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IVES 9 IVES Conference Series 9 OIV 9 OIV 2024 9 Orals - Safety and health 9 Pharmacological basis of the J-shaped curve in biological effects of wine

Pharmacological basis of the J-shaped curve in biological effects of wine

Abstract

The classical pharmacological model assumes that the effect of a drug is proportional to the fraction of receptors occupied by the drug. In the simplest circumstances, the relationship between dose of a drug and response, when plotted on a logarithmic scale for drug concentration, is described by a sigmoidal curve. It presumes the existence of a threshold dose, below which no biological effect appears, and a maximal response in the form of a plateau, when a further increase in the dose of drug has no effect. In this mathematical  concept, however, exceptions are quite common, and different  theories and models have been proposed to explain those exceptions.  In contrast to the standard pharmacological model, in real life it is commonly seen that different compounds exhibit opposite effects as a function of dosage.  The phenomenon of small quantities having effects opposite from that of large quantities is commonly termed “hormesis”. The hormetic type of dose-response relationship may be described as an inverted U-shaped or a J-shaped dose response. Whether the dose response is an inverted u- or j-shape is determined by the endpoint that is measured.  In the context of human nutrition, the hormetic biphasic effects of alcohol consumption on human health has been particularly well studied.  In the case of wine, there are two principal constituents that are considered responsible for the majority of wines’ biological effects: alcohol and phenolic compounds. On the example of results from two different experimental models with different endpoints, it will be shown in this presentation, that both alcohol and wine phenolics obey the hormetic biphasic dose-response relationship. This corresponds well with the epidemiological finding of the J-shaped dose-response association of wine consumption with different diseases and total mortality.

Pharmakologische grundlage der J-förmigen kurve in den biologischen wirkungen von wein

Das klassische pharmakologische modell geht davon aus, dass die wirkung eines arzneimittels proportional zum anteil der vom arzneimittel besetzten rezeptoren ist. Im einfachsten fall wird die beziehung zwischen der dosis eines arzneimittels und seiner reaktion, wenn es auf einer logarithmischen skala für die arzneimittelkonzentration aufgetragen wird, durch eine sigmoidkurve beschrieben. Es geht davon aus, dass es eine schwellendosis gibt, unterhalb derer keine biologische wirkung auftritt, und eine maximale reaktion in form eines plateaus, bei dem eine weitere erhöhung der arzneimitteldosis keine wirkung zeigt. In diesem mathematischen konzept gibt es jedoch recht häufig ausnahmen, und zur erklärung dieser ausnahmen wurden unterschiedliche theorien und modelle vorgeschlagen. Im gegensatz zum pharmakologischen standardmodell zeigt sich im wirklichen leben häufig, dass verschiedene verbindungen je nach dosierung gegensätzliche wirkungen zeigen. Das phänomen, dass kleine mengen entgegengesetzte wirkungen wie große mengen haben, wird allgemein als „hormesis“ bezeichnet. Die hormetische art der dosis-wirkungs-beziehung kann als eine umgekehrt u-förmige oder j-förmige dosis-wirkungs-beziehung beschrieben werden. Ob die dosisreaktion eine umgekehrte u- oder j-form hat, wird durch den gemessenen endpunkt bestimmt. Im kontext der menschlichen ernährung sind die hormetischen biphasischen auswirkungen des alkoholkonsums auf die menschliche gesundheit besonders gut untersucht. Im fall von wein gibt es zwei hauptbestandteile, die für die meisten biologischen wirkungen von weinen verantwortlich sind: alkohol und phenolische verbindungen. Am beispiel der ergebnisse zweier unterschiedlicher versuchsmodelle mit unterschiedlichen endpunkten wird in diesem vortrag gezeigt, dass sowohl alkohol- als auch weinphenole der hormetischen biphasischen dosis-wirkungs-beziehung gehorchen. Dies entspricht gut dem epidemiologischen befund des j-förmigen dosis-wirkungs-zusammenhangs von weinkonsum mit verschiedenen krankheiten und der gesamtmortalität.

Basi farmacologiche della curva J negli effetti biologici del vino

Il modello farmacologico classico presuppone che l’effetto di un farmaco sia proporzionale alla frazione di recettori occupati dal farmaco. Nelle circostanze più semplici, la relazione tra la dose di un farmaco e la sua risposta, quando rappresentata su una scala logaritmica per la concentrazione del farmaco, è descritta da una curva sigmoidale. Si presuppone l’esistenza di una dose soglia, al di sotto della quale non si manifesta alcun effetto biologico, e una risposta massima sotto forma di plateau, quando un ulteriore aumento della dose del farmaco non ha alcun effetto. In questo concetto matematico, tuttavia, le eccezioni sono abbastanza comuni e sono state proposte diverse teorie e modelli per spiegare tali eccezioni. Contrariamente al modello farmacologico standard, nella vita reale si osserva comunemente che diversi composti mostrano effetti opposti in funzione del dosaggio. Il fenomeno delle piccole quantità che hanno effetti opposti a quello delle grandi quantità viene comunemente chiamato “ormesi”.  Il tipo ormetico della relazione dose-risposta può essere descritto come una risposta alla dose a forma di U invertita o a forma di J. Se la risposta alla dose è a forma di u invertita o di J è determinato dall’endpoint misurato. Nel contesto della nutrizione umana, gli effetti ormetici bifasici del consumo di alcol sulla salute umana sono stati particolarmente studiati. Nel caso del vino, sono due i principali costituenti considerati responsabili della maggior parte degli effetti biologici del vino: l’alcol e i composti fenolici. Utilizzando l’esempio dei risultati di due diversi modelli sperimentali con endpoint diversi, in questa presentazione verrà mostrato che sia i composti fenolici dell’alcol che quelli del vino obbediscono alla relazione ormetica bifasica dose-risposta. Ciò corrisponde bene con il risultato epidemiologico dell’associazione dose-risposta a forma di J del consumo di vino con diverse malattie e mortalità totale.

Publication date: November 18, 2024

Issue: OIV 2024

Type: Article

Authors

Mladen Boban¹

¹ University of Split, School of Medicine, Šoltanska 2, Split, Croatia

Contact the author*

Tags

IVES Conference Series | OIV | OIV 2024

Citation

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