1. Introduction
Arachidonic acid (C20:4
n-6, AA) and docosahexaenoic acid (C22:6
n-3, DHA) are long chain polyunsaturated fatty acids (LCPUFA) that have a relevant role in different metabolic and physiological process during embryonic and fetal development, and the first years of life [
1]. Highest concentrations of AA and DHA are found in nervous system, particularly in brain and retina, specifically in the phospholipids of cell membranes [
2,
3]. AA and DHA have an active role in brain development during neurogenesis, synaptogenesis, neuronal migration, neuronal differentiation, and also in gene expression and in the general metabolic energy status [
4]. AA is formed from the precursor linoleic acid (C18:2
n-6 LA) and DHA from the precursor alpha-linolenic acid (C18:3
n-3, ALA) [
5]. Humans can synthesize AA and DHA, mainly in the liver, through a complex metabolic process that includes different enzymatically catalyzed desaturations and elongations of their respective metabolic precursors (LA and ALA); Δ-5 and Δ-6 desaturases are the most relevant enzymes participating in these processes [
6].
Hepatic synthesis of AA and DHA is a fundamental metabolic process necessary to ensure the constant supply of these LCPUFA to other tissues [
7]. Synthesis of AA and DHA in women is more efficient than in men due the active positive control of estrogens over desaturase activities [
8]. Women, in addition, can store LCPUFA during pregnancy and lactation to ensure an adequate flow of AA and DHA to the fetus and newborn [
9]. During pregnancy, the transport of AA and DHA from the mother to embryo and fetus is facilitated by specific transporter proteins that enhance the transfer of these fatty acids through the placenta [
10]. During this period, women can also incorporate AA and DHA in their diet by eating eggs and meat (as sources of preformed AA) and fatty fish (i.e., tuna, mackerel, and salmon, among others) as a sources of preformed DHA [
11]). However, in western countries DHA intake from fish consumption is very low compared to the intake of LA (from vegetable oils) and AA (from eggs and meat) [
11]. In addition to the high dietary intake of
n-6 fatty acids, the synthesis of AA from LA when this fatty acid is highly consumed is more efficient than the synthesis of DHA from ALA [
12].
Several studies have established the relevance of the fatty acid composition of breast milk and its direct association with the diet of the mother during pregnancy and lactation [
13,
14,
15]. The aim of our research was to evaluate the impact of maternal diet, with specific reference to the quality of fatty acids intake, in a sample of Chilean women during the last stage of pregnancy and across the lactation period. The fatty acid composition of erythrocyte phospholipids (during pregnancy and lactation) and of breast milk (during the first sixth months of lactation) were assessed as analytical criteria for
n-6 and
n-3 LCPUFA availability.
4. Discussion
A woman’s diet during pregnancy and lactation has a fundamental role in the adequate contribution of macro and micronutrients for her infant during the fetal life and during lactation [
22,
23]. The tissue levels of fatty acids in a woman during pregnancy and lactation are directly related to her diet, her reserve capacity, and her metabolic utilization of fatty acids (synthesis, oxidation, transport, etc.) [
24,
25]. Therefore, the diet and the metabolism of fatty acids of women during pregnancy and lactation have a relevant role in determining the levels of LCPUFA present in erythrocytes and breast milk [
26,
27]. The availability of LCPUFA for the infant is directly related to the transfer of these fatty acids from the mother to her offspring, first through the placenta (intra-uterine life) [
28] and then through lactation [
29]. Regarding AA and DHA, their availability will depend on the intake of foods that provided these fatty acids [
30] and/or from the capacity of the mother to form these fatty acids from their metabolic precursors [
31]. According to our results we concluded that the Chilean women evaluated have a high intake of
n-6 PUFA, LA, and AA (
Table 4), and a low intake of
n-3 PUFA, ALA, EPA, and DHA (
Table 4). In this context, is also remarkable that among LCPUFA, DHA is one the fatty acid with the most important metabolic characteristics for the physiological period studied [
28,
32]. The low intake of foods that are natural sources of DHA, such as fish or seafood, as was observed in our study (
Table 3), added to an excessive intake of foods that are high in
n-6 fatty acids, especially LA (e.g., consumption of soy or sunflower oil), which can produce a reduction of the capacity of the mother for transferring DHA to her offspring during pregnancy and breast feeding [
13,
26,
27]. In our sample, DHA levels in breast milk were reduced by 38.5% at the 4th month, by 48.7% at the 5th month, and by 64.1% at the 6th month of lactation compared with the 1st month of lactation (
Table 6). This situation was not produced for AA and LA in erythrocytes and breast milk because of the adequate consumption of foods considered good sources of these fatty acids (
Table 3).
The reserve capacity of women for LCPUFA, particularly DHA, is sensitive to the number of pregnancies, because it is produced by a significant decrease in the tissue levels and availability of DHA after frequent pregnancies [
28,
30,
33]. In addition, another interesting aspect to consider is the activity of the Δ-5 and Δ-6 desaturases, key enzymes for the synthesis of LCPUFA from their specific precursors [
8,
31]. The presence of polymorphisms in the genes encoding these enzymes may produce a lower synthesis of both
n-6 and
n-3 LCPUFA, but being the diet sufficient in AA, the effect of polymorphism should be more deleterious for the availability of DHA than AA [
34]. Is important to emphasize that the dietary imbalance of
n-6 to
n-3 PUFA can lower the synthesis of
n-3 LCPUFA, particularly DHA, because of the competition generated between the respective precursors for the active sites of desaturase enzymes [
6,
8,
35]. An excess of
n-6 fatty acid (such as LA) may decrease the synthesis of DHA from ALA [
36]. The increment in the values for DPAn-6 (
Table 5) may be a metabolic compensatory mechanism to form LCPUFA because of the reduction of the
n-3 LCPUFA (DHA), an aspect that remains to be studied. The synthesis of LCPUFA, as well as the availability of precursors and the activity of Δ-5 and Δ-6 desaturase enzymes, is also dependent on the availability of specific nutrients, such as zinc, magnesium, calcium, vitamin B6, and vitamin C [
37]. It is also interesting that while the synthesis of DHA from ALA may be sufficient for the adult human in normal physiological conditions [
38], some diseases, such as non-alcoholic fatty liver, a pathology very prevalent in populations that are overweight or obese [
39] (in our study, women who were overweight or obese reached 48.9% at 6th month of pregnancy), which reduces the activity of Δ-5 and Δ-6 desaturase enzymes [
40], could adversely affect the synthesis of DHA, decreasing the levels of
n-3 LCPUFA in erythrocytes and breast milk, as was observed in this work (
Table 5 and
Table 6). Another aspect observed in this study was the increase in weight of the women from the 6th month of pregnancy until the delivery (average 12.2 kg), in addition to the high prevalence of overweight and obese women at the end of pregnancy (62.8%), along with the birth weight of children, which, on average, was 4.25 kg. In this context, previous studies suggest that Chilean women during the fertile age show a fast and growing tendency towards obesity [
41], and a high prevalence of being overweight (50%) and obese (20%) is observed in pregnant Chilean women [
42]. This nutritional situation has been related to (i) the increasing tendency of the Chilean newborns to have a weight at birth higher than 4.0 kg [
43] and (ii) a high number of births by caesarian intervention, which are associated with overweight and obesity of pregnant women (up to 35%) [
44].
In relation to the Chilean population, Bascuñán et al. [
21] reported that women in the 3rd trimester of pregnancy with a low intake of DHA showed low levels of this fatty acid in erythrocyte phospholipids. In the population evaluated in this study, it was observed that DHA levels in erythrocytes were significantly decreased at the 6th month of lactation (
Table 5) and the content of DHA in breast milk also decreased (
p < 0.05), starting from the 4th month of lactation (
Table 6). In this same context, Valenzuela et al. [
15] reported that in Chilean pregnant women, who included in their diet chia oil (“
Salvia hispanica L.”, 60% ALA) instead of the traditionally consumed oils (soy and sunflower oil) from the 6th month of pregnancy and until the 6th month of lactation, it a significant increase of DHA levels in breast milk was produced, but only until the 3rd month of lactation, without modification of the AA levels during the 6th month of lactation. The same authors reported that AA and DHA in erythrocyte phospholipids were not modified during the dietary intervention [
15], suggesting that the ingestion of oils with high content of ALA (such as chia oil) would not be entirely efficient to increase the levels of DHA in breast milk during a lactation period up to three months [
15].
Concerning the actual background of
n-3 LCPUFA, dietary strategies have been developed to improve the quality of the diet of women during pregnancy and lactation through educational programs focused on promoting consumption of foods that provide DHA (especially from marine origin) [
45,
46,
47]. However, it is not easy to modify the dietary habits of women during these periods [
45,
47], which adds to the concern that currently exists about the contamination of foods from marine origin (heavy metals, dioxins, PGB, etc.) and the questioning in the population about “possible adverse effects” of seafood consumption [
48,
49,
50]. It is remarkable that, in the present study, it was observed that women significantly decreased fish intake after the delivery (
Table 3), even though they were advised by professional nutritionist that they should increase the consumption of fish and other foods from marine origin. In this regard, the decrease of DHA levels (
p < 0.05) observed in erythrocytes and breast milk in women’s sample (
Table 5 and
Table 6) may be a concern, as it has been previously reported that higher levels of DHA in breast milk are associated with better academic performance, particularly in mathematics, in long-term studies on children [
51]. Addressing this dietary and nutritional problem, various studies have used supplements containing DHA or DHA-added foods, evidencing that an increase in the intake of DHA increases the content of the fatty acid in erythrocytes and subsequently in breast milk in pregnant and lactating women [
52,
53,
54,
55]. In consistent with this same direction, the Chilean Ministry of Health has developed a food program that benefits (free of cost) all women during pregnancy and lactation, providing a dairy drink containing DHA (60 mg/200 mL of product), and recommending the intake of two daily portions (120 mg DHA/day) [
56]. Although the program began in 2009, there are no current results regarding the impact of this dairy product, either on DHA levels in erythrocytes and breast milk or on scholarly performance. The results of this program are currently being assessed.