I continued reading on the subject of the polyamines, spermidine and spermine, after posting a summary of what I first read, and found a series of papers from one of the more senior, experienced -- and therefore more knowledgeable -- research groups working in the field. Some of what they have found out about the role of these compounds in mammalian cellular biochemical function and effects differs very importantly from what has been published by newer (and more wild-eyed and aspiring) entrants into this area of medical research – those writers I had been earlier reading.
Fronted by Kuniyasu Soda (MD/Ph.D.) of Jichi Medical University and Saitama Ken-O Hospital, his group has been studying polyamines for more than 30 years. He and his colleagues were the first to observe, for example, that a diet high in polyamines prevents age-related diseases and extends the life of mice:
Rather than represent that improvements in mammalian health by polyamine supplementation occurred because of an increase in cellular autophagy, the Soda group found instead that (Soda 2023):
The ‘test tube’ in vitro experiments providing evidence that human cellular autophagy increases in the presence of heightened concentrations of polyamines unknowingly erred in the use of fetal bovine serum in the cellular growth medium. This serum contains a copper-based enzyme not present in human cells which catalyzes the breakdown of spermine and spermidine, artificially creating cell-toxic compounds from those polyamines that then kill human cells and thus induce the autophagy more recent researchers became prematurely enthused about. This process does not actually occur in the bodies of real living humans, according to Soda 2023.
Rather than being caused by spermine and spermidine-induced autophagy, improvements in mouse (and human) health and lifespan are caused by the strong antioxidant character of the polyamines, and – more importantly – by the ability of spermine in particular to significantly inhibit the development and progression of age-related diseases through gene methylation.
Another important observation made by the Soda research team is that because the enzymes that create and transform the various members of the polyamine chemical series slow down and become less effective with the increasing age of the organism concerned, variation in the polyamine content of the personal diets of older people automatically introduces some significant and telling individual variation in the concentrations of blood and cellular spermine and spermidine levels as they age.
In connection with that last observation, the Soda research group has demonstrated that in cases of age-related diseases of the brain, cardiovascular system, kidney, and muscles, for example, the whole blood ratios of spermine to spermidine are lower in people afflicted with these diseases -- and become lower with the progress of these diseases.
Furthermore, from Soda 2022:
“The properties of spermidine synthase and spermine synthase have not been fully clarified, however, they seem to lack a regulatory or rate-limiting role in polyamine synthesis. The administration of arginine or ornithine stimulates putrescine levels; however, the subsequent synthesis of polyamines [spermidine and then spermine] is not necessarily [subsequently] stimulated in elderly people or aged animals. These findings indicate that the activities of spermine and spermidine synthases decrease gradually with aging.”
Among other things, this set of observations suggests that dietary putrescine (from fruit primarily) and spermidine (from peas and fresh corn, for example) are much more apt to benefit the health (and fertility) of younger people with intact polyamine synthase enzyme systems than they are older people with weak polyamine synthase enzyme systems. In older people, the polyamines putrescine and spermidine obtained from food are far less likely to be transformed into the health- and longevity-promoting spermine.
An obvious work-around for older people seeking to avoid or improve chronic diseases that often develop with the passage of time would appear to be to focus dietary polyamine supplementation using foods especially rich in spermine, spermine that would not need to be first biochemically transformed within the body’s cells in order to become of cellular use and benefit. The following series of graphs from Munoz-Esparza et al., 2021, identify the human foods with higher concentrations of spermine. Wheat germ with its ~9 mg spermine/100 g wheat germ is king, but most meats are generally very significant sources of spermine, too.
Note while decoding the graphs that scaling on each graph is different.
