Linoleic Acid

(BAN, rINN)
Linoleic Acid Chemical formula
Synonyms: Kwas linolowy; Linoleico, ácido; Linolic Acid; Linolsäure. (Z,Z)Octadeca-9,12-dienoic acid.
Cyrillic synonym: Линолевая Кислота.

💊 Chemical information

Chemical formula: C18H32O2 = 280.4.
CAS — 60-33-3.

💊 Adverse Effects and Precautions

Gamolenic and linoleic acids from evening primrose oil, and presumably other sources, can produce minor gastrointestinal disturbances and headache. They can precipitate symptoms of undiagnosed temporal lobe epilepsy, and should be used with caution in patients with a history of epilepsy or those taking epileptogenic drugs, in particular phenothiazines. Hypersensitivity reactions may also occur.

💊 Uses and Administration

Gamolenic and linoleic acid are essential fatty acids of the omega-6 series that act as prostaglandin precursors. Endogenous gamolenic acid is derived from linoleic acid, which is present in many vegetable oils and is an essential constituent of the diet. The most widely-used source of these acids is evening primrose oil. Gamolenic and linoleic acids have been used in skin disorders and mastalgia, and have been investigated in other disorders including multiple sclerosis, rheumatoid arthritis, and the premenstrual syndrome. Preparations containing essential fatty acids (formerly known collectively as vitamin F), including arachidonic acid, linoleic acid, linolenic acid, oleic acid, and their derivatives, have been used similarly. Conjugated linoleic acid (CLA), a mixture of isomers in which cis-9,trans-11-octadecadienoic acid and trans-10,cis-12-octadecadienoic acid predominate, has also been used. Products containing gamolenic-acid rich plant oils are promoted in many countries as dietary supplements, often in combination with fish oils or other sources of omega-3 fatty acids. A derivative of gamolenic acid, lithium gamolenate, has been investigated in pancreatic cancer.

Eczema.

Atopic eczema may be due to a defect in essential fatty acid metabolism1,2 and some beneficial symptomatic effects have been reported with evening primrose oil.1,3 Metaanalysis of 9 studies involving 311 patients4 has reported improvement in disease symptoms, especially itching, but a subsequent study in 123 patients found no therapeutic effect of evening primrose oil, alone or with fish oil.5 Although the design and interpretation of this study has been criticised by the manufacturers of evening primrose oil,6 the authors consider such criticism invalid,7 and point out that an earlier large study yielded similar results.8 No difference was found between placebo and evening primrose oil in a further study9 in children with eczema, and there was also no effect on asthma symptoms in those patients suffering from both disorders. Studies10,11 of borage oil (another source of gamolenic acid) also found no overall efficacy in adults or children with atopic eczema, although one study noted a suggestion of benefit in a subgroup of patients.10 In a study12of a group of formula-fed infants with a high maternal familial risk of developing atopic eczema, borage oil supplementation did not prevent the expression of atopy, although it showed a tendency to alleviate the severity of the condition later in infancy. Benefit has been reported in infants with seborrhoeic dermatitis from local application of borage oil.13
1. Wright S. Essential fatty acids and the skin. Br J Dermatol 1991; 125: 503–15
2. Horrobin DF. Essential fatty acid metabolism and its modification in atopic eczema. Am J Clin Nutr 2000; 71 (suppl): 367S–372S
3. Rustin MHA. Dermatology. Postgrad Med J 1990; 66: 894–905
4. Morse PF, et al. Meta-analysis of placebo-controlled studies of the efficacy of Epogam in the treatment of atopic eczema: relationship between plasma essential fatty acid changes and clinical response. Br J Dermatol 1989; 121: 75–90
5. Berth-Jones J, Graham-Brown RAC. Placebo-controlled trial of essential fatty acid supplementation in atopic dermatitis. Lancet 1993; 341: 1557–60. Correction. ibid.; 342: 564
6. Shield MJ, et al. Essential fatty acid supplementation in atopic dermatitis. Lancet 1993; 342: 377
7. Berth-Jones J, et al. Essential fatty acid supplementation in atopic dermatitis. Lancet 1993; 342: 377–8. Correction. ibid.; 752
8. Bamford JTM, et al. Atopic eczema unresponsive to evening primrose oil (linoleic and gamma-linolenic acids). J Am Acad Dermatol 1985; 13: 959–65
9. Hederos C-A, Berg A. Epogam evening primrose oil treatment in atopic dermatitis and asthma. Arch Dis Child 1996; 75: 494–7
10. Henz BM, et al. Double-blind, multicentre analysis of the efficacy of borage oil in patients with atopic eczema. Br J Dermatol 1999; 140: 685–8
11. Takwale A, et al. Efficacy and tolerability of borage oil in adults and children with atopic eczema: randomised, double blind, placebo controlled, parallel group trial. BMJ 2003; 327:1385–7
12. van Gool CJ, et al. γ-Linolenic acid supplementation for prophylaxis of atopic dermatitis—a randomized controlled trial in infants at high familial risk. Am J Clin Nutr 2003; 77: 943–51
13. Tollesson A, Frithz A. Borage oil, an effective new treatment for infantile seborrhoeic dermatitis. Br J Dermatol 1993; 129: 95.

Mastalgia.

Gamolenic acid (usually given in the form of evening primrose oil) has fewer adverse effects than drugs such as danazol or bromocriptine and has been preferred for mastalgia, especially in patients with less severe symptoms or those who require prolonged or repeated treatment. However, there is no clear evidence of efficacy.

Multiple sclerosis.

There is some evidence that modifying the intake of dietary fats and supplementing the diet with omega-6 polyunsaturated fatty acids, such as linoleic acid, could influence the clinical course of multiple sclerosis and many patients practise dietary modification, including taking evening primrose oil. One study1 has shown a reduction in severity and duration of relapse in patients taking linoleic acid supplements (as sunflower oil), and another2 has reported benefit in patients who limited their intake of dietary saturated fatty acids and supplemented their diet with polyunsaturated fatty acids. A systematic review3 of the relationship between dietary interventions (including linoleic acid supplements) and MS concluded that there was insufficient evidence to determine their benefits or risks.
1. Millar JHD, et al. Double-blind trial of linoleate supplementation of the diet in multiple sclerosis. BMJ 1973; 1: 765–8
2. Swank RL, Dugan BB. Effect of low saturated fat diet in early and late cases of multiple sclerosis. Lancet 1990; 336: 37–9
3. Farinotti M, et al. Dietary interventions for multiple sclerosis. Available in The Cochrane Database of Systematic Reviews; Issu
1. Chichester: John Wiley; 2007 (accessed 22/04/08).

Premenstrual syndrome.

Progressive improvement in premenstrual syndrome was reported over 5 cycles in an open pilot study in 19 patients receiving evening primrose oil.1However, subsequent results have not shown any benefit.2-4Evening primrose oil has been considered for cyclical mastalgia (see above).
1. Larsson B, et al. Evening primrose oil in the treatment of premenstrual syndrome: a pilot study. Curr Ther Res 1989; 46: 58–63
2. Khoo SK, et al. Evening primrose oil and treatment of premenstrual syndrome. Med J Aust 1990; 153: 189–92
3. Collins A, et al. Essential fatty acids in the treatment of premenstrual syndrome. Obstet Gynecol 1993; 81: 93–8
4. Budeiri DJ, et al. Is evening primrose oil of value in the treatment of premenstrual syndrome? Control Clin Trials 1996; 17: 60–8.

Rheumatoid arthritis.

Patients with rheumatoid arthritis taking NSAIDs have shown subjective improvement after 12 months of treatment with evening primrose oil, with or without fish oil, when compared with placebo.1 A clinically important reduction in signs and symptoms of disease activity has also been seen in patients treated with gamolenic acid in the form of borage oil.2 During treatment with evening primrose oil patients with rheumatoid arthritis have increased plasma concentrations of gamolenic, dihomo-gamma-linolenic, and arachidonic acids, and decreased plasma concentrations of oleic and eicosapentaenoic acids and apolipoprotein B.3 The increase in plasma-arachidonic acid and decrease in eicosapentaenoic acid might be unfavourable in such patients, since arachidonic acid is the precursor of inflammatory prostaglandins and eicosapentaenoic acid may have an anti-inflammatory role. However, a systematic review4of these and other studies concluded that there does appear to be some potential benefit for the use of gamolenic acid in rheumatoid arthritis, although optimum dosage and duration of treatment remains to be established.
1. Belch JJF, et al. Effects of altering dietary essential fatty acids on requirements for non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis: a double blind placebo controlled study. Ann Rheum Dis 1988; 47: 96–104
2. Leventhal LJ, et al. Treatment of rheumatoid arthritis with gammalinolenic acid. Ann Intern Med 1993; 119: 867–73
3. Jäntti J, et al. Evening primrose oil in rheumatoid arthritis: changes in serum lipids and fatty acids. Ann Rheum Dis 1989; 48: 124–7
4. Little CV, Parsons T. Herbal therapy for treating rheumatoid arthritis. Available in The Cochrane Database of Systematic Reviews; Issu
4. Chichester: John Wiley; 2000 (accessed 23/05/06).

💊 Preparations

Proprietary Preparations

Austria: Vitamin F; Ger.: Cefafloria†; Linola-Fett 2000†; Sanyrene; Ital.: Ictage 6†; Normogam†; Triene; Vitef; Pol.: Dermovit F; Linola; Linomag; UK: Super GLA. Multi-ingredient: Arg.: Exomega; KW; Quelodin F; Austria: Cehasol; Mamellin; Sulgan 99; Braz.: Glavit; Oleo de Primula; Primoris; Canad.: Bionagre plus E; Chile: Ureadin Pediatrics; Cz.: Linola; Linola-Fett; Fr.: Exomega; Ger.: Hydro Cordes; Linola; Linola-Fett; Lipo Cordes; Unguentacid; Hong Kong: Aderma Exomega†; Eye Q; Welsan Lipocream; Hung.: Linola; Linola-Fett N†; Ital.: Derman-Oil; Dermana Crema; Dermana Pasta; Efagel; Granoleina†; Neuralfa; Osteolip; Pasta Dicofarm; Secril; Tiofort; Topialyse; Trofinerv Antiox; Mex.: Nutrem; NZ: Efamast; Port.: Geriso; Zolium†; S.Afr.: Efamol G†; Spain: Amplidermis; Doctofril Antiinflamat; Mahiou†; Nutracel; Vitamina F99 Topica; Wobenzimal†; Switz.: Keroderm†; Linola; Linola gras; Linola mi-gras; Linoladiol†; Sulgan N; Vitafissan N; Vitamine F99†.
Published May 08, 2019.