High-dose Polyphenol-rich Nutrition Improves Lipid and Inflammation Profiles and Triggers Apoptotic Signaling in Healthy Elderly People (the ErdBEHR Study)

Abstract

Nutritional interventions in healthy individuals may be particularly informative if high, but not excessive, amounts of specific healthy foods are taken to maximize effects without sacrificing safety. We hypothesized that high amounts of polyphenols taken on single days may eliminate senescent blood cells. We conducted a ten-week parallel-group controlled randomized open trial with an escalation of consumption, up to ~4kg fresh strawberries weekly, plus 200g dried strawberries and 240g capers in olive oil on three single "seno-intervention" days, in 168 healthy elderly people aged 50-80 years. Two primary endpoints, LDL cholesterol and high sensitive CRP, were prespecified. We found a significant decline in LDL cholesterol, and in CRP by ~50% in all groups with seno-intervention days (limited to participants with increased baseline values). LDL levels were reduced by 0.0174 mmol/L for any single 500g-increment in the weekly fresh strawberry intake of the average participant. Gene expression analyses of whole blood suggested improvement of mitochondrial and immunological function, suppression of inflammation (in high-intervention groups), and positive regulation of apoptotic signaling (in the highest-intervention group). Overall, a medium-term nutritional intervention improved lipid and inflammation status, and provided specific hints for apoptotic/senolytic effects.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

DRKS00026998

Funding Statement

The study was funded in part by Karls Erdbeerhof (Karl's strawberry farm). We also thank the Interdisziplinaere Fakultaet of the University of Rostock (Altern des Individuums und der Gesellschaft) for intramural financial support. We thank Siemens Healthcare for donating reagents. We thank EFRE (European Fund for Regional Development) [GHS-15-0019, 2016-2021] and the Core facility for Cell sorting and Analysis for infrastructural support. The mass spectrometric analyses of quercetin and fisetin were performed with a triple quadrupole mass spectrometer LCMS-8050 co-funded by the Deutsche Forschungsgemeinschaft (DFG, INST 264/169-1 FUGG). The analysis of micronutrients was funded by the BMBF (FKZ 031B0731E) as part of the joint project "f4f-food for future". G.F., A.K. and D.P. are further supported by the BMBF (FKZ 01ZX1903A and 1DS19049). We thank all participants, all expert advisors consulted before the study, and all helpful people at Karls. We also thank the local teams at the IBIMA and ILAB (A. Brauer, F. Thiesen, S. Schenk, R. Krause, E. Kauffold, L. Werner, A. Werderitsch, A.-L. Rossmann, R. Mueller, Z. Setayeshmehr, C. Rassmus, A. Beier, T. Freitag). The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The ethics board of the Rostock University Medical Center gave ethical approval for this study under the registration number A 2021-0096 (see Supplementary Files, in German).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

Aggregated data that do not require managed access are provided in the Supplementary Files (see listing on page 20). Other data are available from the authors upon request.

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