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Agmatine Sulfate
Agmatine is a metabolite of arginine (specifically, decarboxylated arginine).
- Evidence
- Mixed Evidence
- Category
- Energy & Performance
- Best form
- AgmaPure (Gilead Tiefenbrun's standardized agmatine sulfate, used as a branded raw ingredient by some pre-workout makers)
- Effective dose
- 500-1000mg daily for typical pre-workout use
- Lab tested
- 7 of 8 products
- Category
- Energy & Performance
- Best form
- AgmaPure (Gilead Tiefenbrun's standardized agmatine sulfate, used as a branded raw ingredient by some pre-workout makers)
- Effective dose
- 500-1000mg daily for typical pre-workout use
- Lab tested
- 7 of 8 products
Key takeaways
- →Agmatine's pre-workout pump claims are mechanistically thin. It is not a direct nitric oxide donor and there are no human performance trials.
- →The only positive human trials are in lumbar disc radiculopathy and small fiber neuropathy at 2.67g/day, dosed under research conditions.
- →GI cramping, diarrhea, and nausea are common at 1-2g/day doses. Long-term safety in healthy adults is unstudied.
- →If you take it, pick a single-ingredient product with disclosed dose, not a proprietary pre-workout blend.
What Is Agmatine Sulfate?
Agmatine is a metabolite of arginine (specifically, decarboxylated arginine). It is sold for two completely different reasons that share almost no overlapping evidence base: as a "pump" ingredient in pre-workouts, and as an off-label tool for neuropathic pain or mood. The honest take is that the strongest human data is in a niche pain condition, the pre-workout claims are mechanistically thin, and the mood and cognitive claims rest on case reports and animal models. If you are not in the specific pain population studied by Keynan and Rosenberg, the case for taking agmatine is weak.
The pre-workout pitch is that agmatine boosts nitric oxide, drives vasodilation, and improves muscle pumps. This is misleading. Agmatine is not a direct nitric oxide donor and it does not get converted to NO in any clinically meaningful pathway. Its actual mechanisms involve imidazoline I1 and I2 receptor binding, NMDA receptor antagonism, and modulation of nitric oxide synthase activity (which can go either way depending on tissue). There are no quality randomized human trials showing agmatine improves training performance, pump, vasodilation, or hypertrophy at typical pre-workout doses of 500-1000mg. The ingredient persists in pre-workouts because it sounds plausible on paper, not because it has been demonstrated to work.
The strongest human signal is in lumbar disc-associated radiculopathy. Keynan 2010 (Pain Medicine) ran an open-label dose-escalation study and a small randomized double-blind placebo-controlled trial of 2.67g/day agmatine sulfate for 14 days in patients with herniated disc radicular pain. The agmatine group showed a 26.7% improvement in pain and 70.8% improvement in quality-of-life scores versus 6% and 20% on placebo. Rosenberg 2020 (Nutrients) followed up with an open-label case series of 11 patients with painful small fiber neuropathy at the same 2.67g/day dose, reporting a 46.4% reduction in pain over 2 months. These are real, replicated signals, but they are open-label case work and one small RCT in narrow populations (lumbar radiculopathy and SFN), not broad neuropathy evidence.
The depression and cognitive claims are essentially mechanistic at this point. Shopsin 2013 (Acta Neuropsychiatrica) reported that exogenous agmatine produced an antidepressant response in a tiny case series of major depressive disorder patients, and that the response was not blocked by serotonin depletion (parachlorophenylalanine), suggesting a non-serotonergic mechanism. That is interesting biology but it is three patients, not a clinical signal you can act on. Animal models show NMDA modulation, imidazoline activity, and behavioral antidepressant effects, but no controlled trials in humans for depression, anxiety, or cognitive enhancement exist at supplement-relevant doses. If you are buying agmatine for "mood" or "focus," you are buying a hypothesis, not a result.
Does It Work? The Evidence
How A-F grades workLumbar disc-associated radicular pain (sciatica)
Keynan 2010 Pain Medicine (PMID 20447305): open-label dose-escalation followed by a small randomized double-blind placebo-controlled trial at 2.67g/day for 14 days; 26.7% pain improvement vs 6% on placebo, 70.8% QoL improvement vs 20%. Single-trial signal, never replicated in a larger RCT.
Painful small fiber neuropathy
Rosenberg 2020 Nutrients (PMID 32102167): open-label consecutive case series of 11 patients at 2.67g/day for 2 months; 46.4% pain reduction. Case-series evidence, not a controlled trial.
Pre-workout muscle pump and vasodilation
No controlled human trials demonstrate agmatine increases vasodilation, blood flow, pump, or training performance at 500-1000mg pre-workout doses. The 'arginine to agmatine to NO' marketing claim misrepresents the biochemistry; agmatine is not a direct NO donor.
Strength, endurance, or hypertrophy
Zero quality RCTs in trained or untrained populations show agmatine improves 1RM, time-to-fatigue, training volume, or muscle mass. Mechanistic case is weak.
Major depressive disorder
Shopsin 2013 Acta Neuropsychiatr (PMID 25287313): pilot case series of 3 patients reporting antidepressant response not reversed by parachlorophenylalanine, suggesting non-serotonergic mechanism. Three patients is hypothesis-generating, not clinical evidence.
Cognitive enhancement / nootropic use in healthy adults
Animal-model evidence for NMDA receptor modulation and behavioral effects exists, but zero quality human RCTs in healthy adults for memory, focus, or processing speed.
| Grade | Claimed Benefit | Key Studies | Our Verdict |
|---|---|---|---|
| C | Lumbar disc-associated radicular pain (sciatica) | Keynan 2010 Pain Medicine (PMID 20447305): open-label dose-escalation followed by a small randomized double-blind placebo-controlled trial at 2.67g/day for 14 days; 26.7% pain improvement vs 6% on placebo, 70.8% QoL improvement vs 20%. Single-trial signal, never replicated in a larger RCT. | Early Signal |
| C | Painful small fiber neuropathy | Rosenberg 2020 Nutrients (PMID 32102167): open-label consecutive case series of 11 patients at 2.67g/day for 2 months; 46.4% pain reduction. Case-series evidence, not a controlled trial. | Early Signal |
| F | Pre-workout muscle pump and vasodilation | No controlled human trials demonstrate agmatine increases vasodilation, blood flow, pump, or training performance at 500-1000mg pre-workout doses. The 'arginine to agmatine to NO' marketing claim misrepresents the biochemistry; agmatine is not a direct NO donor. | Not There Yet |
| F | Strength, endurance, or hypertrophy | Zero quality RCTs in trained or untrained populations show agmatine improves 1RM, time-to-fatigue, training volume, or muscle mass. Mechanistic case is weak. | Not There Yet |
| D | Major depressive disorder | Shopsin 2013 Acta Neuropsychiatr (PMID 25287313): pilot case series of 3 patients reporting antidepressant response not reversed by parachlorophenylalanine, suggesting non-serotonergic mechanism. Three patients is hypothesis-generating, not clinical evidence. | Not There Yet |
| F | Cognitive enhancement / nootropic use in healthy adults | Animal-model evidence for NMDA receptor modulation and behavioral effects exists, but zero quality human RCTs in healthy adults for memory, focus, or processing speed. | Not There Yet |
How to Choose: Forms, Doses & What Matters
Clinical dose: 500-1000mg daily for typical pre-workout use; the only positive human pain trial used 2.67g/day. Long-term safety in healthy adults is unstudied.
Best forms: AgmaPure (Gilead Tiefenbrun's standardized agmatine sulfate, used as a branded raw ingredient by some pre-workout makers), Generic agmatine sulfate (most capsules and powders, USP-grade or unspecified), Agmatine sulfate powder (for those who already know their dose and want the cheapest format)
For pain protocols based on Keynan 2010 and Rosenberg 2020, the studied dose is 2.67g/day, typically split into 2-3 doses with food to limit GI upset. This is a pharmacological dose and requires titration; start at 500mg twice daily and increase over 5-7 days. For pre-workout use (despite the weak evidence), the typical product dose is 500-1000mg taken 30-45 minutes before training. Take with food if you are sensitive to nausea or cramping. Do not stack with multiple stim-heavy pre-workout ingredients on first use. Cycle off for 1-2 weeks every 8 weeks; long-term continuous use in healthy adults is not studied for safety.
Who Should Take Agmatine Sulfate?
There is no population for whom agmatine is a default supplement recommendation. The narrowest defensible use is adults with chronic neuropathic pain (lumbar radiculopathy or small fiber neuropathy) who have already failed first-line treatments and want to try a 2-3g/day course under medical supervision based on the Keynan and Rosenberg work. For pre-workout pump or training performance, the evidence does not support buying agmatine on its own; cheaper, better-evidenced options like 6-8g of citrulline malate or 3-6g of beetroot nitrate have actual human pump and exercise data behind them. For mood or cognitive use, agmatine is a hypothesis with case-report support, not a treatment.
Who Should Avoid It?
Not for everyone
Side Effects & Safety
Product Scores
8 products scored on dosing accuracy, third-party testing, cost per effective dose, and label transparency.
The Scorecard: 8 Products Compared
Agmatine Sulfate 250mg, 120 Capsules
Nootropics Depot$24.99 ÷ 30 days at 1000mg/day (4 servings × 250mg)
If documentation matters more than price, Nootropics Depot's per-batch COA practice is the best in this category
Prices checked 2026-04-28. Cost shown is per clinically effective daily dose, not per pill.
Agmatine Sulfate Powder, 250g
Nootropics Depot$39.99 ÷ 250 days at 1000mg/day (1 serving × 1000mg)
The bulk-powder pick if you want documented purity testing and are willing to pay a premium for it
Prices checked 2026-04-28. Cost shown is per clinically effective daily dose, not per pill.
Agmatine Sulfate 500mg, 90 Capsules
Primaforce
$24.99 ÷ 45 days at 1000mg/day (2 servings × 500mg)
The cleanest capsule pick if you want documented third-party testing on a single-ingredient agmatine product
Prices checked 2026-04-28. Cost shown is per clinically effective daily dose, not per pill.
Agmatine Sulfate Powder, 100g
Primaforce
$19.95 ÷ 100 days at 1000mg/day (1 serving × 1000mg)
Best per-gram value with a real third-party testing program; pick this if you are running the Keynan 2.67g/day protocol
Prices checked 2026-04-28. Cost shown is per clinically effective daily dose, not per pill.
Agmatine Sulfate 1000mg, 120 Capsules (500mg per cap)
Nutricost$19.95 ÷ 60 days at 1000mg/day (1 serving × 1000mg)
Best price-per-cap option from a brand with a documented testing program; the value pick if you do not need NSF facility certification
Prices checked 2026-04-28. Cost shown is per clinically effective daily dose, not per pill.
Pure Agmatine Sulfate Powder, 250g
Nutricost$24.95 ÷ 249 days at 1000mg/day (1 serving × 1000mg)
The cheapest defensible bulk option for anyone running the Keynan/Rosenberg pain protocol or daily pre-workout use
Prices checked 2026-04-28. Cost shown is per clinically effective daily dose, not per pill.
Agmatine Sulfate Capsules, 180 Count
BulkSupplements
$23.96 ÷ 89 days at 1000mg/day (1 serving × 1000mg)
Solid mid-tier option if you do not need posted COAs and prefer capsules over powder
Prices checked 2026-04-28. Cost shown is per clinically effective daily dose, not per pill.
Agmatine 500mg, 60 Vegetarian Capsules
Olympian Labs
$17.99 ÷ 30 days at 1000mg/day (2 servings × 500mg)
Sometimes confused with the brand 'Olympus Labs'; Olympian Labs is the actual manufacturer of this product
Prices checked 2026-04-28. Cost shown is per clinically effective daily dose, not per pill.
Full Comparison
| Category | Agmatine Sulfate 250mg, 120 Capsules Nootropics Depot | Agmatine Sulfate Powder, 250g Nootropics Depot | Agmatine Sulfate 500mg, 90 Capsules Primaforce | Agmatine Sulfate Powder, 100g Primaforce | Agmatine Sulfate 1000mg, 120 Capsules (500mg per cap) Nutricost | Pure Agmatine Sulfate Powder, 250g Nutricost | Agmatine Sulfate Capsules, 180 Count BulkSupplements | Agmatine 500mg, 60 Vegetarian Capsules Olympian Labs |
|---|---|---|---|---|---|---|---|---|
| Brand Score | 84/100Winner | 83/100 | 82/100 | 80/100 | 75/100 | 74/100 | 71/100 | 68/100 |
| Dosing & Form | 19/25 | 19/25 | 21/25Winner | 19/25 | 19/25 | 17/25 | 17/25 | 17/25 |
| Purity | 23/25Winner | 23/25 | 22/25 | 22/25 | 19/25 | 19/25 | 19/25 | 17/25 |
| Value | 19/25 | 18/25 | 19/25 | 22/25 | 22/25 | 23/25Winner | 22/25 | 17/25 |
| Transparency | 23/25Winner | 23/25 | 20/25 | 17/25 | 15/25 | 15/25 | 13/25 | 17/25 |
| Cost/Day | $0.83 | $0.16 | $0.56 | $0.20 | $0.33 | $0.10Winner | $0.27 | $0.60 |
| Dose/Serving | 250mg | 1000mg | 500mg | 1000mg | 1000mg | 1000mg | 1000mg | 500mg |
| Form | Agmatine sulfate capsule (250mg per cap, single-ingredient) | Agmatine sulfate powder (single-ingredient) | Agmatine sulfate capsule (single-ingredient) | Agmatine sulfate powder (bulk, single-ingredient) | Agmatine sulfate capsule (500mg per cap, single-ingredient) | Agmatine sulfate powder (single-ingredient) | Agmatine sulfate capsule (2 caps per 1g serving) | Agmatine sulfate vegetarian capsule |
| Third-Party Tested | ✓ Yes | ✓ Yes | ✓ Yes | ✓ Yes | ✓ Yes | ✓ Yes | ✓ Yes | No |
| Proprietary Blend | No | No | No | No | No | No | No | No |
Frequently Asked Questions
Does agmatine actually boost nitric oxide and improve pump?
Not in the way pre-workout marketing implies. Agmatine is not a direct nitric oxide donor. Its effects on nitric oxide synthase are mixed and tissue-dependent (it can inhibit some NOS isoforms). There are no quality human trials showing agmatine increases vasodilation, blood flow, or training pump at 500-1000mg pre-workout doses. The 'arginine becomes agmatine becomes NO' chain is biochemically misleading. If pump is your goal, citrulline malate at 6-8g has actual human data behind it.
Is agmatine actually effective for nerve pain?
There is one small randomized placebo-controlled trial (Keynan 2010) and one open-label case series (Rosenberg 2020) showing meaningful pain reduction at 2.67g/day in lumbar radiculopathy and small fiber neuropathy. That is a real signal, but it is narrow: two studies in two specific neuropathic pain populations. It has not been replicated in a larger trial. If you are a candidate, talk to your physician about a 2-3 month trial at the studied dose with monitoring.
Why do pre-workouts include agmatine if the evidence is weak?
Because it sounds mechanistic and the supplement industry rewards plausible-sounding ingredients more than proven ones. Agmatine has interesting biology (NMDA, imidazoline, neurotransmitter modulation), and it is cheap as a raw ingredient. None of that has translated into demonstrated training benefits in controlled human studies. The label 'NO booster' on a pre-workout containing agmatine is marketing language, not a validated claim.
What is AgmaPure and is it worth paying extra for?
AgmaPure is a branded standardized agmatine sulfate raw ingredient (originally developed by Gilead Tiefenbrun's group) used by some pre-workout and standalone agmatine brands. The branded version offers more predictable purity and identity testing than commodity agmatine. Whether it is worth a price premium depends on whether the finished product publishes third-party COAs. For most users, a third-party tested generic agmatine sulfate at half the price is a defensible choice.
Will agmatine help with depression or anxiety?
There is no quality clinical evidence that it does. The Shopsin 2013 case series in three patients is hypothesis-generating, not a treatment signal. Animal models show NMDA-modulating effects relevant to depression pharmacology, but the translation to humans at supplement doses is unproven. If you are dealing with depression or anxiety, agmatine is not a substitute for evidence-based care.
What dose should I actually take?
It depends on the goal. For neuropathic pain following the Keynan/Rosenberg protocol, the studied dose is 2.67g/day in divided doses, titrated up from 500mg twice daily over a week. For pre-workout use (despite weak evidence), the typical product dose is 500-1000mg pre-training. Avoid stacking high-dose agmatine with other stim-heavy pre-workout ingredients on first use, and take with food if you are GI-sensitive.
Can I take agmatine with antidepressants or blood pressure medications?
Not without clinician input. Agmatine modulates imidazoline and NMDA pathways and may interact with SSRIs, SNRIs, MAOIs, and antihypertensives in unpredictable ways. The interaction profile is not well characterized in humans. Anyone on prescription psychiatric or cardiovascular medications should treat agmatine as a drug-grade decision and discuss it with their prescriber.
Sources
- Keynan O, Mirovsky Y, Dekel S, Gilad VH, Gilad GM. Safety and efficacy of dietary agmatine sulfate in lumbar disc-associated radiculopathy. An open-label, dose-escalating study followed by a randomized, double-blind, placebo-controlled trial. Pain Med. 2010;11(3):356-68.
- Rosenberg ML, Tohidi V, Sherwood K, et al. Evidence for Dietary Agmatine Sulfate Effectiveness in Neuropathies Associated with Painful Small Fiber Neuropathy. A Pilot Open-Label Consecutive Case Series Study. Nutrients. 2020;12(2):576.
- Shopsin B. The clinical antidepressant effect of exogenous agmatine is not reversed by parachlorophenylalanine: a pilot study. Acta Neuropsychiatr. 2013;25(2):113-8.
- Piletz JE, Aricioglu F, Cheng JT, et al. Agmatine: clinical applications after 100 years in translation. Drug Discov Today. 2013;18(17-18):880-93.
- Neis VB, Rosa PB, Olescowicz G, Rodrigues ALS. Therapeutic value of agmatine in neurological and psychiatric disorders. Pharmacol Res. 2017;116:69-76.
- Halaris A, Plietz J. Agmatine: metabolic pathway and spectrum of activity in brain. CNS Drugs. 2007;21(11):885-900.
FDA Disclaimer: These statements have not been evaluated by the Food and Drug Administration. The products discussed on this page are not intended to diagnose, treat, cure, or prevent any disease. Always consult with a qualified healthcare professional before starting any supplement regimen.