Erdbeerstudie Aging Biology
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Introduction

Can food be a preventive medicine and a key to longevity? More specifically, are there particular foods or food combinations and corresponding dosing schemes that provide, on the one hand, both outstanding safety and affordability and yet strong health benefits on the other? Can aging-associated processes be slowed down considerably, stopped, or even partially reversed in humans by dietary geroprotection, that is, by foods containing ingredients that promote health? The nutritional “ErdBEHR” (“Erdbeeren [strawberries] for Biomarker identification for the Extension of Health by Rejuvenation”) trial reported here was designed to approach these questions for polyphenol-rich food, for which some observational and interventional evidence of positive health effects has been described. Polyphenols are natural organic compounds; frequently studied polyphenols are, for example, catechins, stilbens (e.g., resveratrol), and quercetin, which are found in a variety of plant-based foods. In particular, epidemiologically, health improvements in the Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets are attributed in part to their high polyphenol content1. Moreover, short- and long-term consumption of polyphenol-rich berries such as strawberries has been associated with a variety of health improvements in previous human studies, with a focus on cardiovascular disease2.

Here, we studied a food-based high-polyphenol intervention based on strawberries, including capers in olive oil in the highest-intervention group. Previously, strawberries were found to contain the polyphenol fisetin that extends healthspan and lifespan in mice3, and capers include the closely related polyphenol quercetin4. Both polyphenols are frequently mentioned in the literature on interventions aiming at removing senescent cells5. As described in Box 1 (see supplementary files), we found ample amounts of quercetin in both strawberries and capers. Further bioactive ingredients in strawberries are other polyphenols such as pelargonidin (an anthocyanin responsible for red color), fibers, vitamins, and phytosterols6. Furthermore, olive oil is also known for its health benefits on lipid metabolism and cardiovascular function and for reducing mortality, due in part to the polyphenols hydroxytyrosol and oleuropein7.

We had three hypotheses: (a) an intervention with fresh strawberries would trigger improvements in the overall cardiovascular risk profile, specifically cholesterol and inflammation status; (b) the intervention would be further ameliorated by adding “seno-intervention days” (SIDs), on 3 single days over the entire 10-week study participation, whereby large but not excessive amounts of freeze-dried strawberries (and, in the highest-intervention group, also capers in olive oil) are consumed; and (c) SIDs would trigger the apoptosis of senescent blood cells, leading to improvements by eliminating these cells. These improvements could, in part, also be seen as hormetic, triggered by the repair reaction of the body based on the effects of the intervention, resulting in benefits as long as the intervention dose is not too high.

As primary endpoints, we prespecified low-density lipoprotein (LDL) cholesterol and high-sensitive C-reactive protein (hsCRP) in the ethics application (see supplementary files), based on our literature survey2 and a pilot study (see below). We also measured a set of secondary and exploratory endpoints, including gene expression by next-generation sequencing (transcriptomics). We observed no safety issues except self-reported potential allergy in two cases. We met the primary LDL endpoint in the highest-intervention group, culminating a dose-response trend over all intervention groups, which was even stronger for total cholesterol (TC). We found anti-inflammatory effects in the high-intervention groups, superimposed by a pro-inflammatory pattern in the highest-intervention group, just after the last SID, which we attribute to apoptotic processes based on the gene expression data. Hypothetically, the highest-intervention SID enabled the killing of senescent blood cells, an exciting proposition deserving further research. Since polyphenols may interact with medication8,9 (Box 2, see supplementary files), the study was performed on healthy individuals.

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