Thursday, May 20, 2021

Consume stinky stuff to improve cognition

In the second edition of Beating the Dementia Monster, we were cool to the role of dietary supplements in improving cognition in Alzheimer's disease.  However, we noted that some interesting research was in progress on something called spermidine.  Spermidine is a chemical found in the ribosomes of living tissue that contributes to a variety of metabolic functions.  

Ribosomes are an example of a type of structure in the cell called organelles in which proteins are constructed.  Organelles are to the cell what organs are to the body.  Messenger RNA brings design information from DNA to the ribosome, where a polypeptide chains of amino acids is assembled to be shaped into a functional protein.  

Spermidine contributes to maintaining the correct electric charge on membranes, and helps control the pH and volume of fluids between cells.  It does this by synchronizing an array of biological processes.  (Or that's what the Wikipedia says.) 

Spermidine is considered to be an agent of longevity in mammals, because it can, among other things, reduce inflammation and discourage oxidation.  And, of course, inflammation and oxidation play major roles in Alzheimer's disease.

So where do you find spermidine?  Well, it was first isolated in semen, but it can also be found in rotting flesh ... as well as other stuff that's gone bad, such as fermented beans.  But a properly constructed Mediterranean diet will have plenty of spermidine.  Aged cheddar cheese, broccoli, and wheat germ are recognized sources of spermidine.

The question is, can taking spermidine as a supplement improve cognition, perhaps by battling the Alzheimer's disease process?  Maybe, but we don't know yet.

Over the past several years research with fruit flies and mice have suggested that it can, although not strongly.  But what about in people?

An Austrian study, called the Bruneck Prospective Study, evaluated the lifestyles and eating habits of 829 subjects in five-year increments from 1995 through 2010, with followup in 2015.  The study explicitly inferred the amount of spermidine in people's diets and compared that to mortality.  While not a direct objective of the study, the researchers tested cognition of participants at each milestone.

The first finding was that people with spermidine in their diets statistically lived longer, although its not clear that all confounding factors were controlled.  The study also produced a rich database with which the influence of spermidine on cognition could be assessed.  Those who evaluated the data concluded that those with higher spermidine content in their diets were less likely to become cognitively impaired in succeeding years.  

Another study correlated spermidine dietary intake with changes in hippocampus volume and thickness of the cortex.  The study relied on the Mediterranean diet as a source of spermidine.  Since the MIND diet is derived from the Mediterranean diet, it's likely that results would be similar with the MIND diet.  Perhaps the results of the MIND Diet Trial in June will support this correlation.

But what about spermidine supplements?  There are certainly a lot of them on the market.  At this point, there is interest in the prospect that spermidine supplementation will have the same effect as consuming a diet high in spermidine, but there are no completed studies with sufficient credibility to support the idea.  However, there is one study that had promising results with a small cohort of test subjects, and it formed the basis for a larger study.  That study, called the SmartAge study, and a phase 2B is now in progress.  

What will if find?  We'll need to wait and see.  The difficulty is that results with animal models found a positive but disappointingly mild influence of spermidine on cognition.  Will humans fare better? 

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