title: Effects of increasing docosahexaenoic acid intake in human healthy volunteers on lymphocyte activation and monocyte apoptosis.
abstract: Dietary intake of long-chain n-3 PUFA has been reported to decrease several markers of lymphocyte activation and modulate monocyte susceptibility to apoptosis. However, most human studies examined the combined effect of DHA and EPA using relatively high daily amounts of n-3 PUFA. The present study investigated the effects of increasing doses of DHA added to the regular diet of human healthy volunteers on lymphocyte response to tetradecanoylphorbol acetate plus ionomycin activation, and on monocyte apoptosis induced by oxidized LDL. Eight subjects were supplemented with increasing daily doses of DHA (200, 400, 800, 1600 mg) in a TAG form containing DHA as the only PUFA, for 2 weeks each dose. DHA intake dose-dependently increased the proportion of DHA in mononuclear cell phospholipids, the augmentation being significant after 400 mg DHA/d. The tetradecanoylphorbol acetate plus ionomycin-stimulated IL-2 mRNA level started to increase after ingestion of 400 mg DHA/d, with a maximum after 800 mg intake, and was positively correlated (P < 0.003) with DHA enrichment in cell phospholipids. The treatment of monocytes by oxidized LDL before DHA supplementation drastically reduced mitochondrial membrane potential as compared with native LDL treatment. Oxidized LDL apoptotic effect was significantly attenuated after 400 mg DHA/d and the protective effect was maintained throughout the experiment, although to a lesser extent at higher doses. The present results show that supplementation of the human diet with low DHA dosages improves lymphocyte activability. It also increases monocyte resistance to oxidized LDL-induced apoptosis, which may be beneficial in the prevention of atherosclerosis.
authors: INSERM U870, INSA-Lyon, 11 avenue Jean Capelle, Bât. Louis Pasteur, 69621 Villeurbanne Cedex, France.
authors: Saïda
authors: S
authors: Mebarek
authors: Natalia
authors: N
authors: Ermak
authors: Amal
authors: A
authors: Benzaria
authors: Stéphanie
authors: S
authors: Vicca
authors: Madeleine
authors: M
authors: Dubois
authors: Georges
authors: G
authors: Némoz
authors: Martine
authors: M
authors: Laville
authors: Bernard
authors: B
authors: Lacour
authors: Evelyne
authors: E
authors: Véricel
authors: Michel
authors: M
authors: Lagarde
authors: Annie-France
authors: AF
authors: Prigent
mesh_terms: D000704:Analysis of Variance; D000975:Antioxidants / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000032:analysis; D002478:Cells, Cultured; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000032:analysis; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008875:Middle Aged; D010743:Phospholipids / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D005227:Fatty Acids; D007376:Interleukin-2; D010743:Phospholipids; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids