Urolithin A & L-Ergothioneine

Urolithin A promotes mitochondrial biogenesis and improves energy metabolism in muscle tissue. By activating PGC-1α, a key regulator of mitochondrial biogenesis, it increases both the number and function of mitochondria in muscle cells. As a result, muscles become more efficient, enabling greater physical activity, reduced fatigue, and improved overall endurance.

Mechanism of Action:

Urolithin A activates PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), which regulates mitochondrial biogenesis. This process boosts the number of healthy mitochondria, enhances their energy-producing capacity, and supports muscular energy metabolism. Improved mitochondrial regeneration and efficiency reduce muscle fatigue, leading to greater physical strength and endurance.

Practical Significance:

By enhancing mitochondrial function, Urolithin A can be especially beneficial for older adults, athletes, and anyone looking to improve physical performance and recovery after exercise.

Scientific Research:

• Singh et al. (2022): Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults.
• Liu et al. (2022): Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial.
• Zhao et al. (2024): Assessment of Urolithin A effects on muscle endurance, strength, inflammation, oxidative stress, and protein metabolism in male athletes with resistance training: an 8-week randomized, double-blind, placebo-controlled study.

L-Ergothioneine enhances muscle performance by reducing oxidative stress and inflammation—two major contributors to fatigue and muscle damage. As a potent antioxidant, L-Ergothioneine protects muscle cells from free radicals and supports recovery after physical exertion by mitigating oxidative stress-related damage.

Mechanism of Action:

L-Ergothioneine neutralizes free radicals, lowering oxidative stress in muscle tissue. It also exhibits anti-inflammatory properties, which help prevent muscle fatigue and damage. By activating the body's natural cellular defense mechanisms, L-Ergothioneine accelerates muscle recovery after intense activity and reduces post-exercise soreness.

Practical Significance:

L-Ergothioneine supports physical performance and recovery, making it especially valuable for athletes, physically active individuals, and anyone looking to ease muscle pain and fatigue after workouts.

Scientific research:

• Fovet et al. (2024):Ergothioneine Improves Aerobic Performance Without Any Negative Effect on Early Muscle Recovery Signaling in Response to Acute Exercise.
  

Urolithin A and L-Ergothioneine work together to improve muscle strength and endurance:

• Urolithin A: Supports mitochondrial regeneration and biogenesis, enhancing muscle energy metabolism.
• L-Ergothioneine: Protects muscle cells from oxidative stress and aids in recovery, reducing fatigue and muscle damage.

Their synergistic effect leads to significantly improved physical performance, faster recovery, and better muscle condition, making this supplementation effective for both athletes and individuals seeking to enhance their physical health.

Urolithin A helps slow down the aging process by improving cellular health and protecting the body from oxidative stress. It shows promising potential in fighting frailty syndrome, a condition often affecting older adults and characterized by muscle weakness, decreased endurance, slower movement, and increased risk of falls. Additionally, Urolithin A supports skin health by protecting fibroblasts from photoaging and strengthens bone health by inhibiting osteoclastogenesis, which helps prevent osteoporosis.

Mechanism of Action:

Urolithin A activates mitophagy, the process of selectively removing damaged mitochondria and stimulating the generation of new, healthy ones. This enhances the cell’s resilience to oxidative stress, which is a major contributor to aging. Furthermore, Urolithin A protects skin fibroblasts from photoaging by activating the NRF2 pathway, a key regulator of antioxidant responses. It also supports bone health by promoting autophagy in bone marrow macrophages, thereby inhibiting osteoclastogenesis and preserving bone structure.

Practical Significance:

Urolithin A helps older adults maintain muscle strength, skin elasticity, and bone integrity, reducing visible signs of aging such as wrinkles and skeletal weakening. It also combats fatigue and supports a higher quality of life by promoting cellular resilience and energy.

Scientific Studies:

• Liu et al. (2018): Antiaging Effects of Urolithin A on Replicative Senescent Human Skin Fibroblasts.
• Liu et al. (2022): Urolithin A protects human dermal fibroblasts from UVA-induced photoaging through NRF2 activation and mitophagy.
• Tao et al. (2022): Gut Metabolite Urolithin A Inhibits Osteoclastogenesis and Senile Osteoporosis by Enhancing the Autophagy Capacity of Bone Marrow Macrophages.
• Wang et al. (2022): Effects of urolithin A on osteoclast differentiation induced by receptor activator of nuclear factor-κB ligand via bone morphogenic protein 2.
• D'Amico et al. (2021): Impact of the Natural Compound Urolithin A on Health, Disease, and Aging.
• Faitg et al. (2023): Mitophagy Activation by Urolithin A to Target Muscle Aging.
• Kuerec et al. (2024): Targeting aging with urolithin A in humans: A systematic review.
• Kothe et al. (2024): Urolithin A as a Potential Agent for Prevention of Age-Related Disease: A Scoping Review.

L-Ergothioneine helps slow down the aging process by protecting cells from oxidative stress and inflammation.

Its unique antioxidant properties and ability to eliminate aging neuronal cells support cellular and nervous system health, contributing to longevity.

Mechanism of Action:

L-Ergothioneine acts as a powerful antioxidant, neutralizing free radicals that accelerate aging. Its ability to cross the blood-brain barrier allows it to support the removal of aging neuronal cells, helping to maintain nervous system health and cognitive function. It also protects DNA and mitochondria from oxidative damage, supporting cellular integrity throughout the body.

Practical Significance:

L-Ergothioneine may help reduce signs of aging such as decreased skin elasticity, muscle mass loss, and cognitive decline. It is particularly valuable in protecting against aging driven by oxidative stress.

Scientific research:

• Chen et al. (2023): Ergothioneine and its congeners: Anti-aging mechanisms and pharmacophore biosynthesis.
  
• Apparoo et al. (2023): Ergothioneine and its prospects as an anti-aging compound.
  
• Katsube et al. (2024): Ergothioneine promotes longevity and healthy aging in male mice.
  
• Apparoo et al. (2024): Potential role of ergothioneine-rich mushroom as an anti-aging candidate through elimination of neuronal senescent cells.
  

Urolithin A and L-Ergothioneine work together to support anti-aging processes:

• Urolithin A: Stimulates mitophagy, protects skin fibroblasts, and strengthens bone health.

• L-Ergothioneine: Shields cells from oxidative stress, supports the elimination of aging neurons, and promotes longevity.

Their synergistic action supports cellular health, reduces visible signs of aging, improves cognitive function, and enhances the health of muscles, skin, and bones.

Urolithin A supports cognitive function by improving mitochondrial health and reducing neuroinflammation. By stimulating mitophagy and lowering oxidative stress, it promotes the regeneration of nerve cells, which is essential for maintaining mental sharpness and protecting against cognitive decline.

Mechanism of Action:

Urolithin A activates mitophagy, enabling the removal of damaged mitochondria in neurons and their replacement with new, more efficient organelles. Improved mitochondrial function enhances energy production and overall neural health. Additionally, Urolithin A reduces oxidative stress and neuroinflammatory cytokines like IL-1β and TNF-α, protecting neurons from damage that can lead to neurodegenerative diseases such as Alzheimer’s.

Practical Significance:

Thanks to these properties, Urolithin A is beneficial for individuals under cognitive strain, helps prevent early brain aging, and may improve focus and memory—especially in older adults.

Scientific research:

• Lee et al. (2021): Urolithin A suppresses high glucose-induced neuronal amyloidogenesis by modulating TGM2-dependent ER-mitochondria contacts and calcium homeostasis.
• Esselun et al. (2021): Effects of Urolithin A on Mitochondrial Parameters in a Cellular Model of Early Alzheimer Disease.
• Hou et al. (2020): Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions.
• Kim et al. (2020): Neuroprotective effects of Urolithin A against oxidative stress-mediated apoptosis in neuronal cells.
• An et al. (2019): Urolithins: A Prospective Alternative against Brain Aging.
• Velagapudi et al. (2019): Induction of Autophagy and Activation of SIRT-1 Deacetylation Mechanisms Mediate Neuroprotection by the Pomegranate Metabolite Urolithin A in BV2 Microglia and Differentiated 3D Human Neural Progenitor Cells.

L-Ergothioneine supports cognitive function by protecting brain cells from oxidative stress and inflammation. Its ability to accumulate in the brain—especially in areas most vulnerable to damage—helps maintain mental sharpness and delays neurodegenerative processes.

Mechanism of Action:

L-Ergothioneine crosses the blood-brain barrier via the SLC22A4 transporter and accumulates in neurons, where it neutralizes reactive oxygen species (ROS) and reduces inflammation. It protects key brain structures, such as mitochondria and DNA, from oxidative damage, supporting neuronal health and improving brain energy metabolism.

Practical Significance:

L-Ergothioneine enhances cognitive abilities, boosts memory and concentration, and helps prevent mental decline in older adults. It may also offer protection against neurodegeneration in diseases like Alzheimer’s and Parkinson’s.

Scientific research:

• Fu et al. (2024): Ergothioneine as a Natural Antioxidant Against Oxidative Stress-Related Diseases.
• Wu et al. (2021): Low Plasma Ergothioneine Predicts Cognitive and Functional Decline in an Elderly Cohort Attending Memory Clinics.

Urolithin A and L-Ergothioneine work together to support mental performance:

• Urolithin A: Enhances mitochondrial health in neurons, reduces oxidative and neuroinflammatory stress, and supports neuronal regeneration.

• L-Ergothioneine: Protects the brain from oxidative and inflammatory damage, prevents neurodegeneration, and supports the energy metabolism of brain cells.

Their synergistic action supports brain health by improving concentration, memory, and cognitive function, while also slowing down the aging processes of the nervous system.

Urolithin A plays a key role in supporting mitochondrial health by activating the process of mitochondrial autophagy, known as mitophagy.

Mitophagy enables the selective removal of damaged mitochondria, maintaining their quality and functionality. Mitochondria, often referred to as the "powerhouses of the cell," are responsible for producing energy in the form of ATP, which is essential for the body’s metabolic processes.

Mechanism of Action:

Urolithin A activates the PINK1/Parkin signaling pathway, which is crucial for mitophagy. When mitochondria become damaged, the PINK1 kinase accumulates on their outer membrane, recruiting Parkin, an E3 ubiquitin ligase. Parkin tags mitochondrial proteins with ubiquitin chains, marking them for degradation through the proteasomal system. Additionally, Urolithin A supports mitochondrial biogenesis by activating PGC-1α, allowing old mitochondria to be replaced with new, more efficient ones.

Practical Significance:

The mitophagy process promoted by Urolithin A helps the body regenerate damaged mitochondria, enhancing energy production, physical endurance, and overall cellular performance. This is especially important for muscle health in older adults, athletes, and individuals experiencing fatigue or oxidative stress.

Scientific research:

• Andreux et al. (2019): The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans.
  


• D'Amico et al. (2022):Urolithin A improves mitochondrial health, reduces cartilage degeneration, and alleviates pain in osteoarthritis.
  

L-Ergothioneine is a natural amino acid with exceptional antioxidant properties that plays a key role in protecting mitochondria from oxidative stress.

Free radicals generated during energy production in mitochondria can damage these organelles, impairing cellular function. L-Ergothioneine effectively neutralizes these harmful molecules, helping to maintain mitochondrial health.

Mechanism of Action:

L-Ergothioneine acts by activating 3-mercaptopyruvate sulfurtransferase (MPST), a key mitochondrial enzyme that supports mitochondrial respiration. By increasing MPST activity, L-Ergothioneine optimizes cellular energy production and improves mitochondrial efficiency. Moreover, thanks to its ability to accumulate in muscle mitochondria after physical exertion, L-Ergothioneine provides targeted protection against oxidative damage in the most stressed tissues.

Practical Significance:

L-Ergothioneine supports mitochondrial regeneration after physical activity, reduces fatigue, and enhances overall physical performance. It also protects mitochondria in the brain and other organs, making it a valuable ally in preventing aging and diseases associated with oxidative damage.

Scientific research:

• Beelman et al. (2024): Ergothioneine boosts mitochondrial respiration and exercise performance via direct activation of MPST .

Urolithin A and L-Ergothioneine work synergistically to comprehensively support mitochondrial health:

• Urolithin A: regenerates mitochondria through mitophagy and stimulates their biogenesis.

• L-Ergothioneine: protects mitochondria from oxidative stress and enhances their efficiency.

Together, these ingredients promote regeneration, improve physical and energy performance, and slow down aging processes, providing holistic support for cellular health.

Urolithin A exhibits strong anti-inflammatory effects that support tissue regeneration and help reduce discomfort associated with chronic inflammation. By inhibiting the activation of key inflammatory pathways such as NF-κB, Urolithin A reduces the production of pro-inflammatory cytokines. This action accelerates the recovery of muscles and joints after physical exertion and slows down cartilage degeneration, which is especially important in cases of osteoarthritis.

Mechanism of Action:

Urolithin A inhibits the activation of the NF-κB pathway, a major regulator of inflammation in the body. NF-κB controls the expression of genes responsible for the production of cytokines such as TNF-α and IL-6. By limiting their production, Urolithin A reduces the inflammatory response, alleviates pain, and supports tissue repair. This also helps protect cartilage and maintain joint health.

Practical Significance:

The anti-inflammatory action of Urolithin A is particularly beneficial for individuals dealing with chronic muscle and joint pain, athletes prone to micro-injuries, and people suffering from degenerative joint conditions such as osteoarthritis.

Scientific research:

• Zhao et al. (2024): Pharmacological Effects of Urolithin A and Its Role in Muscle Health and Performance.
  
• 
  D'Amico et al. (2022):Urolithin A improves mitochondrial health, reduces cartilage degeneration, and alleviates pain in osteoarthritis.
  

L-Ergothioneine is a natural amino acid with strong anti-inflammatory properties. Thanks to its unique chemical structure, it effectively neutralizes free radicals, which are a major cause of oxidative stress and inflammation. L-Ergothioneine reduces the production of pro-inflammatory cytokines and lowers inflammation markers, supporting the health of muscles and joints.

Mechanism of Action:

L-Ergothioneine acts as an antioxidant, reducing oxidative stress that triggers inflammatory responses. By neutralizing free radicals, it limits the production of cytokines such as IL-1β and TNF-α. As a result, it helps decrease inflammation in muscle and joint tissues, promoting recovery and pain reduction.

Practical Significance:

Thanks to its properties, L-Ergothioneine may benefit individuals suffering from chronic joint pain, muscle inflammation, and also assist in recovery after physical exertion.

Scientific research:

• Fu et al. (2024):Ergothioneine as a Natural Antioxidant Against Oxidative Stress-Related Diseases.
  

• Urolithin A and L-Ergothioneine work together to comprehensively reduce inflammation:Urolithin A: Inhibits key inflammatory pathways such as NF-κB, reduces the production of pro-inflammatory cytokines, and helps prevent cartilage degeneration.
• L-Ergothioneine: Reduces oxidative stress, preventing inflammatory responses, and supports the regeneration of muscle and joint tissues.
  
  Their combined action provides significant benefits in muscle recovery, joint protection, and the reduction of pain and discomfort associated with chronic inflammation.

Urolithin A supports nervous system health by protecting neurons from oxidative stress and enhancing mitochondrial function.

By activating autophagy pathways, Urolithin A facilitates the removal of damaged cellular components, preventing the accumulation of toxic proteins and malfunctioning mitochondria. This process plays a key role in the prevention of neurodegenerative diseases such as Alzheimer’s.

Mechanism of Action:

Urolithin A reduces oxidative stress in neurons by activating autophagy, which eliminates damaged mitochondria and proteins. Improving mitochondrial function in neurons helps maintain cellular homeostasis and supports regenerative processes. Additionally, Urolithin A modulates the communication between the endoplasmic reticulum (ER) and mitochondria, improving calcium homeostasis and preventing amyloidogenesis—a hallmark of Alzheimer’s disease.

Practical Significance:

Thanks to its neuroprotective properties, Urolithin A can support individuals exposed to oxidative and inflammatory brain damage, as well as older adults at increased risk of neurodegenerative conditions.

Scientific research:

• Esselun et al. (2021): Effects of Urolithin A on Mitochondrial Parameters in a Cellular Model of Early Alzheimer Disease.
  
• Hou et al. (2020): Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions.
  
• Kim et al. (2020): Neuroprotective effects of Urolithin A against oxidative stress-mediated apoptosis in neuronal cells.
  
• Lee et al. (2021): Urolithin A suppresses high glucose-induced neuronal amyloidogenesis by modulating TGM2-dependent ER-mitochondria contacts and calcium homeostasis.
  
• Velagapudi et al. (2019): Induction of Autophagy and Activation of SIRT-1 Deacetylation Mechanisms Mediate Neuroprotection by the Pomegranate Metabolite Urolithin A in BV2 Microglia and Differentiated 3D Human Neural Progenitor Cells.
  

L-Ergothioneine exhibits exceptional neuroprotective properties due to its ability to cross the blood-brain barrier and accumulate in areas of the brain particularly vulnerable to oxidative stress.

It neutralizes reactive oxygen species (ROS) and protects neurons from inflammation and oxidative damage—key contributors to neurodegenerative diseases such as Alzheimer’s and Parkinson’s.

Mechanism of Action:

L-Ergothioneine crosses the blood-brain barrier via the specific transporter SLC22A4, allowing it to concentrate in brain cells exposed to oxidative stress. It functions as a powerful antioxidant, neutralizing ROS and preventing neuronal damage. Additionally, L-Ergothioneine supports glucose metabolism in the brain, which enhances cognitive function and slows the accumulation of amyloid plaques.

Practical Significance:

By protecting neurons from oxidative damage, L-Ergothioneine supports brain health and helps prevent cognitive decline, especially in older adults and those at risk of neurodegenerative diseases.

Scientific research:

• Whitmore et al. (2024):Longitudinal Consumption of Ergothioneine Reduces Oxidative Stress and Amyloid Plaques and Restores Glucose Metabolism in the 5XFAD Mouse Model of Alzheimer's Disease.
  


• Ishimoto et al. (2021): Ergothioneine in the Brain.
  

Urolithin A and L-Ergothioneine work together to support nervous system health:

• Urolithin A: Enhances mitochondrial health in neurons, activates autophagy, and prevents the accumulation of toxic proteins.
• L-Ergothioneine: Protects neurons from oxidative stress, supports glucose metabolism, and reduces inflammation in the brain.
  
  Their synergistic action helps protect the brain from oxidative and inflammatory damage, improves cognitive function, and supports the overall health of the nervous system.

Urolithin A exhibits strong antioxidant properties, neutralizing reactive oxygen species (ROS) and reducing oxidative stress in cells. It supports the body’s natural defense mechanisms by increasing the expression of antioxidant enzymes and decreasing ROS production. As a result, it helps protect cells from oxidative damage, which is closely linked to aging and chronic diseases.

Mechanism of Action:

Urolithin A functions as an antioxidant by neutralizing ROS and enhancing the activity of antioxidant enzymes. It also supports autophagy processes that remove damaged mitochondria—the primary source of ROS—and helps reduce free radical levels by limiting their production within mitochondria.

Practical Significance:

By reducing oxidative stress, Urolithin A protects cells from damage, supports mitochondrial health, and improves physical performance and recovery. It also has protective potential against chronic diseases associated with excess ROS, such as cardiovascular disease and cancer.

Scientific research:

• Singh et al. (2022):Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults.
  
• Zhao et al. (2018):Metabolite of ellagitannins, urolithin A induces autophagy and inhibits metastasis in human SW620 colorectal cancer cells.
  

L-Ergothioneine is a unique antioxidant that effectively eliminates free radicals and protects cells from oxidative stress. Its distinctive chemical structure, which includes a thiol group, makes it especially efficient in neutralizing harmful oxidative molecules such as peroxynitrite and hydroxyl radicals. L-Ergothioneine also protects key cellular structures, including mitochondria and DNA, from oxidative damage.

Mechanism of Action:

L-Ergothioneine enters cells and neutralizes reactive oxygen species (ROS), helping to maintain cellular health. Its ability to accumulate in tissues particularly vulnerable to oxidative stress—such as the brain, liver, and muscles—enables targeted protection where it’s needed most. Additionally, its antioxidant action supports the body’s natural defense systems.

Practical Significance:

Thanks to its antioxidant properties, L-Ergothioneine supports cellular health throughout the body, helps prevent premature aging, and reduces the risk of chronic diseases associated with oxidative stress.

Scientific research:

• Fu et al. (2024):Ergothioneine as a Natural Antioxidant Against Oxidative Stress-Related Diseases.
  

Urolithin A and L-Ergothioneine work in a complementary way to protect against oxidative stress:

• Urolithin A: Reduces ROS production in mitochondria and supports autophagy processes, eliminating damaged organelles that are a source of oxidative stress.

• L-Ergothioneine: Neutralizes ROS, protecting cellular structures and supporting cell health in areas most vulnerable to oxidative damage.

Their combined action helps protect the body from oxidative stress, improves mitochondrial function, reduces the risk of chronic diseases, and supports cellular health and regeneration.