Oxis International president Bernie Landes was speaking to NutraIngredients-USA.com after the First International Congress on Ergothioneine at the University of California in LA last week.
He said: “L-ergothioneine was discovered in 1909. It’s produced by microbes in the soil and makes it way into mushrooms, grapes, meats and dairy products.
"But it was close to 100 years before anyone figured out how to synthesize it in an economic price, so it pretty much sat as a curiosity.”
‘It pretty much sat as a curiosity’ for a century
“What’s really exciting about it is that it is the only substance I’m aware of that has a gene and transport system that is specific to it [the SLC22A4 gene codes for the carrier protein OCTN1 that enables ergothioneine to be transported into cells].
“This gene lights up and expresses for this protein when inflammation happens. I think in future more and more attention will be paid to inflammation and less to antioxidants which are transient in the body. Ergothioneine is unusual because it has a very long half life in the body – around 30 days – whereas many antioxidants hang around for more like 30 seconds or 30 minutes.
“Ergothioneine has unparalleled potential benefits for cognitive function, eye health, immune modulation, lung health, reproductive health and skin health, but it cannot be made by the human body.”
Very stable to heat and acidity
He added: “We’re not planning to supply it as an ingredient; our approach is to utilize it in concert with other synergistic and compatible nutrients to create supplements and functional foods to sell directly to consumers.
“We introduced our first Ergo-based product in December - ErgoFlex, a joint-health formula – and will be introducing more Ergo-based products in the coming months.
“In foods, it is very stable to heat and acidity, it doesn’t have to be encapsulated; it is tasteless and soluble.’
He added: “We have patented the synthesis process for producing it but we outsourced manufacturing to a company [Gemini Pharmaceuticals] that is also an investor in our business that can make commercial quantities.
“It’s been in the food supply for a long time and we are a long way along in the GRAS (generally recognized as safe) self-affirmation process [The dossier is being reviewed by an expert panel coordinated by AIBMR Life Sciences].
"We would not have to submit an NDI (new dietary ingredient) notification to use it in dietary supplements as the GRAS status would suffice, but we may choose to do so.”
Oxis has conducted three toxicological studies to establish the safety of l-ergothioneineand concluded that a dosage of around 1.5mg a day was ideal, said Landes. ErgoFlex had 250 micrograms per capsule.
He added: “The only human clinical study I am aware of is on our joint health formula [used in ErgoFlex] which combines l-ergothioneine with vitamin C, glucosamine, curcumin hyaluronic acid and other ingredients. This showed a rather significant and fast response to inflammation.
“But research done by Robert Beelman and others at Penn State University showed that when humans were fed mushroom powder with known amounts of ergothioneine, it showed up in the blood very quickly.
“We’ve formed a research consortium at Oxis and we’ll supply researchers looking at a variety of areas with ERGO. The brain, eyes and the lungs will all be looked at.
“I’ve been in this industry for 35 years and I see it as unique. If you compare it to resveratrol, the difference is that resveratrol is abundantly available. Ergo is not.”
Dr John Repine from the University of Colorado (and a member of Oxis’ advisory board) was recently awarded a $1.34m grant from the US Department of Defense to help fund research into the benefits of l-ergothioneine for tackling lung diseases that could be fatal in combat veterans, he added.
Bruce Ames: Specificity is the key
Bruce Ames, senior scientist at the Children's Hospital Oakland Research Institute and a presenter at the Congress, told NutraIngredients-USA: “As to how useful ergo is for people, the papers in the literature don't quite make the case yet, but that might be sorted out soon.
“Ergo is a very weak antioxidant compared to the other thiol compounds in the cell, which isn't necessarily a bad thing: specificity is the key. Snyder (Cell death & Diff 2009) suggests ergo may turn out to be a vitamin, as have others, as humans transport it into blood, where it is at high concentration, by a very specific transporter (Grundemann et al. PNAS 102, 5256, 2005).
“When a paper is published showing the biochemical mechanism of ergo action, and how that relates to disease, I think the case will be much stronger. Dr. Jung Suh, in my lab, has been working on that problem since the Grundemann paper and plans to publish soon.”
Jeffrey Blumberg, director at the antioxidants research laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging, said he was not an expert on ergothioneine.However, he suspected health claims about it at this stage were “more speculative than substantiated”.
Suite of benefits
According to Oxis, some of the potential benefits of ERGO include its ability to:
- Conserve and maintain the levels of other antioxidants such as vitamins E and C and glutathione;
- Increase respiration and the oxidation of fat;
- Protect mitochondria from damage;
- Reduce the damaging effects of environmental UV rays;
- Tackle oxidative stress by mopping up harmful free radicals;
- Protect against the effects of neurotoxins believed to have a role in cognitive decline.
Production and patents
Oxis is the only firm currently producing commercial quantities of l- ergothioneine. However, Jean-Claude Yadan, president of biotech firm Tetrahedron, told NutraIngredients-USA.com he had developed a three-step, more economical method of synthesis.
“Tetrahedron has designed and developed a proprietary 3-steps synthesis of ergothioneine. Tetrahedron's process is now scaling up. At this time Tetrahedron can produce 2-10kg batches and is working on 50kg batches. Our process is significantly more economic than the Oxis one.”