The Omega 3 Index

The Omega 3 Index (n-3 index)

Dr. Dicken Weatherby & Beth Ellen DiLuglio, MS, RDN, LDN

Omega-3s are important to maintaining the health of the cardiovascular, pulmonary, immune, endocrine, and nervous systems. Omega-3 DHA is especially important in vision. In general, omega-3s EPA and DHA help control inflammation, blood pressure, heart rate, and blood clotting, and they support immune and neurological function. [i] [ii] [iii] [iv] [v]

The n-3 index measures the percentage of long-chain omega-3 fats EPA and DHA in red blood cell membranes (or may be measured in phospholipid portion of blood).

  • It reflects EPA and DHA in tissues including cardiac and GI tissues[vi] [vii] [viii] [ix]
  • Used as a biomarker of cardiovascular risk, especially sudden cardiac death
  • Suboptimal Omega-3 Index below 8% correlates with cardiovascular disease, cognitive impairment, major depression, and premature birth[x]
  • n-3 index between 0 and 4% is associated with an increased risk of sudden cardiac death, acute coronary syndrome, cognitive impairment, dementia, non-alcoholic fatty liver disease, depression, eye disease, and death from all causes. [xi]

2017 meta-analysis

  • Fatal coronary heart disease was significantly reduced by 15% for every standard deviation increase in the Omega-3 Index.
  • Dose-response research suggests that increasing EPA and DHA intake by 1.5 grams per day will increase the index by 4%. (maximal effects at 8 weeks)
  • Researchers confirm that an index below 4% is high risk, while an index above 8% is desirable with ranges from 8-12% observed in clinical research

Results from the Physician Health Study categorized the association of Omega-3 index with sudden death from cardiac causes as follows:[xii] [xiii]

High risk less than 3.45%
45% reduced risk 3.46-4.16%
72% reduced risk 4.17-4.98%
81% reduced risk  Greater than 4.98%

Inflammation [xiv]

  • Increased cell membrane EPA correlated with substantial inhibition of pro-inflammatory compounds, leading to decreased use of NSAIDs.
  • Placebo-controlled trials support the use of fish oil supplementation in chronic inflammatory states such as
    • rheumatoid arthritis, inflammatory bowel disease, lupus, multiple sclerosis, psoriasis, and migraine headaches.
  • Increasing dietary omega-3s and reducing omega-6s may help reduce inflammation in susceptible individuals

Supplementation

Supplementation with 460 mg EPA/380 mg DHA for four weeks, with an increase to 980 mg EPA/760 mg DHA for the next four weeks, resulted in an increase in mean baseline n-3 index from 4.9% to 8.4%.[xv]

Six months of supplementation with fish oil (840 mg EPA, 560 mg DHA) in individuals at high risk of psychosis increased n-3 index from 3% to 4.12%.[xvi]

Food sources[xvii]

Omega-3s

  • EPA, DHA: salmon, herring, oysters, rainbow trout, tuna, Dungeness crab
  • Alpha-linolenic acid: flaxseeds and oil, chia seeds, English walnuts, canola oil, soybean oil, mustard oil, black walnuts, firm tofu

Omega-6s

  • Arachidonic acid: meat, poultry, eggs
  • Linoleic acid: safflower, sunflower, corn, soybean, and sesame oils
  • Pine nuts, pecans, Brazil nuts

References

[i] Linus Pauling Institute Micronutrient Information Center at OSU. Essential fatty acids. Updated May 2019. [R]

[ii] Luxwolda, Martine F et al. “The relation between the omega-3 index and arachidonic acid is bell shaped: synergistic at low EPA+DHA status and antagonistic at high EPA+DHA status.” Prostaglandins, leukotrienes, and essential fatty acids vol. 85,3-4 (2011): 171-8. doi:10.1016/j.plefa.2011.05.004 [R]

[iii] NIH ODS. Omega-3 Fatty Acids. [R]

[iv] Peet, M et al. “Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients.” Biological psychiatry vol. 43,5 (1998): 315-9. [R]

[v] Calder, P C. “Very long-chain n-3 fatty acids and human health: fact, fiction and the future.” The Proceedings of the Nutrition Society vol. 77,1 (2018): 52-72. [R]

[vi] von Schacky, C. “Verwirrung um die Wirkung von Omega-3-Fettsäuren : Betrachtung von Studiendaten unter Berücksichtigung des Omega-3-Index” [Confusion about the effects of omega-3 fatty acids : Contemplation of study data taking the omega-3 index into consideration]. Der Internist vol. 60,12 (2019): 1319-1327. doi:10.1007/s00108-019-00687-x [R]

[vii] Harris, William S. “The omega-3 index as a risk factor for coronary heart disease.” The American journal of clinical nutrition vol. 87,6 (2008): 1997S-2002S. [R]

[viii] von Schacky, Clemens. “Omega-3 index and cardiovascular health.” Nutrients vol. 6,2 799-814. 21 Feb. 2014, [R]

[ix] Gurzell, Eric A et al. “Is the omega-3 index a valid marker of intestinal membrane phospholipid EPA+DHA content?.” Prostaglandins, leukotrienes, and essential fatty acids vol. 91,3 (2014): 87-96. [R]

[x] von Schacky, Clemens. “Omega-3 index and cardiovascular health.” Nutrients vol. 6,2 799-814. 21 Feb. 2014, [R]

[xi] Davinelli, Sergio et al. “Metabolic indices of polyunsaturated fatty acids: current evidence, research controversies, and clinical utility.” Critical reviews in food science and nutrition, 1-16. 14 Feb. 2020, [R] 

[xii] Superko, H Robert et al. “Omega-3 fatty acid blood levels: clinical significance and controversy.” Circulation vol. 128,19 (2013): 2154-61. [R]

[xiii] Albert, Christine M et al. “Blood levels of long-chain n-3 fatty acids and the risk of sudden death.” The New England journal of medicine vol. 346,15 (2002): 1113-8. [R]

[xiv] Simopoulos, Artemis P. “Omega-3 fatty acids in inflammation and autoimmune diseases.” Journal of the American College of Nutrition vol. 21,6 (2002): 495-505. [R]

[xv] Fischer, Robert et al. “Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway.” Journal of lipid research vol. 55,6 (2014): 1150-64. [R]

[xvi] Alqarni, Ayedh et al. “Supplementation with the omega-3 long chain polyunsaturated fatty acids: Changes in the concentrations of omega-3 index, fatty acids and molecular phospholipids of people at ultra high risk of developing psychosis.” Schizophrenia research, S0920-9964(19)30389-5. 9 Oct. 2019, [R]

[xvii] Linus Pauling Institute Micronutrient Information Center at OSU. Essential fatty acids. Updated May 2019. [R]

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