In short, there is no single optimal EPA:DHA ratio. If we are really healthy, with an optimal omega-6 to omega-3 ratio (from a diet rich in omega-3 fatty acids and low in grains and vegetable oils) and have an active, stress-free lifestyle, relying on standard fish oil in the natural 1.5:1 EPA:DHA ratio or simply consuming oily fish is completely adequate.
Your concerns are very valid. The quality of commercially available omega-3 preparations can vary greatly. In our clinical trials we use preparations made by reputable manufacturers with high standards. We also have the preparations analyzed by 2 independent labs to confirm omega-3 content, impurities, and degree of oxidation, prior to initiating the study. While omega-3 fatty acids–like most nutrients–are ideally obtained through dietary practice, because many people may not enjoy omega-3 containing foods, supplements may be a good option for these individuals. Anyone who is interested in using an omega-3 preparation for treating a psychiatric condition should do so preferably under the supervision of a psychiatrist.
The most extensive data of the effect of fish oil on lipoprotein subfractions are based on trials performed before the widespread use of statins. This data were aggregated over a decade ago in a meta-analysis of 16 randomized trials including over 1500 patients.17 In this analysis, low-density lipoprotein (LDL) was increased by an average of 5% and high-density lipoprotein was marginally changed. Although a shift toward less atherogenic, larger and more buoyant LDL particle composition has been shown,74 this has been offset by the observation that the number of apolipoprotein B 100 particles increases and may be more susceptible to oxidation.75 Increased conversion of remnant particles (intermediate density lipoprotein) to LDL has also been observed.76
The hypotriglyceridemic effect of fish oil is well established and is related to both dose and baseline triglyceride level. Patients with triglycerides <90 mg/dL will be negligibly affected unless very high doses of omega-3 FA are used.67,68 However, in patients with triglycerides >200 mg/dL, who are treated with 4 g/d of fish oil, a 30% reduction in triglycerides is expected.17,69 For patients with triglycerides >500 mg/dL who are at risk for pancreatitis, the National Cholesterol Education Program Adult Treatment Panel III guidelines recommend using fish oil supplements as an adjunctive therapy to fibrates and nicotinic acid.70 Lovaza capsules have been shown to be effective, safe, and comparable to gemfibrozil in treating triglycerides at this range.71,72 The official label recommendation for Lovaza is for patients with triglycerides >500 mg/dL.73
Typical Western diets provide ratios of between 10:1 and 30:1 (i.e., dramatically higher levels of omega−6 than omega−3). The ratios of omega−6 to omega−3 fatty acids in some common vegetable oils are: canola 2:1, hemp 2–3:1, soybean 7:1, olive 3–13:1, sunflower (no omega−3), flax 1:3, cottonseed (almost no omega−3), peanut (no omega−3), grapeseed oil (almost no omega−3) and corn oil 46:1.
Omega−3 fatty acids, also called ω−3 fatty acids or n−3 fatty acids, are polyunsaturated fatty acids (PUFAs). The fatty acids have two ends, the carboxylic acid (-COOH) end, which is considered the beginning of the chain, thus "alpha", and the methyl (-CH3) end, which is considered the "tail" of the chain, thus "omega". One way in which a fatty acid is named is determined by the location of the first double bond, counted from the tail, that is, the omega (ω-) or the n- end. Thus, in omega-3 fatty acids the first double bond is between the third and fourth carbon atoms from the tail end. However, the standard (IUPAC) chemical nomenclature system starts from the carboxyl end.
Our scientists also focused on each oil’s freshness, measured by the degree of oxidation. Oxidation occurs in two phases: primary (measured by peroxide values) and secondary (measured by p-anisidine values). Total oxidation is formalized into a quantitative score, TOTOX. While Labdoor conducted tests of both primary and secondary oxidation, advances in rancidity testing confirm that added flavors–particularly added citrus flavors prevalent in liquid formulations–skew p-anisidine values and result in false positive outcomes. Until analytical techniques measuring p-anisidine values that are able to account for added flavors are established, Labdoor will use peroxide values as the primary indicator of freshness. All products recorded measurable levels of oxidation, with the average product recording a peroxide values of 3.7 meq/kg. 14/51 products recorded peroxide levels at or above the upper limit (10 meq/kg).
Additionally, total polychlorinated biphenyl (PCB) content was measured in every product. All product recorded PCB levels within the Food and Drug Administration’s (FDA) 2 PPM limit for the edible parts of fish/shellfish as well as the stricter standards enacted by California’s Proposition 65, which requires products containing greater than 0.09 PPM of PCB content to bear a cancer warning. The worst offender, Now Foods Ultra Omega-3 Fish Oil, recorded 0.04 PPM of PCB content.
A 2014 meta-analysis of eleven trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD) and of eight trials with patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo. The study concluded that: "The use of omega-3 PUFA is effective in patients with diagnosis of MDD and on depressive patients without diagnosis of MDD."
Participants treated with a daily dose of 2000 mg or more of omega-3 PUFAs showed a significantly greater association of treatment with reduced anxiety symptoms. In addition, participants receiving supplements containing less than 60% EPA showed a significant association, but not those receiving supplements containing 60% or more EPA. The depression literature supports the clinical benefits of EPA-enriched formulations (≥60% or ≥50%) compared with placebo for the treatment of clinical depression.9,13,73-75 This opposite effect of EPA-enriched formations on anxiety and depression is intriguing and possibly linked to a distinct underlying mechanism of omega-3 PUFAs. Exploration of the effects of omega-3 PUFAs on anxiety symptoms is just beginning and studies assessing the dose response anxiolytic effects of omega-3 PUFAs have not yet been performed. Further phase 2 trials of anxiety symptoms among participants with neuropsychiatric illness or physical illness should aim to determine the optimal dose.
Henriksen, C., Haugholt, K., Lindgren, M., Aurvag, A. K., Ronnestad, A., Gronn, M., Solberg, R., Moen, A., Nakstad, B., Berge, R. K., Smith, L., Iversen, P. O., and Drevon, C. A. Improved cognitive development among preterm infants attributable to early supplementation of human milk with docosahexaenoic acid and arachidonic acid. Pediatrics 2008;121(6):1137-1145. View abstract.
Only fish and breast milk contain all the members of the omega-3 family, including its two main stars, EPA and DHA. Because Americans as a rule consume far too few omega-3s from fish or fish oil, it’s no surprise that the majority of Americans have low omega-3 index levels as well. A recent study of global omega-3 index levels found that an estimated 95% of Americans (with the exception of folks from Alaska) had an omega-3 index of 4 or below, putting them in the high risk category (5, 6, 7).
Cardiovascular disease is the cause of 38% of all deaths in the United States, many of which are preventable (28). Chronic inflammation is thought to be the cause of many chronic diseases, including cardiovascular disease (29). EPA and DHA are thought to have antiinflammatory effects and a role in oxidative stress (30) and to improve cellular function through changes in gene expression (31). In a study that used human blood samples, EPA+DHA intake changed the expression of 1040 genes and resulted in a decreased expression of genes involved in inflammatory and atherogenesis-related pathways, such as nuclear transcription factor κB signaling, eicosanoid synthesis, scavenger receptor activity, adipogenesis, and hypoxia signaling (31). Circulating markers of inflammation, such as C-reactive protein (CRP), TNF α, and some ILs (IL-6, IL-1), correlate with an increased probability of experiencing a cardiovascular event (32). Inflammatory markers such as IL-6 trigger CRP to be synthesized by the liver, and elevated levels of CRP are associated with an increased risk of the development of cardiovascular disease (33). A study of 89 patients showed that those treated with EPA+DHA had a significant reduction in high-sensitivity CRP (66.7%, P < 0.01) (33). The same study also showed a significant reduction in heat shock protein 27 antibody titers (57.69%, P < 0.05), which have been shown to be overexpressed in heart muscle cells after a return of blood flow after a period of ischemia (ischemia-reperfusion injury) and may potentially have a cardioprotective effect (33).
Attention deficit-hyperactivity disorder (ADHD) in children. Early research shows that taking fish oil improves attention, mental function, and behavior in children 8-13 years-old with ADHD. Other research shows that taking a specific supplement containing fish oil and evening primrose oil (Eye Q, Novasel) improves mental function and behavior in children 7-12 years-old with ADHD.