It’s hardly the most appealing name for a supplement, but the longevity world is full of excitement for it.
The protein, found in the body and in some foods, has shown promising results in trials on yeast, worms and mice, suggesting it can protect the heart, mind and even increase lifespan.
Evidence from human trials is still in its early stages, yet some devotees claim it can have wide-ranging benefits from aiding fertility to improving sleep, boosting gut health, making skin more supple and enhancing 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 is actually found in cells throughout the body and equally in men and women.
Spermidine helps stem cells maintain their ability to divide and create new cells
Its role lies in reducing inflammation and stimulating a process called autophagy (more on that later).
Two-thirds of the spermidine we need to function properly is produced by our bodies (predominantly in the gut). The remainder comes from the food we eat.
But as we age, our bodies don’t produce as much spermidine, which is why some scientists argue that boosting our levels could help delay the onset of ageing and the ill-health that comes with it.
Central to that claim is the vital role spermidine plays in autophagy, a form of bodily housekeeping where dead or diseased cells are broken down, with the parts either reused as fuel or to create new healthy cells.
‘Without autophagy, cells could not develop or function properly,’ says Katja Simon, a professor of immunology heading a team studying autophagy at the Max Delbrück Centre in Berlin. ‘They would age faster without it.’
Autophagy is especially important within the mitochondria, the energy powerhouse of the cell.
As cells age, their mitochondria lose the ability to provide cells with energy and start self-destructing – the result being a drop in our energy levels.
Spermidine combats this by triggering autophagy within the mitochondria, which prompts them to undergo an internal refit and work optimally again.
It also helps stem cells maintain their ability to divide and create new cells – a key factor of many of the health claims for spermidine.
While most of the research to date has involved animal studies, Dr Ghada Alsaleh, a researcher in immunology and autophagy at Oxford University, has been conducting experiments using a spermidine supplement on human cells taken from hip replacement patients.
Jane Alexander says it’s hardly the most appealing name for a supplement, but the longevity world is full of excitement over spermidine
The results (as yet unpublished) demonstrate that the supplement induces autophagy in human tissue.
The finding may be the first step towards an effective therapy for osteoarthritis – where the cushioning cartilage around a joint becomes inflamed and damaged, leading to pain and immobility.
The idea here is that the spermidine could help the cartilage repair and renew.
Already spermidine supplements are becoming easier to find on the high street and online, following studies suggesting it may lead to a fitter, longer life (although largely through diet rather than supplements).
For example, people who ate higher amounts of spermidine-rich foods – such as wholemeal wheatgerm, vegetables (in particular 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 which tracked 829 adults aged 45-84 for 20 years, reported in The American Journal of Clinical Nutrition.
Dr Olivia Lesslar, an Australian longevity doctor who specialises in preventative health and psychoneuroimmunology (how the brain and immune system connect), says: ‘I prescribe spermidine to patients with diseases known to be, in part, due to autophagic dysfunction.
‘This includes, for example, kidney disease, inflammatory bowel disease, non-alcoholic fatty liver disease, diabetes, some cancers and neurodegenerative diseases,’ she says.
‘Those with fatigue report they have more energy. Many also report thicker hair and stronger nails; even reversal of grey hair.
‘I had one 41-year-old patient who felt it was one of the main factors in helping her get pregnant after a few years of trying.’
Spermidine has been found to promote fertility in older female mice, according to a 2023 study, in the journal Nature Ageing.
‘I think spermidine has some interesting long-term benefits to health,’ 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 of a supplement when taken on a daily basis.’
Dietary sources and supplements aren’t the only way to increase spermidine levels.
A study in the journal Nature Cell Biology this month showed that calorie restriction and intermittent fasting also increased levels of spermidine in humans.
Spermidine is not the only compound that can trigger autophagy, so too can some other supplements including resveratrol, quercetin and alpha-lipoic acid.
The difference is that these other compounds tend to rely on one single pathway, whereas spermidine is considered superior as it induces autophagy through a variety of mechanisms (by blocking the action of a gene and enhancing other pathways involved in initiating and maintaining autophagy, for instance.)
Other life-extending compounds have also been investigated.
For example, a drug called rapamycin, originally used for organ transplant patients to stop their bodies 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 it can have side-effects such as headaches, dizziness, chest pain, muscle aches, diarrhoea, fever and mouth sores. It isn’t approved for human use as a longevity drug.
Spermidine meanwhile is ‘generally recognised as safe’ for human consumption by the Food and Drink Administration in the US. Oxford Healthspan (which produces the spermidine supplement, Primeadine) says the European Food Safety Agency has stated doses of up to 6mg a day are safe in humans.
‘It might be that spermidine is an alternative to rapamycin,’ says Professor David Weinkove, chair of the British Society for Research on Ageing.
A study published in Cells (2021) showed that both rapamycin and spermidine affect autophagy in similar ways.
However, Professor Weinkove points out that the majority of clinical research supporting spermidine has not yet been conducted on humans.
‘Studies suggest that spermidine can slow, but not reverse, ageing – and it is not known if it works in humans.’
He cites a 2022 study, reported in the journal Neurology, by researchers in Germany and Austria which gave 100 people daily spermidine supplements or a placebo for a year and found there was no improvement in terms of brain performance and memory.
Dr Mohammed Enayat, a GP and founder of HUM2N, a private London longevity clinic, is also cautious: ‘Spermidine seems to have shown benefit in mice studies through supporting important processes involved in ageing, including cell renewal.’
But there’s little evidence this translates into humans, he says.
More important, he adds, are mobility, strength and ‘a whole-food, predominantly plant-based Mediterranean-style diet – plus an active, stress-free lifestyle.
Dr Clare Nieland, a GP based at HOOKE, an optimal health clinic in London, agrees it’s important to get the foundations of good health right first but adds: ‘Taking spermidine won’t do you any harm.’
And supplements are not cheap: Primeadine (£75 for a month’s supply, oxfordhealthspan.com); Advanced Spermidine (£34 for two month’s supply, vitality-pro.com); Liposomal Spermidine (39.99 for a month’s supply, youthandearth.com).
It’s worth noting that most spermidine supplements contain wheatgerm, which is not suitable for those with coeliac disease or wheat allergies.
Always consult your doctor before making major diet changes or starting a new supplement, especially if you have underlying health problems or take regular medication.
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