Can L-Ergothioneine and Alpha-Ketoglutarate Work Together?
Last time, we showed that L-Ergothioneine (EGT) and Pyrroloquinoline Quinone boost mitochondrial health by forming a “Shield and Spark” combo. This week, we turn to a new pair, EGT and Alpha-Ketoglutarate (AKG). They represent a sophisticated approach to improving cellular longevity. When taken together, EGT provides an enduring shield against oxidative stress, while AKG drives cellular clean-up, helping restore epigenetic youthfulness.
What Is AKG’s Role In Metabolic Signaling?
A critical intermediate in the Krebs cycle, AKG also acts as a "molecular thermostat,” capable of sensing the energy level inside cells. When our body enters a "fasted" or "high-efficiency" state, AKG triggers a cascade of protective and restorative actions, signaling to the cell that it is the time to prioritize repair over growth.
A high level of AKG, either through fasting or supplement, inhibits mTOR. As our body's primary driver for cellular growth, an overactive mTOR sometimes leads to the premature aging. By pumping the brake on mTOR, AKG instructs the cell to prioritize repair and energy-conservation over growth. Subsequently, cells begin to break down and recycle damaged organelles.
Meanwhile, AKG indirectly stimulates AMPK, which in turns tells the body to switch from storing to burning fat. AMPK also increases insulin sensitivity, allowing the body to clear blood sugar more efficiently.
As an essential cofactor, AKG works closely with TET enzymes too. As we age, epigenetic markers begin to accumulate on our DNAs. They are equivalent to the rust on a key. TET enzymes are used by cells to reverse this accumulation. When AKG concentration is high, TET goes to work, remastering the genetic codes and so restoring the cell’s ability to express genes as it did when it was younger.
How Does EKG Come Into Play?
After entering cells, EGT may persist for weeks. Once inside mitochondria, this stability enables EGT to continuously neutralize reactive oxygen species. In parallel, EGT activates the Nrf2 pathway, boosting the endogenous antioxidant production to jack up the cell's internal defense.
While EGT protects mitochondria from the oxidative stress, AKG optimizes energy production and helps clear out cellular debris. Working in concert, EGT and AKG prevent the mitochondrial decay that is characteristic for aging.
Which Organs May Benefit The Most?
Although this combo provides protection to all living cells, three organs stand to benefit the most. Recall EGT’s ability to cross the blood-brain barrier and accumulate in hippocampus. With AKG’s ability to restore long-term potentiation: the electrical signal for memory, those two add a potent defense against brain fog and dementia.
While EGT protects muscle fibers from the oxidative stress during intense physical activity, AKG instructs muscle cells to clean up damaged parts, preventing the accumulation of protein breakdown commonly seen in aging.
Lastly, EGT dampens chronic "inflammaging” by working through OCTN1 transporter, which is highly expressed in immune cells. At the same time, AKG feeds into the Kreb Cycle, releasing the energy needed for a robust immune response.
Why Do American Adults Need It?
Due to industrial farming practice, American foods in general offer too little of EGT to protect against modern environmental toxins. At the same time, when the AKG level plummets naturally as we age, we are more likely to find ourselves stuck in sedentary desk jobs. In this case, additional AKG may help "jumpstart" the metabolism even when we deal with the metabolic inflexibility and weight gain.