Omega 3-6-9 by Indiana Botanic Gardens

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alzheimer disease. Although there has been interest in using oral black currant berry for Alzheimer disease, there is insufficient reliable information about the clinical effects of black currant for this purpose.
• Atopic dermatitis (eczema). Topical black currant seed oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children aged 2-18 years with atopic dermatitis shows that using a specific cream containing black currant seed oil, sunflower oil, and balloon vine (Defensil), with added dexpanthenol and ceramide, twice daily for 4 weeks, improves atopic dermatitis severity scores similarly to urea 5% cream. About 38% of patients had a 50% improvement in severity score with the combination cream, compared with 35% with urea cream (105538).
• Colic. Although there has been interest in using oral black currant leaf for colic, there is insufficient reliable information about the clinical effects of black currant for this purpose.
• Common cold. Although there has been interest in using oral black currant berry for common cold, there is insufficient reliable information about the clinical effects of black currant for this purpose.
• Cough. Although there has been interest in using oral black currant leaf for cough, there is insufficient reliable information about the clinical effects of black currant for this purpose.
• Diarrhea. Although there has been interest in using oral black currant leaf for diarrhea, there is insufficient reliable information about the clinical effects of black currant for this purpose.
• Dry eye. Oral black currant has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adults with dry eye disease shows that taking a specific combination product containing black currant 100 mg, L-carnitine 50 mg, elderberry fruit extract 300 mg, zinc 10 mg, and Eleutherococcus root 50 mg (Meramirt CM) orally once daily improves dry eye symptom scores when compared with no intervention. Contrast sensitivity scores also improved when compared with baseline in the treated group, but not in the control group (111295). It is unclear if this effect is due to black currant, other ingredients, or the combination.
• Dysmenorrhea. Although there has been interest in using oral black currant seed oil for dysmenorrhea, there is insufficient reliable information about the clinical effects of black currant for this purpose.
• Glaucoma. It is unclear if oral black currant is beneficial in patients with glaucoma. Details: Preliminary clinical research in adults with glaucoma shows that taking black currant anthocyanins 50 mg orally daily for 4 weeks decreases intraocular pressure (IOP) by 1.5 mmHg when compared with placebo (93696). However, other preliminary clinical research in patients with open-angle glaucoma shows that taking black currant anthocyanins 50 mg orally daily along with standard medications for glaucoma for 24 months does not improve IOP when compared with placebo (93695). Preliminary subgroup analyses suggest that patients taking one or less antiglaucoma medications, but not more than one, may benefit the most from black currant (93695,93696).
• Gout. Although there has been interest in using oral black currant leaf for gout, there is insufficient reliable information about the clinical effects of black currant for this purpose.
• Hyperlipidemia. It is unclear if oral black currant seed oil is beneficial in patients with hyperlipidemia. Details: Preliminary clinical research in adults with hyperlipidemia shows that taking black currant seed oil 18 grams orally twice daily for 6 weeks reduces total cholesterol by about 16%, reduces triglycerides by about 34%, and increases high-density lipoprotein (HDL) cholesterol by about 35% when compared with baseline (17638). However, the validity of this study is limited by the lack of a comparator group.
• Hypertension. It is unclear if oral black currant seed oil is beneficial in patients with hypertension. Details: Preliminary clinical research in males with borderline hypertension shows that taking black currant seed oil 6 grams orally daily for 8 weeks does not reduce blood pressure when compared with safflower oil 6 grams daily. However, when stress is induced by a mental arithmetic exercise, black currant seed oil appears to induce a 40% reduction in systolic and diastolic blood pressure elevations in these patients (35994).
• Influenza. Although there has been interest in using oral black currant berry for influenza, there is insufficient reliable information about the clinical effects of black currant for this purpose.
• Insect bite. Although there has been interest in using topical black currant leaf for insect bite, there is insufficient reliable information about the clinical effects of black currant for this purpose.
• Japanese cedar pollinosis. It is unclear if oral black currant extract is beneficial in patients with Japanese cedar pollinosis. Details: Preliminary clinical research in patients with Japanese cedar pollinosis shows that taking a black currant polysaccharide extract 540 mg orally twice daily for 8 weeks does not improve nasal symptom scores or swelling when compared with placebo (17635).
• Liver disease. Although there has been interest in using oral black currant leaf for liver disease, there is insufficient reliable information about the clinical effects of black currant for this purpose.
• Menopausal symptoms. Although there has been interest in using oral black currant seed oil for menopausal symptoms, there is insufficient reliable information about the clinical effects of black currant for this purpose.
• Muscle fatigue. It is unclear if oral black currant juice extract is beneficial in patients with muscle fatigue. Details: Preliminary clinical research in office workers shows that black currant juice extract, containing 10.83% anthocyanins, taken once orally and dosed as anthocyanins 17 mg/kg, reduces muscle stiffness scores after typing for 30 minutes when compared with placebo (17633).
• Osteoarthritis. Although there has been interest in using oral black currant leaf for osteoarthritis, there is insufficient reliable information about the clinical effects of black currant for this purpose.
• Peripheral arterial disease (PAD). Although there has been interest in using oral black currant juice for PAD, there is insufficient reliable information about the clinical effects of black currant for this purpose.
• Premenstrual syndrome (PMS). Although there has been interest in using oral black currant seed oil for PMS, there is insufficient reliable information about the clinical effects of black currant for this purpose.
• Rheumatoid arthritis (RA). It is unclear if oral black currant seed oil is beneficial in patients with RA. Details: A small clinical study in patients with RA shows that taking black currant seed oil 10.5 grams orally daily for 24 weeks reduces tenderness scores when compared with placebo (35990).
• Rhinosinusitis. Oral black currant has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients over 12 years of age with chronic sinusitis shows that taking a combination product containing black currant, Boswellia serrata, bromelain, and vitamin D (Flogostop Forte, Humana Italia) with inhaled corticosteroids daily for 30 days reduces rhinorrhea, hyperemia of mucosa, and local inflammation when compared with inhaled corticosteroids alone (111501). It is unclear if these findings are due to black currant, other ingredients, or the combination.
• Seizures. Although there has been interest in using oral black currant leaf for seizures, there is insufficient reliable information about the clinical effects of black currant for this purpose.
• Upper respiratory tract infection (URTI). Although there has been interest in using oral black currant berry for URTIs, there is insufficient reliable information about the clinical effects of black currant for this purpose.
• Urinary tract infections (UTIs). Although there has been interest in using oral black currant leaf for UTIs, there is insufficient reliable information about the clinical effects of black currant for this purpose.
• Venous insufficiency. Although there has been interest in using oral black currant for venous insufficiency, there is insufficient reliable information about the clinical effects of black currant for this purpose.
• Wound healing. Although there has been interest in using topical black currant leaf for wound healing, there is insufficient reliable information about the clinical effects of black currant for this purpose. More evidence is needed to rate black currant for these uses.

(Read more about BLACK CURRANT)

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. Oral evening primrose oil does not seem to improve symptoms in patients with mastalgia. 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).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• 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).
• 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. 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). 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. Research on the effects of evening primrose in labor is conflicting, and information on the dose used is lacking in some studies. Details: Meta-analyses of small, low-quality, clinical trials in healthy term pregnancies show that taking evening primrose oil decreases the duration of labor and reduces the odds of cesarean section by 39%, but does not affect neonatal weight, when compared with placebo. The effect of evening primrose oil on bishop scores is conflicting. Studied utilized evening primrose oil either orally as 1-4500 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. Additionally, the validity of these studies is limited by high heterogeneity (20524,96717,109028,109029). Population research has found that taking evening primrose oil from week 37 of pregnancy until delivery has no effect on gestation duration or cervical ripening, and seems to produce a trend towards prolonged labor and increased oxytocin requirements, in low-risk pregnancies (1411).
• 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.

(Read more about EVENING PRIMROSE)

POSSIBLY INEFFECTIVE

• Bipolar disorder. Oral flaxseed oil does not seem to reduce symptoms of bipolar disorder in children. Details: Clinical research in children ages 6-17 years with bipolar disorder shows that taking flaxseed oil, titrated to provide up to 6.5 grams of the flaxseed oil constituent alpha-linolenic acid, daily for 16 weeks does not improve symptoms of mania or depression when compared with placebo (66044).
• Hyperlipidemia. Oral flaxseed oil does not seem to reduce cholesterol levels. Details: Although some evidence from preliminary, low-quality clinical studies disagrees (21698,26466,76696), most clinical research shows that taking flaxseed oil does not reduce cholesterol or triglyceride levels in patients with or without hypercholesterolemia or hypertriglyceridemia (2317,16791,16794,21693,21694,21696,21697,22177,72228,101947)(101954,101956,111062). A meta-analysis of clinical studies evaluating various flaxseed formulations suggests that flaxseed oil consumption may reduce apolipoprotein A levels, but not apolipoprotein B levels, when compared with control groups (108046). A subgroup analysis from another meta-analysis suggests that flaxseed oil may modestly improve levels of high-density lipoprotein cholesterol (108044). It should be noted that most research suggests that flaxseed, the source of flaxseed oil, can improve lipid levels in adults with hyperlipidemia. This difference may be due to lipid lowering components such as lignans, phytic acid, and polyphenols, that are found in flaxseed, but not flaxseed oil. See the Flaxseed monograph for more information.
• Obesity. Oral flaxseed oil does not seem to improve weight loss. Details: A meta-analysis of clinical research in overweight adults shows that flaxseed oil consumption does not reduce body weight, body mass index, or waist circumference when compared with control (96427). This is in contrast to research suggesting that flaxseed, the source of flaxseed oil, can improve weight loss in obese and overweight adults. See the Flaxseed monograph for more information.
• Rheumatoid arthritis (RA). Oral flaxseed oil does not seem to improve symptoms of RA. Details: A small clinical study in patients with RA shows that taking flaxseed oil daily for 3 months does not seem to improve symptoms of pain and stiffness, and has no effect on laboratory measures of RA, such as C-reactive protein and erythrocyte sedimentation rate (ESR), when compared with control (5898).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atherosclerosis. Small clinical trials show that taking flaxseed oil has modest benefit on metabolic risk factors in patients with plaque in the coronary artery. Details: Observational research in White adults has found that high dietary intake of linolenic acid, a flaxseed oil constituent, is associated with reduced calcified atherosclerotic plaque in the coronary arteries (12990). However, clinical research has not confirmed this finding. A small clinical trial in patients with coronary artery disease shows that taking flaxseed oil 5 grams in milk containing 1.5% fat reduces triglyceride levels by 14% when compared with the milk alone. However, there was no effect on systolic blood pressure, high-density lipoprotein (HDL) cholesterol, or low-density lipoprotein (LDL) cholesterol (101954). Additionally, another small study in a similar patient population shows that taking flaxseed oil 2 grams daily for 12 weeks has no effect on lipid levels when compared with placebo (101956).
• Attention deficit-hyperactivity disorder (ADHD). Oral flaxseed oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in children with ADHD shows that taking flaxseed oil, providing 200 mg of alpha-linolenic acid, in combination with vitamin C 25 mg, twice daily can improve measures of attention, impulsivity, restlessness, and self-control when compared to baseline (14443). This finding is limited by the lack of a control group. Furthermore, it is unclear if the benefit is due to flaxseed oil, vitamin C, or the combination.
• Breast cancer. It is unclear if oral flaxseed oil reduces the risk of breast cancer. Details: Population research has found that females with higher levels of the flaxseed oil constituent, alpha-linolenic acid (ALA), in breast adipose tissue have a lower risk of breast cancer. Fatty acid composition of adipose tissue is thought to reflect past dietary intake, so researchers think high intake of ALA might have a cancer protective effect (7168,21689). Flaxseed oil is one source of ALA; it is unclear what effect, if any, flaxseed oil has on breast cancer risk.
• Burns. It is unclear if oral flaxseed oil improves wound healing and health in people with burns. Details: A small clinical trial in patients with mild to moderate burns shows that eating cookies containing flaxseed oil 30 grams and isolated soy protein (ISP) 50 grams daily for 3 weeks improves the rate of wound healing when compared with control cookies. It seems to take at least 3 weeks before this difference is observed. However, there is no significant difference in the rate of wound healing when compared with cookies containing ISP with corn oil (99401). It is possible that the study was underpowered to detect a difference between these two groups.
• Cardiovascular disease (CVD). It is unclear if oral flaxseed oil reduces the risk of CVD. Details: Flaxseed oil is a source of alpha-linolenic acid (ALA). A meta-analysis of observational studies has found that, overall, increasing dietary intake of ALA by 1.2 grams daily is associated with a 20% reduced risk of fatal coronary heart disease in people with existing heart disease (12978). Some research suggests that ALA has a greater impact on coronary heart disease when intake of fish oils is low (12989). It is unknown if flaxseed oil supplements have these same effects. Additionally, it is difficult to separate effects of dietary ALA in these studies from those of other dietary, lifestyle, or drug interventions (12917).
• Carpal tunnel syndrome. It is unclear if topical flaxseed oil reduces carpal tunnel pain. Details: Preliminary clinical research in patients with carpal tunnel syndrome who wear a wrist splint at night shows that applying flaxseed oil 5 drops topically on the palmar wrist twice daily for 4 weeks improves subjective symptom scores by 30%, function scores by 17%, and sensory nerve conduction velocity of the median nerve by about 7% when compared to baseline. Compared to the changes observed for patients in the placebo group, these improvements were significant (25691). It is unclear if this benefit persists long-term or how topical flaxseed oil compares to other standard treatments for carpal tunnel syndrome.
• Chronic kidney disease (CKD). Although there is interest in using oral flaxseed oil for CKD, there is insufficient reliable information about the clinical effects of flaxseed for this condition.
• Cognitive function. It is unclear if oral flaxseed oil improves cognitive function in healthy adults. Details: Clinical research in healthy older Japanese adults with normal cognitive function shows that taking flaxseed oil 3.7 grams daily for 12 weeks modestly improves verbal fluency when compared with taking placebo. However, there was no effect on other measures of cognitive function, including attention, concentration, and memory (111060).
• Diabetes. Oral flaxseed oil may not improve glycemic control in patients with type 2 diabetes. However, there may be some benefit in patients with gestational diabetes. Details: Most clinical research in patients with type 2 diabetes shows that taking flaxseed oil, providing about 1-16 grams of alpha-linolenic acid, daily for up to 6 months does not improve fasting blood glucose, glycated hemoglobin (HbA1C), or insulin resistance when compared with placebo (16792,66065,96428,96431,101956,111062). While taking flaxseed oil does not seem to be beneficial for type 2 diabetes, it might improve outcomes in gestational diabetes. A small clinical study in pregnant patients (24-28 weeks gestation) with gestational diabetes shows that taking flaxseed oil 1 gram twice daily for 6 weeks reduces fasting levels of glucose and insulin and improves insulin resistance when compared with placebo (101957). Another small clinical study in patients with gestational diabetes shows that taking flaxseed oil 1 gram, containing 400 mg of alpha-linolenic acid, along with vitamin E 400 IU daily for 6 weeks reduces blood glucose levels, insulin levels, and insulin resistance and improves beta-cell function when compared with placebo (96432). It is unclear if the findings from this latter study are due to flaxseed oil, vitamin E, or the combination.
• Diabetic foot ulcers. It is unclear if oral flaxseed oil improves the healing of diabetic foot ulcers. Details: One small clinical trial in adults with grade 3 diabetic foot ulcers shows that taking flaxseed oil 1 gram twice daily for 12 weeks in conjunction with intravenous antibiotics for the first 3 weeks reduces ulcer size when compared with placebo (96431).
• Dry eye. Flaxseed oil, both orally and as an eye drop, has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in patients with dry eye shows that taking a specific combination product (TheraTears Nutrition, Advanced Vision Research) containing eicosapentaenoic acid 450 mg, docosahexaenoic acid 300 mg, and flaxseed oil 1000 mg daily for 90 days reduces subjective symptoms of dry eye and might increase tear production when compared with placebo. However, it did not improve meibomian gland secretions or tear evaporation rate when compared with placebo (17523). Eye drops with flaxseed oil have also been tried for dry eye. A clinical study shows that using a specific product (Refresh Optive MEGA-3 Preservative-Free Lubricant Eye Drops, Allergan plc) which contains flaxseed oil and trehalose in addition to other ingredients such as carboxymethylcellulose (CMC) and castor oil twice daily for 90 days improves dry eye symptoms when compared to baseline, but not when compared with the same eye drops formulated without flaxseed oil and trehalose (101953).
• Dry skin. There is conflicting evidence regarding the use of flaxseed oil for dry skin. Details: Some clinical research suggests that taking flaxseed oil 2.2 grams orally in combination with alpha-tocopherol 10 mg daily for 12 weeks does not improve skin hydration when compared with placebo or borage oil in females with dry skin, although the combination seems to improve the sensitivity of dry skin (21908). Other clinical research suggests that taking flaxseed oil 2.2 grams daily for 12 weeks improves skin hydration and roughness when compared with safflower oil (21909).
• Endometrial hyperplasia. It is unclear if oral flaxseed oil reduces endometrial hyperplasia. Details: A small clinical trial in adults with endometrial hyperplasia shows that taking flaxseed oil 1 gram twice daily for 12 weeks does not induce endometrial regression or reduce cholesterol levels when compared with placebo. However, there appears to be a small benefit on fasting plasma glucose and insulin levels (101955).
• Hypertension. Small studies suggest that flaxseed oil may modestly lower blood pressure in some patients. Details: Epidemiological research has found that high dietary intake of linolenic acid, a flaxseed oil constituent, is associated with a reduced risk of developing hypertension (12991). Meta-analyses of small clinical studies in patients with and without hypertension show that receiving flaxseed oil 1.2-30 grams daily for 4-24 weeks reduces systolic and diastolic blood pressure by 0.5 mmHg to 4 mmHg, when compared with control (96426,111063). One meta-analysis limited to small clinical trials in patients with metabolic syndrome, hypercholesterolemia, or hypertension, shows that taking flaxseed oil 25 mL or 2.2 to 9.2 grams daily for 7-12 weeks reduces systolic blood pressure by about 3.9 mmHg; however, there is no effect on diastolic blood pressure (111067). The small size and heterogeneity of the studies included in these meta-analysis limit the validity of these findings. Also, the effect of taking flaxseed oil in patients specifically with hypertension is unclear from this available research. Flaxseed oil has also been evaluated in combination with other oils and dietary interventions, with mixed evidence of benefit. Flaxseed oil 19 grams, providing 10.5 grams of alpha-linolenic acid, seems to reduce blood pressure when combined with walnuts and walnut oil daily for 6 weeks (21905). However, consuming 60 grams of a combination of flaxseed and safflower oils in a 6:4 ratio daily for 4 weeks does not seem to affect blood pressure when compared with baseline (26466).
• Mastalgia. It is unclear if oral flaxseed oil is beneficial in patients with mastalgia. Details: A clinical study in adults with fibrocystic breasts and mastalgia shows that taking flaxseed oil 1000 mg containing 350 mg alpha-linolenic acid twice daily for 2 months reduces pain when compared with baseline, but is no different than taking vitamin E 200 IU daily (105477).
• Metabolic syndrome. It is unclear if oral flaxseed oil is beneficial in patients with metabolic syndrome. Details: A small clinical study in patients with metabolic syndrome shows that taking flaxseed oil 20 mL daily for 7 weeks does not improve coagulation scores based on prothrombin time, partial thromboplastin time, and the international normalized ratio (INR) when compared with sunflower oil (101951).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral flaxseed oil is beneficial in patients with NAFLD. Details: Clinical research in overweight or obese patients with NAFLD shows that taking flaxseed oil 20 grams daily for 12 weeks as part of a hypocaloric diet improves the grade of fatty liver by 41%, compared with 18% in patients taking sunflower oil. There was also a small effect on body mass index, although there was no effect on liver enzymes, glycemic control, or body composition (101952).
• Parkinson disease. Oral flaxseed oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in patients with Parkinson disease shows that taking flaxseed oil 1 gram daily plus vitamin E 400 IU daily for 12 weeks improves the Unified Parkinson Disease Rating Scale (UPDRS) total score by 3.3 points, compared to a 4.4-point worsening in the placebo group (96430). However, it is unclear if this change is clinically meaningful. The minimal clinically important improvement in UPDRS total score is 4.3 points, while a moderate improvement ranges from 9 to 17 points (95686). Also, it is not clear if these findings are due to flaxseed oil, vitamin E, or the combination.
• Physical performance. It is unclear if oral flaxseed oil improves physical performance in older adults. Details: A small clinical study in elderly adults without previous exercise training suggests that flaxseed oil containing alpha-linolenic acid does not improve muscle strength when compared with placebo (65937).
• Pneumonia. It is unclear if oral flaxseed oil helps to prevent pneumonia. Details: Epidemiological research has found that increasing dietary alpha-linolenic acid, which occurs in flaxseed oil, is associated with a reduced risk of community-acquired pneumonia (13760). However, this research did not specifically assess the effect of flaxseed oil intake on pneumonia.
• Polycystic ovary syndrome (PCOS). Small clinical studies suggest that oral flaxseed oil might help to improve some markers of PCOS. Details: A small clinical study in patients with PCOS shows that taking flaxseed oil, providing 545 mg of alpha-linolenic acid, for 6 weeks lowers triglycerides but does not affect weight, hormone levels, glycemic control, or cholesterol levels when compared to baseline (21906). This finding is limited by the lack of a control group. Another small clinical study in patients with PCOS shows that taking flaxseed oil, providing 1 gram of omega-3 fatty acids, twice daily in addition to metformin for 12 weeks decreases triglyceride and insulin levels, but does not affect fasting blood glucose, testosterone levels, free androgen index, or total cholesterol when compared with placebo (99402).
• Prostate cancer. Oral flaxseed oil does not seem to be linked to prostate cancer risk. Details: Although some epidemiologic research has found that high dietary intake of alpha-linolenic acid, a constituent of flaxseed oil, is associated with an increased risk for prostate cancer (1334,1337,2558,7823,7147,12978,12961), other research has found no association (12961,15736). Furthermore, it appears that alpha-linolenic acid from plant sources, such as flaxseed or flaxseed oil, does not increase prostate cancer risk (12909).
• Ulcerative colitis. It is unclear if oral flaxseed oil is beneficial in patients with ulcerative colitis. Details: A small open-label clinical study in patients with ulcerative colitis shows that taking flaxseed oil 10 grams daily for 12 weeks seems to modestly reduce inflammatory markers and disease severity and improve quality of life when compared with control (101941). More evidence is needed to rate flaxseed oil for these uses.

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POSSIBLY EFFECTIVE

• Benign prostatic hyperplasia (BPH). Taking oral pumpkin seed or pumpkin seed oil may improve symptoms of BPH. Details: One study in patients with BPH shows that taking pumpkin seed 5 grams twice daily for 12 months may be more effective for controlling symptoms than pumpkin seed extract 1000 mg twice daily (92383). A specific pumpkin seed extract (Prosta Pink Forte) 1-2 capsules daily for 12 weeks has also been used (11231). Some preliminary clinical research also suggests that taking pumpkin seed oil (Prostafit, EuRho Vital) two tablets daily for 6 months may be as effective as the medication prazosin (92382). Pumpkin seed oil has also been compared with tamsulosin. A clinical study comparing pumpkin seed oil 360 mg twice daily to tamsulosin 0.4 mg once nightly for 3 months shows that both treatment groups report improvements in BPH symptoms and quality of life when compared with baseline, although improvement appears greater in the tamsulosin group, specifically when measured at 1 month and 3 months. In the pumpkin seed oil group, adverse effects were reported in 0% of patients, compared with 15% of patients taking tamsulosin (107842). The validity of this study is limited due to the short duration of treatment. Pumpkin seed oil or extracts have also been studied in combination with saw palmetto (6777), with saw palmetto, nettle root, and lemon extracts plus beta carotene (5093), and with saw palmetto, small flowered willow herb, lycopene, and pygeum (92379).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Androgenic alopecia. Oral pumpkin seed oil might improve hair regrowth in males with mild to moderate hair loss. Details: Clinical research in males with mild to moderate hair loss shows that taking pumpkin seed oil (Octa Sabal Plus, Dreamplus Co. Ltd.) 400 mg daily in divided doses for 24 weeks increases hair count by 30% when compared with placebo. Self-rated improvement and satisfaction scores were 62% and 52% with pumpkin seed oil and placebo, respectively (92378). Clinical research in patients with female pattern hair loss shows that applying 1 mL of pumpkin seed oil to the scalp daily for 30 days improves hair regrowth similarly to minoxidil 5% foam, 1 mL daily (104974).
• Interstitial cystitis. Although there is interest in using oral pumpkin for interstitial cystitis, there is insufficient reliable information about the clinical effects of pumpkin for this condition.
• Intestinal parasite infection. Although there is interest in using oral pumpkin for intestinal parasite infection, there is insufficient reliable information about the clinical effects of pumpkin for this condition.
• Overactive bladder. Oral pumpkin seed oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in females with overactive bladder shows that taking a specific combination product (Granu Fink femina, Omega Pharma) containing pumpkin seed oil 227 mg, sweet sumac bark extract 56 mg, and hops cone extract 18 mg three times daily for 12 weeks decreases the frequency of urination and leakage and improves quality of life when compared to baseline (103253). The validity of these findings is limited by the lack of a control group. Additionally, it is unclear if these findings are due to pumpkin seed oil, other ingredients, or the combination.
• Urinary tract infections (UTIs). Although there is interest in using oral pumpkin for UTIs, there is insufficient reliable information about the clinical effects of pumpkin for this condition. More evidence is needed to rate pumpkin for these uses.

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LIKELY SAFE ...when used orally and appropriately. Black currant juice, leaves, and flowers have Generally Recognized As Safe (GRAS) status in the US (4912). Black currant juice up to 3000 mL daily for up to 3 weeks (17636,35987), black currant extracts 1080 mg daily for 8 weeks (17635,93695), and black currant seed oil products up to 10.5 grams daily for 24 weeks (4016,17634,17638,35990) have also been used safely in clinical research. There is insufficient reliable information about the safety of black currant when used topically.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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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). 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). Evening primrose oil has also been used safely during the last week of pregnancy to improve cervical ripening (20524,96717), although in one retrospective case series improvement was lacking and there was a trend toward prolonged labor, increased rates of arrest of descent, and increased oxytocin requirements (1411). 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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LIKELY SAFE ...when used orally and appropriately for medicinal purposes, short-term. Flaxseed oil has been used safely in doses up to 2 grams daily for up to 6 months. Higher doses of up to 24 grams daily has been safely used for up to 7 weeks (845,3912,5898,14443,16789,16791,16794,16795,17523,101951,101952,101955).

POSSIBLY SAFE ...when used topically for medicinal purposes, short-term. Flaxseed oil has been used safely on the wrist for up to 4 weeks (25691). ...when used in eye drops twice daily for up to 90 days (101953).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. Some evidence suggests that flaxseed oil, providing 200 mg of alpha-linolenic acid, can be safely used in children for up to 3 months (14443).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately for medicinal purposes, short-term. Although flaxseed oil has been used with apparent safety in clinical research in doses of 1-2 grams daily for up to 6 weeks (96432,101957), some population research has found that consuming flaxseed oil during the second and third trimesters of pregnancy is associated with a four-fold increased risk of premature birth (16797).

LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when used orally and appropriately in amounts commonly found in foods.

POSSIBLY SAFE ...when the seed or seed oil is used orally and appropriately in medicinal amounts, short-term. Pumpkin seed has been used with apparent safety in a dose of up to 10 grams daily for up to 12 months (92383). Pumpkin seed oil has been used with apparent safety in a dose of up to 400 mg daily for up to 6 months (92378). There is insufficient reliable information available about the safety of pumpkin seed oil when used topically.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using amounts greater than those found in food.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, black currant seed oil might increase the risk of bleeding if used in combination with anticoagulant or antiplatelet drugs.  Details Gamma-linolenic acid (GLA), a constituent of black currant seed oil, appears to have antiplatelet effects (1979,35995).

PHENOTHIAZINES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, black currant seed oil might increase the risk of seizure in patients receiving phenothiazines.  Details Black currant seed 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, although there is no evidence that black currant seed oil causes seizures (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 4 grams daily, which contains GLA, was added. One of these patients had a prior history of seizures (21010).

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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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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, using flaxseed oil in combination with anticoagulant or antiplatelet drugs might have additive effects and increase the risk of bleeding.  Details Small clinical studies show that consuming flaxseed oil might decrease platelet aggregation and increase bleeding time (5898,21912).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining flaxseed oil with other antihypertensive drugs might have additive effects and increase the risk of hypotension.  Details Some clinical evidence suggests that long-term consumption of flaxseed oil can modestly lower systolic and diastolic blood pressure, while other clinical research shows no effect (16793,96426,101941,101954,111063,111067).

EZETIMIBE (Zetia) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Concomitant use of flaxseed oil and ezetimibe reduces the absorption of alpha-linolenic acid from flaxseed oil.  Details In one clinical study, concomitant consumption of ezetimibe 10 mg daily with flaxseed oil 2 grams providing 1 gram of alpha-linolenic acid daily blocked the absorption of alpha-linolenic acid, resulting in an overall reduction in alpha-linolenic plasma levels from baseline (96433).

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LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Pumpkin might reduce excretion and increase levels of lithium.  Details Pumpkin is thought to have diuretic properties (92383). Theoretically, this might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.

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General ...Orally, black currant is generally well-tolerated. Topically, there is a limited amount of information on the adverse effects of black currant.

Gastrointestinal ...Of 2154 patients with hyperlipidemia taking black currant seed oil 1. 8 grams twice daily for 6 weeks, 8 reports of mild diarrhea were considered related to the supplement. These adverse reactions were reported 2-10 days after beginning treatment with black currant seed oil (17638).

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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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General ...Orally, flaxseed oil is generally well tolerated. Topically, flaxseed oil seems to be well-tolerated.
Most Common Adverse Effects:
Topically: Itching, redness.
Serious Adverse Effects (Rare):
Orally: Severe allergic reactions such as anaphylaxis.

Endocrine ...Orally, flaxseed oil might cause gynecomastia. In a case report, a 70-year-old male developed gynecomastia after taking flaxseed oil daily for 3 months. Discontinuing flaxseed oil lead to resolution of gynecomastia (105478).

Gastrointestinal ...Orally, flaxseed oil may cause a change in bowel habits, dry mouth, and dyspepsia when taken at a dose of about 5 grams daily. However, these effects have been reported by only a small number of patients (approximately 3%) (16794). High doses of flaxseed oil (30 grams per day and higher) have been associated with loose stools and diarrhea (5898,11025).

Immunologic ...Severe allergic reactions such as anaphylaxis have been reported with flaxseed oil ingestion and also in workers processing flaxseed products (6809).

Ocular/Otic ...Topically, eye drops containing flaxseed oil may cause redness and itching (101953).

Oncologic ...Flaxseed oil has not been linked to increased prostate cancer risk. Although epidemiologic research has found that high dietary intake of alpha-linolenic acid (ALA) is associated with increased prostate cancer risk (1337,2558,7147,7823,12978), this risk does not seem to apply to ALA from plant sources, like flaxseed (12909).

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General ...Orally, pumpkin products are generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal discomfort, diarrhea, nausea, and vomiting.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis.

Dermatologic ...There are two case reports of adult females developing substantial transient hair loss 1-3 weeks after consumption of a meal containing either bitter-tasting pumpkin or undefined squash. This adverse effect was attributed to a high concentration of cucurbitacin, which is commonly found in wild pumpkins (104535).

Gastrointestinal ...Orally, pumpkin seed oil has been reported to cause mild abdominal discomfort in clinical trials (5093,92378). There are also two case reports of adults developing severe nausea, vomiting, and diarrhea following consumption of a meal containing either bitter-tasting pumpkin or undefined squash. These adverse effects were attributed to a high concentration of cucurbitacin, which is commonly found in wild pumpkins (104535).

Immunologic ...Orally, pumpkin seed oil and pumpkin pulp have been reported to cause anaphylactic reactions in children and adults. A case review highlights 4 cases of anaphylaxis in children (3 from pumpkin pulp, 1 from pumpkin seeds), and 7 cases in adults (1 from pumpkin flesh, 6 from pumpkin seeds). Symptoms of anaphylaxis include urticaria, angioedema of the lips or face, dyspnea, dysphagia, and oropharyngeal itching and swelling. A case report describes a 2-year-old male presenting with urticaria, swollen lips, and increased dyspnea 10 minutes after ingesting pumpkin seeds. The patient was found to have elevated allergen-specific immunoglobulin E (IgE) and a positive skin-prick test for pumpkin seeds. Symptoms resolved after treatment with epinephrine, systemic glucocorticoids, salbuterol, and antihistamines (107843).
There may also be concern for allergic reaction due to inhalation or topical exposure. One case report describes an 8-year-old child developing anaphylaxis while carving a pumpkin; another highlights that inhalation of pumpkin seed flour may have potentiated anaphylaxis in 3 individuals following the ingestion of pumpkin seeds (107843). Further research is necessary to assess the relationship between anaphylaxis and route of administration.

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