Effect of a Daily Supplement on Plasma PAI-1 Levels

Aging, Endothelial Dysfunction, Senescence

Endothelial Dysfunction, Senescence

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.

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.

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