By Gerard Bannenberg, Director of Compliance & Scientific Outreach, Global Organization for EPA and DHA Omega-3s (GOED)
Scientific knowledge of omega-3 long-chain polyunsaturated fatty acids (omega-3 LCPUFA), obtained by observation and experimentation, has evolved tremendously over the past 10 years, with scientists eager to understand omega-3 LCPUFA—in particular, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This fascination with omega-3 LCPUFA has led to the publication of more than 14,000 new studies during the period 2008–2017.
In this article (the first in a two-part series), I will explore how our understanding of omega-3 LCPUFA has evolved over the past decade.
Our understanding of the role of omega-3 LCPUFA in tissue development, particularly during gestation, has progressed in the past decade. Whereas in older studies, the role of omega-3 LCPUFA was primarily viewed as a structural component of cellular membranes (in particular given the high local concentrations in specific tissues such as brain and retina), new insight has been obtained that omega-3 LCPUFA are also important for the development of other tissues that are not characterized by extremely high levels of omega-3 LCPUFA, such as the hormone-producing alpha-cells and beta-cells in the pancreas, the development of the peripheral nervous system, and the lung.
These advances have implications for neonatal and infant health outcomes and the reasons for sufficient dietary omega-3 intake. Sufficient dietary intake of omega-3 LCPUFA during pregnancy has been shown to have numerous benefits, including a small but positive influence on gestational length, a marked reduction in the incidence of preterm birth (prior to 34 weeks gestation), and positive effects on maternal health. Interestingly, specific needs for both arachidonic acid (AA) and DHA in tissue development seem to happen during defined periods of fetal development, suggesting the need to guarantee dietary sufficiency of various specific PUFA in the feeding of neonates that have not yet completed their development, especially those born pre-term. Research is also addressing the possibility that perinatal epigenetic effects of omega-3 LCPUFA status are of relevance to infant development, with effects that may last into childhood and adulthood.
Omega-3s and Evolution
From a biological point of view, it has been demonstrated that the transfer of omega-3 LCPUFA from organisms that produce these fatty acids (marine algae and bacteria) upwards the food chain occurs at a higher efficiency than that of macronutrients. This suggests that animal species at all levels of the food chain can somehow sense the presence and levels of essential PUFA available in prey, and that acquisition of essential PUFA is very important for their survival.
In their evolution, hominins developed a layer of body fat during the third trimester of pregnancy that can store sufficient amounts of DHA to support a newborn’s development, and in particular its large brain. The very high demands for brain-selective nutrients such as DHA and AA by humans is quite unique among animal species, and evolutionary biologists have maintained a lively debate in the past few years about how this has come about. Well-argued theories now hold that the early human race has developed on the context of a regular access to foods containing a range of brain-selective minerals (iodine, iron, zinc, copper, and selenium) and PUFA, plentifully found at freshwater and marine shores.
Many people are not getting enough pre-formed DHA. Whereas alpha-linolenic acid (ALA) and linoleic acid (LA) are essential fatty acids for the biosynthesis of the omega-3 and omega-6 PUFA families, respectively, the direct ingestion of sufficient daily dietary doses of pre-formed DHA and AA may be a physiological necessity determined by our evolutionary history.
The very different conditions in which most people today live their lives, compared to our hominin ancestors, may impede our ability to acquire the daily omega-3 LCPUFA intake that most people need. Recent epidemiological studies have indicated that a large part of the world population has low—and in a significant portion, abysmally low—daily intake of omega-3 LCPUFA. What’s more, low global intakes of these fatty acids are associated with tens of millions of preventable deaths from non-communicable diseases every year.
Interestingly, on the backdrop of this awareness, molecular genetics is making incremental strides in demonstrating the enormous human ethnic variation in the essentiality of the omega-3 PUFA ALA. Some genetic polymorphisms that permit the efficient conversion of ALA in some traditionally vegetarian populations are nearly totally absent in other traditionally obligate carnivorous societies that obtain all of their EPA/DHA directly from dietary sources.
In genetically admixed populations (a major part of today’s societies), it is, without testing omega-3 fatty acid status, nearly impossible to say with certainty who will benefit from dietary intake of EPA/DHA and who will be healthy on a vegetarian diet. The situation is more complex in certain life stages where demand for specific fatty acids may be enhanced, such as for DHA and AA in pregnancy.
Genetic studies may ultimately lead to a redefinition of the essentiality of ALA, since ALA will not be essential for individuals unable to convert ALA; for these people, EPA and DHA intake are effectively essential. Ten years ago, the term “conditional essentiality” was coined, referring to specific life stages during which EPA/DHA would be essential, and the foundations of a molecular understanding supporting this term have certainly been advanced today.
A lot of the good news about omega-3 LCPUFA activity for the body may in fact be a reflection of restoring endogenous tissue levels that were poor from the beginning, whether determined in cells, experimental animals, or in human beings. How to best assess and address nutritional deficiencies that are global in nature, but with a marked inter-individual variation in genetic components and dietary habits, is a main line of evolution.
The past few years have also seen a marked recognition of the challenges that nutritional scientists face in assigning biological activity to specific nutrients, as is the case for PUFA. In contrast to randomized controlled intervention studies of drugs, which function on a non-existing background of the test substance in the body and the diet, controlled trials with nutrients are extremely difficult to carry out.
In the case of omega-3 LCPUFA, the reasons for this have been reviewed, and limitations more clearly defined, allowing for a better understanding of how to carry out suitable intervention studies and avoid sub-optimal study designs. This includes measuring baseline omega-3 levels and actual absorption and distribution of dietary or supplemental fatty acids. Still, and likely to be seen repeated over the coming years, the understanding of the role of omega-3s in human health starts out with small studies that are frequently of observational nature and are gradually scaled to larger study groups to better control the host of variables that plague nutritional intervention studies.