A Randomized, Double-blind, Placebo Controlled, Parallel Virtual Clinical Trial to Investigate the Efficacy of Marine Oil Products on Omega-3 Status in Healthy Adults

Cardiovascular diseases are the leading cause of mortality and a major contributor of disability worldwide, with approximately 18.6 million deaths reported in 2021 (1). Early identification of at-risk individuals allows for an opportunity to administer prevention strategies in order to help support longevity and mitigate the progression of disease. In 2004, Omega-3 Index (O3I) was identified as a biomarker for the risk of death from coronary heart disease (2). This indicator of omega-3 status is defined as the combined percentage of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) of total fatty acids in red blood cell membranes. Maintaining an O3I of above 8% has been linked to a lower risk of coronary heart disease (3). Using pooled data from 27,000 participants across 10 studies, a 35% lower risk of mortality from coronary heart disease was reported among those with an O3I of above 8%, compared to those with an O3I of below 4% (3).

Reaching an O3I of above 8% may be attainable with more than two servings of fatty fish each week (4-6), aligning with national dietary recommendations. Dietary Guidelines for Americans recommend fish and seafood intake at least 2 to 3 times per week (7). The previous 2007 Canada's Food Guide recommended at least two servings of fish per week (8), of which was updated to include seafood an example of a healthy protein food source without defining specific amounts (9). However, it is recognized that most individuals fall short of adequate intake leading to a high prevalence of suboptimal O3I and increased risk of chronic disease (10). According to national survey data (Canadian Community Health Survey 2004 and 2015, Nutrition), approximately one in six Canadians reported daily seafood consumption (11), with a similar percentage reported in the United States based on the National Health and Nutrition Examination Survey 2007-2008 and 2015-2016 (12). Despite it being widely known that diet is major contributor of supporting and maintaining overall health, the lack of variation in foods rich in EPA and DHA makes it challenging to overcome personal tastes and preferences (e.g., smells and texture). Additionally, concerns for mercury or environmental toxins in certain fish contributes to lower intakes (13). Thus, improving and maintaining O3I with only foods may not be feasible and cross-sectional studies have shown that the odds of having an O3I above 8% was greatest among those with 3 or more serving of fish per week along with supplementation (6,14). With direct supply of EPA and DHA, marine-derived supplements continue to be a promising strategy for augmenting the diet to promote a range of health benefits.

The investigational products (IP) used in the current study are animal- (e.g., fish oil) and plant-based (e.g., algae oil) marine oil products of varying doses and forms (softgel, liquid, and gummy). In a recent randomized, double-blind, placebo-controlled, parallel clinical trial, the bioavailability of EPA and DHA from algal (1:3) and fish oil (3:2) supplementation were compared in healthy adults aged 21 to 82 at six and 14 weeks (15). Results demonstrated no statistical difference in plasma DHA and EPA bioavailability between the products (15), suggesting the use of algae oil as a sufficient source of EPA and DHA. Independent of the wide variation in dose, intervention period, and study population in this research field, EPA and DHA supplementation is linked to an improvement in O3I (16). However, further investigation is needed to determine the influence of commercially available marine oil products on omega-3 status to support its use for eliciting a O3I response. In a previous randomized, placebo-controlled, double-blind, parallel trial, 115 healthy men and women were provided one of five doses of marine-derived supplements for approximately five months (17). Findings showed a dose-dependent response of O3I (17). However, authors suggested the need for understanding how different ratios of EPA and DHA can influence O3I response.

The objective of this current study is to investigate the efficacy of marine oil products on omega-3 status in healthy adults. Part 1 will consist of softgel study products and Part 2 will consist of liquid, gummy chew and comparator study products. The study will enroll healthy adults aged 18 years or older with low fatty fish intake (\< 4 servings per month). All participants will be required to agree to maintain their current lifestyle habits, including but not limited to diet, physical activity, medications, supplements, and sleep as much as possible throughout the study. Furthermore, participants must be willing to complete all questionnaires, diaries, and assessments, as well as self-report the ability to consume the investigational product. Those with self-confirmed history or current diagnosis of any significant disease of the gastrointestinal tract, or other ongoing and unstable diseases/conditions in the past six months will be excluded. Use of prescribed and/or over-the-counter (OTC) medications, supplements, and/or consumption of food/drinks that may impact the efficacy and/or safety of the investigational product will be prohibited to reduce any confounding effects on study outcomes and ensure the safety of the enrolled study population.