As awareness of spermidine's health benefits grows, many consumers are faced with a crucial question: what is the difference between synthetic and food-derived spermidine supplements available in the market?
The Natural Advantage of Food-Derived Spermidine
Safety and Human Testing
The most critical distinction between synthetic and food-derived spermidine is their testing history. Synthetic spermidine has predominantly been studied in animal models, raising concerns about its applicability to human health. In contrast, food-derived spermidine has been consumed as part of human nutrition for thousands of years, providing a well-documented safety profile supported by numerous studies [1,2]. Research indicates that natural sources of spermidine are generally recognized as safe due to their historical use and more robust testing on human populations when compared to synthetic. Clinical studies (in humans!) have shown its benefits for cognitive function, longevity, and overall cellular health.
Spermidine Dosage
Additionally, The European Food Safety Authority (EFSA) has set a safe upper intake limit of 6 mg per day for food-derived spermidine [3]. This guideline reflects findings from human clinical trials, which have not exceeded this dosage, with most studies utilizing a daily dose of 1 mg in combination with other polyamines like spermine and putrescine [4]. This limit ensures safety while supporting the potential health benefits of spermidine supplementation.
In contrast, synthetic spermidine has not undergone comparable regulatory evaluations for human safety. This lack of oversight allows significantly higher doses in synthetic supplements, entering uncertain territory regarding both safety and long-term health effects. Without established guidelines, synthetic spermidine poses potential risks, particularly as some individuals have previously claimed to take dangerously high doses, such as 1 g per day, which could harm healthy cells.
Given these considerations, adhering to the EFSA's guideline of 6 mg per day for food-derived spermidine is prudent, as it aligns with current scientific understanding.
3 vs 2-Dimensional Molecules
Everyone knows if they are left- or right-handed, but did you know that it's the same for molecules?
We've all seen molecular structures in high school chemistry class, but those images are actually meant to represent 3-dimensional molecules. Synthetics can 'mirror' molecules found in nature, but this does not make them the same - just like a glove for your left hand would not fit your right (this is known as 'chirality'). This is another reason why we wanted to derive our spermidine from food - the body recognizes food-derived molecules the way a right-handed glove fits your right hand.
If you'd like to learn more, you can read this chemistry class review on why handedness, 'chirality' and 3-dimensionality matter.
The Polyamine Synergy Effect
In addition, synthetic molecules will be purely those molecules and will not include any of the co-factors that accompany and often potentiate natural molecules.
In terms of action within the body, food-derived spermidine does not work alone; it is accompanied by other beneficial polyamines called spermine and putrescine. These compounds work synergistically to create a recycling loop within the body that enhances the natural production of spermidine beyond what is supplemented. This natural synergy is absent in synthetic spermidine, lacking these co-factors, and therefore cannot replicate the same biological interactions and potentially disrupting natural polyamine metabolism [5,6].
The Risks of Synthetic Spermidine
While synthetic spermidine may seem like a cost-effective alternative to its natural counterpart, it comes with several significant drawbacks that warrant caution. One major concern is that excess synthetic spermidine can be metabolised into acrolein, a known toxin associated with liver damage in animal studies [7,8]. This conversion raises alarms about the potential risks of high-dose synthetic supplementation.
Additionally, the bioavailability of synthetic spermidine may be lower than that of naturally-occurring spermidine, meaning the body might not utilize it as effectively. This reduced efficacy could limit the intended health benefits that users seek from supplementation. Furthermore, many synthetic versions are produced through harsh chemical processes, which raises concerns about the presence of contaminants and overall quality control in these products.
Given these potential risks, individuals considering spermidine supplementation should prioritize natural sources, which have established safety profiles and are less likely to pose health risks associated with synthetic alternatives.
So what about the products out there with 8-10mg of synthetic spermidine with ingredient labels stating 'wheat germ with spermidine'?
Well, we have tested a few of these back in the lab in Japan and while they do indeed contain wheat germ and spermidine, they contain almost no spermine or putrescine. In nature, wheat will have a ratio of spermidine: spermine: putrescine of around 7:4:1. The fact that these products contain only small traces of spermine or putrescine indicate that their capsule contents have been 'cut' with synthetic spermidine, likely for cost reasons.
The Price of Quality and Safety
Food-derived spermidine may cost more than synthetic alternatives, but the investment is justified by its extensive safety testing, superior bioavailability, and higher quality standards. At Oxford Healthspan, our food-derived spermidine is sourced and manufactured under strict regulations in Japan, undergoing third-party testing to ensure purity and safety. Unlike synthetic options, which often cut corners in production, our formulation prioritises both efficacy and consumer well-being.
Why Primeadine?
As well as being wholly food-derived, Primeadine has other unique features that make it the superior choice.
Supports Natural Spermidine Production
Primeadine Original contains a unique prebiotic fiber that supports natural spermidine production. Our gut biome is capable of manufacturing spermidine for us, though this ability declines as we age and have had exposure to broad spectrum antibiotics and a diet of processed foods. We add a prebiotic to our formula that selectively feeds two strains of gut bacteria that manufacture spermidine in your body for you. As far as we know, we are the only product on the market with a prebiotic (a fructooligosacharide or resistant starch) in it.
Unique, Gluten-Free Version from Okinawa, Japan
Primeadine GF is a special, food-derived formula containing a spermidine-rich sub-strain of Okinawan Chlorella, Shikuwasa Citrus Lime Peel (providing autophagy-inducing nobiletin) and Turmeric, it is the purest and most bioavailable spermidine supplement on the market and suitable for even the most sensitive individuals.
Clean, Pure Ingredients
Sourced in Japan, home to the world's longest-lived people and strict food standards, Primeadine® meets the highest ISO2200 quality control. It also undergoes rigorous third-party testing in Japan and the USA ensures purity (free from toxins like molds and heavy metals) and potency.
Learn more about our quality and testing processes here.
Conclusion: Choose Food-Derived for Safety and Efficacy
The source of your spermidine supplement significantly impacts its effectiveness and safety. Food-derived spermidine offers a proven safety profile, natural polyamine synergy, and superior bioavailability, making it the best choice for those seeking long-term health benefits. At Oxford Healthspan, we remain committed to providing high-quality, scientifically supported supplementation options. Our decision to use only food-derived spermidine in Primeadine® reflects our dedication to excellence and customer well-being.
References
[3] https://www.efsa.europa.eu/sites/default/files/2024-05/ul-summary-report.pdf
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