The phenomenon of hormesis also applies to plant ‘toxins’. Everyone is familiar with the recommendation (from the National Nutrition and Health Programme) to eat at least five portions of fruit and vegetables a day.
Why are they good for your health? Because they contain antioxidants that neutralise toxic free radicals, which are unstable (constantly seeking to gain or lose an electron). Unfortunately, things are not quite that simple. When antioxidants, such as vitamins C, E and A, are isolated and their effects assessed in animals and humans, no benefit is observed in terms of preventing or alleviating diseases.
So what is the ‘secret’ of plants?
To understand this, we need to look at the defence strategies developed by plants over the course of evolution. Plants produce bitter-tasting molecules that act as natural repellents, protecting them from insects and other animals that try to eat them. When we consume plant-based foods, we ingest these molecules in small quantities. They cause mild stress within the body’s cells (the same kind that occurs when we fast or exercise). This moderate stress does not kill the cells; quite the opposite: it makes them stronger! Friedrich Nietzsche (1844–1900) had already written this in 1888 in *The Twilight of the Idols, or How to Philosophise with a Hammer*: ‘What does not kill me makes me stronger’.
The ability of cells to adapt to greater stress, such as oxidative stress caused by free radicals, is thus enhanced. However, certain plant-derived molecules, which are toxic in high doses, can be beneficial: this is where the phenomenon of hormesis comes into play.
When the effects of these substances are measured, a biphasic response is observed. The following graph illustrates the nature of the effects as a function of dose, a phenomenon depicted by a bell-shaped curve. The curve initially rises, indicating that consuming a small amount of the substance has beneficial effects; it then falls, illustrating the fact that larger quantities are toxic.
Thus, consuming too many Brazil nuts (Bertholletia excelsa) risks poisoning the liver and lungs due to the presence of selenium (1 ppm), whilst eating small quantities provides an essential nutrient (helping to prevent heart disease and cancer).
Molecules that induce hormesis are ubiquitous in the plant kingdom: caffeine, opiates, turmeric [a spice extracted from the rhizome of the plant of the same name (Curcuma longa)], catechin (tea) and capsaicin from chillies (compounds that induce the opening of channels in the outer membrane of neurons).
Hormetic plant substances appear to play a role in the interactions between free radicals and antioxidants. Turmeric does not act directly by neutralising free radicals; rather, it recruits enzymes to help cells protect themselves against them. This carefully synchronised process would explain why antioxidant treatments in the form of supplements are ineffective or even counterproductive.
Gradually, the biochemical pathways involved in responses to plant toxins are becoming clearer. One of these involves two proteins, Nrf2 and Keap1, which are normally bound to one another in the cytoplasm. When these proteins are exposed to substances such as turmeric or sulphoraphane from broccoli, Keap1 releases Nrf2, which enters the cell nucleus. There, the protein activates genes encoding antioxidant enzymes that eliminate free radicals.
Another pathway involved in cellular defence involves a family of proteins known as sirtuins. One of these, SIRT1, increases the lifespan of yeast. Resveratrol, found in black grapes and wine, appears to activate SIRT1, which in turn triggers multiple chemical pathways responsible for hormetic effects.
This molecule is thought to improve patients’ memory – albeit modestly – by increasing the concentration of acetylcholine (a neurotransmitter) in the cells. It induces a certain amount of stress in the neurons, which appears to protect them from neurodegeneration whilst enhancing their ability to use molecules and electrical signals to communicate.
References:
MATTSON M. 2017. Les bienfaits des toxines végétales sur le cerveau. Pour la Science. 472. 54-59.