Omega-6 fatty acids

The main ω-6 acid, linoleic, is abundant in the diet today. Although it is essential and we have to take it in with food, we feel that we should not think about it too much as in the case of ω-3 acids which are deficient in the diet. Among ω-6 acids, there is one small health trump card, γ-linolenic acid, which is why started loving evening primrose and borage oil, but also hemp in the diet. Its anti-inflammatory mechanism is paradoxical. From atopy, dry skin, painful menstruation to menopausal discomfort, the culture of taking γ-linolenic acid is extremely popular. Fortunately. But in rheumatoid arthritis where high doses of γ-linolenic acid are most beneficial, we really failed in recommendations. Oils like purple viper’s-bugloss and black currant seeds, who knows, may be the heirs of the older generation of borage and evening primrose.

Oils rich in γ-linolenic acid

ϒ-linolenic acid is conditionally essential ω-6 acid, contained in oils such as borage (Borago officinalis), evening primrose (Oenothera biennis), purple viper’s-bugloss (Echium plantagineum), black currant (Ribes nigrum) and to a lesser extent hemp (Cannabis sativa ssp. sativa). Although we classify them in the same class, these vegetable oils are not identical in the composition of γ-linolenic acid and in the composition of other fatty acids, which has the consequence that they differ in the molecular mechanism of action.

Oilγ-linolenicα-linoleniclinoleicstearidonic
evening primrose7,0-14,0%max 0,5%65,0-85,0%-
borage17,0-27,0%max 0,5%30,0-41,0%-
black currant11,0-18,0%11,0-18,0%44,0-54,0%2,0-4,0%
purple viper's-bugloss 7,0-14,0%30,0-40,0%10,0-20,0%10,0-17,0%
hemp1,0-5,0%14,0-28,0%46,0-65,0%-

Oils rich in γ-linolenic acid (GLA) are most often used in rheumatoid arthritis, inflammatory skin diseases (atopic dermatitis, psoriasis), and menopausal problems, most often as additional nutritional measures.

Mechanism of action

Therefore, the profile of indications is completely different from those for ω-3 rich vegetable oils. Why? Let us recall the picture of fatty acid biosynthesis in the body.

biosinteza masnih kiselina u organizmu

In the picture we see that γ-linolenic acid is in the series is ω-6 acids, and is biosynthetically formed from linoleic acid by the action of Δ6 desaturase. It has already been said that the activity of this enzyme is limited. Therefore, the addition of GLA to the diet can lead to a higher amount of dichomo-γ-linolenic acid (DGLA) by the action of elongase, an enzyme that is not limited in its activity. It is in turn a precursor to a series of eicosanoids that have anti-inflammatory effects (prostaglandins and thromboxanes series 1). The use of oils rich in γ-linolenic acid is based on this mechanism.
boražinaYet, looking at the scheme of fatty acid and eicosanoid biosynthesis, we wonder what prevents the human body from synthesizing arachidonic acid (AA) and proinflammatory eicosanoids? We know that inflammatory cells lack the enzyme Δ5 desaturase, so that at least in part this reduces the synthesis of proinflammatory mediators, i.e. an increase in the DGLA/AA ratio, which is favourable in inflammatory diseases. However, some authors critically review the dominant clinical use of evening primrose and borage. In an excellent review summarizing research over the past decade, Chilton et al. speculate that we can be even more effective and better balance eicosanoids. Namely, borage and evening primrose have very low levels of α-linolenic acid (ALA). Therefore, the entire pathway of synthesis of ω-3 acids EPA and DHA and anti-inflammatory eicosanoids arising from them remains denied. It has been proven that in humans, taking borage and evening primrose increases arachidonic acid levels in the blood after some time because tissues other than immune cells easily convert DGLA to AA. This is potentially undesirable because proinflammatory eicosanoids are formed from it. Therefore, the authors propose two strategies.

The first strategy is to take parallelly EPA-rich oils (fish oil). EPA uses the enzyme Δ5 desaturase and inhibits the rise of AA in the blood in people who use borage and evening primrose. However, this approach of using two vegetable oils is potentially awkward, although there are preparations on the market that have a mixture of GLA and EPA/DHA oils.

Another approach is to use oils that contain along with GLA and stearidonic acid (SDA). Stearidonic acid is easily converted to EPA and DHA because the critical enzyme Δ6 desaturase is skipped. Initial research has shown that oils rich in SDA also prevent the rise of AA, regardless of taking GLA. The most famous example of such an oil that is “all in one” is purple viper’s-bugloss. Unlike borage and evening primrose, it contains higher levels of not only α-linolenic, but also SDA, and the same level of GLA as evening primrose. Theoretically, this would be an ideal oil rich in GLA for application, but unfortunately it is very expensive.

Both concepts, and the addition of stearidonic acid and EPA together with GLA, have been shown to be accurate in humans. Both interventions raise DGLA levels rather than AA, while the addition of pure GLA (evening primrose or borage only) raises AA levels (Miles et al.).

It remains to be seen in actual clinical studies whether the application of SDA/GLA oils has a better effect than borage and evening primrose that have been used so far. Despite the growth of AA, using borage and evening primrose shows a good effect even in diseases such as rheumatoid arthritis. Therefore, interesting years await us in the field of clinical use of GLA rich oils.
Until then, the question remains which oils to use? Based on previous clinical studies, there is no reason to shy away from the use of borage and evening primrose, especially for menopausal problems, polycystic ovaries and painful menstruation. However, in inflammatory diseases such as rheumatoid arthritis, and especially if the patient is at potential risk of vascular disease, the concomitant use of EPA/DHA-rich oils, or SDA-rich oils, is recommended.

Rheumatoid arthritis

As early as the 1990s, studies showed a positive effect of borage oil in patients with rheumatoid arthritis, in randomized, placebo-controlled studies (review papers by Cameron et al.; MacFarlane et al.). Along with Trypterigium wilfordii, it appears to be one of the few herbal remedies that does work in rheumatoid arthritis. But the dose matters. In rheumatoid arthritis, doses of 1.4-2.8g of GLA per day were clinically tested. As borage contains about and over 20% GLA, this would mean that the patient must take 6-14 grams of borage vegetable oil per day. In other words, the optimal dose is about 10mL of oil per day. This is a dose that is impossible or difficult to achieve by taking the classic commercially available capsules of borage vegetable oil. This is the most common mistake people make in self-medication- taking too small a dose. A lower dose does show a lower effect (reviewed in Cameron et al.). One of the advantages of borage oil is the possibility of using it as adjuvant therapy with other drugs such as methotrexate, including biological therapy (chimeric antibodies/antibodies against TNF-α and IL-1β).

A relatively recent study tried to confirm the idea postulated a decade ago – whether the addition of EPA to GLA optimizes its effect. The double-blind and randomised study lasted as long as 18 months and patients were randomized into three groups with the following intervention:

  • 1.8g GLA per day
  • 2.1g EPA + 1.4g DHA daily
  • 1.8g GLA + 2.1g EPA + 1.4g DHA daily

All three groups showed a decrease in disease activity and there was no major difference between the groups. Obviously, the addition of EPA to GLA did not show an enhanced effect on disease activity. Interestingly, both EPA and DHA have shown an effect, but these are about three times higher doses than the classic doses used in vascular disease.

Atopic dermatitis

The first studies of the effectiveness of GLA-rich oils were published in the early 1980s when atopy was not as common a disease as it is today (Lovell et al., Wright et al.). Where did the idea come from?

kožaIn the eighties, it was observed that atopic patients have an imbalance of fatty acids, a deficiency of α-linolenic and γ-linolenic acid metabolites caused by the already mentioned enzyme Δ6-desaturase (Manku et al.) and that a lack of activity of this enzyme is crucial in the development of atopic dermatitis ( Manku et al.). Accordingly, correction by the addition of γ-linolenic acid to “skip” the enzyme Δ6-desaturase is, logically, clinically justified ( Wright S.).

As is already the case in medicine when we try to reach for too simple solutions, the first cracks in theory arose in the same eighties and later nineties when several studies did not show a more convincing effect in the treatment of atopy (Bamford et al., Hederos et al.). The ping pong game continued in which a clear effect was shown in other studies (Bordoni et al., Biagi et al., Fiocchi et al.). Even the first meta-analyses spoke in favour of supplementation (Morse et al.). After many studies in 2013, the Cochrane database analysed 27 clinical studies of GLA-rich oils, 19 with evening primrose and 8 with borage ( Bamford et al.) and concluded that they were ineffective. However, the authors could not include all studies in the meta-analysis due to the diversity of clinical indicators that served to assess the severity of the disease. Dosage inconsistencies, from 50mg to as much as 3g of GLA, can be resented for all studies.

Finally, today we are absolutely aware that atopic dermatitis is not a disease of Δ6-desaturase activity deficiency, but a fatty acid imbalance only involved in a far broader picture of the onset (pathogenesis) of atopy (Werfel et al., Bin et al., Brown SJ). Likewise, our perception of intervention has changed. GLA-rich oils are now viewed as a beneficial nutritional intervention that can help some patients and that includes additional interventions, such as probiotics (Foolad et al.), and a number of other measures that depend on individual assessment. Such nutritional aid is not only limited to evening primrose and borage oil, but also to hemp oil (Callaway et al.) and black currant seed oil (Linnamaa et al.). The mechanism of action on the skin is complex and includes anti-inflammatory action via eicosanoids (Ziboh et al.). In atopy, the main contribution of GLA-rich oils is to reduce transepidermal water loss- that is, they help prevent skin drying out (Callaway et al., Brosche et al., Muggli R., Kawamura et al.).

Do not expect miracles in atopy from GLA oil, but they are a useful supplement to the diet, which, among other interventions, can help. This includes external application. The doses are not determined because there is no consensus. My suggestion is, in children, about 0.25mL/1 kg of body weight per day, which is extracted from studies in adults, and in adults to use the doses mentioned for rheumatoid arthritis.

Psoriasis

Empirically, GLA-rich oils have been used for decades in psoriasis. The first small pilot study on only 17 patients with psoriasis showed that in some patients evening primrose oil along with Ω-3 fatty acids reduced PASI as a measure of an objective assessment of the severity of psoriasis (Kragballe K.). Subsequent studies have not given much optimism (Oliwiecki et al., Veale et al.) although they have indicated a change in fatty acid metabolism of the skin. As with atopy, with evening primrose and borage we have lost the illusion of being a “stand-alone” remedy for psoriasis, primarily due to far greater immune complexity than the fatty acid effect (Diani et al., Wang et al.). The intake of GLA-rich oils for psoriasis is only a nutritional intervention with other treatments.

Menopausal problems

In the mid-1990s, evening primrose oil became increasingly popular in reducing menopausal symptoms, such as hot flashes.

menopauzaThis trend of popularity was emphasized after the published guidelines where an increased risk of hormone-dependent tumours could not be ruled out with classical hormone replacement therapy. Unlike the chaos with doses for atopic dermatitis, doses in clinical studies are far more uniform. In the first study published 30 years ago, Chenoy et al. found a modest impact on reducing the frequency of night hot flashes. Many years later, a study on 56 women showed a better effect of the same dose of evening primrose compared to placebo in reducing the intensity of hot flashes, but also a more significant impact on social activities, quality of sexual life and relationships with other people (Farzaneh et al.). Compared to other “menopausal” plants, oil studies with GLA are indeed modest and with a small number of subjects. The mechanism of action has not been fully elucidated. It is most likely related to the whole of the aforementioned story of stimulating prostaglandin type 1 biosynthesis and reducing the production of series 2 proinflammatory prostaglandins, as evidenced directly in endometrial tissue (Graham et al.).

Despite poor clinical confirmation, GLA-rich oils can be a smart nutritional intervention independent of other ways to treat menopausal ailments. For some time, there was a fear that GLA oils, if used for menopausal symptoms, have a “hormonal” effect, so if they have a hormonal effect, then they have estrogen-like effect and- here are the problems with hormone-dependent tumours. That is not correct. GLA acts on the prostaglandin system. Indeed, in the event that a woman is on anti-estrogen therapy, GLA-rich oils can potentially enhance the action of such a drug (Menendez et al., Menendez et al.). There is no reason why women with hormone-dependent tumours should avoid GLA-rich oils.

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