Agmapure
Also known as: Agmatine sulfate, Agmapure, decarboxylated arginine, C5H14N4, Agmatine
Overview
Agmatine is a biogenic amine synthesized from the amino acid arginine through decarboxylation. It is naturally present in mammals, including humans, with notable concentrations in the brain and peripheral tissues. As a dietary supplement, it is primarily investigated for its roles as a neuromodulator and its potential to influence nitric oxide pathways. Research suggests agmatine may offer antidepressant, neuroprotective, analgesic, and anti-inflammatory benefits. It acts as a neurotransmitter/neuromodulator, impacting NMDA receptors, nitric oxide synthase (NOS) activity, and inflammatory cytokines. While research is emerging, several preclinical and clinical studies, including meta-analyses, support some of its effects, particularly in neuropsychiatric contexts. The quality of evidence is moderate, with some well-conducted RCTs, but large-scale clinical trials are still needed to establish a broader clinical consensus.
Benefits
Agmatine demonstrates several evidence-based benefits, primarily in neuropsychiatric and anti-inflammatory contexts. A meta-analysis of 26 randomized controlled trials (RCTs) involving over 1500 patients indicated that agmatine significantly improves depressive symptoms, suggesting a rapid-onset antidepressant action. This effect is likely mediated by its anti-inflammatory and neurotrophic properties, including an increase in brain-derived neurotrophic factor (BDNF) expression. Agmatine has been shown to reduce pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) and oxidative stress markers in animal models, contributing to its neuroprotective and antidepressant effects. Furthermore, animal studies suggest synergistic antidepressant effects when agmatine is combined with standard antidepressants like fluoxetine and imipramine. While direct evidence for agmatine's metabolic effects is less robust, its precursor, arginine, has been linked to improved glucose metabolism and reduced waist circumference in humans. Agmatine may be particularly beneficial for individuals with depression and neuroinflammation, though more human data are needed for metabolic applications. The meta-analysis indicates statistically significant improvements in depressive symptoms, but further large-scale trials are required to determine precise effect sizes and clinical relevance.
How it works
Agmatine exerts its effects through multiple biological pathways, primarily acting as a neuromodulator. It modulates NMDA receptor activity, which is crucial for learning and memory, and inhibits nitric oxide synthase (NOS), thereby reducing excessive nitric oxide (NO) production that can lead to neurotoxicity. Agmatine also exhibits anti-inflammatory actions by downregulating pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6. Additionally, it enhances the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus, promoting neuroplasticity and neuronal survival. These mechanisms collectively contribute to its central nervous system (CNS) neuromodulation, immune modulation, and vascular effects. Oral agmatine sulfate is absorbed, but its precise bioavailability and pharmacokinetics in humans require further characterization.
Side effects
Agmatine is generally considered safe at typical supplemental doses, with no major adverse effects consistently reported in clinical trials. Common side effects (occurring in >5% of users) have not been identified. Uncommon side effects (1-5%) may include mild gastrointestinal discomfort. Rare side effects (<1%) have not been significantly reported. Regarding drug interactions, agmatine may have a synergistic effect with antidepressants, as observed in animal studies, but severe interactions have not been documented. Caution is advised when combining agmatine with other CNS-active drugs until more comprehensive data are available. Contraindications are not well-defined. Specific populations such as pregnant or nursing women, children, and severely ill patients have limited data, so caution is warranted. Overall, the safety profile appears favorable based on current evidence, but comprehensive long-term studies are still needed.
Dosage
The optimal dosage for agmatine is not definitively established, but clinical studies have utilized doses ranging from 500 mg to 2.67 g of agmatine sulfate per day. Many trials commonly use dosages between 1-2 g per day. There is no established maximum safe dose, but doses up to 2.67 g/day have been well tolerated in short-term studies. The timing of administration is not fully clear in humans, though animal models suggest effects on depression may appear within 7 days. Agmatine sulfate is the most common supplemental form. Oral bioavailability is moderate, but the impact of food co-administration on absorption is unknown. No specific cofactors are established as necessary for its efficacy. Users should start with lower doses and gradually increase while monitoring for effects and tolerance, ideally under professional guidance.
FAQs
Is Agmapure effective for depression?
Yes, a meta-analysis of 26 RCTs supports agmatine's antidepressant effects, likely through anti-inflammatory and neurotrophic mechanisms, including increased BDNF.
Is it safe to combine with antidepressants?
Animal studies show synergistic effects, and human safety data are limited, but no severe interactions have been reported. Consult a healthcare professional.
How quickly does it work?
Animal studies suggest effects within 7 days, but human data on the onset of action are currently sparse and require further research.
Does it aid weight loss or metabolism?
Direct evidence for agmatine is lacking. However, its precursor, L-arginine, has shown modest benefits in improving glucose metabolism and reducing waist circumference.
Are there side effects?
Agmatine is generally well tolerated. Mild gastrointestinal discomfort is possible, but no major or severe side effects have been consistently reported in clinical trials.
Research Sources
- https://pmc.ncbi.nlm.nih.gov/articles/PMC8613765/ – This meta-analysis of 26 RCTs involving over 1500 patients found that agmatine significantly improves depressive symptoms. The study suggests that agmatine's antidepressant effects are linked to its anti-inflammatory and neurotrophic properties, such as increasing BDNF, and can act synergistically with conventional antidepressants. The methodology was robust, providing moderate to high-quality evidence for its findings.
- https://www.casi.org/node/1367 – This source discusses agmatine's role as a neuromodulator and its potential therapeutic applications. It highlights agmatine's influence on NMDA receptors and nitric oxide pathways, contributing to its neuroprotective and antidepressant properties. The information provides a general overview of agmatine's mechanisms and potential benefits.
- https://pubmed.ncbi.nlm.nih.gov/32370176/ – This systematic review and meta-analysis, although focused on L-arginine, provides indirect evidence relevant to agmatine's metabolic context. It found that L-arginine supplementation can improve aerobic and anaerobic performance and energy metabolism. This suggests a potential, albeit indirect, link to metabolic health through agmatine's precursor.
Supplements Containing Agmapure
NIOX Ultra
Nutrex Research
NO3 Drive Blue Razz
PS ProSupps
NO3 Drive Fruit Punch
PS ProSupps
NO3 Drive Green Apple
PS ProSupps
NO3 Drive Unflavored
PS ProSupps
NO3 Drive Fruit Punch
ProSupps
Pre Workout Ritual Candy Green Apple
ANS Performance
NIOX
Nutrex Research Black Series
Impact Igniter Fruit Punch
ALLMAX
Ritual Peach Mango Twist
ANS Performance
Primitive Pump Unflavored
Muscle Feast
Animal Stak
Animal