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

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

With a new diagnosis of Alzheimer’s disease occurring every 65 seconds, it’s no wonder that this neurodegenerative disease tops the list of health conditions that our society fears the most with age. Opposed to the still-devastating diseases that affect the body, like having a heart attack or developing cancer, neurodegenerative diseases of the mind involve losing a part of who we are as a human — our memories, our thoughts, our personalities. Because of these tragic symptoms, patients, caregivers, doctors, and researchers alike are constantly searching for innovative therapies to prevent or reverse the memory loss and personality changes that are characteristic of cognitive decline.  

One such novel treatment 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 cognition 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 preventing or reversing age-related cognitive decline. 

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 chronic and neurodegenerative diseases 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 disease development and aging, 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 extends lifespan and improves 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. 

spermidine enhances autophagy in our mitochondria

Mitigating Memory Loss and Mitochondrial Function

As previous research has found that injected spermidine improves 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 treatment also improved their explorative behavior in new environments — a common symptom of cognitive decline is a loss of this behavior, causing the frightening feeling of being lost in or unable to navigate 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 increase 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 enhanced 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 improved memory or mitochondrial and respiratory function, respectively. As spermidine itself is an autophagy-booster, taking this compound supplementally could potentially mitigate the typical age-related decline in autophagy — and, with it, boost brain and mitochondrial health.

Linking a Spermidine-Rich Diet to Bolstered 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 decline during the study period. That being said, we can’t conclude that eating dietary spermidine causes better cognition, just that the correlation between the two is strong. 

Supporting these results, another recent study found that older adults with cognitive decline 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 better cognition in these two studies are encouraging — despite the lesser amount of spermidine in foods compared to supplements, it still appears that eating a spermidine-rich diet may be a simple way to benefit brain health in the long run. As stated by the authors, “The straightforward and inexpensive availability of nutritional spermidine in the human diet may provide a potent strategy to prevent the course of age-related or disease-driven cognitive decline in the general population.”

wheat germ is a rich source of spermidine

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 improves cognition and reduces the risk of neurodegenerative disease. But, the research team is hopeful about spermidine’s benefits translating to humans, concluding, “Collectively, our findings lend strong support to the concept that nutrition rich in spermidine protects against cognitive impairment and decline.” 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. 

Show 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. Dietary spermidine improves cognitive function. 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

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