Throughout these last two decades, antioxidants have come to be considered from "simple free radical scavengers" (decade of the 90's) to "molecules whose consumption would be synonymous with health" (last decade). Three aspects have had a major impact on this conceptual transition:
Firstly, the recognition that oxidative stress, understood as "imbalance between the speed of production and the speed of free radicals removal", constitutes a common denominator and causal factor of some of the chronic noncommunicable diseases (CNCD) that currently more affect the world population, that is, cardiovascular, tumor and neurodegenerative pathologies (Figure I).
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A second aspect that has helped to build the aforementioned conceptualization around antioxidants, is the experimental recognition that -in animal models of pathologies associated with oxidative stress- the administration of antioxidants not only inhibits the onset of oxidative stress, but also it also delays and / or prevents the development of some of the ECNT associated with this condition (Figure II).
Finally, a third type of observation that has prompted the assumption that "the consumption of antioxidants is synonymous with health", is the accumulation of evidence -mainly the epidemiological type- that the relative risk (RR) of development and / or death by ECNT as mentioned above correlates inversely with the intake of foods rich in antioxidants (such as fruits and vegetables) by the population.
As it is included in the section "Antioxidants in food: main sources and contents" , within our diet, fruits and vegetables stand out among the foods that concentrate the most and contribute antioxidants to our body. While fruits and vegetables are true vectors of: antioxidant vitamins, carotenoids and polyphenols, from a nutritional point of view, only antioxidant vitamins (C, E, and pro-A), and not polyphenols, are really essential.
Antioxidant vitamins and relative risk of ECNT development . Based on its essentiality, and epidemiological evidence that shows that a higher consumption of "foods rich in antioxidant vitamins" is associated with a lower incidence of certain NCDs, in the early 90's, and as a way to reduce the relative risk (RR) of development of such diseases (mainly cardiovascular and tumor), a series of intervention studies were initiated in which the diet of some sub-populations under study with high doses of antioxidant vitamins was supplemented. Today, after almost two decades since the beginning / execution of this type of research, it is possible to affirm that among all the controlled clinical studies, with the exception of a few, the majority leads to the conclusion that "there is still no scientific evidence that merit the use of supplements with high doses of antioxidant vitamins as a way to reduce the RR of development and / or death by ECNT. "
In a manner consistent with the above, at present, most international entities (eg IARC , WCRFI , AHA ) linked to health promotion and / or conservation refrain from recommending the use of high-dose supplements. of antioxidant vitamins as a way to prevent the development of ECNT. Furthermore, recently, through the use of meta-analysis (a powerful statistical technique that allows us to jointly analyze studies that produce results that do not necessarily coincide), it has been suggested that until now, a part of the studies carried out has not only failed to support the "promise that supplements with high doses of antioxidant vitamins would reduce the RR of developing ECNT", but, contrary to expectations, in certain groups of individuals, the consumption of such preparations could increase this risk and affect an increase of mortality. Consequently, the only recommendation of consumption that, up to now can be made, and that is clear from the available scientific evidence, is to increase the consumption of fruits and vegetables, and especially those that concentrate more antioxidants.
It should be mentioned, however, that the supplements may be of clear use when, based on professional diagnoses, they are prescribed to individuals who show an established lack and / or deficiency of said vitamins.
Polyphenols and relative risk of ECNT development . It should be clarified that the results of intervention studies with supplements based on high doses of antioxidant vitamins referred to above do not imply that antioxidant vitamins, being present in fruits and vegetables, will not play an important role in the benefits for the health that are strongly associated with a greater consumption of this type of food.
Along with being a good source of antioxidants, some fruits and vegetables are also a good source of other vitamins, fibers, numerous micro- and macro-minerals, and a wide range of phytochemicals (bioactive compounds of plant origin). ). Within the framework of the hypothesis that states that "the health benefits associated with the consumption of fruits and vegetables rich in antioxidants are primarily related to the contribution of antioxidants that suppose the consumption of such foods", it is worth asking: What others? antioxidant compounds could be attributed the health benefits associated with increased consumption of fruits and vegetables?
Due to its abundance and its recognized bioactivity, among the phytochemicals present in fruits and vegetables, polyphenols stand out. Although some of these compounds possess, among others, anti-inflammatory, vasodilator, antiplatelet-antiplatelet, antimutagenic and antimicrobial properties, within the framework of the hypothesis that involves oxidative stress as a causal factor of ECNT development, the antioxidant property they exhibit all polyphenols, and that allows them to oppose the action of free radicals and other reactive species, has emerged as the most important to explain the health benefits of consuming foods rich in these compounds.
The "molecular logic" of the latter lies in the recognition that by contrasting the action of reactive species, polyphenols prevent or delay the occurrence of oxidative stress within cells and thereby reduce the speed with which various biological targets They are oxidized. As has happened with antioxidant vitamins, several studies have attempted to support the hypothesis that high levels (of intake and) of plasma polyphenols (particularly flavonoids) correlate inversely with the RR of development and / or death by various NCDs. Although numerous experimental studies support this type of assertion, it is currently considered that the validity of the observed correlations would be obligatorily associated with the level of intake of foods rich in this type of polyphenols, particularly fruits and vegetables rich in such compounds.
From a mechanistic point of view, how could the polyphenols present in fruits and vegetables protect against the development of cardiovascular diseases?
The hypothesis that unites polyphenols with the prevention of cardiovascular diseases is part of the oxidative theory of atherosclerosis. This postulates that the oxidation of cholesterol and the unsaturated lipids present in the native LDL particle (low density lipoprotein whose function is to transport cholesterol), which takes place mostly in the subendothelial space, represents a key event in the development (pathogenesis) of atherosclerosis (Figure III). Although the main antioxidant present in the LDL particle is vitamin E, other antioxidants (such as certain carotenoids) are also present in the particle, although in lower concentrations.
Oxidation of LDL in vivo (in the circulation) is initiated by the action of reactive oxygen and nitrogen species generated primarily by endothelial cells (which line the inner walls of blood vessels) and by monocytes (a type of white blood cell). ) / macrophages that infiltrate this area. The hypothesis of oxidative modification, states that oxidized LDL (LDLox) is subsequently captured by "scavenger" receptors present in macrophages that are found in the subendothelium of the affected arteries. This process results in massive uptake of LDLox, determining the transformation of macrophages in so-called foam cells (loaded with LDLox and numerous other products of oxidation), which make up the main components of the atheroma plaque. In addition to promoting the formation of foam cells, LDLox has direct chemotactic effects on monocytes and stimulates the binding of these cells and other leukocytes to the endothelium. The LDLox is also cytotoxic for the vascular cells, increasing the injury-endothelial dysfunction, perpetuating the inflammatory focus and promoting the progression of the atherosclerotic lesion. Finally, oxidized LDL alters the endothelial production and bioavailability of nitric oxide (see below, NO ), which manifests as an alteration of endothelium-dependent vasorelaxation.
Several studies, carried out both in vitro and in vivo in relevant experimental models, indicate that many of the aforementioned processes (such as LDL oxidation and atheroma formation) can be delayed and / or inhibited in the presence, either by addition and / or administration, of antioxidant compounds. For example, it has been observed that polyphenols are capable of retarding and / or preventing the oxidation of LDL in vitro, in both non-cellular systems (isolated native LDL exposed to pro-oxidant conditions) and cellular, and that they manage to do the same in vivo, when administered to animals that serve as a model of atherosclerosis (eg, rodents genetically predisposed to develop it, and / or in animals fed atherogenic diets). It has also been observed that, in vivo, the direct administration (or via dietary supplementation) of high doses of certain polyphenols (and / or extracts or mixtures of these) can also be effective, not only in retarding the oxidation of LDL, but in addition, in preventing various pro-inflammatory and inflammatory phenomena that typically accompany the oxidative and cellular damage that precedes, accompanies and / or leads to the formation of atheromas.
It should be clarified, however, that the mechanism through which polyphenols would promote such effects is not necessarily limited to the recognized ability they have to interact directly as reactive species catchers. In fact, the relatively low plasma and tissue concentrations (in tissues) that are usually reached after the intake of foods rich in these compounds has led to the statement that, in vivo, the antioxidant action of polyphenols would, quite possibly, be exerted on Through mechanisms that involve (via signal transduction) a modulation of the expression of those genes that code for the synthesis of proteins whose activity involves controlling the production and / or removal of the reactive species involved in the oxidation processes that underlie the development of cardiovascular diseases, including atherosclerosis.
For example, certain polyphenols can be opposed to oxidative stress by inducing the expression of genes encoding the synthesis of antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, and sulfoxy-methionine reductase. For this purpose (di novo synthesis) of the polyphenols could be added the capacity of other polyphenols to induce the synthesis of tripeptide glutathione, the main water-soluble antioxidant of cells. Low concentrations of some polyphenols are also capable of inhibiting the expression, synthesis and / or activity of certain pro-oxidant enzymes, involved in the generation of reactive species, such as NADPH-oxidase, xanthine oxidase and myeloperoxidase. It is quite possible that under in vivo conditions, both types of action, induction of (gene expression), the synthesis of antioxidant enzymes and inhibition of synthesis of pro-oxidant enzymes, contribute to control the formation and action of those reactive species acting on biological targets such as LDL, and other targets that in the framework of oxidative theory would be key in the development of atherosclerosis (and other cardiovascular diseases) where oxidative stress plays an important role.
As mentioned above, along with its oxidative nature, atherosclerosis is a disease that comprises a series of events of an inflammatory nature. One of the first pro-inflammatory events associated with the development of this is the recruitment of monocytes from the blood to the sub-endothelial space. This event depends on the expression of adhesion molecules by vascular endothelial cells (such as MCP-1 or monocyte chemoattractant protein-1, and ICAM-1 or intercellular adhesion molecule, involved in the binding of monocytes to the vascular endothelium). Several studies indicate that several of the polyphenols found in fruits and vegetables have anti-inflammatory properties, inhibiting either the production and / or secretion of such molecules and / or the activity of pro-inflammatory enzymes, such as COX-cyclo-oxygenase. 2 and myeloperoxidase. Such anti-inflammatory actions are observed in vitro at concentrations of certain polyphenols that are comparable to those achieved in vivo in the plasma of subjects who have been subjected to diets rich in antioxidants. Indeed, several studies conducted in animal models of atherosclerosis indicate that the sustained administration of certain polyphenols promotes an anti-inflammatory effect that at the vascular level would be relevant for the prevention of the formation of atheromas.
On the other hand, it is known that the oxidative and inflammatory events that affect the vascular endothelium, being sustained over time, are conducive to the loss of the function that the endothelial-vascular cells have to regulate the vascular tone (that is, the degree of contraction or relaxation exhibited by the smooth muscle surrounding the blood vessel). When the endothelium is "dysfunctional" it not only loses its capacity to regulate vascular tone, but also its anti-thrombotic properties (that is, its capacity to produce and release molecules that inhibit the formation of thrombi or clots) and its antiadhesive properties. leukocytes and platelets. The events of oxidative, inflammatory and atherogenic nature that affect the endothelial cells are accompanied, and in turn lead to a "loss of the capacity of the arteries to increase vascular tone". Such loss of function translates into a diminished responsiveness to the occasional need to increase blood flow to a given tissue / organ. The above is part of a global condition that affects the vascular endothelium referred to as "endothelial dysfunction" (ED). ED, when presented before the development of atherosclerotic lesion, is interpreted as an incipient marker of subclinical cardiovascular disease, and is considered to represent the "link that unites the risk factors-arterial hypertension and dyslipidemias-with atherosclerosis".
Platelet aggregation is one of the first steps in the formation of a blood clot. After its formation, it can occlude a coronary or cerebral artery, resulting in a myocardial infarction or cerebrovascular accident, respectively. In this regard, it is worth noting the existence of abundant literature (studies in both experimental animals and human volunteers) that shows the ability of certain different polyphenols, and certain foods rich in such compounds, to inhibit platelet aggregation. This effect is potentially important since it is considered that the inhibition of platelet aggregation is an effective strategy in the prevention of various cardiovascular diseases. In this regard, the practice of recommending the consumption of low doses of acetylsalicylic acid (or aspirin) as a way to reduce the likelihood of platelet aggregation is widely known.
The vascular endothelium has the ability to produce and release vasoactive molecules capable of inducing relaxation of the blood vessel, increasing blood flow. Among these molecules, nitric oxide ( NO • ) stands out. Although NO • is a free radical, its biological reactivity is very low, and as such does not induce biological damage. The synthesis of NO • occurs through the enzyme nitric oxide synthase (NOS) that from the amino acid L-arginine produces NO • and L-citrulline (requiring NAD (P) H as a cofactor and oxygen). When NO • is produced by vasculo-endothelial cells it rapidly diffuses to smooth muscle cells (which surround the blood vessels in the first), where the activation of the enzyme guanylate cyclase induces the production of cGMP (cyclic guanosine monophosphate) . Through a cascade of events, the increase in cGMP results in a relaxation effect of the vessel's musculature. The production of endothelial nitric oxide also inhibits adhesion and platelet aggregation, which results in a lower likelihood of clot formation in the blood. Several studies conducted both in experimental animals and in human volunteers show that the intake of foods rich in certain polyphenols (see below) produces an increase in endothelial production of NO • and through it, a significant vasodilation.
From a cardiovascular health point of view, a vasodilation induced by the consumption of certain foods could be particularly beneficial in individuals who exhibit an incipient degree of endothelial dysfunction (and in those who show a moderate degree of arterial hypertension). It should be clarified that not all polyphenols promote this vasodilatory effect. Particularly effective are cocoa catechins (and products such as bitter chocolate that have a cocoa content, at least over 60% and a proven high concentration of such polyphenols).
Both the oxidation of LDL and the accumulation of foam cells in the subendothelium, leading to the formation of atheromatous plaques, constitute events that take place normally and continuously throughout our lives. However, the process of forming atheromas is accelerated under conditions in which the rate of generation of reactive species exceeds the speed with which our organism is opposed to the generation and / or action of such species. Along with reducing the intake of those foods that accelerate the process of formation of atheromas (those rich in cholesterol and saturated fat), it is possible to delay these processes by increasing the intake of those foods that concentrate more and provide antioxidants to the body. Indeed, numerous clinical trials and epidemiological evidence show an inverse association between the intake of foods rich in antioxidants (particularly in polyphenols) and the relative risk shown by the populations studied to develop clinical manifestations of atherosclerosis and the morbidity and mortality associated with said atherosclerosis. disease.
Soon, the site will incorporate information that aims to answer questions such as the following: What are the clinical evidences that most support the approach that a greater consumption of fruits and vegetables rich in polyphenols would protect my cardiovascular health? Can consumption of dark chocolate be beneficial to my health? Is the consumption of green tea effective to protect my health against diseases associated with oxidative stress? We already appreciate your eventual interest in these topics.