J P Schuchardt1, T Köbe, V Witte, J Willers, A Gingrich, V Tesky, J Pantel, D Rujescu, T Illig, A Flöel, A Hahn. 1. Jan Philipp Schuchardt, Leibniz University Hannover, Institute of Food Science and Human Nutrition, Am Kleinen Felde 30, 30167 Hanover, Schuchardt@nutrition.uni-hannover.de, Telephone number: +49 (0)511 762 2987, Fax number: +49 (0)511 762 5729.
Abstract
BACKGROUND: Long-chain (> 20 C-atoms) polyunsaturated fatty acids (LC PUFAs) of both the omega-6 (n-6) and omega-3 (n-3) series are important for the functional integrity of brain and thereby cognition, memory and mood. Clinical studies observed associations between altered LC PUFA levels and neurodegenerative diseases such as Alzheimer´s disease and its prodromal stage, mild cognitive impairment (MCI). METHODS: The present study examined the LC PUFA status of MCI patients with specific view on the relative LC n-3 PUFA levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocyte membranes (omega-3 index). 12 single nucleotide polymorphisms (SNPs) of the FADS1, FADS2, and FADS3 gene clusters were genotyped in 111 MCI patients and evaluated associations with PUFA levels in erythrocyte membranes (primary outcome). In addition, the associations between FADS SNPs and LC PUFA levels with serum lipid levels as well as depressive symptoms were examined (secondary outcomes). RESULTS: Minor allele carrier of rs174546, rs174548 (FADS1), rs3834458, rs1535, rs174574, rs174575, rs174576, and rs174578 (FADS2) showed significant higher n-6 and n-3 precursor PUFA levels (linoleic acid, and alpha-linolenic acid, respectively) and lower arachidonic acid (AA) levels in erythrocyte membranes compared to the major allele carriers. Differences in EPA and DHA levels were not significant. Minor allele carriers of rs174574, rs174576 and rs174578 (FADS2) and rs174455 (FADS3) exhibited significant higher triglyceride levels, whereas minor allele carriers for rs174449 and rs174455 (FADS3) exhibited significant higher total- and LDL-cholesterol levels compared to the more common variant. The mean omega-3 index of the study cohort was 6.19 ± 1.55 %. In more than 85 % of the patients, the omega-3 index was below 8 % and in 23 % below 5 %. Moreover, it was shown that a low DHA status and omega-3 index was associated with depressive symptoms (Beck's depression-inventory). DISCUSSION AND CONCLUSION: These findings indicate an association between several FADS genotypes for higher n-6 and n-3 precursor PUFA and lower AA levels in erythrocyte membranes in minor compared to major allele carriers. To what extent FADS genotypes and a lower conversion of LA and ALA to biologically important LC PUFAs such as AA, EPA and DHA contributes to cognitive decline should be investigated in further trials. Nevertheless, the omega-3 index in this cohort of MCI patients can be classified as insufficient.
RCT Entities:
BACKGROUND: Long-chain (> 20 C-atoms) polyunsaturated fatty acids (LC PUFAs) of both the omega-6 (n-6) and omega-3 (n-3) series are important for the functional integrity of brain and thereby cognition, memory and mood. Clinical studies observed associations between altered LC PUFA levels and neurodegenerative diseases such as Alzheimer´s disease and its prodromal stage, mild cognitive impairment (MCI). METHODS: The present study examined the LC PUFA status of MCI patients with specific view on the relative LC n-3 PUFA levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocyte membranes (omega-3 index). 12 single nucleotide polymorphisms (SNPs) of the FADS1, FADS2, and FADS3 gene clusters were genotyped in 111 MCI patients and evaluated associations with PUFA levels in erythrocyte membranes (primary outcome). In addition, the associations between FADS SNPs and LC PUFA levels with serum lipid levels as well as depressive symptoms were examined (secondary outcomes). RESULTS: Minor allele carrier of rs174546, rs174548 (FADS1), rs3834458, rs1535, rs174574, rs174575, rs174576, and rs174578 (FADS2) showed significant higher n-6 and n-3 precursor PUFA levels (linoleic acid, and alpha-linolenic acid, respectively) and lower arachidonic acid (AA) levels in erythrocyte membranes compared to the major allele carriers. Differences in EPA and DHA levels were not significant. Minor allele carriers of rs174574, rs174576 and rs174578 (FADS2) and rs174455 (FADS3) exhibited significant higher triglyceride levels, whereas minor allele carriers for rs174449 and rs174455 (FADS3) exhibited significant higher total- and LDL-cholesterol levels compared to the more common variant. The mean omega-3 index of the study cohort was 6.19 ± 1.55 %. In more than 85 % of the patients, the omega-3 index was below 8 % and in 23 % below 5 %. Moreover, it was shown that a low DHA status and omega-3 index was associated with depressive symptoms (Beck's depression-inventory). DISCUSSION AND CONCLUSION: These findings indicate an association between several FADS genotypes for higher n-6 and n-3 precursor PUFA and lower AA levels in erythrocyte membranes in minor compared to major allele carriers. To what extent FADS genotypes and a lower conversion of LA and ALA to biologically important LC PUFAs such as AA, EPA and DHA contributes to cognitive decline should be investigated in further trials. Nevertheless, the omega-3 index in this cohort of MCI patients can be classified as insufficient.
Authors: J V Pottala; J A Talley; S W Churchill; D A Lynch; C von Schacky; W S Harris Journal: Prostaglandins Leukot Essent Fatty Acids Date: 2012-03-29 Impact factor: 4.006
Authors: Avshalom Caspi; Benjamin Williams; Julia Kim-Cohen; Ian W Craig; Barry J Milne; Richie Poulton; Leonard C Schalkwyk; Alan Taylor; Helen Werts; Terrie E Moffitt Journal: Proc Natl Acad Sci U S A Date: 2007-11-05 Impact factor: 11.205
Authors: Peter Rzehak; Joachim Heinrich; Norman Klopp; Linda Schaeffer; Sebastian Hoff; Günther Wolfram; Thomas Illig; Jakob Linseisen Journal: Br J Nutr Date: 2008-05-15 Impact factor: 3.718
Authors: S Hellstrand; E Sonestedt; U Ericson; B Gullberg; E Wirfält; B Hedblad; M Orho-Melander Journal: J Lipid Res Date: 2012-03-26 Impact factor: 5.922
Authors: M Haution-Bitker; T Gilbert; A Vignoles; C Lecardonnel; S Watelet; E Blond; J Drai; M Bonnefoy Journal: J Nutr Health Aging Date: 2018 Impact factor: 4.075
Authors: M Del C Valdés Hernández; J Kyle; J Allan; M Allerhand; H Clark; S Muñoz Manieg; N A Royle; A J Gow; A Pattie; J Corley; M E Bastin; J M Starr; J M Wardlaw; I J Deary; E Combet Journal: J Nutr Health Aging Date: 2017 Impact factor: 4.075
Authors: Maike Wolters; Carmen Dering; Alfonso Siani; Paola Russo; Jaakko Kaprio; Patrizia Risé; Luis A Moreno; Stefaan De Henauw; Kirsten Mehlig; Toomas Veidebaum; Denés Molnár; Michael Tornaritis; Licia Iacoviello; Yannis Pitsiladis; Claudio Galli; Ronja Foraita; Claudia Börnhorst Journal: PLoS One Date: 2017-07-21 Impact factor: 3.240
Authors: Anya Kalsbeek; Jenna Veenstra; Jason Westra; Craig Disselkoen; Kristin Koch; Katelyn A McKenzie; Jacob O'Bott; Jason Vander Woude; Karen Fischer; Greg C Shearer; William S Harris; Nathan L Tintle Journal: PLoS One Date: 2018-04-13 Impact factor: 3.240
Authors: Anna Maria Cybulska; Karolina Skonieczna-Żydecka; Arleta Drozd; Kamila Rachubińska; Jolanta Pawlik; Ewa Stachowska; Anna Jurczak; Elżbieta Grochans Journal: Int J Environ Res Public Health Date: 2019-11-04 Impact factor: 3.390