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Evening Primrose

Plant Part Used

Seed oil

Active Constituents

The omega-6 essential fatty acid gamma-linolenic acid (GLA). (1)

[span class=alert]This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]

Introduction

Evening primrose oil (EPO) is extracted from the dried, ripe seed of Oenothera biennis. EPO is a good source of gamma-linolenic acid (GLA), an important fatty acid normally produced within the human body from enzymatic conversion of linoleic acid (omega-6 EFA) into its longer-chain derivatives. Fatty acids are an important part of normal homeostasis. The human body can produce all but two fatty acids. These are omega-3 and omega-6 fatty acids. Both must be obtained through the diet or by the use of supplements. Obtaining a balance of these two fatty acids is essential. Essential fatty acids play a variety of important roles. They are needed for building cell membranes and are precursors for production of hormones and prostaglandins. Modern diets tend to be lacking in quality sources of fatty acids. In fact, some estimates are that as much as 90 percent of Americans may be deficient in EFA. Fatty acid deficiency may play an important role in the cause and morbidity of many diseases.(53)

Interactions and Depletions

Interactions

Dosage Info

Dosage Range

500mg-8 grams (standardized extract) daily.

Most Common Dosage

1500mg (standardized extract) daily.

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 8% GLA (gamma-linolenic acid) content per dose; expeller pressing is preferred.

Uses

Frequently Reported Uses

  • Source Of GLA (Omega-6 Fatty Acid)
  • Menopausal And Postmenopausal Symptoms
  • Fibrocystic Breast Disease, Breast pain (mastalgia)
  • PMS symptoms
  • Atopic dermatitis
  • Diabetic Neuropathy
  • Cardiovascular Support
  • Chronic Fatigue Syndrome
  • Eczema
Other Reported Uses
  • ADHD
  • Multiple Sclerosis
  • Alcoholism
  • Asthma
  • Sjögren's Syndrome
  • Immune Enhancement
  • Inflammatory Bowel Disease

Toxicities & Precautions

General

No known toxicity.

Health Conditions

Should be used with caution in patients diagnosed with epilepsy.(2) There were 2 reports in the 1980’s of EPO leading to an increase in seizure activity in temporal lobe epilepsy, although further laboratory evidence has found EPO may actually help protect against seizure activity in rats.(55)

Based on pharmacology, use with caution in individuals with bleeding disorders.(3)

Side Effects

Slight nausea, indigestion and loose stools may occur with overdosage.

Pregnancy/ Breast Feeding

If pregnant or nursing, consult a physician before use.

Age Limitations

Do not use in children under 2 years of age unless recommended by a physician.

Pharmacology

Mastalgia

Evening primrose oil EPO) has been used in Europe for decades in the treatment of mastalgia.(56) However, a meta analysis of clinical trials using EPO found there is presently insufficient evidence to recommend the use of EPO in the treatment of breast pain.(57)

 

Diabetic Neuropathy

Evening primrose oil is rich in gamma-linolenic acid which is an omega-6 fatty acid.(4),(5) Diabetics who do not convert linoleic acid to gamma-linolenic acid will need a quality source of GLA.(6),(7) This is said to be essential for proper nerve function, skin integrity, and for the prevention of diabetic neuropathy.(8),(9),(10) Evening primrose oil has been reported beneficial in positively affecting the course of diabetic neuropathy by decreasing microvascular problems associated with diabetes.(11),(12),(13) In a review of randomized controlled trials for diabetic neuropathy, EPO seemed to improve the symptoms without affecting glucose control.(14)

PMS/Menopause

EPO has also been reported useful in PMS,(15),(16),(17) menstrually related irritable bowel syndrome and menopausal complaints. The fatty acids found in EPO reportedly stimulate the production of hormones which may be deficient. Evening primrose was reported safe and effective in relieving problems associated with mastalgia, decreasing both pain and tenderness.(18) Contrarily, another study evaluated the use of gamma linolenic acid for the relief of menopause associated flushing and sweating. The treatment group received evening primrose 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.(19)

Research 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.(41) However, two simultaneous, randomized, controlled trials of the effects of a proprietary product of evening primrose 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.(42) After a total daily dose of the evening primrose oil combination (calcium 1.0 g, evening primrose oil 4.0 g and marine fish oil 440 mg) versus placebo (calcium 1.0 g.) there was no significant difference between treatment groups.

Immunity

Supplementation with essential fatty acids such as EPO has been shown to prevent zinc deficiency, thereby potentially improving immunity.(20) Evening primrose 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).(21) Also, laboratory studies have reported evening primrose oil to have the ability to inhibit thromboxane A2, decreasing platelet aggregation.(22),(23),(24)

Inflammatory Conditions

Fatty acids such as those found in evening primrose oil are effective in inflammatory conditions such as arthritis, altering the arachidonic acid inflammatory pathway by decreasing inflammatory mediators.(25) Some studies of the component of evening primrose oil, gamma-linolenic acid, have reported positive results in the management of arthritis and other inflammatory conditions.(26),(27)

One study examined the effectiveness of a combination of fish oil (omega-3 fatty acids) and evening primrose oil (omega-6 fatty acids) in the treatment of psoriatic arthritis.(28) 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/evening primrose 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.

Reports have suggested that evening primrose oil and its constituents linoleic acid and gamma-linolenic may be useful in hypercholesterolemia, decreasing LDL and potentially increasing HDL along with reducing human platelet adhesion.(29),(30),(31) The authors have reported that evening primrose oil as a dietary supplement enhances 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.(32)

 

Atopic Dermatitis

A small clinical study found that evening primrose oil is a safe and effective in management of atopic dermatitis.(58) Patients were treated for 5 months, with 96% of patients showing improvements of symptoms of atopic dermatitis versus 32% improvement in placebo treated individuals.

 

Other Uses

In part, due to its neurological protective qualities, evening primrose oil may also be effective in reducing the disabling effects, number of relapses, severity and duration of relapses in patients with multiple sclerosis (MS).(33) However, one study reported no benefit in patients with MS when supplemented with evening primrose oil.(34)

Patients with Sjogren’s syndrome have been reported to have abnormalities in essential fatty acid levels in erythrocytes.(35) There is evidence that these abnormalities of essential fatty acid (EFA) metabolism and increases in the inflammatory eicosanoid formation (including leukotrienes, prostacyclin, prostaglandins and thromboxanes) may lead to gland atrophy, particularly the salivary and lacrimal glands, along with immunological and cardiovascular defects.(36) There are strong arguments to indicate that alterations in EFA metabolism may play a role in not only Sjogren's syndrome but, also, in many other rheumatological disorders. Controlled clinical trials of supplementation with gamma-linolenic acid (GLA) as evening primrose oil in both primary Sjogren's syndrome and systemic sclerosis have yielded positive results.(37),(38),(39) 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 evening primrose oil (EPO) found no significant improvement in any symptoms studied.(40)

One laboratory animal study reported the benefit of evening primrose oil (EPO) and its ability to protect the gastric mucosa against injuries caused by pylorus ligation, non-steroidal anti-inflammatory drugs (including aspirin and NSAIDs such as indomethacin and phenylbutazone). EPO produced a significant inhibition of gastric mucosal damage induced by pylorus ligation, NSAIDs, hypothermic restraint ulcers, and had a cytoprotective effective effect against all of the necrotizing agents used in this study. The authors concluded that EPO may have both antisecretory and anti-ulcerogenic effects.

The use of evening primrose oil and its component gamma-linolenic acid has been studied in schizophrenic patients by several groups.(43),(44) 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) Further research needs to be performed in this area.

Essential fatty acid supplementation may be of benefit in individuals suffering from chronic viral infections such as chronic fatigue syndrome.(46),(47),(48) However, one study did not report any significant positive effect when using a combination of evening primrose and fish oils in chronic fatigue.(49)

Of interest, is a recent double-blind, placebo-controlled, crossover study of 18 individuals with attention deficit/hyperactivity disorder (ADHD) treated with evening primrose oil.(50) However, the evening primrose oil benefit was evident only with borderline zinc status individuals. The authors concluded after interpreting the data that evening primrose oil supplementation 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).(51),(52)

A small clinical study reported that EPO supplementation may be beneficial in reducing the risk factors for developing calcium oxalate urolithiasis.(59)

A small clinical trial found that administration of EPO to patients with contact lens associated dry eye had significant improvement in symptoms of dryness, leading to improved overall lens comfort.(60)

References

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  2. View Abstract: Dines KC, et al. Nerve Function in Galactosaemic Rats: Effects of Evening Primrose Oil and Doxazosin. Eur J Pharmacol. 1995;281(3):303-09.
  3. PDR for Herbal Medicines, 2nd ed. Montvale, NJ: Medical Economics Company; 2000:299.
  4. View Abstract: Chapkin RS, et al. Dietary Influences of Evening Primrose and Fish Oil on the Skin of Essential Fatty Acid-deficient Guinea Pigs. J Nutr. 1987;117(8):1360-70.
  5. View Abstract: Dutta-Roy AK, et al. Effects of Linoleic and Gamma-linolenic Acids (Efamol Evening Primrose Oil) on Fatty Acid-binding Proteins of Rat Liver. Mol Cell Biochem. 1990;98(1-2):177-82.
  6. View Abstract: Takahashi R, et al. Evening Primrose Oil and Fish Oil in Non-Insulin-Dependent-Diabetes. Prostaglandins Leukot Essent Fatty Acids. 1993;49(2):569-71.
  7. View Abstract: Stevens EJ, et al. Essential Fatty Acid Treatment Prevents Nerve Ischaemia and Associated Conduction Anomalies in Rats with Experimental Diabetes mellitus. Diabetologia. 1993;36(5):397-401.
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  29. View Abstract: Fukushima M, Matsuda T, Yamagishi K, et al. Comparative Hypocholesterolemic Effects of Six Dietary Oils in Cholesterol-fed Rats After Long-term Feeding. Lipids. Oct1997;32(10):1069-74.
  30. View Abstract: Villalobos MA, De La Cruz JP, Martin-Romero M, et al. Effect of Dietary Supplementation with Evening Primrose Oil on Vascular Thrombogenesis in Hyperlipemic Rabbits. Thromb Haemost. Oct1998;80(4):696-701.
  31. View Abstract: 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. Jan1991;11(1):20-2, 4.
  32. View Abstract: De La Cruz JP, Quintero L, Galvez J, et al. Antioxidant Potential of Evening Primrose Oil Administration in Hyperlipemic Rabbits. Life Sci. 1999;65(5):543-55.
  33. View Abstract: Dworkin RH, et al. Linoleic Acid and Multiple Sclerosis: A Reanalysis of Three Double-blind Trials. Neurology. Nov1984;34(11):1441-45.
  34. View Abstract: McGregor L, Smith AD, Sidey M, et al. Effects of Dietary Linoleic Acid and Gamma Linolenic Acid on Platelets of Patients with Multiple Sclerosis. Acta Neurol Scand. Jul1989;80(1):23-7.
  35. View Abstract: Oxholm P, Asmussen K, Wiik A, et al. Essential Fatty Acid Status in Cell Membranes and Plasma of Patients with Primary Sjogren's Syndrome. Correlations to Clinical and Immunologic Variables Using a New Model for Classification and Assessment of Disease Manifestations. Prostaglandins Leukot Essent Fatty Acids. Oct1998;59(4):239-45.
  36. View Abstract: Horrobin DF. Interactions Between n-3 and n-6 Essential Fatty Acids (EFAs) in the Regulation of Cardiovascular Disorders and Inflammation. Prostaglandins Leukot Essent Fatty Acids. Oct1991;44(2):127-31.
  37. View Abstract: Horrobin DF. Essential Fatty Acid Metabolism in Diseases of Connective Tissue with Special Reference to Scleroderma and to Sjogren's Syndrome. Med Hypotheses. Jul1984;14(3):233-47.
  38. View Abstract: McKendry RJ. Treatment of Sjogren's Syndrome with Essential Fatty Acids, Pyridoxine and Vitamin C. Prostaglandins Leukot Med. Apr1982;8(4):403-8.
  39. View Abstract: Horrobin DF. Essential Fatty Acid and Prostaglandin Metabolism in Sjogren's Syndrome, Systemic Sclerosis and Rheumatoid Arthritis. Scand J Rheumatol Suppl. 1986;61:242-5.
  40. View Abstract: Oxholm P, Manthorpe R, Prause JU, et al. Patients with Primary Sjogren's Syndrome Treated for Two Months with Evening Primrose Oil. Scand J Rheumatol. 1986;15(2):103-8.
  41. View Abstract: Claassen N, Coetzer H, Steinmann CM, et al. The Effect of Different n-6/n-3 Essential Fatty Acid Ratios on Calcium Balance and Bone in Rats. Prostaglandins Leukot Essent Fatty Acids. Jul1995;53(1):13-9.
  42. View Abstract: Bassey EJ, Littlewood JJ, Rothwell MC, et al. Lack of Effect of Supplementation with Essential Fatty Acids on Bone Mineral Density in Healthy Pre- and Postmenopausal Women: Two Randomized Controlled Trials of Efacal v. Calcium Alone. Br J Nutr. Jun2000;83(6):629-35.
  43. View Abstract: Horrobin DF. The Relationship between Schizophrenia and Essential Fatty Acid and Eicosanoid Metabolism. Prostaglandins Leukot Essent Fatty Acids. May1992;46(1):71-7.
  44. View Abstract: Vaddadi KS. Use of Gamma-linolenic Acid in the Treatment of Schizophrenia and Tardive Dyskinesia. Prostaglandins Leukot Essent Fatty Acids. May1992;46(1):67-70.
  45. View Abstract: Joy CB, Mumby-Croft R, Joy LA. Polyunsaturated Fatty Acid (Fish or Evening Primrose Oil) for Schizophrenia. Cochrane Database Syst Rev. 2000;(2):CD001257.
  46. View Abstract: Behan PO, Behan WMH, Horrobin D. The effect of high doses of essential fatty acids in the post-viral fatigue syndrome. Acta Neurol Scand 1990;82:209-16.
  47. Chilton SA. Cognitive Behaviour Therapy for the Chronic Fatigue Syndrome. Evening Primrose Oil and Magnesium have been Shown to be Effective. BMJ. Apr1996;312(7038):1096.
  48. Lewith G. Chronic fatigue syndrome. Update 1995;50:765.
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  50. View Abstract: 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):111-7.
  51. View Abstract: Barr CL, Wigg KG, Feng Y, et al. Attention-deficit Hyperactivity Disorder and the Gene for the Dopamine D5 Receptor. Mol Psychiatry. Sep2000;5(5):548-51.
  52. View Abstract: Sunohara GA, Roberts W, Malone M, et al. Linkage of the Dopamine D4 Receptor Gene and Attention deficit/hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. Dec2000;39(12):1537-42
  53. Bayles B, Usatine R. Evening primrose oil. Am Fam Physician. 15 Dec 2009;80(12):1405-1408.
  54. Riaz A, Khan RA, Ahmed SP. Assessment of anticoagulant effect of evening primrose oil. Pak J Pharm Sci. Oct 2009;22(4):355-359.
  55. Puri BK. The safety of evening primrose oil in epilepsy. Prostaglandins Leukot Essent Fatty Acids. Aug 2007;77(2):101-103. Epub 2007 Aug 30.
  56. 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. Sep 2007;9(3):196-201.
  57. Srivastava A, Mansel RE, Arvind N, et al. Evidence-based management of Mastalgia: a meta-analysis of randomised trials. Breast. Oct 2007;16(5):503-512. Epub 2007 May 16.
  58. Senapati S, Banerjee S, Gangopadhyay DN. Evening primrose oil is effective in atopic dermatitis: a randomized placebo-controlled trial. Indian J Dermatol Venereol Leprol. Sep-Oct 2008;74(5):447-452.
  59. 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. Dec 2009;182(6):2957-2963. Epub 2009 Oct 28.
  60. Kokke KH, Morris JA, Lawrenson JG. Oral omega-6 essential fatty acid treatment in contact lens associated dry eye. Cont Lens Anterior Eye. Jun 2008;31(3):141-146; quiz 170. Epub 2008 Mar 4.

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