In nutritional science, we have a relatively unsung hero for supporting healthy aging and longevity: ergothioneine, also known as l-ergothioneine.

The human body doesn't synthesize this naturally occurring amino acid, yet it plays an important role in cellular health and oxidative stress protection. It's found in various dietary sources like bran, beans, certain meats, and dairy products, but edible mushrooms are the foods most enriched with l-ergothioneine.

In this article, we'll get into the fascinating science behind l-ergothioneine, its role alongside longevity vitamins, and its potential to support healthy aging. We'll also introduce the top supplements that harness the power of ergothioneine, helping you make informed shopping choices for your health and wellness journey.

Let's get right in, starting with the basics.

What Is Ergothioneine? An Antioxidant Nutraceutical

L-ergothioneine is a type of thio-histidine betaine amino acid, which describes a unique building block of proteins featuring sulfur (that's the "thio" part) attached to a histidine molecule [1]. This distinctive combination gives these compounds special properties, including potent antioxidant activities.

It's like a supercharged antioxidant, defending your cells against harmful, DNA-destroying free radicals. It's not just a regular nutrient — it's an antioxidant nutraceutical, which means it's a power-packed nutrient with super-charged benefits, especially for keeping you healthy as you age.

It was first discovered in 1909, isolated from the ergot fungus, hence its name. Fungi and certain bacteria called actinobacteria produce it, but plants and animals, including us, don't make it. 

Instead, plants and animals must get ergothioneine from the environment or diet — Animals absorb it from food, and plants take it from the soil.

What makes ergothioneine such an intriguing compound is that the body has a special way of soaking it up and using it exactly where it's needed most, like in the liver, eyes, and skin. 

What Are The Benefits of Ergothioneine?

Ergothioneine has gained a reputation for its impressive antioxidant properties, which have potential implications across various health domains.

We'll take a closer look at the research surrounding the potential benefits of l-ergothioneine, but please keep in mind that our intent is purely educational, presenting findings for informational purposes only. 

This means this article shouldn't be interpreted as medical advice.

If you're considering integrating any supplement into your regimen, especially if you're on medication, please consult your healthcare professional.

1. Antioxidant Powerhouse

When we say ergothioneine is a "powerful antioxidant," we highlight its exceptional ability to combat oxidative stress, a condition where harmful free radicals outnumber the body's ability to neutralize them [2].

Free radicals are unstable molecules that can damage cells, proteins, and DNA. With its unique molecular structure, ergothioneine efficiently scavenges these radicals, stabilizing them and preventing cellular damage.

This action is key for maintaining cellular health and resilience, especially in organs that are highly susceptible to oxidative stress, such as the heart, brain, and liver. 

By safeguarding cells in this way, we can see how ergothioneine supports overall well-being and health.

2. Healthy Aging Appearance

Ergothioneine's role in promoting healthy aging extends beyond cellular protection, including potential benefits for looking younger. 

As an antioxidant, ergothioneine taken internally or as part of skincare may help to shield the skin from environmental stressors like UV radiation and pollution, which accelerates aging signs [3].

By mitigating these effects, ergothioneine could aid in maintaining the skin's elasticity and reducing the appearance of wrinkles and fine lines.

On top of this, ergothioneine modulates proinflammatory cytokines, which means it helps control substances that cause inflammation [3]. When ergothioneine controls those overactive cytokines, it may help calm inflammation in the skin. 

Why is this relevant? Chronic inflammation can lead to various skin issues, like redness and irritation, and even speed up the signs of aging.

This aspect of ergothioneine is particularly intriguing for skincare formulations, offering a proactive approach to maintaining the skin's natural vitality and resilience against the visible signs of aging.

3. Cellular Protection

Ergothioneine's ability to protect cells from environmental stresses is rooted in its unique physicochemical properties as a thio-histidine betaine amino acid.

As a thiol compound, it has a sulfur atom, which influences its antioxidant activity. This allows it to neutralize harmful substances effectively, like reactive oxygen species (ROS).

Ergothioneine is particularly adept at stabilizing these ROS, preventing them from causing cellular damage. Its unique molecular structure enables it to be effectively transported and concentrated in cells and tissues that are most vulnerable to oxidative stress, such as the liver and eyes [1].

By doing so, ergothioneine helps maintain cellular integrity and function in these critical areas, shielding them from environmental and oxidative challenges.

4. Cognitive Health

Emerging research into ergothioneine's impact on cognitive health is quite promising, though we're still learning about its full effects.

One clinical trial involving 92 healthy adults aged between 40 and 75 years observed the potential sleep and cognitive benefits of ergothioneine supplementation. Researchers found that incorporating ergothioneine supported brain health in adults [4].

Moreover, in research focusing on dementia, scientists have found that blood levels of ergothioneine are often low in patients with mild cognitive impairment and dementia [5].

This observation points towards the possible role of ergothioneine in maintaining cognitive function and suggests that it might be beneficial in managing or even preventing cognitive decline. However, before we get too excited about this, more research is needed to fully understand how ergothioneine treatment can impact cognitive health and its potential role in conditions like dementia.

5. Cardiovascular Health

Preliminary research is uncovering a fascinating connection between ergothioneine and heart health.

A notable study in Sweden involving 3,236 participants found that ergothioneine was associated with a lower risk of coronary disease, cardiovascular mortality, and overall mortality [6]. 

This suggests that ergothioneine could benefit heart health as part of a healthy diet.

The ability of ergothioneine to act as a cytoprotectant is key here. 

It scavenges harmful molecules like reactive oxygen and nitrogen species (ROS, RNS), protects against radiation damage, chelates metal cations, and has anti-inflammatory effects.

These properties are particularly relevant in conditions involving chronic oxidative stress and inflammation, characteristic of cardiometabolic diseases like type 2 diabetes and cardiovascular disease [6].

6. Cancer Research

Research on l-ergothioneine has revealed promising potential in cancer treatment and prevention, especially colorectal cancer.

Studies have shown that ergothioneine can induce necroptosis — a type of cell death — in colorectal cancer cells through the SIRT3/MLKL pathway, suggesting its possible role in cancer prevention [7].

Furthermore, it's been found to enhance the effectiveness of cancer immunotherapy by decreasing the immunosuppressive function of tumor-associated macrophages. 

In simpler terms, it appears that ergothioneine helps make cancer treatments more effective by weakening the power of certain cells, which can sometimes protect the tumor. 

By reducing these cells' ability to suppress the immune system, ergothioneine supports the body's own defense to fight cancer more effectively during treatments [8].

These findings point to ergothioneine's versatile role in cancer therapy, although further studies are necessary to understand its effectiveness fully.

7. Anti-Inflammatory Properties

Some research indicates that l-ergothioneine modulates tumor necrosis factor α (TNF-alpha), a critical component in the body's inflammatory response. TNF-alpha is important for controlling inflammation, but too much can cause problems.

The study found that the diet-derived antioxidant ergothioneine helps calm down TNF-alpha activity.

When cells were exposed to stress and TNF-alpha, ergothioneine stepped in to reduce the activation of NF-kappa B, another component that turns on inflammation and lowers the release of IL-8, a chemical that signals more inflammation [9].

This shows us that l-ergothioneine's anti-inflammatory properties could potentially provide therapeutic benefits in conditions characterized by chronic inflammation.

Health Precautions and Side Effects

Most of the side effects of l-ergothioneine supplements included headaches and stomach discomfort. However, like any supplement, it's important to be mindful of potential side effects and health precautions. 

While adverse effects are rare in ergothioneine, the full spectrum of possible side effects isn't completely understood due to limited research.

If you have concerns, consult a healthcare professional before adding ergothioneine supplements to your regimen. Pregnant or breastfeeding women should be particularly cautious and seek medical advice before use.

Food Sources for Ergothioneine

Mushrooms are the richest source, with types like shiitake, oyster, and king oyster mushrooms being particularly high in this compound [10].

Besides mushrooms, you can also find ergothioneine in animal products, particularly in organ meats like liver and kidney from animals such as chicken, pork, and beef.

Black and red beans are good options for those who prefer plant-based sources. While the content of ergothioneine in these foods can vary, incorporating a variety of these into your diet can help boost your intake of this beneficial compound.

Best Ergothioneine Supplements

When it comes to enhancing your diet with additional antioxidants, ergothioneine supplements are a top choice for many health-conscious individuals.

Certain ergothioneine products stand out for their quality, effectiveness, and popularity in the ever-growing market of health supplements. Below, we highlight three best-selling ergothioneine supplements, each offering advantages to cater to your health and wellness needs.

1. Neurogan Health: L-Ergothioneine Tablets

Our L-Ergothioneine Tablets present a natural and effective way to complement your healthy lifestyle with antioxidant support.

Our ergothioneine is sourced from shiitake and oyster mushrooms, two of the richest natural sources, and manufactured in our cGMP facility in San Diego.

With each dose delivering 5 mg, these tablets are formulated to ensure a steady release and optimal absorption in the body.

This product stands out because of its allergen-free formulation, making it a safe choice for individuals with dietary sensitivities. 

As a plant-based source of ergothioneine, it caters well to those following a vegetarian or vegan lifestyle. Each bottle offers a 60-day supply, ensuring that you have a consistent intake over two months.

In addition to the tablet form, we also offer L-Ergothioneine drops for those who prefer a liquid supplement. The only notable liquid ergothioneine on the market.

The tincture version has a higher ergothioneine content per serving (11.6 mg). This higher concentration makes it an excellent option for individuals seeking a more robust dosage in a convenient liquid form. The tincture allows for easy absorption and can be a great alternative for those with difficulty swallowing tablets.

Price: $23

Count: 60 Tablets

Mg per Tablet: 5 mg

Ingredients:

• Pure L-Ergothioneine
• Magnesium Stearate
• Microcrystalline Cellulose
• Dicalcium Phosphate
• Silicon Dioxide

2. Life Extension: L-Ergothioneine Capsules

Life Extension has L-Ergothioneine capsules made from a proprietary form of ergothioneine named ErgoActive and the inclusion of vitamin C.

Each bottle contains 30 vegan-friendly capsules, aligning with various dietary preferences and restrictions. These capsules provide 5 mg of l-ergothioneine per serving, a moderate amount suitable for daily supplementation.

This formulation aims to optimize the nutrient's bioavailability and efficacy. While this product presents a beneficial option for antioxidant supplementation, consumers need to consider their individual health needs and preferences when choosing among various supplement brands.

Price: $19.50

Count: 30 Tablets

Mg per Tablet: 5 mg

Ingredients:

• ErgoActive (L-Ergothioneine)
• Vitamin C (Ascorbyl Palmitate)
• Microcrystalline Cellulose
• Maltodextrin
• Vegetable Cellulose (Capsule)
• Rice Bran
• Silica

3. Nature's Fusions: Ergothioneine Supplements with Organic Mushroom Complex

Nature's Fusion has an ergothioneine supplement combined with an organic mushroom complex.

Each bottle contains 60 capsules, each delivering 5 mg of l-ergothioneine and 600 mg of mushroom extracts, including oyster, shiitake, and king trumpet mushrooms.

Combining l-ergothioneine with a broad spectrum of mushroom extracts may appeal to those looking for a supplement that leverages the synergy of multiple mushroom types.

Price: $26.99

Count: 60 Tablets

Mg per Tablet: 5 mg

Ingredients:

• L-Ergothioneine
• Organic Oyster Mushroom Extract
• Organic Shiitake Mushroom Extract
• Organic King Trumpet Mushroom
• Organic Pullan (Capsule)

Before Buying an Ergothioneine Supplement

When shopping for an ergothioneine supplement, making informed decisions about your health is important. One key factor is to look for products that have undergone third-party lab testing. This testing verifies the supplement's quality, purity, and potency, ensuring you get what's advertised.

Examining the entire ingredient list for potential allergens is always a good idea.

Even if the primary ingredient is safe, supplements can contain other components, like fillers or binders, that might trigger allergic reactions or sensitivities. Consistently checking the ingredient list helps avoid unwanted side effects and ensures the supplement meets your health needs and dietary restrictions.

The Takeaway: Ergothioneine Benefits

Ergothioneine supplements present a promising option for those seeking to enhance their antioxidant intake.

The potential benefits of this unique nutrient, from supporting cellular health to aiding in healthy aging, make it a noteworthy addition to a balanced health regimen.

While highlighting some top-selling supplements, remember the importance of choosing a product that aligns with your specific health needs, including considerations for third-party testing and allergen content.

As with any supplement, consultation with a healthcare professional is recommended to ensure it's the right choice for your individual health journey.

Resources:

1. Borodina, I., Kenny, L. C., McCarthy, C. M., Paramasivan, K., Pretorius, E., Roberts, T. J., ... & Kell, D. B. (2020). The biology of ergothioneine, an antioxidant nutraceutical. Nutrition Research Reviews, 33(2), 190-217.
2. Cheah, I. K., & Halliwell, B. (2021). Ergothioneine, recent developments. Redox biology, 42, 101868.
3. Markova, N. G., Karaman-Jurukovska, N., Dong, K. K., Damaghi, N., Smiles, K. A., & Yarosh, D. B. (2009). Skin cells and tissue are capable of using L-ergothioneine as an integral component of their antioxidant defense system. Free Radical Biology and Medicine, 46(8), 1168-1176.
4. Katsube, M., Watanabe, H., Suzuki, K., Ishimoto, T., Tatebayashi, Y., Kato, Y., & Murayama, N. (2022). Food-derived antioxidant ergothioneine improves sleep difficulties in humans. Journal of Functional Foods, 95, 105165.
5. Wu, L. Y., Cheah, I. K., Chong, J. R., Chai, Y. L., Tan, J. Y., Hilal, S., ... & Lai, M. K. (2021). Low plasma ergothioneine levels are associated with neurodegeneration and cerebrovascular disease in dementia. Free Radical Biology and Medicine, 177, 201-211.
6. Smith, E., Ottosson, F., Hellstrand, S., Ericson, U., Orho-Melander, M., Fernandez, C., & Melander, O. (2020). Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease. Heart, 106(9), 691-697.
7. D'Onofrio, N., Martino, E., Balestrieri, A., Mele, L., Cautela, D., Castaldo, D., & Balestrieri, M. L. (2022). Diet‐derived ergothioneine induces necroptosis in colorectal cancer cells by activating the SIRT3/MLKL pathway. FEBS letters, 596(10), 1313-1329.
8. Yoshida, S., Shime, H., Matsumoto, M., Kasahara, M., & Seya, T. (2019). Anti-oxidative amino acid L-ergothioneine modulates the tumor microenvironment to facilitate adjuvant vaccine immunotherapy. Frontiers in immunology, 10, 671.
9. Rahman, I., Gilmour, P. S., Jimenez, L. A., Biswas, S. K., Antonicelli, F., & Aruoma, O. I. (2003). Ergothioneine inhibits oxidative stress-and TNF-α-induced NF-κB activation and interleukin-8 release in alveolar epithelial cells. Biochemical and biophysical research communications, 302(4), 860-864.