Educational summary by Dr Srinivasa, Medical Advisor, and team. Based on Servillo L. et al. (2017), DOI: 10.1097/FJC.0000000000000464. Educational only, no product endorsement.
The heart and blood vessels are constantly exposed to environmental toxins. Things such as high blood sugar, stress, poor diet, and even everyday metabolic reactions generate oxidizing toxins that can damage the lining of blood vessels. This "oxidative stress" is a root cause of many cardiovascular diseases, including arterial plaque buildup, and hypertension.
L-Ergothioneine (EGT) is a rare dietary amino acid found in trace amounts in some foods. Because humans cannot synthesize EGT, it must be obtained from food. Unlike other amino acids, it accumulates in tissues such as the liver, kidneys, and heart through a highly specific cellular transport mechanism. This special mechanism has excited scientists to better understand why the body specifically recruits EGT in these tissues.
Here we review research exploring the potential of EGT to defend blood vessels and the cardiovascular system. The experiments described by Dr. Servillo's team reported on chemical and biological ways EGT protects cells from damage caused by oxidative stress.
Short Summary of Findings
If you just want the TL;DR on L-Ergothioneine (EGT):
Protection of Blood Vessel Cells: EGT shields endothelial cells from oxidative and inflammatory stress, reducing damage linked to arterial plaque and diabetes.
Restored Vascular Function: EGT enhances the natural signaling in blood vessels that allows them to relax and maintain healthy circulation. It also reduces inflammatory signaling that drives vascular aging.
Unique Antioxidant Chemistry: EGT neutralizes a wide range of oxidants more stably than other dietary antioxidants.
Together, these findings suggest EGT acts as a precision antioxidant by defending the cardiovascular system from calming inflammation, and preserving healthy vessel function.
Protection of Blood Vessel Cells
Endothelial cells form the inner lining of every blood vessel. When exposed to chronic oxidative stress or high glucose, they lose elasticity, become inflamed, and attract immune cells. This is emblematic of early vascular disease.
Studies reviewed in this paper found that EGT enters endothelial cells via "OCTN1" transporters and directly reduces oxidative stress and inflammation. Even at very low (micromolar) concentrations, EGT lowered unwanted "oxidative" cell byproducts and downregulated several "inflammatory" molecules. Excess inflammatory molecules are undesirable as they promote white-blood-cell adhesion to vessel walls, a precursor to plaque buildup. Oxidative byproducts are undesirable as they can damage DNA and cell machinery.
EGT also up-regulated two protective proteins, SIRT1 and SIRT6, which help maintain genomic stability and delay premature cellular aging. Together, they reduce exposure of the genome to damaging oxidative molecules.
In plain language: EGT acted as a cellular “shield” for the blood vessel wall by calming inflammation, reducing oxidative damage, and keeping endothelial cells youthful and functional.
Restored Vascular Function
Beyond protecting cells, EGT helps restore normal vessel behavior when under chronic stress. In in vivo studies of oxidative or diabetic stress, EGT allowed arteries that had lost flexibility to regain much of their normal relaxation response and sustain blood flow. Scientists found that this happened because EGT made the vessel lining more responsive to the body’s natural nitric-oxide signals that control blood pressure.
In further findings of the chronic cardiovascular stress study, supplementation with EGT for several weeks improved blood vessels' ability to relax in response to normal signaling from 33 % to 73 % of normal. This dramatic recovery of blood vessel responsiveness disappeared if nitric-oxide signaling was blocked, confirming that EGT acts through the body’s natural nitric-oxide pathway.
In plain language: EGT helped blood vessels stay flexible and resilient under stress, promoting healthier circulation and reducing the long-term risks of cardiovascular damage.
Unique Antioxidant Chemistry
EGT’s protective ability starts at the molecular level. Unlike more common antioxidants which are quickly oxidized and worn out, EGT exists mainly in a chemically stable form that resists breakdown and continuously recycles itself.
When EGT encounters toxic oxidants, it forms a temporary compound called "ESSE". Other antioxidants stop here, but ESSE can spontaneously convert back into active EGT. All other dietary antioxidants need help from an external "reducing" chemical reaction to do the same.
During ESSE's spontaneous return to EGT, chemical by-products actually act as reducing agents. This means that ESSE recycles itself into EGT whilst simultaneously jump-starting other protective molecules. In other words, it reinforces the entire antioxidant network. Finally, each EGT molecule can donate far more charge when neutralizing toxins than most dietary antioxidants, making it highly potent.
In plain language: EGT doesn’t just “use itself up” when fighting free radicals, it regenerates and supports other antioxidants, providing long-lasting protection where oxidative stress is strongest.
Final Thoughts
This research review highlights how L-Ergothioneine stands out from ordinary antioxidants. It is chemically stable, biologically selective, and deeply integrated into the body’s vascular defense system.
By protecting blood vessel cells, supporting vascular function, and neutralizing toxic oxidants, EGT shows promise as a nutritional ally for heart and vascular health, especially in conditions involving oxidative stress, such as aging or diabetes.
While more human clinical trials are still needed, EGT’s excellent safety record and strong mechanistic evidence make it a compelling candidate for future cardiovascular support.
