It’s not the most appealing name for a supplement, but the longevity world is buzzing with excitement about it.
The protein, found in the body and some foods, has shown promising results in trials with yeast, worms and mice, suggesting it may protect the heart, mind and even increase life expectancy.
Evidence from human trials is still in its early stages, but some devotees claim it may have wide-ranging benefits, from aiding fertility to improving sleep, boosting gut health, making skin more supple and improving energy levels.
So what exactly is spermidine and why, if it really is the elixir of youth, have so few of us heard of it?
Spermidine was first discovered in human semen (hence the name), but it is actually found in cells throughout the body, equally in men and women.
Spermidine helps stem cells maintain their ability to divide and create new cells.
Its function is to reduce inflammation and stimulate a process called autophagy (we will talk more about this later).
Two-thirds of the spermidine we need to function properly is produced in our body (mainly in the intestine). The rest comes from the food we eat.
But as we age, our bodies don’t produce as much spermidine, so some scientists argue that increasing our levels could help delay the onset of aging and the health problems that come with it.
Central to that claim is the vital role spermidine plays in autophagy, a form of bodily maintenance where dead or diseased cells are broken down and parts are reused as fuel or to create new, healthy cells.
“Without autophagy, cells would not be able to develop or function properly,” says Katja Simon, a professor of immunology who leads a team studying autophagy at the Max Delbrück Center in Berlin. “They would age faster without it.”
Autophagy is especially important within mitochondria, the energy source of the cell.
As cells age, their mitochondria lose the ability to provide them with energy and begin to self-destruct; the result is a drop in our energy levels.
Spermidine combats this by triggering autophagy within the mitochondria, prompting them to undergo internal remodeling and function optimally again.
It also helps stem cells maintain their ability to divide and create new cells, a key factor in many of spermidine’s health claims.
While most of the research to date has been done in animal studies, Dr. Ghada Alsaleh, a researcher in immunology and autophagy at the University of Oxford, has been conducting experiments using a spermidine supplement on human cells taken from hip replacement patients.
Jane Alexander says it’s not the sexiest name for a supplement, but the longevity world is buzzing with excitement about spermidine.
The results (not yet published) demonstrate that the supplement induces autophagy in human tissue.
The discovery may be the first step toward effective therapy for osteoarthritis, where the cartilage that cushions the joint becomes inflamed and damaged, resulting in pain and immobility.
The idea here is that spermidine might help cartilage repair and renew itself.
Spermidine supplements are now easier to find in stores and online, following studies suggesting they can lead to a longer, fitter life (albeit largely through diet rather than supplements).
For example, people who ate higher amounts of spermidine-rich foods (such as whole-grain wheat germ, vegetables (particularly shitake mushrooms, green peppers, and broccoli), and aged cheese) were found to have a lower risk of premature death or heart disease and a longer lifespan, according to a 2018 study that followed 829 adults ages 45 to 84 for 20 years, published in The American Journal of Clinical Nutrition.
Dr Olivia Lesslar, an Australian physician specialising in longevity, preventative health and psychoneuroimmunology (how the brain and immune system connect), says: ‘I prescribe spermidine to patients with diseases known to be due, in part, to autophagic dysfunction.
“This includes, for example, kidney disease, inflammatory bowel disease, non-alcoholic fatty liver disease, diabetes, some types of cancer and neurodegenerative diseases,” he says.
‘People who suffer from fatigue report having more energy. Many also report having thicker hair and stronger nails; they have even lost their grey hair.
‘I had a 41-year-old patient who felt that it was one of the main factors that helped her get pregnant after several years of trying.’
Spermidine has been found to promote fertility in older female mice, according to a 2023 study published in the journal Nature Ageing.
“I think spermidine has some interesting long-term health benefits,” adds Dr Tamsin Lewis, a psychiatrist and neuroscientist who runs a private longevity clinic in London.
“It won’t work on its own, but as part of an overall health strategy that includes diet, exercise, meditation and connection, I can see a benefit from a supplement when taken daily.”
Dietary sources and supplements are not the only way to increase spermidine levels.
A study published in the journal Nature Cell Biology this month showed that calorie restriction and intermittent fasting also increased spermidine levels in humans.
Spermidine is not the only compound that can trigger autophagy, other supplements can do so as well, including resveratrol, quercetin, and alpha lipoic acid.
The difference is that these other compounds tend to rely on a single pathway, whereas spermidine is considered superior because it induces autophagy through a variety of mechanisms (blocking the action of a gene and enhancing other pathways involved in the initiation and maintenance of autophagy, for example).
Other life-extending compounds have also been investigated.
For example, a drug called rapamycin, originally used in organ transplant patients to prevent their bodies from rejecting the new organ, mimics the beneficial effects of fasting, and trials have shown it significantly extends the lifespan of mice.
However, in high doses, rapamycin suppresses the immune system and can have side effects such as headaches, dizziness, chest pain, muscle aches, diarrhea, fever, and mouth sores. It is not approved for human use as a longevity drug.
Meanwhile, the U.S. Food and Drug Administration “generally recognizes that spermidine is safe” for human consumption. Oxford Healthspan (which makes the spermidine supplement, Primeadine) says the European Food Safety Agency has declared doses of up to 6 mg per day to be safe for humans.
“It could be that spermidine is an alternative to rapamycin,” says Professor David Weinkove, president of the British Society for Ageing Research.
A study published in Cells (2021) showed that both rapamycin and spermidine affect autophagy in a similar way.
However, Professor Weinkove points out that most of the clinical research supporting spermidine has not yet been conducted in humans.
‘Studies suggest that spermidine may slow, but not reverse, aging, and it is not known whether it works in humans.’
He cites a 2022 study, published in the journal Neurology, by researchers in Germany and Austria who gave 100 people daily supplements of spermidine or a placebo for a year and found there were no improvements in terms of brain performance and memory.
Dr Mohammed Enayat, a GP and founder of HUM2N, a private longevity clinic in London, is also cautious: “Spermidine appears to have been shown to be beneficial in mouse studies by supporting important processes involved in ageing, including cell renewal.”
But there is little evidence that this translates to humans, he says.
More important, he adds, are mobility, strength and “a Mediterranean diet based predominantly on whole, plant-based foods, plus an active, stress-free lifestyle.”
Dr Clare Nieland, a GP at HOOKE, an optimal health clinic in London, agrees that it is important to lay the foundations for good health first, but adds: “Taking spermidine won’t do you any harm.”
And supplements aren’t cheap: Primeadine (£75 for a one month supply, en.oxfordhealthspan.com); Advanced Spermidine (£34 for a two-month supply, vitality-pro.com); Liposomal spermidine ($39.99 for a one-month supply, youthandearth.com).
It is worth noting that most spermidine supplements contain wheat germ, which is not suitable for those with celiac disease or wheat allergies.
Always consult your doctor before making major changes to your diet or starting a new supplement, especially if you have underlying health conditions or take medications regularly.