The Effect of Omega-3 Deficiency on Brain Health

Most people do not realize that, with a few exceptions, most of the global adult population is experiencing an unprecedented deficiency of omega-3 (eicosapentaenoic acid; EPA and docosahexaenoic acid; DHA) dietary intake and therefore of functional physiological status (1). 

The forces behind this trend include reduced consumption of fatty fish, reductions of omega-3 levels in farmed fish, and that a percentage of the population does not supplement their diet with these essential fats. Making the problem worse is the significant dietary presence of omega-6 fatty acids in processed foods(1,2). Hundreds of years ago, the human diet contained roughly 4:1 omega-6 to omega-3 fatty acids; the ratio is now more in the range of 20:1. The issue is that omega-6 fatty acids tend to promote inflammation while omega-3 fatty acids tend to be anti-inflammatory.

Specific to brain and neurological health, the omega deficiency has severe consequences for our brain structure, function, and overall health. Our brains are dependent on omega-3, especially DHA, as DHA is a major component of brain tissue. DHA comprises 40% of the polyunsaturated fatty acids in the brain and 60% in the retina of the eye (4,5,6).

DHA is transported to the brain by the bloodstream, so the amount of DHA present in our blood is will help determine if our brain and eyes receive adequate levels for proper function and longevity. Since humans do not efficiently synthesize DHA, we need to get DHA from food or supplementation in sufficient amounts throughout life for the proper build-up and maintenance of our brain (3). 

  Additionally, some brain health issues such as atherosclerosis or major depression are associated with types inflammation in the brain (7). High levels of omega-3 fatty acids in blood have been shown to mitigate development of inflammation and facilitate its resolution(8).. Omega-3s help control inflammation by three primary mechanisms:

  • Reducing the levels of pro-inflammatory fats in cell membranes
  • Conversion of cellular omega-3 fats into anti-inflammatory prostaglandins and pro-resolving mediators (resolvins, merasins, lipoxins, protectins)
  • Downregulation of proinflammatory genes (Nutrigenomic effect)

The Best Way to Consume Omega-3s

Conventional nutrition research posits that intake of omega-3s automatically determines the body’s omega-3 status. But it is important to emphasis that in order for fat to be optimally absorbed, fat digestion needs to be initiated by release of emulsifying bile salts as well as pancreatic lipase enzymes (9). This occurs effectively only in the presence of food. Therefore, in order to maximize health ;benefits and to truly get your money’s worth, supplemental omega-3 should be consumed with meals (10).
Of course, if you are eating healthy, clean, fatty fish, your omega-3s are coming a long as part of the nutritional profile of your meal!

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8% Omega-3 in Key Cells is the Magic Number!

Across multiple studies, an Omega-3 Index (level of omega-3 in your red blood cells as a percentage of total fats) in the range of 8%, is shown to be optimal in supporting brain structure maintenance, function, and longer-term health prospect.

A review of recent findings:

  • In a study of individuals aged 67 years on average, who were free of clinical dementia, total brain volume correlated with Omega-3 Index, as did cognitive functions like visual memory, executive function, and abstract thinking (15).
  • In a study of females aged 65 years or older and free of dementia the Omega-3 Index correlated with total brain volume measured 8 years later (16). Also, the progression to dementia was much less likely and occurred later in life in those with a higher Omega-3 Index (14).
  • In younger individuals the Omega-3 Index correlated with executive function and cognitive flexibility (17, 18) while in the oldest individuals yet studied, aged >88 years, cognitive impairment was four times more likely with a mean Omega-3 Index below, 8% (11).
  • A recent meta-analysis also identified low levels of EPA & DHA as a risk factor for cognitive impairment (19,20).

At all ages studied therefore, there is robust support for an Omega-3 Index target range of 8-11% for optimal brain structure, function and health. 

Key Takeaways for Supporting Optimal Brain Health

  • Eat more fatty fish, wild caught and healthy farm raised (please note that recent research shows the omega-3 levels are dropping in most farmed fish).
  • Supplement with a high-quality omega-3 supplement (know the manufacturer, know who does the third-party purity testing), target at least 1-gram total omega-3 per day.
  • Consume an anti-inflammatory dietary approach that includes plenty of fruits, vegetables, grains, low-fat proteins, and avoid pro-inflammatory fats and simple sugars.
  • Get exercise often, stay hydrated, get your sleep, banish stress, smile more often, read books, learn a new language.

References

  1. Blasbalg TL, Hibbeln JR, Ramsden CE, Majchrzak SF, Rawlings RR. Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am J Clin Nutr. 2011;93:950-62
  2. Sprague M, Dick JR, Tocher DR. Impact of sustainable feeds on omega-3 long-chain fatty acid levels in farmed Atlantic salmon, 2006-2015. Sci Rep. 2016;6:21892.
  3. von Schacky C. w-3 Fettsäuren und Hirnfunktion. Orthomol Med 2016;2:6-10
  4. Amen DG, Harris WS, Kidd PM, Meysami S, Raji CA. Quantitative Erythrocyte Omega-3 EPA Plus DHA Levels are Related to Higher Regional Cerebral Blood Flow on Brain SPECT. J Alzheimers Dis. 2017;58:1189-1199
  5. Joris PJ, Mensink RP, Adam TC, Liu TT. Cerebral Blood Flow Measurements in Adults: A Review on the Effects of Dietary Factors and Exercise. Nutrients. 2018;10. pii: E530.
  6. Schwarz C, Wirth M, Gerischer L, et al. Effects of Omega-3 Fatty Acids on Resting Cerebral Perfusion in Patients with Mild Cognitive Impairment: A Randomized Controlled Trial. J Prev Alzheimers Dis. 2018;5:26-30.
  7. Setiawan E, Wilson AA, Mizrahi R, et al. Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes. JAMA Psychiatry. 2015;72:268-75
  8. Calder PC. Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochem Soc Trans. 2017;45:1105-1115.
  9. Schuchardt JP, Hahn A. Bioavailability of long-chain omega-3 fatty acids. Prostaglandins Leukot Essent Fatty Acids. 2013;89:1-8.
  10. Davidson MH, Johnson J, Rooney MW, Kyle ML, Kling DF. A novel omega-3 free fatty acid formulation has dramatically improved bioavailability during a low-fat diet compared with omega-3-acid ethyl esters: the ECLIPSE (Epanova(®) compared to Lovaza(®) in a pharmacokinetic single-dose evaluation) study. J Clin Lipidol. 2012;6:573-84.
  11. Dyerberg J, Madsen P, Møller JM, Aardestrup I, Schmidt EB. Bioavailability of marine n-3 fatty acid formulations. Prostaglandins Leukot Essent Fatty Acids. 2010;83:137-41.
  12. Harris WS and von Schacky C. The Omega-3 Index: A New Risk Factor for Death from CHD? Preventive Medicine 2004;39:212-20.
  13. Lukaschek K, von Schacky C, Kruse J, Ladwig K. Cognitive impairment is associated with low Omega-3 Index in the elderly. Results from the KORA-Age study. Dementia Geriatr Cogn Dis 2016;42:236-45
  14. Ammann EM, Pottala JV, Robinson JG, Espeland MA, Harris WS. Erythrocyte omega-3 fatty acids are inversely associated with incident dementia: Secondary analyses of longitudinal data from the Women's Health Initiative Memory Study (WHIMS). Prostaglandins Leukot Essent Fatty Acids. 2017;121:68-75
  15. Tan ZS, Harris WS, Beiser AS, et al. Red Blood Cell Omega-3 Fatty Acid Levels and Markers of Accelerated Brain Aging. Neurology 2012;78:658-64
  16. Pottala JV, Yaffe K, Robinson J, Espeland MA, Wallace R, Harris WS. Higher RBC EPA+DHA corresponds with larger total brain and hippocampal volumes: WHIMS-MRI study. Neurology 2014;82:435-42
  17. Johnston DT, Deuster PA, Harris WS, Macrae H, Dretsch MN. Red blood cell omega-3 fatty acid levels and neurocognitive performance in deployed U.S. Servicemembers. Nutr Neurosci. 2013;16:30-8
  18. Bigornia SJ, Scott TM, Harris WS, Tucker KLs. Prospective Associations of Erythrocyte Composition and Dietary Intake of n-3 and n-6 PUFA with Measures of Cognitive Function. Nutrients 2018;10,1253
  19. Lin PY, Chiu CC, Huang SY, Su KP. A meta-analytic review of polyunsaturated fatty acid compositions in dementia. J Clin Psychiatry. 2012;73:1245-54
  20. Coley N, Raman R, Donohue MC, Aisen PS, Vellas B, Andrieu S. Defining the Optimal Target Population for Trials of Polyunsaturated Fatty Acid Supplementation Using the Erythrocyte Omega-3 Index: A Step Towards Personalized Prevention of Cognitive Decline? J Nutr Health Aging. 2018;22:982-998
  21. West, A. L., Kindberg, G. M., Hustvedt, S. O. & Calder, P. C. A Novel Self-Micro-Emulsifying Delivery System Enhances Enrichment of Eicosapentaenoic Acid and Docosahexaenoic Acid after Single and Repeated Dosing in Healthy Adults in a Randomized Trial. The Journal of Nutrition (2018). doi:10.1093/jn/nxy127
  22. Qin, Y., Nyheim, H., Haram, E. M., Moritz, J. M. & Hustvedt, S. O. A novel self-micro-emulsifying delivery system (SMEDS) formulation significantly improves the fasting absorption of EPA and DHA from a single dose of an omega-3 ethyl ester concentrate. Lipids Health Dis. 16, 204 (2017).

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