Tuesday, January 10, 2017

Spermidine in Alzheimer's

About three years I had written a blogpost (1) on spermidine or polyamine rich foods in dementia or Alzheimer’s. Some scientists from the universities of Berlin and Graz (2) were considering that eating polyamine rich foods could help to stop the dementia. This idea is based on a publication of research results by the scientists S. Sigrist (Freie Universität Berlin) and F. Madeo (University of Graz). "The biologists were able to prove that the body's substance, spermidine, triggers a cellular cleansing process, which increases the memory of older brains from fruit flies to youthful levels." I consider a conclusion from fruit fly to man and after that to a possible therapy not only bold or better precarious but also irrational and irresponsible. Sigrist himself, however, said: "Even a slight shift could be a big step for the individual patient as well as for society, but up till then there is still a long way to go." [Translation and italics by myself]

Spermidine belongs to the polyamines as well as putrescine and cadaverine. The names of these substances are already program, since these substances are formed during putrefaction and are also referred to as ptomaine (the German word “Leichengift”, literally corpse’s poison, is much more in use than ptomaine).

Z.Q. Zhou and colleagues (March 2016) looked at fifteen dicaffeoylspermidine derivatives, which were isolated from the fruit of Lycium barbarum (wolfberry) (3). “The short-term memory assay on a transgenic fly Alzheimer's disease (AD) model showed that 1-15 exhibited different levels of anti-AD activity.” The authors concluded beneficial antiaging, neuroprotective, anti-AD, and antioxidant effects of wolfberry. I think that the results don’t support such broad conclusions.

S. Jamwal and colleagues looked at spermidine in rats with Huntington’s disease. (4) The authors concluded: “The neuroprotective effect of spermidine against QA[quinolinic acid]-induced excitotoxic cell death is attributed to its antioxidant, N-methyl-D-aspartate receptor antagonistic, anti-inflammatory properties, and prevention of neurotransmitters alteration in striatum.” 

J. Lou and colleagues publishes a study: “Cellular polyamines promote amyloid-beta (Aβ) peptide fibrillation and modulate the aggregation pathways.” (5) The study shows that the polyamines spermine, spermidine, and their metabolic precursor putrescine “promote aggregation of amyloid-beta (Aβ) peptides into fibrils and modulate the aggregation pathways. NMR measurements showed that the three polyamines share a similar binding mode to monomeric Aβ(1-40) peptide.” The authors cautiously look into the future: “The results reinforce the notion that designing suitable ligands which modulate the aggregation of Aβ peptides toward minimally toxic pathways may be a possible therapeutic strategy for Alzheimer's disease.”

Frank Madeo, Professor at the Institute of Molecular Biosciences at the University of Graz, told us: “Our finding has led to a "boom" in research.” (6) I can’t see this boom. In the interview he mentioned a study on humans; “the first clinical trial, in which we administer a spermidine rich extract from wheat germs to elderly people, is currently ongoing.” “High concentrations of spermidine are for example available in wheat germs, mushrooms, strongly fermented cheese, meat, green salad, and pears.” As wheat germ, fermented good, and lots more have a high content of histamine or are liberators of histamine, one would have to look first into the histamine contents of the propagated foods. There might be limitations as histamine intolerance is diagnosed more often nowadays (up to 8%). One would also have to differentiate between effects of polyamines and histamine as histamine might play a role in the pathogenesis of the senile dementia of Alzheimer’s type (7,8).

If you like wheat seedlings or natto (Japanese product made from fermented soybeans like I do), for example, nothing but an intolerance should keep you from consuming these foods. Just don’t think it’s preventing dementia or Alzheimer’s. Don’t “do” neutriceuticals containing spermidine until it’s proven to be effective.

https://www.ncbi.nlm.nih.gov/pubmed/23677734 (8)


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