Prostaglandins, Leukotrienes and Essential Fatty Acids
A dairy fat matrix providing alpha-linolenic acid (ALA) is better than a vegetable fat mixture to increase brain DHA accretion in young rats
Introduction
In an attempt to mimic breast milk efficiency to improve brain DHA levels, we evaluated the impact replacing the palm oil used in standard European formula by a dairy fat based formula in which the linoleic (LA) and alpha-linolenic (ALA) acids content and the LA/ALA ratio followed the recommended guidelines. For this purpose, we conducted a study on young deficient rats.
Docosahexaenoic acid (DHA; 22:6n−3) and arachidonic acid (AA; 20:4n−6) are highly concentrated in mammalian nervous and visual systems [1]. There is an increased demand for n−3 long-chain polyunsaturated fatty acids (LCPUFA), particularly DHA, to support optimal visual and cognitive development in infants during fetal life and newborn nursing [2], [3], [4]. Linoleic acid (LA; 18:2n−6) and alpha-linolenic acid (ALA; 18:3n−3) are the precursors of long-chain n−6 and n−3 fatty acids, respectively. Although LCPUFA can be synthesized from their respective precursor fatty acids [5], and, although it has been shown in rats that supplementation of mothers with ALA or DHA leads to the same LCPUFA accretion in maternal, fetal and newborn brains [6], [7], [8], DHA synthesis could be insufficient to cover growth needs [9], [10], [11]. Therefore, it may be necessary to increase the dietary intake of DHA and/or increase the synthetic capacity for metabolizing ALA to DHA in mothers and newborns [12].
Infant formulas have been gradually replacing mother's milk for more than 50 years and, at least in Europe, are usually prepared with vegetable oils. The compositions of these formulas are controlled in terms of fat for most fatty acids and especially essential fatty acids [12], [13], [14], [15]. Throughout the ages, infant formulas have been prepared with dairy fat, which, to some extent, is less different from breast milk for some components that are not present in vegetable fat formulas (i.e., cholesterol, short-chain FA, etc.) [16]. For example, the short- or medium-chain fatty acids in milk fat are more efficiently absorbed and might be beneficial for health [17]. Some studies reported the beneficial impact of dairy products on the bioconversion of ALA in humans or animal studies [18], [19], [20]. Some others have shown that infants fed formulas based on dairy fats [21] or evaporated milk [22] have LCPUFA status midway between those fed formulas enriched with LA-rich vegetable oils and those fed breast milk. However, the use of dairy fat for infant formulas is still a matter of debate in various countries [23].
Breast feeding is promoted all over the world as the gold standard, at least for the two to six first months. However, the nutritional adequacy of infant formulas for the following months is an important issue and the use of dairy fat during this period could be of interest as well.
In an attempt to validate the potential replacement of vegetable fats with dairy fat in infant formulas, we used the rat as a nutritional model. This can be considered as a valuable model to determine the needs of the human brain as shown by numerous studies over the last 30 years [24]. We first compared the effects on brain fatty acids (specifically DHA) of dietary blends based on dairy fat instead of palm oil, which provide the same quantities of essential FA. The levels of ALA and LA in these experimental diets followed the recommended and commonly used values in most commercial vegetable fat formulas [13], [14], [15].
During the 1990s the LA/ALA ratio in the adult diet was estimated around 20 or even more, and was far above the second millennium french recommendations proposal which was close to 10 for adults [25]. However, these last years it has been demonstrated that the LA/ALA ratio could impact the bioconversion of n−3 precursor to its longer chains n−3, and this has been related to health or behavior in youngs, adults or elderly [26]. Recently, the 2010 French recommendations [27], as well as many others, proposed a further reduction of the LA/ALA ratio for adults from 10 to 5 or even less, but there is still a controversy about the level which should be desirable. For infant formula, it should be noted that when both the LA/ALA ratio and the total of PUFA level are low, infant tissue levels of n−3 LCPUFA including docosahexaenoic acid (DHA), are higher than when milks high in PUFA are consumed [21], [22]. It has been suggested that the LA/ALA ratio in infant formulas is generally in the range 5–15:1, according to the second official ISSFAL statement which was approved by the ISSFAL Board in May 2008 at the Kansas City meeting, relating to infant feeding [15]. The balance may be thus more important when LCPUFA are not present in infant formulas.
The comparative efficiency of differently ALA-enriched dairy fat blends to a regular ALA-palm oil blend counterpart to improve the brain DHA status was evaluated in the present study on post-weaning rats born from ALA-deficient mothers. Furthermore, an additional comparison was made with post-weaning rats fed with a so-called “ALA-rich control” reference diet made up with 8.3% of rapeseed oil. The data reported here are pooled from published [28] and yet unpublished studies which will be part of a paper in preparation.
Section snippets
Animals and experimental design
The protocol was conducted following the Guidelines for the Care and Use of Experimental Animals edited by the French “Ministere de l'Alimentation, de l'Agriculture et de la Peche” and the 2003/65 CE European directives for animal experimentations.
Rats were housed in our animal facility under controlled conditions for light (lights on from 8:00 A.M. –8:00 P.M.), temperature (22±1 °C) and hygrometry (55–60%). They received a semi-synthetic diet and water ad libitum.
The restoration of n−3 fatty
Results
At the end of the postweaning period, the bodyweights did not differ in the male groups (372±35 g, 379±26 g, 360±60 g and 380±30 g, for P1.5, B1.5, B2.3 and C8.3, respectively). In addition, the food intake was similar across dietary treatments, as monitored during the last two weeks of the post-weaning period (22.6±2.3, 22.2±1.9 and 22.8±1.3 and. 22.0±1 g/d, for P1.5, B1.5, B2.3 and C8.3 groups, respectively).
Discussion
This study investigates the ability of dairy-fat-based diets to modulate the brain fatty acid restoration in young male rats by a comparison to corresponding vegetable saturated-fat-based diets. ALA deficiency over both gestation and lactation in the dams was achieved by feeding a palm-oil-blend-based diet (0.4%ALA), and the rat pups were then switched at weaning to either a palm-oil-blend diet (P1.5) or a butter diet (B1.5) supplemented with sunflower and rapeseed oils to maintain the same 16%
Funding
This work was partially funded by Lactalis.
Acknowledgements
We thank S Van der Gheest for animal care and technical assistance. This work was partly presented at ISSFAL June 2010, Maastricht, NL and at Journées Chevreul March 2011, Paris, France.
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