In general, an antioxidant compound can be defined as an atom or a molecule that avoids or blocks reactive oxygen species (ROS), thus preventing oxidative damage of other molecules. Its mechanism of action is based on direct interaction with ROS, forming a less active radical, or blocking oxidative chain reactions that lead to damage of substrates, such as lipids, proteins, carbohydrates, and DNA. A broader definition would also include those molecules responsible for repairing oxidative damage caused by ROS.

In reproductive function, antioxidant compounds have been shown to play an important role in countering the action of ROS and preventing oxidative stress , which is characterized by damage to sensitive lipid structures and the cell DNA aimed at fertilization [28]. In human males, an impaired or depleted antioxidant defense and an oxidative environment surrounding the sperm can alter their development and maturation, and can cause oxidative damage to their plasma membranes and cell apoptosis. These phenomena produce morphological and functional changes expressed in terms of deficient sperm count, morphology, and motility [29–31], which are the predictors most commonly used nowadays to define a man’s reproductive capacity.

Meanwhile, in women, there is a complex balance (which is not yet fully understood) between antioxidants and ROS throughout the whole process, from the growth and development of the oocyte in the ovary to follicle growth and the maintenance of the corpus luteum if pregnancy has occurred. In all these phenomena, antioxidants appear to act mainly as promoters, while ROS act as inhibitory or apoptotic agents, from the selection of the dominant oocyte to the regression of the corpus luteum when pregnancy has not occurred [32, 33].

In terms of classification, all antioxidants can be grouped, according to their nature, into enzymatic and nonenzymatic antioxidants. Enzymatic antioxidants constitute complex cellular detoxification pathways formed by numerous families of enzymes with antioxidant capacity. Whereas non-enzymatic antioxidants exert their antioxidant action directly, whether by chelating transition metals and stopping them from catalyzing ROS production or allowing the activity of some antioxidant enzymes.

Nonenzymatic antioxidants are of particular interest because of their relation to dietary intake, and of these, there are a variety of compounds that can act on an intracellular or extracellular level, or in both compartments (Table 19.2). In this regard, it has been demonstrated in animal models that the antioxidants naturally present in foods, once ingested, have sufficient bioavailability to significantly improve the damage to the reproductive organs caused by experimentally induced oxidative stress [34].

Regular physical exercise and a healthy diet provide obvious benefits in the prevention and treatment of chronic diseases such as diabetes, metabolic syndrome, and some cancers [35–37] . A healthy diet is one that, in addition to providing the energy required for all physiological processes, contributes the different nutrients which are functionally essential for good health. Among these substances, the antioxidants usually ingested in food have constituted an important line of research and have furthered our understanding of the pathophysiology and therapy used for different health disorders, including infertility.

The relationship between antioxidant intake and fertility in women is still largely unknown. A recent study including a large sample size assessed the relationship between time to pregnancy and antioxidant intake in women undergoing treatment for unexplained infertility (n = 437; age = 21–39 years) [38]. The detailed analysis of the mean intake of total, dietary, and dietary supplement sources of beta-carotene and vitamins C and E showed that increased intake of these antioxidant vitamins was associated with shorter time to pregnancy, depending on age and body mass index (BMI). However, more studies are needed to evaluate the effect of different antioxidants and their sources on female fertility, as well as the influence of other cofactors that may affect the oxidative balance, such as exercise.

On the other hand, several studies have linked a low habitual intake of dietary antioxidants with problems in fertility, associated with phenomena of oxidative damage in men (Table 19.3). In particular, the level of vitamin C intake seems to have a positive relationship with semen volume and sperm motility in healthy young adults [39–41]. Its antioxidant potential, its activity in an aqueous medium, and its presence in high concentrations in seminal plasma are arguments that have been used to explain the importance of this nutrient. Similarly, higher intake levels of beta-carotene and lycopene have been associated with increased sperm concentration and higher sperm quality and motility [40, 41]. Other antioxidants such as vitamin E and selenium have also been reported to improve sperm motility in healthy individuals [41] .

However, the available evidence is not particularly robust since many of the associations established between the different antioxidant nutrients and the fertility parameters analyzed have not produced uniform results within the different studies. A possible cause of this controversy could be found in the methods used to measure dietary intake in fertility studies. It is certain that the food frequency questionnaire (FFQ) is the dietary assessment instrument of choice for large-scale nutritional epidemiological studies. However, these same studies have also shown that the use of FFQ presents important limitations of validity and accuracy, overestimating or underestimating the real intakes, and altering the associations between diet and health outcomes. The sample size in fertility studies is obviously one of the main limitations for the interpretation of associations between antioxidant intake parameters of fertility. In addition, the FFQ assessments in studies that include populations with heterogeneity of age, body size, and socioeconomic status may lack validity and accuracy when dietary information obtained has not been statistically adjusted [46, 47]. Interestingly, none of the studies shown in Table 19.3 have considered the level of physical activity or exercise daily as co-variables in their research design.

Regarding the quality of dietary information, not all studies investigating the association between antioxidant intake and fertility published to date (Table 19.3) have made an analysis using energy-adjusted nutrient intake. In this sense, there is a consensus between nutritional epidemiologists, proposing that energy-adjusted nutrient intake is essential to improve the accuracy of the specific dietary composition measured by FFQ, allowing detection of moderate statistical associations in large health cohort studies [47, 48]. However, neither the energy-adjusted nutrient intake nor the use of 24-h or multiple-day food records chosen as instruments for calibration/validation of FFQ ensures the absence of bias, the magnitude of which is unknown. This is because 24-h or multiple-day food records not only imperfect the measurements they perform but also share with FFQ the origin of that imperfection; therefore, they are not independent and there is doubt about their usefulness as a reference method [49] .

Furthermore, to date, there are no dietary biomarkers capable of serving as instruments of valid reference. An example is the case of vitamin C and beta-carotene for which different confounders (physical activity, smoking, comorbidities, etc.) have made it impossible to detect a valid relationship between the measured plasma levels or its metabolites and referred dietary intake [50]. In this regard, recent data have shown that even when using a 7-day food diary and an antioxidant intake questionnaire to determine the total antioxidant intake, only a small correlation (correlation 0.29, 90 % confidence limits ± 0.27) with blood antioxidant biomarkers can be observed [51].

Finally, enough is known to ensure that FFQ is technically overdependent on the respondents’ memory: They have to try to remember their food intake over long periods of time, usually 12 months. Furthermore, over these periods, the sensitivity to reflect seasonal changes in the consumption of antioxidant-rich foods such as different varieties of fruit and vegetables is low .

All these problems can significantly limit the possibility of analyzing and interpreting the causality between the intake of dietary antioxidants and declining fertility parameters. The minimum criterion for studies investing the effect of diet on fertility is to utilize the FFQ and subsequent calculation of energy-adjusted nutrient intake in order to obtain a more accurate dietary composition. Measurement of relevant antioxidants in seminal plasma should also be considered to give greater support to the associations between intake and fertility parameters.

The content of antioxidant nutrients in an athlete’s diet , as in the general population, is not necessarily linked to the energy it supplies. In dietary restriction conditions, antioxidant intake is usually a linear function of the energy input, while in states of overnutrition, a high energy input combined with low content in antioxidant nutrients can occur [52]. This is what happens in the globalized Western dietary patterns and trends, which are high-energy and low-nutrient density diets featuring a low intake of fruit, vegetables, and seeds but a high intake of carbohydrates and/or fats. Moreover, dietary patterns and the quality of an athlete’s diet seem to depend on multiple factors including personal characteristics (e.g., sex), sociocultural conditions, and even the type of sport they do [53].

Conversely, the competitive level does not seem to be directly related to lower availability of dietary antioxidants. In this regard, different studies have shown that elite athletes have an adequate dietary intake of antioxidant vitamins (especially vitamins C and E), and in some cases higher than their recommended daily intake (RDI) [54].