Latest Review Date: October 2024

POLICY:

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.

DESCRIPTION OF PROCEDURE OR SERVICE:

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. 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 that this measurement may be clinically useful as a cardiac risk factor for sudden cardiac death. In addition to the Omega-3 Index (OI) as a proposed marker of coronary artery disease risk, it is also a proposed predictor of accelerated cognitive and structural brain aging.

KEY POINTS:

This policy has been updated with literature review performed through October 3, 2024.

Summary of Evidence

Some studies were identified that examine the association between fish consumption and risk of coronary heart disease, but lack proof of clinical utility in measurement of long chain omega-3 fatty acids in red blood cell membranes, as this measurement was not taken into consideration when recommending fish consumption. There are no published articles identified that explore how the measurement of red blood cell membrane omega-3 fatty acids may be used to improve patient management, treat, or prevent cardiac disease.  

A study was identified that examined the association of red blood cell omega-3 fatty acid levels and markers of accelerated brain aging, however, the population of this study only included one ethnic group, thus limiting the generalizability of these findings. The association between lower RBC omega-3 fatty acid levels and markers of accelerated cognitive and structural brain aging observed here should be confirmed in other populations and extended in the future to include dementia outcomes.

Well-designed trials and studies are needed to demonstrate the potential impact of this technology on clinical outcomes. There is insufficient evidence to support the clinical utility of measurement of long-chain omega-3 fatty acids in red blood cell membranes. This technology does not demonstrate improvement in net health outcomes.

KEY WORDS:

Long-chain omega-3 fatty acids, coronary heart disease, Omega-3 fatty acids, fatty acids, heart disease risk, fish oil

APPROVED BY GOVERNING BODIES:

Not applicable.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits. Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP contracts: Special benefit consideration may apply. Refer to member’s benefit plan.

CURRENT CODING:

CPT codes:

For dates of service 1/1/21 and after, there are no specific codes related to this test.  An unlisted code would be submitted, such as:

PREVIOUS CODING:

CPT codes:

REFERENCES:

1. Albert CM, Campos H, Stampfer MJ, Ridker PM, Manson JE, Willett WC, Ma J. Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N Engl J Med. 2002 Apr 11; 346(15):1113-8.
2. Albert CM, Hennekens CH, O'Donnell CJ, Ajani UA, Carey VJ, Willett WC, Ruskin JN, Manson JE. Fish consumption and risk of sudden cardiac death. JAMA. 1998 Jan 7; 279(1):23-8.
3. Covington MB. Omega-3 fatty acids. Am Fam Physician. 2004 Jul 1; 70(1):133-40.
4. Daviglus ML, Stamler J, Orencia AJ, Dyer AR, Liu K, Greenland P, Walsh MK, Morris D, Shekelle RB. Fish consumption and the 30-year risk of fatal myocardial infarction. N Engl J Med. 1997 Apr 10; 336(15):1046-53.
5. Demonty I, Langlois K, Greene-Finestone LS, Zoka R, Nguyen L. Proportions of long-chain ω-3 fatty acids in erythrocyte membranes of Canadian adults: Results from the Canadian Health Measures Survey 2012-2015. Am J Clin Nutr. 2021 Apr 6; 113(4):993-1008.
6. Gillum RF, Mussolino M, Madans JH. The relation between fish consumption, death from all causes, and incidence of coronary heart disease. The NHANES I Epidemiologic Follow-up Study. J Clin Epidemiol. 2000 Mar 1; 53(3):237-44.
7. Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB Sr, Gibbons R, Greenland P, Lackland DT, Levy D, O'Donnell CJ, Robinson JG, Schwartz JS, Shero ST, Smith SC Jr, Sorlie P, Stone NJ, Wilson PWF. 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. J Am Coll Cardiol. 2014 Jul 1; 63(25 Pt B):2935-2959.
8. Gonçalinho GHF, Sampaio GR, Soares-Freitas RAM, Damasceno NRT. Omega-3 Fatty Acids in Erythrocyte Membranes as Predictors of Lower Cardiovascular Risk in Adults without Previous Cardiovascular Events. Nutrients. 2021;13(6):1919. Published 2021 Jun 3.
9. Grieger JA, Miller MD, Cobiac L. Investigation of the effects of a high fish diet on inflammatory cytokines, blood pressure, and lipids in healthy older Australians. Food Nutr Res. 2014 Jan 15; 58.
10. Harris, W. S., Tintle, N. L., Imamura, F., Qian, F., Korat, A. V. A., Marklund, M., Djoussé, L., Bassett, J. K., Carmichael, P. H., Chen, Y. Y., Hirakawa, Y., Küpers, L. K., Laguzzi, F., Lankinen, M., Murphy, R. A., Samieri, C., Senn, M. K., Shi, P., Virtanen, J. K., Brouwer, I. A., … Fatty Acids and Outcomes Research Consortium (FORCE) (2021). Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies. Nature communications, 12(1), 2329.
11. He K, Rimm EB, Merchant A, Rosner BA, Stampfer MJ, Willett WC, Ascherio A. Fish consumption and risk of stroke in men. JAMA. 2002 Dec 25; 288(24):3130-6.
12. He K, Song Y, Daviglus ML, Liu K, Van Horn L, Dyer AR, Goldbourt U, Greenland P. Fish consumption and incidence of stroke: a meta-analysis of cohort studies. Stroke. 2004 Jul; 35(7):1538-42.
13. He K, Song Y, Daviglus ML, Liu K, Van Horn L, Dyer AR, Greenland P. Accumulated evidence on fish consumption and coronary heart disease mortality: a meta-analysis of cohort studies. Circulation. 2004 Jun 8; 109(22):2705-11.
14. Holub BJ. Clinical nutrition: 4. Omega-3 fatty acids in cardiovascular care. CMAJ. 2002 Mar 5; 166(5):608-15.
15. Hu FB, Bronner L, Willett WC, Stampfer MJ, Rexrode KM, Albert CM, Hunter D, Manson JE. Fish and omega-3 fatty acid intake and risk of coronary heart disease in women. JAMA. 2002 Apr 10; 287(14):1815-21.
16. Hu FB, Cho E, Rexrode KM, Albert CM, Manson JE. Fish and long-chain omega-3 fatty acid intake and risk of coronary heart disease and total mortality in diabetic women. Circulation. 2003 Apr 15; 107(14):1852-7.
17. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
18. Kris-Etherton PM, Harris WS, Appel LJ; American Heart Association. Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002 Nov 19; 106(21):2747-57.
19. Lee KW, Lip GY. The role of omega-3 fatty acids in the secondary prevention of cardiovascular disease. QJM. 2003 Jul; 96(7):465-80.
20. Lemaitre RN, King IB, Mozaffarian D, Kuller LH, Tracy RP, Siscovick DS. N-3 polyunsaturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study. Am J Clin Nutr. 2003 Feb; 77(2):319-25.
21. Mozaffarian D, Lemaitre RN, Kuller LH, Burke GL, Tracy RP, Siscovick DS; Cardiovascular Health Study. Cardiac benefits of fish consumption may depend on the type of fish meal consumed: the Cardiovascular Health Study. Circulation. 2003 Mar 18; 107(10):1372-7.
22. Ness AR, Hughes J, Elwood PC, Whitley E, Smith GD, Burr ML. The long-term effect of dietary advice in men with coronary disease: follow-up of the Diet and Reinfarction trial (DART). Eur J Clin Nutr. 2002 Jun; 56(6):512-8.
23. Pietinen P, Ascherio A, Korhonen P, Hartman AM, Willett WC, Albanes D, Virtamo J. Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Epidemiol. 1997 May 15; 145(10):876-87.
24. Superko HR, Superko AR, Lundberg GP, Margolis B, Garrett BC, Nasir K, Agatston AS. Omega-3 Fatty Acid Blood Levels Clinical Significance Update. Curr Cardiovasc Risk Rep. 2014; 8(11):407.
25. Tan ZS, Harris WS, Beiser AS, Au R, Himali JJ, Debette S, Pikula A, Decarli C, Wolf PA, Vasan RS, Robins SJ, Seshadri S. Red blood cell ω-3 fatty acid levels and markers of accelerated brain aging. Neurology. 2012 Feb 28; 78(9):658-64.
26. Whelton SP, He J, Whelton PK, Muntner P. Meta-analysis of observational studies on fish intake and coronary heart disease. Am J Cardiol. 2004 May 1; 93(9):1119-23.
27. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K; Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007 Mar 31; 369(9567):1090-8.
28. Yuan JM, Ross RK, Gao YT, Yu MC. Fish and shellfish consumption in relation to death from myocardial infarction among men in Shanghai, China. Am J Epidemiol. 2001 Nov 1; 154(9):809-16.

POLICY HISTORY:

Medical Policy Group, July 2005 (3)

Medical Policy Administration Committee, August 2005

Available for comment August 13-September 26, 2005

Medical Policy Group, July 2008 (1)

Medical Policy Group, July 2010 (1): Key points updated, Policy retired

Medical Policy Group, July 1, 2010; Active Policy but no longer scheduled for regular literature reviews and updates.

Medical Policy Group, September 2019 (9): Literature review completed with updates made to Key Points, Description, and References. Added key words: heart disease risk, fish oil. No change to policy statement.

Medical Policy Group, October 2020:  2021 Annual Coding Update. Moved CPT code 0111T from Current coding section. Created Previous Coding section to include code 0111T.

Medical Policy Group, November 2020: 2021 Annual Coding Update. Added CPT code 84999 to the Current coding section.

Medical Policy Group, August 2021 (9): Updates to Key Points, Description, References. Policy statement updated to remove “not medically necessary,” no change to policy intent.

Medical Policy Group, October 2021 (9): Reviewed by consensus. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

Medical Policy Group, July 2022 (9): Reviewed by consensus. References added. No new published peer-reviewed literature available that would alter the coverage statement in this policy. Updates to Key Points, Description.

Medical Policy Group, September 2023 (5): Updates to Key Points, Benefit Application, and References. No change to Policy Statement. Reviewed by consensus. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

Medical Policy Group, October 2024 (5): Reviewed by consensus. Updates to Key Points, and References. No change to Policy Statement. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.