Life Extension Magazine January 2011
The Beneficial Omega-6 Fatty Acid
By Kirk Stokel
Most health-conscious people already know about the broad-spectrum benefits of omega-3 fatty acids, particularly EPA/DHA from fish and other sources.
The typical American diet, however, contains too much omega-6 fatty acids. Health-conscious individuals try to reduce this type of fat in their diet. Sources of excess omega-6s include most vegetable oils such as corn oil, safflower oil, soybean oil, as well as poultry and eggs.
There is one omega-6, however, called gamma linolenic acid (GLA) with an impressive set of disease-fighting powers. New research reveals this nutrient’s power to combat chronic inflammation, eczema, dermatitis, asthma, rheumatoid arthritis, atherosclerosis, diabetes, obesity—even cancer!1-8
Most people don’t obtain sufficient quantities of it owing to dietary deficiency, and also because the enzyme in the body governing its metabolism becomes less active with age.9
In this article, we uncover the latest research on gamma linolenic acid and provide compelling evidence for its ability to combat a range of chronic age-related disorders—alone and in combination with EPA/DHA.
GLA: An Anti-Inflammatory Essential Fat
GLA (gamma linolenic acid) is a plant-derived omega-6 most abundant in seeds of an Eastern flower known as borage.1,10,11 Although a member of the omega-6 family, it’s metabolized differently than other omega-6s.
Our modern Western diet is rife with omega-6 fats and generally deficient in omega-3 fats, a fatal imbalance that sets in motion the inflammatory processes implicated in most killer diseases of aging.12-14
The threat this poses to aging humans is compounded by the aging process itself.
Aging results in defects occurring in human enzymes responsible for producing anti-inflammatory molecules from dietary fats. The result is an increased risk for inflammatory conditions of all kinds. Supplemental GLA can counteract this acquired enzyme defect, supplying vital biochemical precursors with powerful anti-inflammatory effects.
By converting into beneficial prostaglandins (PGE1s), GLA compensates for this deficiency.15,16 The results can be a profound reduction in the impact of inflammation on cardiovascular disease, lung function, autoimmune conditions, and metabolic abnormalities including diabetes.17-20
Another way GLA exerts a beneficial effect is to compete with harmful arachidonic acid or AA. When one eats foods like meat or egg yolk, excess levels of arachidonic acid accumulate that is then broken down into toxic byproducts by the enzymes cyclooxygenase-2 (COX-2) and lipoxygenase (LOX). GLA inhibits these destructive enzymes, thus impeding the ability of AA to convert to detrimental inflammatory molecules (like leukotriene B4).1
GLA plays an important role in modulating inflammation throughout the body, especially when incorporated into the membranes of immune system cells.18,21 Early in 2010, a team of Taiwanese researchers discovered that GLA regulates the inflammatory “master molecule” nuclear factor-kappaB or NF-kB, preventing it from switching on genes for inflammatory cytokines in cell nuclei.22
A separate mechanism by which GLA and other beneficial fatty acids reduce inflammation is by activating the powerful peroxisome proliferator-activated receptor (PPAR) system.23 PPARs are intracellular receptors that modulate cell metabolism and responses to inflammation. The class of antidiabetic drugs called thiazolidinediones (such as Actos® or pioglitazone) acts by targeting PPARs—but unlike GLA, they can be deadly.24
Novel Cardiac Defense
Atherosclerosis is in large part the result of chronic, low-grade inflammation.25 The GLA-producing enzyme delta 6-desaturase (D6D) declines with advancing age and stress. Some experts believe that this may both partially explain the age-related increase in atherosclerosis and indicate GLA as an attractive intervention to reduce arterial disease risk by bypassing this enzymatic defect.26 When incorporated into membranes of platelets, white blood cells, and endothelial cells, GLA works via multiple mechanisms to shift the cardiovascular system back towards its natural, non-inflamed state.27
In both human and animal studies, GLA reduces the tendency of platelets to aggregate, or clump together, within small blood vessels.28,29 This activity is related to its effect of reducing activity of thromboxane, a signaling molecule involved in blood clotting, and may be helpful in reducing the risk of heart attack and strokes.19,29 Laboratory research shows that cholesterol-induced stimulation of platelet aggregation, for example, is prevented with the addition of GLA.5
GLA also shows promise in lowering low-density lipoprotein (LDL) and triglyceride levels, while increasing high-density lipoprotein (HDL) concentration.5,19 GLA supplementation reduced the formation of atherosclerotic plaques in rats fed a high-cholesterol diet, reducing total cholesterol and triglycerides and dramatically inhibiting oxidation of LDL, an important first step in atherosclerosis.30
In the middle stages of atherosclerosis, smooth muscle cells in vessel walls proliferate, stiffening arteries and making them less responsive to blood pressure and flow. Cells from animals supplemented with GLA inhibit that smooth muscle proliferation.31 And in atherosclerosis-prone mice, GLA supplementation markedly suppressed proliferation in the aorta, while reducing the size of atherosclerotic lesions.32
These combined, multitargeted effects account for GLA’s promise in combating systemic vascular disease. In combination with EPA, GLA has significantly reduced blood pressure in patients with peripheral arterial disease, a painful and potentially crippling set of conditions resulting from restricted blood flow in the extremities. The combination of GLA and EPA also produced a trend towards fewer coronary events.33
A diet containing a balanced mixture of omega-3s (EPA and DHA) plus GLA was able to lower blood pressure in spontaneously hypertensive rats, while simultaneously enhancing antioxidant status, diminishing platelet aggregation, and lowering plasma lipids.34
Combating Diabetes and Obesity
New research reveals a surprising link between GLA and diabetes.
A defect in the enzyme that converts dietary fatty acids to GLA may predispose people to develop insulin resistance (“pre-diabetes”), suggesting that GLA supplementation may be preventive.7 Rapidly accumulating data support this observation.
Animal studies reveal that GLA can prevent chemically-induced diabetes while restoring normal antioxidant status in tissues.35 It can also prevent diabetic neuropathy, a painful condition resulting from exposure of nerves to high glucose levels.36 Excitingly, treatment with GLA plus alpha-lipoic acid (ALA) in diabetic rats not only prevents diabetes-induced changes in certain kinds of nerve cells—it partially reverses the condition.37
In humans, GLA supplements (360 mg per day) for six months significantly improved symptoms of diabetic neuropathy; nerve conduction velocity was also dramatically increased.38,39 These effects are most prominent in individuals whose diabetes is well-controlled.40
Children with type 1 diabetes display evidence of increased inflammation at an early age; GLA produces significant reductions in the inflammatory prostaglandin PGE2 after 8 months.41 Adult diabetics supplemented with GLA, EPA, DHA, and vitamin E experienced an improvement in metabolism of platelet-activating thromboxanes, which may reduce the risk of diabetic cardiovascular complications.42
Obesity is a risk factor for diabetes, and worsens diabetic complications by contributing massive amounts of inflammatory mediators. A fascinating study from the University of California at Davis found that, in formerly obese people who had recently achieved major weight loss, GLA supplementation for one year slashed the amount of weight they regained (just under 5 pounds vs. more than 19 pounds in control patients).6
Potent Anticancer Intervention
As early as 1989, it was revealed that GLA could slow the growth of certain cancer cells in culture.43 A blend of omega-3s (EPA and DHA) plus GLA reduced levels of a host of inflammatory cytokines in patients with colon cancer, one of the many cancers that rely on inflammation to stimulate their growth.44
In pre-clinical models, prostate cancer growth was slowed with GLA as a result of reduced production of inflammatory prostaglandins.45 Growth of a human lung cancer implanted in mice was inhibited by 56% while the animals were on a GLA-enriched diet.46 Cell cultures of three human tumor lines completely stopped DNA synthesis (a requirement for continued growth) after GLA treatment.47 GLA increases brain cancer cells’ sensitivity to being killed by radiation treatments; the supplement also produced direct toxicity to cancer cells, but not to normal tissue.48-50 This could mean greater effectiveness of radiation treatment with fewer distressing side effects such as skin damage.51
Human results with GLA supplementation have been encouraging. Patients with pancreatic cancer, a malignancy with a uniformly dismal prognosis, experienced longer survival times after intravenous treatment with a lithium salt of GLA.8 These changes were shown to be related to a GLA-induced increase in blood flow to cancerous tissue, which may permit larger doses of chemotherapy to reach tumors.52
GLA treatment in breast cancer has had remarkable results, now being included along with tamoxifen as an adjuvant therapy.53 And certain kinds of human leukemia cells can be induced to die by GLA treatment, which turns on the cells’ “suicide” enzymes.54 Leukemia cells resistant to chemotherapy drugs become vulnerable to drug treatment following exposure to GLA, which changes expression of several genes and causes the drugs to accumulate in high levels in the diseased cells.55
We now know that GLA inhibits tumor growth and spread through a host of interrelated mechanisms.56 As is always the case, however, the evidence suggests that GLA supplementation is much more effective used as prevention than as treatment after cancer has developed.57,58
Eliminating Eczema and Atopic Dermatitis
Eczema is an inflammatory skin condition characterized by dryness and flaking of the upper skin layers, with redness, itching, and often pain of the skin beneath. Mild in many people, severe eczema sufferers experience chronic misery that can be debilitating, and that may respond only to fairly large doses of steroids, which can produce dangerous side effects. Many people with eczema also suffer from asthma and other conditions related to allergic responses—together these conditions are referred to as atopic conditions, which involve an immune response within the body. As with asthma, the global incidence of atopic eczema is rising at an alarming rate.59
Studies from 20 years ago first showed that people with eczema may have a defect in their bodies that inhibits their ability to form GLA naturally from the dietary source linoleic acid.2,60 Breast milk from mothers of children with newly developed atopic eczema was shown to have low levels of GLA and its metabolites, supporting this notion.61
Supplementation with GLA was immediately successful. Studies in both children and adults revealed less inflammation, dryness, scaling, and overall eczematic severity compared to controls.2,62,63
In parallel with these beneficial changes, significant changes in plasma fatty acid composition were also noted.2,63 Subsequent analyses showed that there was a positive correlation between improvements in clinical eczema scores and the rise in beneficial fatty acid levels.64 In addition, GLA supplementation produced an increase in the immune system “suppressor” cells known as CD8, adding another layer of protection against inflammation.65