Although it is made from wheat germ and contains a minuscule amount of wheat, thus requiring a warning to celiacs, polyamines are very unique and in fact may be emerging as useful to treat celiac complications!
The Science Translated
As a polyamine, spermidine has unique properties that make it less inflammatory and in many cases actually protective to those with Celiac’s Disease or gluten sensitivities. Though there are a small percentage of people who have difficulties tolerating spermidine supplementation, the vast majority (even those with Celiac’s or gluten intolerance) experience no negative side effects of taking supplemental spermidine from wheat germ extract.
The primary reason for this is that spermidine works to inhibit a key enzyme responsible for the inflammatory response some people have to gluten. It does this by competing with other substrates to make the active enzyme unavailable to react with gliadin (aka a key component of gluten). Because spermidine does not convert the same way as the gliadin, it does not lead to the same immune response typically incited when consuming gluten. As a result of not going through the transamination that provokes the typical immune response in Celiac’s, it may well actually be protective for those with Celiac’s or gluten sensitivities.
Excerpted from: Yoosuf S, Makharia GK. Evolving Therapy for Celiac Disease. Front Pediatr. 2019;7:193. Published 2019 May 14. doi:10.3389/fped.2019.00193 [R]
Inhibitors of human tissue transglutaminase 2 (tTG-2) have been designed to prevent the conversion of gliadin to deamidated gliadin peptides, which are what possess the enhanced immunogenicity as antigens in Celiac disease and cause the problems associated with gluten intake. tTG-2 is a multi-functional enzyme that catalyzes the linkage of glutamine and lysine side-chains to modify proteins. The enzyme is known to be associated with pathogenesis of not only Celiac, but also some cancers and Parkinson's, Alzheimer's, and Huntington's diseases (this is why celiac is associated with other diseases as well!). Therefore, tTG-2 inhibitors are being tested in many of the aforementioned conditions.
Three broad varieties of tTG-2 inhibitors have been well-described so far, namely competitive amine inhibitors, reversible inhibitors, and irreversible inhibitors. Competitive inhibitors compete with other natural amine substrates for tTG-2, thereby making the active enzyme unavailable for transamidating gliadin. These include putrescine, cystamine, spermidine, histamine, and cadaverine.