MD, PhD, FMedSci, FRSB, FRCP, FRCPEd.

Spermidine is a polyamine which is a natural component of our cells. It has its name from the fact that it was first found in sperm. It can also be found in varying concentrations in different fruits, vegetables, meat and cheese. About one third of the spermidine levels in our body is produced by our own cells, the rest is absorbed through food and certain bacteria found in our digestive tract. A balanced diet can therefore help maintain high levels of spermidine.

There has been a flurry of research into spermidine, not least because epidemiologic evidence supports to the concept that nutrition rich in spermidine is linked to increased survival in humans. Unsurprisingly, many spermidine supplements are now available for sale (at around £50 for one month’s supply). In order to check whether there is any clinical evidence to suggest that they are effective, I ran a quick Medline search for placebo-controlled, double-blind RCTs. I found 4 such studies; here are their abstracts:

1st study

Introduction: Nutritional intervention with the natural polyamine spermidine, an autophagy-enhancing agent, can prevent memory loss in aging model organisms. This is the first human study to evaluate the impact of spermidine supplementation on memory performance in older adults at risk for the development of Alzheimer’s disease.

Methods: Cognitively intact participants with subjective cognitive decline (n = 30, 60-80 years of age) were included in this three-months, randomized, placebo-controlled, double-blind Phase IIa pilot trial with a spermidine-rich plant extract supplement. Effects of intervention were assessed using the behavioral mnemonic similarity task, measured at baseline and post-intervention visits. Data analysis was focused on reporting and interpreting effectiveness based on effect sizes.

Results: Memory performance was moderately enhanced in the spermidine group compared with placebo at the end of intervention [contrast mean = .17, 95% confidence interval (CI): -.01, .35, Cohen’s d = .77, 95% CI: 0, 1.53]. Mnemonic discrimination ability improved in the spermidine-treated group with a medium effect size (mean difference = -.11, 95% CI: -.19, -.03, Cohen’s d = .79, 95% CI: .01, 1.55). A similar effect was not found in the placebo-treated group (mean difference = .07, 95% CI: -.13, .27, Cohen’s d = -.20, 95% CI: -.94, .54).

Discussion: In this pilot trial, nutritional spermidine was associated with a positive impact on memory performance in older adults with subject cognitive decline. The beneficial effect might be mediated by stimulation of neuromodulatory actions in the memory system. A follow-up Phase IIb randomized controlled trial will help validate the therapeutic potential of spermidine supplementation and delineate possible neurophysiological mechanisms of action.

2nd study

Supplementation of spermidine, an autophagy-inducing agent, has been shown to protect against neurodegeneration and cognitive decline in aged animal models. The present translational study aimed to determine safety and tolerability of a wheat germ extract containing enhanced spermidine concentrations. In a preclinical toxicity study, supplementation of spermidine using this extract did not result in morbidities or changes in behavior in BALBc/Rj mice during the 28-days repeated-dose tolerance study. Post mortem examination of the mice organs showed no increase in tumorigenic and fibrotic events. In the human cohort (participants with subjective cognitive decline, n=30, 60 to 80 years of age), a 3-month randomized, placebo-controlled, double-blind Phase II trial was conducted with supplementation of the spermidine-rich plant extract (dosage: 1.2 mg/day). No differences were observed between spermidine and placebo-treated groups in vital signs, weight, clinical chemistry and hematological parameters of safety, as well as in self-reported health status at the end of intervention. Compliance rates above 85% indicated excellent tolerability. The data demonstrate that spermidine supplementation using a spermidine-rich plant extract is safe and well-tolerated in mice and older adults. These findings allow for longer-term intervention studies in humans to investigate the impact of spermidine treatment on cognition and brain integrity.

3rd study

Recently, it was demonstrated that spermidine-induced autophagy reduces the risk of cardiovascular disease in mice. Intestinal bacteria are a major source of polyamines, including spermidine. We previously reported that the intake of both Bifidobacterium animalis subsp. lactis (Bifal) and arginine (Arg) increases the production of putrescine, a spermidine precursor, in the gut. Here, we investigated the effects of Bifal and Arg consumption on endothelial function in healthy subjects. Healthy individuals with body mass index (BMI) near the maximum value in the “healthy” range (BMI: 25) (n = 44) were provided normal yogurt containing Bifal and Arg (Bifal + Arg YG) or placebo (normal yogurt) for 12 weeks in this randomized, double-blinded, placebo-controlled, parallel-group comparative study. The reactive hyperemia index (RHI), the primary outcome, was measured using endo-peripheral arterial tone (EndoPAT). The change in RHI from week 0 to 12 in the Bifal + Arg YG group was significantly higher than that in the placebo group, indicating that Bifal + Arg YG intake improved endothelial function. At week 12, the concentrations of fecal putrescine and serum putrescine and spermidine in the Bifal + Arg YG group were significantly higher than those in the placebo group. This study suggests that consuming Bifal + Arg YG prevents or reduces the risk of atherosclerosis.

4th study

Background: Spermidine has been shown both in vitro and in mice models to have an anagen-prolonging effect on hair follicles (HFs).

Objectives: To evaluate the effects of a spermidine-based nutritional supplement on the anagen phase of HFs in healthy human subjects in a randomized, double-blind, placebo-controlled trial.

Methods: One hundred healthy males and females were randomized to receive a tablet containing a spermidine-based nutritional supplement or a placebo once daily for 90 days. At the beginning and the end of the treatment period, 100 HFs were plucked and subjected to microscopic evaluation to determine the number of anagen V-VI HFs, and immunohistochemical examination was performed to quantify the Ki-67 and c-Kit levels in the hair bulbs. Pull test was performed after three and six months.

Results: The spermidine-based nutritional supplement increased the number of anagen V-VI HFs after three months of treatment, accompanied by increased Ki-67, a marker for cellular proliferation, and decreased c-Kit, a marker for apoptosis, levels. All results were also significantly better when compared to the placebo group. The pull test remained negative after six months in all patients receiving the spermidine supplement, while 68% of the subjects in the placebo group had a positive pull test.

Conclusions: This preliminary study shows that a spermidine-based nutritional supplement can prolong the anagen phase in humans, and therefore might be beneficial for hair loss conditions. Further studies are needed to evaluate its effects in specific different clinical settings.

_____________________

Convinced?

I could certainly do with a few more hair on my head.

And living longer with less cognitive decline would also be not a bad prospect.

Do I therefore rush to the next health food shop to buy a spermidine supplement?

No.

Yes, the evidence – particularly the pre-clinical one – is fascinating. But it seems to me that a normal diet will provide all the spermidine I need (and for £50 I can buy a lot of good food).

15 Responses to Spermidine, the new ‘wonder supplement’? SADLY NOT!

  • Thanks. Here’s another study for you: Neuroprotective potential of spermidine against rotenone induced Parkinson’s disease in rats https://pubmed.ncbi.nlm.nih.gov/29501454/

    • … in rats!!!!

      • Rats are mammals and not so distantly related.
        .
        $50 a month for a potential 10% increase in healthspan is a modest bet.

        Life Extension will be relegated to the Wealthy and the Bold. The timid and poors will simply die out according to their natural programming.

  • You should read these reviews on spermidine:

    https://science.sciencemag.org/content/359/6374/eaan2788

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128428/

    It’s very compelling. I take spermidine. Anything that enhances autophagy with no side effects is worth a shot. It’s too new as a drug to rely on clinical trials. Also, there is no way to patent spermidine, so pharma is not likely to bankroll any clinical trials anytime soon.

    • You are easily compelled. However, you should be aware that:

      1. In vitro and animal studies rarely translate to useful treatments in humans.

      2. Observational studies are not randomised and are strongly subject to bias from unidentified confounding factors; they should only be regarded as hypothesis-generating and never form the basis for clinical practice. I would recommend that you have a look at any undergraduate textbook on medical statistics for a more detailed explanation of why this is the case.

    • I want to believe, too. But when several of the authors are partners in a company that makes the product under investigation, I remain sadly unconvinced. (Is it my imagination, or is it almost impossible to find a “scientific” paper these days WITHOUT conflicts of interest?)

  • Unfortunately, all research is industry funded in some way, and the University training programs are influenced by industry too, so there will never be unbiased studies. Studies are easy to fake because you’re allowed to change the aims/goals of the study in retrospect to fit what you want. For example, study 1 may have tested a whole lot of variables such as blood pressure, exercise performance etc, and found no results except in mental performance, then they state the reaearch was only interested in mental performance. That’s just an example though, I’m not accusing them of that.

    But I have some confidence in the results, and keep in mind the stuff is found cheaply in wheat germ, there’s no need to buy expensive supplements (unless you’re allergic to wheat!).

  • Is it possible that spermadine could cause/ accelerate cancer? I haven’t read too far into this but I was sold on NMN until I read that there is a possible link to causing brain tumors. I could be wrong I don’t have a science background… just a PhD in google search hah.

    • I’m wondering the same thing. I have a medical background (physician assistant) but had cancer 7 years ago. I am a rheumatoid arthritis patient and would love a good anti-inflammatory.

      • The best anti-inflammatory is eating a diet that leads to less inflammation.
        After that I would consider CBD or THC.

        Pharma meds for chronic conditions may help the pain while causing other chronic conditions.

      • Look into stem cells for the RA. Available in Tijuana, Mexico for $4k for 50M, and they throw in some exosomes. I have a personal experience with this with a family member. Closest thing to a miracle I’ve seen. R3stemcell.com

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