Effects of Omega-3 Docosapentaenoic Acid on Lipids and Other Risk Factors for Cardiovascular Disease

Summary

Elevated plasma triglycerides (TG) are due to an excess of TG-rich lipoproteins of several different types, most commonly of very-low-density lipoproteins (VLDL), but also intermediate-density lipoproteins (IDL, or VLDL remnants), chylomicrons, and/or chylomicron remnants. Epidemiologic evidence that a moderate elevation in TG is often associated with increased atherosclerotic cardiovascular disease (ASCVD) risk, and more recent evidence from Mendelian randomization studies has shown that elevated TG associated with genetic variants may be a causal factor for ASCVD and possibly for premature all-cause mortality.\[1-6\] Fasting plasma TG concentrations may be categorized as: normal (\< 150 mg/dL ), borderline (150-199 mg/dL), high TG (HTG, 200-499 mg/dL), and very high TG (VHTG, ≥ 500 mg/dL).\[7, 8\] Risk of acute pancreatitis is increased in VHTG patients, especially those with TG ≥ 1000 mg/dL.\[9\] For VHTG, the primary goal of therapy is to reduce TG to \< 500 mg/dL,\[10\] whereas there is no specific treatment goal for HTG nor prescription indication. However, the omega-3 fatty acids, EPA and DHA have well-established efficacy in reducing TG in the range of 150-500 when administered at doses of \> or = 3 g/d EPA+DHA (reviewed in Skulas-Ray et al. in press). Importantly, administration of omega-3 fatty acids to people with TG in this range lead to a 25% reduction in major adverse cardiovascular endpoints in the recently completed "Reduction of Cardiovascular Events with EPA Intervention Trial" (REDUCE-IT).\[11\]

The results of REDUCE-IT provide compelling evidence for the use 3 g/d omega-3 fatty acid supplementation to reduce cardiovascular risk among patients with TG 150-500 mg/dL. The concentrated EPA supplement used in REDUCE-IT is just one of three long chain n-3 omega-3 fatty acids that influence lipids and lipoproteins and other aspects of cardiovascular risk.

Most research has focused on the evaluation of EPA and DHA, which are the two predominant n-3 FA in fish and in n-3 agents, but docosapentaenoic acid (DPA) is present in fish oil, as well, and accumulates in the blood at similar concentrations. The carbon length of the n-3 FA appears important for physiological effects. EPA has a carbon length of 20, DHA has a carbon length of 22, and DPA, the metabolic intermediate of EPA and DHA, is a 22-carbon n-3 FA. DPA may have significant potential for treating HTG and VHTG,\[12, 13\] but research on this fatty acid remains limited. In a 2-week open-label crossover comparison of 4 g/d of a DPA concentrate (containing unspecified amounts of free DPA and EPA) vs. 4 g/d EPA concentrate in people with HTG, plasma TG were reduced 33% by the DPA concentrate, which was significantly more than the 11% reduction with EPA.\[13\] Thus, a recent scientific advisory from the American Heart Association (Skulas-Ray et al, in press) concluded that more research is needed to elaborate the lipid and lipoprotein effects of DPA.

Additional biomarker research suggests DPA similarly can influence health outcomes that respond to EPA and DHA. For instance, decreased serum concentrations of DPA and DPA + DHA have been associated with increased risk of risk of acute coronary events\[14\] and myocardial infarction\[15\], respectively. Plasma DPA was also inversely associated with incident cardiovascular disease (CVD) in some ethnic groups.\[16\]

In conclusion evidence supports a potential role of DPA in improving health, but results from clinical supplementation studies are needed to clarify the effect of DPA supplementation on lipids and lipoproteins as well as other cardiovascular disease risk factors-relative to supplementation with EPA and DHA-to ascertain whether enrichment of omega-3 concentrates with DPA could offer health benefits above and beyond concentrates that only contain EPA and DHA.

Conditions

• Elevated Triglycerides
• Cardiovascular Risk Factor

Interventions

DIETARY_SUPPLEMENT

DPA enriched n-3

4 g/d DPA enriched n-3 concentrate (\~980 mg DPA, 380 mg EPA, 1720 mg DHA)

DIETARY_SUPPLEMENT

n-3 control

4 g/d n-3 control (\~980 oleic acid, 380 mg EPA, 1720 mg DHA)

DIETARY_SUPPLEMENT

Placebo

4 g/d placebo control ("light" olive oil)

Sponsors & Collaborators

• University of Arizona

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2019-09-04

Primary Completion

2021-01-31

Completion

2021-01-31

Countries

• United States

Study Locations