Gamma-linolenic acid as a dietary supplement

DEFINITION: Natural substance essential for health and promoted as a dietary supplement for specific health benefits.

• PRINCIPAL PROPOSED USE: Diabetic neuropathy
• OTHER PROPOSED USES:
• PROBABLY NOT EFFECTIVE USE: Eczema

Overview

Gamma-linolenic acid (GLA) is one of the two main types of essential fatty acids. These are good fats that are as necessary as vitamins for health. Specifically, GLA is an omega-6 fatty acid. The body uses essential fatty acids to make various prostaglandins and leukotrienes. These substances influence inflammation and pain—some increase symptoms, while others decrease them. Taking GLA may swing the balance to the more favorable prostaglandins and leukotrienes, making it helpful for diseases that involve inflammation.

There is some evidence that GLA may be helpful for diabetic neuropathy. The supplement is widely used in the United Kingdom and other parts of Europe to treat eczema and cyclic mastalgia (a condition marked by breast pain associated with the menstrual cycle). Evidence, however, suggests that it may not help. There are many other proposed uses of GLA based on fairly weak evidence.

Requirements and Sources

The body ordinarily makes all the GLA it needs from linolenic acid, an omega-6 essential fatty acid found in many foods. In certain circumstances, however, the body may not be able to convert linolenic acid to make GLA efficiently. These circumstances include advanced age, diabetes, high alcohol intake, eczema, cyclic mastitis, viral infections, excessive saturated fat intake, elevated cholesterol levels, and deficiencies of vitamin B₆, zinc, magnesium, biotin, or calcium. In such cases, taking GLA supplements may make up for a genuine deficiency.

A small amount of GLA is found in the diet. Borage oil is the richest supplemental source (17 to 25 percent GLA), followed by black currant oil (15 to 20 percent) and evening primrose oil (7 to 10 percent). Borage and evening primrose are the most common sources used in studies.

It is commonly stated that people require a certain optimum ratio of omega-3 to omega-6 fatty acids in the diet; however, there is no real evidence that this is true, and some evidence that it is false.

Therapeutic Dosages

The typical dosage of GLA when it is used in hopes of alleviating cyclic mastalgia or eczema is about 200 to 400 milligrams (mg) daily (about 2 to 4 grams [g] of evening primrose oil or 1 to 2 g of borage oil). Diabetic neuropathy is typically treated with about 400 to 600 mg daily (about 4 to 6 g of evening primrose or 2 to 3 g of borage oil). In rheumatoid arthritis, doses as high as 2 to 3 thousand mg have been tried. (Doses this high can only be obtained from purified GLA, as one would need impractically high doses of evening primrose oil or borage oil to get enough.)

GLA should be taken with food. Full benefits (if there are any) may take more than six months to develop.

Therapeutic Uses

GLA has shown some promise for the treatment of diabetic neuropathy, a complication of diabetes. This condition consists of pain and numbness caused by progressive nerve damage. However, supporting evidence that GLA is effective for this use is quite limited.

Perhaps the most common use of GLA has been as a treatment for eczema. It was once widely dispensed for this purpose by the British healthcare system, but the balance of the evidence indicates that for eczema, GLA is just a placebo treatment.

GLA is also a popular treatment for cyclic mastalgia, but the evidence regarding its effectiveness is more negative than positive. GLA is additionally said to be useful for general premenstrual syndrome (PMS) symptoms, but the supporting evidence for this use is very weak.

Despite many positive anecdotes, GLA has failed to prove effective for attention deficit hyperactivity disorder (ADHD). One study that used GLA plus fish oil did find weak evidence of benefits. Weak evidence hints that evening primrose oil might be more effective for ADHD if combined with zinc, but this is more of an untested hypothesis than a conclusion.

GLA has been studied for numerous other conditions, such as rheumatoid arthritis, Raynaud’s phenomenon (a condition in which the fingers and toes react to cold in an exaggerated way), weight loss, ulcerative colitis, kidney stones, multiple sclerosis, indomethacin-induced gastric ulcers (in rats), and increasing the effectiveness of the drug tamoxifen in the treatment of breast cancer. Persons undergoing cancer treatment should not take GLA (or any other supplement) except under physician supervision.

Other studies have investigated the potential benefits of combination treatment using GLA and fish oil. Conditions studied include osteoporosis, chronic fatigue syndrome, periodontitis (gum disease), and Huntington’s disease. In these trials, some promising (but far from definitive) results have been seen. However, this combination therapy failed to prove effective for cyclic mastalgia.

GLA is sometimes suggested as a treatment for tardive dyskinesia, but two double-blind studies have failed to find it helpful for this disorder. GLA has also failed to prove effective for the itching caused by kidney dialysis.

There is some evidence that GLA may benefit people with eye problems. One randomized trial indicated that orally administered evening primrose oil was more effective than olive oil (placebo) at reducing dry eye symptoms and improving comfort in users of soft contact lenses. In addition, Sjögren’s syndrome, an autoimmune condition in which the immune system destroys moisture-producing glands, often causes dry eyes because of a lack of tears. One small double-blind study found that a combination of GLA and the omega-6 fatty acid linolenic acid (found in many vegetable oils) may improve dry eye symptoms in Sjögren’s. Finally, persons who undergo laser surgery for vision correction (photorefractive keratectomy) are sometimes left with a hazy appearance to their cornea. Another small randomized trial found some potential benefits of a supplement containing omega-6 fatty acids in preventing this complication.

Only a fraction of the conditions for which GLA has been proposed as a treatment have been discussed here. Other conditions include asthma, allergies, bursitis, endometriosis, heart disease, irritable bowel syndrome, prostate cancer, benign prostatic hyperplasia, and Sjögren’s disease. However, none of these potential uses have been scientifically evaluated to a statistically significant extent.

Scientific Evidence

Diabetic neuropathy. Diabetic neuropathy is a gradual degeneration of nerves caused by diabetes. There is some evidence that GLA can be helpful if it is given time to work. In one double-blind, placebo-controlled study, 111 people with mild diabetic neuropathy received 480 mg daily of either GLA or a placebo. After twelve months, the group taking GLA was doing significantly better than the placebo group. Good results were seen in a smaller study, too. However, these promising findings lack further research validation. There is some preliminary evidence that GLA may be more effective for diabetic neuropathy when it is combined with lipoic acid.

Eczema. Despite GLA (usually as evening primrose oil) being widely used in Europe to treat eczema, the treatment is unlikely to be effective. The anecdotes of cure that abound are likely testimonials to the placebo effect (and to a strong marketing campaign by one evening primrose oil supplier).

A 1989 review of the literature found significant benefits in the nine double-blind controlled studies performed to that date, all involving evening primrose oil. This study led to widespread sales of one evening primrose oil product. However, this review has been sharply criticized for including poorly designed studies and for possibly misinterpreting study results.

Improvements in symptoms were also seen in a later double-blind study of forty-eight children with eczema. However, other research failed to find any benefit. For example, a sixteen-week, double-blind study involving fifty-eight children with eczema found no difference between the effects of evening primrose oil and the placebo (substantial improvements were seen but to the same extent for the placebo and evening primrose oil). Lack of specific benefit was also seen with evening primrose oil or evening primrose oil plus fish oil in a sixteen-week, double-blind, placebo-controlled study of 102 persons with eczema. Finally, a double-blind trial followed thirty-nine people with hand dermatitis for twenty-four weeks; it again found no greater benefits than those produced by the placebo.

GLA taken orally from borage oil has also failed to prove effective. In a twenty-four-week, double-blind study of 160 adults with eczema, the treatment provided no greater benefits than the placebo. The same was seen in a twelve-week, double-blind, placebo-controlled study of 151 adults and children with eczema. Finally, in a double-blind, placebo-controlled study of 118 infants at high risk for developing eczema, a GLA supplement made from borage oil failed to provide a significant protective effect.

However, a double-blind study tested the use of undershirts coated with borage oil for the treatment of eczema. In this two-week study of thirty-two children aged one to ten years, these coated undershirts appeared to reduce eczema symptoms. However, additional, higher-quality research studies need to be undertaken to establish whether or not this method of delivery works.

Cyclic mastalgia. Cyclic mastalgia, also known as fibrocystic breast disease, cyclic mastitis, and mastodynia, is a condition in which a woman’s breasts become painful during the week or two before her menstrual period. The discomfort is accompanied by swelling, inflammation, and sometimes actual cysts that form in the breasts. It is often associated with other PMS symptoms.

The cause of cyclic mastalgia is not known, but some researchers believe that it is associated with an imbalance of fatty acids in the body. On this basis, evening primrose oil became a popular treatment for cyclic mastalgia. However, there are considerable doubts regarding whether it is effective.

The main supporting evidence comes from three controlled studies that appeared to find benefits. All these studies had significant limitations in design and reporting and cannot be taken as reliable. A better-quality study found that evening primrose oil, by itself or with fish oil, is not more effective than the placebo for cyclic breast pain. A randomized trial involving eighty-five women also did not support the effectiveness of evening primrose (alone or with vitamin E) for treating breast pain. Other studies have found evening primrose oil ineffective for established breast cysts.

Other premenstrual symptoms. Although several small studies suggest that GLA as evening primrose oil helps reduce overall PMS symptoms, all these studies had serious flaws that make the results difficult to trust.

Rheumatoid arthritis. According to many studies, fish oil, a source of omega-3 essential fatty acids, improves symptoms of rheumatoid arthritis. A few studies suggest that GLA may also help. One six-month double-blind study followed fifty-six people with rheumatoid arthritis. Participants received either 2.8 g daily of purified GLA or the placebo. The group taking GLA experienced significantly fewer symptoms than the placebo group, and the improvements grew over time.

Other small studies have found similar results. The overall conclusion indicates that purified GLA might offer some benefit for rheumatoid arthritis, especially when used with standard treatment for rheumatoid arthritis, but the evidence is weak.

Raynaud’s phenomenon. High doses of evening primrose oil may be useful for Raynaud’s phenomenon, a condition in which a person’s hands and feet show abnormal sensitivity to cold temperatures. A small double-blind study found that GLA produced significantly better results than the placebo. Similar results have been obtained with the omega-3 fatty acids found in fish oil. However, larger studies would be necessary to establish effectiveness.

Osteoporosis. There is some evidence that essential fatty acids may enhance the effectiveness of calcium for the treatment or prevention of osteoporosis. In one study, sixty-five postmenopausal women were given calcium with either a placebo or a combination of omega-6 fatty acids (from evening primrose oil) and omega-3 fatty acids (from fish oil) for eighteen months. At the end of the study period, the group receiving essential fatty acids had higher bone density and fewer fractures than the placebo group. However, a twelve-month, double-blind trial of forty-two postmenopausal women found no benefit.

The explanation for the discrepancy may lie in the differences between the women studied. The first study involved women living in nursing homes, while the second studied healthier women living on their own. The latter group of women may have been better nourished and might already have been receiving enough essential fatty acids in their diet.

Attention deficit hyperactivity disorder (ADHD). Based on evidence that essential fatty acids are necessary for the proper development of brain function in growing children, essential fatty acids have been tried for the treatment of ADHD and related conditions. A preliminary double-blind, placebo-controlled trial found some evidence that a supplement containing fish oil and evening primrose oil might improve ADHD symptoms. However, a high rate of dropouts makes the results of this study unreliable. A repeat study found this combination no better than the placebo.

Evening primrose oil by itself was found to be no better than the placebo in a double-blind, placebo-controlled trial. In another small placebo-controlled, comparative trial, evening primrose oil proved less effective than standard medical treatment.

Weight loss. A twelve-week, double-blind study that enrolled one hundred significantly overweight women compared the effectiveness of evening primrose oil to the placebo. No difference was seen between the groups. However, there was a high dropout rate in this trial (more than 25 percent), which somewhat decreased the meaningfulness of the results. Additionally, many participants were known to have “refractory obesity,” meaning that they had already failed to respond to other forms of treatment.

Another double-blind trial involving forty-seven people tested the unusual hypothesis that evening primrose might only work in persons with a family history of obesity. The results showed that the use of evening primrose oil produced a small but significant loss of weight. Participants whose parents were obese showed even better responses. Similarly, in a randomized, double-blind, placebo-controlled trial investigating the impact of using borage oil rich in gamma-linolenic acid for weight loss in postmenopausal women with hypertension, results indicated positive, short-term results. However, considering the contradictory nature of this evidence, more research is necessary to determine whether evening primrose oil is useful for weight loss.

Safety Issues

Most of the safety information on GLA comes from experience with evening primrose oil. Animal studies suggest that evening primrose oil is completely nontoxic and noncarcinogenic. Thousands of people have taken GLA or evening primrose oil in scientific studies, and no significant adverse effects have been consistently noted. Early reports suggested GLA might worsen temporal lobe epilepsy, but this finding was not confirmed. The maximum safe dosage of GLA for young children, pregnant or nursing women, or those with severe liver or kidney disease has not been established. Individuals should consult a medical professional before beginning to take any supplement.

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