Pending Policies - Medicine

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


Effective Date:05-15-2018



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 experimental, investigational and/or unproven.


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 clinically useful as a cardiac risk factor for sudden cardiac death.


This policy was originally developed in 2005 and has been updated with searches of scientific literature through March 2018. The following is a summary of the key literature to date.

A literature search identified many observational studies exploring the relationship between fish consumption and coronary heart disease (CHD) mortality in different populations of patients. (1-6) These studies suggest that mortality from CHD 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 of 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. There were no studies that focused on this application of this laboratory test. 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. Now, 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.

The Japan Eicosapentaenoic Acid 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)

A search of peer reviewed literature through August 2009 identified no new clinical trial publications or any additional information in which 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. Therefore, the coverage position of this policy is unchanged.

In 2014, Grieger et al. published an 8-week randomized, parallel study of 80 participants, which was stratified by CRP (<3 mg/L vs. ≥3 mg/L) on entry to the study. Compliance was measured using 3-day weighed food records in weeks 1 and 7 of the study. A 12-h fasting blood sample was taken at baseline and 8-weeks for erythrocyte fatty acids as confirmation of compliance, and measurement of serum cytokines and lipids. Blood pressure was measured at both time points. They concluded that eight weeks consumption of four servings of fish per week did not affect serum cytokine concentrations, blood pressure or lipids compared to a diet low in fish. In healthy older adults with low inflammatory burden, they reported that their results do not support that short-term consumption of mixed fish has a beneficial effect on selected cardiovascular biomarkers. (8)

American College of Cardiology (ACC)/American Heart Association (AHA)

The 2013 guidelines do not address long-chain omega-3 fatty acids to assess initial cardiovascular disease (CVD) risk.

Summary of Evidence

There are multiple published studies addressing the potential benefits of adding omega-3 fatty acids to one’s diet. However, there are no additional studies evaluating the clinical application of measuring long-chain omega-3 fatty acids to determine risk of cardiovascular disease.

The literature search for this medical policy identified no additional clinical trial publications that would prompt reconsideration of the coverage statement which remains unchanged.


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Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does not have a national Medicare coverage position. Coverage may be subject to local carrier discretion.

A national coverage position for Medicare may have been developed since this medical policy document was written. See Medicare's National Coverage at <>.


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. PMID: 15184295

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. PMID: 12668520

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. PMID: 15155968

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. PMID: 15110203

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. PMID: 15668367

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. PMID: 11948270

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. PMID: 17398308

8. Grieger JA, Miller MD, et al. Investigation of the effects of a high fish diet on inflammatory cytokines, blood pressure, and lipids in healthy older Australians. Food Nutr Res January 2014 15; 58. PMID: 24454276

9. Measurement of Omega-3 Fatty Acids in Red Blood Cell Membranes as a Cardiac Risk Factor. (Archived) Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2009 March) Medicine 2.04.40.

10. Superko, HR, Superko, AR, et al. Omega-3 Fatty Acid Blood Levels Clinical Significance Update. Curr Cardiovasc Risk Rep. 2014: 8:407. PMID: 25285179

11. Goff, DC, Lloyd-Jones DM, Bennett G, et al. ACC/AHA Prevention Guideline 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk a Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014; 129: S49-S73. PMID: 24222018

Policy History:

Date Reason
5/15/2018 Document updated with literature review. Coverage unchanged.
6/15/2017 Reviewed. No changes.
6/1/2016 Document updated with literature review. Coverage unchanged.
5/15/2015 Reviewed. No changes.
4/15/2014 Document updated with literature review. Coverage unchanged.
5/1/2011 Document updated with literature review. Coverage unchanged.
11/1/2009 Policy updated with literature review. No change in coverage position.
9/14/2007 Revised/Updated Entire Document
7/1/2005 New Medical Document

Archived Document(s):

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