Folic acid is a vitamin needed by a number of enzymes essential for DNA synthesis and amino acid metabolism . This nutrient is an important co-factor in the methionine pathway, the most important source of methyl groups in the human organism . Low folic acid intake is known to contribute to increased levels of homocysteine (Hcy) as a result of its interrelation with methionine metabolism [2–6]. Inadequate intake of folic acid has been described in athletes who practice different sports , and athletes are often deficient in their intake of total calories, carbohydrate, protein, and micronutrients . Some authors consider supplementation with folic acid as an efficient way to reduce elevated Hcy levels [8, 9], and it has been suggested that in certain cases, folic acid supplementation should be used for preventive purposes . Earlier findings have suggested that doses of 0.2 to 0.4 mg/d can achieve maximal reductions in Hcy in healthy young populations, whereas doses up to 0.8 mg/d are needed to reduce Hcy in individuals with coronary heart disease .
Regular physical activity (PA) can alter the requirements for some micronutrients . This makes it important to choose foods carefully, taking into account the quality and quantity of macronutrient intakes, since requirements can vary depending on the type of exercise performed .
Elevated plasma levels of Hcy are considered a risk factor for cardiovascular disease (CVD) . Regular physical activity is now well established as a key component in the maintenance of good health and disease prevention, and has been specifically recognized to reduce the risk of appearance of CVD by reducing chronic inflammation, which plays a key role in the atherogenic process, blood pressure, body composition, insulin sensitivity and psychological behavior [14, 15].
In contrast, acute intense exercise has been shown to increase plasma Hcy concentrations . Several factors have been reported to be associated with increases in Hcy, such as endothelial cell injury, which stimulates vascular smooth muscle cell growth, increases platelet adhesiveness, enhances LDL cholesterol oxidation and deposition in the arterial wall, and directly activates the coagulation cascade . Some research has concluded that Hcy levels may be influenced by the duration, intensity and type of exercise [6, 14, 17, 18], whereas other studies have identified lifestyle factors such as smoking, eating habits and alcohol consumption [6, 19, 20], as well as age, elevated blood pressure, renal failure [17, 21] and genetic factors , as factors that contribute to increased plasma concentrations of Hcy. In addition, nutritional factors such as reduced folic acid intake have been implicated [3, 13].
Several authors [4, 13, 22, 23] have established a direct relationship between regular physical exercise (PA) and a reduction in CVD risk, although the data regarding the effect of PA on plasma Hcy concentrations remain controversial because of methodological differences among different studies. Murakami et al.  noted that these discrepancies may reflect differences in the methods used to evaluate PA, the lack quantitative information on training intensity or training time, and in some cases the lack of adjustment for folate intake status . However, Venta et al.  suggested three possible mechanisms that may explain the increase in Hcy with increasing exercise intensity: increased free radical production , increases in methylated forms such as creatine and acetylcholine, and increases in the amino acid pool as a result of protein catabolism. The need for research in athletes who take part in different sports has been suggested to be important in order to account for the high prevalence of hyperchromocysteinemia . To date, however, there have been no studies that evaluated plasma Hcy levels while taking into account nutrient intakes, training intensity and training time, and rate of perceived exertion (RPE). Moreover, the relationship between PA and Hcy has not been studied in team sports such as handball, in which intermittent activity alternates with periods of intense aerobic activity .
In the present study our aims were to evaluate macronutrient and folic acid nutritional status in high-performance athletes (handball players), and to determine the effect on these parameters of training and a nutritional intervention based on dietary supplementation with folic acid. We analyzed the data in the light of training load and plasma Hcy concentrations.