Evidence for Dietary Agmatine Sulfate Effectiveness in Neuropathies Associated with Painful Small Fiber Neuropathy. A Pilot Open-Label Consecutive Case Series Study

Abstract

Peripheral neuropathies associated with painful small fiber neuropathy (SFN) are complex conditions, resistant to treatment with conventional medications. Previous clinical studies strongly support the use of dietary agmatine as a safe and effective treatment for neuropathic pain. Based on this evidence, we conducted an open-label consecutive case series study to evaluate the effectiveness of agmatine in neuropathies associated with painful SFN (Study Registry: ClinicalTrials.gov, System Identifier: NCT01524666). Participants diagnosed with painful SFN and autonomic dysfunctions were treated with 2.67 g/day agmatine sulfate (AgmaSet® capsules containing G-Agmatine® brand of agmatine sulfate) for a period of 2 months. Before the beginning (baseline) and at the end of the treatment period, participants answered the established 12-item neuropathic pain questionnaire specifically developed to distinguish symptoms associated with neuropathy and to quantify their severity. Secondary outcomes included other treatment options and a safety assessment. Twelve patients were recruited, and 11 patients—8 diagnosed with diabetic neuropathy, two with idiopathic neuropathy and one with inflammatory neuropathy—completed the study. All patients showed improvement in neuropathic pain to a varied extent. The average decrease in pain intensity was 26.0 rating points, corresponding to a 46.4% reduction in overall pain (p < 0.00001). The results suggest that dietary agmatine sulfate has a significant effect in reducing neuropathic pain intensity associated with painful SFN resistant to treatment with conventional neuropathic pain medications. Larger randomized placebo-controlled studies are expected to establish agmatine sulfate as a preferred treatment.

The Yin and Yang of ACE/ACE2 Pathways: The Rationale for the Use of Renin-Angiotensin System Inhibitors in COVID-19 Patients

“…Of note, NOS pathway has been shown to be upregulated by both Ang (1-7)/MasR and Ang (1-9)/AT2 receptor pathways that are downstream ACE2 activity [38,39,41,43]. Moreover, agmatine has a regulated plasma concentration in the range of 20-80 ng/mL and the use of dietary agmatine has been shown to be safe and effective in reducing neuropathic pain [129]. Moreover, agmatine sulfate is regularly taken as a bodybuilding supplement.…”

Risk Associated with the Use of Selected Ingredients in Food Supplements

“…Scientific studies indicate the synergism of agmatine with analgesic drugs from the opioid group in terms of analgesic activity. Agmatine reduces the addictive potential of opioids and limits the development of tolerance [204,205,206] …”

“…Few clinical trials have been performed on the use of agmatine. In a clinical trial in patients with neuropathic pain, agmatine was shown to have analgesic activity [205] . In a study on patients with depression, the application of agmatine at the dose of 2–3 g per day led to remission of depression symptoms.…”

Yin-Yang Balance of ACE/ACE2 Pathways: The Rational for Administration of ACE2 Pathway Inhibitors in Patients Infected by SARS-CoV-2

“…Indeed, NAAE is a weak ACE2 inhibitor, it is in fact more than a thousand-fold less potent than MLN-4760; however, if agmatine will be proven to have ACE2 inhibitory activity, it might be helpful to prevent the trigger of the positive feedback loops in the first mild phases of the disease. To this regard, the use of dietary agmatine has been shown to be safe and effective in reducing neuropathic pain [76] and agmatine sulfate is regularly taken as a bodybuilding supplement.…”