Spd8.0

Spermidine Research

38 peer-reviewed studies · Evidence score: 8/10

Unlocking diagnosis of sarcopenia: The role of circulating biomarkers - A clinical systematic review

Veronesi F et al. • Mechanisms of ageing and development (2024)

Additionally, they had lower levels of irisin, free triiodothyronine, and insulin, with reduced phosphatidylcholines and elevated spermidine.

Additionally, they had lower levels of irisin, free triiodothyronine, and insulin, with reduced phosphatidylcholines and elevated spermidine.
The studies were generally of fair to good quality, but due to heterogeneity, a meta-analysis was not feasible.
The review underscores the need for standardized biomarkers and diagnostic criteria and suggests that improving outcomes for sarcopenic patients may involve addressing inflammation, metabolic, and hormonal issues through nutrition, medication, and exercise.Copyright © 2024 Elsevier B.V.

Systematic Reviewn=641,730

DOI

Discovery of Gut Bacteria Specific to Alzheimer's Associated Diseases is a Clue to Understanding Disease Etiology: Meta-Analysis of Population-Based Data on Human Gut Metagenomics and Metabolomics

Paley EL • Journal of Alzheimer's disease : JAD (2019)

ADAS is attributable to potentially modifiable risk factors of AD associated diseases.

Biogenic amines (histamine, tryptamine, tyramine, phenylethylamine, cadaverine, putrescine, agmatine, spermidine) that present in food and are produced by gut microbiota are significantly higher in C&A (e.g., histamine/histidine 95-fold) versus NNI (histamine/histidine 16-fold).
The seizure-eliciting tryptamine induced cytoplasmic vacuolization and vesiculation with cell fragmentation.
Present additions of ADAS-carriers at different ages including infants led to an ADAS-comprising human sample size of 2,830 from 27 studies from four continents (North America, Australia, Asia, Europe).

Meta-Analysisn=2,830

DOI

Mechanism and clinical implication of gut dysbiosis in degenerative abdominal aortic aneurysm: A systematic review

Chui ESH et al. • Asian journal of surgery (2024)

With our expanding knowledge of the downstream pathogenic mechanisms of gut dysbiosis, novel therapeutics such as short-chain fatty acids and spermidine, as well as prognostic biomarkers such as TM...

With our expanding knowledge of the downstream pathogenic mechanisms of gut dysbiosis, novel therapeutics such as short-chain fatty acids and spermidine, as well as prognostic biomarkers such as TMAO have yielded promising preclinical results.
In conclusion, there is strong evidence corroborating the role of gut dysbiosis in the pathogenesis of AAA, wherein its therapeutic and prognostic potential deserves further exploration.

Systematic Review

DOI

The impact of BMI on sperm parameters and the metabolite changes of seminal plasma concomitantly

Guo D et al. • Oncotarget (2017)

This systematic review with meta-analysis has confirmed there was a relationship between BMI and sperm quality, suggesting obesity may be a detrimental factor of male infertility.

This study found standardized weighted mean differences (SMD) in sperm parameters (total sperm count, sperm concentration, and semen volume) of abnormal weight groups decreased to different degree compared to normal weight.
Dose-response analysis found SMD of sperm count, sperm concentration and semen volume respectively fell 2.4%, 1.3% and 2.0% compared with normal weight for every 5-unit increase in BMI.
Metabolomic analysis of seminal plasma showed that spermidine and spermine were likely to play a vital role in the spermatogenesis progress.

Meta-Analysisn=26,814

DOI

Metabolomics in Glaucoma: A Systematic Review

Wang Y et al. • Investigative ophthalmology & visual science (2021)

In this review, we summarize existing metabolomic studies related to glaucoma biomarker identification and point out a series of metabolic disorders in OAG patients, providing information on the molecular mechanism changes in glaucoma.

In this review, we summarize existing metabolomic studies related to glaucoma biomarker identification and point out a series of metabolic disorders in OAG patients, providing information on the molecular mechanism changes in glaucoma.
Additional studies are needed to validate existing findings, and future research will need to explore the potential overlap between different biological fluids.
Further research warranted to confirm findings

Systematic Reviewn=13

DOI

High Plasma Polyamine Levels Are Associated With an Increased Risk of Poststroke Cognitive Impairment: A Multicenter Prospective Study From CATIS

He Y et al. • Journal of the American Heart Association (2025)

Higher plasma polyamine levels were associated with increased risk of PSCI among patients with ischemic stroke.

The adjusted odds ratios of PSCI for the highest versus lowest quartile of putrescine, spermidine, and spermine were 1.81 (95% CI, 1.09-3.00), 1.81 (95% CI, 1.09-3.01), and 1.92 (95% CI, 1.15-3.20), respectively.
Higher plasma polyamine levels were associated with increased risk of PSCI among patients with ischemic stroke.
Our findings suggest that plasma polyamines should be implicated in the pathophysiologic processes of PSCI and may be the potential intervention targets for PSCI.

RCTn=619

DOI

Plasma Polyamines and Short-Term Adverse Outcomes Among Patients With Ischemic Stroke: A Prospective Cohort Study

Yang P et al. • Journal of the American Heart Association (2024)

Among patients with ischemic stroke, high plasma putrescine levels were associated with a decreased risk of adverse outcomes, whereas high plasma spermidine and spermine levels were associated with an increased risk of adverse outcomes.

During a 3-month follow-up period, 877 participants (25.1%) experienced the primary outcome.
Increased putrescines were associated with a decreased risk of the primary outcome (the highest versus the lowest tertile: odds ratio, 0.72 [95% CI, 0.58-0.91]; P=0.005) and major disability (odds ratio, 0.59 [95% CI, 0.47-0.74]; P<0.001).
Among patients with ischemic stroke, high plasma putrescine levels were associated with a decreased risk of adverse outcomes, whereas high plasma spermidine and spermine levels were associated with an increased risk of adverse outcomes.

RCTn=877

DOI

Lubiprostone in chronic kidney disease: Insights into mitochondrial function and polyamines from a randomized phase 2 clinical trial

Watanabe S et al. • Science advances (2025)

Lubiprostone is a previously unknown and safe therapeutic option to mitigate renal decline in CKD.

Lubiprostone did not alter uremic toxin levels but improved or preserved estimated glomerular filtration rate and its slope in the 16-microgram group.
Mild-to-moderate gastrointestinal events occurred in the placebo and 16-microgram groups.
Multiomics analysis revealed that lubiprostone modulated the gut microbial agmatine pathway and increased spermidine levels, thereby improving renal mitochondrial function.

RCTn=150

DOI

Dietary polyamine intake and risk of colorectal adenomatous polyps

Vargas AJ et al. • The American journal of clinical nutrition (2012)

This study showed a role for dietary polyamines in colorectal adenoma risk.

A dietary intake of polyamines above the median amount in the study population was associated with 39% increased risk of colorectal adenoma at follow-up (adjusted OR: 1.39; 95% CI: 1.06, 1.83) in the pooled sample.
In addition, younger participants (OR: 1.94; 95% CI: 1.23, 3.08), women (OR: 2.43; 95% CI: 1.48, 4.00), and ODC GG genotype carriers (OR: 1.59; 95% CI: 1.00, 2.53) had significantly increased odds of colorectal adenoma if they consumed above-median polyamine amounts.
This study showed a role for dietary polyamines in colorectal adenoma risk.

RCTn=1,164

DOI

Supplementation of spermidine at 40 mg/day has minimal effects on circulating polyamines: An exploratory double-blind randomized controlled trial in older men

Keohane P et al. • Nutrition research (New York, N.Y.) (2024)

These findings suggest that hpSPD at 40 mg/day for up to 28 days is safe and well-tolerated in healthy older men.

These findings suggest that hpSPD at 40 mg/day for up to 28 days is safe and well-tolerated in healthy older men.
The study is consistent with preclinical results and provides important evidence supporting the safety of high-purity spermidine supplementation, enabling further research with single-molecule spermidine to investigate its potential biology for improving human health.
This trial was registered at clinicaltrials.gov (NCT05459961).

RCTn=37

DOI

Treatment of peri-implant mucositis using spermidine and calcium chloride as local adjunctive delivery to non-surgical mechanical debridement: a double-blind randomized controlled clinical trial

Iorio-Siciliano V et al. • Clinical oral investigations (2024)

Whitin the limitations of the present study, results indicate that the clinical parameters improved following non-surgical mechanical debridement regardless the adjunct of spermidine and calcium chloride gel.

After 3 months, a statistically significant improvement of all parameters were recorded in each group (p < 0.05).
However, no statistically significant differences were found between test and control procedures (p > 0.05).
At 3 months, 85% of test implants and 70% of control implants resulted in disease resolution.

RCTn=40

DOI

Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial

Schwarz C et al. • JAMA network open (2022)

In this randomized clinical trial, longer-term spermidine supplementation in participants with subjective cognitive decline did not modify memory and biomarkers compared with placebo.

A total of 100 participants (51 in the spermidine group and 49 in the placebo group) were included in the analysis (mean [SD] age, 69 [5] years; 49 female participants [49%]).
Over 12 months, no significant changes were observed in mnemonic discrimination performance (between-group difference, -0.03; 95% CI, -0.11 to 0.05; P = .47) and secondary outcomes.
In this randomized clinical trial, longer-term spermidine supplementation in participants with subjective cognitive decline did not modify memory and biomarkers compared with placebo.

RCTn=100

DOI

Cinnamon (Cinnamomum cassia) water extract improves diarrhea symptoms by changing the gut environment: a randomized controlled trial

Park SY et al. • Food & function (2023)

These results indicate that cinnamon intake relieves diarrhea symptoms through metabolic changes due to changes in intestinal microbial groups.

CWE intake significantly increased colonic transit time (p = 0.019) and fecal isobutyric acid (p = 0.008) and spermidine (p = 0.009) contents compared to placebo intake.
In contrast, CWE decreased fecal indole (p = 0.032) and agmatine (p = 0.018) contents.
Gut microbiota analysis showed increased alpha diversity and significant changes in strains such as Bifidobacterium longum ATCC 55813 (LDA = 1.38) in the CWE group compared with the placebo group.

RCTn=70

DOI

Absorption, anti-inflammatory, antioxidant, and cardioprotective impacts of a novel fasting mimetic containing spermidine, nicotinamide, palmitoylethanolamide, and oleoylethanolamide: A pilot dose-escalation study in healthy young adult men

Rhodes CH et al. • Nutrition research (New York, N.Y.) (2024)

Intake of the combined supplements showed they were bioavailable and increased in plasma in a dose-dependent manner and provide preliminary data showing enhanced plasma anti-inflammatory and antiox...

Intake of the combined supplements showed they were bioavailable and increased in plasma in a dose-dependent manner and provide preliminary data showing enhanced plasma anti-inflammatory and antioxidant functions.
This trial was registered at clinicaltrials.gov (NCT05017428).

RCTn=5

DOI

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

Senekowitsch S et al. • Nutrients (2023)

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

The plasma metabolome was investigated using nuclear magnetic resonance (NMR) metabolomics. (3) Results: Compared with a placebo, spermidine supplementation significantly increased spermine levels in the plasma, but it did not affect spermidine or putrescine levels.
No effect on salivary polyamine concentrations was observed. (4) Conclusions: This study's results suggest that dietary spermidine is presystemically converted into spermine, which then enters systemic circulation.
Presumably, the in vitro and clinical effects of spermidine are at least in part attributable to its metabolite, spermine.

RCTn=12

DOI

Human fasting modulates macrophage function and upregulates multiple bioactive metabolites that extend lifespan in Caenorhabditis elegans: a pilot clinical study

Rhodes CH et al. • The American journal of clinical nutrition (2023)

The results of this study reveal multiple functionalities and immunological pathways affected by PF in humans, identify candidates for the development of fasting mimetic compounds, and uncover targets for investigation in longevity research.

Furthermore, we found that these metabolites and their combination significantly extended the median lifespan of C. elegans by as much as 96%.
The results of this study reveal multiple functionalities and immunological pathways affected by PF in humans, identify candidates for the development of fasting mimetic compounds, and uncover targets for investigation in longevity research.
Further research warranted to confirm findings

RCTn=20

DOI

Endothelial Function is improved by Inducing Microbial Polyamine Production in the Gut: A Randomized Placebo-Controlled Trial

Matsumoto M et al. • Nutrients (2019)

This study suggests that consuming Bifal + Arg YG prevents or reduces the risk of atherosclerosis.

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.
This study suggests that consuming Bifal + Arg YG prevents or reduces the risk of atherosclerosis.

RCTn=44

DOI

Effects of Spermidine-Rich Rice Germ Extract Supplement on Biomarkers of Healthy Aging and Autophagy-Proof-of-Concept Pilot Study

Bruno G et al. • Alternative therapies in health and medicine (2025)

This pilot study found that 3.3 mg/day of spermidine from Miricell® rice germ extract tends to improve biomarkers of autophagy, neuroprotection, and cardiometabolic health.

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%.
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.
This pilot study found that 3.3 mg/day of spermidine from Miricell® rice germ extract tends to improve biomarkers of autophagy, neuroprotection, and cardiometabolic health.

RCTn=12

The positive effect of spermidine in older adults suffering from dementia : First results of a 3-month trial

Pekar T et al. • Wiener klinische Wochenschrift (2021)

By comparison, the group which had a lower spermidine intake showed consistent or declining cognitive performance.

Blood samples were taken for the determination of spermidine concentration and measurement of metabolic parameters.
The results demonstrated a clear correlation between the intake of spermidine and the improvement in cognitive performance in subjects with mild and moderate dementia in the group treated with the higher spermidine dosage.
The most substantial improvement in test performance was found in the group of subjects with mild dementia with an increase of 2.23 points (p = 0.026) in the mini mental state examination (MMSE) and 1.99 (p = 0.47) in phonematic fluidity.

RCTn=85

DOI

Spermidine supplementation in older adults

Wirth M et al. • Cortex (2018)

Spermidine supplementation improved memory performance in older adults.

Improved memory function
Safe in older adults
Potential cognitive benefits

RCTn=30

DOI

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