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Pascale Benlian, Alain Zourdani, Khaldia Belabbas, Giuseppe Querques, Eric H. Souied, NAT2 Study Group; Omega-3, Essential and Monounsaturated Fatty Acid Deficiency in Exudative Age-related Macular Degeneration: A survey from the NAT-2 Study. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2935.
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To evaluate lipid, lipoprotein and fatty acid profile in patients with advanced exudative Age-related Macular Degeneration (AMD) participant to the NAT2 study compared to normal sighted non-AMD individuals (CON). The NAT2 study (ARVO2011 #6642) showed overall reduced 3-year incidence (27% vs 33% expected) of choroidal neovessels (CNV), similarly in patients randomly allocated oral Docosa-Hexaenoic Acid (DHA 840mg/d) or Olive Oil (OLO 602mg/d). Since cohort studies suggested that daily OLO or DHA intake could prevent exudative AMD, here we explored if changes in circulating and cellular FA could account for main findings of the NAT2 study.
Exudative AMD patients (N=289, 188F/101M, Age=74.2 ±6.6y) had legal blindness (LogMar 1.044) and CNV in one eye at study entry. Age and sex matched normal sighted controls (n=102, 60F/42M, Age=73.0 ±6.0y) were recruited in parallel with NAT2 participants after ophthalmologic and fundus examination. Fasting plasma lipoproteins were measured enzymatically. Plasma and erythrocyte membrane fatty acid (FA) profile was assessed by Gas Chromatography.
Except for lower plasma TG (1.12 vs 1.33 mmol/L, p=0.002) plasma lipoprotein profile was similar in AMD and CON groups. In both groups HDL cholesterol was higher in women than in men (AMD: 1.89F vs 1.56M, CON: 1.89F vs 1.70M mmol/L, p<0.001). In contrast, FA profile was altered in exudative AMD compared with CON. AMD patients had cellular EPA/DHA insufficiency assessed by lower erythrocyte membrane EPA+DHA index (3.94% vs 4.41%, p<0.001). An imbalance in circulating and cellular monounsaturated FA, assessed by decreased Oleic Acid/Oleic Acid n-7 ratio was observed in serum (OA/OAn-7: 11.7 vs 13.2, p<0.001) and membranes (OA/OAn-7: 10.8 vs 12.6, p<0.001). Circulating and cellular essential FA deficiency was assessed by higher levels of EicosaTrienoic Acid/Arachidonic Acid ratio in plasma (ETA/ARA: 0.10 vs 0.04, p<0.001) and membranes (ETA/ARA: 0.09 vs 0.02, p<0.001). Interestingly, at 3-year follow-up of the NAT2 study, while circulating and cellular EPA, DHA and OA increased accordingly in DHA or OLO allocated groups, in both groups the EPA+DHA index, the OA/OAn-7 and ETA/ARA ratio returned to balanced levels observed in the CON group.
Exudative AMD at the stage of legal blindness and CNV is associated with EPA/DHA, monounsaturated and essential fatty acid deficiency compared with non-AMD normal sighted elderly individuals. A return at 3-y to balanced FA profile in all NAT2 study participants, suggests that nutritional changes occurred on top of oral DHA and OLO supplementation, possibly accounting for lower overall CNV incidence.
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