From Our Mitochondria to Our Memory, the Antioxidant Compound Spermidine Supports Cognition and Healthy Aging

Conditions involving a loss of memory or cognition affect millions of Americans, leading patients, doctors, and researchers alike to constantly search for innovative ways to support cognitive function with age.

One option may be the compound spermidine, an antioxidant found in a variety of foods, including wheat germ, soy, aged cheese, mushrooms, and rice bran. Previous research has found that spermidine, when injected in animals, provides beneficial effects on cognition and behavior. However, two things have yet to be confirmed: one, that orally consumed spermidine has the same effects as when injected, and two, that these effects are translatable to humans. 

In a recent study published in Cell Reports, Schroeder and colleagues aim to answer these questions, as they test the effects of supplemental spermidine in animals and add to the evidence that dietary spermidine intake correlates with cognitive support in older adults. With these results that span multiple species, this primarily Austrian-based research team suggests that spermidine may soon be a leader in the space for supporting brain health with age. 

Spermidine Enhances Our Cells’ Crucial Clean-Up Crew

One of spermidine’s well-documented functions is its ability to boost autophagy — our body’s internal recycling program that removes damaged or dysfunctional proteins and cell parts to maintain healthy and functional cells. With advancing age, our autophagic abilities decline progressively. This leads to a buildup of dysfunctional or toxic cells and proteins, increasing the risk of neurodegeneration and other age-related bodily changes. 

While autophagy encompasses recycling any cell part or protein, the term mitophagy refers specifically to clearing out damaged mitochondria — our cells’ energy production centers. As mitochondrial dysfunction plays a critical role in age-related conditions, researchers believe that boosting mitophagy may be a promising target for improving health and longevity. 

Previous research from the same team has found that spermidine’s ability to induce autophagy and mitophagy extended lifespan and improved mitochondrial function and respiration (the conversion of food into energy) in mice. As our body’s spermidine stores tend to decline with age, taking supplements of this compound may be the best way to combat the loss. Despite spermidine’s presence in many common foods, the amount of spermidine found in supplements far exceeds typical dietary intake. 

Supporting Memory and Mitochondrial Function

As previous research has found that injected spermidine supported memory and cognition in animals, Schroeder and colleagues looked at how taking the compound orally impacted mitochondrial function and cognition in mice.

After adding spermidine to the drinking water of aged mice for six months, the research team assessed their cognitive abilities with various tests designed to evaluate memory, behavior, and learning patterns. The spermidine-supplemented mice showed significantly improved scores on these cognitive tests, including fewer age-related memory deficits and better spatial memory, or the ability to recall where objects or places are in relation to one another. Spermidine also improved their explorative behavior in new environments.  

Oral spermidine also boosted the mitochondrial function of the hippocampus — the region of the brain most responsible for memory and learning — indicating that spermidine can support brain cell energy levels. Because spermidine can cross the blood-brain barrier (the highly selective border of cells protecting the brain from toxins or foreign substances), and the 6-month supplementation period led to a steady accumulation of spermidine in the mouse brain, Schroder and colleagues believe that these cognitive and mitochondrial benefits could potentially translate to humans.

Moving on from mice, the research team studied the effects of spermidine on memory and mitochondrial health in fruit flies and looked at whether or not autophagy was necessary for these benefits to occur.

They found that the spermidine-supplemented flies had improved mitochondrial function, elevated ATP (energy) production, and supported memory. Autophagy and mitophagy were found to be essential for these beneficial changes, as flies with deleted autophagy- and mitophagy-regulating genes did not experience better memory or mitochondrial and respiratory function, respectively. As spermidine itself is an autophagy booster, taking this compound supplementally could potentially support autophagy with age — and, with it, brain and mitochondrial health.

Linking a Spermidine-Rich Diet to Brain Health

Lastly, Schoeder and colleagues took their research from flies to humans, looking at dietary spermidine intake and cognitive test scores from a cohort of over 800 older adults. Five years from the baseline measurements, adults who consumed greater amounts of food-based spermidine had higher cognitive test scores and a reduced risk of developing cognitive loss during the study period. That being said, we can’t conclude that eating dietary spermidine leads to better cognition, just that the correlation between the two is strong. 

Supporting these results, another recent study found that older adults with cognitive loss who consumed more dietary spermidine had significantly increased volume of the hippocampus and other brain regions related to learning and memory. The correlations found between spermidine consumption and cognition in these two studies are encouraging. Despite the reduced amount of spermidine in foods compared to supplements, it still appears that eating a spermidine-rich diet may be a simple way to support brain health in the long run. 

A Cup of Wheat Germ Per Day Keeps the Doctor Away?

Although these across-species results are promising, more studies — especially long-term clinical trials with humans — are needed to definitively say whether or not spermidine supplementation supports cognition in older adults.

Until we know for sure, consuming a spermidine-rich diet seems beneficial to bolster your brain health with age. If you’re not too keen on eating cups of wheat germ (we don’t blame you), try adding aged cheddar cheese, potatoes, and mushrooms to your weekly shopping list. 

References: 

Eisenberg T, Abdellatif M, Schroeder S, et al. Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat Med. 2016;22(12):1428-1438. doi:10.1038/nm.4222

Schroeder S, Hofer SJ, Zimmermann A, et al. Cell Rep. 2021;35(2):108985. doi:10.1016/j.celrep.2021.108985

Schwarz C, Horn N, Benson G, et al. Spermidine intake is associated with cortical thickness and hippocampal volume in older adults. Neuroimage. 2020;221:117132. doi:10.1016/j.neuroimage.2020.117132