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MP 2.04.40 Measurement of Long-Chain Omega-3 Fatty Acids in Red Blood Cell Membranes as a Cardiac Risk Factor


Medical Policy    
Original Policy Date
Last Review Status/Date
Reviewed with literature search/3:2008
  Return to Medical Policy Index


Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract.  Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage.  Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.




Epidemiologic studies have reported that subjects who eat a diet high in fish have a reduced risk of sudden cardiac death. Fish are rich in long-chain omega-3 fatty acids, and it has been hypothesized that these fatty acids may be responsible for the beneficial effect. Long-chain omega-3 fatty acids may be detected in the red cell membrane using gas chromatography. It has been suggested this measurement may be clinical useful as a cardiac risk factor for sudden cardiac death.




Measurement of long-chain omega-3 fatty acids in red blood cell membranes, including but not limited to its use as a cardiac risk factor, is considered investigational.



Policy Guidelines

This policy was developed to address a new category III CPT code that became effective July 1, 2005:

0111T: Long-chain (C20-22) omega-3 fatty acids in red blood cell membranes

CPT code 82725 (fatty acids, nonesterified) might also be used to describe measurement of omega-3 fatty acids.



Benefit Application

BlueCard/National Account Issues

No applicable information




A search of the literature identified many observational studies exploring the relationship between fish consumption and coronary heart disease mortality in different populations of patients. (1-6) These studies suggest that mortality from coronary heart disease may be reduced by including fish as a regular part of the diet. However, the search did not identify any published articles that explored how the measurement of red blood cell membrane omega-3 fatty acids may be used to improve patient management. For example, studies establishing the diagnostic parameters of omega-3 fatty acids, i.e., the definition normal, high, and low values were not identified. It has been suggested that measurement of omega-3 fatty acids may be incorporated into a cardiac risk panel in patients with a prior cardiac event. No studies focused on this application of this laboratory test. As noted in other policies focusing on cardiac risk factors (see policies Nos. 2.04.32 ), improved risk prediction does not by itself result in better health outcomes. To improve outcomes, clinicians must have the tools to translate this information into clinical practice. At the present time, patients with coronary artery disease are offered the general dietary recommendation to increase fish consumption, a recommendation not based on red blood cell membrane levels of omega-3 fatty acids.

2006 Update

A literature search for the period of 2005 through January 2006 did not identify any new published literature that would prompt reconsideration of the policy statement, which remains unchanged.

2007 - 2008 update
A MEDLINE search was performed for the period February 2006 – February 2008. No trials were identified where prospective measurement of omega-3 fatty acids (Omega-3 Index) was used to direct treatment to prevent or treat cardiac disease. As noted above, these trials are needed to demonstrate the potential impact of this index on clinical outcomes.

The Japan EPA Lipid Intervention Study (JELIS) trial compared fish oil capsules plus statins to statins alone in 18,645 patients with hypercholesterolemia. In this primary and secondary prevention study, if hypercholesterolemia remained uncontrolled, the dose of the statin could be raised by protocol. No measurements of the efficacy of fish oil treatment were performed and the dose remained constant throughout the study. The fish oil plus statin group had 18% (p=0.132) and 19% (p=0.015) fewer non-fatal (primary and secondary, respectively) cardiac events over a mean of 4.6 years compared to the statin only group. (7)


  1. He K, Song Y, Daviglus ML et al. Accumulated evidence of fish consumption and coronary heart disease mortality: a meta-analysis of cohort studies. Circulation 2004; 109(22):2705-11.
  2. Hu FB, Cho E, Rexrode KM et al. Fish and long-chain omega-3 fatty acid intake and risk of coronary heart disease and total mortality in diabetic women. Circulation 2003; 107(14):1852-7.
  3. He K, Song Y, Daviglus ML et al. Fish consumption and incidence of stroke: a meta-analysis of cohort studies. Stroke 2004; 35(7):1538-42.
  4. Whelton SP, He J, Whelton PK et al. Meta-analysis of observational studies on fish intake and coronary heart disease. Am J Cardiol 2004; 93(9):1119-23.
  5. Mozaffarian D, Longstreth WT, Lemaitre RN et al. Fish consumption and stroke risk in elderly individuals: the cardiovascular health study. Arch Intern Med 2005; 165(2):200-6.
  6. Albert CM, Campos H, Stampfer MJ et al. Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N Engl J Med 2002; 346(15):1113-8.
  7. Yokoyama M, Origasa H, Matsuzaki M et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 2007; 369(9567):1090–8.





CPT  0111T  Long-chain (C20-22) omega-3 fatty acids in red blood cell membranes 
  82725  Fatty acids, nonesterified 
ICD-9 Diagnosis Codes   Investigational for all codes 




Long-chain Omega-3 fatty acid
Omega-3 fatty acid



Policy History

Date Action Reason
04/1/05 Add policy to Medicine section, Pathology/ Laboratory subsection New policy
04/25/06 Replace policy Policy updated with literature search; policy statement unchanged
03/13/08 Replace policy  Policy updated with literature search; policy statement unchanged. Reference 7 added.


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