Omega-3 and omega-6 are polyunsaturated fatty acids that can only be obtained from food. In the body, these essential fatty acids are components of cell membranes, particularly in the retina and brain tissue. They are also precursors of prostaglandins and leukotrienes, which modulate inflammatory processes. 1
The discovery of the preventive effects of a diet rich in omega-3 against cardiovascular diseases, as well as their anti-inflammatory properties, has generated considerable interest from the public and the scientific community. Studies undertaken to explore the therapeutic potential of essential fatty acids have revealed that they can contribute to the prevention and treatment of chronic inflammatory diseases such as arthritis and lupus, as well as dyslipidemia, diabetes, depression, and osteoporosis. All of these therapeutic applications are related to acute or low-grade inflammation.
Active ingredients
Eicosapentaenoic acid (EPA), 20:5*; docosahexaenoic acid (DHA), 22:6*.
* These numbers indicate the number of carbon atoms in the chain and the number of double bonds. For example, 20:5 corresponds to a molecule containing 20 carbon atoms and 5 double bonds. Source: Simopoulos AP. Am J Clin Nutr. 1999 .
Regular consumption of fish reduces the risk of coronary heart disease, death from heart attacks, and myocardial damage. 2
A study among Inuit shows that high levels of omega-3 increase HDL and lower triglycerides. 3
Long-chain omega-3 significantly reduced cardiovascular death (OR: 0.87, 95% CI: 0.79–0.95, p = 0.002); sudden cardiac death (OR: 0.87, 95% CI: 0.76–0.99, p = 0.04); all-cause mortality (OR: 0.92, 95% CI: 0.85–0.99, p = 0.02) and non-fatal cardiovascular events (OR: 0.92, 95% CI: 0.85–0.99, p = 0.02). 4
Omega-3 Index: The level of long-chain omega-3s (EPA & DHA) in red blood cell membranes is inversely associated with the incidence of heart disease (≥ 8% offers the most protection <equivalent to an intake of 1 g of omega-3 per day>). 5
Omega-3 intake (900 mg/day) combined with diet reduced systolic (-12.2%) and diastolic (-8.2%) pressure, serum triglycerides (-21.4%), insulin resistance (-13.1%) (P<0.05) and serum IL-6 concentration (-28.5%) (P=0.034) compared to diet alone. 6
Omega-3s decrease insulin and adiponectin resistance and lower inflammation and triglycerides. 7
4g per day of omega-3 reduces the percentage of fat in the liver (non-alcoholic fatty liver disease). 8
In adolescents (10-18 years) with MetS, 2.4 g of omega-3 per day increased blood HDL and significantly reduced VEGF. 9
In patients with moderate hypertriglyceridemia (fasting triglycerides: 150 to 500 mg/dL <1.69 to 5.65 nmol/l>), 3.4 g of omega-3 daily for 8 weeks significantly reduced triglycerides by 27% compared to placebo (173 ± 17.5 vs. 237 ± 17.5 mg/dL <1.95 to 2.68 nml/l>; p = 0.002). 10
In patients with severe hypertriglyceridemia (TG ≥ 500 mg/dL <5.65 nmol/L>, < 2000 mg/dL <22.6 nmol/L>), 2 to 4 g of omega-3 per day for 12 weeks significantly reduced triglycerides and non-HDL cholesterol. 11
A low-carb diet combined with omega-3 supplementation significantly helps control polycystic ovarian syndrome and normalize FSH and testosterone. 12
Taking 4 g of omega-3 per day for 12 weeks reduces the vicious cycle of inflammation by reducing the number of adipose tissue macrophages, increasing adipose capillaries, and decreasing macrophage chemotactic protein type 1 (MCP-1) levels in volunteers with insulin resistance. 13
The effect of omega-3 on membrane fluidity and inflammation is useful in pain relief. 14
Omega-3 normalizes the adrenal response (catecholamines). 15
Neuropathies
Omega-3 (640 mg, 3 times daily) helps prevent chemotherapy-induced neuropathy (paclitaxel). 16
Leaky gut
Prevent injuries to the gastrointestinal mucosa caused by irritants (e.g., anti-inflammatories). 17
Omega-3s maintain intestinal barrier function following loss of blood perfusion (in vivo). 18
Indications
Reduction of inflammation; 19,20
Prevention of cardiovascular diseases 21 (antithrombogenic, blood pressure, 22 cholesterol and triglycerides 23 );
Inflammatory diseases: rheumatoid arthritis, lupus, irritable bowel syndrome;
Central nervous system: depression, attention deficit hyperactivity disorder, bipolar disorder 24 , schizophrenia 25 , improves fetal and newborn development up to 4 months 26 , prevention of cognitive decline and Alzheimer's disease;
Asthma and COPD. 27
Psoriasis: treatment adjuvant. 28
Autoimmune diseases. 29
Pregnancy: Despite poor study methodology, there is sufficient evidence to establish that taking fish oil supplements improves pregnancy outcome and reduces the risk of postpartum depression. 30,31
Fetal development: Omega-3 consumption during pregnancy reduces several health risks in infants, such as allergies. 32 However, even though they improve the neurological development of the fetus and baby, omega-3s do not make the baby more intelligent, unless perhaps the mother comes from a poor and deficient background.
Dosages
The doses commonly used to achieve a therapeutic anti-inflammatory effect vary between 3,000 and 9,000 mg of omega-3 (EPA + DHA) per day, in several doses. 33 However, there are no contraindications for the use of higher doses. On the other hand, there is no consensus regarding a minimum recommended intake.
Cardiovascular and metabolic syndrome
Dietary prevention: 3 portions of oily fish per week.
Primary prevention: 500 to 650 mg omega-3 (EPA & DHA), once a day.
Secondary prevention or intervention (1 or more risk factors): 1,000 mg omega-3 or more per day.
Triglycerides: 2,400 to 4,000 mg per day.
A study in overweight but otherwise healthy young adults did not note changes in inflammatory markers (dose too low <1700 mg per day> and duration too short <4 weeks>). 34
Ophthalmology
1,800 mg of omega 3 (EPA and DHA) per day.
Side effects
Fish oils in high doses can cause mild digestive problems: loose and/or oily stools, belching (intercourse), halitosis (bad breath).
Cod liver and halibut oils are not recommended. Their high vitamin A content may cause you to exceed the tolerable upper intake of 3 mg (or 10,000 IU) per day.
Interactions
The theoretical interaction with anticoagulants (warfarin, heparin) and antiplatelet drugs is not significant. For very high dosages, INR should be closely monitored, but below 3000 mg (EPA+DHA), this is not necessary. 35,36,37
According to the FDA, omega-3s have GRAS ( generally recognized as safe ) status up to 3g of omega-3 (10g of oil).
Pregnancy and breastfeeding
Omega-3s are not only safe during pregnancy but are increasingly recommended.
Contraindication
Fish allergy. (Anaphylaxis)
Notes
One concept about fish oil is particularly misused by marketing: the concentration ratio between EPA and DHA. In fact, the only documented EPA/DHA ratio concerns indications related to the nervous system: mood disorders, depression, stress resistance, anxiety, etc. In these cases, we will prefer products containing a high content of EPA and a low amount of DHA (the EPA/DHA ratio should be between 7:1 and 20:1). In all other cases, the ratio between the two is not documented. We will therefore be interested in the total dose (EPA+DHA) and not in any relationship between the two.
Products made in Canada and bearing a Natural Product Number (NPN) are toxin-free and have adequate quality control.
International Fish Oil Standards have established the highest quality standards. Visit the IFOS website for a list of companies that adhere to these standards.
Omega 3: what ratio?
What type of omega-3 product should I take: high in EPA, high in DHA, or both?
Omega-3 products found on shelves contain two fatty acids: EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). Do they have different roles? Is the ratio of these two omega-3s (EPA/DHA) important?
What do the studies say?
With the exception of products targeted for depression and mood disorders, the EPA/DHA ratios of products on the market are based on… very little.
So here is the current state of knowledge on this subject:
Depression and mood disorders
For these indications, the weight of evidence goes towards a product containing at least 1000 mg of EPA and as little DHA as possible. 1,2 Omega-3 products will therefore be in the form of ethyl ester (EE) or monoglycerides (MG), forms which make it easier to modulate the EPA/DHA ratio than the triglyceride (TG) form.
Inflammation
For inflammatory indications (such as arthritis), logic dictates that EPA should be used primarily since it is the precursor to certain anti-inflammatory chemical mediators produced by our cells (eicosanoids). However, almost all studies have been conducted with fish oils in the TG form (therefore containing a significant proportion of DHA). 3 In addition, anti-inflammatory chemical mediators derived from DHA have recently been discovered, which are collectively called docosanoids. 4 Some of these molecules have very suggestive names, such as defensins and protectins. Ultimately, the EPA/DHA ratio is probably not very important.
Cardiovascular
Regarding cardiovascular indications, there is no consensus on the predominance of one omega-3 over the other. You will find several studies that use products richer in DHA, and just as many that use products richer in EPA. Experts agree on recommending overall dosages of omega-3, without mentioning a ratio.
Brain development
The brains of fetuses, infants, and children through early adolescence (the final period of brain growth) have the capacity to utilize DHA as a building material. Therefore, it is important that children do not lack it.
Adults have much less of this ability. Thus, DHA has shown the ability to prevent cognitive decline if and only if it is consumed over a very long period, that is, for life. Here, DHA is no longer considered a single compound, but rather a marker of fish consumption, a lifestyle habit. Praising the merits of a DHA-rich product to prevent Alzheimer's or cognitive decline is not based on the most rigorous science... It may be useful, but it does not reverse the disease. So, here too, what matters most is the total amount of omega-3, not a specific ratio.
Conclusion
Long-chain omega-3s are among the most important substances for health and the most useful for a range of indications.
The important thing to remember is that, with the exception of mood disorders, the total dose of omega-3 is more important than the EPA/DHA ratio or the chemical structure (TG, EE or MG) in which they are presented to us. To have significant effects, the dose of omega-3 must be high (depending on the initial blood level, the condition and the weight of the person) to have an impact on the blood level, which is called the omega-3 index.
References
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Additional references:
· Kruger MC, Coetzer H, de Winter R, Gericke G, van Papendorp DH. Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging (Milano). 1998 Oct;10(5):385-94. PMID: 9932142.
· Griel AE, Kris-Etherton PM, Hilpert KF, Zhao G, West SG, Corwin RL. An increase in dietary n-3 fatty acids decreases a marker of bone resorption in humans. Nutr J. 2007 Jan 16; 6:2. PMID: 17227589.
· Tartibian B, Hajizadeh Maleki B, Kanaley J, Sadeghi K. Long-term aerobic exercise and omega-3 supplementation modulate osteoporosis through inflammatory mechanisms in post-menopausal women: a randomized, repeated measures study. Nutr Metab (Lond). 2011 Oct 15; 8:71. PMID: 21999620.
· Rahman MM, Bhattacharya A, Banu J, Kang JX, Fernandes G. Endogenous n-3 fatty acids protect ovariectomy induced bone loss by attenuating osteoclastogenesis. J Cell Mol Med. 2009 Aug;13(8B):1833-44. PMID: 20141608.
· Salari P, Rezaie A, Larijani B, Abdollahi M. A systematic review of the impact of n-3 fatty acids in bone health and osteoporosis. Med Sci Monit. 2008 Mar;14(3):RA37-44. Review. PMID: 18301367.
· Zainal Z, Longman AJ, Hurst S, Duggan K, Caterson B, Hughes CE, Harwood JL. Relative efficacies of omega-3 polyunsaturated fatty acids in reducing expression of key proteins in a model system for studying osteoarthritis. Osteoarthritis Cartilage. 2009 Jul;17(7):896-905.
· Micallef MA, Munro IA, Garg ML. An inverse relationship between plasma n-3 fatty acids and C-reactive protein in healthy individuals. Eur J Clin Nutr. 2009 Sep;63(9):1154-6. Epub 2009 Apr 8. PubMed PMID: 19352379.
· Kalogeropoulos N, Panagiotakos DB, Pitsavos C, Chrysohoou C, Rousinou G, Toutouza M, Stefanadis C. Unsaturated fatty acids are inversely associated and n-6/n-3 ratios are positively related to inflammation and coagulation markers in plasma of apparently healthy adults. Clin Chim Acta. 2010 Apr 2;411(7-8):584-91. Epub 2010 Jan 26. PubMed PMID: 20097190.
· Mas E, Woodman RJ, Burke V, Puddey IB, Beilin LJ, Durand T, Mori TA. The omega-3 fatty acids EPA and DHA decrease plasma F (2)-isoprostanes: Results from two placebo-controlled interventions. Free Radic Res. 2010 Jun 14.
· Simopoulos AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr. 1999 Sep;70(3 Suppl):560S-569S.
· Lspérance F, Frasure-Smith N, St-André E, Turecki G, Lspérance P, Wisniewski SR. The efficacy of omega-3 supplementation for major depression: a randomized controlled trial. J Clin Psychiatry. 2011 Aug;72(8):1054-62. doi: 10.4088/JCP.10m05966blu. Epub 2010 Jun 15. PubMed PMID: 20584525.
· Martins JG. EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. J Am Coll Nutr. 2009 Oct;28(5):525-42. Review. PubMed PMID: 20439549.
· Nilsson A, Radeborg K, Salo I, Björck I. Effects of supplementation with n-3 polyunsaturated fatty acids on cognitive performance and cardiometabolic risk markers in healthy 51 to 72 year old subjects: a randomized controlled cross-over study. Nutr J. 2012 Nov 22; 11:99. doi:10.1186/1475-2891-11-99. PubMed PMID: 23173831; PubMed Central PMCID: PMC3564898.
· Simopoulos AP. Dietary omega-3 fatty acid deficiency and high fructose intake in the development of metabolic syndrome, brain metabolic abnormalities, and non-alcoholic fatty liver disease. Nutrients. 2013 Jul 26;5(8):2901-23. doi:10.3390/nu5082901. Review. PubMed PMID: 23896654; PubMed Central PMCID: PMC3775234. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775234/
· Martins JG. EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. J Am Coll Nutr. 2009 Oct;28(5):525-42. Review. PubMed PMID: 20439549. https://www.ncbi.nlm.nih.gov/pubmed/20439549
· Appleton KM, Rogers PJ, Ness AR. Is there a role for n-3 long-chain polyunsaturated fatty acids in the regulation of mood and behavior? A review of the evidence to date from epidemiological studies, clinical studies and intervention trials. Nutr Res Rev. 2008 Jun;21(1):13-https://www.ncbi.nlm.nih.gov/pubmed/19079852
· Wall R, Ross RP, Fitzgerald GF, Stanton C. Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr Rev. 2010 May;68(5):280-9. doi: 10.1111/j.1753-4887.2010.00287. x. Review. PubMed PMID: 20500789. https://www.ncbi.nlm.nih.gov/pubmed/20500789
· Schunck WH. EPA and/or DHA? A test question on the principles and opportunities in utilizing the therapeutic potential of omega-3 fatty acids. J Lipid Res. 2016 Jul 19. pii: jlr.C071084.
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