New Research Alert! Further Evidence for Spermidine’s Power to Induce Autophagy

A recent study [1] has added exciting new insights to the ongoing discourse on the potential of spermidine in rectifying dysfunctional autophagy. They looked specifically at two rare cell trafficking disorders that involve problems with how cells transport materials inside the body. They found that both disorders were underpinned by dysfunctional autophagy, emphasizing the importance of this natural “clean-up” system to keep cells healthy and the need for a safe, effective treatment to target this. Now, here’s where spermidine comes in: In the study, researchers supplemented individuals with food-derived spermidine, and it proved to help manage these disorders by supporting the body’s autophagy process. 

Study Overview 

 So what exactly did they find?

This study investigated the role of autophagy in two specific cell trafficking disorders caused by gene mutations. They then explored whether spermidine, known to induce autophagy, can help correct the autophagy defects associated with these conditions. They opted for wheat germ extract of 0.1% spermidine, providing a total spermidine amount of 6 mg/day, split into three 2 mg doses.

A Note on Spermidine Dosage: 

The US FDA has not set a safe upper limit for food-derived spermidine, but the European Food Safety Authority considers up to 6 mg safe. Most studies use a daily dose of 1 mg of natural spermidine, along with spermine and putrescine, which are absent in synthetic versions. Synthetic spermidine has not been tested for human safety or efficacy.

If you do not feel results on our standard dose of 1mg, then you may want to experiment with double dosing. We recommend that you taper up slowly.

Their initial results demonstrated autophagy alterations as a shared feature across the different cell trafficking disorders* tested. This is of note as dysfunctional autophagy has been named as a hallmark of aging by Lopez-Otin and the research team [2], translating these findings to several age-related diseases that are underpinned by dysfunctional autophagy. This opens up the discussion of autophagy modulation, an active area of research currently experimenting with targeted therapeutic approaches to tackle this hallmark. In this study, they proceed to demonstrate food-derived spermidine as a promising option. 

Their two patients received spermidine supplementation (6mg/day, divided into three 2mg doses) derived from wheat germ extract, over the course of 3 months. Before and after this treatment, they measured autophagic flux* and conducted neurodevelopmental assessments giving a measure of both physiological and behavioural changes. This gave very exciting results on both fronts! Following spermidine supplementation on a cellular level they observed:

• Improved autophagic flux (particularly during starving conditions)
• Improved autophagosome-lysosome fusion*
• Normalized overall autophagy function

These findings at the cellular level further presented changes in symptoms, demonstrating measurable improvements in both patients including: 

• Motor function
• Socialisation skills
• Enhanced communication ability
• Reduction in symptom flare ups
•  Improved sleeping patterns
• Along with no reported adverse affect during the treatment period.

Wider Implications

Dysfunctional autophagy is being increasingly recognised as a major contributor to a number of age-related and neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and cardiovascular conditions. Spermidine’s ability to enhance autophagy suggests its potential in:

• Neuroprotection and cognitive health [3]
• General cellular maintenance and resilience to combat other hallmarks of aging [4]
• Anti-aging and longevity strategies [5]

This study therefore adds valuable human data to the growing body of research supporting spermidine’s therapeutic potential. Given its natural origin and lack of adverse effects presented in this study, corroborating with other research, spermidine presents a compelling case for further exploration as a safe, long-term intervention to regulate autophagy and improve patient outcomes in a range of disorders. Additionally, these findings suggest that spermidine could also serve as a preventative measure to maintain cellular health and reduce the risk of developing autophagy-related diseases before symptoms arise.

Incorporating Spermidine into your Diet

If you're looking to integrate spermidine into your routine, consider Primeadine - high-quality, wheat germ-derived spermidine supplement, akin to that used in this study. Primeadine Original is formulated with pure, food-derived spermidine to promote cellular health and longevity.

For those with dietary sensitivities, Primeadine GF offers a gluten-free alternative, ensuring accessibility without compromising quality.

Given the promising results of this study, Primeadine offers a scientifically backed option for those looking to harness the autophagy-enhancing benefits of spermidine for both therapeutic and preventative health purposes.

We also consider increasing spermidine-rich foods like shiitake mushrooms, green peas and fermented soybean, like natto or tempeh, in your diet.

Scientific Jargon Explained

*Cell trafficking Disorders: Cell trafficking disorders are genetic or acquired conditions that disrupt the normal transport of molecules, organelles, or proteins within or between cells, leading to cellular dysfunction and disease. Examples include cystic fibrosis, lysosomal storage disorders, and some neurodegenerative diseases.

*Autophagic flux: The process by which your cells clean up and recycle their own parts. It’s like a cellular "housekeeping" system where damaged or unnecessary components (like old proteins or organelles) get broken down and reused. The "flux" part refers to how efficiently and actively this recycling process is happening in the cell. In summary: it’s a measure of how well your cells are cleaning and renewing themselves.

*Neurodevelopmental: How the brain is affected and works over time.

*Autophagosome-lysosome fusion: The process where a "recycling bag" (autophagosome) inside a cell merges with a "trash disposal unit" (lysosome). The autophagosome collects unwanted or damaged cell parts, and then fuses with the lysosome, which contains special enzymes that break down and recycle these materials. This helps the cell stay clean and function properly.

References

[1] Díaz-Osorio Y, Gimeno-Agud H, Mari-Vico R, Illescas S, Ramos JM, Darling A, García-Cazorla À, Oyarzábal A. Spermidine Recovers the Autophagy Defects Underlying the Pathophysiology of Cell Trafficking Disorders. J Inherit Metab Dis. 2025 Jan;48(1):e12841. doi: 10.1002/jimd.12841

[2] López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell. 2023 Jan 19;186(2):243-278. doi: 10.1016/j.cell.2022.11.001

[3] Ghosh I, Sankhe R, Mudgal J, Arora D, Nampoothiri M. Spermidine, an autophagy inducer, as a therapeutic strategy in neurological disorders. Neuropeptides. 2020 Oct;83:102083. doi: 10.1016/j.npep.2020.102083

[4] Madeo F, Bauer MA, Carmona-Gutierrez D, Kroemer G. Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans? Autophagy. 2019 Jan;15(1):165-168. doi: 10.1080/15548627.2018.1530929

[5] Ni YQ, Liu YS. New Insights into the Roles and Mechanisms of Spermidine in Aging and Age-Related Diseases. Aging Dis. 2021 Dec 1;12(8):1948-1963. doi: 10.14336/AD.2021.0603