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The Evolution of Omega 3's

Credit: Hindawi.com

              When it comes to Omega 3's, form and source are quite important, both from a health and evolutionary perspective. There are three kinds of these fatty acids: alpha linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ALA is the shorter plant form, and currently the only form considered essential; ALA can be elongated into the longer chain EPA/DHA, found in fish and phytoplankton, via fatty acid desaturases (enzymes your liver produces).

              Referring to ALA as the only essential omega 3 fatty acid has been an issue of contention in the field of nutritional sciences. EPA/DHA, at low doses, are thought to be potent anti-inflammatory agents, lower triglycerides, and help maintain cholesterol homeostasis, via decreasing lipogenic gene expression in the liver (2), all having profound implications for Cardiovascular Disease risk. They are also used widely in cases of Inflammatory Bowel Disease, joint pain and Rheumatoid Arthritis. EPA/DHA may reduce the risk of breast cancer via reductions in growth factor production (3), though ALA may also have a protective effect. EPA/DHA are important structural components of membranes, with areas of the brain being specifically enriched with DHA. The major factor fueling the debate comes from studies measuring the synthesis of DHA from ALA, which have yielded conflicting results about the efficacy of this conversion. It is generally accepted that all humans can convert ALA to DHA, though it varies widely, is usually less than a 5% conversion rate (pregnant women can convert more), with infants have shown a wide variability in conversion rates (4). Nutrition is all about dosage, and nailing down a how much dietary EPA/DHA is necessary, if any, has eluded researchers.

            Although DHA/EPA have a number of roles as nuclear ligands/transcription factors regulating gene expression, the debate over their essentiality is most relevant to human evolution because of DHA's structural role in brain development. One of the major changes seen throughout the Pleistocene was a drastic increase in cranial capacity (cc). It has been argued that DHA was an essential nutrient for the evolution of homo sapiens' larger brains, because the brain preferentially uptakes DHA over other fatty acids, allowing its membranes to be enriched with DHA (10). Rapid brain development occurs during fetal development and the early years of life, representing the most critical period, susceptible to variations in DHA availability. About half of the 10mg/day that accumulates in the first 6 months of a newborn's life is found in the brain. It is recommended that growing infants get at least 20mg/day of DHA (5), with breast-milk providing a huge variation in milk, from 60mg/d to >1g/day(10).

Credit: Massey University
            While some argue that DHA deficiencies aren't a sufficient selective pressure, individuals with Zellweger syndrome (dysfunctional/absent peroxisomes) exemplify the critical role of DHA in brain development; this phenotype is associated with  impaired brain development and neural migration, renal cysts, and eye abnormalities (6). DHA deficiency is associated with impaired learning and vision, as well as cognitive decline in older individual's (7).

            This whole debate boils down to whether or not humans, who evolved to be skilled hunters and were able to consume sea-food sources, evolved to be able to endogenously synthesize enough DHA from ALA for brain development and maintenance. It has been suggested that humans, evolving on the southern coastal plain of Africa, may have dealt with regular sea-level fluctuations, and competition for resources may have selected for humans with skilled fishing abilities. If members of the genus homo had regular access to large dietary sources of DHA throughout the evolution of a larger brain, there would not have been selection for increased bio-synthesis of DHA.

             Interestingly, some evidence exists to show variation in the activities of the FADS gene cluster, potentially allowing for enhanced conversion of shorter chain PUFAs (ALA/LA) into longer (AA/EPA/DHA) (8). There is also evidence for selection at the FADS loci (11), with a pattern consistent for positive selection found in individuals of African descent, with significant linkage disequilibrium in the African haplotype block including FADS1. However, European populations, and Africans with European admixture, do not show similar signs of selection. Of note, the authors found a specific derived allele of FADS1 that is fixed in the African population, but varies in frequency in non-African populations. This fixed allele has been shown to be associated with a phenotype capable of synthesizing more long chain fatty acid products from their shorter/plant precursors (9). The proposed interpretation of this data is that Africans, leaving the shoreline for the mainland, required a more functional FADS1, to obtain sufficient DHA from the ALA in their diets. It is thought that the reason that Europeans and Asians have varied frequencies of this allele in their populations is due to agriculture and farming, which would have provided other sources of DHA (eggs, grass-fed meats/milk), negating any selective pressure and allowing for mutations to accumulate in this gene cluster, resulting in the allele frequencies that we currently see. 

           I love this kind of research, because it shows the application of evolutionary analyses to modern day health. While the evidence of selection for this genotype is not a be-all-end-all for debates of omega 3 fatty acid recommendations, it does provide some insight to the idea that a bit more DHA/EPA in the diet may be beneficial for specific populations. As the health sciences move into a realm of personalized medicine, it is a very real possibility that some individuals may be recommended lower DHA/EPA supplementation, and some may require more. An individual's FADS1 genotype, as well as their intake of omega 6's and a few other micronutrients required as cofactors for fatty acid elongation, can provide an accurate dosage recommendation for their DHA/EPA intake to promote optimal growth, development, and future health.



1. Stephen Cunnane, Commentary, Docosahexaenoic acid and human brain evolution: missing the forest for the trees,  British Journal of Nutrition , 2007
2. http://www.ncbi.nlm.nih.gov/pubmed/16919514
3. http://jn.nutrition.org/content/137/3/548.full
4.  http://www.ncbi.nlm.nih.gov/pubmed/11844977
5.https://www.ncbi.nlm.nih.gov/m/pubmed/10695931/?i=6&from=/8286154/related
6. http://www.ncbi.nlm.nih.gov/pubmed/11478386
7.http://www.ncbi.nlm.nih.gov/pubmed/10479465
8.http://www.ncbi.nlm.nih.gov/pubmed/21733300
9.. http://www.ncbi.nlm.nih.gov/pubmed/21366865
10. http://jn.nutrition.org/content/137/4/855.full
11. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044926
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  1. KevinMarch 27, 2014 at 7:53 AM

    I'm curious about your take on vegetable oils and whether they are unhealthy because they are too unstable. And what about the stability of Fish Oil? Also, what about the recent study that links Fish Oil to prostate cancer? I have seen recommendations to keep omega 3/6 ratio closer by reducing intake of man-made omega 6 (like veggie oils) rather than increasing intake of Fish Oil.

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    1. Kevin C. Klatt, PhD, RDMarch 27, 2014 at 9:08 AM

      Hi Kevin,
      I guess that would depend on your definition of unhealthy. There's studies going back to the early 70's, that I discuss here (http://nutrevolve.blogspot.com/2014/03/another-meta-analysis-on-saturated-fat.html), that show an improvement in cardiovascular outcomes from replacing saturated fat with vegetable oil. All vegetable oils, however, are purely oil, dense in calories, and contain little, if any, other nutrients. My goal is to use as little added oil as possible, because it's not very nutrient dense. It's one thing to deep fry potato chips, or make chocolate chip cookies with your veggie oils, and it's another to use a tbsp to saute some veggies - context matters.

      Encapsulated fish oil will be stable - the reason you don't see it being added to everyday food products is because of it is easily oxidized and food scientists haven't found a great way to fortify foods with it yet. You'll know if fish/fish oil has gone rancid by the smell.

      Regarding fish oil and prostate cancer, there are actually a few researchers who have raised issue with the obsession with fish oil, and question its essentiality. Yes, it is anti-inflammatory, but inflammation is good thing for the immune - chronic inflammation is the issue that drives/underlies many modern diseases. However, the prostate cancer study was just one study, and we can't make recommendations based off of one study. We need a lot more research to understand when taking fish oil/DHA is most important. Everything in nutrition is about the dose - Pregnant/lactating women take about 200mg/day to grow/develop an entire new brain. I don't think there's reason to believe anyone needs more than that 200mg, or eating fatty fish 2x/wk. Unfortunately, what many people are getting in fish oil supplements is significantly higher than that. The strongest evidence for DHA/EPA supplementation comes from studies of individuals who have already had a cardiovascular event. To say that the everyday healthy person MUST consume DHA is not supported by scientific literature. This prostate cancer study reminds us that there may be too much of a good thing.

      The recommendation to keep omega 3:6 closer is to ensure your bodies ability to convert the omega 3 ALA to EPA/DHA. If you're consuming pre-formed DHA already, I wouldn't worry about following the extreme recommendations by some groups (paleo, vegan, etc) to get down to a 1:1 or 3:1 recommendation that many advise. Your body regulates how much of the inflammatory molecules it makes from omega 6's (I discuss that here, http://nutrevolve.blogspot.com/2013/11/omega-6s-and-inflammation.html). There is a concern that very high intakes of PUFAs may have detrimental effects due to lipid peroxidation, and the IoM set the upper end of the AMDR at 10% of calories.

      **With any supplementation, I highly encourage you discuss this with your primary care provider/dietitian, as I don't know your past medical history, medication use, or general health status.

      Hope that helps!
      -KCK

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    2. Kevin C. Klatt, PhD, RDMarch 27, 2014 at 9:08 AM

      And as always, like and share if you enjoyed it! :)

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