High-Dose Spermidine Supplements: Impact on Blood and Saliva Levels

This summary is based on the scientific article titled High-Dose Spermidine Supplementation Does Not Increase Spermidine Levels in Blood Plasma and Saliva of Healthy Adults: A Randomized Placebo-Controlled Pharmacokinetic and Metabolomic Study by Stefan Senekowitsch et al., explores the effects of spermidine supplementation in humans. Spermidine, a biogenic polyamine crucial for cellular functions like growth and autophagy, declines with age and is linked to age-related diseases. The study investigated whether high oral spermidine doses could elevate blood and saliva levels. Conducted as a randomized, placebo-controlled trial with 12 healthy adults, the research utilized advanced techniques like LC-MS/MS and NMR metabolomics to measure spermidine, spermine, and putrescine levels. The findings indicated that spermidine supplementation increased spermine levels in the blood but did not affect spermidine or putrescine levels, suggesting presystemic conversion of spermidine to spermine.

Spermidine is a natural compound in our bodies that helps keep cells healthy and working well. As we age, spermidine levels decrease, which might be linked to aging and diseases that come with age. Researchers wanted to see if spermidine supplements could also increase its levels in our bodies, particularly in our blood and saliva. This study aimed to determine if high-dose spermidine supplements could raise spermidine levels in healthy adults.

2. Gut Bacteria: The bacteria in our gut also produce spermidine, which gets absorbed into our bodies.

The study notes, "The average daily nutritional intake of spermidine in European countries varies from approximately 10 to 15 mg," showing how diet plays a big role in our spermidine levels.

The study was a randomized, placebo-controlled trial. This means some participants got spermidine supplements while others got a placebo (a pill with no active ingredient). Neither the participants nor the researchers knew who received which treatment until the end.

Twelve healthy adults, both men and women aged 18 to 45, participated. They were chosen to ensure they were healthy and had no conditions that could affect the study.

Participants took either 15 mg of spermidine or a placebo every day for five days. After a nine-day break, they switched to the other treatment. Blood and saliva samples were collected to measure spermidine, spermine (a related compound), and putrescine (another related compound). Researchers used advanced techniques like liquid chromatography-mass spectrometry (LC-MS/MS) to measure these compounds.

They also used nuclear magnetic resonance (NMR) metabolomics to study changes in small molecules in the blood. The study says, "This study investigated the pharmacokinetics of oral spermidine supplementation for the first time," highlighting the importance of this research.

The study found that taking spermidine supplements increased spermine levels in the blood but did not significantly change spermidine or putrescine levels. In saliva, there were no significant changes in any of these compounds. This suggests that when we consume spermidine, it is quickly converted into spermine before it enters our bloodstream.

According to the study, "Compared with a placebo, spermidine supplementation significantly increased spermine levels in the plasma, but it did not affect spermidine or putrescine levels."

The metabolomic analysis, which looked at various small molecules in the blood, did not show significant differences between those who took spermidine and those who took the placebo. This means spermidine supplementation did not broadly impact other metabolites in the blood.

"No significant differences were observed in the plasma metabolome between the verum and placebo interventions," the study reports.

The findings suggest that dietary spermidine is converted to spermine before circulating in the blood. This process, known as presystemic metabolism, likely happens in the intestines or liver. The study emphasizes, "Dietary spermidine is presystemically converted into spermine, which then occurs in the systemic circulation."

The study suggests higher doses of spermidine might be needed for supplements to be effective. The researchers found doses less than 15 mg daily are unlikely to have short-term effects. This highlights the importance of considering spermine, the metabolite of spermidine, in future research and supplement strategies.

"It is rather unlikely that spermidine supplements with doses <15 mg/d exert any short-term effects," the study notes.

Future studies should explore higher doses of spermidine to see if they can achieve more significant effects. Researchers should also investigate gut bacteria's role in spermidine metabolism. Understanding these factors can help design more effective supplementation strategies.

The study concludes, "Detailed knowledge of spermidine pharmacokinetics is essential for future translational research," indicating the need for more in-depth studies.

The study found that high-dose spermidine supplementation increases spermine levels in the blood but does not change spermidine or putrescine levels. This suggests spermidine's benefits might be due to its conversion to spermine.

The findings challenge the idea that lower doses of spermidine supplements are effective and highlight the need for further research to determine the optimal doses and mechanisms of action. Future studies should focus on higher doses and consider the role of gut bacteria in spermidine metabolism.