Dataset Information

Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline.

ABSTRACT: Supplementation of spermidine, an autophagy-inducing agent, has been shown to protect against neurodegeneration and cognitive decline in aged animal models. The present translational study aimed to determine safety and tolerability of a wheat germ extract containing enhanced spermidine concentrations. In a preclinical toxicity study, supplementation of spermidine using this extract did not result in morbidities or changes in behavior in BALBc/Rj mice during the 28-days repeated-dose tolerance study. Post mortem examination of the mice organs showed no increase in tumorigenic and fibrotic events. In the human cohort (participants with subjective cognitive decline, n=30, 60 to 80 years of age), a 3-month randomized, placebo-controlled, double-blind Phase II trial was conducted with supplementation of the spermidine-rich plant extract (dosage: 1.2 mg/day). No differences were observed between spermidine and placebo-treated groups in vital signs, weight, clinical chemistry and hematological parameters of safety, as well as in self-reported health status at the end of intervention. Compliance rates above 85% indicated excellent tolerability. The data demonstrate that spermidine supplementation using a spermidine-rich plant extract is safe and well-tolerated in mice and older adults. These findings allow for longer-term intervention studies in humans to investigate the impact of spermidine treatment on cognition and brain integrity.

SUBMITTER: Schwarz C

PROVIDER: S-EPMC5807086 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline.

Schwarz Claudia C Stekovic Slaven S Wirth Miranka M Benson Gloria G Royer Philipp P Sigrist Stephan J SJ Pieber Thomas T Dammbrueck Christopher C Magnes Christoph C Eisenberg Tobias T Pendl Tobias T Bohlken Jens J Köbe Theresa T Madeo Frank F Flöel Agnes A

Aging 20180101 1

Supplementation of spermidine, an autophagy-inducing agent, has been shown to protect against neurodegeneration and cognitive decline in aged animal models. The present translational study aimed to determine safety and tolerability of a wheat germ extract containing enhanced spermidine concentrations. In a preclinical toxicity study, supplementation of spermidine using this extract did not result in morbidities or changes in behavior in BALBc/Rj mice during the 28-days repeated-dose tolerance st ...[more]

PMID: 29315079

Similar Datasets

Project description:ImportanceDeveloping interventions against age-related memory decline and for older adults experiencing neurodegenerative disease is one of the greatest challenges of our generation. Spermidine supplementation has shown beneficial effects on brain and cognitive health in animal models, and there has been preliminary evidence of memory improvement in individuals with subjective cognitive decline.ObjectiveTo determine the effect of longer-term spermidine supplementation on memory performance and biomarkers in this at-risk group.Design, setting, and participantsThis 12-month randomized, double-masked, placebo-controlled phase 2b trial (the SmartAge trial) was conducted between January 2017 and May 2020. The study was a monocenter trial carried out at an academic clinical research center in Germany. Eligible individuals were aged 60 to 90 years with subjective cognitive decline who were recruited from health care facilities as well as through advertisements in the general population. Data analysis was conducted between January and March 2021.InterventionsOne hundred participants were randomly assigned (1:1 ratio) to 12 months of dietary supplementation with either a spermidine-rich dietary supplement extracted from wheat germ (0.9 mg spermidine/d) or placebo (microcrystalline cellulose). Eighty-nine participants (89%) successfully completed the trial intervention.Main outcomes and measuresPrimary outcome was change in memory performance from baseline to 12-month postintervention assessment (intention-to-treat analysis), operationalized by mnemonic discrimination performance assessed by the Mnemonic Similarity Task. Secondary outcomes included additional neuropsychological, behavioral, and physiological parameters. Safety was assessed in all participants and exploratory per-protocol, as well as subgroup, analyses were performed.ResultsA 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. Exploratory analyses indicated possible beneficial effects of the intervention on inflammation and verbal memory. Adverse events were balanced between groups.Conclusions and relevanceIn this randomized clinical trial, longer-term spermidine supplementation in participants with subjective cognitive decline did not modify memory and biomarkers compared with placebo. Exploratory analyses indicated possible beneficial effects on verbal memory and inflammation that need to be validated in future studies at higher dosage.Trial registrationClinicalTrials.gov Identifier: NCT03094546.

Project description:BackgroundGiven the global increase in the aging population and age-related diseases, the promotion of healthy aging is one of the most crucial public health issues. This trial aims to contribute to the establishment of effective approaches to promote cognitive and brain health in older individuals with subjective cognitive decline (SCD). Presence of SCD is known to increase the risk of objective cognitive decline and progression to dementia due to Alzheimer's disease. Therefore, it is our primary goal to determine whether spermidine supplementation has a positive impact on memory performance in this at-risk group, as compared with placebo. The secondary goal is to examine the effects of spermidine intake on other neuropsychological, behavioral, and physiological parameters.MethodsThe SmartAge trial is a monocentric, randomized, double-blind, placebo-controlled phase IIb trial. The study will investigate 12 months of intervention with spermidine-based nutritional supplementation (target intervention) compared with 12 months of placebo intake (control intervention). We plan to recruit 100 cognitively normal older individuals with SCD from memory clinics, neurologists and general practitioners in private practice, and the general population. Participants will be allocated to one of the two study arms using blockwise randomization stratified by age and sex with a 1:1 allocation ratio. The primary outcome is the change in memory performance between baseline and post-intervention visits (12 months after baseline). Secondary outcomes include the change in memory performance from baseline to follow-up assessment (18 months after baseline), as well as changes in neurocognitive, behavioral, and physiological parameters (including blood and neuroimaging biomarkers), assessed at baseline and post-intervention.DiscussionThe SmartAge trial aims to provide evidence of the impact of spermidine supplementation on memory performance in older individuals with SCD. In addition, we will identify possible neurophysiological mechanisms of action underlying the anticipated cognitive benefits. Overall, this trial will contribute to the establishment of nutrition intervention in the prevention of Alzheimer's disease.Trial registrationClinicalTrials.gov, NCT03094546 . Registered 29 March 2017-retrospectively registered.Protocol versionBased on EA1/250/16 version 1.5.

Project description:Background and Objectives:Subjective cognitive decline (SCD), the self-reported experience of worsening or more frequent confusion or memory loss, may be associated with the development or worsening of chronic conditions or complicating their self-management. The objectives of this study were to (i) establish the prevalence of chronic conditions and multiple chronic conditions among adults with SCD, and (ii) compare the prevalence of chronic conditions among people with and without SCD and SCD-related functional limitations. Research Design and Methods:Data were analyzed from the Cognitive Decline module of the Behavioral Risk Factor Surveillance System administered in 49 states, DC, and Puerto Rico during 2015-2017. Analyses included 220,221 respondents aged 45 years or older who answered the SCD screening question and reported their chronic conditions. Weighted estimates were calculated and chi-square tests were used for comparisons. Results:Persons with a history of stroke, heart disease, and chronic obstructive pulmonary disorder had significantly higher prevalence of SCD compared to those without. The prevalence of having at least one chronic condition was higher among adults with SCD compared to adults without SCD in each age group (45-64 years: 77.4% vs 47.1%, p < .001; ?65 years: 86.3% vs 73.5%, p < .001). Among those with SCD, the prevalence of an SCD-related functional limitation was higher among those with at least one chronic condition compared to those with none (45-64 years: 63.3% vs 42.4%, p < .001; ?65 years: 40.0% vs 25.1%, p < .001). Only half of adults with SCD and a chronic condition had discussed their SCD with a health care professional. Discussion and Implications:SCD and chronic conditions commonly co-occur. Having a chronic condition was associated with greater SCD-related functional limitations. SCD might complicate the management of chronic conditions, and patients and providers should be aware of increased risk for cognitive decline in the presence of chronic diseases.

Project description:BackgroundOlder adults with mild cognitive impairment (MCI) have slower gait speed and poor gait performance under dual-task conditions. However, gait kinematic and kinetic characteristics in older adults with MCI or subjective cognitive decline (SCD) remain unknown. This study was designed to explore the difference in gait kinematics and kinetics during level walking among older people with MCI, SCD, and normal cognition (NC).MethodsThis cross-sectional study recruited 181 participants from July to December 2019; only 82 met the inclusion criteria and consented to participate and only 79 completed gait analysis. Kinematic and kinetic data were obtained using three-dimensional motion capture system during level walking, and joint movements of the lower limbs in the sagittal plane were analyzed by Visual 3D software. Differences in gait kinematics and kinetics among the groups were analyzed using multivariate analysis of covariance (MANCOVA) with Bonferroni post-hoc analysis. After adjusting for multiple comparisons, the significance level was p < 0.002 for MANCOVA and p < 0.0008 for post-hoc analysis.ResultsTwenty-two participants were MCI [mean ± standard deviation (SD) age, 71.23 ± 6.65 years], 33 were SCD (age, 72.73 ± 5.25 years), and 24 were NC (age, 71.96 ± 5.30 years). MANCOVA adjusted for age, gender, body mass index (BMI), gait speed, years of education, diabetes mellitus, and Geriatric Depression Scale (GDS) revealed a significant multivariate effect of group in knee peak extension angle (F = 8.77, p < 0.0001) and knee heel strike angle (F = 8.07, p = 0.001) on the right side. Post-hoc comparisons with Bonferroni correction showed a significant increase of 5.91° in knee peak extension angle (p < 0.0001) and a noticeable decrease of 6.21°in knee heel strike angle (p = 0.001) in MCI compared with NC on the right side. However, no significant intergroup difference was found in gait kinetics, including dorsiflexion, plantar flexion, knee flexion, knee extension, hip flexion, and hip extension(p > 0.002).ConclusionAn increase of right knee peak extension angle and a decrease of right knee heel strike angle during level walking were found among older adults with MCI compared to those with NC.

Dataset Information

Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline.

Publications

Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets