**1. Introduction**

*The Tower of Babel Model: A Challenge for Pharma-Food Science Communication on EVOO Polyphenols*

Nowadays, there is considerable attention toward the functional properties of extra virgin olive oil (EVOO), the main product obtained from olives, fruits that come from evergreen trees [1,2]. EVOO is a characteristic element of the Mediterranean diet (MD) because of the health-beneficial effects deriving from its chemical composition [3–5] as well as its appreciable taste and usefulness in flavoring a large variety of foods.

The overall literature studies report a wide variety of chemical and enzymatic analyses in vitro, in vivo, and ex vivo to reveal the beneficial effects of EVOO polyphenols on human health. EVOO is one of the foods naturally rich in polyphenols and is the main lipid source in MD. Numerous scientific papers and reviews have shown that the potential health benefits of EVOO are correlated to its high content of functional compounds such as polyphenols, tocopherols, carotenoids, sterols, fatty acids, and squalene. This specific

**Citation:** Clodoveo, M.L.; Muraglia, M.; Crupi, P.; Hbaieb, R.H.; De Santis, S.; Desantis, A.; Corbo, F. The Tower of Babel of Pharma-Food Study on Extra Virgin Olive Oil Polyphenols. *Foods* **2022**, *11*, 1915. https:// doi.org/10.3390/foods11131915

Academic Editor: Marco Poiana

Received: 25 May 2022 Accepted: 24 June 2022 Published: 28 June 2022

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chemical composition helps to prevent the incidence of multiple diseases such as cardiac, vascular, neurodegenerative, metabolic, and inflammatory ones [1,6–9].

In agreemen<sup>t</sup> with Visioli et al. [10], there is an urgen<sup>t</sup> need to provide unequivocal scientific evidence that can rationalize EVOO consumption, as an integral and essential part of a balanced diet and healthy lifestyle, to quality of life in terms of prevention and health maintenance. In fact, despite an exorbitant number of papers, only one effect of the EVOO polyphenols has been officially accredited as a health claim by the European Food Safety Authority (EFSA).

The need for new research able to deal systematically with the issue of phenolic compounds present in EVOO and the related actions on human health is confirmed by the fact that many of the requests of authorization to apply health claims on EVOO health effects have received a negative scientific opinion from the EFSA. The latter could be ascribed to different reasons, including the insufficient characterization of food constituent(s), the lack of beneficial physiological effects of the proposed claimed effect, and, most of all, the quality of the studies provided for the scientific substantiation of the claims. Among the numerous olive oil claims that were submitted to EFSA, only one was allowed: "Protection of LDL particles from oxidative damage" [11]. Specifically, the panel based its decision on "a well-conducted and powered study, and two smaller-scale studies that showed dosedependent and significant effects of olive oil polyphenol consumption (for three weeks) on appropriate markers of LDL peroxidation (oxLDL)".

Moreover, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) considered that the quantity of olive oil required to obtain the claimed effect is 20 g (two tablespoons) containing at least 5 mg of hydroxytyrosol and its derivatives (e.g., oleuropein complex and tyrosol). This can reasonably be consumed within a balanced diet, and the proposed wording (although the terminology can be considered excessively technical and not fully understandable for most consumers) reflected the scientific evidence, complying with the criteria for the use of claims specified in the EU Regulation 1924/2006 [11,12].

However, no other health claim on EVOO polyphenols has been approved by the competent authorities to date. The critical and objective analysis of this result reveals that most of the scientific investigations so far aimed at highlighting the health value of polyphenols in EVOO have not met the requirements for the authorization of a novel health claim while denouncing the inappropriate choice of investigative tools and the insufficient evidence provided to establish a cause–effect relationship between the daily consumption of polyphenols in EVOO and the claimed beneficial effect.

This evidence sheds new light on the need to bring together skills belonging to different scientific areas, from food sciences to medical sciences, in a context of skills that still do not communicate effectively due to excessively clear boundaries between the different methods of investigation and specific languages of each discipline. To achieve a better understanding of the real potential beneficial effects of EVOO polyphenols on consumers' health and well-being, there is a need to create osmotic communication among different scientific areas, building bridges through a clear evaluation of the information coming out from the various methodologies of investigation in each step of health benefits assessment. The failure rate of applications for the approval of health claims concerning EVOO is enormous compared to the intellectual, human, and financial resources spent to prepare the application reports supporting the cause-and-effect relationship. Unfortunately, science, focusing on bridging information deficits about the health value of EVOO polyphenols, has underestimated the need to rework its communication models to overcome regulatory difficulties in favor of valuing the health claims of EVOOs.

Therefore, this circumstance represents clear evidence of the need to point out some aspects concerning the EVOO phenols, such as the mechanisms of action and the laboratory methods used to identify, quantify, and test the antioxidant and anti-inflammatory properties; these analytical tools need to be critically evaluated to verify their method of defining the mechanisms of action and their practical utility in the transfer of information in the subsequent phases of the cause-dose-effect evaluation, when the tests on humans

will have to confirm the studies of drug dynamics, pharmacokinetics, and the potential toxicity, to define the effective dose and limitations of use.

However, each research tool has a different efficacy in the health benefit validation process. Most of them need to be harmonized to accelerate the progression of functional food research through a highly active interconnection with related fields.

The challenge for communication across scientific fields, then, is not to discuss which experimental protocol to adopt to improve the health value of EVOO, but to link scientific knowledge and expertise in a transdisciplinary way by making it objective, meaningful, reproducible, and transferable to public health policy authorities.

Thus, cross-science intellectual fertilization is needed, overcoming the current stratification of the various scientific fields through a fluid and osmotic communicative process among stakeholders. Herein, we purpose the Tower of Babel as a metaphor for a scientific approach made of different disciplines and backgrounds that need to be integrated by the synthesis of methodological procedures which draw upon more than one scientific area, challenging conventional disciplinary approaches to generate the emerging sector of pharma-food research (Figure 1).

**Figure 1.** The metaphor of the Tower of Babel of the functional food research sector.

A specialized disciplinary language favors more efficient intra-disciplinary communication but is a tool that excludes outsiders in a particular field. Thus, the Tower of Babel is also a metaphor for different forma mentis. In this regard, a meta-disciplinary awareness is necessary, as the ability to think about the goals, methods, and forms of communication of disciplines harmonizes the focus of disciplinary knowledge and inquiry, and recognizes the roles and constraints imposed by individual disciplines in the goal attainment.

In this work, we report an overview of the main methodologies adopted by the different disciplinary areas involved in characterizing the polyphenolic and antioxidant profile of EVOOs and evaluating the antioxidant and anti-inflammatory properties potentially useful for obtaining a health claim. This paper aims to sugges<sup>t</sup> a strategic, unique, and efficient integration of cross-disciplinary expertise and technology in a harmonized workflow (Figure 2), organized to build factual understanding that can be translated thanks to industry into consumer health benefits, by marketing EVOOs as having certified health benefits, and not only as seasonings.

**Figure 2.** Workflow for pharma-food study on extra virgin olive oil polyphenols.
