds α2-adrenergic and imidazoline receptors. The team showed that agmatine binds both receptor types, that brain tissue contains the enzyme that makes it (arginine decarboxylase), and proposed that it may act as a neurotransmitter.

Since then, lab and animal studies have linked agmatine to several targets (Piletz et al., Drug Discov Today 2013; Molderings and Haenisch, Pharmacol Ther 2012):

  • imidazoline and α2-adrenergic receptors;
  • NMDA receptors, a type of glutamate receptor involved in pain signaling and learning;
  • nitric oxide (NO) synthesis;
  • polyamine metabolism.

Supplement marketing often presents agmatine as a nitric oxide booster. The research does not support that simple picture. Animal and lab studies describe agmatine as inhibiting or modulating NO synthase enzymes (Roberts et al., JPET 2005), and a 2025 systematic review of 60 preclinical studies found that agmatine could either raise or lower blood pressure and heart rate depending on dose, route and receptors involved (Manole et al., Med Sci 2025).

The library also has a page on Citrulline Malate, another supplement that acts on the arginine pathway.

How it works in the body

Agmatine in tissues comes from two sources: the body’s own synthesis, and agmatine absorbed from the gut (Molderings and Haenisch, Pharmacol Ther 2012). Gut bacteria make it (Haenisch et al. 2008), and many foods contain small amounts (Gilad et al., Toxicol Rep 2024). It carries a positive charge at body pH, so it needs a transporter to cross cell membranes.

Human data are limited to levels of the body’s own agmatine and how the liver handles it:

Measure Finding Source
Plasma agmatine, healthy adults 8.4–65.1 ng/mL (n = 10) Regunathan et al. 2009
Cerebrospinal fluid agmatine 24.3–54.0 ng/mL (n = 10) Regunathan et al. 2009
Liver clearance The liver removed substantial agmatine from blood when portal vein levels were above 14 ng/mL Haenisch et al. 2008
Gut bacteria Ten common gut bacterial strains differed widely in how much agmatine they made Haenisch et al. 2008

No study has measured the half-life or oral bioavailability of supplemental agmatine in people. The best data come from rats (Clements et al., JPET 2023):

Parameter (rats) Value
Plasma half-life, intravenous ≈15–19 minutes
Plasma half-life, oral ≈74–117 minutes (slow absorption prolongs it)
Oral bioavailability 29–35%
Brain and spinal cord Agmatine reached both; its half-life there was substantially longer than in plasma

In mice given agmatine directly into the spinal canal, it stayed in spinal tissue with a half-life of about 12 hours, while its half-life in blood was under 10 minutes (Roberts et al., JPET 2005). Oral agmatine sulfate in mice raised agmatine levels in the brain (Bergin et al., Sci Rep 2019). Whether the same happens at supplement doses in humans has not been measured.

Regulatory status

  • United States. Agmatine sulfate is marketed as a dietary supplement ingredient (Gilad et al., Toxicol Rep 2024), and the NIH Dietary Supplement Label Database lists products containing it. A search of the FDA’s Drugs@FDA database returns no approved drug with agmatine as an active ingredient.
  • Sport. Agmatine is not named on the WADA 2026 Prohibited List. The list’s S0 class bans pharmacological substances that have no regulatory approval for human therapeutic use. The list does not say whether that class covers supplement ingredients such as agmatine.

What the research shows

Sciatica from a herniated lumbar disc

This is the only randomized, placebo-controlled trial of agmatine sulfate on its own (Keynan et al., Pain Med 2010). It had two parts.

First, an open-label dose-escalation study tested safety in four cohorts:

Cohort Agmatine sulfate Duration
1 1.335 g/day 10 days
2 2.670 g/day 10 days
3 3.560 g/day 10 days
4 3.560 g/day 21 days

Safety measures stayed within normal values. Three people in the highest-dose cohort had mild-to-moderate diarrhea and mild nausea, which stopped when they stopped taking it.

Second, people with disc-related radiculopathy (nerve-root pain radiating down the leg) were randomized to 2.67 g/day agmatine sulfate or placebo for 14 days. 51 were assigned to agmatine and 48 to placebo, but only 31 and 30 were analyzed. Both groups improved. Improvement from baseline was larger with agmatine:

Outcome (improvement vs baseline) Agmatine Placebo
Average pain measures 26.7% 6.0% (p ≤ 0.05)
Quality of life scores 70.8% 20.0% (p ≤ 0.05)

No treatment-related adverse events were reported. Limits worth noting: the trial was short, 38 of 99 randomized participants were not in the analysis, and two of the authors (V.H. Gilad and G.M. Gilad) later declared patents on agmatine products and equity in Gilad&Gilad LLC, which sells a branded agmatine sulfate (Gilad et al., Toxicol Rep 2024; Rosenberg et al., Nutrients 2020).

Painful small fiber neuropathy

In an open-label case series without a control group, 12 patients with painful small fiber neuropathy took 2.67 g/day agmatine sulfate for 2 months, and 11 completed it (Rosenberg et al., Nutrients 2020). Eight had diabetic neuropathy. Average pain intensity fell by 46.4% (p under 0.00001). Without a placebo group, this cannot separate the effect of agmatine from placebo response or natural change. The study was co-authored by G.M. Gilad, who declared a patent and stock interest.

Depression and OCD

Evidence here is limited to small uncontrolled reports:

  • Major depression. A pilot report described three patients whose depression remitted while taking agmatine (Shopsin, Acta Neuropsychiatr 2013). One had stomach discomfort and loose stools that resolved within days.
  • Treatment-resistant OCD. In a 2026 open-label series, five adults added agmatine sulfate (650 mg/day for one week, then 1,300 mg/day) to their antidepressant for 112 days (Salvi, Front Psychiatry 2026). Two of five had at least a 25% drop in symptom scores. Two had mild, transient stomach symptoms; no one stopped because of side effects.

Neither report can show that agmatine caused the improvement.

Spinal cord injury (combination product)

A 2026 randomized trial in 120 patients with subacute spinal cord injury compared standard care with standard care plus a fixed-dose combination of inosine monophosphate, agmatine sulfate and L-carnosine for 6 months (Kundnani et al., J Orthop Case Rep 2026). The combination group had greater improvement in motor scores, functional independence and quality of life, but not in sensory scores. The trial was not placebo-controlled, and because agmatine was one of three ingredients, it cannot show what agmatine itself contributed.

Exercise, muscle and body composition

We found no published controlled human trials of agmatine sulfate for strength, muscle mass, endurance, exercise blood flow or fat loss. Claims that it improves “pumps” or performance rest on its link to arginine and nitric oxide, not on human exercise data.

In rats, adding agmatine to drinking water for 4 or 8 weeks reduced weight gain on a high-fat diet, lowered fat mass and increased protein mass (Nissim et al., J Biol Chem 2014). This has not been tested in people.

Side effects and risks

What human studies report

Across the small human studies, the main reported side effects were digestive:

Study Dose Reported effects
Keynan 2010, dose escalation 3.56 g/day Mild-to-moderate diarrhea and mild nausea in 3 people, resolved after stopping
Keynan 2010, randomized phase 2.67 g/day, 14 days No treatment-related adverse events
Rosenberg 2020 2.67 g/day, 2 months One dropout due to bad taste; no lab abnormalities
Salvi 2026 650–1,300 mg/day, 112 days Mild transient GI symptoms in 2 of 5

The longest human exposure is a self-report by the two Gilad researchers, who took 2.67 g/day for 4–5 years and reported normal exams and lab results (Gilad and Gilad, J Med Food 2014). Two people, who also had a commercial interest in the product, cannot establish long-term safety.

Animal and lab safety data

  • In rats, agmatine sulfate in drinking water for 95 days caused small but significant drops in body weight and blood pressure, which recovered within 20 days of stopping; no organ damage was seen at necropsy (Gilad and Gilad, Food Chem Toxicol 2013).
  • In mice, oral doses up to 900 mg/kg for a week, or 300 mg/kg for 15 weeks, were well tolerated with no organ pathology (Bergin et al., Sci Rep 2019).
  • A branded agmatine sulfate was negative in standard tests for mutations and chromosome damage (Ames test, chromosomal aberration test, mouse micronucleus test) (Gilad et al., Toxicol Rep 2024).

Some animal findings point the other way and are unresolved:

  • In rats after partial liver removal, 250–500 mg agmatine by gavage for 6 days reduced liver regeneration by 20–22% (Molderings et al., Ann N Y Acad Sci 2003).
  • In a mouse model of colorectal cancer, agmatine made by gut bacteria activated a pro-tumor signaling pathway (Wnt) and inflammation (Lu et al., Gut Microbes 2024). This involved agmatine from gut bacteria, not supplements, and has not been studied in people.

Blood pressure and drug interactions

Agmatine binds the same receptors as clonidine, and it lowered blood pressure slightly in rats (Gilad and Gilad, Food Chem Toxicol 2013). Preclinical studies show it can push blood pressure in either direction (Manole et al., Med Sci 2025). Interactions with blood-pressure drugs, antidepressants or other medicines have not been studied in humans, and there is no safety data in pregnancy, breastfeeding or children.

Product quality

Most human studies used a single brand made under cGMP (current Good Manufacturing Practice) conditions (Rosenberg et al., Nutrients 2020), so their results may not apply to other products. We found no published testing of agmatine supplement contents.

Key takeaways

  • An arginine metabolite sold as a supplement. Agmatine is made in the body from L-arginine and binds imidazoline, α2-adrenergic and NMDA receptors in lab and animal studies. No approved drug contains it.
  • One small placebo-controlled trial. In sciatica, 2.67 g/day for 14 days improved pain more than placebo (26.7% vs 6.0%), in 61 analyzed patients.
  • No evidence for exercise or muscle. There are no controlled human trials for strength, muscle mass, endurance or “pumps.”
  • Human half-life is unknown. In rats, plasma half-life is about 15–19 minutes after IV dosing and up to about 2 hours after oral dosing.
  • Short-term tolerability looks reasonable, long-term safety is unproven. Diarrhea and nausea appeared at 3.56 g/day. Long-term data come from two researchers with a commercial interest, and some animal findings (liver regeneration, colon tumors) remain unresolved.
  • Industry ties are common. Much of the human and safety research was co-authored by the patent holders of a branded agmatine sulfate.

Sources

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