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Omega-3 fatty acids are polyunsaturated fatty acids classified as essential because they cannot be synthesized in the body; they must be obtained from food. Important omega-3 fatty acids in human nutrition are: α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Chemistry
Daily values As fats are macronutrients they are not assigned recommended daily allowances. Macronutrients have AI (Acceptable Intake) and AMDR (Acceptable Macronutrient Distribution Range) instead of RDAs. The AI for n-3 is 1.6 grams/day for men and 1.1 grams/day for women while the AMDR is 0.6% to 1.2% of total energy. "A growing body of literature suggests that higher intakes of α-linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) may afford some degree of protection against coronary heart disease. Because the physiological potency of EPA and DHA is much greater than that for α-linolenic acid, it is not possible to estimate one AMDR for all n-3 fatty acids. Approximately 10 percent of the AMDR can be consumed as EPA and/or DHA." There was insufficient evidence as of 2005 to set a UL (upper intake limit) for n-3 fatty acids. Researchers believe the ideal omega-6 intake should be no more than 4-5 times that of our omega-3 intake. The National Institutes of Health recently published recommended daily intakes of fatty acids, specific recommendations include 650 mg of EPA and DHA, 2.22 g/day of alpha-linolenic acid and 4.44 g/day of linoleic acid. The greatest risk of fish oil omega-3 supplementation is heavy metal poisoning by the body's accumulation of traces of heavy metals, in particular mercury, lead, nickel, arsenic and cadmium as well as other contaminants (PCBs, furans, dioxins), which may be found especially in less refined fish oil supplements. For these reasons, the FDA recommends that total dietary intake of omega-3 fatty acids from fish be limited to 3 grams per day, of which no more than 2 grams per day are from nutritional supplements. Historically, the Council for Responsible Nutrition (CRN) and the World Health Organization (WHO) have published acceptable standards regarding contaminants in fish oil. The most stringent current standard is the International Fish Oils Standard (IFOS). Fish oils that typically make this highest grade are those that are molecularly distilled under vacuum, and have virtually no measurable level of contaminants (measured parts per billion and parts per trillion). Biological significance The biological effects of the ω-3 fatty acids are largely mediated by their interactions with the ω-6 fatty acids, see Essential fatty acid interactions for detail. A 1992 paper by biochemist William E.M. Lands provides an overview of the research into omega-3 fatty acids, and is the basis of this section. The 'essential' fatty acids were given their name when researchers found that they were essential to normal growth in young children and animals. (Note that the modern definition of 'essential' is more strict.) A small amount of omega-3 in the diet (~1% of total calories) enabled normal growth, and increasing the amount had little to no additional benefit. Likewise, researchers found that omega-6 fatty acids (such as γ(gamma)-linolenic acid and arachidonic acid) play a similar role in normal growth. However they also found that omega-6 is "better" at supporting dermal integrity, renal function, and parturition. This led researchers to concentrate study on omega-6, and it is only in recent decades that omega-3 has become of interest. In 1963 it was discovered that the omega-6 arachidonic acid is converted by the body into pro-inflammatory agents called prostaglandins,. By 1979 more of what are now known as eicosanoids were discovered: thromboxanes, prostacyclins and the leukotrienes. The eicosanoids, which have important biological functions, typically have a short active lifetime in the body, starting with synthesis from fatty acids and ending with metabolism by enzymes. However if the rate of synthesis exceeds the rate of metabolism, the excess eicosanoids may have deleterious effects. Researchers found that omega-3 is also converted into eicosanoids, but at a much slower rate. If both omega-3 and omega-6 are present, they will "compete" to be transformed, so the amount of omega-3 present is directly related to a decrease in the rate of eicosanoid production. This competition was recognized as important when it was found that thromboxane is a factor in the clumping of platelets, which leads to thrombosis. The leukotrienes were similarly found to be important in immune/inflammatory-system response, and therefore relevant to arthritis, lupus, and asthma. These discoveries led to greater interest in finding ways to control the synthesis of omega-6 eicosanoids; one way being, of course, the consumption of greater amounts of omega-3. Health benefits On September 8, 2004, the U.S. Food and Drug Administration gave "qualified health claim" status to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) omega-3 fatty acids, stating that "supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease." A 2006 report in the Journal of the American Medical Association concluded that their review of literature covering cohorts from many countries with a wide variety of demographic characteristics failed to demonstrate a link between omega-3 fatty acids and cancer prevention. This is similar to the findings of a review by the British Medical Journal of studies up to February 2002 that failed to find clear effects of long and shorter chain omega-3 fats on total mortality, combined cardiovascular events and cancer. In April 2006, a team led by Lee Hooper at the University of East Anglia in Norwich, UK, published a review of almost 100 separate studies into omega-3 fatty acids, found in abundance in oily fish. It concluded that they do not have a significant protective effect against cardiovascular disease.Bijal Trivedi The good, the fad, and the unhealthy New Scientist, 23 September 2006, pp 42-49. The above stands in stark contrast with two different reviews also performed in 2006 by the American Journal of Clinical Nutrition Wang C, Harris WS, Chung M, et al. n-3 fatty acids from fish or fish-oil supplmenets but not a-linoleic acid, benefit cardiovascular outcomes in primary and secondary prevention studies: a systematic review. Am J. Clin Nutr 2006;84:5-17 and a second JAMA review Mozaffarian D, & Rimm EB. Fish Intake, Contaminants, and Human Health: Evaluating the Risks and the Benefits. JAMA, October 18, 2006—Vol 296, No. 15 that both indicated decreases in total mortality and cardiovascular incidents (i.e. myocardial infarctions) associated with the regular consumption of fish and fish oil supplements. Of particular importance is that no or very few complications were documented. Research in 2005-06 has suggested that the in-vitro anti-inflammatory activity of omega-3 acids translates into clinical benefits. Cohorts of neck pain patients and of rheumatoid arthritis sufferers have demonstrated benefits comparable to those receiving standard NSAIDs. Those who follow a Mediterranean-style diet tend to have higher HDL ("good") cholesterol levels.Kris-Etherton P, Eckel RH, Howard BV, St. Jeor S, Bazzare TL. AHA Science Advisory: Lyon Diet Heart Study. Benefits of a Mediterranean-style, National Cholesterol Education Program/American Heart Association Step I Dietary Pattern on Cardiovascular Disease. Circulation 2001;103:1823 Similar to those who follow a Mediterranean diet, Arctic-dwelling Inuit - who consume high amounts of omega-3 fatty acids from fatty fish - also tend to have increased HDL cholesterol and decreased triglycerides (fatty material that circulates in the blood). In addition, fish oil supplements containing EPA and DHA have been shown to reduce LDL ("bad") cholesterol and triglycerides. Finally, walnuts (which are rich in ALA) have been shown to lower total cholesterol and triglycerides in people with high cholesterol.Zambón D, Sabate J, Munoz S, et al. Substituting walnuts for monounsaturated fat improves the serum lipid profile of hypercholesterolemic men and women. Ann Intern Med. 2000;132:538-546. Health risks In a letter dated October 31, 2000 entitled Letter Regarding Dietary Supplement Health Claim for omega-3 Fatty Acids and Coronary Heart Disease, the U. S. Food and Drug Administration Center for Food Safety and Applied Nutrition, Office of Nutritional Products, Labeling, and Dietary Supplements noted that the known or suspected risks of omega-3 fatty acids may include: The following risks have been attributed to the FDA but are not mentioned in the above letter: Warning for persons with congestive heart failure|CHF Persons with congestive heart failure, chronic recurrent angina or evidence that their heart is receiving insufficient blood flow are advised to talk to their doctor before taking omega-3 fatty acids. It may be prudent for such persons to avoid taking omega-3 fatty acids or eating foods that contain them.• Psychological disorders Omega-3s are definitively known to have membrane-enhancing capabilities in brain cells. One medical explanation is that omega-3s play a role in the fortification of the myelin sheaths. Not coincidentally, omega-3 fatty acids comprise approximately eight percent of the average human brain according to the late Dr. David Horrobin, a pioneer in fatty acid research. Ralph Holman of the University of Minnesota, another major researcher in studying essential fatty acids, who gave it the name, surmised how omega-3 components are analogous to the human brain by stating that "DHA is structure, EPA is function." A benefit of Omega-3s is helping the brain to repair damage by promoting neuronal growth. In a six-month study involving people with schizophrenia and Huntington's disease who were treated with EPA or a placebo, the placebo group had clearly lost cerebral tissue, while the patients given the supplements had a significant increase of grey and white matter.B. Puri. International Review of Psychiatry, vol 18, p 149, 2006. Consequently, the past decade of omega-3 fatty acid research has procured some Western interest in omega-3s as being a legitimate 'brain food.' Still, recent claims that one's intelligence quotient, psychological tests measuring certain cognitive skills, including numerical and verbal reasoning skills, are increased on account of omega-3s consumed by pregnant mothers remain unreliable and controversial. An even more significant focus of research, however, lies in the role of omega-3s as a non-prescription treatment for certain psychiatric and mental diagnoses and has become a topic of much research and speculation. In 1999, Andrew L. Stoll, MD and his colleagues at Harvard University conducted a small double-blind] placebo-controlled study in thirty patients diagnosed with Bipolar disorder. Over the course of nine months, he gave 15 subjects capsules containing olive oil, and another 15 subjects capsules containing nine grams of pharmaceutical-quality EPA and DHA. In doing, so he was able to make the general distinction between the placebo group failing to improve while the Omega-3 group experienced a noticeable degree of recovery. Though Stoll believes that the 1999 experiment was not as optimal as it could have been and has accordingly pursued further research, the foundation has been laid for more researchers to explore the theoretical association between absorbed omega-3s and signal transduction inhibition in the brain.Stoll et al. Omega 3 Fatty Acids in Bipolar Disorder: A Preliminary Double-blind, Placebo-Controlled Trial "Arch Gen Psychiatry". 1999;56:407-412. Andrew Stoll MD also owns a company called Omegabrite that sells an Omega 3 oil supplement. Should enough research that is currently underway come to confirm the legitimacy of this association, then a debate and reassessment will of course be necessitated between Omega-3s and such prescription bipolar treatments as lithium, or brand Eskalith and various FDA approved and "off label" use pharmacologic agents. Some physicians and psychiatric specialists in the United States do allow willing bipolar patients to use Omega-3 supplements as complementary or conditional treatments. Omega-3s, unlike many psychopharmacologic medication treatments, are less expensive and do not commonly induce such side effects as diarrhea, drowsiness, and fatigue. At present, more research is needed before recommending that people with bipolar disorder or other mental illnesses take Omega-3 supplements. Fish The most widely available source of EPA and DHA is cold water oily fish such as salmon, herring, mackerel, anchovies and sardines. The oil from these fish have a profile of around seven times as much omega-3 as omega-6. Other oily fish such as tuna also contain omega-3 in somewhat lesser amounts. Consumers of oily fish should be aware of the potential presence of heavy metals and fat-soluble pollutants like PCBs and dioxins which may accumulate up the food chain. Some supplement manufacturers remove heavy metals and other contaminants from the oil through various means, such as molecular distillation (see above), which increases purity, potency and safety. Even some forms of fish oil may not be optimally digestible. Of four studies that compare bioavailability of the triglyceride form of fish oil vs. the ester form, two have concluded that the natural triglyceride form is better, and the other two studies did not find a significant difference. No studies have shown the ester form to be superior although it is cheaper to manufacture. Although fish is a dietary source of omega-3 fatty acids, fish do not synthesize them; they obtain them from the algae in their diet. For this reason, there is often a significant difference in EPA and DHA concentrations in farmed vs wild caught fish. Flax Flax (aka linseed) (Linum usitatissimum) and its oil are perhaps the most widely available botanical sources of omega-3. Flaxseed oil consists of ca. 55% ALA (alpha-linolenic acid). Flax, like chia, contains approximately three times as much omega-3 as omega-6. 15g of flaxseed oil provides ca. 8g of ALA, which is converted in the body to EPA and then DHA at an efficiency of (5%-10%), and (2%-5%) respectively. Botanical sources Eggs Eggs produced by chickens fed a diet of greens and insects produce higher levels of omega-3 fatty acids than chickens fed corn or soybeans. Other sources Krill, a small, shrimp-like zooplankton, is a less-known source of omega-3. Oil extracted from the krill contains omega-3 fatty acids, such as EPA and DHA, and antioxidants, such as astaxanthin and flavonoids. One advantage of extracting omega-3s from krill is that they are at the bottom of the food chain and do not contain nearly the amount of heavy metals and PCBs as predatory fish. Thus they require little or no distillation. However in comparison to fish, krill contain much lower amounts of omega-3 fatty acids per gram. Meat from grass-fed animals is often higher in omega-3 than meat from the corresponding grain-fed animal. The omega-6 to omega-3 ratio of grass-fed beef is about 2:1, making it a more useful source of omega-3 than grain-fed beef, which usually has a ratio of 4:1. Commercially available lamb is almost always grass-fed, and subsequently higher in omega-3 than other common meat sources. Milk and cheese from grass-fed cows may also be good sources of omega-3. One UK study showed that half a pint of milk provides 10% of the recommended daily intake (RDI) of ALA, while a piece of organic cheese the size of a matchbox may provide up to 88%". The microalgae Crypthecodinium cohnii and Schizochytrium are rich sources of DHA (22:6 ω-3) and can be produced commercially in bioreactors. Oil from brown algae (kelp) is a source of EPA. Acai palm fruit also contains omega-3 fatty acids. The omega-6 to omega-3 ratio Clinical studiesSimopoulos AP, Cleland LG (eds): "omega-6/omega-3 Essential Fatty Acid Ratio: The Scientific Evidence." World Rev Nutr Diet. Basel, Karger, 2003, Vol 92. Okuyama H. High n-6 to n-3 ratio of dietary fatty acids rather than serum cholesterol as a major risk factor for coronary heart disease. Eur J Lipid Sci Technol. 2001; 103:418-22. indicate that the ingested ratio of omega-6 to omega-3 (especially Linoleic vs Alpha Linolenic) fatty acids are important to maintaining cardiovascular health. Both omega-3 and omega-6 fatty acids are essential, i.e. humans must consume them in the diet. Omega-3 and omega-6 compete for the same metabolic enzymes, thus the omega-6:omega-3 ratio will significantly influence the ratio of the ensuing eicosanoids (hormones), (e.g. prostaglandins, leukotrienes, thromboxanes etc.), and will alter the body's metabolic function. Metabolites of omega-6 are significantly more inflammatory (esp. arachidonic acid) than those of omega-3. This necessitates that omega-3 and omega-6 be consumed in a balanced proportion; the ideal ratio of omega-6:omega-3 being from 3:1 to 5:1. Studies suggest that the evolutionary human diet, rich in seafood, nuts and other sources of omega-3, may have provided such a ratio. Simopoulos, et alSimopoulos AP, Leaf A, Salem Jr N. Statement on the essentiality of and recommended dietary intakes for omega-6 and omega-3 fatty acids. Prostaglandins, Leukotrienes and Essential Fatty Acids 2000;63:119-121. recommend daily intakes of three omega-3 forms: 650 mg of EPA and DHA, and 2.22 g of ALA, and one omega-6 form: 4.44 g of LA. This translates to a 3:2 omega-6 to omega-3 ratio. (i.e. 1.5:1) Typical Western diets provide ratios of between 10:1 and 30:1 - i.e., dramatically skewed toward omega-6. Here are the ratios of omega-3 to omega-6 fatty acids in some common oils: flaxseed 5:1, soy 1:8, sunflower (no omega-3), cottonseed (almost no omega-3), canola 1:2, peanut (no omega-3), grapeseed oil (almost no omega-3) and corn oil 1:80. Essential Fats in Food Oils, NIH page - http://efaeducation.nih.gov/sig/esstable.html See also Further reading | |||||||||
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