This is how Professor Fulvio Ursini’s position on the relationship between alcohol and cancer can be defined, which we bring to you. And to make you understand “from what pulpit” we add his impressive academic record.
Fulvio Ursini, born in 1951, is. Professor Emeritus of Biological Chemistry at the University of Padua. He graduated in Medicine and Surgery in Padua with subsequent specialization in Internal Medicine at the same university, and has been Full Professor of Biological Chemistry at the University of Udine (Food Science and Technology)., from 1990 to 1996, then at the Faculty of Medicine at the University of Padua where he directed the School in Food Science.. It has been Adjunct Professor of Biochemistry at USC Los Angeles..
A common thread throughout his academic career has been the study of the antioxidant effect. This research has helped clarify the relationships between chemistry, biochemistry and cell biology of free radical oxidations, integrating the information produced by basic science in a context of nutrition and medicine. He discovered the enzyme that primarily accounts for the nutritionally essential biological effect of selenium. As part of studies on radical reactions, he described postprandial oxidative stress and its link to the protective role of antioxidant-containing foods: fruits and vegetables and not least wine.
He first proposed the adaptive mechanism of para-hormesis to explain how the increase in antioxidant defenses is triggered by contained oxidations acting as a signal that activates the response. It has been founder and co-organizer of the Wine & Health Congress series held between 1995 and 2016 in Italy, France, USA, Chile, South Africa, Australia, and Spain. He is a member of the Confrérie des Chevaliers du Tastevin (Baune, Burgundy) and the Academy of Life and Wine (Conegliano).
The following is his talk on a topic that is as hot as it is topical.
Limits of EBM in Cancer Risk Assessment: Nutrition, Ethanol, Wine and Hormesis
by Fulvio Ursini, University of Padua
The evidence-based medicine (EBM) has played a key role in the understanding of cancer prevention and treatment, but it has significant limitations when it comes to addressing the evolving and complex nature of risk when you want to trace it back to a single variable. These limitations are particularly evident when considering factors such as the nutrition which, by including ethanol as a nutrient, introduce nonlinear dose-effect dynamics in risk assessment. U- or Y-curves cannot be the same in different populations with different dietary behaviors, and when analyzed overall on a very large scale, they flatten out leading to a artificial linearity which in turn supports a deterministic conclusion in the dose-effect relationship. Just as an example, it is on the basis of approaches of this nature that it has been concluded that even a single glass of wine increases the risk of breast cancer!
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Nonlinear Dynamics in the Risk of Cancer
The development of cancer is a dynamic and multifactorial process, influenced by genetic mutations, environmental exposures, and stochastic events. Unlike the deterministic models often inferred in EBM, cancer risk evolves in a nonlinear fashion, where small changes in one factor can have large effects. For example, dietary factors such as different forms of alcohol intake do not uniformly influence risk; their impact is modulated by genetics, metabolism, and a host of other behavioral variables.
EBM, which relies primarily on linear cause-effect relationships derived from epidemiological studies of large and heterogeneous populations, cannot capture the complexity of these interactions. The most relevant example is to use in risk calculations weekly alcohol intake without any timing or relationship to meals and in the disregard the nature of the alcoholic beverage whereby vodka is equated with wine only in terms of alcohol content.
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Hormesis and Nutritional Influence
The concept of hormesis – where low doses of substances that are typically harmful in experimental models or in humans at high doses can have beneficial effects at low doses-is opposed to the deterministic approach of EBM. Added to this is the effect of other components, such as. The largely protective effect of wine polyphenols, completely ignored in the analysis of large populations. These dose-dependent interactions cannot be fully explained by the traditional EBM framework, which only highlights the average responses of very large populations neglecting critical elements even relevant ones often seen as “confounding factors.”
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Dual Role of Ethanol in Cancer Risk.
Excessive ethanol consumption is an established risk factor for various cancers, but its carcinogenic effects vary widely depending on genetic factors, metabolic pathways, and exposure to other dietary components. While high alcohol consumption contributes to cancer through mechanisms such as acetaldehyde-induced DNA damage, moderate consumption can trigger well-known cellular responses that are protective by activating adaptive mechanisms. This phenomenon is compounded by the primary protective role of polyphenols in wine. The deterministic approach of EBM fails to adequately consider this complexity, as it ignores the variability and dose-dependent risks posed by different dietary habits in alcoholic beverage intake when placed in a complex and varied nutritional context in different populations.
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Toward a More Integrated Understanding of Cancer Risk and the Formulation of Nutritional Recommendations
To more effectively address the cancer risk, there is a need to integrate insights from evolutionary biology, stochastic processes and hormesis with EBM. A more holistic approach should consider in addition to alcohol intake. How nutrition and nonalcoholic beverage components, e.g., wine, interact with genetic factors. An approach that should once again confirm how moderate-level exposures have clear protective effects compared with abstention. This integrated model would go beyond the linear assumptions of EBM, noting the complexity of the evolution of the biological phenomenon. What is then to be avoided would be the frequent paternalistic attitude, supported by an EBM produced by the analysis of large and heterogeneous populations, in imposing rules on behavior. Ethically, the tendency to scare with numbers, moreover questionable, to control the life habits of individuals seems unacceptable.
Conclusion:
Although EBM has provided important guidelines for cancer treatment and prevention, it proves inadequate when applied to the intricate and nonlinear nature of cancer risk, in case we analyze the role of ethanol forgetting the nature of the alcoholic beverage and the relevance of hormesis. Cancer is not a static and predictable disease, but an evolving process shaped by genetic variability, environmental exposures, and chance events.
To improve our understanding and management of cancer risk, we should adopt a more multifaceted approach that includes stochastic models and recognizes the beneficial effects of hormetic exposures from nutrition and the environment. This change, which of necessity will also need to consider the results of nonclinical basic research, will enable more personalized and effective prevention strategies that better reflect the true complexity of cancer biology Avoiding harmful as well as unnecessary prohibition.
