In November 2013, Health Canada’s Food Directorate received an application for a therapeutic claim about eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and triglyceride lowering. The information below is a summary of Health Canada’s review based on the Guidance Document for Preparing a Submission for Food Health Claims.
In 2010, Health Canada reconsidered the classification of food products with disease risk reduction claims or therapeutic claims in light of clarified principles for the classification of foods at the Food-Natural Health Product interface. Health Canada’s position is that when food products are marketed for a disease risk reduction or therapeutic benefit, which comes as a result of the food’s normal use as part of the diet, these products may be classified and regulated as foods. In other words, the use of a disease risk reduction claim or a therapeutic claim alone is not sufficient to classify the product as a natural health product.
Scientific evidence supporting the claim
The foods that are the subject of the health claim are foods containing eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA). EPA and DHA are long-chain omega-3 fatty acids with lipid structures of 20:5(n-3) and 22:6(n-3), respectively.
The petitioner provided a literature search covering a period up to September 2012 to substantiate the proposed health claim. The literature search was updated by Health Canada’s Food Directorate to encompass studies published to September 2014. References were included if they reported on randomized intervention studies or prospective observational studies; included a suitable control group; included at least 5 subjects; included generally healthy and non-medicated adults (≥18 years of age); administered 5 g/day or less of EPA+DHA without co-administering another treatment known to affect blood lipids; lasted a minimum of 4 weeks (+ 4 week washout for crossover studies); reported changes in fasting triglyceride levels; and reported on statistical significance between groups. A total of 77 relevant references, comprising 108 relevant treatment arms and 1 observational study were identified.
Of the 77 relevant studies, 59 were parallel studies, 17 were crossover studies and one was a prospective observational study. Sample sizes among parallel studies ranged from 15 to 274, while it ranged from 6 to 312 in the crossover studies. The observational study analyzed the data of 1689 men.
The studies were conducted in healthy or non-medicated hyperlipidemic males and females. Ages at baseline ranged from 18 to 85 years. Studies were carried out in Europe, America, Oceania, Asia and Africa. The intake of EPA+DHA ranged from 0.013 g/day to 5 g/day. Treatment duration ranged from 4 to 26 weeks for the clinical trials. The follow-up of the observational study lasted 4 years.
EPA and/or DHA were consumed from supplements in 54 studies, from fortified foods in 10 studies and from fish in 14 studies. One study used supplements for some trial arms and fish for other trial arms. Supplements were mainly capsules containing fish oil, krill oil, seal oil or algal oil while fortified foods included milk, soy milk, yoghurt, cheese, cheese spread, butter, margarine, shortening, biscuits, bread, pancakes, muffins, chocolate, instant oats, dips, salad dressing, dry soup mix, eggs and pork. A variety of fish species were consumed in the studies including trout, herring, salmon, mackerel, tuna and sardines.
The outcome considered is fasting triglycerides levels (TG). A fasting plasma or serum triglyceride concentration greater than 1.7 mmol/L is considered unhealthy and is one of the defining characteristics of metabolic syndrome.
The direction of effect was highly consistent (89% of treatment arms) towards a reduction in triglyceride levels with EPA and DHA consumption. However, a low proportion of studies showed a statistically significant reduction in triglyceride levels (50%). These conclusions were similar when only higher quality studies were taken into account.
Similar results were observed when treatment arms were grouped by method of consumption of EPA+DHA (supplements, fortified foods or fish), except that for the subgroup of fortified foods the direction of effect was slightly less consistent (67%) and a lower proportion of studies showed a statistically significant reduction in triglyceride levels (25%). This could be due to the lower doses of EPA+DHA used in the studies administering EPA+DHA from fortified foods.
When only studies with at least 30 participants and administering a daily intake of EPA+DHA of at least 1.5 g or 2 g were taken into account, a large proportion of studies showed a statistically significant reduction in triglyceride levels (82% and 88% of treatment arms, respectively). These studies were all of higher quality.
A daily intake of 1.5 g of EPA+DHA was chosen as the minimum effective intake because the vast majority (>80%) of the treatment arms from the larger studies (≥30 participants) administering a daily intake of at least 1.5 g of EPA+DHA demonstrated a statistically significant reduction in triglyceride levels. This was also the case for the treatment arms from the larger studies administering a daily intake of at least 2 g of EPA+DHA. A minimum effective intake of 1 g/day was not retained because none of the 4 treatment arms from higher quality and larger studies (≥30 participants) administering between 1 g/day and 1.5 g/day of EPA+DHA showed a statistically significant reduction in triglyceride levels. Two of these 4 studies are especially relevant to the claim since either fish or foods fortified with EPA and DHA were consumed.
The EPA:DHA ratio in the studies showing a statistically significant reduction in triglyceride levels ranged from 0:1 to 1:0. Therefore, no minimum and maximum ratios have been established for this claim.
The reduction of triglyceride levels with the consumption of EPA and/or DHA ranged from −48% to −3% (−1.52 to −0.02 mmol/L) in the treatment arms from larger studies (n≥30) administering a daily intake of at least 1.5 g of EPA+DHA. The mean triglyceride reduction among these treatment arms was −23% (−0.39 mmol/L). This effect is consistent with other systematic reviews investigating the effect of EPA and DHA on triglyceride levels. Reductions in triglycerides of 20% to 24% and in the range of 20% to 50% have been respectively described as
substantial reductions and as a
marked triglyceride-lowering effect.
Results from the observational study are consistent with the results from the clinical trials: the odds ratio of having high triglyceride levels was lower (0.54; 95% CI 0.34 to 0.86) in men eating fish daily than in men eating less than one serving of fish per week.
Health Canada’s Food Directorate conclusion
The evidence consistently supports a highly consistent direction of effect towards a reduction in triglyceride levels when EPA and DHA are consumed. The vast majority (>80%) of the treatment arms from the larger studies (≥30 participants) administering a daily intake of at least 1.5 g of EPA+DHA demonstrated a statistically significant reduction in triglyceride levels.
Health Canada’s Food Directorate has concluded that scientific evidence exists to support a claim about EPA+DHA and triglyceride lowering. The claim is relevant and generally applicable to the Canadian adult population on the basis that approximately 25% of Canadian adults aged 20 to 79 had unhealthy triglyceride levels (>1.7 mmol/L) from 2007 to 2009.