Brain atrophy in cognitively impaired elderly: the importance of long-chain v-3 fatty acids and B vitamin status in a randomized controlled trial 1,2 Fredrik Jernerén, 3* Amany K Elshorbagy, 3,4 Abderrahim Oulhaj, 5 Stephen M Smith, 6 Helga Refsum, 3,7 and A David Smith 3 3 From the Oxford Project to Investigate Memory and Ageing (OPTIMA), Department of Pharmacology, University of Oxford, Oxford, United Kingdom; 4 Department of Physiology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt; 5 Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates; 6 Functional Magnetic Resonance Imaging of the Brain Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; and 7 Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway ABSTRACT Background:Increased brain atrophy rates are common in older people with cognitive impairment, particularly in those who eventually convert to Alzheimer disease. Plasma concentrations of omega-3 (v-3) fatty acids and homocysteine areassociated with the development of brain atrophy and dementia. Objective:We investigated whether plasmav-3 fatty acid concentrations (eicosapentaenoic acid and docosahexaenoic acid) modify the treatment effect of homocysteine-lowering B vitamins on brain atrophy rates in a placebo-controlled trial (VITACOG). Design:This retrospective analysis included 168 elderly people ($70 y) with mild cognitive impairment, randomly assigned either to placebo (n= 83) or to daily high-dose B vitamin supplementation (folic acid, 0.8 mg; vitamin B-6, 20 mg; vitamin B-12, 0.5 mg) (n=85).Thesubjects underwent cranial magnetic resonance imaging scans at baseline and 2 y later. The effect of the intervention was analyzed according to tertiles of baseline v-3 fatty acid concentrations.
Results:There was a significant interaction (P= 0.024) between B vitamin treatment and plasma combinedv-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) on brain atrophy rates. In subjects with high baselinev-3 fatty acids (.590mmol/L), B vitamin treatment slowed the mean atrophy rate by 40.0% compared with placebo (P= 0.023). B vitamin treatment had no significant effect on the rate of atrophy among subjects with low baselinev-3 fatty acids (,390mmol/L). High baselinev-3 fatty acids were associated with a slower rate of brain atrophy in the B vitamin group but not in the placebo group. Conclusions:The beneficial effect of B vitamin treatment on brain atrophy was observed only in subjects with high plasmav-3 fatty acids. It is also suggested that the beneficial effect ofv 3 fatty acids on brain atrophy may be confined to subjects with good B vitamin status. The results highlight the importance of identifying subgroups likely to benefit in clinical trials. This trial was registered at www. controlled-trials.com as ISRCTN94410159. Am J Clin Nutr 2015;102:215–21.
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n‑3 PUFA Esterified to Glycerol or as Ethyl Esters Reduce Non‑Fasting Plasma Triacylglycerol in Subjects with Hypertriglyceridemia: A Randomized Trial
Anne Hedengran • Pal B. Szecsi • Jørn Dyerberg • William S. Harris • Steen Stender
Received: 25 August 2014 / Accepted: 31 October 2014
© AOCS 2014
Long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) has been investigated solely in fasting and postprandial subjects. However, non-fasting triacylglycerols are more strongly associated with risk of cardiovascular disease. The objective of this study was to investigate the effect of long-chain n-3 PUFA on non-fasting triacylglycerol levels and to compare the effects of n-3 PUFA formulated as acyl glycerol (AGPUFA) or ethyl esters (EE-PUFA). The study was a double blinded randomized placebo-controlled interventional trial, and included 120 subjects with non-fasting plasma triacylglycerol levels of 1.7–5.65 mmol/L (150–500 mg/dL). The participants received approximately 3 g/day of AG-PUFA, EE-PUFA, or placebo for a period of eight weeks. The levels of non-fasting plasma triacylglycerols decreased 28 % in the AG-PUFA group and 22 % in the EE-PUFA group (P < 0.001 vs. placebo), with no significant difference between the two groups. The triacylglycerol lowering effect was evident after four weeks, and was inversely correlated with the omega-3 index (EPA + DHA content in erythrocyte membranes). The omega-3 index increased 63.2 % in the AG-PUFA group and 58.5 % in the EE-PUFA group (P < 0.001). Overall, the heart rate in the AG-PUFA group decreased by three beats per minute (P = 0.045). High density lipoprotein (HDL) cholesterol increased in the AG-PUFA group (P < 0.001). Neither total nor non-HDL cholesterol changed in any group. Lipoprotein-associated phospholipase A2 (LpPLA2) decreased in the EE-PUFA group (P = 0.001). No serious adverse events were observed. Supplementation with long-chain n-3 PUFA lowered non-fasting triacylglycerol levels, suggestive of a reduction in cardiovascular risk. Regardless of the different effects on heart rate, HDL, and LpPLA2 that were observed, compared to placebo, AG-PUFA, and EE-PUFA are equally effective in reducing non-fasting triacylglycerol levels.
Distribution and Dosing of Omega- 3 Fatty Acids in Humans Linda M.Arterburn,PhD Eileen Bailey- Hall,BS Harry Oken,MD Martek Biosciences Corporation University of Maryland,Baltimore
- DHA is principal n-3 fatty acid in tissues.
- Limited inter- conversion of n-3 FAs.
- ALA not adequate source of LCn-3.
- Plasma response to dietary intake.
- ALA does not accumulate appreciably.
- Dose dependent increases in EPA and DHA.
- Plasma levels equilibrate within 4 wks.
- 2 g DHA/ day gives close to maximal DHA response.
- Tissue levels LCn-3 increase with supplementation.
- Milk DHA levels reflect maternal dietary intake
- Infant DHA levels determined by dietary intake
Omega Omega –3 fatty acids in inflammation:3 fatty acids in inflammation: Actions &impact on rheumatoid arthritis,Actions &impact on rheumatoid arthritis, inflammatory bowel disease and asthma inflammatory bowel disease and asthma
Philip Calder Philip Calder Professor of Nutritional Immunology Professor of Nutritional Immunology University of Southampton University of SouthamptonSummary.
- Eicosanoids derived from arachidonic acid are involved as mediators and regulators of inflammation
- EPA and DHA from oily fish/ fish oil can partially replace arachidonic acid in membrane phospholipids
- W-3 fatty acids (especially EPA) lead to decreased production of eicosanoids from arachidonic acid
- EPA and DHA give rise to anti –inflammatory resolvins (cell culture & animal work)
- W-3 fatty acids lead to decreased production of inflammatory cytokines
- Through these effects W-3 fatty acids act to decrease inflammation
- W-3 fatty acids may protect against and provide therapy for diseases with an overt orcovert inflammatory component
- Evidence for therapeutic benefit from n-3 fatty acids is reasonably strong in RA but is weaker elsewhere — doses used are quite high (approx.3.5 g/ day)
- a-Linolenic acid is not anti –inflammatory at intakes <10 g/d