Nutrition, hormetic stress and health

Abstract

Hormesis defines an effect where exposure to a low dose of a toxic agent results in a beneficial response. It has been described in organisms exposed to low-dose radiation, heat stress, and chemicals. The effect is characterised by a J-shaped dose-response as opposed to a linear doseresponse. Confirmation of the general phenomena of hormesis has proved difficult due to the lack of appropriate methodology and the absence of well-defined mechanisms to support the experimental observations. In the nutritional field there are few reports of its existence. The clearest illustration of the effect is seen in animals that are energy restricted when there is a clear benefit in the reduction of age-related disease, and an extension of maximum lifespan. DNA microarray experiments have shown that there is a down regulation of the stress-response genes that are up regulated through the ageing process. Electrophilic phytochemicals, that have been shown to have beneficial health effects at low doses, up regulate the antioxidant -electrophile response element. This probably occurs through an alteration in the redox state of the target cells which causes activation of protein kinases, the activation of the Nrf2 transcription factor and the up regulation of the phase II enzymes, similar to responses that occur under mild chemical stress. This situation might enable organisms to adapt to stress such that the effects of a subsequent exposure to a harmful challenge are reduced. There may be a permanent alteration in cellular homeostasis, or redox state, if the low level exposure is maintained. It remains to be proven if such a situation occurs in response to chronic low-dose exposure to dietary phytochemicals such that the target cells are better able to respond to a subsequent stress challenge.

Dietary isoflavones and vascular protection: Activation of cellular antioxidant defenses by SERMs or hormesis?

“…However, many studies have reported use of high micromolar concentrations in both in vitro and ex vivo experimental models which exceed the serum concentrations that can be achieved by isoflavone consumption (Setchell, 1998;Mann et al, 2009). The ability of isoflavones to alter the redox state of cells, leading to activation of intracellular kinases and Nrf2/ARE-linked antioxidant enzymes, may underlie the adaptation of vascular and other cell types to environmental and dietary stresses (Lindsay, 2005). However, the clinical evidence for therapeutic benefits of long-term isoflavone supplementation on vascular redox homeostasis remains to be established (Hooper et al, 2008;Reynolds et al, 2006).…”

“…Estrogen and isoflavones acutely activate intracellular kinases linked to gene transcription (Mahn et al, 2005;Joy et al, 2006;Siow et al, 2007;Mann et al, 2007;Borras et al, 2006) and inhibition of NADPH oxidase mediated superoxide production (Xu et al, 2004). In view of their non-genomic actions on kinase signaling pathways (Joy et al, 2006;Mann et al, 2007;Martin et al, 2008) and the mitochondrial respiratory chain (Fuchs et al, 2007;Rasbach and Schnellmann, 2008;Borras et al, 2010), it is likely that hormetic properties of isoflavones play a significant role in mediating longer-term cardiovascular protection (Lindsay, 2005;Son et al, 2008).…”

Bioflavonoids as Important Component of Biological Protection from Ionizing Radiation

“…474 mental chronic stress under the influence of pharmacological agents is from a classic study by Selye [44] and additional research in this area, including studies investigating into the formation of different adaptive stages, depending on the strength and duration of the impact of adverse environmental factors [45][46][47].…”

Hormetics: Dietary Triggers of an Adaptive Stress Response

“…Last but not least, ROS mediate the adaptive stress response of cells. This concept, often termed as hormesis, was addressed recently by excellent reviews in a comprehensive manner (9)(10)(11)(12)(13)(14). This review will give a brief introduction into small molecules within our diet that induce an adaptive stress response and thereby act as indirect antioxidants.…”