An Amino Acid Associated with Healthy Aging

L-ergothioneine is an amino acid associated with longevity and cognitive health.

It is found in mushrooms and fermented foods.¹

In preclinical studies, L-ergothioneine activates proteins tied to longevity,^2-4 reduces inflammation^3,5 and oxidative damage,^3-6 and may help preserve telomere length.⁷

Studies have linked higher L-ergothioneine body levels to a lower risk for age-related diseases, including cognitive decline,^8,9 dementia,^1,10,11 and cardiovascular disease.^1,12

In a large population study, higher blood L-ergo-thioneine levels were associated with roughly 14% lower risk of overall death and about 21% lower risk of cardiovascular death.¹²

Early clinical studies of L-ergothioneine supplementation in older adults showed promise for improving cognitive function,^13,14 and sleep quality,¹⁵ suggesting L-ergothioneine may help support healthy aging.

To deliver higher L-ergothioneine levels than can typically be obtained through diet alone, researchers have developed a process to increase potency.

What Is L-Ergothioneine?

L-ergothioneine is a naturally occurring amino acid that the human body cannot make,^5,16 so it must come from diet or supplements.

Early studies suggest it helps activate the body's natural defenses against aging, protecting cells while supporting mitochondrial health.^2,3,7

Humans have evolved a specific transporter that carries L-ergothioneine into cells.^5,6,16,17

Cells lacking this transporter cannot accumulate it and become more vulnerable to oxidative stress and cell death.¹⁸

Biologic Effects

There are several reasons why L-ergothioneine is so beneficial.

For one, it has a unique structure that gives it stable, long-lasting antioxidant activity.¹⁶ Unlike many other antioxidants, it resists being used up and stays effective even after repeated rounds of neutralizing free radicals and other toxins.¹⁹

In addition, in laboratory studies it activates the protein Nrf2, which ramps up cells' natural defenses against a range of threats.^6,16 It also inhibits NF-kB (nuclear factor-kappa B), a protein complex that drives chronic inflammation.¹⁶

One proposed anti-aging effect of L-ergothioneine is that it may help slow the shortening of telomeres—the protective end caps on chromosomes—and possibly help preserve their length.^3,7 Shorter telomere length is associated with higher mortality and a shorter, less healthy lifespan.^20,21 In preclinical (cell and animal) studies, L-ergothioneine has also been tied to:

• Protecting cells against ultraviolet damage, a driver of skin aging, by reducing oxidative DNA damage and collagen breakdown,^22-24
• Warding off the onset of cellular senescence, when old cells become dysfunctional,^22,25
• Activating sirtuins (SIRT1/SIRT6), cellular defense proteins tied to longevity,²⁵
• Providing neuroprotection, helping to forestall neurodegeneration, including in Parkinson's disease models,^26,27 and
• Supporting healthy mitochondria, the cell's energy "powerhouses' in part by activating the enzyme MPST.^27,28

Together, these mechanisms are thought to contribute to L-ergothioneine's potential role in healthy aging, though most of this evidence remains preclinical.

Tied to Better Health

In population studies, lower blood levels of L-ergothioneine are associated with increased risk of age-related disorders,⁶ including neurodegenerative disorders,^9-11,29 cardiovascular disease,¹² and frailty.³⁰

Blood levels of L-ergothioneine are consistently lower in people with dementia, including Alzheimer's disease, and track with greater brain atrophy.¹⁰

In one study that followed elderly adults attending memory clinics for up to five years, lower L-ergothioneine levels were associated with worse cognitive performance at the start of the study and predicted a significantly faster rate of cognitive decline, particularly in those without established dementia.⁸

Lower L-ergothioneine levels are also linked to cardiovascular and all-cause mortality.^6,12,31 In a population study that followed 3,236 adults for 20 years, higher blood levels of L-ergothioneine were associated with a 21% lower risk of cardiovascular mortality and a 14% lower risk of death from any cause.¹²

A larger study of adults spanning a wide age range likewise identified L-ergothioneine among metabolites associated with lower mortality risk.³¹

What Clinical Studies Show

Studies in cell and animal models have shown that L-ergothioneine may help improve health and lifespan. For example, male mice given L-ergothioneine experienced an approximately 21% increase in their average lifespan.³²

In humans, body levels of L-ergothioneine tend to decline with age.^33,34 Direct oral intake reliably raises blood levels, as ergothioneine is efficiently absorbed and retained.³⁵

In one clinical trial of adults with mild cognitive impairment, taking 5 mg of L-ergothioneine daily for 12 weeks improved multiple measures of cognitive function compared with a placebo.¹³

In a 2025 randomized, placebo-controlled trial, healthy older adults with subjective memory complaints took either 10 mg or 25 mg of L-ergothioneine daily for 16 weeks. From baseline, both doses were associated with improvements in complex attention, cognitive flexibility, and executive function (the ability to plan and carry out goals). The 25 mg group additionally showed improvement in verbal memory and in overall cognitive function and reported better prospective memory (remembering to carry out intended future actions) on a self-report questionnaire.³⁶

In another clinical study, adults with mild cognitive impairment received 25 mg of L-ergothioneine or a placebo three times per week for a year. The placebo group showed no improvement, and a blood marker of neurodegeneration worsened.¹⁴

But in the group receiving L-ergothioneine, learning and memory performance improved and the marker of neurodegeneration stabilized.¹⁴

L-ergothioneine may also improve sleep. In one placebo-controlled study, healthy adults aged 40–75 with poor sleep and high anxiety who took 20 mg of L-ergothioneine daily for four weeks reported less difficulty sleeping than those who received placebo. EEG (brainwave) recordings showed the L-ergothioneine group woke less often during the night and spent less time in the lightest stage of sleep.¹⁵

A separate 2025 study found that a lower dose— 8 mg of L-ergothioneine daily for 16 weeks—was also associated with better subjective sleep quality, with participants reporting more refreshing sleep and longer sleep duration than those receiving placebo.³⁷

Ensuring adequate L-ergothioneine intake may help support multiple aspects of healthy aging.

Summary

L-ergothioneine, an amino acid found in mushrooms, may contribute to some of the health benefits associated with mushroom consumption.

Observational studies have linked higher L-ergo-thioneine levels to longer survival and lower risk of several chronic age-related diseases.

In small clinical studies, L-ergothioneine supplementation improved measures of cognitive function and sleep quality and was associated with stabilization of a biomarker linked to neurodegeneration.

If you have any questions on the scientific content of this article, please call a Life Extension Wellness Specialist at 1-866-864-3027.

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