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Cover of Effects of Omega-3 Fatty Acids on Organ Transplantation

Effects of Omega-3 Fatty Acids on Organ Transplantation

Evidence Reports/Technology Assessments, No. 115

Investigators: , MD, Project Leader, , MPH, Research Associate, , MD, Research Associate, , DDS, Research Fellow, , BA, Research Associate, , DSc, Primary Technical Expert, , MD, Primary Technical Expert, , MPH, Research Associate, , MLitt, Project Manager, and , MD, Principal Investigator.

Rockville (MD): Agency for Healthcare Research and Quality (US); .
Report No.: 05-E012-2

Structured Abstract

Context:

Laboratory studies and human studies in the non-transplant setting have suggested a potential benefit of omega-3 fatty acid supplementation on several outcome measures, some of which may benefit patients undergoing organ transplantation.

Objectives:

To perform a systematic review of the literature and to assess the effects of supplementation with omega-3 fatty acids (eicosapentaenoic acid [EPA; 20:5 n-3], docosahexaenoic acid [DHA; 22:6 n-3], commonly referred to as “fish oil”, and alpha-linolenic acid [ALA, 18:3 n-3]) on various transplant-related outcomes.

Data Sources:

The following electronic databases were searched for potentially relevant studies: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Biological Abstracts, and Commonwealth Agricultural Bureau databases. Bibliographies of retrieved citations were reviewed to identify additional studies. Members of the Technical Expert Panel, authors of major controlled trials, and experts in the individual areas of transplantation were contacted to identify other sources of data including unpublished studies.

Study Selection:

The literature search identified 1,281 abstracts, which (after screening for relevance) led to the retrieval of 78 full-text articles. Of these, 39 were rejected while 8 represented duplicate reports of the same patients, resulting in 31 unique studies. There were 23 kidney transplant studies with a total of 846 patients, 6 heart transplant studies with 233 patients, 1 liver transplant study with 26 patients, and 1 bone marrow study with 17 patients. There were a total of 21 randomized controlled trials (13 of which were in kidney transplantation), 6 prospective cohort studies, 2 non-randomized controlled trials, and 2 case reports.

Data Extraction:

Data from each eligible study were extracted related to study design, population demographics, the amount and type of omega-3 fatty acids consumed, and outcomes. Features of methodological quality were also recorded, including (for randomized controlled trials) information about randomization, allocation concealment, and blinding techniques.

Data Synthesis:

All but 1 study used fish oil as the source of omega-3 fatty acids. Major concerns in all evaluated studies were their small size and methodological deficiencies. There was variability in the rigor with which endpoints were defined and measured. Important covariates (such as use of antihypertensive agents or the intensity of immunosuppression) were often poorly described or inconsistently applied even when the study considered outcomes that may have been confounded by these factors.

No consistent benefits of fish oil supplementation were observed for any outcome with the exception of a modest benefit on triglycerides in kidney transplantation. Improvement in renal function was described in several studies, although discordant results were also reported. There were no clear patient- or study-related characteristics to account for the heterogeneity. At best, the degree of improvement was modest and did not translate into other clinically important outcomes such as improved graft survival, although the duration of the studies was generally less than one-year.

A meta-analysis of rejection episodes in kidney transplantation found no significant benefit on either early (<6 months post transplant) or late rejection episodes. The overall relative risk of having at least one rejection episode in those receiving fish oil supplementation was 0.91 (95% CI 0.74, 1.10) in 4 studies with a total of 224 patients, all of which had a follow-up of 1 year (the longest follow-up reported). A meta-analysis of 7 randomized controlled trials (with a total of 470 patients) of graft survival in kidney transplantation found no significant benefit from fish oil supplementation (relative risk 1.00, 95% CI 0.96, 1.05). There was no significant heterogeneity between the studies. No clinically important interactions were observed between fish oil supplementation and the dose or trough-levels of cyclosporin A.

Conclusions:

Fish oil supplementation in organ transplant recipients is associated with a modest reduction in triglyceride concentrations, a benefit that has been established in the non-transplant setting. Inconsistent benefits on renal function across studies may suggest a potential benefit in a subset of patients, the characteristics of whom remain unclear. Whether administration of omega-3 fatty acids prior to transplantation would improve its benefits is unclear. Long-term studies are needed to determine whether benefits on renal function translate into improved renal outcomes. Similarly, long-term follow-up in recipients of heart transplants will be required to determine whether fish oil supplementation reduces the risk of post-transplant atherosclerosis. Because of the scarcity of data, the effects of ALA supplementation in the transplant setting cannot be determined.

Applicability of the results to contemporary transplantation procedures is uncertain since most of the studies were performed several years ago, with some more than a decade old. The technology for all transplantation procedures continues to improve with a larger choice of immunosupressive agents, a better understanding of how to use them, and means to address the known complications of transplantation including some of the important outcomes (such as hyperlipidemia and hypertension).

Contents

540 Gaither Road, Rockville, MD 20850. www​.ahrq.gov

Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services.1 Contract No. 290-02-0022. Prepared by: Tufts-New England Medical Center EPC, Boston, Massachusetts.

Suggested citation:

Bonis PA, Chung M, Tatsioni A, Sun Y, Kupelnick B, Lichtenstein A, Perrone R, Chew P, DeVine D, Lau J. Effects of Omega-3 Fatty Acids on Organ Transplantation. Evidence Report/Technology Assessment No. 115 (Prepared by Tufts-New England Medical Center Evidence-based Practice Center under Contract No. 290-02-0022). AHRQ Publication No. 05-E012-2. Rockville, MD. Agency for Healthcare Research and Quality. February 2005.

This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

AHRQ is the lead Federal agency charged with supporting research designed to improve the quality of health care, reduce its cost, address patient safety and medical errors, and broaden access to essential services. AHRQ sponsors and conducts research that provides evidence-based information on health care outcomes; quality; and cost, use, and access. The information helps health care decision makers—patients and clinicians, health system leaders, and policymakers—make more informed decisions and improve the quality of health care services.

The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services of a particular drug, device, test, treatment, or other clinical service.

1

540 Gaither Road, Rockville, MD 20850. www​.ahrq.gov

Bookshelf ID: NBK37665
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