Pierre Astorg

Dietary intakes and food sources of n−6 and n−3 PUFA in french adult men and women

The intake of individual n−6 and n−3 PUFA has been estimated in 4,884 adult subjects (2,099 men and 2,785 women), volunteers from the French SU.VI.MAX intervention trial. The food intakes of each subject were recorded in at least ten 24-h record questionnaires completed over a period of 2.5 yr, allowing the estimation of the daily intake of energy; total fat; and linoleic, α-linolenic, arachidonic, eicosapentaenoic (EPA), n−3 docosapentaenoic (DPA), and docosahexaenoic (DHA) acids. The mean total fat intake corresponded to 94.1 g/d (36.3% of total energy intake) in men and 73.4 g/d (38.1% of energy) in women. The intake of linoleic acid was 10.6 g/d in men and 8.1 g/d in women, representing 4.2% of energy intake; that of α-linolenic acid was 0.94 g/d in men and 0.74 g/d in women, representing 0.37% of energy intake, with a mean linoleic/α-linolenic acid ratio of 11.3. The mean intakes of long-chain PUFA were: arachidonic acid, 204 mg/d in men and 152 mg/d in women; EPA, 150 mg/d in men and 118 mg/d in women; DPA, 75 mg/d in men and 56 mg/d in women; DHA, 273 mg/d in men and 226 mg/d in women; long-chain n−3 PUFA, 497 mg/d in men and 400 mg/d in women. Ninety-five percent of the sample consumed less than 0.5% of energy as α-linolenic acid, which is well below the current French recommendation for adults (0.8% of energy). In contrast, the mean intakes of long-chain n−6 and n−3 PUFA appear fairly high and fit the current French recommendations (total long-chain PUFA: 500 mg/d in men and 400 mg/d in women; DHA: 120 mg/d in men and 100 mg/d in women). The intakes of α-linolenic acid, and to a lesser extent of linoleic acid, were highly correlated with that of lipids. Whereas the main source of linoleic acid was vegetable oils, all food types contributed to α-linolenic acid intake, the main ones being animal products (meat, poultry, and dairy products). The main source of EPA and DHA (and of total long-chain n−3 PUFA) was fish and seafood, but the major source of DPA was meat, poultry, and eggs. Fish and seafood consumption showed very large interindividual variations, the low consumers being at risk of insufficient n−3 PUFA intake.

Food carotenoids and cancer prevention : An overview of current research

Carotenoids are plant pigments that are present in the human diet as microcomponents of fruit and vegetables. Since 1980, a consistent bulk of the results from both epidemiologic and experimental studies has strongly suggested that β-carotene, a widespread food carotenoid with provitamin A activity, could prevent the onset of cancers, especially lung cancer. Unfortunately, subsequent large-scale intervention studies failed, with one exception, to demonstrate any chemopreventive potency for β-carotene supplementation in humans, revealing a lack of knowledge of the mechanisms involved. In addition to their antioxidant properties, which have long been thought to be the clue to their biological effects, carotenoids appear to have a variety of cellular actions that make them remarkable ‘physiological modulators’. Research is still needed before new chemoprevention trials can eventually be undertaken on a strong scientific basis.

Dietary n - 6 and n - 3 polyunsaturated fatty acids and prostate cancer risk: a review of epidemiological and experimental evidence

AbstractObjective: This study reviews epidemiological and experimental works dealing with the effects of dietary n–6 or n–3 polyunsaturated fatty acids (PUFA) on prostate cancer (PCa) development and PCa risk. Methods: Systematic literature searches were made using Medline. The epidemiological studies reviewed (ecological, case–control, cohorts, and nested case–control) were those having tested the association of PCa risk with the dietary intake or the blood or adipose tissue levels of PUFA (n–6 PUFA, n–3 PUFA, long-chain n–3 PUFA, linoleic acid, α-linolenic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid), and with the dietary intake of fish and seafood. Experimental studies dealing with the effects of PUFA on PCa development in animal models or with PCa cell growth in vitro were also reviewed, as well as studies on the mechanisms of the effects of PUFA on PCa. Results: There is no or little evidence of an association of linoleic or arachidonic acids with PCa risk. Most epidemiological studies failed to find an association of PCa risk with fish or long-chain n–3 PUFA intake, but two recent cohort studies did find an inverse association of fish consumption with the risk of the latest stages of PCa. α-linolenic acid intake was associated with an increase of PCa risk in a majority of epidemiological studies, but other studies did not find this association. Experimental work in vitro and in vivo, as well as mechanistic studies, support a protective effect of long-chain n–3 PUFA on PCa, but data on the effects of linoleic and α-linolenic acids are scarce. Conclusions: Long-chain n–3 PUFA from fish are possible promising nutrients for the dietary prevention of PCa, but to-date with little epidemiological support. In contrast, studies suggest that α-linolenic acid intake might be a risk factor. New work, both epidemiological and experimental, is awaited to clarify these results.

Dietary lycopene decreases the initiation of liver preneoplastic foci by diethylnitrosamine in the rat

To test whether carotenoids can modulate the initiation of liver preneoplasia by diethylnitrosamine (DEN) or by 2-nitropropane (2-NP) in a sequential protocol of hepatocarcinogenesis, male weanling rats were fed for three or four weeks (respectively) diets containing beta-carotene, canthaxanthin, astaxanthin, or lycopene (300 mg/kg diet) or an excess of vitamin A (15,000 retinol equivalents/kg diet) or were treated intraperitoneally with 3-methylcholanthrene. During this period, all rats were injected intraperitoneally with the initiator carcinogen, either 2-NP (6 times at 100 mg/kg body wt) or DEN (once at 100 mg/kg body wt). Three weeks after the termination of carotenoid or vitamin A feeding, the rats received 50 ppm of 2-acetylaminofluorene in their diet for a two-week period, in the middle of which they were subjected to two-thirds partial hepatectomy, and were sacrificed one week later. gamma-Glutamyl transpeptidase- and placental glutathione S-transferase-positive foci were detected in frozen-cut liver sections by histochemical and histoimmunochemical techniques, respectively. None of the treatments tested had any influence on the number and size of preneoplastic liver foci induced by 2-NP, despite a significant incorporation and persistence in the liver of the carotenoids, except astaxanthin, and of supplemental vitamin A. Feeding the rats lycopene significantly decreased the size of gamma-glutamyl transpeptidase- and glutathione S-transferase-positive foci induced by DEN (by 64% and 65%, respectively), as well as the fraction of liver volume occupied by foci (by 84% and 79%, respectively), but did not significantly reduce their number. The other carotenoids, including beta-carotene, exerted no significant effects on DEN-induced preneoplasias. Lycopene does not appear to act through its antioxidant properties, but rather through its modulating effect on the liver enzyme activating DEN, cytochrome P-450 2E1.

β-Apo-8′-carotenal, but not β-carotene, is a strong inducer of liver cytochromes P4501A1 and 1A2 in rat

1. The catalytic activities of several phase I and II xenobiotic-metabolizing enzymes and their immunochemical detection have been investigated in liver microsomes and cytosol of the male rat, which had been fed for 15 days with diets containing 300 mg/kg β-carotene isomers (all-trans β-carotene or β-carotene from Dunaliella salina rich in 9-cis isomer or isomerized β-carotene), or apocarotenoids as β-apo-8′-carotenal, ethyl β-apo-8′-carotenoate and citranaxanthin.2. β-carotene, either all-trans or containing cis isomers, did not induce any significant change in the measured activities. By contrast, β-apo-8′-carotenal increased the liver content of cytochrome P450, the activity of NADH- and NADPH-cytochrome c reductase, and strongly increased some cytochrome P450-dependent activities, particularly ethoxyresorufin O-deethylase (x158), methoxyresorufin O-demethylase (x 22), pentoxy- and benzoxyresorufin O-dealkylases, but did not affect erythromycin N-demethylase nor nitrosodimethylamine N-demethylase activ...

Inhibition of aflatoxin B1‐ and N‐nitrosodiethylamine‐induced liver preneoplastic foci in rats fed naturally occurring allyl sulfides

The anti-initiating properties of allyl sulfides on rat liver carcinogenesis induced by N-nitrosodiethylamine (NDEA) or aflatoxin B1 (AFB1) were evaluated by using a three-step medium-term hepatocarcinogenesis assay. Diallyl sulfide (DAS) or diallyl disulfide (DADS) was added to the diet of rats (2 g/kg) for three weeks, during which NDEA or AFB1 was administered by intraperitoneal injection. The rats were submitted later to eight days of 2-acetylaminofluorene administration and to two-thirds hepatectomy, then to phenobarbital administration. After eight weeks, liver preneoplastic foci expressing the placental form of glutathione S-transferase were detected. The results show that DAS and DADS strongly reduced the number and the size of preneoplastic foci initiated by NDEA and AFB1, but especially by AFB1; DADS is more efficient than DAS. Most likely, the inhibition of the first step of hepatocarcinogenesis by allyl sulfides is related to the modulating effects that these compounds exert on the enzymes involved in activation and/or detoxication of the carcinogens. Our study demonstrated the chemopreventive potencies of dietary allyl sulfides in liver carcinogenesis induced by two potent hepatic carcinogens.

Plasma n-6 and n-3 polyunsaturated fatty acids as biomarkers of their dietary intakes: a cross-sectional study within a cohort of middle-aged French men and women

Objective:To measure the correlations between habitual intakes of individual n-6 and n-3 polyunsaturated fatty acids (PUFA) and their percentages in total plasma fatty acids in a population of adult men and women.Subjects/Methods:Two hundred and seventy-six men and 257 women aged 45–60 (men) or 35–60 (women) at baseline, volunteers of the French SU.VI.MAX cohort. Fifteen 24-h record questionnaires were used to estimate the habitual intake of energy, total fat and linoleic, α-linolenic acid, arachidonic, eicosapentaenoic (EPA), n-3 docosapentaenoic (DPA) and docosahexaenoic (DHA) acids. Fatty acid composition of fasting plasma total lipids has been determined at baseline.Results:Dietary intakes of linoleic acid, arachidonic acid, EPA and DHA were weakly but significantly correlated (0.16<r<0.28, P<0.01) with their respective percentages in plasma total fatty acids in both men and women. No correlation was observed between the plasma levels of α-linolenic acid and its dietary intake, and between the plasma levels of arachidonic acid and long-chain n-3 PUFA and the intakes of their 18-carbon precursors, linoleic and α-linolenic acid, respectively.Conclusions:The percentages of linoleic acid, arachidonic acid, EPA and DHA in plasma total fatty acids, but not that of α-linolenic acid, are acceptable markers of their habitual levels of intake. The plasma levels of long-chain n-6 and n-3 PUFA are not influenced by the intake levels of their precursors, linoleic and α-linolenic acids.

Association of fish and long-chain n-3 polyunsaturated fatty acid intakes with the occurrence of depressive episodes in middle-aged French men and women

This study aimed to seek whether habitual fish and seafood or n-3 long-chain PUFA intake could influence the occurrence of depressive episodes. In a subsample from the French SU.VI.MAX cohort, dietary habits have been assessed during the first 2 years of the follow-up (six 24-h records) and declarations of antidepressant prescription, taken as markers of depressive episodes, have been recorded during the 8-year follow-up. Subjects consuming fatty fish or with an intake of long-chain n-3 PUFA higher than 0.10% of energy intake had a significantly lesser risk of any depressive episode and of recurrent depressive episodes, but not of single depressive episode. These associations were stronger in men and in non-smokers. In contrast, smokers eating fatty fish had an increased risk of recurrent depression. These results suggest that a usual intake of fatty fish or long-chain n-3 PUFA may decrease the risk of recurrent depression in non-smokers.

Effects of β-Carotene and canthaxanthin on liver xenobiotic-metabolizing enzymes in the rat

The activities of several phase I and phase II xenobiotic-metabolizing enzymes have been measured in liver microsomes and cytosol of male rats that had been fed for 15 days with diets containing beta-carotene or canthaxanthin (300 mg/kg diet) or an excess of vitamin A (70,000 IU/kg diet), or to which beta-carotene had been administered by ip injections (7 x 10 mg/kg body weight). Microsomal cytochrome P-450 and the associated NADH- and NADPH-cytochrome c reductases were assayed, as well as several phase I and phase II enzyme activities. Phase I activities were markers of the families 1, 2, 3 and 4 of P-450; phase II activities were microsomal UDP glucuronosyl transferases (UGT) and cytosolic glutathione S-transferase (GST). Canthaxanthin accumulated in liver to a much higher level than did ingested or injected beta-carotene. Canthaxanthin increased the liver content of cytochrome P-450 (control value x 1.7), and the activity of NADH-cytochrome c reductase (x 1.5), and of some P-450-dependent enzymes (ethoxy-, methoxy-, pentoxy- and benzoxyresorufin O-dealkylases; x98, x15, x6.5 and x13, respectively), but not of others (erythromycin N-demethylase, nitrosodimethylamine N-demethylase and laurate omega-hydroxylase). Phase II activities were also increased: UGT1 (x3.4), UGT2 (x1.2) and GST (x1.2). This induction profile, characterized by the very strong increase of the activity associated with P4501A1, and the co-induction of UGT1, closely resemble that of a classical inducer, 3-methylcholanthrene. By contrast, neither beta-carotene (fed or injected), nor an excess of vitamin A induced any significant variation of the enzyme activities measured.

Association of folate intake with the occurrence of depressive episodes in middle-aged French men and women

A low folate intake or a low folate status have been found to be associated with a higher frequency of depression in populations, but the existence and the direction of a causal link between folate intake or status and depression is still uncertain. The aim of this study was to seek the relation between the habitual folate intake in middle-aged men and women and the occurrence of depressive episodes. In a subsample of 1864 subjects (809 men and 1055 women) from the French SU.VI.MAX cohort, dietary habits have been measured at the beginning of the follow-up (six 24 h records) and declarations of antidepressant prescription, taken as markers of depressive episodes, have been recorded during the 8-year follow-up. No significant association was observed between folate intake and the risk of any depressive episode or of a single depressive episode during the follow-up, in both men and women. In contrast, the risk of experiencing recurrent depressive episodes (two or more) during the follow-up was strongly reduced in men with high folate intake (OR 0.25 (95 % CI 0.06, 0.98) for the highest tertile v. the lowest, P for trend 0.046). This association was not observed in women. These results suggest that a low folate intake may increase the risk of recurrent depression in men.