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DHA omega-3 fundamental for optimal brain structure, function and health

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Modern crisis of global omega-3 deficiency and brain health consequences

In the last century, with few geographical exceptions, the global adult population has experienced an unprecedented deficiency of omega-3 (eicosapentaenoic acid; EPA and docosahexaenoic acid; DHA) measured in blood (1). 

The drivers of this trend include reduced consumption of fatty fish, reductions of omega-3 levels in farmed fish and the significant dietary increase of competing omega-6 e.g. from seed oils (1,2).

Brain functions related to omega-3 status

Importantly, this ongoing deficiency has severe consequences for our brain structure, function and overall health because our brains are dependent on omega-3, especially DHA, with high levels in blood shown to support optimal brain function and health (4,5,6).

DHA can only reach the brain via the bloodstream, so the amount of DHA present in our blood is decisive. Since humans cannot synthesize large amounts of 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). 

 

Figure 1. Brain functions related to Omega-3 status

Additionally, some brain health issues such as atherosclerosis or major depression are associated with (phases of) inflammation in the brain (e.g. 7). High levels of EPA and DHA in blood however, have been shown to mitigate development of inflammation and facilitate its resolution (8).

In short: our brain is nourished via the bloodstream. For optimal brain structure, function and health, optimal levels of omega-3 EPA and especially DHA, need to be present in our blood throughout life.

Uptake (not intake) of omega-3 to blood cells critical for increasing Omega-3 Index

Conventional nutrition research has focused on the intake of EPA and DHA based on the logic that intake determines uptake of omega-3 in the body. For fat to be absorbed however, fat digestion needs to be initiated by release of emulsifying bile salts as well as pancreatic lipases (9). This occurs effectively only after a high-fat meal, explaining why small amounts of EPA and DHA are on average 13 times better absorbed with a high-fat than a low-fat meal (10).
While other individual and dietary factors further impact absorption variability, it must be clarified that the chemical form of EPA and DHA (e.g. ethyl-ester vs triglyceride vs. phospholipid etc.) has a minor impact with a mean factor of 1.5 – 2.0 (11).

It’s therefore critical when looking to increase and maintain our omega-3 levels, that sufficient and​ efficient omega-3 absorption are top priorities.

The data above were all generated by measuring levels of EPA and DHA in blood cells, using the omega-3 Index i.e. the percentage of EPA and DHA in red blood cells (12). The Omega-3 Index has a low biological variability, reflects omega-3 status of all other cells of the human body, including the brain and therefore assesses an individual’s omega-3, EPA and DHA (3). Leading industry thinkers propose the Omega-3 Index as best practice for any truly accurate assessment of Omega-3 status in individuals or broader populations.

Omega-3 Index status >8% correlates positively with brain structure, function and health

Across multiple studies, the Omega-3 Index correlates positively with better brain structure, function and health:

  • 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. 

How to achieve an optimal Omega-3 Index for optimal brain health? 

Knowing that intake does not predict Omega-3 index status, BASF recently launched a technology solution that delivers optimal omega-3 content optimal and ​absorption; Accelon is a self-micro emulsifying delivery system designed to mitigate the need for fatty food intake at the same time as supplementation and is now available in a new, high-DHA variant. In validating the technology in non-clinical and clinical tests, Accelon high-DHA increased absorption by a minimum of three times compared to standard fish oil concentrates (21, 22). These absorption levels were achieved when the supplement was taken first thing in the morning in the absence of specific meals or conditions.

Increased DHA omega-3 absorption from Accelon also results in more people achieving Omega-3 Index levels associated with improved cognitive function. In a 12-week trial of healthy people with starting index levels of 6.5% or lower, 70% of people who took Accelon high-DHA achieved 8% index levels by the end of the study. The rate was 25% among the group that received high concentrate omega-3 oil only, suggesting Accelon high-DHA is far more efficient and consistent in helping raise the Omega-3 Index than regular products in a representative population.

The growth opportunity is for brand owners to take advantage of Accelon high-DHA technology and clinical results, combined with insights on how people take omega-3 supplements and the proven benefits between DHA and brain, eye and cell health.

Conclusions for optimal brain structure, function and health

  • Optimal brain structure, function and health depend on sufficient levels of omega-3 EPA & DHA in blood throughout life.
  • A target Omega-3 Index for optimal brain structure, function and health is in the range of 8-11%.
  • Uptake of omega-3 is not determined by intake, so efficient omega-3 absorption should be a primary consideration when an individual is looking to increase their Omega-3 index to 8-11%.
  • In all age groups studied so far, brain structure and numerous brain functions, like executive function, aspects of memory, reaction time, age-dependent brain loss, cognitive impairment and many others could be improved with an Omega-3 Index increased to 8-11%.
  • Importantly, with an optimal Omega-3 Index, a longer life can be expected than with lower Omega-3 Index levels; with brain structure, function and health being maintained to match.
  • BASF Accelon high-DHA has been recently launched and is clinically proven to provide a minimum 3X absorption and ​help increase Omgea-3 Index status more efficiently, compared to standard fish oil concentrates.

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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