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Omega-3 in Health and Disease


Omega-3

Naturally occurring fatty acids (FAs) can be classified into three categories based on the number of double bonds present; saturated, monounsaturated and polyunsaturated FAs (PUFAs). FAs can be further classified according to their length and the position of the first double bond on the methyl terminal. Like all FAs, PUFAs consist of long chains of carbon atoms with a carboxyl group at one end of the chain and a methyl group at the other. The two major classes of PUFAs are the omega-3 (n-3) and omega-6 (n-6) FAs.

The three main n-3 FAs are alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Oils containing these FAs, originate primarily from certain plant sources or are modified in plants, marine, algal, and single-cell sources. Long-chain (LC) FAs such as EPA and DHA accumulate in the body of marine animals; which consume plants rich in n-3 FAs.


Linoleic acid (LA) and ALA are essential FAs, as they cannot be synthesized by humans, meaning they must be obtained from the diet. ALA is the parent FA of n-3 PUFAs, that is converted to EPA or DPA by chain elongation and desaturation. EPA, DHA and arachidonic acid (ARA), all play key roles in regulating body homeostasis.



Role

Omega-3s play important roles in the body as components of the phospholipids that form the structures of cell membranes. DHA is especially high in the retina, brain, and sperm. In addition to their structural role in cell membranes, n-3s provide energy for the body and are used to form eicosanoids. Eicosanoids are biologically active molecules that have similar chemical structures to the fatty acids from which they are derived (ARA, EPA and DHA). They act as modulators of numerous physiological processes, including reproduction, cardiovascular, pulmonary, immune, and endocrine systems, thereby influencing health.


LA and ALA have competing roles in the synthesis of eicosanoids. High intake of ALA favours the production of anti-inflammatory eicosanoids since n-3 FAs are preferred substrates the enzymes involved in eicosanoid biosynthesis. Despite being present in higher plants, algae, some fungi, and lower animals, humans are deficient in the desaturases necessary to convert oleic acid into LA, and desaturases to convert LA to ALA. Thus, LA and ALA are considered essential FAs in human diet.


In general, ARA gives rise to pro-inflammatory eicosanoids whereas EPA and DHA give rise to anti-inflammatory eicosanoids. As such, a proportionally higher consumption of n-3 PUFAs could confer protection against the pathogenesis of many chronic diseases, such as cardiovascular disease, cancer and inflammatory and immunological response.


Sources

Omega-3s are found naturally in some foods and are added to some fortified foods. Marine algae are the predominant producers of n-3s in the biosphere. Omega-3 FAs, especially EPA and DHA, are synthesized by phytoplankton and algae, eventually being transferred via the food web, to be deposited into the lipids of fish and marine mammals.

Although marine organisms are the major source of n-3 FAs, some plant seeds also contain them. Flax, chia, and canola seeds are exceptionally abundant sources of ALA, which serves as a precursor to the synthesis of LC PUFAs in the human body. However, production of n-3 FAs from ALA in the body is limited, with rates of conversion reported from 4%-15%. Most crop seeds and vegetable oils, including canola, soybean, corn, and sunflower oils, contain small amounts of n-3 FAs (ALA).



Some foods, such as certain brands of eggs, yogurt, juices, milk, and soy beverages, are fortified with DHA and other n-3s. In the United States, since 2002, manufacturers have added DHA and ARA (the two most prevalent LC PUFAs in the brain) to most infant formulas available.


Omega-3s are present in several dietary supplement formulations, including fish oil, krill oil, cod liver oil, and algal oil. Typical, a 1,000 mg fish oil supplement could provide around 180 mg EPA and 120 mg DHA, but doses vary widely. Plant-based sources n-3s from algal oil usually provide around 100–300 mg DHA, with some also containing EPA. Studies have shown the bioavailability of DHA from algal oil to be equivalent to that from cooked salmon.


Role in Health and Disease

The potential health benefits of consuming n-3s are the focus of a great deal of scientific research. The majority of research has focused on EPA and DHA from foods (fish) and dietary supplements (fish oil) as opposed to ALA from plant-based foods. Many observational studies link higher intakes of fish and other seafood with improved health outcomes. However, it is difficult to ascertain whether these benefits are due to the n-3 content of the seafood, or confounding variables- other components in the seafood, the substitution less healthful foods for seafood, other healthful behaviours, or a combination of these factors. Data from randomized clinical trials are needed to elucidate this matter.


A deficiency of essential FAs can cause rough, scaly skin and dermatitis. Plasma and tissue concentrations of DHA decrease when an n-3 FA deficiency is present. However, there are no known cut-off concentrations of DHA or EPA below which normal function ceases.


Requirements and Toxicity

Experts have not established recommended amounts for n-3 FAs, except for ALA. When the Institute of Medicine (IOM) last reviewed n-3s, insufficient data were available to establish an estimated average requirement, so Adequate Intakes (AIs) were established for all ages, based on n-3 intakes in healthy populations. The IOM (2010) and Dietitians of Canada (2013), state the AI of ALA level varies between 1.1 and 1.6 g per day, depending on the age and gender. The IOM did not establish specific intake recommendations for EPA, DHA or other LC n-3s.


The IOM has not established an upper limit for any n-3s, though it has noted that high doses of DHA and/or EPA (900 mg/day of EPA plus 600 mg/day DHA or more for several weeks) might reduce immune function, due to suppression of inflammatory responses. The recommended dietary ratio of n-6 to n-3 FAs for health benefits is 1:1–2:1. However, in the typical Western diets, the ratio of n-6 to n-3 is 15-1 to 16.7-1.


Conclusion

There is supportive, but not conclusive evidence that an increased intake of n-3 PUFAs is beneficial for the prevention of cardiovascular disease. However, research findings reveal that n-3 and health issue controversies continue, evident in stroke, diabetes, cancer and a variety of mental illnesses. Plant-based sources of n-3 are free from dietary factors known to promote disease in humans, including saturated fat, cholesterol and methyl mercury (a toxic heavy metal found in varying amounts in seafood). In order to reduce the risk of developing chronic diseases and optimise health, it is vital to consume rich, plant-based sources of n-3 daily.

References

Mann, J. & Truswell, S. (2017). Essentials of human nutrition. (5th ed.). London, United Kingdom: Oxford University Press.


Cholewski, M., Tomczykowa, M., & Tomczyk, M. (2018). A Comprehensive Review of Chemistry, Sources and Bioavailability of Omega-3 Fatty Acids. Nutrients, 10(11). doi:10.3390/nu10111662


Saini, R. K., & Keum, Y. S. (2018). Omega-3 and omega-6 polyunsaturated fatty acids: Dietary sources, metabolism, and significance - A review. Life Sci, 203, 255-267. doi:10.1016/j.lfs.2018.04.049


Shahidi, F., & Ambigaipalan, P. (2018). Omega-3 Polyunsaturated Fatty Acids and Their Health Benefits. Annu Rev Food Sci Technol, 9, 345-381. doi:10.1146/annurev-food-111317-095850

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