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Antioxidants of food origin (tocopherols, carotenoids, ascorbate, polyphenols) exert synergistic (tocopherols and ascorbate, carotenoids and ascorbate) or complementary (tocopherols ands carotenoids, ascorbate and polyphenols) antioxidant actions. It is strongly suggest that high (supranutritional) intakes of tocopherols and carotenoids may turn out to be deleterious if it is not balanced by ascorbate and/or polyphenols adequate intakes, or in ascorbate and polyphenols deficiency which particularly takes place in tabagism or in cases of low fruit/vegetable consumption.

The French Food Safety Agency (Agence Française de Sécurité Sanitaire des Aliments, AFSSA) has recently adopted a definite position on risks and benefits of food trans fatty acids (TFA) for human health. After considering available data on origins and biological activities of all types of TFA, including conjugated fatty acids (CLA), it has been proposed a regulatory definition of these fatty acids which is the chemical one : « the trans fatty acids are all unsaturated fatty acids that contain at least one double bond in a trans configuration ». This definition includes the CLA and TFA of animal origin. Daily intakes of TFA (except CLA) in France was found to be 3 g/d in adults, i.e. 1.3 % total energy intake (E %). The male children are the most exposed to high TFA intakes which culminate at 2.5 E % for the 95 th percentile of the 12-14 year-old male children. Consumption of usual foods (not including the consumption of synthetic CLA supplements) leads to a rumenic acid daily intake inferior to 200 mg/d (0.08 E %). The contribution of TFA of animal origin is 60 % in adult (55 % for milk and dairy products) and 55 % (44 %) for male children, showing a higher consumption of TFA of technological origin in the form of bakery products in children than in adults. According to epidemiological data, TFA intakes (except CLA) of 2 E % are associated to a 25 % increased risk of the coronary heard disease. Clinical studies show that the CLA 10t,12c at the dose of 2.6 g/d should be considered potentially proatherogenic. The loss of body fat mass (the anti-obesity effect) with the administration of CLA mixture 9c,11t + 10t,12c (or 10t,12c alone) is obtained at a daily doses ranging from 1.6 to 6.8 g/d (2.6 g/d), but the loss is generally low even in the case of long term administration and adverse effects are observed in particular with 2.6 g/d CLA 10t,12c regarding insuline resistance, insulinemia, C-peptide, glycemia, HDL-C, enzymatic and non enzymatic peroxydations. The main AFSSA’s recommendations (non exhaustive list) are as follows : people should decrease their consumption of bakery products by 30 %, TFA contents of bakery products should not exceed 1 g per 100 g of the commercialized product, TFA contents of every types of margarines bought by the consumer should be lower than 1% of total fatty acids. Because of the prevalence of calcium deficiency particularly in children, declining consumption of dairy products is not recommended, but consumption of (half-)skimmed milk or products elaborated with (half-)skimmed milk should be preferred. Considering the lack of information on the relationship between animal traditional feeding and TFA contents of animal products that people consume, no content upper-limit is proposed for animal (or more specifically dairy) products. AFSSA points out that administration of the synthetic CLA supplement is not justified in humans and animals as well. Information on trans fatty acid in nutrition labeling should be mandatory for contents higher than 0.1 g/100 g in bakery and dairy products, and 0.1% for vegetable oils, margarines and butter. Given the very low levels of CLA in foods usually consumed, the CLA labeling is assumed to be purposeless.

Les propriétés anti-oxydantes de la vitamine E – qui font l’objet d’une large majorité des travaux effectués actuellement sur cette vitamine – n’ont été reconnues qu’au cours des années 50. La vitamine E avait cependant été découverte quelque trente ans plus tôt. Mais, paradoxe intéressant, son rôle comme micronutriment essentiel n’a été reconnu qu’à la fin des années 60. Cette vitamine jouit d’un certain nombre de particularités. C’est l’anti-oxydant majeur des milieux lipidiques (huiles, membranes biologiques, lipoprotéines). Elle présente différentes formes moléculaires : des vitamères a, b, g et d, chaque vitamère existant sous différentes formes stéréo-isomériques dont une seule, parmi les huit formes possibles, est naturelle : la forme RRR (figure 1). La molécule présente deux parties : un noyau 6-OH-chromane qui possède la fonction anti-oxydante, et une chaîne latérale à 16 atomes de carbone de structure isoprénique, celle-ci définissant deux grandes familles : les tocophérols à chaîne latérale saturée et les tocotriénols avec une chaîne latérale présentant trois doubles liaisons. Cette chaîne latérale détermine la lipophilicité et la stéréochimie de la molécule. C’est la stéréochimie de la molécule qui détermine à son tour la reconnaissance préférentielle de la forme RRR-a-tocophérol par un transporteur hépatique spécifique dont le rôle physiologique est aujourd’hui reconnu. Chacune de ces formes moléculaires (le nombre théorique est de 64) peut être caractérisée par une activité vitaminique E, définie par référence au pouvoir anti-abortif chez la rate gestante. Les tableaux 1 et 2 donnent cette activité en fonction de la molécule considérée. La forme naturelle de l’a-tocophérol, le RRR-a-tocophérol, possède l’activité la plus élevée, alors que la stéréo-isomérie de la molécule n’exerce aucun effet sur ses propriétés anti-oxydantes. Enfin, c’est à partir de la fin des années 70 et du début des années 80 que les propriétés cellulaires régulatrices de la vitamine E vont être révélées. Elles font aujourd’hui l’objet de recherches actives sur les cascades de signalisation affectant différentes fonctions cellulaires. Elles ne semblent pas corrélées aux propriétés anti-oxydantes mais pourraient impliquer des étapes de reconnaissance stéréo-dépendantes.

Ce qui frappe aujourd’hui, c’est une évolution rapide des connaissances sur les quatre vitamines liposolubles qui font l’objet des revues générales présentées dans ce dossier, et plus particulièrement peut-être sur les vitamines A, D et E. On savait ces vitamines indispensables en raison de leur implication dans les réactions cellulaires, pas uniquement métaboliques d’ailleurs, mais on ne pouvait les soupçonner d’intervenir dans des phénomènes complexes touchant aux régulations cellulaires et à l’expression des gènes avant l’explosion des techniques de biologie moléculaire. Ces trois vitamines ont ainsi, entre autres, la capacité de réguler la prolifération et la différenciation cellulaire selon des mécanismes qui peuvent paraître différents aujourd’hui dans certains cas (pour la vitamine E par exemple), ou souvent proches (cas des vitamine A et D). Les quatre vitamines sont capables en revanche d’intervenir dans la mort cellulaire programmée (apoptose). Dans le cas du tissu osseux, ce sont les vitamines A, D et K qui agissent sur l’accrétion calcique. La vitamine E, quant à elle, pourrait prévenir, au moins théoriquement, l’ostéoporose.

It is largely admitted nowadays that the early stage of the atherosclerotic lesion involves formation of oxidized (and minimally oxidized) low-density lipoprotein. Their properties are briefly reviewed. It is recalled that a lipolytic process also takes place both at the lumenal surface and in the subendothelial space of the vessels implying lipoprotein lipase (LpL) activity. Recent studies emphasize the role of LpL in accumulating LDL in the vascular tissue (Rutledge & Golberg, J. Lipid Res., 1994, 35, 1152-1160), but the role of LpL-generated unesterified fatty acids (UEFA) in these two locations and their possible implication in atherogenesis are largely neglected. Physiological and pathophysiological significance of UEFA in the human adherent monocyte modulation of the superoxide anion (O2.-) production has been examined by our group, leading to a possible mechanism of modulation of LDL oxidative modification. The O2.- production-modulating effect of a 30-min UEFA preincubation has been studied in intact human adherent monocytes (HAM) after stimulation by a direct effector of protein kinase C (PKC). It has been established that UEFA alone (in the absence of PKC effectors) were not able to modulate the O2.- production of HAM whereas they had such a capacity in the presence of PKC effectors, phorbol myristate acetate (PMA) or diacylglycerol (DAG). In this case inhibitors of PKC such as GF 109203 X suppressed the modulating effect. UEFA have also been shown to possess a bimodal action in the presence of PKC effectors: they depressed or enhanced O2.- production at micromolar or nanomolar concentrations, respectively. All these results contrasted with others obtained in neutrophils or nonadherent monocytes, suggesting an absolute requirement of PKC for the phagocyte-NADPH oxydase (PHOX) activation especially in the case of HAM. In HAM, the maximal enhancing effects were obtained with monomethyl ramified saturated (MMRS) and linear unsaturated (LU) FAs such as arachidonic, eicosapentaenoic and docosahexaenoic acids (with exception of oleic, linoleic and linolenic acids which were without effect), whereas the maximal depressing effects were obtained with MMRS-FAs and LU-FAS such as oleic, linoleic and docosahexaenoic acids. Further investigations in HAM led us to examine the UEFA capacity at modulating the translocation of PKC, on the one hand, and the endogenous phosphorylation and membrane translocation of p47phox, on the other, in the presence of PMA or DAG. Using 13-methyl myristic (iso15:0) as FA model, it has been established that i) it was able to amplify or diminish PKC translocation at nanomolar and micromolar concentrations, respectively (this was also the case with arachidonic acid) ii) it enhanced and depressed the endogenous phosphorylation and the membrane translocation of p47phox at nanomolar/micromolar concentrations and iii) it was inactive in the absence of PMA or DAG. Taken together, our results strongly suggest that the active UEFA act directly on the monocyte PKC, modifying its kinase activity through interactions with PMA/DAG binding site of the regulatory domain of the protein. This leads to modulate the phosphorylation and translocation of p47phox, which in turn allows the assembling of the active PHOX complex and triggers the O2.- production. The direct action of UEFA on the PKC regulatory-domain known to strongly interact with the membrane lipids was also supported by the fact that linear saturated FAs that have already been reported to be unable to penetrate a lipid layer were devoided of effect on monocytic O2.- production. The free form of oleic and linoleic acids and, to a lesser extent, docosahexaenoic acid (in the case of oral administration of fish oil) are present at micromolar concentrations in the plasma.(ABSTRACT TRUNCATED AT 400 WORDS)