n−3 fatty acids (popularly referred to as ω−3 fatty acids or omega-3 fatty acids) are a family of unsaturated fatty acids that have in common a carbon–carbon double bond in the n−3 position; that is, the third bond from the end of the fatty acid. An unsaturated fat is a Fat or Fatty acid in which there are one or more Double bonds in the fatty acid chain In Chemistry, especially Biochemistry, a fatty acid is a Carboxylic acid often with a long unbranched Aliphatic tail ( chain) which Essential fatty acids, or EFAs are Fatty acids that cannot be constructed within an organism from other components (generally all references are to humans by any known chemical

Important nutritionally essential n−3 fatty acids are: α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). α -Linolenic acid ( ALA) is an organic compound found in many common vegetable oils. Eicosapentaenoic acid (EPA or also icosapentaenoic acid is an Omega-3 fatty acid. Docosahexaenoic acid (commonly known as DHA; 226(ω-3 all-cis -docosa-4710131619-hexa- enoic acid Trivial name cervonic The human body cannot synthesize n−3 fatty acids de novo, but it can form 20- and 22-carbon unsaturated n−3 fatty acids from the eighteen-carbon n−3 fatty acid, α-linolenic acid. De novo is a Latin phrase, meaning "from the new" anew or from the beginning These conversions occur competitively with n−6 fatty acids, which are essential closely related chemical analogues that are derived from linoleic acid. Both the n−3 α-linolenic acid and n−6 linoleic acid are essential nutrients which must be obtained from food. An essential nutrient is a Nutrient required for normal body functioning that cannot be synthesized by the body and must be obtained from a dietary source Synthesis of the longer n−3 fatty acids from linolenic acid within the body is competitively slowed by the n−6 analogues. Thus accumulation of long-chain n−3 fatty acids in tissues is more effective when they are obtained directly from food or when competing amounts of n−6 analogs do not greatly exceed the amounts of n−3.

Chemistry

Chemical structure of alpha-linolenic acid (ALA), an essential n−3 fatty acid, (18:3Δ9c,12c,15c, which means a chain of 18 carbons with 3 double bonds on carbons numbered 9, 12 and 15). Although chemists count from the carbonyl carbon (blue numbering), physiologists count from the n (ω) carbon (red numbering). Note that from the n end (diagram right), the first double bond appears as the third carbon-carbon bond (line segment), hence the name "n−3". This is explained by the fact that the n end is almost never changed during physiologic transformations in the human body, as it is more stable energetically, and other carbohydrates compounds can be synthetized from the other carbonyl end, for example in glycrids, or from double bonds in the middle of the chain.

The term n−3 (also called ω−3 or omega-3) signifies that the first double bond exists as the third carbon-carbon bond from the terminal methyl end (n) of the carbon chain. In Chemistry, a methyl group is a Hydrophobic Alkyl Functional group named after Methane (4 Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6

n−3 fatty acids which are important in human nutrition are: α-linolenic acid (18:3, n−3; ALA), eicosapentaenoic acid (20:5, n−3; EPA), and docosahexaenoic acid (22:6, n−3; DHA). These three polyunsaturates have either 3, 5 or 6 double bonds in a carbon chain of 18, 20 or 22 carbon atoms, respectively. In nutrition polyunsaturated fat is an abbreviation of polyunsaturated Fatty acid. All double bonds are in the cis-configuration, i. e. the two hydrogen atoms are on the same side of the double bond.

Most naturally-produced fatty acids (created or transformed in animalia or plant cells with an even number of carbon in chains) are in cis-configuration where they are more easily transformable. The trans-configuration results in much more stable chains that are very difficult to further break or transform, forming longer chains that aggregate in tissues and lacking the necessary hydrophilic properties. This trans-configuration can be the result of the transformation in alkaline solutions, or of the action of some bacterias that are shortening the carbonic chains. Natural transforms in vegetal or animal cells more rarely affect the last n−3 group itself. However, n−3 compounds are still more fragile than n−6 because the last double bond is geometrically and electrically more exposed, notably in the natural cis configuration.

List of n−3 fatty acids

This table lists several different names for the most common n−3 fatty acids found in nature.

Biological significances

The biological effects of the n−3 are largely mediated by their interactions with the n−6 fatty acids; see Essential fatty acid interactions for detail. α -Linolenic acid ( ALA) is an organic compound found in many common vegetable oils. Stearidonic acid is an ω-3 Essential fatty acid, sometimes called moroctic acid. Eicosatetraenoic acid, ETA designates any straight chain 204 Fatty acid. Eicosapentaenoic acid (EPA or also icosapentaenoic acid is an Omega-3 fatty acid. Docosapentaenoic acid designates any straight chain 225 Fatty acid. Docosahexaenoic acid (commonly known as DHA; 226(ω-3 all-cis -docosa-4710131619-hexa- enoic acid Trivial name cervonic The actions of the &omega-3 and &omega-6 essential fatty acids (EFAs are best characterized by their interactions; they cannot be understood separately

A 1992 article by biochemist William E.M. Lands^[1] provides an overview of the research into n−3 fatty acids, and is the basis of this section. Year 1992 ( MCMXCII) was a Leap year starting on Wednesday (link will display full 1992 Gregorian calendar) Biochemistry is the study of the chemical processes in living Organisms It deals with the Structure and function of cellular components such as William EM Lands (born July 22 1930 is an American nutritional biochemist who is the world's foremost authority on essential fatty acids

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. Essential fatty acids, or EFAs are Fatty acids that cannot be constructed within an organism from other components (generally all references are to humans by any known chemical ) A small amount of n−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 n−6 fatty acids (such as γ-linolenic acid and arachidonic acid) play a similar role in normal growth. n −6 fatty acids (popularly referred to as ω−6 fatty acids or omega-6 fatty acids) are a family of unsaturated Fatty acids γ -Linolenic acid ( gamma-linolenic acid or GLA, sometimes called gamolenic acid) is an Essential fatty acid found primarily in Arachidonic acid (AA sometimes ARA is an Omega-6 fatty acid 204(ω-6 However, they also found that n−6 was "better" at supporting dermal integrity, renal function, and parturition. The dermis is a layer of Skin beneath the epidermis that consists of Connective tissue, and cushions the body from stress and strain The kidneys are complicated organs that have numerous biological roles Childbirth (also called labour, birth, partus or parturition) is the culmination of a Human Pregnancy or These preliminary findings led researchers to concentrate their studies on n−6, and it was only in recent decades that n−3 has become of interest.

In 1963 it was discovered that the n−6 arachidonic acid was converted by the body into pro-inflammatory agents called prostaglandins. Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens A prostaglandin is any member of a group of Lipid compounds that are derived enzymatically from Fatty acids and have important functions in the Animal body By 1979 more of what are now known as eicosanoids were discovered: thromboxanes, prostacyclins and the leukotrienes. In biochemistry eicosanoids are signaling molecules made by Oxygenation of twenty-carbon Essential fatty acids (EFAs Thromboxane is a member of the family of Lipids known as Eicosanoids. Prostacyclin (or PGI2) is a member of the family of Lipid Molecules known as Eicosanoids. Leukotrienes are naturally produced Eicosanoid lipid mediators, which may be responsible for the effects of an inflammatory response 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 n−3 is also converted into eicosanoids, but at a much slower rate. Eicosanoids made from n−3 fats often have opposing functions to those made from n−6 fats (ie, anti-inflammatory rather than inflammatory). If both n−3 and n−6 are present, they will "compete" to be transformed, so the ratio of n−3:n−6 directly affects the type of eicosanoids that are produced.

This competition was recognized as important when it was found that thromboxane is a factor in the clumping of platelets, which leads to thrombosis. Thromboxane is a member of the family of Lipids known as Eicosanoids. Platelets, or Thrombocytes, are small cytoplasmic bodies derived from cells They circulate in the Blood of Mammals and are involved Thrombosis is the formation of a blood Clot ( Thrombus) inside a Blood vessel, obstructing the flow of Blood through the Circulatory The leukotrienes were similarly found to be important in immune/inflammatory-system response, and therefore relevant to arthritis, lupus, and asthma. Leukotrienes are naturally produced Eicosanoid lipid mediators, which may be responsible for the effects of an inflammatory response Arthritis (from Greek arthro-, joint + -itis, inflammation plural arthritides is a group of conditions involving damage to the Joints of the body Systemic lupus erythematosus ( SLE or lupus,) is a chronic autoimmune disease that can be fatal though with recent medical advances fatalities are becoming Asthma is a chronic Condition involving the Respiratory system in which the airways occasionally constrict become inflamed, and are These discoveries led to greater interest in finding ways to control the synthesis of n−6 eicosanoids. The simplest way would be by consuming more n−3 and fewer n−6 fatty acids.

Health benefits

On September 8, 2004, the U. Events 70 - Roman forces under Titus sack Jerusalem. 1264 - The Statute of Kalisz "MMIV" redirects here For the Modest Mouse album see " Baron von Bullshit Rides Again " S. Food and Drug Administration gave "qualified health claim" status to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) n−3 fatty acids, stating that "supportive but not conclusive research shows that consumption of EPA and DHA [n−3] fatty acids may reduce the risk of coronary heart disease. Coronary disease (or coronary heart disease) refers to the failure of Coronary circulation to supply adequate circulation to Cardiac muscle and surrounding "^[2] This updated and modified their health risk advice letter of 2001 (see below).

People with certain circulatory problems, such as varicose veins, benefit from fish oil. Varicose veins are Veins that have become enlarged and twisted Fish oil is Oil derived from the tissues of Oily fish. Fish oil is recommended for a healthy diet because it contains the Omega-3 Fish oil stimulates blood circulation, increases the breakdown of fibrin, a compound involved in clot and scar formation, and additionally has been shown to reduce blood pressure. This is an article about the rock music band "Circulatory System" Fibrin (also called Factor Ia) is a Protein involved in the clotting of blood Blood pressure is also the title of a short story by Damon Runyan in Guys and Dolls and Other Stories ^[3][4] There is strong scientific evidence that n−3 fatty acids significantly reduce blood triglyceride levels^[5][6][7][8] and regular intake reduces the risk of secondary and primary heart attack. (more properly known as, TAG or triacylglyceride) is Glyceride in which the Glycerol is Esterified with three Fatty acids It is the Myocardial infarction ( MI or AMI for acute myocardial infarction) also known as a heart attack, occurs when the blood supply ^{[9][10][11][12]}

Some benefits have been reported in conditions such as rheumatoid arthritis^[13][14] and cardiac arrhythmias. ^[15][16][17]

There is a promising preliminary evidence that n-3 fatty acids supplementation might be helpful in cases of depression^[18][19] and anxiety. ^[20][21] Studies report highly significant improvement from n-3 fatty acids supplementation alone and in conjunction with medication. ^[22]

Some research suggests that fish oil intake may reduce the risk of ischemic and thrombotic stroke. ^[23][24][25] However, very large amounts may actually increase the risk of hemorrhagic stroke (see below). Lower amounts are not related to this risk,^[25] and many studies used substantially higher doses without major side effects (for example: 4. 4 grams EPA/2. 2 grams DHA in 2003 study). ^[18][26][27] No clear conclusion can be drawn at this time, however.

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 demonstrating a link between n−3 fatty acids and cancer prevention gave mixed results. JAMA The Journal of the American Medical Association is an international peer-reviewed general Medical journal, published 48 times per year by the American A cohort study or panel study is a form of Longitudinal study used in Medicine and Social science. Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled ^[28] 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 n−3 fats on total mortality, combined cardiovascular events and cancer. ^[29]

In 1999, the GISSI-Prevenzione Investigators reported in the Lancet, the results of major clinical study in 11,324 patients with a recent myocardial infarction. Gissi is a town located in the Province of Chieti, Abruzzo, Italy. This article is about the journal For other uses of the term "lancet" see Lancet (disambiguation. Treatment 1 gram per day of n−3 fatty acids reduced the occurrence of death, cardiovascular death and sudden cardiac death by 20%, 30% and 45% respectively. ^[30] These beneficial effects were seen already from three months onwards. ^[31]

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 n−3 fatty acids, found in abundance in oily fish. The University of East Anglia is a campus-based University located in Norwich, England, and founded in 1963 History Roman The Romans had their regional capital at Venta Icenorum on the river to the south which is near modern-day Caistor St Edmund It concluded that they do not have a significant protective effect against cardiovascular disease. ^[32] This meta-analysis was controversial and stands in stark contrast with two different reviews also performed in 2006 by the American Journal of Clinical Nutrition^[33] and a second JAMA review^[34] that both indicated decreases in total mortality and cardiovascular incidents (i. JAMA The Journal of the American Medical Association is an international peer-reviewed general Medical journal, published 48 times per year by the American e. myocardial infarctions) associated with the regular consumption of fish and fish oil supplements. Myocardial infarction ( MI or AMI for acute myocardial infarction) also known as a heart attack, occurs when the blood supply Fish oil is Oil derived from the tissues of Oily fish. Fish oil is recommended for a healthy diet because it contains the Omega-3 In addition n−3 has shown to aid in other mental disorders such as aggression and ADHD (Attention-deficit hyperactivity disorder). Attention-Deficit Hyperactivity Disorder (ADHD is a neurobehavioral developmental disorder affecting about 3-5% of the world's population ^[35]

Several studies published in 2007 have been more positive. In the March 2007 edition of the journal Atherosclerosis, 81 Japanese men with unhealthy blood sugar levels were randomly assigned to receive 1800 mg daily of eicosapentaenoic acid (EPA - an n−3 essential fatty acid from fish oil) with the other half being a control group. Atherosclerosis is a Disease affecting arterial Blood vessels It is a chronic inflammatory response in the walls of arteries in large part due to the accumulation For a topic outline on this subject see List of basic Japan topics. Blood sugar, used in a physiological context is a misnomer and misleading The thickness of the carotid arteries and certain measures of blood flow were measured before and after supplementation. In Human anatomy, the common carotid artery is an Artery that supplies the head and neck with Oxygenated blood; it divides in the neck to form the This went on for approximately two years. A total of 60 patients (30 in the EPA group and 30 in the control group) completed the study. Those given the EPA had a statistically significant decrease in the thickness of the carotid arteries along with improvement in blood flow. The authors indicated that this was the first demonstration that administration of purified EPA improves the thickness of carotid arteries along with improving blood flow in patients with unhealthy blood sugar levels. ^[36] In another study published in the American Journal of Health System Pharmacy March 2007, patients with high triglycerides and poor coronary artery health were given 4 grams a day of a combination of EPA and DHA along with some monounsaturated fatty acids. Those patients with very unhealthy triglyceride levels (above 500 mg/dl) reduced their triglycerides on average 45% and their VLDL cholesterol by more than 50%. Cholesterol is a Lipid found in the Cell membranes and transported in the Blood plasma of all Animals It is an essential component of mammalian VLDL is a bad type of cholesterol and elevated triglycerides can also be deleterious for cardiovascular health.

There was another study published on the benefits of EPA in The Lancet in March 2007. This study involved over 18,000 patients with unhealthy cholesterol levels. The patients were randomly assigned to receive either 1,800 mg a day of EPA with a statin drug or a statin drug alone. The trial went on for a total of five years. It was found at the end of the study those patients in the EPA group had superior cardiovascular function. Non-fatal coronary events were also significantly reduced in the EPA group. The authors concluded that EPA is a promising treatment for prevention of major coronary events, especially non-fatal coronary events. ^[37]

Another study regarding fish oil was published in the Journal of Nutrition in April 2007. Sixty four healthy Danish infants from nine to twelve months of age received either cow's milk or infant formula alone or with fish oil. It was found that those infants supplemented with fish oil had improvement in immune function maturation with no apparent reduction in immune activation. ^[38]

There was yet another study on n−3 fatty acids published in the April 2007 Journal of NeuroScience. A group of mice were genetically modified to develop accumulation of amyloid and tau proteins in the brain similar to that seen in people with poor memory. The mice were divided into four groups with one group receiving a typical American diet (with high ratio of n−6 to n−3 fatty acids being 10 to 1). The other three groups were given food with a balanced 1 to 1 n−6 to n−3 ratio and two additional groups supplemented with DHA plus long chain n−6 fatty acids. After three months of feeding, all the DHA supplemented groups were noted to have a lower accumulation of beta amyloid and tau protein. Some research suggests that these abnormal proteins may contribute to the development of memory loss in later years. ^[39]

There is also a study published regarding n−3 supplementation in children with learning and behavioral problems. This study was published in the April 2007 edition of the Journal of the Developmental and Behavioral Pediatrics (5), where 132 children, between the ages of seven to twelve years old, with poor learning, participated in a randomized, placebo-controlled, double-blinded interventional trial. A total of 104 children completed the trial. For the first fifteen weeks of this study, the children were given polyunsaturated fatty acids (n−3 and n−6, 3000 mg a day), polyunsaturated fatty acids plus multi-vitamins and minerals or placebo. After fifteen weeks, all groups crossed over to the polyunsaturated fatty acids (PUFA) plus vitamins and mineral supplement. Parents were asked to rate their children's condition after fifteen and thirty weeks. After thirty weeks, parental ratings of behavior improved significantly in nine out of fourteen scales. The lead author of the study, Dr. Sinn, indicated the present study is the largest PUFA trial to date with children falling in the poor learning and focus range. The results support those of other studies that have found improvement in poor developmental health with essential fatty acid supplementation. ^{[40][41][42][43][44][45]}

Research in 2005 and 2006 has suggested that the in-vitro anti-inflammatory activity of n−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. Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAID s or NAID s, are drugs with Analgesic, Antipyretic and in higher Those who follow a Mediterranean-style diet tend to have less heart disease, higher HDL ("good") cholesterol levels^[46] and higher proportions of n−3 in tissue highly unsaturated fatty acids. ^[47] Similar to those who follow a Mediterranean diet, Arctic-dwelling Inuit - who consume high amounts of n−3 fatty acids from fatty fish - also tend to have higher proportions of n−3, increased HDL cholesterol and decreased triglycerides (fatty material that circulates in the blood) and less heart disease. Eating walnuts (the ratio of n−3 to n−6 is circa 1:4 respectively^[48]) was reported to lower total cholesterol by 4% relative to controls when people also ate 27% less cholesterol. Walnuts (genus Juglans) are Plants in the family Juglandaceae. ^[49]

A study^[50] examining whether omega-3 exerts neuroprotective action in Parkinson's disease found that it did, using an experimental model, exhibit a protective effect (much like it did for Alzheimer's disease as well). The scientists exposed mice to either a control or a high omega-3 diet from two to twelve months of age and then treated them with a neurotoxin commonly used as an experimental model for Parkinson's. The scientists found that high doses of omega-3 given to the experimental group completely prevented the neurotoxin-induced decrease of dopamine that ordinarily occurs. Since Parkinson's is a disease caused by disruption of the dopamine system, this protective effect exhibited could show promise for future research in the prevention of Parkinson's disease.

A study carried out involving 465 women showed serum levels of eicosapentaenoic acid is inversely related to the levels of anti-oxidized-LDL antibodies. Eicosapentaenoic acid (EPA or also icosapentaenoic acid is an Omega-3 fatty acid. Low-density lipoprotein ( LDL) is a type of Lipoprotein that transports Cholesterol and Triglycerides from the Liver to peripheral Oxidative modification of LDL is thought to play an important role in the development of atherosclerosis. Atherosclerosis is a Disease affecting arterial Blood vessels It is a chronic inflammatory response in the walls of arteries in large part due to the accumulation ^[51]

In 2008 a German study suggested that Omega-3 fatty acids have a positive effect on atopic dermatitis^[52]

Health risks

In a letter published October 31, 2000,^[53] the United States Food and Drug Administration Center for Food Safety and Applied Nutrition, Office of Nutritional Products, Labeling, and Dietary Supplements noted that known or suspected risks of EPA and DHA n−3 fatty acids may include the possibility of:

• Increased bleeding if overused (normally over 3 grams per day) by a patient who is also taking aspirin or warfarin. Atopic dermatitis, also known as atopic eczema, is a disease characterized by Chronic inflammation of the skin which is atopic, hereditary and non-contagious Events 445 BC – Ezra reads the Book of the Law to the Israelites in Jerusalem (see Nehemiah 91 NLTse 2000 ( MM) was a Leap year that started on Saturday of the Common Era, in accordance with the Gregorian calendar. Aspirin, or acetylsalicylic acid (ASA (əˌsɛtɨlsælɨˌsɪlɨk ˈæsɨd is a Salicylate drug, often used as an Analgesic to relieve Warfarin (also known under the brand names Coumadin, Jantoven, Marevan, and Waran) is an Anticoagulant. However, this is disputed. ^[54]
• Hemorrhagic stroke (only in case of very large doses, called "Eskimo amounts"). A stroke is the rapidly developing loss of brain functions due to a disturbance in the blood vessels supplying blood to the brain ^[55]
• Oxidation of n−3 fatty acids forming biologically active oxidation products.
• Reduced glycemic control among diabetics.
• Suppression of immune and inflammation responses, and consequently, decreased resistance to infections and increased susceptibility to opportunistic bacteria.
• An increase in concentration of LDL cholesterol in some individuals.

Subsequent advices from the FDA and national counterparts have permitted health claims associated with heart health.

Cardiac risk

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 n−3 fatty acids. Heart failure is a Cardiac condition that occurs when a problem with the structure or function of the Heart impairs its ability to supply It may be prudent for such persons to avoid taking n−3 fatty acids or eating foods that contain them in substantial amounts. ^[56]

In congestive heart failure, cells that are only barely receiving enough blood flow become electrically hyperexcitable. This, in turn, can lead to increased risk of irregular heartbeats, which, in turn, can cause sudden cardiac death. n−3 fatty acids seem to stabilize the rhythm of the heart by effectively preventing these hyperexcitable cells from functioning, thereby reducing the likelihood of irregular heartbeats and sudden cardiac death. For most people, this is obviously beneficial and would account for most of the large reduction in the likelihood of sudden cardiac death. Nevertheless, for people with congestive heart failure, the heart is barely pumping blood well enough to keep them alive. In these patients, n−3 fatty acids may eliminate enough of these few pumping cells that the heart would no longer be able to pump sufficient blood to live, causing an increased risk of cardiac death. ^[56]

Research frontiers

Developmental differences

Essential fatty acid supplements have gained popularity for children with ADHD, autism, and other developmental differences. Attention-Deficit Hyperactivity Disorder (ADHD is a neurobehavioral developmental disorder affecting about 3-5% of the world's population Language development. The terminology ^[57] A 2004 Internet survey found that 29% of surveyed parents used essential fatty acid supplements to treat children with autism spectrum disorders. The autism spectrum, also called autism spectrum disorders (ASD or autism spectrum conditions (ASC with the word autistic sometimes replacing autism ^[58]

Results from controlled trials are mixed. Fish oils appear to help ADHD-related symptoms in some children. Larger trials are needed. ^[59] A 2007 double-blind, placebo-controlled trial of small groups of children found that omega-3 fatty acids reduced hyperactivity in children with autism spectrum disorders,^[60] suggesting that further research is needed. The autism spectrum, also called autism spectrum disorders (ASD or autism spectrum conditions (ASC with the word autistic sometimes replacing autism ^[61]

Low birth weight

In a study of nearly 9,000 pregnant women, researchers found women who ate fish once a week during their first trimester had 3. 6 times less risk of low birth weight and premature birth than those who ate no fish. Low consumption of fish was a strong risk factor for preterm delivery and low birth weight. ^[62] However, attempts by other groups to reverse this increased risk by encouraging increased pre-natal consumption of fish were unsuccessful. ^[63]

Psychiatric disorders

n−3 fatty acids are known to have membrane-enhancing capabilities in brain cells. ^[32] One medical explanation is that n−3 fatty acids play a role in the fortification of the myelin sheaths. Myelin is an electrically-insulating Dielectric Phospholipid layer that surrounds only the Axons of many Neurons It is an outgrowth Not coincidentally, n−3 fatty acids comprise approximately eight percent of the average human brain according to Dr. David Horrobin, a pioneer in fatty acid research. David Frederick Horrobin ( 6 October 1939 - 1 April 2003) was a medical researcher entrepreneur author and editor Ralph Holman of the University of Minnesota, another major researcher in studying essential fatty acids, who gave Omega-3 its name, surmised how n−3 components are analogous to the human brain by stating that "DHA is structure, EPA is function. Ralph Holman (1917 -) is a biochemist whose research focused on Lipids and Fatty acids especially the Omega-3 fatty acid. The University of Minnesota Twin Cities ( U of M or The U) is the oldest and largest part of the University of Minnesota system. "

A benefit of n−3 fatty acids is helping the brain to repair damage by promoting neuronal growth. ^[32] 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. Schizophrenia ( from the Greek roots schizein (σχίζειν "to split" and phrēn Huntington's disease, also called Huntington's chorea, chorea major, or HD, is a genetic neurological disorder characterized after ^[64]

In the prefrontal cortex (PFC) of the brain, low brain n−3 fatty acids are thought to lower the dopaminergic neurotransmission in this brain area, possibly contributing to the negative and neurocognitive symptoms in schizophrenia. The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain Neurotransmission (latin transmissio = passage crossing from transmitto = send let through also called synaptic transmission, is an electrical movement Schizophrenia ( from the Greek roots schizein (σχίζειν "to split" and phrēn This reduction in dopamine system function in the PFC may lead to an overactivity in dopaminergic function in the limbic system of the brain which is suppressively controlled by the PFC dopamine system, causing the positive symptoms of schizophrenia. Dopamine is a Hormone and Neurotransmitter occurring in a wide variety of animals including both vertebrates and invertebrates The limbic system, or Paleomammalian brain is a term for a set of brain structures including the Hippocampus and Amygdala and anterior thalamic nuclei and a limbic Schizophrenia ( from the Greek roots schizein (σχίζειν "to split" and phrēn This is called the n−3 polyunsaturated fatty acid/dopamine hypothesis of schizophrenia (Ohara, 2007). This mechanism may explain why n−3 supplementation shows effects against both positive, negative and neurocognitive symptoms in schizophrenia. A symptom' (from Greek σύμπτωμα, "accident misfortune that which befalls" from συμπίπτω, "I befall" from Schizophrenia ( from the Greek roots schizein (σχίζειν "to split" and phrēn

Consequently, the past decade of n−3 fatty acid research has procured some Western interest in n−3 fatty acids as being a legitimate 'brain food. The term Western world, the West or the Occident ( Latin: occidens -sunset -west as distinct from the Orient) can have multiple meanings ' 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 n−3 fatty acids consumed by pregnant mothers remain unreliable and controversial. An Intelligence Quotient or IQ is a score derived from one of several different Standardized tests attempting to measure Intelligence. An even more significant focus of research, however, lies in the role of n−3 fatty acids as a non-prescription treatment for certain psychiatric and mental diagnoses and has become a topic of much research and speculation.

In 1998, 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. The blind method is a part of the Scientific method, used to prevent research outcomes from being influenced by either the Placebo effect or the Observer Placebo is a substance or procedure a patient accepts as medicine or therapy but which has no specific therapeutic activity Most subjects in this study were already undergoing psychopharmacological treatment (e. g. 12 out of the 30 were taking lithium). Over the course of four months, he gave 15 subjects capsules containing olive oil, and another 15 subjects capsules containing nine grams of pharmaceutical-quality EPA and DHA. Olive oil is a fruit oil obtained from the olive ( Olea europaea; family Oleaceae along with Lilacs Jasmine and ash trees The study showed that subjects in the n−3 group were less likely to experience a relapse of symptoms in the four months of the study. Moreover, the n−3 group experienced significantly more recovery than the placebo group. However, a commentary on the Stoll study notes that the improvement in the n−3 group was too small to be clinically significant. ^[65] 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 n−3 fatty acids and signal transduction inhibition in the brain. ^[66]

"Several epidemiological studies suggest covariation between seafood consumption and rates of mood disorders. Biological marker studies indicate deficits in omega−3 fatty acids in people with depressive disorders, while several treatment studies indicate therapeutic benefits from omega-3 supplementation. A similar contribution of omega-3 fatty acids to coronary artery disease may explain the well-described links between coronary artery disease and depression. Deficits in omega-3 fatty acids have been identified as a contributing factor to mood disorders and offer a potential rational treatment approach. "^[67] In 2004, a study found that 100 suicide attempt patients on average had significantly lower levels of EPA in their blood as compared to controls. ^[68]

In 2006, a review of published trials in the American Journal of Clinical Nutrition found that "the evidence available provides little support" for the use of fish or the n–3 long-chain polyunsaturated fatty acids contained in them to improve depressed mood. The study used results of twelve randomized controlled trials in its meta-analysis. The review recommended that "larger trials with adequate power to detect clinically important benefits" be performed. ^[69]

Dietary sources

Daily values

As macronutrients, fats are not assigned recommended daily allowances. The Dietary Reference Intake (or DRI is a system of Nutrition recommendations from the Institute of Medicine (IOM of the US National Academy of Sciences 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^[70] while the AMDR is 0. 6% to 1. 2% of total energy. ^[71]

"A growing body of literature suggests that higher intakes of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) may afford some degree of protection against coronary heart disease. Coronary disease (or coronary heart disease) refers to the failure of Coronary circulation to supply adequate circulation to Cardiac muscle and surrounding 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. "^[71] There was insufficient evidence as of 2005 to set a UL (upper tolerable limit) for n−3 fatty acids. ^[70]

Researchers believe the ideal n−6 intake should be no more than 4 to 5 times that of our n−3 intake. n −6 fatty acids (popularly referred to as ω−6 fatty acids or omega-6 fatty acids) are a family of unsaturated Fatty acids 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.

A perceived risk of fish oil n−3 supplementation has been 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 potentially might be found especially in less-refined fish oil supplements. Mercury (ˈmɜrkjʊri also called quicksilver or hydrargyrum, is a Chemical element with the symbol Hg ( Latinized hydrargyrum Characteristics Lead has a dull luster and is a dense, Ductile, very soft highly Nickel (ˈnɪkəl is a metallic Chemical element with the symbol Ni and Atomic number 28 Arsenic (ˈɑrsənɪk is a Chemical element that has the symbol As and Atomic number of 33 Cadmium (ˈkædmiəm is a Chemical element with the symbol Cd and Atomic number 48 Polychlorinated biphenyls ( PCB s are a class of Organic compounds with 1 to 10 Chlorine atoms attached to Biphenyl which is a molecule composed Furan, also known as furane and furfuran, is a heterocyclic Organic compound. Not to be confused with Dioxane or Digoxin. Dioxin is a heterocyclic, organic, antiaromatic compound An independent test in 2006 of 44 fish oils on the US market found that all of the products passed safety standards for potential contaminants. ^[72] The FDA recommends that total dietary intake of n−3 fatty acids from fish not exceed 3 grams per day, of which no more than 2 grams per day are from nutritional supplements. ^[2]

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). Vacuum distillation is a method of Distillation whereby the pressure above the liquid mixture to be distilled is reduced to less than its Vapor pressure (usually

n−3 supplementation in food has been a significant recent trend in food fortification, with global food companies launching n−3 fortified bread, mayonnaise, pizza, yogurt, orange juice, children's pasta, milk, eggs, confections and infant formula.

Fish

Early humans ate animals that ate grass, which gave those animals a higher Omega-3 profile than today's grain-fed animals. Now, the most widely available source of EPA and DHA is cold water oily fish such as salmon, herring, mackerel, anchovies and sardines. Eicosapentaenoic acid (EPA or also icosapentaenoic acid is an Omega-3 fatty acid. Docosahexaenoic acid (commonly known as DHA; 226(ω-3 all-cis -docosa-4710131619-hexa- enoic acid Trivial name cervonic Salmon is the common name for several species of Fish of the family Salmonidae. Herring are small Oily fish of the genus Clupea found in the shallow temperate waters of the North Atlantic, the Baltic Sea, the North Mackerel is a common name applied to a number of different species of Fish, mostly but not exclusively from the family Scombridae. The anchovies are a family ( Engraulidae) of small common salt-water fish For the hide and seek-like game see Hide and seek. Sardines, or pilchards, are a group of several types of small Oily Oils from these fish have a profile of around seven times as much n−3 as n−6. Other oily fish such as tuna also contain n−3 in somewhat lesser amounts. Tuna, are several Species of ocean-dwelling Fish in the family Scombridae, mostly in the genus Thunnus. 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. Polychlorinated biphenyls ( PCB s are a class of Organic compounds with 1 to 10 Chlorine atoms attached to Biphenyl which is a molecule composed Not to be confused with Dioxane or Digoxin. Dioxin is a heterocyclic, organic, antiaromatic compound Bioaccumulation occurs when an organism absorbs a toxic substance at a rate greater than that at ftudruinsubstance is lost ^[73] 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. ^[74][75]

Although fish is a dietary source of n−3 fatty acids, fish do not synthesize them; they obtain them from the algae in their diet. Algae ( sing. alga are a large and diverse group of simple typically Autotrophic organisms ranging from Unicellular to Multicellular forms

Flax

Flax seeds produce linseed oil, which has a very high n−3 content

Six times richer than most fish oils in n−3,^[76] Flax (aka linseed) (Linum usitatissimum) and its oil are perhaps the most widely available botanical source of n−3. Flax (also known as common flax or linseed) (binomial name Linum usitatissimum) is a member of the genus Linum Linseed oil, also known as flax seed oil or simply flax oil, is a clear to yellowish Drying oil derived from the dried ripe seeds of the Flax Flax (also known as common flax or linseed) (binomial name Linum usitatissimum) is a member of the genus Linum Botany, plant science(s, phytology, or plant biology is a branch of Biology and is the scientific study of plant Life Flaxseed oil consists of ca. Linseed oil, also known as flax seed oil or simply flax oil, is a clear to yellowish Drying oil derived from the dried ripe seeds of the Flax 55% ALA (alpha-linolenic acid). Flax, like chia, contains approximately three times as much n−3 as n−6.

15 grams of flaxseed oil provides ca. 8 grams of ALA, which is converted in the body to EPA and then DHA at an efficiency of 2–15% and 2–5%, respectively. ^[77]

Botanical sources of n−3 fatty acids

Table 1. n−3 content as the percentage of ALA in the seed oil. α -Linolenic acid ( ALA) is an organic compound found in many common vegetable oils. ^[78]

Table 2. Chia ( Salvia hispanica) is a plant of the genus Salvia in the Mint family Chia ( Salvia hispanica) is a plant of the genus Salvia in the Mint family Chia ( Salvia hispanica) is a plant of the genus Salvia in the Mint family The kiwifruit (or kiwi is the edible Berry of a cultivar group of the woody Vine Actinidia deliciosa and The kiwifruit (or kiwi is the edible Berry of a cultivar group of the woody Vine Actinidia deliciosa and Actinidia chinensis is a Fruit tree and Medicinal plant native to China. Perilla is a genus of annual Herb that is a member of the mint family Lamiaceae. Perilla frutescens ( Green Shiso; Syn Perilla nankinensis ( Lour Flax (also known as common flax or linseed) (binomial name Linum usitatissimum) is a member of the genus Linum Flax (also known as common flax or linseed) (binomial name Linum usitatissimum) is a member of the genus Linum Flax (also known as common flax or linseed) (binomial name Linum usitatissimum) is a member of the genus Linum The Vaccinium vitis-idaea &ndash often called lingonberry also called cowberry, foxberry, mountain cranberry, red whortleberry The Vaccinium vitis-idaea &ndash often called lingonberry also called cowberry, foxberry, mountain cranberry, red whortleberry The Vaccinium vitis-idaea &ndash often called lingonberry also called cowberry, foxberry, mountain cranberry, red whortleberry Camelina sativa, usually known in English as gold-of-pleasure or false flax, also occasionally wild flax, linseed dodder, Camelina sativa, usually known in English as gold-of-pleasure or false flax, also occasionally wild flax, linseed dodder, Camelina sativa, usually known in English as gold-of-pleasure or false flax, also occasionally wild flax, linseed dodder, Portulaca ( purslane) is the Type genus of the purslane family Portulacaceae, comprising about 40-100 species (probably much fewer and potentially Portulaca ( purslane) is the Type genus of the purslane family Portulacaceae, comprising about 40-100 species (probably much fewer and potentially Portulaca oleracea ( Common Purslane, also known as Verdolaga, Pigweed, Little Hogweed or Pusley) is an annual Rubus occidentalis is a species of Rubus native to eastern North America. Rubus occidentalis is a species of Rubus native to eastern North America. n−3 content as the percentage of ALA in the whole food. α -Linolenic acid ( ALA) is an organic compound found in many common vegetable oils. ^[79][80]

Eggs

Eggs produced by chickens fed a diet of greens and insects produce higher levels of n−3 fatty acids (mostly ALA) than chickens fed corn or soybeans. An egg is a round or oval body laid by the female of many animals consisting of an Ovum surrounded by layers of Membranes and an outer casing which acts to nourish ^[81]In addition to feeding chickens insects and greens, fish oils are added to their diet to increase the amount of fatty acid concentrations in eggs. ^[82]

Other sources

Krill, which are small, shrimp-like zooplankton, also contain the n−3 fatty acids EPA and DHA. Krill are a type of Shrimp -like marine Invertebrate animal These small Crustaceans are important organisms of the Zooplankton, particularly Zooplankton are the Heterotrophic (sometimes detritivorous) type of Plankton. One advantage of extracting n−3 fatty acids from krill, as opposed to sources higher in the food chain, is that krill contain fewer heavy metals and PCBs harmful to humans. However, in comparison to higher animals, they also contain fewer n−3 fatty acids per gram.

The n−6 to n−3 ratio of grass-fed beef is about 2:1, making it a more useful source of n−3 than grain-fed beef, which usually has a ratio of 4:1. Different cattle feeding production systems have separate advantages and disadvantages ^[83] Commercially available lamb is almost always grass-fed, and subsequently higher in n−3 than other common meat sources. Milk and cheese from grass-fed cows may also be good sources of n−3. Milk is an opaque white liquid produced by the Mammary glands of female Mammals (including Monotremes. Cheese is a Food made from Milk, usually the milk of cows, Buffalo, Goats or sheep, by coagulation. 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%". ^[84]

The microalgae Crypthecodinium cohnii and Schizochytrium are rich sources of DHA (22:6 n−3) and can be produced commercially in bioreactors. Microphytes are microscopic Algae, typically found in Freshwater and marine systems and are often called microalgae Docosahexaenoic acid (commonly known as DHA; 226(ω-3 all-cis -docosa-4710131619-hexa- enoic acid Trivial name cervonic Biochemical engineering is a branch of Chemical engineering or Biological engineering that mainly deals with the design and construction of unit processes that Oil from brown algae (kelp) is a source of EPA. The Phaeophyceae or brown algae, (singular alga is a large group of mostly marine multicellular Algae including many Seaweeds of colder Walnuts are one of few nuts that contain appreciable n−3 fat, with approximately a 1:4 ratio of n−3 to n−6. Walnuts (genus Juglans) are Plants in the family Juglandaceae. ^[48] Acai palm fruit also contains n−3 fatty acids. The açaí palm ( is a member of the genus Euterpe, which contains 7 species of palms native to tropical Central and South America, from

The n−6 to n−3 ratio

Main article: Essential fatty acid interactions

Clinical studies^{[1][85][86][87]} indicate that the ingested ratio of n−6 to n−3 (especially Linoleic vs Alpha Linolenic) fatty acids is important to maintaining cardiovascular health. The actions of the &omega-3 and &omega-6 essential fatty acids (EFAs are best characterized by their interactions; they cannot be understood separately

Both n−3 and n−6 fatty acids are essential, i. e. humans must consume them in the diet. n−3 and n−6 compete for the same metabolic enzymes, thus the n−6:n−3 ratio will significantly influence the ratio of the ensuing eicosanoids (hormones), (e. g. prostaglandins, leukotrienes, thromboxanes etc. A prostaglandin is any member of a group of Lipid compounds that are derived enzymatically from Fatty acids and have important functions in the Animal body Leukotrienes are naturally produced Eicosanoid lipid mediators, which may be responsible for the effects of an inflammatory response Thromboxane is a member of the family of Lipids known as Eicosanoids. ), and will alter the body's metabolic function. ^[88]Generally, grass-fed animals accumulate more n−3 than do grain-fed animals which accumulate relatively more n−6. Metabolites of n−6 are significantly more inflammatory (esp. Metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind" - specifically the study of their small-molecule metabolite arachidonic acid) than those of n−3. Arachidonic acid (AA sometimes ARA is an Omega-6 fatty acid 204(ω-6 This necessitates that n−3 and n−6 be consumed in a balanced proportion; healthy ratios of n−6:n−3 range from 1:1 to 4:1. ^[89][90] Studies suggest that the evolutionary human diet, rich in seafood and other sources of n−3, may have provided such a ratio. ^[85][91]

Typical Western diets provide ratios of between 10:1 and 30:1 - i. e. , dramatically skewed toward n−6. ^[92] Here are the ratios of n−6 to n−3 fatty acids in some common oils: canola 2:1, soybean 7:1, olive 3–13:1, sunflower (no n−3), flax 1:3^[93] cottonseed (almost no n−3), peanut (no n−3), grapeseed oil (almost no n−3) and corn oil 46 to 1 ratio of n−6 to n−3. Canola is a type of Edible oil derived from plants initially bred in Canada by Keith Downey and Baldur Stefansson in the 1970s The Olive ( Olea europaea) is a Species of small Tree in the family Oleaceae, native to the coastal areas of the eastern The sunflower ( Helianthus annuus) is an Annual plant in the family Asteraceae and native to the Americas, with a large flowering Flax (also known as common flax or linseed) (binomial name Linum usitatissimum) is a member of the genus Linum Cotton is a soft staple Fibre that grows around the seeds of the cotton plant ( Gossypium sp The peanut, or Groundnut ( Arachis hypogaea) is a species in the Legume family Fabaceae native to South America, Mexico Not to be confused with Rapeseed oil. Grape seed oil (also called grapeseed oil or grape oil) is a Vegetable oil pressed from the seeds Corn oil is Oil extracted from the germ of corn ( Maize) Its main use is in cooking where its high Smoke point makes it a valuable Frying ^[94] It should be noted that olive, peanut and canola oils consist of approximately 80% monounsaturated fatty acids, (i. For discussion how dietary fats affect cardiovascular health see Diet and heart disease. e. neither n−6 nor n−3) meaning that they contain relatively small amounts of n−3 and n−6 fatty acids. Consequently, the n−6 to n−3 ratios for these oils (i. e. olive, canola and peanut oils) are not as significant as they are for corn, soybean and sunflower oils.

Conversion efficiency of ALA to EPA and DHA

It has been reported that conversion of ALA to EPA and further to DHA in humans is limited, but varies with individuals. ^[95] Women have higher ALA conversion efficiency than men, probably due to the lower rate of utilization of dietary ALA for beta-oxidation. This suggests that biological engineering of ALA conversion efficiency is possible. In the online book of The Benefits of Omega 3 Fatty Acids found in Seal Oil, as Opposed to Fish and Flaxseed Oils, Dr. Ho listed the several factors that inhibit the ALA conversion,^[96] which again indicate that the efficiency of ALA conversion could be adjusted by altering one's dietary habits, such as rebalancing the ratio of n−3 and n−6 fatty acid intake,^[95][97] restraining direct alcohol consumptions, and supplementing vitamins and minerals. However, Goyens et al. argues that it is the absolute amount of ALA, rather than the ratio of n−3 and n−6 fatty acids, which affects the conversion. ^[98]

See also

Notes and references

Additional sources

Further reading

External links