Ergothioneine: A Vitamin with Antiaging and Neuroprotective Roles?

Educational summary by Dr. Srinivasa, Medical Advisor, and team. Based on Paul B.D. (2022), DOI 10.1089/ars.2021.0043. Educational only, no product endorsement.

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Ergothioneine (EGT), a naturally occurring amino acid, has recently gained attention for its potential health benefits, particularly in the realms of antiaging and neuroprotection. Trace amounts are found in foodstuffs such as certain mushrooms. It is considered a vitamin because it has a role in metabolism (function of cells), and has to be consumed directly since the body can't build it using anything else you eat. In this post, we will use plain language to explore antiaging and neuroprotection research on EGT that was recently summarized by P. Bindu. The original article is here.

Short Summary of Findings

If you just want the TLDR on L-Ergothionine (EGT) from the article;

Antiaging in cells: Healthy cells divide and maintain tissue. As we age, cells become senescent and lose this ability. EGT delays onset of senescence in cells. Read details here.

Antiaging in skin: UV rays from the sun create free radical oxygen in skin, which damages it over time. EGT neutralizes the free radical oxygen and prevents inflamation which also damages the skin. Read details here.

Neuroprotection: Unlike almost all materials in the bloodstream, EGT has a natural gateway into the brain. In the brain, EGT neutralizes free radicals and several neurotoxins which damage brain tissue. Read details here, here, here, and here.

There are a bevy of other interesting effects studied but we'll focus on these three in this summary article.

Antiaging in Cells

Healthy cells replicate themselves by first copying your DNA, then copying the cells machinery, and finally splitting into two complete cells in a process called differentiation.

Because your DNA is used to build and control this cell machinery, it is essential the DNA copying process is correct, or no later replication steps will work properly.

Unfortunately DNA is damaged over time by oxidative stress, where small pieces of DNA are chipped off by oxidizing particles that find their way inside your cells. If not many of these particles find their way to the DNA, the stress caused by the oxidizing particles is low, and your cell's natural DNA maintenance machinery can repair the damage. However, this damage control can be overwhelmed if the environmental oxidative stress is high enough. When this happens your cell will enter a "senescent", or aged state, judging itself too damaged to safely replicate.

EGT was found to turn on two parts of the DNA repair machinery known as "SIRT1" and "SIRT6". SIRT1 Activates DNA repair pathways, and can slow down aging processes. SIRT6 hides surface of your DNA from damaging oxidizing particles, and replenishes “end caps” on DNA that act like the plastic tips on shoelaces. Without those caps, the DNA would start to unravel and the cell would age or malfunction.

Antiaging in Skin

Your skin cells are constantly exposed to sunlight and oxygen, which together create the highly reactive oxidizing particles called free radicals. These can damage DNA, proteins, and collagen that keep your skin flexible. If that damage isn’t repaired, skin becomes dryer, loses elasticity, and permanent wrinkles form.

Skin cells treated with EGT showed less inflammation and less breakdown of collagen after UV exposure. That is very intriguing, but lets understand better why.

EGT naturally collects in skin cells, where it has three distinct functions that counter sunlight damage. Firstly, it is an antioxidant, meaning it neutralizes free radicals by removing the electrical charge from them that would otherwise chip away at the DNA structure. EGT is an unusually effective antioxidant because it is much more stable than its chemical cousins. Secondly, as we just learned, EGT helps the skin’s own repair systems fix UV-related injuries by activating the cells DNA repair machinery. Thirdly, EGT’s structure lets it catch some of the UV wavelengths that can damage DNA. When a UVB photon hits an EGT molecule, that energy is absorbed and dissipated harmlessly as heat instead of causing a DNA strand break.

So in summary, EGT uses three different mechanisms to help skin cells maintain structure and slow the formation of age-related damage.

Neuroprotection

Your brain is protected from many disease causing pathogens by the "Blood Brain Barrier" which stops almost anything in the blood from entering it. Unfortunately, this extreme defense system makes it very challenging to introduce beneficial elements to your brain.

We learned earlier that oxidizing particles are a major factor of aging. Because the brain burns so much energy (20% of all oxygen!) it creates an abnormally large amount of these particles which are accidentally made when the oxygen reactions glitch.

EGT has a natural gateway into the brain thanks to a dedicated natural "transporter" your neurons have evolved, allowing it to cross the blood brain barrier. There are no other known dietary antioxidants with this super highway, so it is a big deal. EGT accumulates in brain regions responsible for movement, learning, and memory.

Once inside the brain, EGT works in several ways to protect it.

Earlier we talked about how over time, oxidizing particles chip away at DNA in cells. EGT neutralizes two major types of these particles. Firstly, glitchy byproducts caused by high oxygen use are neutralized. Secondly it deactivates toxic heavy metals that find their way into the brain. When active, these heavy metals greatly increase the rate of DNA damage.

Beyond protection, EGT appears to support repair. It activates two signaling pathways "mTOR-S6K1" and "TrkB" receptors, both of which promote growth of neurons and differentiation which is the process by which new or damaged nerve cells mature and reconnect.

Final Thoughts

Ergothioneine, or EGT, is a fascinating compound with promising antiaging and neuroprotective research that explores how it works.

As this research continues to unfold, ergothioneine may play a significant role in our understanding of aging and neuroprotection, paving the way for healthier, longer lives.