Understanding Essential Fatty Acids

CLA: Beneficial Fatty Acid · References

From sea to shining sea, and the amber waves of grain, a range of foods supply fats that are crucial to a healthy lifestyle.

Fat is essential for human life. It is one of the three basic nutritional categories, together with protein and carbohydrates. However, it is also significantly misunderstood. It is not the only nutrient to blame for increased rates of obesity and heart disease--in fact, the advent of the low-fat frenzy coincided with the fast growth of obesity, diabetes and cardiovascular disease. Instead, fat provides energy, assists with neurotransmission and helps form prostaglandins--hormone-like compounds that regulate almost all body functions. Unfortunately, most people do not understand what makes up fat.

Fatty acids are chains of carbon and hydrogen atoms that form triglycerides by joining with a glycerol molecule. Approximately 95 percent of the fat ingested by humans is in this form. Within the fatty acid category, there are several groupings based on specific chemical format.

Fatty acids can be first separated into saturated and unsaturated fatty acids. The saturated type includes butter or lard; they have a high melting temperature and the chemical links between the carbon atoms are single links, indicating the maximum amount of hydrogen is present. Because no more hydrogen can be inserted, the fat is saturated.

The unsaturated fatty acids have some double bonds in their carbon links. If there is one double bond present, the fatty acid has a lower melting point and is called monounsaturated. Monounsaturated fats include those found in olive oil and sesame oil; these oils supply oleic acid, an omega-9 fatty acid that has its double bond nine carbons up from the tail. If more than one double bond is present, the fatty acid is polyunsaturated; the presence of two or more bonds lowers the melting point further. Polyunsaturated fats can be found in such sources as fish and flax.

Polyunsaturates are further divided into classes of essential fatty acids (EFAs), which include omega-6s and omega-3s. Omega-6s include linoleic acid (LA) and its derivatives, gamma linolenic acid (GLA) and arachidonic acid (AA). Omega-3s include alpha linolenic acid (ALA) and ALA's derivatives, eicosapentaenoic acid (EPA) and doscosahexaenoic acid (DHA). Theoretically, only LA and ALA are absolutely "essential," but their derivatives are generally considered essential as well.

Marine plants such as plankton are the primary sources of omega-3 fatty acids in the food chain; fish feed on the plankton and absorb the ALA into their tissues as DHA and EPA. The richest land source of omega-3s is flaxseed oil. ALA is one of the primary structural components in cellular membranes, and serves as a precursor for the series 3 prostaglandins, which regulate the body's blood pressure, immune function and more.

ALA is an 18-carbon fatty acid; an enzymatic process in the body produces additional double bonds, converting ALA into the 20-carbon fatty acid EPA. A further enzymatic process converts EPA into DHA, a 22-carbon fatty acid with six double bonds. EPA and DHA are also known as long-chain polyunsaturated fatty acids (LCPUFAs). EPA appears to be the omega-3 that is primarily responsible for lowering triglyceride levels and promoting cardiovascular health, while DHA is one of the most abundant fatty acids in the brain and is responsible for proper brain development and neural transmission.

The omega-6 LA is fairly prevalent in the human diet, as it is found in a wide variety of vegetable and seed oils. However, many people do not have good enzymatic conversion by the delta-6 desaturase enzyme of LA to GLA. GLA and dihomogamma linolenic acid (DGLA) are the precursors for the series 1 prostaglandins. As such, they regulate a number of body functions, including skin integrity and joint lubrication. AA, which is supplied by animal fats, is the precursor for the series 2 prostaglandins that increase inflammation in the body.

High intakes of essential fatty acids can swing the balance from type 2 prostaglandins to the more beneficial types 1 and 3. A recent research review found that fish oil intake resulted in partial replacement of pro-inflammatory AA in cell membranes by EPA, decreasing the production of AA-derived mediators.¹ In addition, these LCPUFAs from fish oil may suppress production of pro-inflammatory cytokines (immune proteins) and protect against inflammatory challenges.

There are many health conditions associated with inflammation, from cardiovascular disease and arthritis to dermatitis and premenstrual syndrome (PMS). The actions of EFAs on inflammation are among their positive attributes in many different health conditions.

Cardiovascular Disease: EFAs may be best known for their benefits to the cardiovascular system. In fact, in November 2002, the American Heart Association published recommendations that healthy adults eat at least two servings of fish per week, particularly those containing more EPA and DHA.² They added that those at higher risk of cardiovascular disease may need more EPA and DHA than can be consumed strictly through the diet, and that supplements may be a viable alternative. "We have found that the effects of omega-3 fatty acids on heart disease risk is seen in relatively short periods of time," said Penny Kris-Etherton, lead researcher. "The research shows that all omega-3 fats have cardioprotective benefits, especially those in fish."

Previous research supports the conclusion that fish oil is linked to cardioprotective effects. In fact, an Italian study found that treatment with LCPUFAs from fish oil significantly reduced the cumulative rate of all causes of death, nonfatal myocardial infarction and nonfatal stroke.^3,4 Other studies have not found similar results for omega-6 EFAs. A recent research review concluded that only when ALA, DHA and EPA were added to the diet (rather than LA) was there a lowered rate of sudden cardiac death and nonfatal myocardial infarction.⁵

Other researchers have come to similar conclusions. Researchers conducting one double blind study of 38 subjects reviewed systemic arterial compliance (SAC), a reflection of arterial elasticity, in response to EPA, DHA or placebo.⁶ They found that EPA increased SAC by 36 percent, and DHA increased SAC by 27 percent; in conclusion, the researchers noted, "EPA and DHA increase SAC and tend to reduce pulse pressure and total vascular resistance, effects that may reduce the risk of adverse cardiovascular effects."

The effect on blood pressure has been noted in other studies. A metaregression analysis of randomized trials on fish oil and blood pressure concluded that a high intake of fish oil may lower blood pressure, especially in older and hypertensive subjects.⁷ The median dose was high in most trials (approximately 3.7 g/d), leading the researchers to suggest further study on the effects of lower doses.

Cholesterol and blood lipid levels are also impacted by omega-6 EFAs. In a 2001 study, researchers found that replacing 10 percent of saturated fats in a rat's diet with perilla oil, borage oil or evening primrose oil (EPO) inhibited the increases of serum total cholesterol and LDL cholesterol concentrations.⁸ And while the vast majority of research on EFAs and cardiovascular disease has dealt with fish oil, one study examined the ability of flaxseed--particularly its lignan components--to improve lipid profiles.⁹ The researchers found that 40 g/d of ground flaxseed along with 1,000 mg/d of calcium and 400 IU/d of vitamin E lowered total and non-HDL cholesterol by 6 percent.

While omega-3 EFAs have extensive research on their ability to protect the cardiovascular system, omega-3 and omega-6 EFAs impact many other health conditions.

Arthritis: EFAs--particularly EPA and DHA--are thought to reduce the pain and inflammation found in arthritic conditions. Typically, human inflammatory cells contain high proportions of the omega-6 AA and low levels of the omega-3s EPA and DHA. By supplementing with omega-3s, the AA in inflammatory cell membranes is partially replaced by EPA, possibly reducing inflammatory immune response. One recent research review noted fish oil supplementation had beneficial effects in rheumatoid arthritis, which supports the idea that the omega-3s in fish oil have anti-inflammatory properties.¹⁰

Skin disorders: Skin conditions such as eczema and psoriasis have shown susceptibility to treatment with EFAs, particularly GLA. An animal study comparing diets of EPO and borage oil found the treatments decreased excessive skin cell production.¹¹ They noted that borage was slightly more effective than EPO in this study. Another study comparing omega-3 to omega-6 supplementation for atopic dermatitis found that omega-3 did not decrease symptoms, while the omega-6 group saw marked long-term improvement.¹²

The mechanism of action as to how GLA helps skin conditions has been unclear. A study out of Inha University, Korea, found that administering EPO to patients with atopic dermatitis improved skin lesions and affected serum levels of immunoglobulins, leading the researchers to conclude the action might be linked to immunomodulation.¹³

Mental wellness/depression: EFAs may also assist in treating depression and other mental health conditions. Low levels of omega-3 EFAs are common in depression. In one 2002 study, researchers found that treatment with 1 g/d of EPA improved outcomes in patients with persistent depression.¹⁴ Another study found that EPA may prove an effective add-on treatment in schizophrenia.¹⁵

Part of omega-3's effectiveness in treating brain disorders may be linked to its role in neurotransmission and brain development. DHA in particular is crucial for proper brain function, and pregnant women are advised to consume adequate levels for fetal brain development. Review studies have concluded LCPUFAs are essential to the quality of growth and development of infants and children.¹⁶ Even in adults, clinical research indicated LCPUFAs may improve the condition of the blood-brain barrier, keeping the brain healthier, longer.¹⁷

Women's health: EFAs, particularly GLA, have been studied for their application in treating conditions such as PMS. Studies and research reviews have been contradictory in their findings of the use of EPO or borage as a source of GLA to treat PMS. One review found that "evening primrose oil may be a reasonable treatment alternative for some patients with PMS,"¹⁸ while another only found that trials have not been conclusive.¹⁹

The Right EFA for the Right Purpose

With the increased profile of EFAs has come a tremendous increase in the number of products available delivering these important nutrients. Different ingredients deliver different types and percentages of EFAs. On the omega-6 side, LA can be found in many vegetable sources. Corn, sunflower and safflower oils all contain more than 60-percent LA. Other sources include EPO (72%), borage oil (60%) and black currant seed oil (44%); many of these seeds also supply converted GLA. Borage oil supplies the highest level of GLA (26%), while black currant seed (18%) and evening primrose oil (9%) are also good sources.

Some plant sources of omega-6s also supply omega-3 fatty acids. Flaxseed contains approximately 60-percent ALA and 20-percent LA; hemp seed has a similar profile. However, there are no plant sources of converted EPA and DHA. Consumers looking to specifically augment their intake of these EFAs must look to marine sources, such as fatty fish, fish oil or algal-fortified products (such as eggs from chickens that eat an algal-enriched diet).

"While flax oil is high in ALA, extremely large amounts of flaxseed oil are required to achieve the optimal EPA and DHA levels that can be easily achieved with 1 g of fish oil," said Timothy Johanek, quality control educational coordinator with Arlington Heights, Ill.-based J.R. Carlson Laboratories.

The conversion rate of ALA to EPA and DHA also varies between the sexes and among individuals. For example, researchers in Southampton, England, conducted two studies on the conversion of ALA into its derivatives--one study on men and one on women.^20,21 The study on women demonstrated that after 21 days, individual omega-3 fatty acids targeted specific tissues. Researchers concluded that women may possess a greater capacity for ALA conversion than men, which would be particularly important when meeting the demands for adequate DHA during pregnancy for the fetus. The male study found almost no increase in DHA status, leading the researchers to suggest that taking pre-formed DHA in the diet may be "critical" to maintain adequate DHA concentration in men.

Luckily for consumers taking fish oil, it has come a long way from the bad-tasting cod liver oil of old. In part, this is due to increased care in product development by manufacturers, and retailers should question manufacturers about their quality control procedures. The first issue is purity of source. Many cold water fish that are good sources of LCPUFAs can contain high levels of toxins such as heavy metals or dioxins. Reputable suppliers of fish oil products should be able to supply retailers with documentation demonstrating the products have been treated and tested to show the oils are free of detectable levels of contaminants.

Second, because omega-3s are so susceptible to oxidation, rancidity can be a major problem with finished products. "Freshness is crucial next to purity," said Bonnie Johnson, corporate technical trainer with Watsonville, Calif.-based Nordic Naturals. "Freshness affects the taste, absorption and results by preventing the introduction of peroxides. Burping is a signal that the GI [gastrointestinal] tract cannot absorb the fish oil. When fish oils turn rancid, they have a fishy taste and smell."

Finally, retailers helping consumers select an EFA product should consider balance. As noted in the research on skin conditions, many women lack the ability to convert LA to GLA. Increasingly, manufacturers are offering products that combine fish or flax oil with a GLA source such as EPO or borage. "EFAs are crucial for cellular health," Johnson said. "Retailers need to be educated so that they can provide the purest, freshest oils available to deliver effective products that are beneficial for a myriad of medical conditions. Consumers will stay with a brand that gives them results."

CLA: Beneficial Fatty Acid

EFAs Outside of the "essential" fatty acids, there are additional fats that are beneficial to human health. Conjugated linoleic acid (CLA) is structurally similar to the omega-6 linoleic acid (LA); however, CLA's two double bonds occur in different locations. LA has double bonds at nine and 12 carbons up from the tail. The two active isomers of CLA have their bonds at cis-9,trans-11 and trans-10,cis-12 (trans- and cis- refer to the direction of the carbons in the bonds).

CLA has a wide range of biological effects. Studies in animals^22,23 and humans²⁴ indicate that CLA supplementation decreases body fat and increases lean muscle mass. The increase in lean muscle mass is most pronounced in individuals who are exercising regularly. CLA appears to reduce the ability of fat cells to take up fats from the bloodstream; it also inhibits the formation of new fat cells. CLA also helps cells burn fat at a higher rate, while fueling and preserving muscle, leading to a reduction in fat and an increase in lean muscle mass.

CLA has also been studied for its ability to serve as a chemopreventive agent, primarily in preventing breast cancer. A recent study conducted at the Roswell Park Cancer Institute in Buffalo, N.Y., indicated both c9,t11 and t10,c12 isomers of CLA were effective at inhibiting angiogenesis (formation of new blood vessels) in vitro in a dose-dependent fashion.²⁵ Similar in vivo research in rats found CLA significantly inhibited the formation of premalignant lesions and stimulated apoptosis (cell death).²⁶ It is suggested by other researchers that the mechanism of action may include reduced cell proliferation, alterations in the cell cycle and induction of apoptosis.²⁷

Another positive aspect of CLA is its impact on lipid metabolism. In vivo research in rats found that dietary CLA lowered liver lipid concentrations through reduced triglyceride synthesis and enhanced fatty acid oxidation.²⁸

EFA References

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2. Kris-Etherton P et al. "Fish consumption, fish oil, omega-3 Fatty acids, and cardiovascular disease." Circulation, 106, 21:2747-57, 2002.

3. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardio. "Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial." Lancet, 354, 9177:447-55, 1999.

4. Stone NJ. "The [GISSI]-Prevenzione Trial on fish oil and vitamin E supplementation in myocardial infarction survivors." Curr Cardiol Rep, 2, 5:445-51, 2000.

5. Renaud S, Lanzmann-Petithory D. "Dietary fats and coronary heart disease pathogenesis." Curr Atheroscler Rep, 4, 6:419-24, 2002.

6. Nestel P et al. "The n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid incrase systemic arterial compliance in humans." Am J Clin Nutr, 76, 2:326-30, 2002.

7. Geleijnse JM et al. "Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials." J Hypertens, 20, 8:1493-9, 2002.

8. Fukushima M et al. "Effects of diets enriched in n-6 or n-3 fatty acids on cholesterol metabolism in older rats chronically fed a cholesterol-enriched diet." Lipids, 36, 3:261-6, 2001.

9. Lucas EA et al. "Flaxseed improves lipid profile without altering biomarkers of bone metabolism in postmenopausal women." J Clin Endocrinol Metab, 87, 4:1527-32, 2002.

10. Calder PC. "Dietary modification of inflammation with lipids." Proc Nutr Soc. 61, 3:345-58, 2002.

11. Chung S et al. "Gamma linolenic acid in borage oil reverses epidermal hyperproliferation in guinea pigs." J Nutr, 132, 10:3090-7, 2002.

12. Mayser P et al. "A double-blind, randomized, placebo-controlled trial of n-3 versus n-6 fatty acid-based lipid infusion in atopic dermatitis." J Parenter Enteral Nutr, 26, 3:151-8, 2002.

13. Yoon S, Lee J, Lee S. "The therapeutic effect of evening primrose oil in atopic dermatitis patients with dry scaly skin lesions is associated with the normalization of serum gamma-interferon levels." Skin Pharmacol Appl Skin Physiol, 15, 1:20-5, 2002.

14. Peet M et al. "A dose ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs." Arch Gen Psychiatry, 59:913-9, 2002.

15. Emsley R et al. "Randomized, placebo controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia." Am J Pyschiatry, 159, 9:1596-8, 2002.

16. Larque E et al. "Perinatal supply and metabolism of long-chain polyunsaturated fatty acids: importance for the early development of the nervous system." Ann NY Acad Sci, 967:299-310, 2002.

17. de Wilde MC et al. "The effect of n-3 polyunsaturated fatty acid rich diets on cognitive and cerebrovascular parameters in chronic cerebral hypoperfusion." Brain Res, 947, 2:166-73, 2002.

18. Hardy ML. "Herbs of special interest to women." J Am Pharm Assoc (Wash), 40, 2:234-42, 2000.

19. Bendich A. "The potential for dietary supplements to reduce premenstrual syndrome symptoms." J Am Coll Nutr, 19, 1:3-12, 2000.

20. Burdge GC, Wootton SA. "Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women." Br J Nutr, 88, 4:411-20, 2002.

21. Burdge GC, Jones AE, Wootton SA. "Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men." Br J Nutr, 88, 4:355-64, 2002.

22. West DB et al. "Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse." Am J Physiol, 44:R667-72, 1998.

23. Park Y et al. "Evidence that the trans-10,cis-12 isomer of conjugated linoleic acid induces body composition changes in mice." Lipids, 34:235-41, 1999.

24. Blankson H et al. "Conjugated linoleic acid reduces body fat mass in overweight and obese humans." J Nutr, 130:2943-8, 2000.

25. Masso-Welch PA et al. "Inhibition of angiogenesis by the cancer chemoprotective agent conjugated linoleic acid." Cancer Res, 62, 15:4383-9, 2002.

26. Ip C et al. "Induction of apoptosis by conjugated linoleic acid in cultured mammary tumor cells and premalignant lesions of the rat mammary gland." Cancer Epidemiol Biomarkers Prev, 9, 7:689-96, 2000.

27. Belury MA. "Inhibition of carcinogensis by conjugated linoleic acid: potential mechanisms of action." J Nutr, 132, 10:2995-8, 2002.

28. Rahman SM et al. "Short-term administration of conjugated linoleic acid reduces liver triglyceride concentration and phosphytidate phosphohydrolase activity in OLEFT rats." J Biochem Mol Biol, 35, 5:494-7, 2002.