The Alphabet Soup of EFAs

Fatty acid supplementation benefits multiple health conditions

The Other Healthy Fat: CLA
Last But Not Least: Omega-9
References

“Fat is not our enemy,” wrote Marie Moneysmith, author of User’s Guide to Good Fats and Bad Fats (Basic Health Publications, 2003). “In fact, in many ways fat is our friend. It cushions many of our internal organs and provides insulation that protects us against plummeting temperatures— something our Ice Age ancestors probably appreciated much more than we do.”

Fats are not the enemy— as long as they are the right kinds of fat, since not all fats are made the same. Fats, also known as lipids, are a more extended family than most people know. Some family members include cholesterol, triglycerides, phospholipids, sterols, vitamins and fatty acids.

In regard to fatty acids, researchers have found them to benefit practically all areas of health, be it boosting heart health, enhancing eye health, easing the effects of rheumatoid arthritis, even solving skin problems. This is because they help build the body’s cell membranes; fatty acids also help the body produce hormone-like prostaglandins and the lipids leukotrienes— which both regulate the body’s inflammatory response.

Unsaturated fats are classified into omega-3s, -6s and -9s. Omega-3s and -6s are polyunsaturated and considered essential because the body can’t make them. The omega-9s include oleic acid, which can come from olive and avocado oils. (To read more on omega-9s.) And then there’s the little-heard-of monounsaturated omega-7, palmitoleic acid, found in palm kernel and coconut oils.

Omega-3 fatty acids first became recognized when scientists in the 1970s found that Inuits in Greenland who consumed a diet very high in omega-3 fatty acids had surprisingly low rates of heart attacks. The primary omega-3, alpha linolenic acid (ALA), is an unsaturated fat that comes mainly from plants such as flaxseed, rape seed (canola oil), walnuts and green leafy vegetables. It is converted in the body into longer chain, polyunsaturated fatty acids (LC-PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which is considered the most unsaturated omega-3.

“In the late 1950s, doctors began to urge people to increase their intake of polyunsaturated fatty acids. They forgot about the omega-3s, however,” wrote Clara Felix in All About Omega-3 Oils (Avery Publishing, 1998). “The food industry responded with tank-fulls of polyunsaturated oils, for both commercial and household use. The country was soon awash in corn, safflower, peanut, sunflower and cottonseed oils, all full of omega-6 but with little or no omega-3.” She added that today’s typical American diet still contains too many omega-6s, compared to omega-3s.

“High levels of the omega-6 oils without the restraining effects of the omega-3s actually promotes the diseases that are supposed to be prevented,” Felix said. “This includes heart disease, allergies, asthma, autoimmune diseases, obesity, diabetes, depression—even cancer.”

The scientific community even recommends a 1-to-1 ratio of omega-3s-toomega- 6s for optimum health effects. However, it is reported that many Americans consume an omega-6-toomega- 3 ratio of about 30-to-1.

Omega-6s, despite the bad rap, are also considered essential. Longer chain fatty acids of the omega-6 family are led by linoleic acid (LA), from which gammalinolenic acid (GLA) is derived. GLA is the precursor for dihomogamma-linolenic acid (DGLA), which is the precursor to the PGE1 series prostaglandins, and arachidonic acid (AA), which is the precursor to the PGE2 series prostaglandins.

“Theoretically, only LA and ALA are absolutely essential,” wrote Lorna Vanderhaeghe in Healthy Fats for Life (Quarry Health Books, 2003). “However, the fatty acids derived from them are also generally considered essential.” She added that deficiencies in EFAs are common today for three reasons: modern dietary and lifestyle choices, environmental pollution and, for some people, trouble converting LA and ALA to their by-products. “EFA deficiency is a serious health concern that can eventually lead to disease and even death,” she wrote.

EFAs & Serious Health Conditions

EFAs, be it in the form of LA, ALA or their derivatives—DHA, EPA, GLA and AA—exert their benefits all over the place, such as in diabetes, cardiovascular health, cognitive decline, brain development, depression, eye health, joint and bone health, and cancer.

Both omega-3s and -6s play a role in protecting against diabetes and some of its side effects, including heart problems and neuropathy—a disease of the nervous system. In the end, the disease and its related conditions may be linked to diabetes-induced oxidative stress. For example, 4 g/d of purified EPA or DHA was seen to reduce in vivo oxidant stress without changing markers of inflammation in Type II diabetics.¹

Oxidation also appears to affect nerve perfusion and contribute to the development of peripheral neuropathy. In a study using GLA-rich evening primrose oil or ALA, the treatments effectively corrected the deficits in nerve function and blood flow to the nerves.²

Oxidative stress and defective fatty acid metabolism in diabetes may also lead to endothelial dysfunction, according to research out of the University of Aberdeen, Scotland; diabetes reportedly inhibits a pathway used by omega-6s in the body—a pathway also important for vascular health. However, this defect may be overcome through consuming a diet enriched with GLA-rich oils, such as evening primrose oil, which was found to have potential therapeutic relevance for diabetic microvascular complications.³

In terms of overall cardiovascular health, omega-3s protect against many heart issues, including myocardial infarction, arrhythmia, atherosclerosis and hypertension. The protective effects of omega-3s are attributable to their direct effects on vascular smooth muscle cell functions. Recent data suggests that modulation of these functions contribute to the beneficial effects of omega-3s on various cardiovascular disorders.⁴

EPA and DHA appear to have antiatherosclerotic effects by decreasing LDL uptake and working against other inflammatory markers of atherosclerosis.⁵ Research out of Southampton, England, also indicates omega-3s reduce the extent of atherosclerosis in stroke patients. Researchers found 1.4 g/d of omega-3s had an anti-inflammatory effect, reducing the risk of atherosclerotic plaques from rupturing or clots from forming in stroke patients.⁶ (The product used in the study was Norway-based Pronova Biocare’s Omacor, which contains 84 percent of its EPA and DHA as ethyl esters.)

Although fish-derived omega-3s are the ones in the EFA limelight, there are other healthy fats proving their mettle in heart health. Serum total cholesterol, triglyceride and phospholipid levels were decreased in the presence of perilla oil (which contains the omega-3 ALA).⁷ GLA (as evening primrose oil) may have a heart-protective effect against high-cholesterol diets. In a rat model, GLA supplementation led to reduced atherosclerotic lesions, thereby retarding the development of diet-induced atherosclerosis.⁸

Japanese researchers reported both omega-3s and -6s appear to combat the cholesterol-raising effects of high-fat diets. The results of this study demonstrated both omega-6 fatty acids (such as GLA) and omega-3 fatty acids (such as ALA) inhibited the increase of serum total cholesterol and very low LDL cholesterol concentrations of aged rats in the presence of excess dietary cholesterol compared with dietary saturated fatty acid.⁹

Another condition found in the aged is cognitive decline. Advanced age is associated with reduced brain levels of long-chain polyunsaturated fatty acids such as AA and DHA. In a rat model, EFAsufficient rats were fed fish oil (with 11-percent DHA); DHA but not AA was seen to be restored to the levels of those found in young rats. Fish oil reduced AA in the older rat brains, although it did not make the rats perform better in maze tests than control rats.¹⁰

In a prospective study conducted from 1993 through 2000 to investigate the effects of omega-3s on Alzheimer’s, participants who ate fish once per week or more had a 60-percent lower risk of contracting Alzheimer’s disease compared with those who rarely or never ate fish. Total intake of omega-3s, particularly DHA, was associated with reduced risk of Alzheimer’s disease.¹¹ And research out of Japan indicated chronic administration of DHA (as 300 mg/kg/d) was effective in decreasing the level of hippocampal lipid peroxidation in an animal model with aged rats, thus improving learning ability.¹²

Not only the aging brain benefits from EFA supplementation—so does the developing brain. Human milk not only supplies EFAs, but it also contains up to 2 percent of the total fatty acids as LC-PUFAs, of which AA and DHA are considered the most important. In support of this theory, plasma and blood cell levels of both AA and DHA are found to be decreased in infants fed artificial standard milk formula.¹³ However, supplementation with formula containing LC-PUFAs in amounts similar to that found in human breast milk leads to tissue LC-PUFA patterns similar to those found in breast-fed infants. In fact, a research review of breast fed infants and infants fed AA- and DHA-enriched formula indicated both feedings led to comparable AA and DHA levels in red blood cells and plasma.¹⁴ These effects may be attributed to DHA and AA’s role in altering fetal brain growth via benefits to neurotransmitters and even serotonin levels.¹⁵

Research indicates that pre-term, low-birth-weight infants would benefit from DHA- and AA-enriched formula when mother’s milk is not available post-discharge since the endogenous production of these important compounds from their respective precursors can be reduced in the first months of life.¹⁶ In similar research, researchers in Munich, Germany, reported formula enriched with both omega-3 and -6 LC-PUFAs had the same effects as mother’s milk in pre-term infants.¹⁷ However, the addition of highly polyunsaturated fatty acids to infant formulas raises the possibility of increased lipid peroxidation. Using an animal model, Hungarian researchers fed piglets DHA and AA at levels that were one-fold, two-fold and fivefold of that seen in infant formulas, all containing equal amounts of vitamin E. The results showed dietary vitamin E effectively prevented lipid peroxidation.¹⁸

In another condition associated with motherhood, observational studies suggest an association exists between low DHA status after pregnancy and the occurrence of postpartum depression. Researchers compared the biochemical plasma DHA status among women with and without postpartum depression. It was found that the availability of DHA in the postpartum period is less in women developing depressive symptoms.¹⁹

Omega-3s could improve short-term major depression, too. Patients with depression have been reported to have low levels of EPA and DHA in red blood cell membranes, plasma and dietary intake. In an eight-week trial, researchers out of Taiwan found patients with major depression experienced a significant improvement in symptoms compared to those on placebo.²⁰

Just as they’re important for a mother’s emotional well-being, EFAs are also important for a child’s eye health. Researchers giving women either fish oil capsules rich in DHA or placebo from week 15 of pregnancy until delivery reported that at 50 and 66 weeks postconceptional age, infants with higher DHA status showed more maturation in terms of central visual pathways.²¹

DHA may also help retinal health. In a study investigating the effect of dietary intake of specific types of fatty acids on retinal degeneration, the affliction was seen to be prevented in rats fed a diet that was 9.5-percent DHA.²²

A study of LA and GLA—both precursors of series 1 prostaglandins—indicated they induced tear production after photorefractive keratectomy (a surgery that reduces nearsightedness).²³ Researchers found supplementation reduced corneal sensitivity, which could be the main reason for a decrease in tear production and for a reduced blinking rate.

Just as EFAs help with the degeneration of eye health, so do they with joint and bone health. Researchers postulated altering the fatty acid content of the diet could modify some of these effects with the same power as NSAIDs. They suggested a diet rich in evening primrose oil, which elevates concentrations of DGLA, could result in the production of series 1 prostaglandins. Increasing DGLA intake may allow DGLA to act as a competitive inhibitor of series 2 prostaglandins and leukotrienes, thus suppressing inflammation.²⁴

Tumor necrosis factor-alpha has been shown to be a central mediator of inflammatory and joint destructive processes in rheumatoid arthritis. Research indicates borage oil’s GLA increases prostaglandin E levels, which in turn suppress tumor necrosis factor-alpha synthesis.²⁵

Research has also shown that bone is sensitive to changes in dietary omega-3 intake, and that DHA is more effective than ALA (as flaxseed oil) in maintaining DHA levels in bone tissue.²⁶

Cancer is another condition linked with fatty acid intake. Marinederived fatty acids are known to inhibit proliferation or induce cell death in several cancer cell lines, according to researchers at the University of Oslo, Norway.²⁷ In fact, EPA has shown an antiproliferative effect on the three types of cancer cell lines: urothelium, breast and colon.²⁸

EPA also has been seen to reduce a range of early cancer markers, such as sunburn, indicating it protects against acute UVR induced genotoxicity—and possibly skin cancer in humans. In a study of healthy subjects taking 4 g/d of purified EPA for three months, skin levels of EPA showed an eight-fold rise from baseline, and sunburn sensitivity was reduced in those using EPA.²⁹

DHA, in particular, may be useful against colon cancer. In a rat model, animals fed a high-fat golden algae oil (high in DHA) experienced a 90-percent inhibition in tumor growth compared to those consuming low-fat corn oil, high-fat corn oil or high-fat menhaden oil.³⁰ (Martek Biosciences Corp in Columbia, Md., provided the DHA for the study.) Some EFAs appear to work in tandem with cancer therapies.

For example, EPA may be useful for the treatment of tamoxifenresistant breast cancer cells. Co-treatment with EPA and tamoxifen, a cancer-prevention drug, made breast cancer cells 35- percent more responsive to the inibitory effects of the drug.³¹ In an investigation of possible interactions between GLA and the chemotherapeutic drug 5-fluorouracil (5-FU) against pancreatic cancer cell lines in vitro, researchers found there was a synergy between GLA and 5-FU.³² In addition, daily GLA-rich evening primrose oil supplementation reduced the sensitivity of skin to radiation side effects, including preventing the radiationassociated increase in blood flow that was observed in this tissue; however, it did not alter tumor sensitivity to radiation.³³

A Final Word on EFAs

Not only should fats not be feared, but consumers should also be aware of how to choose the product that’s right for them. According to Randy Wysong, president of the Midland, Mich.- based Wysong Corp., retailers should remind their customers that the typical diet is filled with processed fats, rendering them both non-nutritive and toxic. “Fats are not a dietary enemy,” he said.

“They are a savior if eaten in the right form. Fats are the preferred energy source for the body, and fats perform a broad range of important structural and metabolic effects to help prevent the plethora of modern degenerative diseases.”

Wysong also said heat, light and air degrade EFAs, and proper packaging and antioxidant methods are important for keeping these fats efficacious. According to Andreas Papas, Ph.D., founder and president of Yasoo Health, taking polyunsaturated fatty acids increases the need for antioxidants, such as vitamin E. “This has been known for a long time,” he said. “These fats are very prone to oxidation and becoming rancid. Not only does it keep it fresh in the softgel, but for providing extra vitamin E to the body.”

Parris Kidd, Ph.D., technical consultant to Carlsbad, Calif.-based Science and Ingredients Inc., also touted the benefits of EFAs and antioxidants. “The antioxidants and healthy fats are crucial for the prevention of disease and healthy aging. There is a functional association and synergism between the healthy fats and antioxidants,” he said. “To get the full benefits of the fats, you need antioxidants because they protect the fats.”

Kidd added, “Most of the processes of life occur on cell membranes, and it is these healthy fats, as part of phospholipids, that make up cell membranes and keep people metabolically efficient.”

The Alphabet Soup of EFAs References

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21.. Malcolm CA et al. "Maternal docosahexaenoic acid supplementation during pregnancy and visual evoked potential development in term infants: a double blind, prospective, randomised trial." Arch Dis Child Fetal Neonatal Ed. 88, 5:F383-90, 2003.
22.. Moriguchi K et al. "Dietary docosahexaenoic acid protects against N-methyl-N-nitrosourea-induced retinal degeneration in rats." Exp Eye Res. 77, 2:167-73, 2003.
23.. Macri A et al. "Effect of linoleic acid and gamma-linolenic acid on tear production, tear clearance and on the ocular surface after photorefractive keratectomy." Graefes Arch Clin Exp Ophthalmol. 241, 7:561-6, 2003.
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34. Thom E, et al. "Conjugated linoleic acid reduces body fat in healthy exercising humans." J Int Med Res. 29, 5:392-6, 2001. 
35 Cheng JL et al. "Dose response study of conjugated fatty acid derived from safflower oil on mammary and colon carcinogenesis pretreated with 7,12-dimethylbenz[a]anghracene (DMBA) and 1,2-dimethylhydrazine (DMH) in female Sprague-Dawley rats." Cancer Lett. 196, 2:161-8, 2003. 
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39. A presentation by Argus Research presented at the Phytomedicine Society, March 2003.

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