EVENING PRIMROSE OIL

TABLE OF CONTENTS

The role of essential fatty acids and prostaglandins in the premenstrual syndrome

Effectiveness of natural oils as sources of gamma‑linolenic acid to correct peripheral nerve conduction velocity abnormalities in diabetic rats: Modulation by thromboxane A2 inhibition

Comparison of the effects of evening primrose oil and triglycerides containing gamma-linolenic acid on nerve conduction and blood flow in diabetic rats.

Multiple sclerosis: The rational basis for treatment with colchicine and evening primrose oil

Effects of a combination of evening primrose oil (gamma linolenic acid) and fish oil (eicosapentaenoic + docahexaenoic acid) versus magnesium, and versus placebo in preventing pre‑eclampsia.

Deficient nitric oxide responsible for reduced nerve blood flow in diabetic rats: effects of L‑NAME, L‑arginine, sodium nitroprusside and evening primrose oil.

Effects of dietary supplementation on autoimmunity in the MRL/lpr mouse: A preliminary investigation

A double-blind placebo controlled trial of Efamol Marine on skin and joint symptoms of psoriatic arthritis.

Evening primrose oil in patients with rheumatoid arthritis and side-effects of non-steroidal anti-inflammatory drugs.

Essential fatty acid and prostaglandin metabolism in Sjogren’s syndrome, systemic sclerosis and rheumatoid arthritis.

A randomized controlled study of evening primrose oil and fish oil in ulcerative colitis


EVENING PRIMROSE OIL

The role of essential fatty acids and prostaglandins in the premenstrual syndrome

Horrobin DF

J Reprod Med (USA), 1983, 28/7 (465-468)

 

Many of the features of the premenstrual syndrome are similar to the effects produced by the injection of prolactin. Some women with the premenstrual syndrome have elevated prolactin levels, but in most the prolactin concentrations are normal. It is possible that women with the syndrome are abnormally sensitive to normal amounts of prolactin. There is evidence that prostaglandin Esub 1, derived from dietary essential fatty acids, is able to attenuate the biologic actions of prolactin and that in the absence of prostaglandin Esub 1 prolactin has exaggerated effects. Attempts were made, therefore, to treat women who had the premenstrual syndrome with gamma-linolenic acid, an essential fatty acid precursor of prostaglandin Esub 1. Gamma-linolenic acid is found in human, but not cows', milk and in evening primrose oil, the preparation used in these studies. Three double-blind, placebo-controlled studies, one large open study on women who had failed other kinds of therapy for the premenstrual syndrome and one large open study on new patients all demonstrated that evening primrose oil is a highly effective treatment for the depression and irritability, the breast pain and tenderness, and the fluid retention associated with the premenstrual syndrome. Nutrients known to increase the conversion of essential fatty acids to prostaglandin Esub 1 include magnesium, pyridoxine, zinc, niacin and ascorbic acid. The clinical success obtained with some of these nutrients may in part relate to their effects on essential fatty acid metabolism.

 

Effectiveness of natural oils as sources of gamma‑linolenic acid to correct peripheral nerve conduction velocity abnormalities in diabetic rats: Modulation by thromboxane A2 inhibition

Dines KC, Cotter MA, Cameron NE.
Department of Biomedical Sciences, University of Aberdeen, Marischal College, Scotland, UK

Prostaglandins Leukotrienes and Essential Fatty Acids (United Kingdom), 1996, 55/3 (159‑165)

 

Reduced nerve conduction velocity (NCV) in experimental diabetes can be prevented by evening primrose oil (EP), which is rich in gamma‑linolenic acid (GLA). This study examined the efficacy of natural GLA sources, blackcurrant (BC), borage (BO) and fungal (FU) oils, compared with EP, in correcting motor and sensory NCV deficits in streptozotocin‑diabetic rats, and any potential contribution of thromboxane (TX) A2 synthesis using the TX antagonist, ZD1542, alone and jointly with GLA‑rich oils. Sciatic motor NCV, 20% reduced by 8 weeks of diabetes, was partially (16%) corrected by 2 weeks ZD1542 treatment. 1% BC, BO, FU and EP dietary supplementation caused 11%, 32%, 41% and 53% NCV ameliorations, respectively. A 2% EP diet, more closely matching the GLA intake from the other oils, caused 67% correction. Joint oil/ZD1542 treatment produced further motor NCV improvements for BC and, particularly, BO. A 13% sensory saphenous NCV deficit in diabetic rats was ameliorated by 31%, 24%, 49%, 81%, 70% and 94% for ZD1542, BC, BO, FU, EP and 2% EP, respectively. Joint ZD1542‑oil treatment further improved NCV, particularly for BO. Therefore, efficacy against experimental diabetic neuropathy is not predictable from the GLA content of natural oils, EP consistently outperforming BC, BO and FU. Increased TXA2 with diabetes made a minor contribution to NCV deficits, but blockade improved the response to BO.

 

Comparison of the effects of evening primrose oil and triglycerides containing gamma-linolenic acid on nerve conduction and blood flow in diabetic rats.

Dines KC, Cameron NE, Cotter MA.
Department of Biomedical Sciences, University of Aberdeen, Scotland, UK

J Pharmacol Exp Ther (United States) Apr 1995

 

The aim was to ascertain whether the ability of evening primrose oil (EPO) treatment to correct peripheral nerve dysfunction in streptozotocin-diabetic rats depends on a gamma-linolenic acid (GLA)-containing triglyceride constituent, di-linolein mono-gamma-linolenat e (DLMG). A second objective was to investigate whether the triglyceride conformation of GLA affects efficacy, using tri-gamma-linolenate (TGLA), which is not present in EPO. Third, we examined the actions of these omega-6 essential fatty acid-containing oils on sciatic nerve blood flow to establish a common mechanism. After 6 weeks of diabetes, sciatic motor nerve conduction velocity (NCV) was 21% reduced. EPO treatment caused dose-dependent increases in NCV that reached asymptote within 7 days. DLMG and TGLA, at doses matched for GLA content, had effects indistinguishable from those of EPO. Sciatic blood flow, 47.2% reduced by diabetes, was partially normalized by EPO, DLMG and TGLA. In contrast, sunflower oil (which does not contain GLA) did not alter NCV or blood flow. The data therefore provide strong evidence that DLMG is the active component of EPO and suggest that correction of nerve dysfunction involves a vascular action. The precise triglyceride configuration of GLA does not appear crucial to its effects in experimental diabetic neuropathy.

 

Multiple sclerosis: The rational basis for treatment with colchicine and evening primrose oil

Horrobin DF

Med Hypotheses (England), 1979, 5/3 (365‑378)

 

Multiple sclerosis (MS) is a disease with no known treatment. In view of this and of its distressing nature patients are attracted by any new concepts. As a reaction to this neurologists are sometimes excessively sceptical and fail to consider new approaches seriously. Recent attempts have been made to treat multiple sclerosis with polyunsaturated fatty acids and with colchicine. This approach is not arbitrary and is firmly grounded in fundamental basic scientific concepts. In patients with multiple sclerosis there is evidence of both an abnormality in essential fatty acid metabolism and an abnormality in lymphocyte function. It is now apparent that the fatty acid abnormality may cause the lymphocyte abnormality and that both may be improved by dietary manipulation. There is also evidence that the demyelination may be associated with recurrent inflammatory episodes and with entry of calcium into the cytoplasm. In vitro colchicine has been shown to have actions compatible with regulation of cytoplasmic calcium and in two diseases characterized by intermittent inflammatory episodes (Behcet's syndrome and familial Mediterranean fever) it has been found to prevent or to reduce the severity of such episodes. Preliminary results suggest that combined therapy with evening primrose oil and colchicine may be of considerable value.

 

Effects of a combination of evening primrose oil (gamma linolenic acid) and fish oil (eicosapentaenoic + docahexaenoic acid) versus magnesium, and versus placebo in preventing pre‑eclampsia.

D'Almeida A, Carter JP, Anatol A, Prost C.
Nutrition Program, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA

Women Health (United States) 1992, 19 (2‑3) p117‑31

 

In a placebo controlled, partially double‑blinded, clinical trial, a combination of evening primrose oil and fish oil was compared to Magnesium Oxide, and to a Placebo in preventing Pre‑Eclampsia of Pregnancy. All were given as nutritional supplements for six months to a group of primiparous and multiparous pregnant women. Some of these women had personal or family histories of hypertension (21%). Only those patients who received prenatal care at the Central Maternity Hospital for Luanda were included in the study. Compared to the Placebo group (29%), the group receiving the mixture of evening primrose oil and fish oil containing Gamma‑linolenic acid (GLA), Eicosapentaenoic acid (EPA), and Docosahexaenoic acid (DHA) had a significantly lower incidence of edema (13%, p = 0.004). The group receiving Magnesium Oxide had statistically significant fewer subjects who developed hypertension of pregnancy. There were 3 cases of eclampsia, all in the Placebo group.

 

Deficient nitric oxide responsible for reduced nerve blood flow in diabetic rats: effects of L‑NAME, L‑arginine, sodium nitroprusside and evening primrose oil.

Omawari N, Dewhurst M, Vo P, Mahmood S, Stevens E, Tomlinson DR.
Department of Pharmacology, Queen Mary and Westfield College, London

Br J Pharmacol (England) May 1996, 118 (1) p186‑90

 

1. This study examined the potential role of impaired nitric oxide production and response in the development of endoneurial ischaemia in experimental diabetes. Rats were anaesthetized (Na pentobarbitone 45 mg kg‑1, diazepam 2 mg kg‑1) for measurement of sciatic nerve laser Doppler flux and systemic arterial pressure. Drugs were administered into the sciatic endoneurium via a microinjector attached to a glass micropipette. 2. In two separate studies comparing diabetic rats (streptozotocin‑induced; 8‑10 wk duration) with controls, nerve Doppler flux in diabetic rats (Study 1, 116.6 +/‑ 40.4 and Study 2, 90.1 +/‑ 34.7 (s.d.) in arbitrary units) was about half that measured in controls (219.6 +/‑ 52.4 and 212.8 +/‑ 95.5 respectively; P < 0.005 for both). There were no significant differences between the two in systemic arterial pressure. 3. Inhibition of nitric oxide production by microinjection of 1 nmol L‑NAME into the endoneurium halved flux in controls (to 126.3 +/‑ 41.3 in Study 1 and 102.1 +/‑ 38.9 in Study 2; both P < 0.001), with no significant effect in diabetic rats, indicating markedly diminished tonic nitric oxide production in the latter. D‑NAME was without effect on nerve Doppler flux. 4. L‑Arginine (100 nmol), injected after L‑NAME, markedly increased flux in controls (by 65.8% (P < 0.03) and 97.8% (P < 0.01) in the two studies) and by proportionally similar amounts in diabetic rats [75.8% (P < 0.001) and 60.2% (P < 0.02)]. The nitro‑donor, sodium nitroprusside (SNP; 10 nmol) had similar effects to L‑arginine in both groups (increases of 66.0% in controls and 77.5% in diabetics; both P < 0.002). 5. A second diabetic group, treated with evening primrose oil performed exactly like control rats in respect of responses to L‑NAME, L‑arginine and SNP. 6. These findings implicate deficient nitric oxide in nerve ischaemia of diabetes and suggest correction thereof as a mechanism of action of evening primrose oil.

 

Effects of dietary supplementation on autoimmunity in the MRL/lpr mouse: A preliminary investigation

Godfrey DG, Stimson WH, Watson J, Belch JF, Sturrock RD

Ann Rheum Dis (UK), 1986, 45/12 (1019-1024)

 

The effects of dietary fatty acid supplementation on various disease parameters in the spontaneously autoimmune MRL-mp-lpr/lpr mouse model of systemic lupus erythematosus before onset of disease were investigated. A fat deficient diet was supplemented with the following oils: olive oil, sunflower oil, evening primrose oil (EPO), fish oil, and a fish oil/EPO mixture. The mice receiving a diet enriched with EPO showed an increase in survival, as did those receiving a fish oil/EPO mixture. These results, taken together with those of the other parameters monitored, suggest that EPO may be of benefit in alleviating the murine form of the disease.

 

A double-blind placebo controlled trial of Efamol Marine on skin and joint symptoms of psoriatic arthritis.

Veale DJ, Torley HI, Richards IM, O'Dowd A, Fitzsimons C, Belch JJ, Sturrock RD.
University Department of Medicine, Ninewells Hospital and Medical School, Dundee

Br J Rheumatol (England) Oct 1994, 33 (10) p954-8

 

Fish oil may be beneficial in the treatment of psoriasis and in RA. We examined the potential benefit of Efamol Marine, a combination of evening primrose oil and fish oil in the treatment of 38 patients with PsA. Patients with PsA were entered in a double-blind placebo controlled study and received either 12 Efamol Marine capsules or 12 placebo capsules daily for 9 months. All patients received placebo capsules for a further 3 months. At month 3 of the study patients were asked to reduce their intake of NSAIDs and maintain that decrease provided there was no worsening of their joint symptoms. Clinical assessments of skin and joint disease severity and activity were performed at 0, 1, 3, 6, 9 and 12 months. All measures of skin disease activity including severity, percentage body affected and itch were unchanged by Efamol Marine. The NSAID requirement remained the same between both treatment groups. In addition, there was no change demonstrated in the activity of arthritis as measured by duration of morning stiffness. Ritchie articular index, number of active joints, ESR and CRP. However, a rise in serum TXB2 was observed in the active group during the placebo phase; in addition a fall in leukotriene B4 production occurred during the active phase period followed by a marked rise during the placebo phase suggesting some laboratory documented anti-inflammatory effect. In conclusion, this study suggests that Efamol Marine may alter prostaglandin metabolism in patients with PsA, although it did not produce a clinical improvement and did not allow reduction in NSAID requirement. A larger dose of essential fatty acid may be needed to produce a clinical benefit.

 

Evening primrose oil in patients with rheumatoid arthritis and side-effects of non-steroidal anti-inflammatory drugs.

Brzeski M, Madhok R, Capell HA.
University Department of Medicine, Royal Infirmary, Glasgow

Br J Rheumatol (England) Oct 1991, 30 (5) p370-2

 

Forty patients with rheumatoid arthritis and upper gastrointestinal lesions due to non-steroidal anti-inflammatory drugs entered a prospective 6-month double-blind placebo controlled study of dietary supplementation with gamma-linolenic acid 540 mg/day. Nineteen patients received active therapy (as evening primrose oil 6 g/day) and 21 received placebo (olive oil 6 g/day). No patient stopped non-steroidal anti-inflammatory therapy but three patients in each group reduced their dose. Other results showed a significant reduction in morning stiffness with gamma-linolenic acid at 3 months and reduction in pain and articular index at 6 months with olive oil. Whilst gamma-linolenic acid may produce mild improvement in rheumatoid arthritis, olive oil may itself have hitherto unrecognized benefits.

 

Essential fatty acid and prostaglandin metabolism in Sjogren’s syndrome, systemic sclerosis and rheumatoid arthritis.

Horrobin DF

Scand J Rheumatol Suppl (Sweden) 1986, 61 p242-5

 

Evidence from biochemical studies and from experimental animals indicates that abnormalities of essential fatty acid (EFA) and eicosanoid metabolism could lead to salivary and lacrimal gland atrophy and to immunological and cardio-vascular defects. Measurements of EFA levels in erythrocytes from patients with primary Sjogren’s syndrome have shown that abnormalities are indeed present. Controlled clinical trials of supplementation with gamma-linolenic acid (GLA) as evening primrose oil (Efamol) in both primary Sjogren’s syndrome and systemic sclerosis have given positive results. There are strong arguments to indicate that sophisticated manipulation of EFA metabolism may have a role to play, not only in Sjogren’s syndrome but also in other rheumatological disorders. (16 Refs.)

 

A randomized controlled study of evening primrose oil and fish oil in ulcerative colitis

Greenfield S.M.; Green A.T.; Teare J.P.; Jenkins A.P.; Punchard N.A.; Ainley C.C.; Thompson R.P.H.

Gastrointestinal Laboratory, The Rayne Institute, St Thomas' Hospital, London SE1 7EH United Kingdom

Aliment Pharmacol Ther (United Kingdom), 1993, 7/2 (159‑166)

 

In a placebo‑controlled study, 43 patients with stable ulcerative colitis were randomized to receive either MaxEPA (n = 16), super evening primrose oil (n = 19), or olive oil as placebo (n = 8) for 6 months, in addition to their usual treatment. Treatment with MaxEPA increased red‑cell membrane concentrations of eicospentaenoic acid (EPA) at 3 months by three‑fold and at 6 months by four‑fold (both P < 0.01), and doubled docosahexaenoic acid (DHA) levels at 6 months (P < 0.05). Treatment with super evening primrose oil increased red‑cell membrane concentrations of dihomogamma‑linolenic acid (DGLA) by 40% at 6 months (P < 0.05), whilst treatment with placebo reduced levels of DGLA and DHA at 6 months (both P < 0.05). Clinical outcome was assessed by patient diary cards, sigmoidoscopy and histology of rectal biopsy specimens. Super evening primrose oil significantly improved stool consistency compared to MaxEPA and placebo at 6 months, and this difference was maintained 3 months after treatment was discontinued (P <0.05). There was however, no difference in stool frequency, rectal bleeding, disease relapse, sigmoidoscopic appearance or rectal histology in the three treatment groups. Despite manipulation of cell‑membrane fatty acids, fish oils do not exert a therapeutic effect in ulcerative colitis, while evening primrose oil may be of some benefit.