Omega-3 fish oil may keep aging brains from shrinking and dimming, according to a study presented in June at the International Conference on Alzheimer's Disease in Paris.
Researchers at Rhode Island Hospital reported that their study linked fish oil supplements to better cognitive functioning as well as to bigger brains.
The study was led by Lori Daiello, PharmD, at the Rhode Island Hospital Alzheimer's Disease and Memory Disorders Center.
The data for the analyses was obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a large, NIH-funded study that followed older adults with normal cognition, mild cognitive impairment, and Alzheimer's Disease.
The 819 study participants were followed for more than three years, and underwent periodic memory testing and brain MRIs.
Study links fish oil to better thinking, bigger brains
Among the volunteers, 117 – or 14 percent – reported taking fish oil supplements regularly, before and during the three-year study.
The researchers compared cognitive functioning and brain atrophy (shrinkage) in those who reported that they routinely took omega-3 fish oil, versus the 702 (86 percent) who said they took no fish oil.
Ms. Daiello's team reported that compared to non-users, use of fish oil supplements was associated with better cognitive functioning during the study.
However, this association was significant only in those who showed normal thinking and memory capacity at the start of the study.
And better cognition was not seen in individuals who had a genetic risk factor for Alzheimer's Disease, known as APOE4.
The unique, novel finding of this study was a clear association between fish oil supplements and bigger brain volume.
As Daiello said, “We found a significant positive association between fish oil supplement use and average brain volumes in two critical areas utilized in memory and thinking – cerebral cortex and hippocampus – as well as smaller brain ventricular volumes compared to non-users at any given time in the study.
“In other words,” she continued, “fish oil use was associated with less brain shrinkage in patients taking these supplements during the ADNI study compared to those who didn't report using them.”
But, as with the thinking and memory advantages, the brain-size benefit was not seen in those who had the APOE4 gene variation.
Daiello continues, “These observations should motivate further study of the possible effects of long-term fish oil supplementation on important markers of cognitive decline and the potential influence of genetics on these outcomes.”
Prior findings render results plausible
This was not a controlled clinical trial, in which people would have been assigned to take fish oil or a placebo.
But its positive findings seem plausible, given the prior evidence showing that omega-3s can improve thinking/memory capacity, increase brain volume, and stimulate growth of new networks among brain cells (neurons).
The brain-volume benefit has been seen in some but not all prior studies (Puri BK et al. 2001; Quinn JF et al. 2010; McNamara RK 2010) … including three we reported on: “Omega-3s Boost Brain Networks Critical to Memory”, “Harvard Team Finds Key Cause of Age-Related Brain Fog”, and the “Study 1” section of “Omega-3s Display More Brain-Mood Benefits.”
Gene variation regulates Alzheimer's risk … and omega-3 benefit
The finding that fish oil did not benefit people with the APOE4 gene fits with most research related to late-onset Alzheimer's.
However, fish oil has may reduce agitation symptoms in APOE4 carriers, and improve symptoms of depression in patients who carry APOE2 or APOE3. See “Omega-3 DHA Alleviates Agitation in Early-Onset Alzheimer's” and the “Study #4” section of “Brain Benefits of Fish (and Veggies) Gain Support.”
Most cases of Alzheimer's disease (AD) are the “late-onset” form, which develops after age 60.
The APOE gene comes in several different forms, or alleles, three of which – APOE2, APOE3, and APOE4 – occur most often.
People who develop Alzheimer's are more likely to have an APOE4 allele than people who do not develop the disease.
APOE4 is present in about 25 to 30 percent of all people, and in about 40 percent of people with late-onset Alzheimer's.
People who inherit one or two APOE4 alleles also tend to develop the disease at an earlier age than those who do not have any APOE4 alleles.
Carriers of two E4 alleles have between 10 and 30 times the risk of developing AD by 75 years of age, compared to those not carrying any E4 alleles.
Why would the APOE variant matter?
Alzheimer's disease is characterized by – though not necessarily caused by – build-up of beta-amyloid protein plaque and tau protein tangles in the brain.
And some evidence suggests that people with APOE4 alleles are not as efficient at removing amyloid plaque.
The jury is still out, however, until research finds the link(s) between APOE4 and Alzheimer's risk and severity.
Calderon F, Kim HY. Docosahexaenoic acid promotes neurite growth in hippocampal neurons. J Neurochem. 2004 Aug;90(4):979-88. Erratum in: J Neurochem. 2004 Sep;90(6):1540.
Cansev M, Watkins CJ, van der Beek EM, Wurtman RJ. Oral uridine-5'-monophosphate (UMP) increases brain CDP-choline levels in gerbils. Brain Res. 2005 Oct 5;1058(1-2):101-8. Epub 2005 Aug 29.
Cao D, Xue R, Xu J, Liu Z. Effects of docosahexaenoic acid on the survival and neurite outgrowth of rat cortical neurons in primary cultures. J Nutr Biochem. 2005 Sep;16(9):538-46.
Darios F, Davletov B. Omega-3 and omega-6 fatty acids stimulate cell membrane expansion by acting on syntaxin 3. Nature. 2006 Apr 6;440(7085):813-7.
Issa AM, Mojica WA, Morton SC, Traina S, Newberry SJ, Hilton LG, Garland RH, Maclean CH. The efficacy of omega-3 fatty acids on cognitive function in aging and dementia: a systematic review. Dement Geriatr Cogn Disord. 2006;21(2):88-96. Epub 2005 Dec 9. Review.
Lim WS, Gammack JK, Van Niekerk J, Dangour AD. Omega 3 fatty acid for the prevention of dementia. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005379. Review.
Marszalek JR, Lodish HF. Docosahexaenoic acid, fatty acid-interacting proteins, and neuronal function: breastmilk and fish are good for you. Annu Rev Cell Dev Biol. 2005;21:633-57. Review.
McEvoy LK, Holland D, Hagler DJ Jr, Fennema-Notestine C, Brewer JB, Dale AM; Alzheimer's Disease Neuroimaging Initiative. Mild cognitive impairment: baseline and longitudinal structural MR imaging measures improve predictive prognosis. Radiology. 2011 Jun;259(3):834-43. Epub 2011 Apr 6.
McNamara RK. DHA deficiency and prefrontal cortex neuropathology in recurrent affective disorders. J Nutr. 2010 Apr;140(4):864-8. Epub 2010 Feb 10.
Puri BK, Counsell SJ, Hamilton G, Richardson AJ, Horrobin DF. Eicosapentaenoic acid in treatment-resistant depression associated with symptom remission, structural brain changes and reduced neuronal phospholipid turnover. Int J Clin Pract. 2001 Oct;55(8):560-3.
Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, Galvin JE, Emond J, Jack CR Jr, Weiner M, Shinto L, Aisen PS. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA. 2010 Nov 3;304(17):1903-11.
Rhode Island Hospital (RHI). Rhode Island Hospital Study Identifies Fish Oil's Impact On Cognition And Brain Structure. August 17, 2011. Accessed at http://www.lifespan.org/news/2011/08/17/rhode-island-hospital-study-identifies-fish-oils-impact-on-cognition-and-brain-structure/
Shrivastava R, Vincent B, Gobron S, Cucuat N, John GW. Evidence for growth-promoting effects of omega n - 3 fatty acids alone and in combination with a specific vitamin and mineral complex in rat neuroblastoma cells. Nutr Neurosci. 2005 Oct-Dec;8(5-6):317-21.
Tosun D, Schuff N, Mathis CA, Jagust W, Weiner MW; Alzheimer's Disease NeuroImaging Initiative. Spatial patterns of brain amyloid-beta burden and atrophy rate associations in mild cognitive impairment. Brain. 2011 Apr;134(Pt 4):1077-88. Epub 2011 Mar 22.
Wang L, Pooler AM, Albrecht MA, Wurtman RJ. Dietary uridine-5'-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats. J Mol Neurosci. 2005;27(1):137-45.
Wurtman R, Ulus I, Cansev M, Watkins W, Wang L, Marzloff G. Increased dendritic spine density in adult gerbil hippocampus following oral UMP and DHA supplementation. The International Academy of Nutrition & Aging 2006 SYMPOSIUM II Nutrition and Alzheimer's Disease/Cognitive Decline. Oral Presentation May 2, 2006, InterContinental Chicago.
Wurtman RJ, Ulus IH, Cansev M, Watkins CJ, Wang L, Marzloff G. Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. Brain Res. 2006 Apr 19; [Epub ahead of print]