1. INTRODUCTION:

Omega fatty acids are essential fatty acids that the human body needs for metabolic functioning but cannot produce, and therefore has to be acquired from food or diet¹. Examples of foods high in polyunsaturated fats include vegetable oils, corn, sunflower, and soya bean. It supports the cardiovascular, reproductive, immune, and nervous systems. The human body needs EFAs to manufacture and repair cell membranes, enabling the cells to obtain optimum nutrition and expel harmful waste products. A primary function of EFAs is the production of prostaglandins, which regulate body functions such as heart rate, blood pressure, blood clotting, fertility, conception, and play a role in immune function by regulating inflammation and encouraging the body to fight infection. Essential Fatty Acids are also needed for proper growth in children, particularly for neural development and maturation of sensory systems, with male children having higher needs than females. Fetus and breast-fed infants also require an adequate supply of EFAs through the mother's dietary intake.

2. CLASSIFICATION:

Omega fatty acids are broadly classified into three types²

2.1. Omega -3 fatty acids: This is also known as linolenic acid or popularly as ω −3 fatty acids. Omega-3 fatty acids are a class of essential polyunsaturated fatty acids with the double bond in the third carbon position

from the methyl terminal (hence the use of "3" in their description, a second family of related fatty acids essential to human health but lacking from most Western diets³. There are three major types of omega 3 fatty acids that are ingested in foods and used by the body,

a) Alpha-linolenic acid (ALA;18:3, n−3)

b) Eicosapentaenoic acid (EPA; 20:5, n−3) and

c) Docosahexaenoic acid (DHA;22:6, , n−3).

Once eaten, the body converts ALA to EPA and DHA, the two types of omega-3 fatty acids more readily used by the body.

Alpha Linolenic Acid (ALA) is the principal Omega-3 fatty acid, which a healthy human will convert into eicosapentaenoic acid (EPA), and later into docosahexaenoic acid (DHA). EPA and the GLA synthesized from linoleic (Omega-6) acid are later converted into hormone-like compounds known as eicosanoids, which aid in many bodily functions including vital organ function and intracellular activity.

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). Chemists count from the carbonyl carbon (Blue Numbering), physiologists count from the n (ω) carbon (red numbering). Note that from the n end , 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 synthesized from the other carbonyl end, for example in glycerids, 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 .

Fig-1: classification of omega fatty acids

Source:

Omega-3 fatty acids can be found in cold-water fish such as fatty fish such as mackerel, lake trout, herring, sardines, albacore tuna, halibut, and salmon other marine life such as algae and Krill, which are small, shrimp-like zooplankton. Flaxseed is the best source of omega-3s in the vegetable kingdom. One rounded tablespoon of milled flaxseed (or one teaspoon of flaxseed oil) supplies 2000 mg of the omega-3 alpha-linolenic acid (ALA), the essential fatty acid that humans cannot make. Flaxseed also contains valuable cancer-fighting lignans (although the oil does not). Of these, purslane and walnuts are the best sources.Eggs, meat, Milk, cheese, also contain the n−3 fatty acids EPA and DHA.

Mechanism of action:

There are 2 classes of essential fatty acids, the Omega -6 and Omega -3 fatty acids (FA). Omega -3 FA, found primarily in fatty fish with high oil content, consists of both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Arachidonic acid, and omega -6 FA, is converted into inflammatory prostaglandins and leukotrienes via the enzymes cyclooxygenase and lipoxygenase, respectively. Increased intake of Omega -3 FA reduces incorporation of arachidonic acid into cell membranes, thereby promoting a net anti-inflammatory response.

Fish oil has been shown to significantly decrease potent inflammatory markers, including leukotrienes, prostaglandins, interleukins, and tumor necrosis factor^4-7. The inhibition of arachidonic acid by Omega -3 FA also produces a potential antithrombotic effect by decreasing production of thromboxane A₂. Membrane stabilization in cardiac tissue by Omega -3 FA confers potential antiarrhythmic effects, whereas triglyceride-lowering effects are caused by the reduction and secretion of very low density lipoprotein particles from the liver. With its unique and varied mechanism of actions, the potential uses of fish oil have been studied in various clinical situations.

Dosage:

As macronutrients, fats 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.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. The World Health Organization and various countries around the world recommend daily intakes averaging 300-500 mg/day of EPA plus DHA.

Role of Omega-3s in metabolic processes:

In addition to their value for cell membranes, omega-3 fatty acids play an important role in regulating the body's metabolic processes. Eicosanoids are hormone-like compounds that act like thermostats throughout the body, either raising or lowering a wide range of bodily activities. Eicosanoids have only been discovered recently because their action is localized rather than originating from a specific gland, such as the pancreas or adrenals. Eicosanoids are composed entirely of omega-3 and -6 fatty acids. Eicosanoids typically come in pairs: one to increase and the other to decrease whatever bodily function the pair is regulating. When omega-3s are lacking in the diet, the body produces less of one of the pairs, with the result that these internal thermostats don't work correctly. The body spirals uncontrollably in a single direction.

Uses:

Clinical studies suggest that omega-3 fatty acids may be helpful in treating a variety of health conditions. The evidence is strongest for heart disease and problems that contribute to heart disease, but the range of possible uses for omega-3 fatty acids include:

High cholesterol:

Those who follow a Mediterranean-style diet tend to have higher high density lipoprotein (HDL or "good”) cholesterol levels. Similar to those who follow a Mediterranean diet, Inuit Eskimos, 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 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been reported in several large clinical studies to reduce low density lipoprotein (LDL or "bad") cholesterol and triglyceride levels. Finally, walnuts (which are rich in alpha linolenic acid or ALA) have been reported to lower total cholesterol and triglycerides in individuals with high cholesterol levels⁸.

High blood pressure:

Several clinical studies suggest that diets or supplements rich in omega-3 fatty acids lower blood pressure significantly in individuals with hypertension. An analysis of 17 clinical studies using fish oil supplements found that supplementation with 3 or more grams of fish oil daily can lead to significant reductions in blood pressure in individuals with untreated hypertension.

Fig-2: Indicating the conversion of ALA to DHA

Heart disease:

One of the best ways to help prevent and treat heart disease is to eat a low-fat diet and to replace foods rich in saturated and trans-fat with those that are rich in monounsaturated and polyunsaturated fats (including omega-3 fatty acids). Clinical evidence suggests that EPA and DHA found in fish oil help reduce risk factors for heart disease including high cholesterol and high blood pressure. There is also strong evidence that these substances can help prevent and treat atherosclerosis by inhibiting the development of plaque and blood clots, each of which tends to clog arteries. Clinical studies of heart attack survivors have found that daily omega-3 fatty acid supplements dramatically reduce the risk of death, subsequent heart attacks, and stroke. Similarly, people who eat an ALA-rich diet are less likely to suffer a fatal heart attack⁹.

Strong evidence from population-based clinical studies suggests that omega-3 fatty acid intake (primarily from fish) helps protect against stroke caused by plaque buildup and blood clots in the arteries that lead to the brain. In fact, eating at least 2 servings of fish per week can reduce the risk of stroke by as much as 50%.

Diabetes:

Individuals with diabetes tend to have high triglyceride and low HDL levels. Omega-3 fatty acids from fish oil can help lower triglycerides¹⁰ and apoproteins (markers of diabetes), and raise HDL, so people with diabetes may benefit from eating foods or taking supplements that contain DHA and EPA. ALA (from flaxseed, for example) may not have the same benefit as DHA and EPA because some people with diabetes lack the ability to efficiently convert ALA to a form of omega-3 fatty acids that the body can use readily.

Fig- 3: structure of EPA, DHA and Palmitic acid

There have been slight increases reported in fasting blood sugar levels in patients with type 2 diabetes while taking fish oil supplements.

Weight loss:

Many individuals who are overweight suffer from poor blood sugar control, diabetes, and high cholesterol. Clinical studies suggest that overweight people who follow a weight loss program that includes exercise tend to achieve better control over their blood sugar and cholesterol levels when fish rich in omega-3 fatty acids (such as salmon, mackerel, and herring) is a staple in their low-fat diet.

Arthritis:

Most clinical studies investigating the use of omega-3 fatty acid supplements for inflammatory joint conditions have focused almost entirely on rheumatoid arthritis. Several articles reviewing the research in this area conclude that omega-3 fatty acid supplements reduce tenderness in joints, decrease morning stiffness, and allow for a reduction in the amount of medication needed for people with rheumatoid arthritis.

In addition, laboratory studies suggest that diets rich in omega-3 fatty acids (and low in the inflammatory omega-6 fatty acids) may benefit people with other inflammatory disorders, such as osteoarthritis. In fact, several test tube studies of cartilage-containing cells have found that omega-3 fatty acids decrease inflammation and reduce the activity of enzymes that destroy cartilage. Similarly, New Zealand green lipped mussel (Perna canaliculus), another potential source of omega-3 fatty acids, has been reported to reduce joint stiffness and pain, increase grip strength, and enhance walking pace in a small group of people with osteoarthritis. In some participants, symptoms worsened before they improved.

An analysis was conducted of 17 randomized, controlled clinical trials assessing the pain relieving effects of omega-3 fatty acid supplementation in patients with rheumatoid arthritis or joint pain caused by inflammatory bowel disease (IBS) and painful menstruation (dysmenorrhea). The results suggest that omega-3 fatty acids are effective treatment, along with conventional therapies such as anti-inflammatory drugs, for joint pain associated with rheumatoid arthritis, inflammatory bowel disease, and dysmenorrhea.

Fig-4: showing carbonyl carbon (red numbering) and omega carbon (blue numbering)

Osteoporosis:

Clinical studies suggest that omega-3 fatty acids such as EPA help increase levels of calcium in the body, deposit calcium in the bones, and improve bone strength. In a study of women over 65 with osteoporosis, those given EPA and GLA supplements experienced significantly less bone loss over 3 years than those who were given a placebo. Many of these women also experienced an increase in bone density.

Depression:

People who do not get enough omega-3 fatty acids or do not maintain a healthy balance of omega-3 to omega-6 fatty acids in their diet may be at an increased risk for depression. The omega-3 fatty acids are important components of nerve cell membranes. They help nerve cells communicate with each other, which is an essential step in maintaining good mental health. In particular, DHA is involved in a variety of nerve cell processes. In a clinical study of individuals with depression, those who ate a healthy diet consisting of fatty fish 2 - 3 times per week for 5 years experienced a significant reduction in feelings of depression and hostility.

Attention deficit/hyperactivity disorder (ADHD):

Children with attention deficit /hyperactivity disorder (ADHD) may have low levels of certain essential fatty acids (including EPA and DHA) in their bodies. In a clinical study of nearly 100 boys, those with lower levels of omega-3 fatty acids demonstrated more learning and behavioral problems (such as temper tantrums and sleep disturbances) than boys with normal omega-3 fatty acid levels. In animal studies, low levels of omega-3 fatty acids have been shown to lower the concentration of certain brain chemicals (such as dopamine and serotonin) related to attention and motivation. Clinical studies that examine the ability of omega-3 supplements to improve symptoms of ADHD are still needed. At this point in time, eating foods high in omega-3 fatty acids is a reasonable approach for someone with ADHD. A clinical study used omega-3 and omega-6 fatty acid supplementation in 117 children with ADHD. They study found significant improvements in reading, spelling, and behavior in the children over the 3 months of therapy. Another clinical study found that omega-3 fatty acid supplementation helped to decrease physical aggression in school children with ADHD.

Fig-5: Arachidonic acid is converted to leukotrienes by the enzyme lipoxygenase (LPO) and to thromboxane A2 and prostaglandins by the enzyme cyclooxygenase (COX).n-3 fatty acids, in essence reduces the breakdown of arachidonic acid.

Burns:

Essential fatty acids have been used to reduce inflammation and promote wound healing in burn victims. Animal research indicates that omega-3 fatty acids help promote a healthy balance of proteins in the body and protein balance is important for recovery after sustaining a burn. Further research is necessary to determine whether omega-3s benefit people in the same way.

Skin disorders:

In one clinical study, 13 people with a particular sensitivity to the sun known as photo dermatitis showed significantly less sensitivity to UV rays after taking fish oil supplements. Still, research indicates that topical sunscreens are much better at protecting the skin from damaging effects of the sun than omega-3 fatty acids. In another study of 40 people with psoriasis, those who were treated with medications and EPA supplements did better than those treated with the medications alone. In addition, many clinicians believe that flaxseed (which contains omega-3 fatty acids) is helpful for treating acne.

Inflammatory bowel disease (IBD):

When added to medication, such as sulfasalazine (a standard medication for IBD), omega-3 fatty acids may reduce symptoms of Crohn's disease and ulcerative colitis and the 2 types of IBD. More studies to investigate this preliminary finding are under way. In animals, it appears that ALA works better at decreasing bowel inflammation than EPA and DHA.

Asthma:

Clinical research suggests that omega-3 fatty acid supplements (in the form of perilla seed oil, which is rich in ALA) may decrease inflammation and improve lung function in adults with asthma¹¹. Omega-6 fatty acids have the opposite effect: they tend to increase inflammation and worsen respiratory function. In a small, well-designed clinical study of 29 children with asthma, those who took fish oil supplements rich in EPA and DHA for 10 months had improvement in their symptoms compared to children who took a placebo pill.

Macular Degeneration:

A questionnaire administered to more than 3,000 people over the age of 49 found that those who consumed more fish in their diet were less likely to have macular degeneration (a serious age-related eye condition that can progress to blindness) than those who consumed less fish. Similarly, a clinical study comparing 350 people with macular degeneration to 500 without the eye disease found that those with a healthy dietary balance of omega-3 and omega-6 fatty acids and higher intake of fish in their diets were less likely to have this particular eye disorder. Another larger clinical study confirms that EPA and DHA from fish, 4 or more times per week may reduce the risk of developing macular degeneration.

Menstrual pain:

In a clinical study of nearly 200 Danish women, those with the highest dietary intake of omega-3 fatty acids had the mildest symptoms, such as hot flashes and increased sweating, during menstruation.

Colon cancer:

Consuming significant amounts of foods rich in omega-3 fatty acids appears to reduce the risk of colorectal cancer. For example, Eskimos, who tend to follow a high-fat diet but eat significant amounts of fish rich in omega-3 fatty acids, have a low rate of colorectal cancer. Animal studies and laboratory studies have found that omega-3 fatty acids prevent worsening of colon cancer while omega-6 fatty acids promote the growth of colon tumors. Clinical studies have reported that low levels of omega-3 fatty acids in the body are a marker for an increased risk of colon cancer.

Breast cancer:

Although not all experts agree, women who regularly consume foods rich in omega-3 fatty acids over many years may be less likely to develop breast cancer. In addition, the risk of dying from breast cancer may be significantly less for those who eat large quantities of omega-3 from fish and brown kelp seaweed (common in Japan). This is particularly true among women who substitute fish for meat. The balance between omega-3 and omega-6 fatty acids appears to play an important role in the development and growth of breast cancer.

Prostate cancer:

Laboratory and animal studies indicate that omega-3 fatty acids (specifically, DHA and EPA) may inhibit the growth of prostate cancer. Similarly, population based clinical studies of groups of men suggest that a low-fat diet with the addition of omega-3 fatty acids from fish or fish oil help prevent the development of prostate cancer. Like breast cancer, the balance of omega-3 to omega-6 fatty acids appears to be particularly important for reducing the risk of this condition.

Other:

Although further research is needed, preliminary evidence suggests that omega-3 fatty acids may also prove helpful in protecting against certain infections and treating a variety of conditions, including autism, ulcers, migraine headaches, preterm labor, emphysema, psoriasis, glaucoma, Lyme disease, systemic lupus erythmatosus (lupus), irregular heart beats (arrhythmias), multiple sclerosis, and panic attacks. Omega-3 fatty acid supplementation may also help to reduce stress and the effects it has on the body.

Deficiency disorders:

Omega-3 deficiencies are linked to decreased memory and mental abilities, tingling sensation of the nerves, poor vision, increased tendency to form blood clots, diminished immune function, increased triglycerides and "bad" cholesterol (LDL) levels, impaired membrane function, hypertension, irregular heart beat, learning disorders, menopausal discomfort, itchiness on the front of the lower leg(s), and growth retardation in infants, children, and pregnant women.

Side effects:

Omega-3 fatty acids may increase the risk of bleeding. High doses have also been associated with nosebleed and blood in the urine. Potentially harmful contaminants such as dioxins, methylmercury, and polychlorinated biphenyls (PCBs) are found in some species of fish. Methylmercury accumulates in fish meat more than in fish oil, and fish oil supplements appear to contain almost no mercury. Heavy metals are most harmful in young children and pregnant/nursing women. Increases (worsening) in low-density lipoprotein levels ("bad cholesterol") by 5-10% are observed with intake of omega-3 fatty acids. Effects are dose-dependent.

2.2. Omega-6 Fatty Acid:

This is also known as linoleic acid. It is one of the poly unsaturated fatty acid and a healthy human with good nutrition will convert linoleic acid into gamma linolenic acid (GLA), which will later by synthesized, with EPA from the Omega-3 group, into eicosanoids. Although most Americans obtain an excess of linoleic acid, often it is not converted to GLA because of metabolic problems caused by diets rich in sugar, alcohol, or trans fats from processed foods, as well as smoking, pollution, stress, aging, viral infections, and other illnesses such as diabetes. It is best to eliminate these factors when possible, but some prefer to supplement with GLA-rich foods such as borage oil, black currant seed oil, or evening primrose oil¹².

Source:

Flaxseed oil, flaxseed meal, hempseed oil, grapeseed oil, pumpkin seeds, pine nuts, pistachio nuts, sunflower seeds (raw), olive oil, olives, borage oil, evening primrose oil, black currant seed oil, chestnut oil, chicken, among many others. Avoid refined and hydrogenated versions of these foods.

Uses:

Some Omega-6s improve diabetic neuropathy, rheumatoid arthritis¹³, skin disorders (e.g. psoriasis and eczema), and aid in cancer treatment.

Side effects:

Excess of the latter can cause inflammation, water retention, increased blood pressure, sticky platelets, and decreased immune response.

2.3. Omega-9 fatty acids:

This is also known as monounsaturated oleic acid. Oleic acid is also the most abundant fatty acid in human adipose tissue¹⁴. It is essential but technically not an EFA, because the human body can manufacture a limited amount, provided essential EFAs are present.

Source:

Olive oil (extra virgin or virgin), olives, avocados, almonds, peanuts, sesame oil, pecans, pistachio nuts, cashews, hazelnuts, macadamia nuts, etc.

Uses:

It lowers heart attack risk and arteriosclerosis, and aids in cancer prevention.

3. Essential balance:

The balance of w6 to w3 fatty acids that leads to optimum health. Researchers consider four or five omega 6 to each omega 3 a good balance. Most Western diets are between 10 and 20 to 1 in favour of omega 6, far too high in omega 6, which encourages overproduction of series 2 prostoglandins with negative effects on health. Therapeutic w6:w3 balance for Western diets is about 1 to 2. Typical Western diets provide ratios of between 10:1 and 30:1 - i.e., dramatically skewed toward n−6. 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, 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. It should be noted that olive, peanut and canola oils consist of approximately 80% monounsaturated fatty acids, (i.e. neither n−6 nor n−3) meaning that they contain relatively small amounts of n−3 and n−6 fatty acids¹⁵.

CONCLUSION:

Omega fatty acids plays an significant role in human body that saves lives and physicians must recognize this potential life-saving treatment choice in patients with cardiovascular disease. In addition, family physicians can safely offer patients an alternative therapeutic approach for difficult-to-treat conditions such as hypertriglyceridemia and rheumatoid arthritis. Omega -3 and 6 has a crucial role in treating the number of disorders in human. For those without cardiovascular disease, including young mothers and women, it is reasonable to recommend 650 to 1000 mg of low-risk fish oils per day through dietary approaches as suggested by the National Institutes of Health working group. The availability of safe and reliable supplements is paramount in further exploring and unlocking the health benefits of omega fatty acids.

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Received on 25.03.2009 Modified on 15.04.2009

Asian J. Research Chem. 2(2): April.-June, 2009 page 93-99