Polyunsaturated Fatty Acids, PUFAs


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What are Fatty Acids and PUFAs?

What are fatty acids? Let's begin with a simple explanation of what defines an acid. An acid is any substance that can donate a hydrogen ion (also referred to as a proton; written as H+), with the "loss" of the hydrogen ion resulting in the acid being negatively charged. Donating hydrogen ions to the surrounding solution, thus increases the concentration of protons in solution with the result being a decrease in pH. The lower the pH, the more acidic is a solution. For a detailed explanation of acid-base chemistry visit The Medical Biochemistry Page. Fatty acids are defined as compounds that are composed of long chains of carbon and hydrogen atoms (referred to as hydrocarbon molecules) containing a carboxylic acid moiety at one end (a carboxylic acid is written –COOH). See the structure of the 16 carbon fatty acid, palmitic acid, in the Figure below. When fatty acids donate their hydrogen ion, which occurs readily at physiological pH, the hydroxyl group (–OH) is negatively charged. The numbering of carbons in fatty acids begins with the carbon of the carboxylic acid group.

Carbon atoms can form covalent bonds to four other atoms. In nature these other atoms are either carbon (C), hydrogen (H), nitrogen (N) or oxygen (O). In some cases, the C or O atoms bound to a C are bound via a double bond (written –C=C– or –C=O; e.g. see palmitic acid Figure below). Fatty acids that contain no carbon-carbon double bonds are termed saturated fatty acids because the carbon atoms are "saturated" with four single covalent bonds. Fatty acids that contain carbon-carbon double bonds are unsaturated fatty acids and fatty acids with multiple sites of unsaturation are termed polyunsaturated fatty acids (PUFAs). The numeric designations used for fatty acids is derived from the number of carbon atoms, followed by the number of sites of unsaturation (e.g. palmitic acid is a 16-carbon fatty acid with no unsaturation and is designated by 16:0).

Structure of palmitic acid

Palmitic Acid

The site of unsaturation in a fatty acid is indicated by the symbol Δ and the number of the first carbon of the double bond relative to the carboxylic acid group (–COOH) carbon which is designated carbon #1. For example, linoleic acid is a 18-carbon fatty acid with two sites of unsaturation: one between carbons 9 and 10 and the other between carbons 12 and 13, and is designated by 18:2Δ9,12 (see the Table below).

Saturated fatty acids of less than eight carbon atoms are liquid at body temperature, whereas those containing more than ten are solid at this temperature. The presence of carbon-carbon double bonds in fatty acids significantly lowers the melting point relative to that of a saturated fatty acid of the same number of carbon atoms. In the food industry, many animal and plant derived polyunsaturated fatty acids (which are liquid at room temperature) are chemically treated to introduce hydrogen atoms onto the carbon atoms that are double bonded in order to make these PUFAs solid at room temperature. This process, termed "hydrogenation", generates the partially hydrogenated oils found in numerous cooking ingredients such as margarine.

The majority of fatty acids found in the body are acquired in the diet. However, the human body can synthesize all the various fatty acid structures needed from other carbon compounds (see The Medical Biochemistry Page for details of fatty acid synthesis). Two key exceptions to this are the PUFAs known as linoleic acid and alpha-linolenic (α-linolenic) acid, abbreviated ALA. These two fatty acids cannot be synthesized from precursors in the body, and are thus considered the essential fatty acids; essential in the sense that they must be provided in the diet. Since plants are capable of synthesizing linoleic acid and ALA, humans can acquire these fats by consuming a variety of plants or else by eating the meat of animals that have consumed these plant fats. These two essential fatty acids are also referred to as omega fatty acids. Linoleic acid is an omega-6 PUFA and α-linolenic is an omega-3 PUFA. See the Table below for structures and the next section for the explanation of what exactly makes a fatty acid an omega fatty acid.

Structures of Common Omega Fatty Acids

Numerical Symbol Common Name and Struture Comments
18:1Δ9 Oleic acid
Structure of oleic acid
An omega-9 monounsaturated fatty acid
18:2Δ9,12 Linoleic acid
Structure of linoleic acid
An omega-6 polyunsaturated fatty acid
18:3Δ9,12,15 α-Linolenic acid (ALA)
Structure of linolenic acid
An omega-3 polyunsaturated fatty acid
20:4Δ5,8,11,14 Arachidonic acid
Structure of arachidonic acid
An omega-6 polyunsaturated fatty acid
20:5Δ5,8,11,14,17 Eicosapentaenoic acid (EPA)
Structure of arachidonic acid
An omega-3 polyunsaturated fatty acid
enriched in fish oils
22:6Δ4,7,10,13,16,19 Docosahexaenoic acid (DHA)
Structure of arachidonic acid
An omega-3 polyunsaturated fatty acid
enriched in fish oils

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What are Omega-3, -6, and -9 Fatty Acids

The term omega, as it relates to fatty acids, refers to the terminal carbon atom farthest from the functional carboxylic acid group (–COOH). The designation of a polyunsaturated fatty acid (PUFA) as an omega-3 fatty acid, for example, defines the position of the first site of unsaturation relative to the omega end of that fatty acid . Thus, an omega-3 fatty acid like α-linolenic acid (ALA), which harbors three carbon-carbon double bonds (i.e sites of unsaturation), has a site of unsaturation between the third and fourth carbons from the omega end (see Figure in Table above). There are three major types of omega-3 fatty acids that are ingested in foods and used by the body: ALA, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Once eaten, the body converts ALA to EPA and then to DHA as shown in the Figure below. EPA and DHA are the two types of omega-3 fatty acids that serve as important precursors for lipid-derived modulators of cell signaling, gene expression and inflammatory processes. There are numerous other omega-3 PUFAs found in nature but for the purposes of this discussion focus is placed on ALA, EPA, and DHA.

It is important to denote that when discussing omega-3 fatty acids, their dietary origin is quite important. Omega-3 fats from plants, such as those in flaxseed oil, are enriched in ALA. As indicated above, ALA must first be converted to EPA (requiring three independent reactions) and then to DHA (requiring and additional four reactions). Omega-3 fats from fish are enriched in EPA and DHA and thus do not need to undergo the complex conversion steps required of ALA. In addition, the conversion of ALA to EPA and then EPA to DHA is inefficient in individuals consuming a typical Western diet rich in animal fats. Therefore, direct dietary intake of omega-3 fats rich in EPA and DHA are of the most benefit clinically.

Conversion of ALA to EPA and DHA

Pathway for ALA conversion to EPA and DHA

Most of the omega-6 PUFAs consumed in the diet are from vegetable oils such as soybean oil and corn oil and consist of linoleic acid. Linoleic acid is the precursor for the 20-carbon PUFA, arachidonic acid which is the principal omega-6 PUFA found in humans (see Figure above). The significance of arachidonic acid is that it serves as the precursor molecule for the synthesis of a family of bioactive lipids called the eicosanoids (eicosa means 20). A detailed description of the synthesis and biological actions of the eicosanoids can be found in The Medical Biochemistry Page (some actions are described below).

Upon consumption, linoleic acid is converted to gamma-linolenic acid (γ-linolenic acid, GLA). GLA should not be confused with ALA which, as pointed out above, is an essential omega-3 PUFA. GLA itself can be ingested from several plant-based oils including borage oil, and acai berry. GLA, like EPA and DHA, is an important dietary PUFA as described below.

GLA is then converted to dihomo-γ-linolenic acid (DGLA) and then to arachidonic acid. The activity of the enzyme that converts linoleic acid to GLA (called delta-6-desaturase; written Δ6-desaturase) is slow and can be further compromised due to nutritional deficiencies as well as during inflammatory conditions. Therefore, maximal capacity for synthesis of arachidonic acid occurs with ingestion of GLA thus, bypassing the Δ6-desaturase reaction. Like the Δ6-desaturase, the activity of the enzyme that converts DGLA to arachidonic acid (called Δ5-desaturase) is limiting in arachidonic acid synthesis and its activity is also influenced by diet and environmental factors.

Due to the limited activity of the Δ5-desaturase most of the DGLA formed from GLA is inserted into membrane lipids in the same place as is arachidonic acid. This leads to a competition between membrane lipids containing DGLA and those containing arachidonic acid. This becomes significant when comparing the different biological activities that are attributable to bioactive lipids derived from DGLA versus those derived from arachidonic acid as pointed out below.

Oleic acid is the primary omega-9 fatty acids found in the human body and it is a monounsaturated fatty acid (see Figure above). Oleic acid is not an essential fatty acid because the body can introduce the unsaturation from saturated fatty acid precursors. Because omega-9 fatty acids lack the unsaturation at the omega-6 position they cannot participate in the synthesis of the eicosanoids and as such are not important in modulation of inflammatory responses.

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What are Common Sources of Omega Fats

Omega-3 Fats

The highest concentrations of the critical omega-3 PUFAs, EPA and DHA, are found in cold-water fish such as salmon, mackerel, halibut, sardines, tuna, and herring. ALA is found in flaxseed oil (flaxseed oil has the highest linolenic content of any food), flaxseeds, flaxseed meal, hempseed oil, hempseeds, walnuts, pumpkin seeds, Brazil nuts, sesame seeds, avocados, some dark leafy green vegetables (kale, spinach, purslane, mustard greens, collards, etc.), canola oil (cold-pressed and unrefined), soybean oil, and wheat germ oil. Other sources of omega-3 fatty acids include krill oils and algae. Algae is the greatest source of EPA and DHA for consumption by individuals adhering to a strict vegan diet.

Consumption of fish oil supplements should be based on the amount of EPA and DHA, not on the total amount of fish oil. Supplements vary in the amounts and ratios of EPA and DHA. A common amount of omega-3 fatty acids in fish oil capsules is 0.18 grams (180 mg) of EPA and 0.12 grams (120 mg) of DHA. Five grams of fish oil contains approximately 0.17–0.56 grams (170–560 mg) of EPA and 0.072–0.31 grams (72–310 mg) of DHA. Different types of fish contain variable amounts of omega-3 fatty acids, and different types of nuts or oil contain variable amounts of ALA. Fish oils contain approximately 9 calories per gram of oil.

Omega-6 Fats

Omega-6 PUFAs are found in flaxseed oil, flaxseeds, flaxseed meal, hempseed oil, hempseeds, 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, and chicken. Corn, safflower, sunflower, soybean, and cottonseed oils also contain high concentrations of linoleic acid but because of processing may be nutrient deficient when used in products found on store shelves. Borage oil contains the highest concentration of the clinically significant omega-6 PUFA, GLA.

Omega-9 Fats

Omega-9 monounsaturated fatty acids (primarily oleic acid) are found in olive oil (extra virgin or virgin), olives, avocados, almonds, peanuts, sesame oil, pecans, pistachio nuts, cashews, hazelnuts, and macadamia nuts.

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Clinical Significance of Omega-3, and -6, and -9 PUFAs

The clinical significance of omega fatty acids lies primarily in the role they play in inflammatory events in the body. Indeed, the interplay between pro-inflammatory molecules derived from omega-6 PUFAs and the anti-inflammatory actions of molecules derived from omega-3 PUFAs underlies the significant cardiovascular benefits attributable to increasing ones consumption of omega-3 PUFAs while at the same time decreasing consumption of omega-6 PUFAs. The typical Western diet rich in animal fats and partially hydrogenated vegetable oils contributes to the high ratio of omega-6 PUFAs relative to omega-3 PUFAs found in cellular lipids.

While it is not the intention of this discussion to cover the science of omega PUFAs in detail, it is important to have a basic understanding in order to fully appreciate the significant clinical benefits that can be gained from simple changes in ones dietary habits or supplement intake.

Omega-3 PUFAs

It is important to denote that when discussing omega-3 fatty acids, their dietary origin is quite important. Omega-3 fats from plants, such as those in flax seed oil, are enriched in ALA. As indicated above, ALA must first be converted to EPA (requiring three independent reactions) and then to DHA (requiring an additional four reactions). Omega-3 fats from fish are enriched in EPA and DHA and thus do not need to undergo the complex conversion steps required of ALA. In addition, the conversion of ALA to EPA and DHA is inefficient in individuals consuming a typical Western diet rich in animal fats.

When omega-3 and omega-6 fatty acids are consumed they are incorporated into cell membranes in all tissues of the body. Because of this fact, dietary changes in the composition of PUFAs can have profound effects on a cell's function because the membrane lipids serve as a source of precursors for the synthesis of important signaling molecules involved in cell growth and development as well as modulation of inflammation. Another important consequence of dietary alteration in fatty acid composition is the fact that omega-3 and omega-6 PUFAs compete for incorporation into cell membranes.

Dietary omega-3 PUFAs compete with the inflammatory, pyretic (fever), and pain promoting properties imparted by omega-6 PUFAs because they displace arachidonic acid from cell membranes. In addition, omega-3 PUFAs compete with the enzymes that convert arachidonic acid into the pro-inflammatory eicosnaoids (PGE2, TXA2, and LTB4). The net effect of increasing dietary consumption of omega-3 PUFAs, relative to omega-6 PUFAs, is to decrease the potential for monocytes, neutrophils, and eosinophils (i.e. white blood cells called leukocytes) to synthesize potent mediators of inflammation and to reduce the ability of platelets to release TXA2, a potent stimulator of the blood coagulation cascade.

Probably the most important role of the omega-3 PUFAs, EPA and DHA, is that they serve as the precursors for potent anti-inflammatory lipids called resolvins (Rvs) and protectins (PDs). The Rvs exert their anti-inflammatory actions by promoting the resolution of the inflammatory cycle, hence the derivation of their names as resolvins. The resolvins are synthesized either from EPA or DHA. The D series resolvins are derived from DHA and the E series from EPA. An additional anti-inflammatory lipid derived from DHA is protectin D1 (PD1). The E series resolvins reduce inflammation, regulate polymorphonuclear leukocyte (PMN, a type of  white blood cell) infiltration by blocking transendothelial migration, reduce dendritic cell function (dendritic cells are potent antigen presenting cells which prime T cell mediated inflammatory responses), regulate IL-12 production (a potent pro-inflammatory cytokine) and lead to resolution of the inflammatory responses. More information on the synthesis and actions of the Rvs and PDs can be found on The Medical Biochemistry Page.

The omega-3 fatty acids DHA and EPA have also been shown to be important for normal brain development and function. Several studies have demonstrated that DHA is essential for proper development of the prenatal and postnatal central nervous system. The benefits of EPA appear to be in its effects on behavior and mood. In clinical studies with DHA and EPA there has been good data demonstrating benefit in treating attention deficit hyperactivity disorder (ADHD), autism, dyspraxia (motor skills disorder), dyslexia, and aggression. In patients with affective disorders consumption of DHA and EPA has confirmed benefits in major depressive disorder and bipolar disorder. In addition, some studies have demonstrated promising results in treatment of schizophrenia with some minor benefits in patients with borderline personality disorder. Of significance to these effects of EPA and DHA on cognition, mood and behavior is the fact that administration of omega-3 fatty acid containing phospholipids (such as those present in Krill oils) are significantly better than omega-3 containing triacylglycerides such as those that predominate in fish oils.

Omega-6 PUFAs

The most important omega-6 PUFA is arachidonic acid. When cells are stimulated by a variety of external stimuli, arachidonic acid is released from cell membranes through the action of phospholipase A2 (PLA2). The released arachidonate then serves as the precursor for the synthesis of the biologically active eicosanoids, the prostaglandins (PGs), thromboxanes (TXs), and leukotrienes. (LTs) The arachidonate-derived eicosanoids function in diverse biological phenomena such as platelet and leukocyte activation, signaling of pain, induction of bronchoconstriction, and regulation of gastric secretions. These activities are targets of numerous pharmacological agents such as the non-steroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, and leukotriene antagonists.

Research over the past 10–15 years has demonstrated the physiological benefits (i.e. anti-inflammatory) of alternative pathways of polyunsaturated fatty acid metabolism. Much of this topic is covered in more detail in The Medical Biochemistry Page. As described above for the synthesis of arachidonate, much of the DGLA derived from ingested linoleic acid or GLA is diverted into membrane phospholipids due to the inefficiency of the Δ5-desaturase catalyzing the conversion of DGLA to arachidonic acid. Incorporation of DGLA into membrane phospholipids competes with the incorporation of arachidonate so that diets enriched in GLA result in an alteration in the ratio of membrane arachidonate to DGLA. Release of membrane DGLA occurs in response to the same signals that lead to release of arachidonate. Once DGLA is released it will compete with arachidonate for COXs and LOXs. The products of COX action on DGLA are series-1 prostaglandins (PGE1) and thromboxanes (TXA1). These eicosanoids are structurally similar to the series-2 eicosanoids except, of course, they have a single double bond. Although structurally similar, the series-1 eicosanoids have distinctly different biological actions. PGE1 and TXA1 are anti-inflammatory, they induce vasodilation, and they inhibit platelet aggregation. These latter two responses represent significant anti-coagulant properties that have profound cardiovascular benefits such as in the prevention of atherosclerosis. When DGLA is a substrate for 15-LOX, the product (15-hydroxyeicosatrienoic acid, 15-HETrE) is a potent inhibitor of 5-LOX which is the enzyme responsible for the conversion of arachidonic acid to LTB4. LTB4 is a potent inflammatory molecule through its action on neutrophils, thus, DGLA serves to inhibit inflammation via the lpathway through which arachidonic acid is converted to a pro-inflammatory lipid.

Due to the vasodilating action of PGE1 it is used pharmaceutically as aprostadil for the treatment of erectile dysfunction (ED). The ED applications of PGE1 are sold as MUSE® and Caverject®. MUSE is a urethral suppository and Caverject is an injectable version. Aprostadil is also used clinically to treat newborn infants with a type of congenital heart defect. The administration of aprostadil in these infants maintains a patent ductus arteriosus until surgery can carried out to correct the underlying heart defect. Ductus arteriosus is a normal structure of the fetal heart that allows blood to bypass circulation to the lungs since the fetus does not use his/her lungs in utero. The ductus arteriosus shunts blood flow from the left pulmonary artery to the aorta. Shortly after birth the ductus closes due to the high levels of oxygen the newborn is exposed to at birth. However, in newborns with certain congenital heart defects, maintaining a patent ductus arteriosus is clinically significant.

Omega-9 Fatty Acids

Oleic acid, since monounsaturated is not a PUFA, but it is a clinically relevant omega-9 fatty acid. Oleic acid has been shown to be of benefit in reducing level of cholesterol in the circulation. This reduction in cholesterol reduces the incidence of atherosclerosis and therefore the risk for heart attacks. In addition, oleic acid may aid in the prevention of certain types of cancer. However, there is some controversy in the area of cancer since evidence has been obtained that indicates that the level of saturated and monounsaturated fatty acids found in membranes of erythrocytes (red blood cells, these cells carry oxygen in the blood) is a good predictor of post-menopausal breast cancer.

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Why Change My Dietary Omega Fats

Changing dietary intake such that the proportion of omega-3 PUFAs is in excess of omega-6 PUFAs has been shown to have significant clinical impact in a number of different circumstances and disease states. The highest clinical benefits come from directly increasing the intake of EPA, DHA, GLA, and DGLA. This benefit is due to the fact that the precursor lipids to these complex PUFAs are not effectively converted by the enzymes in the human body. Listed below are several pathophysiological situations shown to be affected by increased omega PUFA intake.

High cholesterol, blood pressure and heart disease:

People who follow a Mediterranean-style diet tend to have higher levels of plasma high density lipoproteins (HDLs; the so-called "good cholesterol"), which help promote heart health. Inuit Eskimos, who get high amounts of omega-3 fatty acids from eating fatty fish, also tend to have increased HDL and decreased triglycerides. Several studies have shown that fish oil supplements reduce triglyceride levels. Finally, walnuts (which are rich in ALA have been reported to lower total cholesterol and triglycerides in people with high cholesterol levels. Several clinical studies suggest that diets or fish oil supplements rich in omega-3 fatty acids lower blood pressure in people with hypertension. Clinical studies using fish oil supplements have found that taking 3 or more grams of fish oil daily may reduce blood pressure in people with untreated hypertension. One of the best ways to help prevent heart disease is to eat a diet low in saturated fat and to eat foods that are rich in monounsaturated and polyunsaturated fats (including omega-3 fatty acids). Clinical evidence suggests that EPA and DHA help reduce risk factors for heart disease, including high cholesterol and high blood pressure. Fish oil has been shown to lower levels of triglycerides (fats in the blood), and to lower risk of death, heart attack, stroke, and abnormal heart rhythms in people who have already had a heart attack. Fish oil also appears to help prevent and treat atherosclerosis (hardening of the arteries) by slowing the development of plaque and blood clots, which can clog arteries. Large population studies suggest that getting omega-3 fatty acids in the diet, primarily from fish, helps protect against stroke caused by plaque buildup and blood clots in the arteries that lead to the brain. Eating at least 2 servings of fish per week can reduce the risk of stroke by as much as 50%. However, high doses of fish oil and omega-3 fatty acids may increase the risk of bleeding. People who eat more than 3 grams of omega-3 fatty acids per day (equivalent to 3 servings of fish per day) may have higher risk for hemorrhagic stroke, a potentially fatal type of stroke in which an artery in the brain leaks or ruptures.

Diabetes:

People with type 2 diabetes often have high triglyceride and low HDL levels due to disruptions in normal insulin actions. Consumption of omega-3 fatty acids from fish oil have been  shown to result in lower triglycerides and to increase the level of HDLs (the so-called "good cholesterol"). Thus, eating foods or taking fish oil supplements may help people with diabetes. Because the pathopysiological disruptions that occur in persons with type 2 diabetes lead to greater reductions in the conversion of ALA to EPA and DHA, the use of supplements enriched in ALA (from flaxseed, for example) may not have the same benefit as fish oil.

Cancers of various types:

Eating foods rich in omega-3 fatty acids seems to reduce the risk of colorectal cancer. For example, Eskimos, who tend to have 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. Preliminary studies suggest that taking fish oil daily may help slow the progression of colon cancer in people with early stages of the disease. If you have colorectal cancer, ask your doctor before taking any supplements. Although not all experts agree, women who eat foods rich in omega-3 fatty acids over many years may be less likely to develop breast cancer. More research is needed to understand the effect that omega-3 fatty acids may have on the prevention of breast cancer. Population based studies of groups of men suggest that a low-fat diet including omega-3 fatty acids from fish or fish oil help prevent the development of prostate cancer.

Rheumatoid arthritis:

Most clinical studies examining omega-3 fatty acid supplements for arthritis have focused on rheumatoid arthritis (RA), an autoimmune disease that causes inflammation in the joints. A number of small studies have found that fish oil helps reduce symptoms of RA, including joint pain and morning stiffness. One study suggests that people with RA who take fish oil may be able to lower their dose of non-steroidal anti-inflammatory drugs (NSAIDs). However, unlike prescription medications, fish oil does not appear to slow progression of RA, only to treat the symptoms. Joint damage still occurs. Laboratory studies suggest that diets rich in omega-3 fatty acids (and low in the inflammatory omega-6 fatty acids) may help people with osteoarthritis, although more study is needed. 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 improve walking pace in a small group of people with osteoarthritis. For some people, symptoms got worse before they improved. Controlled clinical trials have analyzed the pain relieving effects of omega-3 fatty acid supplements in people with RA or joint pain caused by inflammatory bowel disease (IBS) and painful menstruation (dysmenorrhea). The results suggest that omega-3 fatty acids, along with conventional therapies such as NSAIDs, may help relieve joint pain associated with these conditions.

Systemic lupus erythematosus (SLE):

Several small studies suggest that EPA and fish oil may help reduce symptoms of lupus, an autoimmune condition characterized by fatigue and joint pain. However, two small studies found fish oil had no effect on lupus nephritis (kidney disease caused by lupus, a frequent complication of the disease).

Osteoporosis:

Some studies suggest that omega-3 fatty acids may help increase levels of calcium in the body and improve bone strength, although not all results were positive. Some studies also suggest that people who don’t get enough of some essential fatty acids (particularly EPA and gamma-linolenic acid [GLA], an omega-6 fatty acid) are more likely to have bone loss than those with normal levels of these fatty acids. In a study of women over 65 with osteoporosis, those who took EPA and GLA supplements had less bone loss over 3 years than those who took placebo. Many of these women also experienced an increase in bone density.

Inflammatory bowel disease (IBD):

Results are mixed as to whether omega-3 fatty acids can help reduce symptoms of Crohn’s disease and ulcerative colitis, the two types of IBD. Some studies suggest that omega-3 fatty acids may help when added to medication, such as sulfasalazine (a standard medication for IBD). Others find no effect. More studies are needed. Fish oil supplements can cause side effects that are similar to symptoms of IBD (such as flatulence, belching, bloating, and diarrhea).

Asthma:

Studies examining omega-3 fatty acids for asthma are mixed. In one small, well-designed clinical study of 29 children with asthma, those who took fish oil supplements rich in EPA and DHA for 10 months reduced their symptoms compared to children who took placebo. However, most studies have shown no effect.

Macular Degeneration:

A questionnaire given to more than 3,000 people over the age of 49 found that those who ate more fish were less likely to have macular degeneration (a serious age-related eye condition that can progress to blindness) than those who ate 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 more fish in their diets were less likely to have macular degeneration.

Potential Drug Interactions:

Due to the potential for interactions between the effects of omega-3 fatty acid supplements and other prescribed medications it is important to consult your physician and inform him/her of your intent to begin taking these types of supplements (e.g. EPA, DHA, and ALA). Some potential contraindications or beneficial effects due to drug interactions include:

Blood-thinning medications Omega-3 fatty acids may increase the effects of blood thinning medications, including aspirin, warfarin (Coumadin), and clopidogrel (Plavix). Taking aspirin and omega-3 fatty acids may be helpful in some circumstances (such as in heart disease), but they should only be taken together under the supervision of a health care provider.

Diabetes medications Taking omega-3 fatty acid supplements may increase fasting blood sugar levels. Use with caution if taking medications to lower blood sugar, such as glipizide (Glucotrol and Glucotrol XL), glyburide (Micronase or DiaBeta), glucophage (Metformin), or insulin. Your doctor may need to increase your medication dose.

Cyclosporine Cyclosporine is a medication given to people with organ transplants. Taking omega-3 fatty acids during cyclosporine (Sandimmune) therapy may reduce toxic side effects, such as high blood pressure and kidney damage, associated with this medication.

Etretinate and topical steroids Adding omega-3 fatty acids (specifically EPA) to the drug therapy etretinate (Tegison) and topical corticosteroids may improve symptoms of psoriasis.

Cholesterol-lowering medications Following dietary guidelines, including increasing the amount of omega-3 fatty acids in your diet and reducing the omega-6 to omega-3 ratio, may help a group of cholesterol lowering medications known as statins to work more effectively. These medications include Lipitor (atorvastatin), Mevacor (lovastatin), and Zocor (simvastatin).

Nonsteroidal anti-inflammatory drugs (NSAIDs) In an animal study, treatment with omega-3 fatty acids reduced the risk of ulcers from nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs include ibuprofen (Motrin or Advil) and naproxen (Aleve or Naprosyn). Whether these same benefits are seen in humans is yet to be determined.

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Supporting Research

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Berbert AA, Kondo CR, Almendra CL, Matsuo, T and Dichi, I 2005. Supplementation of fish oil and olive oil in patients with rheumatoid arthritis. Nutrition. 21:131-136

Chapkin, RS, Kim, W, Lupton, JR and McMurray, DN 2009. Dietary docosahexaenoic and eicosapentaenoic acid: emerging mediators of inflammation. Prost., Leuk., and Essent. Fatty Acids 81:187-191

Richardson AJ, and Puri BK. 2006. The potential role of fatty acids in attention-deficit/hyperactivity disorder. Prost., Leuk., and Essent. Fatty Acids. 63(1/2):79-87

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Freund-Levi YF, Eriksdotter-Jönhagen M, Cederholm T, Basun H, Faxén-Irving G, Garlind A, Vedin I, Vessby B, Wahlund LO, and Palmblad J 2006. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD Study. Arch Neurol. 63:1402-1408

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