Longevity supplements have flooded the market, and thanks to growing research, they're in the center of attention. However, as an end-consumer, the fear of the side effects of taking such supplements always looms over your head. As a popular longevity supplement, spermidine, for example, seems an excellent choice to improve health and for healthy aging. Among other benefits, it induces autophagy — a process by which your body degrades or removes old and damaged cells (1). Autophagy is critical for longevity. Unfortunately, its rate decreases as we age (2).
However, just like every product you consume, checking if spermidine has any side effects is also essential. This has your head scratching as everyone on the internet seems to discuss the benefits only and misses this crucial aspect. You may have heard of polyamine toxicity, which could cause brain, liver, and kidney problems. (3). No wonder you feel exhausted and are here now trying to find reliable information.
Let's look at the research to see if spermidine is safe and if it has any side effects.
Is Spermidine Safe To Take?
First things first, is spermidine safe to take? Well, the short answer is yes. At the daily recommended dose of about 5 to 10 mg, spermidine is an extremely safe substance with excellent tolerability and has no known adverse effects to date (4). The reason is that spermidine is naturally produced in the human body and also occurs in the food we eat. Thus, our body not only needs polyamines to maintain health but is also well adapted to these compounds. Furthermore, research also supports these claims.
For example, a 1997 study on lab mice revealed that spermidine showed some adverse outcomes. At doses of about 600mg/kg body weight -- which is extremely high compared to the typical daily dose. However, at this higher intake, spermidine began to show signs of toxicity, such as a decrease in appetite, weight, and blood levels of calcium and potassium in male rats and an increase in plasma activity of aspartate aminotransferase and alanine aminotransferase -- two enzymes used to assess liver function (5).
In addition, a 2018 study evaluated the toxicity of spermine and spermidine found in foods toward the intestinal cells. The researchers found that while both polyamines are nontoxic to the intestine at normal doses found in food, at very high doses (1.5g/kg body weight), they induce death of the intestinal cells (6). However, the researchers say that it is spermine that is more toxic at these levels than spermidine (about 5.5 times more toxic).
Safety study for Spermidine on humans
Besides these lab studies, research on humans is also promising. For example, a 2018 study involving 30 human participants showed that taking spermidine-rich wheat germ extract for three months did not cause any disturbances in weight, electrolytes, blood parameters of safety and blood pressure, or other vital signs (7). Instead, the study showed that spermidine improved cognitive function in elderly participants. The same study was performed on laboratory mice and yielded similar results.
Also, the European Union has already approved spermidine-rich foods like wheat germ extract, which has become very popular with consumers. As time passes and more research continues to support the claims of longevity supplements, spermidine will only increase in popularity. In the meantime, however, one thing is for sure, spermidine is an extremely safe polyamine with excellent tolerability. And as goes with any poison, it is always the dose that is poisonous rather than the compound itself
Spermidine vs Other Polyamines
The actual misconception about spermidine having side effects begins with it being a biogenic amine -- compounds having one or more amine groups and formed as decarboxylation products of amino acids. Early researchers thought that like other biogenic amines such as tyramine, histamine, cadaverine, phenylethylamine, and tryptamine, spermidine and other polyamines would also carry side effects (8). Some of the side effects of these biogenic amines can cause include headache, heart palpitations, vomiting, diarrhea, allergy, and hypertensive crises (9).
As discussed, spermidine is different from other biogenic compounds. It does not induce oxidative stress in the body and, as a result, does not cause health problems. Spermidine has no known side effects up to this date, even at very high doses. Instead, it benefits the body in many different ways, including acting as an anti-inflammatory and inducing autophagy to help extend an individual's lifespan. Thus, spermidine supplements are highly unlikely to cause any side effects.