by Harry B. Rice, Ph.D.
In general, the majority of consumers discount the results from research conducted in animals. Id be a hypocrite if I didnt fess up to doing the same at times. That doesnt mean I dont feel some shame since Im a scientist trained to conduct animal research. While those in the omega-3 industry seem to justify the dismissal of animal research because so much research has been conducted in humans, its important to realize animal research represents an important part of the totality of scientific evidence, and it needs to be appreciated for what it isa piece of the puzzle.
The totality of evidence can be viewed as two parts. The first is basic research, which includes evidence from animals. One of the most useful things about this type of evidence is the identification of potential mechanisms of action. Basic research is precise because the investigators are in direct control. The second part is human research, which provides the most relevant information, but less precision due to an assortment of environmental confounds. Determining the human relevance of results from research conducted in animals can be difficult, but that doesnt mean animal models are inferior to human models. In fact, the U.S. Public Health Service has stated, virtually every medical achievement of the last century has depended directly or indirectly on research in animals." Look at the following examples:
Identification of the causes of polio and development of a vaccine
Determining the effectiveness of penicillin and other antibiotics as treatments for bacterial infections
Providing one of the earliest cancer models for growth and metastasis
Specific to omega-3 research, the understanding of resolvins and protectinsmetabolites derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectivelycouldnt have advanced to where it is today without animal research.
While animal research is part of the totality of any body of available scientific evidence, the question of what direct relevance it has to humans is an ongoing debate and must be determined on a case-by-case basis.
In the past year, some scientists have taken the liberty of over-extrapolating their omega-3 findings in animals and generalizing them to humans. Unfortunately, this irresponsible practice can result in consumers decreasing their intake of omega-3smaking for a public health concern. Below are two examples of such heinous over extrapolation.
In the first study1, investigators fed old transgenic mice a high-fat (40 percent energy), isoenergetic and isonitrogenous diet composed of rapeseed oil, maize oil or maize oil supplemented with omega-3 polyunsaturated fatty acid (PUFA) via fish oil, and then examined the gut flora for immune cells and oxidative stress. The high omega-6 PUFA diets resulted in increased gut inflammation. While fish oil supplementation restored the gut flora, it resulted in increased oxidative stress as measured by the increased presence of 4-hydroxynonenal, a product of lipid peroxidation. The investigators concluded that the combination of omega-6 and omega-3 PUFA, like DHA/EPA, leads to increased oxidative stress, which could exacerbate gastrointestinal disorders in the elderly. REALLY?
It is not clear what role oxidative stress in the small intestine plays in the pathogenesis of small intestinal diseases in old mice, not to mention humans.
Within the last couple years, both the European Food Safety Authority (EFSA) and the Norwegian Scientific Committee for Food Safety (VKM) published safety evaluations about omega-3 long-chain (LC) PUFAs and reported no evidence that they induce changes in lipid peroxidation that might raise a concern with respect to risk for any disease. In general, EFSAs absence of safety concerns is for supplemental intakes of EPA and DHA combined at doses up to 5 g/d and the VKMs is for 6.9 g/d. GOEDs safety assessment is in line with both EFSAs and VKMs.
Methods used to assess lipid peroxidation in tissue samples are indirect, and the evidence that the methods actually reflect lipid peroxidation in vivo is limited. Due to the lack of validation of lipid oxidation or oxidative stress end points as biomarkers for disease or health-compromised states, or risk thereof, it is not possible to interpret the present results in old mice to determine any potential hazard to health in humans from ingestion of EPA+DHA.
In the second publication2, a review focusing on the immunomodulatory effects of EPA and DHA, the authors expressed undue concern about the safety of excessive" intake of the omega-3 LC-PUFAs. The supporting studies cited were about bacterial, viral and fungal infections in animal models of infectious disease, demonstrating that omega-3 LC-PUFA intake dampens immunity and alters pathogen clearance. As with the first study, theres no evidence to suggest the same would happen in humans. Even if excessive" intakes dampened immunity and altered pathogen clearance, omega-3 intake in the United States is so low that it seems futile to make an issue out of excessive intakes. To put this into perspective, according to a recent analysis using data from NHANES, daily EPA and DHA intake (food and dietary supplements) in the United States in the highest consumers (males of 51+ years) at the 90th percentile is 69 mg and 234 mg, respectively. The combined total is just 1/10 of the FDA daily limit of 3 g. As mentioned above, more recent safety assessments support a much higher intake without any known safety issues.
In closing, we must never forget that its basic research, which includes animal research, that formed the foundation of where we are today. Important omega-3 animal research continues to be conducted, and Its direct relevance to humans will continue to be an ongoing debate. What we shouldnt do is just discount the research without understanding its value.
1Ghosh S et al. "Diets rich in n-6 PUFA induce intestinal microbial dysbiosis in aged mice." Br J Nutr. 2013;110:515-523.
2Fenton JI et al. "Immunomodulation by dietary long chain omega-3 fatty acids and the potential for adverse health outcomes." Prostaglandins Leukot Essent Fatty Acids. 2013;89:379-390.
Harry B. Rice, Ph.D. is vice president, regulatory and scientific affairs at the Global Organization for EPA and DHA Omega-3s ( GOED ).