Gérard Pascal

Vitamin A in pregnancy: requirements and safety limits.

Most of the functions of vitamin A are mediated through the binding of retinoic acid to specific nuclear receptors that regulate genomic expression. Recent experimental work in transgenic mice showed clearly that normal embryonic development depends on the correct spatial and temporal expression of the receptors in the differentiating cells and on the binding of specific forms of retinoic acid. This implies that the parent compound, vitamin A, is available in adequate forms and quantities. Excessive dietary intake of vitamin A has been associated with teratogenicity in humans in <20 reported cases over 30 y. However, caution must be exercised to avoid unnecessary supplementation of women of childbearing age. Hypovitaminosis A affects millions of women and children worldwide. The main consequence of a poor vitamin A supply during pregnancy is a low vitamin A status at birth and in the next few months. Vitamin A deficiency is strongly associated with depressed immune function and higher morbidity and mortality due to infectious diseases such as diarrhea, measles, and respiratory infections. Vitamin A deficiency is often associated with an increased mother-to-child transmission of HIV-1. The initiation of vitamin A supplementation should be carefully examined in each case according to the risk-to-benefit ratio. The final decision should take into account the estimated vitamin A status of the woman, the availability of vitamin A-rich foods in her diet, and whether supplementation can be supervised.

Dietary linoleic acid and polyunsaturated fatty acids in rat brain and other organs. Minimal requirements of linoleic acid.

Starting three weeks before mating, 12 groups of female rats were fed different amounts of linoleic acid (18∶2n−6). Their male pups were killed when 21-days-old. Varying the dietary 18∶2n−6 content between 150 and 6200 mg/100 g food intake had the following results. Linoleic acid levels remained very low in brain, myelin, synaptosomes, and retina. In contrast, 18∶2n−6 levels increased in sciatic nerve. In heart, linoleic acid levels were high, but were not related to dietary linoleic acid intake. Levels of 18∶2n−6 were significantly increased in liver, lung, kidney, and testicle and were even higher in muscle and adipose tissue. On the other hand, in heart a constant amount of 18∶2n−6 was found at a low level of dietary 18∶2n−6. Constant levels of arachidonic acid (20∶4n−6) were reached at 150 mg/100 g diet in all nerve structures, and at 300 mg/100g diet in testicle and muscle, at 800 mg/100 g diet in kidney, and at 1200 mg/100 g diet in liver, lung, and heart. Constant adrenic acid (22∶4n−6) levels were obtained at 150, 900, and 1200 mg/100 g diet in myelin, sciatic nerve, and brain, respectively. Minimal levels were difficult to determine. In all fractions examined accumulation of docosapentaenoic acid (22∶5n−6) was the most direct and specific consequence of increasing amounts of dietary 18∶2n−6. Tissue eicosapentaenoic acid (20∶5n−3) and 22∶5n−3 levels were relatively independent of dietary 18∶2n−6 intake, except in lung, liver, and kidney. In several organs (muscle, lung, kidney, liver, heart) as well as in myelin, very low levels of dietary linoleic acid led to an increase in 20∶5n−3. Dietary requirements for 18∶2n−6 varied from 150 to 1200 mg/100 g food intake, depending on the organ and the nature of the tissue fatty acid. Therefore, the minimum dietary requirement is estimated to be about 1200 mg/100 g (i.e., the level that ensures stable and constant amounts of arachidonic acid).

Dietary α-linolenic acid deficiency in adult rats for 7 months does not alter brain docosahexaenoic acid content, in contrast to liver, heart and testes

In adult rats, 22:6(n - 3) dietary deficiency does not affect brain membranes, but has a significant effect on some other visceral organs. 60-day-old male rats fed a diet containing sufficient amounts of both linoleic and alpha-linolenic acid were divided into three groups. One group continued the same diet; the second was fed a diet containing 2% sunflower oil, the third was fed 10% sunflower oil (sunflower oil contains linoleic acid, but trace amount of alpha-linolenic acid). Animals were killed different times after receiving the new diets (1 to 31 weeks). For animals fed the diets containing only sunflower oil, deficiency in cervonic acid content (DHA, docosahexaenoic acid, 22:6(n - 3)) was not detected in whole brain, myelin or nerve endings within 31 weeks. In contrast, this acid progressively declined in liver, heart and testes up to 3 weeks and remained nearly stable thereafter. In parallel to the reduction of cervonic acid content, 22:5(n - 6) content increased in liver and heart, but not in testes. It also increased in brain, nerve endings and myelin from week 3, 6 and, 9 respectively. These results suggest that brain cervonic acid is highly preserved or is maintained at the expense of other organs.

Effects of age and dietary essential fatty acids on desaturase activities and on fatty acid composition of liver microsomal phospholipids of adult rats.

The combined effects of age and dietary n−6 and n−3 fatty acids were studied in 3-, 6- and 9-month-old rats. At each age, two groups were fed diets containing 5% (w/w) of vegetable oils rich in either 18∶3n−6 (borage group) or 18∶3n−6 plus 18∶4n−3 (black currant group), for a period increasing with age. A control group was fed the essential fatty acids 18∶2n−6 and 18∶3n−3 only. For each group, Δ6, Δ5 and δ9 desaturase activities were measured in liver microsomes, and fatty acid composition was determined in microsomal phospholipids. Desaturase activity varied as a function of age and dietary lipids. Δ6 Desaturation of 18∶3n−3 was more sensitive to these factors while Δ6 desaturation of 18∶2n−6 and Δ9 desaturation were more dependent on season than the other two. Desaturase activity was influenced more by the black currant than by the borage diet, especially at 6 and 9 months of age. A large proportion of arachidonic acid was maintained in the microsomes independent of the diet. Changes in the fatty acid composition did not strictly reflect the differences in desaturase activities. The effects of the two factors (age and diet) on the activities of the desaturases are complex, suggesting that the enzymes are susceptible to other factors as well.

Tissue phospholipid fatty acid composition in genetically lean (Fa/-) or obese (fa/fa) Zucker female rats on the same diet.

The fatty acid composition of serum total lipids, of phospholipids of various organs (liver, heart, kidney), and of nervous structures (brain, retina, sciatic nerve, myelin, synaptosomes) have been compared in lean (Fa/−) and genetically obese (fa/fa) Zucker female rats. Both received a standard commercial diet including 37% of 18∶2n−6 and 5% of n−3 polyunsaturated fatty acids (PUFA), 1.7% of which were in the form of 20∶5n−3 and 22∶6n−3. In comparison with lean rats, the results for the obese rats pointed out (i) no difference in the fatty acid composition of nervous structures: (ii) a decrease of 18∶2n−6 (from −8% to −35%) and of 20∶4n−6 (from −9% to −49%) in serum, liver and in kidney; this was compensated for by an increase in 20∶3n−6 (from +30% to +320%) and in total n−3 PUFA (from +68% to +76%); (iii) a decrease of 20∶4n−6 (−18%) and of 22∶6n−3 (−24%) in heart compensated for by an increase in 18∶2n−6 (+39%) and in 20∶3n−6 (+233%); and (iv) constant levels of total PUFA (n−6 and n−3) in the various fractions studied, except in serum where this level decreased (−23%). Finally, except for the nervous structures, tissue phospholipids of obese rats included a lower proportion of 20∶4n−6 and a higher proportion of 20∶3n−6. This resulted in a significant reduction in the 20∶4n−6/20∶3n−6 ratio; by contrast, the 20∶3n−6/18∶2n−6 ratio increased. The results suggest that in Zucker rats, the obese character (fa/fa) affects the desaturation-elongation process of 18∶2n−6 to 20∶4n−6 by specifically decreasing Δ5-desaturase activity.

Slow Recovery of the Fatty Acid Composition of Sciatic Nerve in Rats Fed a Diet Initially Low in n-3 Fatty Acids

The sciatic nerve of rats fed sunflower oil (6 mg 18∶3n−3/100 g of diet) presented dramatic alterations in the long chain polyunsaturated fatty acids in comparison with those fed soy oil (130 mg 18∶3n−3/100 g of diet). In both 15-day-old and 60-day-old animals fed sunflower oil, 22∶6n−3 (cervonic acid) was fourfold less, 22∶5n−6 was 10-fold greater; adrenic acid (22∶4n−6) was slightly greater and arachidonic acid (20∶4n−6) was close to that in rats fed soy oil. The percentage distribution of total polyunsaturated fatty acids as well as the individual saturated and monounsaturated fatty acids were the same in both groups.When the sunflower oil-fed animals were switched to a soy oil-containing diet for either 15 or 60 days, the percentage distribution of 22∶6n−3 increased slowly to reach the control value 2.5 months later. Conversely 22∶5n−6 decreased slowly. The decay of 22∶5n−6 was more rapid than the increase of 22∶6n−3.

Polyunsaturated Fatty Acids of the n-3 Serie and Nervous System Development

It is necessary to ensure that brain cells receive adequate supplies, especially of lipids, during their differentiation and multiplication. A lipidic anomaly could result in altered function of the membranes and a greater susceptibility of the membranes to aggression, particularly toxic.

Redécouverte des propriétés fonctionnelles de l’aliment : fondements scientifiques généraux

Resume Historiquement les liens entre alimentation et sante sont mentionnes depuis tres longtemps. Les disettes ont conduit a privilegier les progres technologiques pour assurer dans un premier temps la production et la conservation de quantite suffisante d’aliments. Apres la couverture des besoins nutritionnels classiques par une alimentation equilibree et diversifiee, on (re)decouvre aujourd’hui les possibles roles de l’aliment sur les fonctions physiologiques, le bien-etre et la reduction de facteurs de risques de maladies. C’est le concept d′« aliment fonctionnel » qui a ete explore et formalise par un vaste travail d’experts multidisciplinaires dans le cadre d’un programme EU (FUFOSE), et que nous resumons ici.

Effects of congeneric polychlorinated biphenyls on liver and kidney retinoid levels

Abstract Liver and kidney retinol and retinyl palmitate levels were studied in male Sprague Dawley rats receiving a single ip injection of one of several polychlorinated biphenyls (PCBs) or DDT. Only the administration of 3,3′,4,4′-tetrachlorobiphenyl resulted in progressively lowered liver vitamin A levels (to 40 % of control values by day 7). During this time, kidney total vitamin A content increased 3 fold (due primarily to increased retinol content), but this increase was only equal to approximately 1 40 of total vitamin A which had disappeared from the liver. The activity of retinyl palmitate hydrolase, the key enzyme in the hydrolysis of hepatic retinyl palmitate, was not increased, indicating that this enzyme is probably not involved in the depletion of liver vitamin A stores by 3,3′-4,4′-tetrachlorobiphenyl.

Démonstration scientifique des fonctions des aliments associées à la santé

Resume A la suite de l’article ou etait rappelee l’existence des proprietes fonctionnelles de certains aliments-ingredients, le present article resume les principales etapes de la demonstration scientifique qui permettent de justifier les proprietes fonctionnelles alleguees. Cette base scientifique comporte quatre grandes etapes : l’identification et la caracterisation de l’aliment-ingredient, qui sera porteur de l’allegation ; la construction des arguments scientifiques obtenus par des etudes cliniques conduites sur l’homme avec l’aliment/ingredient considere ; la selection et la mise en œuvre de marqueurs pertinents dans les etudes cliniques clef et enfin l’analyse de l’ensemble des donnees obtenues. Les benefices fonctionnels ainsi demontres peuvent s’appliquer, pour le consommateur, soit a l’amelioration de fonctions physiologiques, soit a la reduction de certains facteurs de risque. Ces aliments fonctionnels doivent, bien sur, s’integrer dans une alimentation raisonnable et diversifiee.