Effect of a Daily Supplement on Plasma PAI-1 Levels

Effect of a Daily Nitric Oxide-Stimulating Supplement on Plasma PAI-1 Levels: a Six-Week, Open-Label Clinical Trial

In a healthy person, the production of nitric oxide (NO) by the endothelium, the inner lining of the blood vessel, is responsible for a) the ability of the blood vessel to dilate so it can increase its blood flow and b) act as an anti-clotting product to prevent blood clotting in those vessels. Under physiological stress either due to the development of a disease such as diabetes or simply from aging, the endothelial cells can be impacted and become dysfunctional, thereby impairing their ability to make NO and even promoting the development of blood clots. When such endothelial dysfunction occurs, it may be a precursor for the future development of cardiovascular (CV) disease like hypertension or coronary artery disease later on in life in these patients. Therefore, the ability to enhance the local production or availability of NO within such affected blood vessels in patients identified as prone to endothelial dysfunction could play a positive role in either preventing or delaying the onset of endothelial dysfunction and subsequent CV disease in such patients.

RM is an oral supplement consisting of natural ingredients and the amino acid, L-citrulline. In laboratory experiments with cells from the inner lining of blood vessels, the four components of RM have been shown to increase the concentration of NO and decrease the levels of some aging markers. In our recently completed study (manuscript currently in review), 31 young men and women took the supplement for 14 days and had no serious side effects. The supplement caused the expected potentially beneficial dilation of the blood vessels and decrease in the levels of Plasminogen Activator Inhibitor-1 (PAI-1), whose levels correlate with aging and risk of cardiovascular disease.

In this study, healthy participants will consume the supplement for a 6-week period to determine if PAI-1 levels continue to be suppressed and also examine whether the supplement has an effect on other blood markers whose levels can change with aging or cardiovascular disease and may also be indicative or predictive of an illness.

Study Overview

• Status: Recruiting
• Conditions: Aging; Endothelial Dysfunction; Senescence
• Intervention / Treatment: Dietary supplement: Supplement with ginger extract, L-citrulline, Paullinia cupana, and muira puama

Detailed Description

This study examines the effect of six weeks of daily supplementation on a panel of blood markers associated with vascular aging and inflammation.

The blood markers Plasminogen Activator Inhibitor-1 (PAI-1), Interleukin-8 (IL-8), Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), Fibroblast Growth Factor 23 (FGF-23), C-Reactive Protein (CRP), and Klotho will be measured. PAI-1 is a protein involved in blood clotting whose elevated levels are associated with increased cardiovascular risk and aging. IL-8 is a pro-inflammatory cytokine linked to chronic inflammation. PCSK9 is involved in lipid metabolism and cardiovascular risk. FGF-23 is a regulator of phosphate metabolism and vascular calcification. CRP is a general marker of system inflammation, and Klotho is an anti-aging protein with protective effects on vascular and renal function.

By assessing these markers, this study seeks to determine whether a natural oral supplement can modulate key pathways involved in vascular inflammation and aging, potentially positioning it as a natural oral supplement that may support vascular health in the context of age-related decline.

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sriram V Eleswarapu, MD, PhD; Phone Number: 3107943058; Email: seleswarapu@mednet.ucla.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90034
      • Recruiting
      • UCLA
      • Contact: Sriram V Eleswarapu, MD, PhD; Phone Number: 310-794-3058; Email: seleswarapu@mednet.ucla.edu
    • Santa Monica, California, United States, 90403
      • Recruiting
      • UCLA The Men's Clinic
      • Contact: Sriram V Eleswarapu, MD, PhD; Phone Number: 310-794-3058; Email: seleswarapu@mednet.ucla.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• People of any gender at least 18 years of age who do not have a history of acute or chronic cardiovascular illnesses are eligible.

Exclusion Criteria:

• Younger than 18 years of age
• Currently pregnant (which will be confirmed by pregnancy test for participants capable of pregnancy)
• Using hormonal birth control
• Current smoker
• Allergy to ginger, muira puama, Paullinia cupana, or L-citrulline
• Previous use of Revactin® or RM
• History of serious cardiovascular events, including myocardial infarction (heart attack) or stroke
• History of coronary, cardiac, or carotid surgery such as a stent, heart surgery, or endarterectomy
• Active cancer of any type other than skin cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Supplement; All subjects recruited in this study will be in the experimental group receiving the oral supplement to consume twice daily for 42 days.	Dietary supplement: Supplement with ginger extract, L-citrulline, Paullinia cupana, and muira puama; Participants will consume a supplement called RM, which is composed of ginger extract, L-citrulline, and the herbal components Paullinia cupana and muira puama.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Blood Level of Plasminogen Activator Inhibitor-1 Between Baseline and 6 Months	Blood levels of Plasminogen Activator Inhibitor-1 (PAI-1), a marker that correlates with aging and risk of cardiovascular disease, will be measured through a standard blood draw. Measurement units are ng/mL.	From enrollment to the end of treatment at 6 weeks +/- 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Blood Level of Interleukin-8 Between Baseline and 6 Months	The blood marker Interleukin-8 (IL-8) will be measured through a standard blood draw. IL-8 is a pro-inflammatory cytokine linked to chronic inflammation. Measurement units are pg/mL.	From enrollment to the end of treatment at 6 weeks +/- 7 days
Change in Blood Level of Proprotein Convertase Subtilisin/Kexin Type 9 Between Baseline and 6 Months	The blood marker Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) will be measured through a standard blood draw. PCSK9 is involved in lipid metabolism and cardiovascular risk. Measurement units are ng/mL.	From enrollment to the end of treatment at 6 weeks +/- 7 days
Change in Blood Level of Fibroblast Growth Factor 23 (FGF-23) Between Baseline and 6 Months	The blood marker Fibroblast Growth Factor 23 (FGF-23) will be measured through a standard blood draw. FGF-23 is a regulator of phosphate metabolism and vascular calcification. Measurement units are pg/mL.	From enrollment to the end of treatment at 6 weeks +/- 7 days
Change in Blood Level of C-Reactive Protein Between Baseline and 6 Months	The blood marker C-Reactive Protein (CRP) will be measured through a standard blood draw. CRP is a general marker of systemic inflammation. Measurement units are mg/dL.	From enrollment to the end of treatment at 6 weeks +/- 7 days
Change in Blood Level of Klotho Between Baseline and 6 Months	The blood marker Klotho will be measured through a standard blood draw. Klotho is an anti-aging protein with protective effects on vascular and renal function. Measurement units are pg/mL.	From enrollment to the end of treatment at 6 weeks +/- 7 days
Change in Blood Pressure Between Baseline and 6 Months	Systolic and diastolic blood pressure will be measured. Measurement units are mm Hg.	From enrollment to the end of treatment at 6 weeks +/- 7 days

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Investigators: Principal Investigator: Sriram V Eleswarapu, MD, PhD, University of California, Los Angeles

Publications and helpful links

General Publications

• Whisner CM, Angadi SS, Weltman NY, Weltman A, Rodriguez J, Patrie JT, Gaesser GA. Effects of Low-Fat and High-Fat Meals, with and without Dietary Fiber, on Postprandial Endothelial Function, Triglyceridemia, and Glycemia in Adolescents. Nutrients. 2019 Nov 2;11(11):2626. doi: 10.3390/nu11112626.
• Haptonstall KP, Choroomi Y, Moheimani R, Nguyen K, Tran E, Lakhani K, Ruedisueli I, Gornbein J, Middlekauff HR. Differential effects of tobacco cigarettes and electronic cigarettes on endothelial function in healthy young people. Am J Physiol Heart Circ Physiol. 2020 Sep 1;319(3):H547-H556. doi: 10.1152/ajpheart.00307.2020. Epub 2020 Jul 31.
• Papamichael CM, Aznaouridis KA, Karatzis EN, Karatzi KN, Stamatelopoulos KS, Vamvakou G, Lekakis JP, Mavrikakis ME. Effect of coffee on endothelial function in healthy subjects: the role of caffeine. Clin Sci (Lond). 2005 Jul;109(1):55-60. doi: 10.1042/CS20040358.
• Nguyen S, Rajfer J, Shaheen M. Safety and efficacy of daily Revactin(R) in men with erectile dysfunction: a 3-month pilot study. Transl Androl Urol. 2018 Apr;7(2):266-273. doi: 10.21037/tau.2018.03.22.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 5, 2026
• First Submitted That Met QC Criteria: March 10, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Endothelial Dysfunction; Senescence
• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Amino Acids; Amino Acids, Diamino; ginger extract; Citrulline
• Other Study ID Numbers: IRB #25-1948

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No