Antioxidants in foods and their effects on cardiovascular disease

An antioxidant (AO) can be defined as any substance that, when present at a concentration lower than that of an oxidizable substrate, significantly slows down or inhibits the oxidation of the substrate itself (Halliwell and Gutteridge, 1999). It is clear that the definition is exclusively functional, and that this class of compounds includes substances with highly diverse structures. In addition, while a classical distinction between AO considers only water-soluble and lipid-soluble compounds, a wide range of compounds with potent AO properties in various systems, but also with additional effects on various cellular functions (e.g. interactions with enzymes), is characterized by amphiphilic features. This type of characteristic is not generally considered in describing AO compounds.

Actions of antioxidants

Removal of oxygenRemoval of ions with catalytic activitiesRemoval of key intermediates in the oxidation processTrapping of initiating radicalsChain-breakers

The main actions of antioxidants are listed above. The contexts in which antioxidants operate may differ as follows.

The past decades have brought about major changes, both in quantitative and qualitative terms, in our way of eating. Before the Second World War, food, mainly as unprocessed natural food items, was purchased in relatively small quantities, to be consumed quickly, stored for short times, in the presence of unsophisticated refrigeration systems, and cooked by few experienced persons in a family. In recent times, instead, foods are purchased and stored in bulk, as LSV (oils or solid fats, artefacts introduced by humans), which tend to oxidize at the surface, or, frequently, as fast foods, preprocessed mechanically or by heat or freezing. The antioxidant actions in LSV systems are based mainly on the presence and activities of a few natural antioxidants, such as tocopherols, carotenoids and, in special conditions, glutathion and ascorbic acid. Some antioxidant compound from natural sources, however, have been shown to be antioxidant in bulk lipids, but do not function as antioxidant in tissues.

The main natural antioxidants acting in LSV systems are hydrophilic phenols, such as the tocopherols. They are true membrane, organelle and adipocyte, or oil droplet antioxidants, since this is the way lipids are displayed in natural tissues. Supporting the tocopherols is the reductive glutathione±ascorbic acid cascade. The tocopherols show some paradoxical behaviour: a-tocopherol is almost ineffective in vegetable oils, modestly effective by itself in animal fats, but more effective, even, than the synthetic antioxidants buthyl hydrox anisole (BHA) and buthyl hydroxy tyrosol (BHT), in HSV situations (Porter, 1993). In bulk oils the effectiveness of tocopherols in the descending order is S, -y, a and a, the opposite of the order predicted from common indexes (e.g. reduction potential).

A general feature of antioxidants in natural foods, especially from plant sources, is that most of them (e.g. phenolics) are produced as protective compounds against several stressful conditions (oxidative and other), and are present as complex mixtures, with somewhat diversified functional features (redundance) and in given quantitative proportions. Some of the latter properties are transferred to animals through the food chain.

The generation of oxygen-derived radicals in biological systems, through cell-independent and cell-mediated processes, results in the production of a variety of oxidation products, generated from lipids, proteins, nucleic acids and sugars. Owing to the complexity of the processes leading to substrate oxidation, it is relevant that the antioxidant defence strategies in biological systems are generally highly evolved. In fact, although several complex biological molecules (e.g. lipoproteins) are quite susceptible to oxidation in vitro, i.e. after isolation from biological systems, they are instead rather resistant to oxidative stress in the physiological medium (plasma).

Also, cells in vivo appear to behave rather differently, with respect to susceptibility to ROS, from cultured cells, frequently used for several types of studies. Cells in culture are often exposed to unphysiological states of oxidative stress, while being depleted of AO (Visioli et al., 2000), and the consequence is that effects are produced that are largely artefactual owing to an abnormal generation of ROS. Several studies on the effects of antioxidants may therefore have been affected by these artefacts (Halliwell, 2003).