‘A pivotal moment for spermidine research’

“This publication marks a pivotal moment for spermidine research,” said Gene Bruno, DBM, MS, RH(AHG), chief scientific officer of Nutraland USA and study co-author.

“While previous research has highlighted the benefits of polyamines through epidemiological studies, this is the first study we’re aware of to demonstrate an effective dose for a spermidine supplement in a human clinical setting. These findings, while preliminary, open the door for future research and suggest that Miricell may play a meaningful role in supporting healthy aging.”

The study, published in the journal Alternative Therapies in Health and Medicine, was conducted in collaboration with The Center for Applied Science contract research organization.

Spermidine and healthy aging

Originally isolated from human semen in the 1920s, following the 1678 discovery of related polyamine compound spermine by Dutch microscopist Antonie van Leeuwenhoek, it was not until the mid-19th century that scientists discovered that spermidine was not unique to semen but ubiquitous in all living cells.

Spermidine began to draw increasing attention in the 1990s for its role in cellular homeostasis and autophagy—the body’s way of cleaning out damaged cells. Along with spermine and fellow polyamine putrescine, it has has been shown to provide potent antioxidant and anti-inflammatory properties, cell and gene protection and autophagy activation.

In 2009, a key study published in Nature Cell Biology sparked further interest in the compound’s associations with anti-aging, neuroprotection and cardiovascular health, and a series of epidemiological studies followed, linking higher spermidine intake with longer lifespan and reduced incidence of age-related diseases.

“The role of autophagy extends far beyond simple waste disposal, influencing organellar quality control, immune function, cancer biology, metabolism and cellular stress resistance,” the researchers on the current study noted. “These diverse roles make autophagy a key regulator of aging, neurodegeneration, cardiovascular health and metabolic balance, with broad implications for disease prevention and longevity.”

Miricell, a polyamine extract from upcycled rice germ, is standardized to 1% and 2% spermidine and also contains spermine, putrescine and other nutrients. It is marketed as dietary supplement ingredient across healthy aging, skin and hair health, immunity support, neuroprotection, cardioprotection, women’s health and fertility categories.

Study details

The 56-day, single-blind, interventional trial evaluated daily supplementation with Miricell at either a 1.5 mg or 3.3 mg spermidine dose in 12 healthy men and women.

Primary outcome measures included biomarkers of autophagy (Beclin-1 and Unc-51-like kinase 1) and indices of neuroprotection (brain-derived neurotrophic factor), homocysteine and cardiometabolic health (high sensitivity C-reactive protein, lipid panel). This exploratory, proof-of-concept study was not powered to assess statistical significance.

“Compared to baseline, only the 3.3 mg dose of spermidine from Miricell increased Beclin-1 by 7.3%, ULK-1 by 13.4% and BDNF by 12.1%,” the researchers reported. “Compared to baseline, the same dose resulted in a 20.8% decrease in hs-CRP, a 20.1% decrease in VLDL and a 26.9% decrease in triglycerides.”

They added that the clinical chemistry panel, complete blood count, vital signs and adverse events assessment support the ingredient’s safety profile for the use of 3.3 mg/day of spermidine.

In contrast, the 1.5 mg group showed undesirable increases or decreases in ULK1, BDNF, hs-CRP, very-low-density lipoprotein (VLDL)—results which the researchers said would likely have been evident in a placebo group had this pilot study included a placebo arm. Instead, the 1.5 mg group simply provided an insufficient dose of spermidine to offset these changes.

Although promising, the study highlighted that the results are preliminary and should be interpreted with caution. A randomized, placebo-controlled clinical trial to validate these observations is scheduled to launch later in 2025.

Source: Alternative Therapies in Health and Medicine. Published online ahead of print. “Effects of Spermidine-Rich Rice Germ Extract Supplement on Biomarkers of Healthy Aging and Autophagy-Proof-of-Concept Pilot Study”. Authors: Gene Bruno, Michael La Monica and Tim Ziegenfuss.