Dietary Supplements and Cardiovascular Health: Getting to the Heart of Omega-3 Claims

While a wealth of scientific evidence demonstrates the beneficial role of long-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for general wellness and multiple health conditions, the strongest evidence by far is in the area of cardiovascular health.

This year, in both the European Union and the United States, the Global Organization for EPA and DHA Omega-3 (GOED) plans to capitalize on the strength of this science and gain ground on omega-3 health claims to further promote the awareness of EPA and DHA.

European Union
GOED plans to prepare and submit an application for the authorization of an Article 14 (disease-risk reduction) health claim under the European Commission’s (EC) Regulation No. 1924/2006 on nutrition and health claims made on foods. The suggested claim will be: “EPA and DHA omega-3s may reduce the risk of cardiovascular disease” or some variation thereof.

Note: Until recently, the preparation and submission of this Article 14 application was of the highest priority. However, there is now a reduced sense of urgency given that the European Food Safety Authority (EFSA) adopted on October 19, 2010, an Article 13 (general function) health claim opinion (1) that a cause-and-effect relationship had been established between the consumption of EPA and DHA and the maintenance of normal cardiac function.

While our primary priority in the EU remains the preparation and submission of an Article 14 health claim application, the focus has now turned from cardiovascular health to brain health.

At the time this article went to print, it was anticipated that the General Food Law Section of the Standing Committee on the Food Chain and Animal Health (SCFCAH) would vote on January 27, 2011, to authorize the claim “Alpha-linolenic acid (ALA) contributes to the brain development of children.” While this claim is based on a positive opinion (2) from EFSA, the European Commission appears unwilling to recognize EFSA’s advice that ALA’s effect is due to its conversion to DHA. That advice was delivered on May 26, 2010, at a meeting of the EC’s Ad Hoc Working Group on Omega-3 Claims-a meeting in which GOED participated.

The goal of the Working Group was to define the conditions of use of omega-3 and the target populations for the omega-3 claims that had received positive opinions from EFSA. With respect to the claim “ALA contributes to brain development in children,” upon questioning from the Commission, EFSA acknowledged that if ALA works by being converted to DHA, then DHA would qualify for this claim as well-and thus, an ALA brain-development claim should be extended to include DHA.

Assuming that the SCFCAH approves the ALA brain-development claim, GOED plans to prepare and submit an application for the authorization of an Article 14 health claim that “DHA contributes to the brain development of children.”

United States
In 2004, FDA concluded that the available scientific evidence linking long-chain omega-3s and heart health fell short of meeting the “significant scientific agreement” requirement for an unqualified health claim per section 403(r)(3) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 343(r)(3)) and 21 CFR 101.14(c). Significant scientific agreement refers to the extent of agreement among qualified experts in the field. In the spectrum ranging from very limited to conclusive evidence, significant scientific agreement lies closer to consensus.

Based on its conclusion, FDA considered permitting the following qualified health claim: “Supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease. One serving of [Name of the food] provides [X] g of EPA and DHA omega-3 fatty acids.”

Without debating the merits of qualified health claims, GOED believes the qualified health claim for EPA and DHA omega-3s is of limited value in the marketplace. Perhaps more importantly, it does not accurately reflect the current state of the science.

While scientific evidence cannot be measured by the quantity of studies alone, GOED monitors the peer-reviewed scientific literature and has found that the number of published studies related to the benefits of EPA and DHA has more than doubled since FDA chose to exercise its enforcement discretion over the EPA and DHA omega-3 qualified health claim. Many of those publications are of the highest quality and relate the cardiovascular benefits of EPA and DHA.

In fact, GOED member companies have sponsored two meta-analyses on the science related to omega-3s and cardiovascular disease. The first meta-analysis was published in Nutrition Reviews and concerns the dose-dependent reduction in triglycerides.(3) The second meta-analysis is under review for publication in the British Journal of Nutrition and concerns the reduced risk of coronary heart disease mortality.(4)

While FDA does not recognize triglycerides as a surrogate endpoint (risk biomarker) for cardiovascular disease-risk reduction, the British Journal of Nutrition meta-analysis will undoubtedly add to the body of evidence in support of a health claim.

To “upgrade” FDA’s qualified health claim into an unqualified health claim that reflects the current science, GOED believes there are two viable options to pursue:

1) Submit a notification of a health claim based on an authoritative statement of a scientific body. While there is much debate about satisfying the requirements for an authoritative statement, FDA has been clear that it does not believe a valid authoritative statement exists from a scientific body about the benefits of EPA and DHA. GOED is hopeful that this will change in the near future.

Last year, GOED, along with nine other organizations, submitted a Citizen’s Petition to the Food and Nutrition Board of the Institute of Medicine (IOM), asking that a special expert panel be convened to re-examine the Dietary Reference Intakes (DRIs) for EPA and DHA. Because FDA recognizes the IOM as a scientific body capable of producing an authoritative statement, results from a re-examination of the DRIs for EPA and DHA could fulfill the requirements for this option.

At the end of November, the IOM released its report entitled Dietary Reference Intakes for Calcium and Vitamin D.(5) The industry is hopeful that the next nutrients for review will be EPA and DHA.

2) Submit a petition for an authorized health claim. This option requires a systematic evaluation of the peer-reviewed literature, in addition to any credible unpublished data.

If the IOM launches a DRI review for EPA and DHA, this option does not make the most sense because FDA is unlikely to rule on a health claim petition prior to the release of IOM’s report. In the unfortunate event that there is a delay in the DRI review for EPA and DHA, or should the IOM choose to review another nutrient(s) prior to EPA and DHA, however, this then would be the best route.

References:

(1) EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and maintenance of normal cardiac function (ID 504, 506, 516, 527, 538, 703, 1128, 1317, 1324, 1325), maintenance of normal blood glucose concentrations (ID 566), maintenance of normal blood pressure (ID 506, 516, 703, 1317, 1324), maintenance of normal blood HDL-cholesterol concentrations (ID 506), maintenance of normal (fasting) blood concentrations of triglycerides (ID 506, 527, 538, 1317, 1324, 1325), maintenance of normal blood LDL-cholesterol concentrations (ID 527, 538, 1317, 1325, 4689), protection of the skin from photo-oxidative (UV-induced) damage (ID 530), improved absorption of EPA and DHA (ID 522, 523), contribution to the normal function of the immune system by decreasing the levels of eicosanoids, arachidonic acid-derived mediators and pro-inflammatory cytokines (ID 520, 2914), and “immunomodulating agent” (4690) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA Journal 2010;8(10):1796. [32 pp.]. doi:10.2903/j.efsa.2010.1796. Available online: www.efsa.europa.eu/efsajournal.htm

(2) Scientific Opinion of the Panel on Dietetic Products, Nutrition and Allergies on a request from Kraft Biscuits Europe R&D on ALA and contribution to brain development. The EFSA Journal (2009) 1005, 1-9

(3) Musa-Veloso K, Binns MA, Kocenas AC, Poon T, Elliot JA, Rice H, Oppedal-Olsen H, Lloyd H, Lemke S (2010). Long-chain Omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid dose-dependently reduce fasting serum triglycerides. Nutrition Reviews 68: 155-167.

(4) Musa-Veloso K, Binns MA, Kocenas AC, Chung C, Rice H, Oppedal-Olsen H, Lloyd H, Lemke S (2010). The impact of low versus moderate intake of long-chain omega-3 fatty acids on risk of coronary heart disease. British Journal of Nutrition Submitted.

(5) IOM (Institute of Medicine). 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press.