Everything is poison, nothing is poison: it’s the dose that makes the poison! A team of scientists from the University of Freiburg has described the mechanisms that lead our cells to naturally produce hydrogen cyanide. This gas, toxic in excessive doses, plays a major role in the proper functioning of our bodies. The therapeutic implications of this discovery are considerable.
Considered toxic, hydrogen cyanide is not only a gas produced endogenously and naturally by mammalian cells, but also plays a fundamental role in their proper functioning. Such a compelling statement would simply not have been possible without the work of Professor Csaba Szabo and his international team. In an article published on March 3, 2025 in the journal Nature Metabolism, the scientists reveal, for the first time, the mechanisms behind the production of this gas and the consequences for health when it becomes too abundant or, on the contrary, becomes scarce.
A lick of cyanide
Using experiments on human cells and living mice, Csaba Szabo and his colleagues were able to observe that hydrogen cyanide was systematically present in the body. We were able to demonstrate that this gas is produced naturally, without external intervention or contamination", explains Csaba Szabo. This phenomenon, already known in plants and bacteria, had not yet been demonstrated in mammals.
Like any self-respecting pharmacologist, Csaba Szabo then set out to determine what elements were responsible for producing this hydrogen cyanide.
By adding glycine to cell cultures, he and his colleagues observed an increase in hydrogen cyanide production: ’We have thus demonstrated that glycine, an amino acid present in our body, stimulates hydrogen cyanide production in certain cells, such as those of the liver.’
The importance of accurate measurement
For the research team, it remained to understand how the body goes about regulating this production in order to avoid a toxic build-up. With this in mind, they turned their attention to rhodanese, an enzyme well known for its role in hydrogen cyanide detoxification.
As with glycine, several in vitro and in vivo experimental approaches have enabled us to demonstrate that rhodanese is a kind of demining agent capable of defusing hydrogen cyanide", says the Fribourg pharmacologist. This enzyme transforms it into a non-toxic form (thiocyanate), protecting cells from potential poisoning.
Therapeutic implications
Csaba Szabo is convinced that the discovery and understanding of these mechanisms of hydrogen cyanide production and regulation can have important medical implications. Here are two examples to illustrate the point:
In laboratory experiments, the research team observed that cells survive oxygen deprivation (hypoxia) better when a small amount of hydrogen cyanide is present. For Csaba Szabo, this discovery could contribute to better treatment of stroke victims: ’During a stroke, brain cells suffer precisely from a lack of oxygen. Since we now know that hydrogen cyanide protects the cells, it’s not hard to imagine that it could help limit the damage caused by a stroke.
The research team also discovered that certain diseases, such as non-ketotic hyperglycemia (NKH), cause the body to excessively produce hydrogen cyanide. The accumulation of this gas, in such cases, poisons cells and disrupts their metabolism, with deleterious effects on health that can go as far as serious neurological disorders. Understanding the role of glycine and rhodanese could lead to therapeutic interventions.
Major discoveries
In a nod to Paracelsus, the famous Swiss physician, a group of pharmacologists based in Fribourg confirm that everything is poison, nothing is poison: it’s always a question of quantity. This five-century-old rule also applies to cyanide, whose toxicity is well known!
Already the author of numerous scientific publications and regularly among the world’s most cited researchers, Csaba Szabo nevertheless considers this publication to be a real milestone in his career: ’I’m convinced that this is one of the greatest discoveries I’ve ever made, and that it will fundamentally change the way we think about cell biology and metabolism’.
Szabo, C. (2025) et al. Regulation of mammalian cellular metabolism by endogenous cyanide production. Nature Metabolism. https://doi.org/10.1038/s42255-025-01225-w
