• DOI:10.1177/0960327110383623
• Corpus ID: 34683050

Resveratrol: An assessment of its dose response an introduction

@article{Calabrese2010ResveratrolAA,
  title={Resveratrol: An assessment of its dose response an introduction},
  author={Edward J. Calabrese},
  journal={Human \& Experimental Toxicology},
  year={2010},
  volume={29},
  pages={977 - 979}
}

• E. Calabrese
• Published 1 December 2010
• Biology
• Human & Experimental Toxicology

Resveratrol has become a major focus of biomedical research over the past two decades. This interest was initially based on reproducible epidemiological investigations showing an inverse relationship between the consumption of red wine and various types of cardiovascular disease. According to the Web of Science Database the first citation of resveratrol was in 1977. Scientific interest in resveratrol grew slowly with approximately 200 cumulative citations over the next 15 years. However, from the mid-1990s to the present, this field has expanded considerably. For example, in the year 2001 alone, there were nearly 3100 citations concerning resveratrol. In 2009, this number had jumped to nearly 18,000 (Figure 1) with 2010 projected to easily exceed 20,000 citations. These citations are based on the publication of now over 5000 articles on resveratrol in the biomedical literature (Figure 2). While the initial biomedical interest in resveratrol focused on its implications for cardiovascular health, research interest has broadly expanded, now involving a plethora of biological endpoints and disease conditions that may be affected by consumption of resveratrol. These areas are very broad and significant, affecting neurodegenerative diseases, immunological responsiveness, a broad spectrum of cancers, and the aging process, amongst others. These findings have lead to numerous efforts to explore how resveratrol can be used to enhance the public health. Despite this rather striking proliferation of research on the biomedical and public health implications of resveratrol, there has been a surprising lack on focus on the nature of its dose response and how this type of information could guide both research activities as well as recommendations concerning the consumption of resveratrol. Clarification of the nature of the dose response for resveratrol is therefore an important consideration. The nature of the dose response in toxicology and pharmacology has become a topic of considerable interest. During the past century, the fields of toxicology and pharmacology came to accept the assumption that the most fundamental nature of the dose response was that of a threshold. Despite never validating this assumption via scientific evaluation, regulatory agencies in the middle decades of the 20th century adopted the use of the threshold model and built major regulatory programs based on it. The only exception to this general dose response perspective was the introduction of linearity at low-dose modeling for genotoxic carcinogens, a perspective based principally on a public health protectionist philosophy in the late 1950s for ionizing radiation and the late 1970s for chemical carcinogens. However, over the past two decades, acceptance of these 2 dose response theories (i.e., the threshold model and the linear at low dose model) have been challenged by the hormetic dose response model. These findings indicate that the biphasic hormetic dose response was very common and highly generalizable, being independent of biological model, endpoint measured, and chemical class. Furthermore, in head-to-head competition, the hormetic dose-response model has repeatedly far outperformed the threshold and linear doseresponse models in making accurate predictions of biological responses in the low-dose area. These findings lead to the conclusion that the hormetic dose response is more fundamental, common, and generalizable than the threshold and linear dose-response models. It also strongly suggested that the hormetic