Ergothioneine (EGT) is the thiol-containing amino acid that is the master antioxidant of the mitochondria — it is synthesised by the fungi and the mycobacteria, it is not synthesised by the humans, and it is accumulated in the human tissues (particularly in the mitochondria-rich tissues such as the liver, the kidney, the bone marrow, and the brain) through a specific transporter (the OCTN1 transporter) that is encoded by the SLC22A4 gene. The ergothioneine is unique among the antioxidants because it is not a simple scavenger of the reactive oxygen species (like the vitamin C or the vitamin E) — it is a highly specialised antioxidant that is specifically localised to the mitochondria, that is constitutively active at low concentrations (because it is always present in the mitochondria at the mM concentrations), and that has a very low redox potential (which makes it one of the most reactive thiol antioxidants and one of the most effective protectors of the mitochondrial DNA, the mitochondrial proteins, and the mitochondrial lipids from the oxidative damage). Without adequate ergothioneine and mitochondrial antioxidant protection, the mitochondrial DNA accumulates the mutations, the mitochondrial proteins are oxidised and lose their function, and the mitochondrial lipids are peroxidised and lose their integrity — producing the mitochondrial dysfunction, the neurodegeneration, and the accelerated ageing that are the hallmark of the ergothioneine deficiency. The typical dietary ergothioneine intake from the mushrooms (particularly the porcini, the shiitake, and the oyster mushrooms), the black beans, and the oat bran is 1-5mg daily — which is sufficient to maintain the normal ergothioneine levels in most tissues, but which may be insufficient for the optimal mitochondrial protection in people with the high oxidative stress (smokers, people with the chronic inflammatory conditions, people with the neurodegenerative diseases).
Ergothioneine and the Mitochondrial Protection
The ergothioneine protects the mitochondria from the oxidative damage through multiple mechanisms — it directly scavenges the hydroxyl radical, the peroxynitrite, and the hypochlorous acid (the reactive species that are generated by the mitochondrial electron transport chain and by the activated neutrophils), it chelates the transition metals (iron, copper) and thereby prevents the Fenton reaction and the metal-catalysed ROS generation in the mitochondria, it preserves the reduced glutathione levels in the mitochondria (by recycling the oxidised glutathione and by preventing the oxidation of the glutathione), and it regulates the expression of the antioxidant genes through the Nrf2 pathway (by activating the Nrf2 and by promoting the expression of the phase 2 detoxification enzymes). This multi-target antioxidant mechanism of the ergothioneine makes it one of the most comprehensive and most effective mitochondrial antioxidants available — and it explains why the ergothioneine has been shown to protect against the neurodegeneration, the cardiotoxicity, and the nephrotoxicity in multiple animal models of oxidative stress.
The clinical importance of the ergothioneine for the mitochondrial health is underscored by the observation that the ergothioneine levels decline with age and with the neurodegenerative diseases. A study in 100 individuals found that the ergothioneine levels in the blood decline with age (by approximately 30-40% between the ages of 30 and 70), and that the low ergothioneine levels are associated with the increased risk of the Alzheimer’s disease, the Parkinson’s disease, and the cardiovascular disease. Another study found that the ergothioneine supplementation protects the neurons from the oxidative stress and reduces the beta-amyloid toxicity in the in vitro models of the Alzheimer’s disease — suggesting that the ergothioneine may be a useful neuroprotective agent for the prevention and the treatment of the neurodegenerative diseases.
Practical Application
For general ergothioneine supplementation for the mitochondrial and antioxidant support, the evidence-based approach is to supplement with 5-30mg of ergothioneine daily (as the standardised extract from the mushrooms or as the pure ergothioneine, which is available as the L-ergothioneine). The ergothioneine should be taken in the morning with the breakfast (to align with the circadian pattern of the oxidative stress, which peaks in the morning and is associated with the increased mitochondrial activity). The ergothioneine is generally well-tolerated with no significant adverse effects at doses up to 100mg daily, and it does not have any known drug interactions or contraindications. For comprehensive mitochondrial and neuroprotective support, ergothioneine pairs well with the CoQ10 (which is the electron carrier in the electron transport chain and which works synergistically with the ergothioneine for the mitochondrial antioxidant defence), with the alpha-lipoic acid (which is another mitochondrial antioxidant that works through a complementary mechanism), with the NAC (which is a precursor of the glutathione and which supports the mitochondrial antioxidant defence), and with the selenium (which is required for the activity of the glutathione peroxidase and which works synergistically with the ergothioneine for the antioxidant defence).
Leave a Reply