Gamma-linolenic acid (GLA), eicosapentaenoic acid (EPA) and docosahexanaeoic acid (DHA) are arguably the most well-known and widely used fatty acid supplements. GLA is a conditionally essential, omega-6 fatty acid found in some plant seed oils such as borage, evening primrose and hemp oils, while EPA/DHA are omega-3 fatty acids commonly found in fish, krill and algal oils. Here I will address the value of these fatty acids, and potential advantages of their joint use.
The Value of These Fatty Acids
GLA’s value is that, in the body, it can be converted into a prostaglandin known as PGE1, which has anti-inflammatory, antithrombotic (i.e. reducing blood clot formation), anti-proliferative (i.e. inhibits growth of tumor cells), and lipid-lowering properties, while also enhancing smooth muscle relaxation and vasodilation.1 The benefits of EPA/DHA are too numerous to be discussed here in any detail, but include reducing the risk of atherosclerosis, increasing “good” HDL cholesterol, decreasing high blood pressure, reducing inflammation in such disorders as rheumatoid arthritis, asthma, colitis, Crohn’s disease and lupus—and reducing the symptoms of other disorders including angina, migraine headaches, psoriasis and tinnitus.2 While each of these fatty acids offer a range of benefits, some overlapping, there is good reason to consider concurrent supplementation with GLA and EPA/DHA—especially when considering the problematic pathway of GLA.
The Problematic Pathway of GLA
The problem is that GLA’s valuable properties may not end up being expressed for two reasons, both of which have to do with metabolic conversion processes. First, while GLA is not common in our food supply, the body is capable of converting linoleic acid (LA)—one of the most commonly occurring essential fatty acids—into GLA. However, the enzyme (delta-6-desaturase) that converts LA into GLA is hindered by numerous factors, including aging, nutrient deficiency, trans-fatty acids, hydrogenated oils, smoking to and excessive alcohol consumption and gastritis.3 In fact, research has shown that individuals with gastritis had significantly lower GLA levels than individuals without gastritis.4
The second problem is that GLA has to be converted into dihomo-gamma-linolenic acid (DGLA) before it can then be converted into PGE1 and provide all of its valuable properties. The issue is that DGLA can then go down two different pathways. One of those is being converted to PGE1, which is good. The other is that DGLA can be converted into arachidonic acid (AA), which in turn can be converted into PGE2—an inflammatory prostaglandin that has the opposite effect of PGE1. Another possibility is that it can be converted to both PGE1 and PGE2, in which case it will have beneficial and detrimental effects at the same time.
Solution to the Two Problems
The first problem is easily solved by using a borage or evening primrose oil supplement, which already provides GLA without the metabolic requirement of first converting it from LA. There is also a way to solve the second problem, and mitigate the ultimate conversion of GLA to AA, and subsequently to PGE2: use an omega-3 fatty acid rich fish oils at the same time as taking a GLA supplement.
In a clinical study,5 42 healthy adults took 1.5 g/day of GLA, which increased plasma levels of AA—not a good thing. However, 250 mg or 1 g of EPA included along with the GLA prevented the increase in plasma AA concentrations. In another clinical study,6 adult subjects took 3.0 g/day of GLA and EPA. The results were that EPA levels were significantly increased, as were DGLA levels—but AA levels did not increase. The researchers concluded, “This study revealed that a GLA and EPA supplement combination may be utilized to reduce the synthesis of pro-inflammatory AA metabolites, and importantly, not induce potentially harmful increases in serum AA levels.” Similar results were seen in other research.7
In addition to mitigating the potential formation of inflammatory PGE2, there are other specific situations, which may benefit from the concurrent use of GLA and EPA/DHA. These include asthma, metabolic syndrome/diabetes, acne, cognitive development, cystic fibrosis, high triglycerides, high blood pressure and osteoporosis.
Leukotrienes are additional inflammatory mediators, which are produced by the oxidation of AA. Inhibiting leukotriene synthesis is also an effective means to help treat asthma. In a randomized, prospective, double-blind, placebo-controlled, parallel group trial,8 patients with mild-to-moderate asthma were treated with 0.75 g GLA + 0.5 g EPA (low dose), 1.13 g GLA + 0.75 g EPA (high dose) or placebo daily. The results were that leukotriene synthesis decreased (p < 0.05) and self-reported asthma status and bronchodilator use improved in subjects consuming low- and high-dose treatments between week 2 and week 4 (p < 0.01). Similar studies in asthma patients also demonstrated that low and high dose treatments with these fatty acids reduced leukotriene synthesis9 and improved patient perceived, quality of life and asthma management as evidenced by reduced asthma symptoms.10
Fifty-nine subjects with early-stage type-2 diabetes or metabolic syndrome (prediabetes) participated in an eight-week, randomized, single-blind, parallel intervention study11 where they received either corn oil (CO), a GLA-rich borage oil with echium oil (BO) or an EPA/DHA-rich fish oil (FO). The results were as follows: Participants in the CO group showed no improvements, whereas supplementation with BO significantly lowered total and LDL cholesterol levels, while supplementation with FO reduced serum triglycerides, hemoglobin A1c (a marker for long-term glucose control), and increased HDL-cholesterol. Researchers concluded that short-term dietary supplementation with BO and FO improved biomarkers associated with type-2 diabetes/metabolic syndrome.
In a 10-week, randomized, controlled parallel dietary intervention study,12 45 participants with mild to moderate acne received either omega-3 fatty acids as 2 g EPA and DHA, borage oil containing 400 mg GLA, or a control (placebo). The results were that omega-3 fatty acids and borage oil supplementation both significantly decreased inflammatory and non-inflammatory acne lesions. No severe adverse effect was reported. This study showed for the first time that omega-3 fatty acids and GLA were effective adjuvant treatments for acne patients.
In a randomized, placebo-controlled trial,13 409 children (aged 3-13) were given a supplement with 750 mg DHA plus EPA and 60 mg GLA/school day or a placebo for 20 school weeks. The results were that children using the supplement showed improvements in non-verbal cognitive development compared with the placebo, with strongest effects in 7-12 year olds (p=0.008). The placebo group showed significant within-group improvements after switching to treatment (p<0.001).
Chronic inflammation plays a major role in lung deterioration in cystic fibrosis (CF) patients and anti-inflammatory strategies have beneficial effects. To study14 the changes seen after a one-year course of low-dose dietary supplements with a mixture of fatty acids in 17 adult patients with CF in chronic inflammation, pulmonary status (lung function, respiratory exacerbations and antibiotic consumption), quality of life and anthropometric parameters, subjects received 324 mg of EPA, 216 mg of DHA, 480 mg of LA and 258 mg of GLA daily. Results were that at the end of the treatment period TNF alpha levels and other inflammatory markers fell significantly and spirometry (a breath measure test of lung function) improved significantly. Annual respiratory exacerbations and days of antibiotic treatment also fell significantly. Furthermore fat-free mass and hand grip dynamometry improved significantly. These results led the researchers to conclude that low-dose supplements of EPA/DHA and GLA over a one-year period improved pulmonary status, inflammatory and anthropometric parameters in adults with CF.
To determine the effects of different levels of GLA supplementation together with EPA plus DHA, or EPA plus DHA alone on triglyceride levels, a 28-day study15 was conducted with 31 women were assigned to one of four supplement groups: 4 g EPA+DHA (4:0, control group), 4 g EPA+DHA plus 1 g GLA (4:1), 4 g EPA+DHA plus 2 g GLA (4:2), or 4 g EPA+DHA plus 4 g GLA (4:4) daily for 28 d. The result were that triglyceride levels were significantly lower on day 28 than on day 0 in the 4 g EPA+DHA group, the 4 g EPA+DHA plus 1 g GLA group, and the 4 g EPA+DHA plus 2 g GLA group. LDL cholesterol decreased significantly (by 11.3 percent) in the 4 g EPA+DHA plus 2 g GLA group. The researchers concluded that 4 g EPA+DHA and 2 g GLA favorably altered blood lipid and fatty acid profiles in healthy women, and was estimated to have a 43 percent reduction in the 10-year risk of myocardial infarction.
High Blood Pressure
A two-year, randomized, placebo-controlled trial16 was conducted to determine the cardiovascular benefits associated with GLA and EPA supplementation or placebo in 75 men and women with lower-limb atherosclerosis (i.e. stable intermittent claudication). The results were that systolic blood pressure was significantly lower after 2 years (150|mmHg compared with 161.8|mmHg, </= 0.05), and there was a reduction in non-fatal coronary events in the fatty acid group (10 percent compared with 15 percent, P > 0.05).
A pilot study17 was set up to test the interactions between calcium and GLA + EPA in humans. Sixty-five women (mean age 79.5) with a low calcium diet were randomly assigned to GLA + EPA or coconut oil placebo capsules. All subjects also received 600 mg/day calcium as calcium carbonate. Results showed that, over the first 18 months, lumbar spine density remained the same in the treatment group, but decreased 3.2 percent in the placebo group. Femoral bone density increased 1.3 percent in the treatment group, but decreased 2.1 percent in the placebo group. During the second period of 18 months with all patients now on active treatment, lumbar spine density increased 3.1 percent in patients who remained on active treatment, and 2.3 percent in patients who switched from placebo to active treatment; femoral BMD in the latter group showed an increase of 4.7 percent. This pilot controlled study suggests that GLA and EPA have beneficial effects on bone in this group of elderly patients, and that they are safe to administer for prolonged periods of time.
The concurrent use of GLA with EPA/DHA is well advised to help reduce the potential conversion of GLA to AA and ultimately to the inflammatory prostaglandin PGE2. Furthermore, the combination of GLA and EPA/DHA may offer a range of additional benefits as discussed in this article. VR
1 Mayes P. Metabolism of unsaturated fatty acids and eicosanoids. In: Murray R, Granner D, Mayes P, Rodwell, V, eds. Harper’s Biochemistry. 24th ed. Stamford, CT: Appleton & Lange; 1996:236-244.
2 Bruno G. Omega-3 Fatty Acids. Smart Supplementation Knoxville, TN: Huntington College of Health Sciences; 2009.
3 Gamma-Linolenic Acid Monograph. Altern Med Rev. 2004;9(1):70-78.
4 Ito Y, Suzuki K, Imai H, et al. Effects of polyunsaturated fatty acids on atrophic gastritis in a Japanese population. Cancer Letters 2001; 163:171-178.
5 Surette ME, Koumenis IL, Edens MB, Tramposch KM, Chilton FH. Inhibition of leukotriene synthesis, pharmacokinetics, and tolerability of a novel dietary fatty acid formulation in healthy adult subjects. Clin Ther. 2003 Mar; 25(3): 948-71.
6 Barham JB, Edens MB, Fonteh AN, Johnson MM, Easter L, Chilton FH. Addition of eicosapentaenoic acid to gamma-linolenic acid-supplemented diets prevents serum arachidonic acid accumulation in humans. J Nutr. 2000 Aug; 130(8): 1925-31.
7 Miles EA, Banerjee T, Calder PC. The influence of different combinations of gamma-linolenic, stearidonic and eicosapentaenoic acids on the fatty acid composition of blood lipids and mononuclear cells in human volunteers. Prostaglandins Leukot Essent Fatty Acids. 2004 Jun; 70(6): 529-38.
8 Surette ME, Stull D, Lindemann J. The impact of a medical food containing gammalinolenic and eicosapentaenoic acids on asthma management and the quality of life of adult asthma patients. Curr Med Res Opin. 2008 Feb; 24(2):559-67.
9 Surette ME, Koumenis IL, Edens MB, Tramposch KM, Clayton B, Bowton D, Chilton FH. Inhibition of leukotriene biosynthesis by a novel dietary fatty acid formulation in patients with atopic asthma: a randomized, placebo-controlled, parallel-group, prospective trial. Clin Ther. 2003 Mar; 25(3): 972-9.
10 Lindemann J, David Pampe E, Peterkin JJ, Orozco-Cronin P, Belofsky G, Stull D. Clinical study of the effects on asthma-related QOL and asthma management of a medical food in adult asthma patients. Curr Med Res Opin. 2009 Dec; 25(12): 2865-75.
11 Lee TC, Ivester P, Hester AG, Sergeant S, Case LD, Morgan T, Kouba EO, Chilton FH. The impact of polyunsaturated fatty acid-based dietary supplements on disease biomarkers in a metabolic syndrome/diabetes population. Lipids Health Dis. 2014 Dec 16; 13:196.
12 Jung JY, Kwon HH, Hong JS, Yoon JY, Park MS, Jang MY, Suh DH. Effect of dietary supplementation with omega-3 fatty acid and gamma-linolenic acid on acne vulgaris: a randomised, double-blind, controlled trial. Acta Derm Venereol. 2014 Sep; 94(5): 521-5.
13 Parletta N, Cooper P, Gent DN, Petkov J, O’Dea K. Effects of fish oil supplementation on learning and behaviour of children from Australian Indigenous remote community schools: a randomised controlled trial. Prostaglandins Leukot Essent Fatty Acids. 2013 Aug; 89(2-3): 71-9.
14 Olveira G, Olveira C, Acosta E, Espíldora F, Garrido-Sánchez L, García-Escobar E, Rojo-Martínez G, Gonzalo M, Soriguer F. Fatty acid supplements improve respiratory, inflammatory and nutritional parameters in adults with cystic fibrosis. Arch Bronconeumol. 2010 Feb; 46(2): 70-7.
15 Laidlaw M, Holub BJ. Effects of supplementation with fish oil-derived n-3 fatty acids and gamma-linolenic acid on circulating plasma lipids and fatty acid profiles in women. Am J Clin Nutr. 2003 Jan; 77(1): 37-42.
16 Leng GC, Lee AJ, Fowkes FG, Jepson RG, Lowe GD, Skinner ER, Mowat BF. Randomized controlled trial of gamma-linolenic acid and eicosapentaenoic acid in peripheral arterial disease. Clin Nutr. 1998 Dec; 17(6): 265-71.
17 Kruger MC, Coetzer H, de Winter R, Gericke G, van Papendorp DH. Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging (Milano). 1998 Oct; 10(5): 385-94.
Gene Bruno, MS, MHS, the dean of academics for Huntington College of Health Sciences, is a nutritionist, herbalist, writer and educator. For more than 30 years he has educated and trained natural product retailers and health care professionals, has researched and formulated natural products for dozens of dietary supplement companies, and has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications. He can be reached at firstname.lastname@example.org.