Evening Primrose Oil by 21st Century

POSSIBLY INEFFECTIVE

• Asthma. Oral evening primrose oil does not seem to be effective for asthma treatment. Details: Several small clinical trials show that taking evening primrose oil 15-20 mL or 4-6 grams daily in divided doses for 8-16 weeks does not improve symptoms of asthma when compared with placebo (7565,20545,20546).

LIKELY INEFFECTIVE

• Mastalgia. Most clinical research in patients with mastalgia shows that oral evening primrose oil does not seem to reduce pain. However, research results are conflicting. Details: Although some low-quality studies have suggested that evening primrose oil 1-4 grams daily for 3-6 months can reduce breast pain (9794,20519,20520,49303,49339,88182,104140), higher quality clinical research shows that taking evening primrose oil 3-4 grams in 2-3 divided doses daily for 6-12 months only decreases breast pain when compared to baseline, but not when compared with placebo (9156,20518,49212,49338,49357). A meta-analysis of these and other randomized clinical trials also shows that taking evening primrose oil 1-4 grams daily for 2-12 months does not reduce pain severity when compared with placebo. One subgroup analysis suggests that taking evening primrose oil may reduce pain scores when compared with topical non-steroidal anti-inflammatory drugs (NSAIDs); however, the validity of this result is limited by a small sample size and high heterogeneity (96713,96716,109426). In contrast, a moderate-sized clinical study in patients with cyclical mastalgia shows that taking evening primrose oil 1000 mg twice daily, with or without vitamin E 400 mg once daily, for 6 months reduces breast pain severity when compared with placebo. Taking evening primrose oil and vitamin E together reduces pain severity more effectively than either ingredient alone (114809). However, it is unclear if the reduction in pain scores is clinically significant.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Abortion. Although there has been interest in using intravaginal administration of evening primrose oil for abortion, there is insufficient reliable information about the clinical effects of evening primrose oil for this purpose. Oral evening primrose oil has not been evaluated for this use. Details: One moderate-sized clinical study in patients in Iran undergoing abortion for intrauterine fetal death shows that intravaginal administration of evening primrose oil 1000 mg , in combination with misoprostol, every 4 hours up to 5 times reduces the mean induction-to-fetal-expulsion interval, pain intensity, and the average dose of misoprostol required when compared with misoprostol alone. Another moderate-sized clinical study in patients undergoing abortion for intrauterine fetal death shows that intravaginal administration of evening primrose oil 2000 mg the night before hospitalization, followed by misoprostol upon hospital admission, reduces the mean induction-to-fetal-expulsion time when compared with misoprostol alone (114806,114808).
• Acne. Although there has been interest in using oral or topical evening primrose oil for acne, there is insufficient reliable information about the clinical effects of evening primrose for this condition.
• Alzheimer disease. Although there has been interest in using oral evening primrose oil for Alzheimer disease, there is insufficient reliable information about the clinical effects of evening primrose for this condition.
• Atopic dermatitis (eczema). It is unclear if oral or topical evening primrose oil is beneficial for adults or children with atopic dermatitis; the available research is conflicting. Details: The majority of studies have used the specific evening primrose oil products Epogam (Scotia Pharmaceuticals), Efamol (Efamol Ltd.), or Efamol Marine (Efamol Ltd.). In some studies in adults, taking evening primrose oil 2-3 grams orally twice daily for 3 weeks to 5 months seems to reduce the extent of atopic dermatitis and symptoms of itching and dryness (7569,20512,20515,21019,49288). However, in other studies, evening primrose oil 6-8 grams daily in 1-2 divided doses for 12-16 weeks did not improve atopic dermatitis when compared with baseline or placebo (7566,7567,49286). Furthermore, using a combination of evening primrose oil 2.58 grams and fish oil 0.642 grams (Efamol Marine, Efamol Ltd.) orally twice daily for 16 weeks is associated with worsening of erythema and skin cracking when compared with placebo (7566). In children up to 18 years of age, some small clinical studies show that taking evening primrose oil orally in age-dependent doses of 0.5-6 grams daily for 2 weeks to 5 months reduces the extent and severity of atopic dermatitis, and improves symptoms such as itching, dryness, and pruritus, when compared with placebo (7568,20512,21019,49188,49273,49288). However, in other studies, using evening primrose oil (Epogam or Efamol) 2-4 grams daily divided into two doses for 12-16 weeks does not improve atopic dermatitis when compared with placebo (7565,49285,49286). The differing findings may be due to the small size and methodological weaknesses of the available studies. Also, conflicting results may be due to differences in the severity of atopic dermatitis at baseline, the length of time since diagnosis, or the dose of evening primrose oil used.
• Attention deficit-hyperactivity disorder (ADHD). Some small clinical studies suggest that oral evening primrose oil is not beneficial in children with ADHD. Details: Two small clinical studies in children with ADHD show that taking 3 or 4 capsules of a specific product containing evening primrose oil (Efamol) twice daily for 4 weeks, does not improve ADHD symptoms when compared with placebo (6443,6462). However, some clinical research in children and adolescents shows that taking 3 capsules of a specific product (Eye Q, Equazen / Novasel) containing evening primrose oil 100 mg/capsule and fish oil 400 mg/capsule twice daily for 12-15 weeks has positive effects on some symptoms of ADHD, such as inattention, hyperactivity/impulsivity, and restlessness/impulsivity, when compared with placebo (15739,65864). However it is unclear if any benefit is due to evening primrose oil, fish oil, or the combination.
• Biliary disorders. It is unclear if oral evening primrose oil is beneficial for patients with biliary disorders. Details: One preliminary clinical trial shows that taking evening primrose oil (Efamol, Scotia Pharmaceuticals) 2 grams orally twice daily for 12 weeks might improve pruritus in some patients with biliary cirrhosis. In responders, clinical improvement seems to occur within 1-2 weeks of starting treatment, but relapse occurs within 1-2 weeks after treatment discontinuation (49337).
• Chronic fatigue syndrome (CFS). It is unclear if oral evening primrose oil is beneficial for patients with CFS. Details: One preliminary clinical trial shows that taking two 500 mg capsules of a specific product (Efamol Marine, Scotia Pharmaceuticals) containing evening primrose oil plus fish oil four times daily for 3 months improves total symptom scores in 85% of people with symptoms of CFS after a viral infection, compared with 17% of those receiving placebo (7563). However, a later clinical trial using the same regimen in people with a confirmed diagnosis of CFS shows that taking this product does not significantly reduce symptoms of CFS when compared with placebo (7564). The product used in these two trials (Efamol Marine, Scotia Pharmaceutical) is standardized to contain gamma linolenic acid (GLA) 36 mg, eicosapentaenoic acid (EPA) 17 mg, docosahexaenoic acid (DHA) 11 mg, and linoleic acid 255 mg per capsule.
• Coronary heart disease (CHD). Although there has been interest in using oral evening primrose oil for CHD prevention, there is insufficient reliable information about the clinical effects of evening primrose for this purpose.
• Developmental coordination disorder (DCD). Oral evening primrose oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in children with DCD shows that taking a tuna fish oil product providing DHA 480 mg daily for 4 months, in combination with evening primrose oil providing arachidonic acid 35 mg and gamma linolenic acid 96 mg, thyme oil 24 mg, and vitamin E 80 mg (Efalex, Efamol Ltd.), modestly decreases movement disorders as determined by objective measures when compared with baseline (5708). It is unclear if these benefits are due to evening primrose oil, other ingredients, or the combination. Also, the validity of this finding is limited by the lack of a comparator group.
• Diabetes. Oral evening primrose oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with gestational diabetes and low vitamin D levels, clinical research shows that taking a capsule containing evening primrose oil 1000 mg and vitamin D 1000 IU daily for 6 weeks reduces fasting plasma glucose and plasma insulin levels, reduces insulin resistance, and improves beta cell function when compared with placebo. Taking evening primrose oil and vitamin D also results in a reduction in triacylglycerol, total cholesterol, low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL) cholesterol levels when compared with placebo (96719). It is not clear if these effects are due to evening primrose oil, vitamin D, or the combination.
• Diabetic neuropathy. It is unclear if oral evening primrose oil is beneficial for patients with diabetic neuropathy. Details: One clinical study shows that taking evening primrose oil standardized to contain gamma linolenic acid 480 mg once daily for 12 months does not improve measures of vibration perception or measures of autonomic nervous system function, such as postural hypotension and cardiac rhythm changes induced by deep breathing or the Valsalva maneuver, in people with painful diabetic neuropathy (49360). However, other clinical research shows that taking evening primrose oil providing gamma linolenic acid 360-480 mg daily for 6-12 months improves measures of nerve conduction velocity, muscle and nerve action potential amplitudes, reflexes, and temperature sensation in patients with mild diabetic neuropathy (8926,20528). Reasons for the discrepancies are not entirely clear, but may be due to the severity of diabetic neuropathy at baseline.
• Dry eye. It is unclear if oral evening primrose oil is beneficial for patients with dry eye. Details: Preliminary clinicical research shows that taking a specific evening primrose oil product (Qarma, Equazen) 3 grams daily for 6 months improves some symptoms of dry eye associated with soft contact lens use when compared with placebo (20531).
• Dry skin. It is unclear if oral evening primrose oil is beneficial for patients with dry skin. Details: Preliminary clinical research in adults treated with isotretinoin for acne vulgaris shows that taking evening primrose oil 510 mg orally daily for 9 months improves skin moisture scores when compared with no intervention (109430).
• Dyslexia. Oral evening primrose oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in children with dyslexia shows that taking an evening primrose oil product providing arachidonic acid 35 mg and gamma linolenic acid 96 mg daily in combination with a tuna fish oil product providing DHA 480 mg daily (Efalex, Efamol Ltd.) for 5 months modestly improves subjective measures of reading speed and motoric-perceptual velocity when compared to baseline in children with dyslexia (20530). The validity of these findings is limited by the lack of a comparator group.
• Endometriosis. Although there has been interest in using oral evening primrose oil for endometriosis, there is insufficient reliable information about the clinical effects of evening primrose for this condition.
• Hepatitis B. It is unclear if oral evening primrose oil is beneficial for patients with hepatitis B. Details: There is preliminary clinical evidence that taking evening primrose oil (Efamol, Scotia Pharmaceuticals) 2 grams twice daily for 12 months is no more effective than placebo for improving liver function tests or liver damage in people with chronic hepatitis B infection (20548).
• Hyperlipidemia. It is unclear if oral evening primrose oil is beneficial for improving lipid levels. Details: A meta-analysis of six low-quality clinical studies in patients with or without hyperlipidemia shows that taking evening primrose oil for 6-17 weeks does not reduce total cholesterol, low-density lipoprotein (LDL) cholesterol, or triglycerides, nor does it increase high-density lipoprotein (HDL) cholesterol, when compared with placebo (104139). However, only one of the studies in the analysis specifically evaluated patients with hyperlipidemia. Other preliminary clinical research in patients with hyperlipidemia shows that taking evening primrose oil 3-4 grams daily orally in two divided doses for 1-3 months can decrease total cholesterol by 15% to 18% and triglycerides by 13% to 24%, as well as increase HDL cholesterol by 16%, when compared to baseline (20533,20534). However, other preliminary clinical research in patients with hyperlipidemia shows that taking evening primrose oil 2.2-6.6 grams daily orally for 3 months does not improve cholesterol levels when compared to baseline (20523). Other clinical research shows that taking a specific product containing evening primrose oil 250 mg along with policosanol, tomato extract, and grape seed procyanidins (CholActive, Indena S.p.A.) twice daily for 6 weeks decreases total cholesterol by 13% and LDL cholesterol by 17% when compared with placebo in patients with primary hypercholesterolemia and mixed dyslipidemia (20536). It is unclear if these effects are due to evening primrose oil, other ingredients, or the combination.
• Hysteroscopy. It is unclear if intravaginal evening primrose oil is beneficial for cervical ripening prior to hysteroscopy. Oral evening primrose oil has not been evaluated for this use. Details: A large clinical study of females in Iran shows that inserting evening primrose oil 1000 mg intravaginally once 6 hours prior to hysteroscopy reduces the need for mechanical dilation, limits the time to completion of dilation, and improves the ease of dilation, without increasing complications (i.e. cervical or uterine rupture), when compared with placebo (110571). The interpretation of these results is limited by lack of comparison with standard therapy (i.e. misoprostol). Another small clinical study in adults undergoing gynecological procedures including hysteroscopy and dilation and curettage shows that inserting intravaginal evening primrose oil 2000 mg one time 2 hours prior to the procedure increases cervical dilation by about 2 mm and reduces pain but does not reduce vaginal bleeding, vomiting, or uterine cramps when compared with misoprostol as an active control (112129).
• Ichthyosis. It is unclear if oral evening primrose oil is beneficial for patients with ichthyosis. Details: Preliminary clinical research shows that taking evening primrose oil orally, 3 grams daily for adults or 2 grams daily for children 12 years and under, for 9 weeks does not improve symptoms of ichthyosis vulgaris when compared to baseline (20537).
• Infant development. It is unclear if oral evening primrose oil is beneficial for infant development. Details: There is preliminary clinical evidence that adding evening primrose oil and fish oil to newborn infant formulas might produce plasma and blood cell levels of long chain polyunsaturated fatty acids that are closer to those of breastfed infants than standard formula (20549,49174). In one study this was associated with improved visual acuity in infants at 16 and 30 weeks of age when compared with standard formula, but not when compared with breast milk (20549).
• Intermittent claudication. Although there has been interest in using oral evening primrose oil for intermittent claudication, there is insufficient reliable information about the clinical effects of evening primrose for this condition.
• Irritable bowel syndrome (IBS). Although there has been interest in using oral evening primrose oil for IBS, there is insufficient reliable information about the clinical effects of evening primrose for this condition.
• Liver cancer. It is unclear if oral evening primrose oil is beneficial for patients with liver cancer. Details: One small clinical study shows that taking evening primrose oil orally, 18 grams daily, does not affect liver size, average survival, or subjective feelings of well-being in patients with primary liver cancer when compared with placebo (1983). However, this study may have been inadequately powered to detect differences between groups.
• Menopausal symptoms. It is unclear if oral evening primrose oil is beneficial for reducing menopausal symptoms. Clinical research results are conflicting. Details: Two small clinical trials in patients with menopause who were not currently receiving hormone therapy shows that taking evening primrose oil 1-2 grams orally daily for 2-8 weeks reduces psychological symptoms, such as depressive moods, irritability, mental exhaustion, and anxiety, by 45% to 73% when compared with baseline. These changes were statistically significant when compared with placebo (102556,109427). However, a moderate-sized clinical study in patients with menopause and not receiving hormone therapy shows that taking evening primrose oil 1 gram twice daily for 8 weeks does not improve overall symptom of menopause when compared with placebo (114807). Evening primrose oil has also been evaluated for reducing hot flashes, with mixed findings. Small clinical trials in patients with menopause show that taking evening primrose oil 1-4 grams daily for 1.5-6 months does not reduce the frequency of hot flashes when compared with placebo (274,88184,109428). However, one small clinical trial shows that taking evening primrose oil does moderately reduce the frequency and severity of night sweats and hot flashes when compared with placebo (109428). Evening primrose has also been evaluated in combination with other ingredients. One clinical trial shows that taking one capsule daily of a combination of evening primrose oil with soy isoflavones, black cohosh, and Vitex agnus-castus (Estosalus, Max Biocare Pty Ltd) for 12 weeks moderately reduces the severity of hot flushes, sweating, sleep problems, depressed mood, and irritability when compared with placebo. There was no effect on plasma lipids, joint discomfort, heart discomfort, anxiety, exhaustion, or sexual problems (105102). Another preliminary clinical trial shows that taking a combination product providing evening primrose oil 440-880 mg daily with isoflavones and vitamin E for 6 months induces 57% to 63% reductions in subjective menopausal symptoms when compared with baseline (21002). It is unclear if these effects are due to evening primrose, other ingredients, or the combinations.
• Multiple sclerosis (MS). It is unclear if oral evening primrose oil is beneficial for patients with MS; some research suggests that evening primrose oil may actually worsen MS. Details: Preliminary clinical research shows that using a specific evening primrose oil product (Naudicelle, Bio Oil Research Ltd.), 8 capsules daily for 2 years, increases the number of patients with acute remitting MS who deteriorate when compared with placebo (49364). However, preliminary clinical research in adults with relapsing-remitting MS shows that taking a combination of evening primrose oil 0.6-0.7 grams and hempseed oil three times daily for 6 months reduces disability scores and relapse rate when compared to baseline (88183). The validity of this finding is limited by the lack of a comparator group. Also, it is unclear if these benefits are due to evening primrose oil, hemp seed oil, or the combination.
• Obesity. It is unclear if oral evening primrose oil is beneficial for individuals with obesity. Details: Preliminary clinical research shows that taking evening primrose orally, 1200 mg four times daily for 12 weeks, does not improve weight loss in individuals with obesity on a reduced calorie diet when compared with a reduced calorie diet alone (20540).
• Osteopenia. Oral evening primrose oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a combination of evening primrose oil 4 grams, fish oil 440 mg, and calcium 1 gram (Efacal, Scotia Pharmaceuticals) orally in divided doses daily for 12 months does not improve bone mineral density (BMD) when compared with calcium alone in healthy pre- and post-menopausal females whose baseline BMD is within 2 standard deviations of normal (21001).
• Osteoporosis. Although there has been interest in using oral evening primrose oil for osteoporosis, there is insufficient reliable information about the clinical effects of evening primrose for this condition.
• Parturition. Most clinical studies in term or late term pregnant adults show that oral and intravaginal evening primrose oil increases cervical ripening and may reduce the duration of labor and need for cesarean section. However, research on other pregnancy-related outcomes is unclear. Details: Meta-analyses of small to moderate-sized, low-quality clinical trials in healthy term pregnancies show that taking oral or intravaginal evening primrose oil 500-4500 mg daily beginning as early as 37 weeks gestation for 7-10 days or until birth, or as a single dose at either 37 weeks or 6 hours prior to labor induction, decreases the, duration of labor, and the odds of cesarean section by up to 39%, but does not affect the length of the second stage of labor, the need for oxytocin, the duration of oxytocin use, or neonatal weight when compared with placebo. Evidence is conflicting on whether evening primrose oil improves Apgar scores at 1, 5, and 10 minutes. (20524,96717,109028,109029,112130,112131,114810). One meta-analysis of 5 clinical studies shows that oral or intravaginal evening primrose oil improves cervical ripening (112131). Additionally, another moderate-sized clinical study in nulliparous late-term pregnant adults shows that intravaginal administration of evening primrose oil pearls 1000 mg repeated every 6 hours in the absence of a treatment response up to a maximum of 4 times increases cervical readiness when compared with active control misoprostol (112130). Similarly, a small clinical study in low-risk, term pregnant adults shows that intravaginal evening primrose oil 1000 mg daily improves cervical ripening when compared with placebo (114810). One small, older observational study suggests that taking evening primrose oil from week 37 of pregnancy until delivery is not associated with improvements in cervical ripening or the duration of gestation, and might be associated with a trend toward prolonged labor and increased oxytocin requirements, in low-risk pregnancies (1411). Studies utilized evening primrose oil either orally as 1000-4500 mg daily for 7-14 days, or vaginally as 1000-3000 mg daily for 1-14 days, but subgroup analyses did not identify the most effective regimen. Overall, the validity of these studies is limited by high heterogeneity (20524,96717,109028,109029).Additionally, most clinical studies were conducted in the Middle East which may limit generalizability of results (109028,109029,112131).
• Peptic ulcers. Although there has been interest in using oral evening primrose oil for peptic ulcers, there is insufficient reliable information about the clinical effects of evening primrose for this condition.
• Polycystic ovary syndrome (PCOS). Oral evening primrose oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with PCOS and low vitamin D levels shows that taking a capsule containing evening primrose oil 1000 mg and vitamin D 1000 IU daily for 12 weeks reduces triglyceride levels and very low-density lipoprotein (VLDL) cholesterol levels and improves some markers of oxidative stress when compared with placebo. However, there is no change in the clinical features of PCOS, including hirsutism, acne, and alopecia (96720). An expression of concern has been published related to the integrity of this publication. Until more is known, interpret the information related to these findings with caution (104685).
• Postoperative pain. It is unclear if oral evening primrose oil is beneficial for postoperative pain. Details: Preliminary clinical research in adults undergoing an appendectomy shows that taking a specific evening primrose oil (Natural Life) postoperatively, 1000 mg every 30 minutes for 3 doses, reduces pain scores by 50% when compared with baseline. Subjects taking a placebo did not show a reduction in pain scores from baseline; however, a between-group statistical comparison was not conducted (109429).
• Pre-eclampsia. It is unclear if oral evening primrose oil is beneficial for the prevention or treatment of pre-eclampsia. Details: Some very small clinical studies show that taking evening primrose oil (Efamol, Efamed Ltd.) 4 grams daily or a specific product (Preglandin), providing linoleic acid 375 mg and gamma linolenic acid 45 mg daily, does not reduce blood pressure, proteinuria, or rate of edema in patients with pre-eclampsia (1409,20525). Another very small clinical study shows that taking 8 capsules containing evening primrose plus fish oil, standardized to contain gamma linolenic acid 37 mg/capsule, eicosapentaenoic acid (EPA) 18 mg/capsule, and docosahexaenoic acid (DHA) 10 mg/capsule, daily for 6 months during pregnancy reduces the incidence of edema by 32%, but does not reduce the risk of hypertension, when compared with placebo (1042).
• Premenstrual syndrome (PMS). It is unclear if oral evening primrose oil is beneficial in patients with PMS. Details: Two small clinical studies show that taking a specific evening primrose oil product (Efamol, Efamol Ltd.) orally, either 4 grams daily for 3 months or 3 grams daily from day 15 to the end of the menstrual cycle for 4 cycles, improves subjective symptoms of PMS when compared with placebo (21005,49335). However, other clinical research shows that taking evening primrose oil (Efamol, Efamol Ltd.) 3-6 grams daily for 2-4 menstrual cycles is not beneficial when compared with placebo (1106,21004,49323).
• Psoriasis. Oral evening primrose oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Two small, preliminary clinical trials in patients with chronic stable plaque psoriasis shows that taking a combination of evening primrose oil 4.32-5.16 grams plus fish oil 1.072-1.284 grams orally in two divided doses daily for 6-7 months does not reduce the severity of psoriasis or prolong remission when compared with placebo (21006,21007).
• Psoriatic arthritis. Oral evening primrose oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with psoriatic arthritis shows that taking 12 capsules of a specific product (Efamol Marine, Scotia Pharmaceuticals) providing 0.4 grams of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) plus gamma linolenic acid 0.5 grams daily for 9 months does not improve skin or joint symptoms when compared with placebo (20544).
• Raynaud syndrome. It is unclear if oral evening primrose oil is beneficial in patients with this condition. Details: Preliminary clinical research in patients with Raynaud syndrome shows that taking evening primrose oil (Efamol, Efamol Ltd.) 6 grams daily for 10 weeks improves the frequency and duration of attacks of digital ischemia based on subjective measures. However, it does not improve objective measurements of finger temperature and cold-induced vasospasm (49365).
• Rheumatoid arthritis (RA). It is unclear if oral evening primrose oil is beneficial in patients with RA. Details: One small clinical study shows that taking evening primrose oil 6 grams daily for 12 months improves subjective, but not objective, symptoms of RA when compared with placebo (12036). Another small clinical study shows that taking evening primrose oil 6 grams daily for 6 weeks does not reduce morning stiffness or joint tenderness when compared to baseline in RA patients (20542). Evening primrose oil has also been evaluated in combination with other ingredients. One preliminary clinical study shows that taking evening primrose oil (Natural Wealth) 2.6 grams daily with a fish oil product (Omega-3 Cardio, Natural Wealth) 2 grams daily for 12 weeks modestly reduces total symptom scores, pain severity, and the number of painful joints when compared with placebo, but not when compared with taking the same fish oil product (Omega-3 Cardio, Natural Wealth) 5 grams daily without evening primrose oil (96714). Other preliminary clinical research shows that using evening primrose oil 10 mL orally twice daily for 12 weeks, or a combination of evening primrose oil plus a vitamin supplement containing vitamin C, niacin, pyridoxine, and zinc sulfate (Efavite, Efamol) daily for 12 weeks, does not improve objective symptoms of RA (12035,20543).
• Schizophrenia. It is unclear if oral evening primrose oil is beneficial in patients with schizophrenia. Details: One preliminary clinical study shows that taking evening primrose oil (Efamol) 6 grams daily for 16 weeks induces psychological and memory improvements based on the Comprehensive Psychopathological Rating Scale in patients with schizophrenia and tardive dyskinesia (21009). However, taking evening primrose oil (Efamol, Efamol Ltd.) 4 grams daily along with a supplement (Efavite, Efamol Ltd.) containing vitamin E 40 mg, vitamin C 1000 mg, vitamin B6 200 mg, vitamin B3 200 mg, and zinc sulfate 40 mg daily for 2-4 months does not improve scores on the Brief Psychiatric Rating Scale or the MACC Behavioral Adjustment Scale in patients hospitalized with chronic, severe schizophrenia (21010).
• Sjogren syndrome. It is unclear if oral evening primrose oil is beneficial in patients with this condition. Details: Preliminary clinical studies show that taking evening primrose oil (Efamol, Primrose Research Inc.) orally, either alone or combined with vitamin C and vitamin B6 for 8-10 weeks does not improve ocular or oral symptoms associated with Sjogren syndrome when compared with baseline or placebo (12037,12038).
• Tardive dyskinesia. It is unclear if oral evening primrose oil is beneficial in patients with tardive dyskinesia. Details: Preliminary clinical research shows that taking evening primrose oil 6 grams daily for 6-16 weeks does not improve neuroleptic-induced tardive dyskinesia in patients with schizophrenia (21009,49271).
• Ulcerative colitis. Oral evening primrose oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with ulcerative colitis shows that taking a combination of evening primrose oil and borage oil orally, 3 grams daily for one month then 1.5 grams daily for 5 months, improves stool consistency, but does not have an effect on rectal bleeding, stool frequency, disease relapse, or rectal histology when compared with placebo (1037).
• Water warts. It is unclear if topical evening primrose oil improves the resolution of water warts in children. Details: Preliminary clinical research in children 2-10 years of age shows that applying evening primrose oil to water wart lesions twice daily for 3 months produces complete resolution of lesions within 3 months in about 29% of children. The known natural course of the infection involves spontaneous resolution in only about 4% to 7% of children at 3 months and 58% of children at 12 months. For those that did not experience complete resolution with evening primrose oil, approximately 24% had partial resolution at 3 months, 42% had no response, and 5% experienced worsening infection (96718). More evidence is needed to rate evening primrose for these uses.

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LIKELY SAFE ...when used orally and appropriately. Evening primrose oil has been used safely in doses up to 6 grams daily for up to 1 year (7566,7567,8926,12036,20512,49286,49360,109426,114807,114809). There is insufficient reliable information available about the safety of evening primrose oil when used topically. There is also insufficient reliable information available about the safety of evening primrose seed, flower, or leaf when used orally or topically.

CHILDREN: POSSIBLY SAFE
when evening primrose oil is used orally and appropriately, short-term. In children up to 5 years of age, doses of evening primrose oil up to 3 grams daily have been used safely for 5 months (20512,49273), and 0.5 grams/kg daily has been used safely for 8 weeks (7570). In children up to 12 years of age, doses of 4-6 grams daily have been used safely for 3-5 months (7565,7566,20512,49286). ...when used topically and appropriately, short-term. In children 2-10 years of age, evening primrose oil has been applied to affected areas of the skin twice daily for up to 3 months (96718). There is insufficient reliable information available about the safety of evening primrose seed, flower, or leaf when used orally or topically.

PREGNANCY: POSSIBLY SAFE
when evening primrose oil is used orally and appropriately. In small studies of evening primrose oil for pre-eclampsia, 4 grams has been used orally daily for up to 10 weeks during pregnancy with apparent safety (1409,20525). ...when evening primrose oil is used orally or intravaginally to improve cervical ripening. Evening primrose oil has been used safely during the last 1-3 weeks of pregnancy to improve cervical ripening (20524,96717,112130,112131,114810). Intravaginally, evening primrose oil 500-1000 mg as either a single dose or administered daily starting at week 38 until pregnancy has been used with apparent safety for this purpose (112130,112131). Orally, evening primrose oil 1500-4500 mg in divided doses daily for 1-3 weeks has been used with apparent safety for this purpose, although one study found 5 cases of meconium-stained amniotic fluid (112131). Some studies report that improvement was lacking and there was a trend toward prolonged labor, prolonged rupture of membranes, increased rates of arrest of descent, and increased oxytocin requirements (1411,112131). Intravaginally, evening primrose oil, 1000 mg every 4 hours up to 5 times or 2000 mg as a single dose, has been used as an adjunct to misoprostol for a medication abortion with apparent safety for this purpose (114806,114808). Evening primrose oil has also been linked to a case report of petechiae and ecchymoses in a newborn infant whose mother took a total of 6.5 grams during the week before giving birth (16303); use with caution, especially in high doses.

LACTATION: POSSIBLY SAFE
when evening primrose oil is used orally. Supplementation with evening primrose oil during lactation results in the secretion of high levels of the constituent gamma linolenic acid into breast milk (1982); however, this fatty acid is normally present in significant amounts in breast milk (11884).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, evening primrose oil may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details Evening primrose oil contains gamma linolenic acid (GLA). There is preliminary clinical evidence that GLA can reduce platelet aggregation and prolong bleeding time (1979).

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = D Theoretically, evening primrose may increase the levels and clinical effects of CYP2C9 substrates.  Details In vitro research shows that linoleic acid, a constituent of evening primrose oil, inhibits CYP2C9 (21017).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of lithium with evening primrose oil might decrease lithium levels and effects.  Details In a case report, a patient on a stable dose of lithium for 10 years experienced a reduction in lithium levels after taking evening primrose oil 500 mg daily. Baseline levels were 0.69 mmol/L, which decreased to 0.37 mmol/L after 2 months and 0.23 mmol/L after 3 months of use. Lithium levels increased within 6 weeks of discontinuing evening primrose oil, to 0.73 mmol/L; no clinical effects were noted (96715).

LOPINAVIR/RITONAVIR (Kaletra) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, evening primrose oil might increase the levels and effects of lopinavir.  Details In a case report, an HIV patient who took evening primrose oil (Efamol) along with lopinavir/ritonavir experienced an increase in serum levels of lopinavir to 15.2 mg/L. Six weeks after discontinuing evening primrose oil, levels of lopinavir returned to the normal range of 5-10 mg/L. When re-challenged with evening primrose oil for a week, the patient's lopinavir levels increased from 6.69 to 8.11 mg/L. It is suspected that evening primrose oil increases levels of lopinavir by inhibiting cytochrome P450 3A4 (CYP3A4), which metabolizes lopinavir (93578). However, this effect has not been reported in other research.

PHENOTHIAZINES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking evening primrose oil with phenothiazines might increase the risk of convulsions.  Details Evening primrose oil contains gamma-linolenic acid (GLA). There is some concern that taking supplements containing GLA might cause seizures, or lower the seizure threshold, when taken with phenothiazines (88187). In one report, three patients with schizophrenia who had received phenothiazines developed EEG changes suggestive of temporal lobe epilepsy after starting treatment with GLA, although none experienced an actual seizure (21013). In another report, two patients with schizophrenia who were stabilized on phenothiazines developed seizures when evening primrose oil 4 grams daily was added. One of these patients had a prior history of seizures (21010). It is unclear whether evening primrose oil had any additive epileptogenic effects with the phenothiazines; there is no evidence that taking evening primrose oil alone causes seizures (88187).

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General ...Orally and topically, evening primrose oil is generally well tolerated. There is limited reliable information available regarding the safety or adverse effects of other parts of the plant.
Most Common Adverse Effects:
Orally: Abdominal pain and distention, diarrhea, dyspepsia, flatulence, nausea, and vomiting.

Dermatologic ...Orally, use of evening primrose oil has been associated with reports of skin rash and acne (9156,9794,49338). There is a case report of extensive but transient petechiae and purpuric ecchymoses in a newborn infant whose mother had consumed raspberry leaf tea and a total of 6.5 grams of evening primrose oil orally and vaginally during the week prior to delivery. The infant had a normal platelet count and no signs of hemorrhage, and was discharged healthy at 3 days of age (16303).

Gastrointestinal ...Gastrointestinal complaints, including abdominal pain, distension and fullness, nausea and vomiting, diarrhea, dyspepsia, and flatulence are the most common adverse effects of evening primrose (8926,9794,20533,49188,49286,49339,49365,65864,88184,102556). Often these effects resolve with continued use. Altered taste has also been reported (49339).

Hematologic ...There is preliminary clinical evidence that evening primrose oil can decrease platelet aggregation and prolong bleeding time. In a small study of patients with hyperlipidemia, taking evening primrose oil 3 grams daily for 4 months was associated with a 40% increase in bleeding time, and decreases in ADP- and epinephrine-induced platelet aggregation of 50% and 60% respectively (1979). There is also a case report of diffuse ecchymoses and petechiae in a neonate whose mother had consumed 6.5 grams of evening primrose oil over the week prior to delivery (16303).

Neurologic/CNS ...Cases of dizziness (9794) and headache (88184) have been reported with evening primrose oil when used orally.
There is a report of seizures in a patient taking evening primrose oil and receiving anesthesia; however, the patient was also taking other drugs and it is therefore unclear if evening primrose was the cause (613). There is also concern that evening primrose oil might cause seizures, or lower the seizure threshold, in patients with schizophrenia who are treated with phenothiazines. This is based on limited data from two studies published in the 1980s. In one report, three patients with schizophrenia who had received phenothiazines developed EEG changes suggestive of temporal lobe epilepsy after starting treatment with evening primrose, although none experienced an actual seizure (21013). In the other report, two patients with schizophrenia who were stabilized on phenothiazines developed seizures when evening primrose oil 4 grams daily was added. One of these patients had a prior history of seizures (21010). There is no evidence that evening primrose taken alone, without medications known to lower the seizure threshold, can cause seizures (88187).

Other ...Weight gain has been reported in individuals receiving evening primrose oil (49338).

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