Oenothera biennis L.

Last updated: 18 May 2017

Scientific Name

Oenothera biennis L.

Synonyms

Brunyera biennis Bubani, Oenothera biennis var. biennis, Oenothera biennis f. biennis, Oenothera biennis subsp. chicaginensis (de Vries ex Renner & Cleland) Á. Löve & D.Löve, Oenothera biennis f. grandiflora (L’Hér.) D.S.Carp., Oenothera biennis var. grandiflora (L’Hér.) Torr. & A.Gray, Oenothera biennis var. muricata (L.) Torr. & A. Gray, Oenothera chicaginensis de Vries ex Renner & Cleland, Oenothera chicagoensis Renner ex R.E.Cleland & Blakeslee, Oenothera grandiflora L’Hér., Oenothera muricata L., Oenothera renneri H.Scholz, Oenothera rubricaulis Kleb., Oenothera suaveolens Pers., Oenothera suaveolens var. latipetala Soldano, Onagra biennis (L.) Scop., Onagra biennis var. grandiflora (L’Hér.) Lindl., Onagra chrysantha Spach [Unresolved], Onagra europaea Spach [Unresolved], Onagra muricata (L.) Moench, Onagra vulgaris Spach [Unresolved]. [1]

Vernacular Name

English Common evening primrose, evening primrose, fever plant, field primrose, German rampion, sundrops, tree primrose [2]
China Yue jian cao [2]
South Africa Gewone nagblom, ngablom [2].

Geographical Distributions

Oenothera biennis is commonly found in open, disturbed areas; near sea level to 1500 m. This plant is distributed in Anhui, Guangdong, Guangxi, Guizhou, Hebei, Heilongjiang, Henan, Hubei, Hunan, Jiangsu, Jilin, Liaoning, Nei Mongol, Sichuan, Taiwan, Yunnan [Bhutan, Japan, Kazakhstan, Korea, Kyrgyzstan, Russia; native to E North America; widely naturalized in SW Asia, Europe, Pacific islands (New Zealand), and S South America]. [3]

Botanical Description

O. biennis is a member of Onagraceae family. It is an erect, biennial herb, with basal rosette. [3]

The stems are 30-200 cm tall, simple or sparsely branched, densely to very sparsely strigillose and with longer spreading and usually pustulate-based hairs, inflorescence often also glandular puberulous. [3]

The leaves are green or pale green, with inconspicuous veins, sessile or shortly petiolate; rosette blade 10-30 × 2-5 cm; cauline blade narrowly oblanceolate to elliptic, 5-22 × (1-)1.5-5(-6) cm, base acute to attenuate, margin dentate to subentire, often lobed near base, apex acute. [3]

The inflorescence is a dense mostly unbranched spike. [3]

The flowers are open near sunset; floral tube (2-)2.5-4 cm. Sepals 1.2-2.2(-2.8) cm, with free tips 1.5-3 mm, erect. Petals yellow, fading to orange, 1.2-2.5(-3) cm. Anthers 3-6(-9) mm; pollen ca. 50% fertile. Ovary densely glandular puberulous and sparsely villous or with very sparse pustulate-based hairs, sometimes only densely strigillose; stigma surrounded by anthers. [3]

The capsules are green, narrowly lanceoloid to lanceoloid, 2-4 cm, sessile. [3]

The seeds are in two rows per locule, brown to nearly black, 1.1-2 mm, irregularly pitted. [3]

Cultivation

No documentation.

Chemical Constituent

O. biennis was found to contain omega-6 essential fatty acid known as gamma-linolenic acid (GLA). [4]

Plant Part Used

Seed oil [5]

Traditional Use

No documentation.

Preclinical Data

Pharmacology

Antidiabetic activity

Gamma-linoleic acid content in O. biennis was found to enhance the capacity to reverse the signs of epidermal hyperproliferation, acanthosis and hypergranulosis that are characteristic of EFA deficiency. [6]

Feeding of EPO supplemented diet to rats (n = 9) for 2 months decreases the oleate binding capacity of purified L-FABP of rat liver whereas the palmitate binding activity was increased by 38%. [7]

O. biennis oil was found to prevent nerve ischaemia and associated conduction anomalies in rats with experimental diabetes mellitus. [8]

O. biennis supplies gamma-linoleic acid (GLA) to improve vasodilator eicosanoid synthesis in diabetes, correcting nerve blood flow and NCV deficits [9]. This was reported in experiment conducted by Cameron et al [10] studied in streptozotocin-induced diabetic rats.

O. biennis oil has been reported beneficial in positively affecting the course of diabetic neuropathy by decreasing microvascular problems associated with diabetes. [11][12]

Research conducted in animal study has reported that the fatty acids gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA) may be involved in the absorption, delivery and bone deposition of dietary calcium, thereby helping to maintain bone strength. [13]

Immunostimulatory activity

Supplementation with essential fatty acids such as EPO has been shown to prevent zinc deficiency, thereby potentially improving immunity [14]. O. biennis oil may also alter immunity by increasing cytokine production along with interferon-gamma (IFN-gamma), monocyte chemotactic protein-1 (MCP-1), and tumour necrosis factor-alpha (TNF-alpha) [15].

Platelet aggregation activity

Laboratory animal studies have reported O. biennis oil to have the ability to inhibit thromboxane A2 and decreasing platelet aggregation. [16][17]

 Antihypocholesterolemic activity

Reports have suggested that O. biennis oil and its constituent linoleic acid and gamma-linolenic may be useful in hypercholesterolemia, decreasing LDL and potentially increasing HDL along with reducing human platelet adhesion. [18][19]

Antioxidant activity

O. biennis oil as a dietary supplement was reported to enhance the antithrombotic capacity of the endothelium, reduces subendothelial thrombogenicity, and diminishes the extent of vascular wall lesions caused by a hyperlipemic diet in laboratory animals. Dietary supplementation with evening primrose oil was reported to reduce tissue lipid peroxidation (61% in liver, 57% in brain, 42% in heart, 24% in aorta, 33% in platelets) along with increasing total glutathione levels [especially in the aorta (90%) and platelets (200%)] with a reduction in glutathione peroxidase activity and an increase in the activities of glutathione reductase and transferase. [20]

Toxicity

No documentation.

Clinical Data

Clinical findings

Analgesic activity

A double blind study that was conducted on 80 patients with cyclical mastalgia showed that low intensity laser therapy is comparable to bromocriptine-O. biennis oil [21]. However, a meta-analysis of clinical trials using O. biennis oil found there is presently insufficient evidence to recommend the use of EPO in the treatment of breast pain [22].

Antidiabetic activity

O. biennis oil was found useful in improving abnormal lipid and thromboxane (TX)A2 metabolism in diabetic patients. [23]

O. biennis oil has been reported beneficial in positively affecting the course of diabetic neuropathy by decreasing microvascular problems associated with diabetes. [24]

In a review of randomized controlled trials for diabetic neuropathy, O. biennis oil seemed to improve the symptoms without affecting glucose control. [25]

Analgesic activity

O. biennis oil has also been reported useful in PMS, menstrual related irritable bowel syndrome and menopausal complaints [26][27]. The fatty acids found in O. biennis oil reportedly stimulate the production of hormones which may be deficient. O. biennis was reported safe and effective in relieving problems associated with mastalgia, decreasing both pain and tenderness [28].

Another study evaluated the use of gamma linolenic acid for the relief of menopause associated flushing and sweating. The treatment group received O. biennis oil as the source of gamma linolenic acid and vitamin E. This group was compared to a placebo group. Although there was a reduction in the maximum number of night time flushes, the study concluded that overall, gamma linolenic acid was no better than placebo in treating menopausal flushing. [29]

However, two simultaneous, randomized, controlled trials of the effects of a proprietary product of O. biennis oil on total body bone mineral density (BMD) and markers of bone turnover was conducted in healthy pre- and postmenopausal women did not produce positive results. After a total daily dose of the O. biennis oil combination (calcium 1.0 g, O. biennis oil 4.0 g and marine fish oil 440 mg) versus placebo (calcium 1.0 g.) there was no significant difference between treatment groups. [30]

Anti-inflammatory activity

Fatty acids such as those found in O. biennis oil are effective in inflammatory conditions such as arthritis, altering the arachidonic acid inflammatory pathway by decreasing inflammatory mediators. [31]

Some studies of the component of O. biennis oil, gamma-linolenic acid, have reported positive results in the management of arthritis and other inflammatory conditions. [32][33]

One study examined the effectiveness of a combination of fish oil (omega-3 fatty acids) and O. biennis oil (omega-6 fatty acids) in the treatment of psoriatic arthritis. Although there was no change in morning stiffness, NSAID requirement and all measures of skin disease activity including severity, percentage body affected and itching, there was a reported anti-inflammatory effect as seen in a fall in leukotriene B4 production. The authors concluded the fish/O. biennis oil combination may alter prostaglandin metabolism in patients with psoriatic arthritis, although no clinical improvement was seen or a reduction in NSAID requirement. A larger dose of essential fatty acid may be needed to produce a clinical benefit. [34]

Reports have suggested that O. biennis oil and its constituent linoleic acid and gamma-linolenic may be useful in hypercholesterolemia, decreasing LDL and potentially increasing HDL along with reducing human platelet adhesion. [35]

A small clinical study found that O. biennis oil is a safe and effective in management of atopic dermatitis. Patients were treated for 5 months, with 96% of patients showing improvements of symptoms of atopic dermatitis versus 32% improvement in placebo treated individuals. [36]

Neuroprotective activity

In part, due to its neurological protective qualities, O. biennis oil may also be effective in reducing the disabling effects, number of relapses, severity and duration of relapses in patients with multiple sclerosis (MS) [37]. However, one study reported no benefit in patients with MS when supplemented with evening primrose oil [38].

Controlled clinical trials of supplementation with gamma-linolenic acid (GLA) as O. biennis oil in both primary Sjogren's syndrome and systemic sclerosis have yielded positive results. [39][40][41]

However, a randomized, double-blind, placebo-controlled, cross-over trial in twenty eight patients with Sjogren's syndrome were treated for 8 weeks with a proprietary product of O. biennis oil found no significant improvement in any symptoms studied. [42]

The use of O. biennis oil and its component gamma-linolenic acid has been studied in schizophrenic patients by several groups. [43][44]

However, there is limited evidence with studies that the symptoms of schizophrenia may result from altered neuronal membrane structure and metabolism. Several studies have reported those with schizophrenia often have low levels of the particular essential fatty acids necessary for normal nerve cell membrane metabolism. [45]

Essential fatty acid supplementation from O. biennis may be of benefit in individuals suffering from chronic viral infections such as chronic fatigue syndrome [46][47]. However, one clinical study did not report any significant positive effect when using a combination of evening primrose and fish oils in chronic fatigue [48].

A double-blind, placebo-controlled, crossover study of 18 individuals with attention deficit/hyperactivity disorder (ADHD) treated with O. biennis oil had beneficial effects in the ADHD patients, most likely by improving or compensating for sub-optimal zinc status. Zinc is an important element in neurotransmitter metabolism (including dopamine), immune function, fatty acids synthesis, prostaglandin and melatonin formation. Dopamine regulation is believed to be closely related to attention-deficit/hyperactivity disorder (ADHD). [49][50][51]

Nephroprotective activity

A small clinical study reported that O. biennis oil supplementation may be beneficial in reducing the risk factors for developing calcium oxalate urolithiasis. [52]

Visual activity

A small clinical trial found that administration of O. biennis oil to patients with contact lens associated dry eye had significant improvement in symptoms of dryness, leading to improved overall lens comfort. [53]

Precautions

No documentation.

Side effects

Slight nausea, indigestion and loose stools may occur with over dosage of O.biennis. [54]

Pregnancy/Breast Feeding

If pregnant or nursing, consult a physician before use. [54]

Age limitation

No documentation.

Adverse reaction

No documentation.

Interaction & Depletion

Interaction with drug

Studies have reported that O. biennis affects the blood's clotting ability and may alter the effects of these medications and possibly the dose needed for treatment. These drugs include warfarin, heparin, dalteparin, tinzaparin, enoxaparin, danaparoid sodium, antithrombin III, lipirudin, argatroban, bivalirudin, aspirin, dipyridamole, anagrelide, cilostazol, clopidogrel, ticlopidine, abciximab, tirofiban, and eptifibatide. Use with caution.  [17]

Human case reports described O. biennis oil having caused schizophrenia to worsen in three individuals. This may alter the dose needed for treatment of these medications. A later study disagreed with these observations. These drugs include clozapine, olanzapine, quetiapine, chlorpromazine, prochlorperazine, perphenazine, haloperidol, thiothixene, pimozide, risperidone, lithium, ziprasidone, thioridazine, fluphenazine, trifluoperazine, molindone, mesoridazine, and loxapine. Use with caution.  [45][55]

A human study has reported that evening primrose oil may increase the chance of seizures in certain individuals. This may alter the effects of these medications and possibly the dose needed for treatment. Please contact your healthcare professional if you may be at a high risk of having a seizure. These drugs include phenytoin, carbamazepine, primidone, gabapentin, valproic acid, felbamate, lamotrigine, mephenytoin, fosphenytoin, clonazepam, ethosuximide, diazepam, clorazepate dipotassium, levatiracetam, tiagabine, topiramate, methsuximide, phensuximide, trimethadione, magnesium sulfate, acetazolamide, oxcarbazepine, zonisamide, and ethotoin. Use with caution. [56]

Interaction with other Herbs

No documentation.

Contraindications

No documentation.

Dosage

No documentation.

Poisonous Management

No documentation.

Line drawing

No documentation.

References

  1. The Plant List. Ver1.1. Oenothera biennis L. [homepage on the Internet]. c2013 [updated 2012 Mar 23; cited 2017 May 18]. Available from: http://www.theplantlist.org/tpl1.1/record/kew-2399189.
  2. Quattrocchi U. CRC world dictionary of medicinal and poisonous plants: Common names, scientific names, eponyms, synonyms, and etymology. Volume IV M-Q. Boca Raton, Florida: CRC Press, 2012; p. 309-310.
  3. Flora of China. Oenothera biennis Linnaeus. [homepage on the Internet]. No date [cited 2017 May 18]. Available from: http://www.efloras.org/florataxon.aspx?flora_id=2&taxon_id=220009399.
  4. Li Wan Po A. Evening primrose oil. Pharm J. 1991;246:670-676.
  5. Bayles B, usatine R. Evening primrose oil. Am Fam Physician. 2009;80(12):1405-1408.
  6. Chapkin RS, Ziboh VA, McCullough JL. Dietary influences of evening primrose and fish oil on the skin of essential fatty acid-deficient guinea pigs. J Nutr. 1987;117(8):1360-1370.
  7. Dutta-Roy AK, Demarco AC, Raha SK, Shav J, Garvey M, Horrobin DF. Effects of linoleic and gamma-linoleic acids (efamol evening primrose oil) on fatty acid-binding proteins of rat liver. Mol Cell Biochem. 1990;98(1-2):177-182.
  8. Stevens EJ, Lockett MJ, Carrington AL, Tomlinson DR. Essential fatty acid treatment prevents nerve ischaemia and associated conduction anomalies in rats with experimental diabetes mellitus. Diabetologia. 1993;36(5):397-401.
  9. Cameron NE, Cotter MA. Metabolic and vascular factors in the pathogenesis of diabetic neuropathy. Diabetes. 1997;46 Suppl 2:S31-S37.
  10. Head RJ, McLennan PL, Raederstorff D, Muggli R, Burnard SL, McMurchie EJ. Prevention of nerve conduction deficit in diabetic rats by polyunsaturated fatty acids. Am J Clin Nutr. 2000;71( 1 Suppl):386S-392S.
  11. Horrobin DF. The effect of gamma-linoleic acid on breast pain and diabetic neuropathy: Possible non-eicosanoid mechanisms. Prostaglandins Leukot Essent Fatty Acids. 1993;48(1):101-104.
  12. Jack AM, Kaegan A, Cotter MA, Cameron NE. Effects of diabetes and evening primrose oil treatment on responses of aorta, corpus cavernosum and mesenteric vasculature in rats. Life Sci. 2002;71(16):1863-1877.
  13. Claassen N, Coetzer H, Steinmann CM, Kruger MC. The effect of different n-6/n-3 essential fatty acid ratios on calcium balance and bone in rats. Prostaglandins Leukot Essent Fatty Acids. 1995;53(1):13-19.
  14. Dib A, Carreau JP. Effects of gamma-linoleic acid supplementation on pregnant rats fed a zinc-deficient diet. Ann Nutr Metab. 1987;31(3):312-319.
  15. Dirks J, van Aswegen CH, du Plessis DJ. Cytokine levels affected by gamma-linoleic acid. Postaglandins Leukot Essent Fatty Acids. 1998;59(4):273-277.
  16. Dines KC, Cotter MA, Cameron NE. Effectiveness of natural oils as sources of gamma-linoleic acid to correct peripheral nerve conduction velocity abnormalities in diabetic rats: Modulation by thromboxane A2 inhibition. Prostaglandins Leukot Essent Fatty Acids. 1996;55(3):159-165.
  17. De La Cruz JP, Martin-Romero M, Carmona JA, Villalobos MA, Sánchez de la Cuesta F. Effect of evening primrose oil on platelet aggregation in rabbits fed an atherogenic diet. Thromb Res. 1997;87(1):141-149.
  18. Fukushima M, Matsuda T, Yamagishi K, Nakano M. Comparative hypocholesterolemic effects of six dietary oils in cholesterol-fed rats after long-term feeding. Lipids. 1997;32(10):1069-1074.
  19. Villalobos MA, De La Cruz JP, Martin-Romero M, Carmona JA, Smith-Agreda JM, Sánchez de la Cuesta F. Effect of dietary supplementation with evening primrose oil on vascular thrombogenesis in hyperlipemic rabbits. Thromb Haemost. 1998;80(4):696-701.
  20. De La Cruz JP, Quintero L, Galvez J, Villalobos MA, Sánchez de la Cuesta F. Antioxidant potential of evening primrose oil administration in hyperlipemic rabbits. Life Sci. 1999;65(5):543-555.
  21. Saied GM, Kamel RM, Dessouki N. Low intensity laser therapy is comparable to bromocriptine-evening primrose oil for the treatment of cyclical mastalgia in Egyptian females. Tanzan Health Res Bull. 2007;9(3):196-201.
  22. Srivastava A, Mansel RE, Arvind N, Prasad K, Dhar A, Chabra A. Evidence-based management of Maltalgia: A meta-analysis of randomised trial. Breast. 2007;16(5):503-512.
  23. Takahashi R, Inoue J, Hibino H. Evening primrose oil and fish oil in non-insulin-dependent-diabetes. Protaglandins Leukot Essent Fatty Acids. 1993;49(2):569-571.
  24. Keen H, Payan J, Allawi J, et al. Treatment of diabetic neuropathy with gamma-linoleic acid. The Gamma-Linoleic Acid Multicenter Trial Group. Diabetes Care. 1993;16(1):8-15.
  25. Halat KM, Dennehy CE. Botanicals and dietary supplements in diabetic peripheral neuropathy. J Am Board Fam Pract. 2003;16(1):47-57.
  26. Horrobin DF. The role of essential fatty acids and prostaglandins in the premenstrual syndrome. J Reprod Med. 1983;28(7):4650468.
  27. Khoo SK, Munro C, Battistutta D. Evening primrose oil and treatment of premenstrual syndrome. Med J Aust. 1990;153(4):189-192.
  28. Pye JK, Mansel RE, Hughes LE. Clinical experience of drug treatment for mastalgia. Lancet. 1985;2(8451):373-377.
  29. Chenoy R, Hussain S, Tayob Y, O’Brien PM, Moss MY, Morse PF. Effect of oral gamolenic acid from evening primrose oil on menopausal flushing. BMJ. 1994;308(6927):501-503.
  30. Bassey EJ, Littlewood JJ, Rothwell MC, Pye DW. Lack of effect of supplementation with essential fatty acids on bone mineral density in healthy pre- and postmenopausal women: Two randomized controlled trial of Efacal v. Calcium alone. Br J Nutr. 2000;83(6):629-635.
  31. Belch JJ, Hill A. Evening primrose oil and borage oil in rheumatologic conditions. Am J Clin Nutr. 2000;71(1 Suppl):352S-356S.
  32. Leventhal LJ, Boyce EG, Zurier RB. Treatment of rheumatoid arthritis with gammalinoleic acid. Ann Intern Med. 1993;119(9):867-873.
  33. Jäntti J, Nikkari T, Solakivi T, Vapaatalo H, Isomäki H. Evening primrose oil in rheumatoid arthritis: Changes in serum lipids and fatty acids. Ann Rheum Dis. 1989;48(2):124-127.
  34. Veale DJ, Torley HI, Richards IM, et al. A double-blind placebo controlled trial of Efamol Marine on skin and joint symptoms of psoriatic arthritis. Br J Rheumatol. 1994;33(10):954-958.
  35. Liang XC, Guo SS. Effect of jiang-zhi zhong-yao-pian on total cholesterol triglyceride, TXB2, 6-keto-PGF1 alpha in hyperlipemic patients. Zhong Xi Yi Jie He Za Zhi. 1991;11(1):20-22, 4. Chinese.
  36. Senapati S, Banerjee S, Gangopadhyay DN. Evening primrose oil is effective in atopic dermatitis: A randomized placebo-controlled trial. Indian J Dermatol Venereol Leprol. 2008;74(5):447-452.
  37. Dworkin RH, bates D, Millar JH, Paty DW. Linoleic acid and multiple sclerosis: A reanalysis of three double-blind trials. Neurology. 1984;34(11):1441-1445.
  38. Mcgregor L, Smith AD, Sidey M, Belin J, Zilkha KJ, MGregor JL. Effects of dietary linoleic acid and gamma linoleic acid on platelets of patients with multiple sclerosis. Acta Neurol Scand. 1989;80(1):23-27.
  39. Horribin DF. Essential fatty acid metabolism in diseases of connective tissue with special reference to scleroderma and to Sjogren’s syndrome. Med Hypotheses. 1984;14(3):233-247.
  40. Mckendry RJ. Treatment of Sjogren’s syndrome with essential fatty acids, pyridocine and vitamin C. Prostaglandins Leukot Med. 1982;8(2):403-408.
  41. Horrobin DF. Essential fatty acid and prostaglandin metabolism in Sjogren’s syndrome, systemic sclerosis and rheumatoid arthritis. Scand J Rheumatol Suppl. 1986;61:242-245.
  42. Oxholm P, Manthorpe R, Prause JU, Horrobin D. Patients with primary Sjogren syndrome treated for two months with evening primrose oil. Scand J Rheumatol. 1986;15(2):103-108.
  43. Horrobin DF. The relationship between schizophrenia and essential fatty acid and eicosanoid metabolism. Prostaglandins Leukot Essent Fatty Acids. 1992;46(1):71-77.
  44. Vaddadi KS. Use of gamma-linoleic acid in the treatment of schizophrenia and tardive dyskinesia. Prostaglandins Leukot Essent Fatty Acids. 1992;46(1):67-70.
  45. Joy CB, Mumby-Croft R, Joy LA. Polyunsaturated fatty acid (fish or evening primrose oil) for schizophrenia. CoChrane Database Syst Rev. 2000;(2):CD001-267.
  46. Behan PO, Behan WM, Horrobin D. Effect of high doses of essential fatty acids on the postviral fatigue syndrome. Acta Neurol Scand. 1990;82(3):209-216.
  47. Chilton SA. Cognitive behaviour therapy for the chronic fatigue syndrome. Evening primrose oil and magnesium have been shown to be effective. BMJ. 1996;312(7038):1096.
  48. Warren G, McKendrick M, Peet M. The role of essential fatty acids in chronic fatigue syndrome. A case-controlled study of red-cell membrane essential fatty acids (EFA) and a placebo-controlled treatment study with high dose of EFA. Acta Neurol Scand. 1999;99(2):112-116.
  49. Arnold LE, Pinkham SM, Votolato N. Does zinc moderate essential fatty acid and amphetamine treatment of attention-deficit/hyperactivity disorder? J Child Adolesc Psychopharmacol. 2000;10(2):111-117.
  50. Barr CL, Wigg KG, Feng Y, et al. Attention-deficit hyperactivity disorder and the gene for the dopamine D5 receptor. Mol Psychiatry. 2000;5(5):548-551.
  51. Sunohara GA, Roberts W, Malone M, Schachar RJ, Tannock R, Basile VS. Linkage of the dopamine D4 receptor gene and attention deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2000;39(12):1537-1542.
  52. Rodgers A, Lewandowski S, Allie-Hamdulay S, Pinnock D, Baretta G, Gambaro G. Evening primrose oil supplementation increases citraturia and decreases other urinary risk factors for calcium oxalate urolithiasis. J Urol. 2009;182(6):2957-2963.
  53. Kokke KH, Morris JA, Lawrenson JG. Oral omega-6 essential fatty acid treatment in contact lens associated dry eye. Cont Lens Anterior Eye. 2006;31(3):141-146.
  54. Mayo Clinic. Drugs and Supplements. Evening primrose (Oenothera spp.). [homepage on the Internet]. c1998-2017 [cited 2017 May 18]. Available from: http://www.mayoclinic.org/drugs-supplements/evening-primrose/safety/hrb-20059889.
  55. Vaddadi KS. The use of gamma-linolenic acid and linoleic acid to differentiate between temporal lobe epilepsy and schizophrenia. Prostaglandins Med. 1981;6(4):375-379.
  56. Holman CP, Bell AFJ. A trial of evening primrose oil in the treatment of chronic schizophrenia. J Orthomol Med. 1983;12(4):302-304.