Pump Princess [Discontinued] by Legendairy Milk

POSSIBLY EFFECTIVE

• Acne. Topical black seed extract hydrogel seems to improve acne. Details: In patients with mild to moderate acne, clinical research shows that topical application with a hydrogel containing black seed extract 0.1% twice daily for 60 days reduces the number of comedones, papules, and pupules by a large amount when compared with placebo. The overall improvement, as rated by a physician, was 78% for the black seed extract hydrogel, compared with 3% for the placebo gel (101551).
• Allergic rhinitis (hay fever). Oral black seed oil seems to reduce symptoms of allergic rhinitis over 4-8 weeks. It is unclear if black seed is beneficial long-term. Details: Clinical research shows that taking capsules containing black seed oil 0.5 mL daily for 1 month can reduce symptoms such as itching, nasal congestion, sneezing, and runny nose when compared with placebo in adults with allergic rhinitis (95989). Other preliminary clinical research shows that taking a specific product containing black seed oil 500 mg (Immerfit, Phyt-Immun) for a total dose of 40-80 mg/kg orally daily for 4-8 weeks improves patient-scored symptoms of allergic rhinitis in 81% of patients, compared to 45% of patients taking placebo (36071). More research is needed to determine if black seed is beneficial long-term and how it compares to conventional allergy medications.
• Asthma. Oral black seed seems to be beneficial for symptoms like wheezing and coughing and might improve lung function measures in patients with poor pulmonary function. Details: Some clinical research shows that taking black seed extract for 3 months can improve symptoms such as wheezing and coughing when compared with placebo in patients with moderate to severe asthma who already take conventional asthma medication (36175). Other research shows that taking black seed oil (Cuminmar, Marnys) 500 mg twice daily for 4 weeks can improve self-reported asthma control and daily functioning when compared with placebo in adults with inadequately controlled asthma despite using maintenance inhalers (95987). The effects of black seed on pulmonary function are conflicting. Some research shows that taking black seed can improve lung function measures such as forced expiratory flow (36175,36280,94490,101556), while other research shows no significant benefit (95987,101556). Doses used in studies showing benefit include ground black seed 2 grams daily for 12 weeks, black seed extract 15 mL/kg daily for 3 months, or a single dose of 50-100 mg/kg (36175,36280,94490). Differing findings may relate to pulmonary function at baseline. Taking black seed extract or black seed oil seems to improve pulmonary function in patients with abnormally low pulmonary function at baseline, but not those with predicted forced expiratory volume in 1 second (FEV1) of at least 80% (36175,95987). Also, single doses of black seed extract do not appear to improve pulmonary function as effectively as bronchodilators such as theophylline or salbutamol (36280).
• Chronic obstructive pulmonary disease (COPD). Oral black seed seems to improve lung function measures in patients with COPD using inhaled corticosteroids. Details: In middle-aged adults undergoing routine treatment with inhaled corticosteroids for COPD, clinical research shows that taking black seed oil (Amazing Herbs) 1 gram twice daily for 3 months improves pulmonary function tests by a small to moderate amount when compared with placebo (104663).
• Diabetes. Oral black seed powder in doses of at least 2 grams daily or black seed oil 1 gram daily seem to improve glucose control in patients with type 2 diabetes. Details: One clinical study shows that taking black seed powder 1 gram twice daily for 3-12 months improves glycated hemoglobin (HbA1c) and decreases fasting blood glucose by 17% to 26% when compared to baseline in patients with diabetes who are already using antidiabetes medications (94479,94485). These improvements were significant when compared with placebo at 3 months and 9 months, but not at 12 months (94485). Clinical research also shows that taking black seed powder 1 gram twice daily also improves levels of total cholesterol by 10% to 12% when compared with placebo in patients with diabetes (94478); a lower dose of 1 gram daily does not seem to be beneficial (94479). The effect of black seed oil has also been investigated. Clinical research shows that taking black seed oil 450 mg three times daily for 12 weeks decreases fasting blood glucose by around 14 mg/dL and HbA1c by 0.3% in patients with newly diagnosed diabetes when compared with baseline. However, these improvements were inferior to those reported in patients taking metformin 2000 mg daily (102062). Other clinical research shows that taking black seed oil 1 gram daily for 8 weeks decreases fasting blood glucose by 23.0 mg/dL and HbA1c by 0.69% from baseline. These changes, as well as reductions in low-density lipoprotein (LDL) cholesterol, triglycerides, and systolic and diastolic blood pressure were significant when compared with placebo (110269). Other clinical research also shows that taking black seed oil 1 gram daily for 8 weeks reduces fasting blood glucose, triglyceride, and low-density lipoprotein (LDL) cholesterol levels when compared with placebo. However, baseline levels for each of these parameters were higher in the treatment group when compared with the placebo group, raising concerns about the validity of these findings (101552). The black seed constituent thymoquinone has also been investigated in clinical research. Clinical research in patients with type 2 diabetes shows that taking thymoquinone 50 mg or 100 mg daily in addition to metformin 1 gram daily for 90 days increases the number of patients with HbA1c levels of less than 7.0% when compared with metformin alone. However, it is unclear if fasting blood glucose levels are further reduced (110270).
• Helicobacter pylori. Oral black seed 2 grams daily seems to improve H. pylori eradication when used in combination with standard therapies. Details: Clinical research shows that in patients receiving quadruple therapy with metronidazole, amoxicillin, bismuth subcitrate, and omeprazole, the eradication of H. pylori occurred in 88% of patients receiving quadruple therapy plus black seed powder 1 gram twice daily for 8 weeks, compared with 55% of patients taking quadruple therapy alone. Quality of life was also improved (101555). Clinical research also shows that taking black seed powder (BioExtract Ltd) 2 grams daily along with omeprazole 40 mg daily for 4 weeks produces H. pylori eradication in 67% of patients, compared to 83% of patients taking standard triple therapy with clarithromycin, amoxicillin, and omeprazole taken for 1 week. However, this study also found that taking black seed powder 1 gram or 3 grams daily along with omeprazole was less effective than standard triple therapy (95980). The reasons for this discrepancy are unclear.
• Hypertension. Oral black seed powder and black seed oil seem to reduce blood pressure by a small amount. However, if it is unclear if taking black seed is beneficial in patients with hypertension. Details: A pooled analysis of results from small clinical studies in patients with or without hypertension shows that taking black seed powder 0.5-2 grams daily or black seed oil up to 3 grams daily for 4-12 weeks reduces systolic and diastolic blood pressure by about 3 mmHg when compared with placebo (94489). Only one of the studies included in the analysis investigated the effect of black seed in males with hypertension. This small study showed that taking black seed oil 100-200 mg twice daily for 8 weeks modestly reduces systolic and diastolic blood pressure by about 2 mmHg (16437). Another study in the analysis that included patients with or without hypertension found that taking black seed oil 2.5 mL twice daily after meals for 8 weeks reduces systolic and diastolic blood pressure by about 11 mmHg and 10 mmHg, respectively, when compared with baseline (96929).
• Male infertility. Oral black seed oil seems to improve sperm quality and function. It is unclear if this increases the rate of successful pregnancies. Details: Clinical research shows that taking black seed oil 2.5 mL twice daily for 2 months improves sperm count by 40%, sperm morphology by 32%, and sperm motility by 13% when compared with placebo in infertile males (94486).
• Mastalgia. Topical black seed oil seems to reduce breast pain. Details: Clinical research shows that applying 2 grams of gel containing 30% black seed oil at the site of pain twice daily for two menstrual cycles reduces breast pain by about 82% when compared to baseline. This improvement is similar to diclofenac gel and significantly greater than placebo gel, which reduces pain by only 18% (94483).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anthracycline cardiotoxicity. It is unclear if oral black seed oil reduces cardiac toxicity associated with doxorubicin treatment. Details: Preliminary clinical research in children aged 2-16 years with acute lymphoblastic leukemia shows that taking black seed oil 80 mg/kg in three divided doses daily for one week, starting with each doxorubicin infusion therapy, is protective against some, but not most, measures of cardiac toxicity associated with doxorubicin. However, it is unclear if any of these changes are associated with clinically meaningful improvements in outcome (101554).
• Atopic dermatitis (eczema). It is unclear if oral or topical black seed oil is beneficial for reducing symptoms of atopic dermatitis. Details: One small study reports that using 15% black seed oil ointment topically for 4 weeks does not improve disease severity, pruritus, or hydration in patients with atopic dermatitis (36316). Other preliminary clinical research shows that taking a specific product containing black seed oil 500 mg (Immerfit, Phyt-Immun) for a total dose of 40-80 mg/kg daily for 4-8 weeks improves subjective patient-scored symptoms of atopic dermatitis in 50% of patients when compared to baseline (36071).
• Autoimmune thyroiditis. It is unclear if oral black seed is beneficial for patients with autoimmune thyroiditis. Details: Clinical research in patients with Hashimoto's thyroiditis shows that taking black seed powder 2 grams daily for 8 weeks increases thyroid stimulating hormone levels by 36% and anti-thyroid peroxidase (anti-TPO) antibody levels by 50% when compared to baseline; these improvements are significant when compared with placebo. However, black seed powder does not improve thyroxine or triiodothyronine levels when compared with placebo (94481).
• Cancer. Although there is interest in using oral black seed for cancer, there is insufficient reliable information about the clinical effects of black seed for this condition.
• Cardiovascular disease (CVD). It is unclear if oral black seed is beneficial for patients with coronary artery disease. Details: A small clinical trial shows that taking black seed oil 2 grams daily for 8 weeks reduces systolic and diastolic blood pressure by 9.52 mm Hg and 8.26 mm Hg, respectively, when compared with placebo. Fasting blood glucose, body mass index, and waist and hip circumferences were also modestly reduced. There was no effect on other glycemic indices. There was also no effect on blood lipids; however, most patients were taking statins (110276).
• Chemotherapy-induced lymphocytopenia. It is unclear if oral black seed is beneficial for preventing febrile neutropenia. Details: Preliminary clinical research in children undergoing chemotherapy for brain tumors shows that taking whole or ground black seed 5 grams daily as part of the diet for 3-9 months of chemotherapy reduces the incidence of febrile neutropenia episodes by 88% when compared with placebo. To prevent one case of febrile neutropenia, six patients would need to be treated with black seed. The duration of hospital stay was also reduced by 2.5 days when compared with placebo (96931).
• Chemotherapy-induced phlebitis. It is unclear if oral black seed is beneficial for reducing the severity of phlebitis in patients receiving intravenous chemotherapy. Details: Preliminary clinical research in cancer patients receiving intravenous chemotherapy shows that applying 5 drops of black seed oil around the peripheral vein catheter twice daily for 3 days decreases phlebitis severity and reduces the relative risk of phlebitis at 72 hours by 35% when compared with no treatment. These results suggest that for every 3 patients treated with black seed oil for 3 days, one additional case of phlebitis will be prevented (102060).
• Chronic kidney disease (CKD). It is unclear if oral black seed oil is beneficial for patients with CKD. Details: Preliminary clinical research in patients with stages 3 and 4 CKD shows that taking black seed oil (Kalonji oil, Mohammedia products) 2.5 mL once daily for 12 weeks as add-on therapy with alpha-keto analogues of essential amino acids improves measures of kidney function by a small amount when compared with taking the alpha-keto analogues alone (101550).
• Cognitive function. Oral black seed might improve some measures of memory or cognitive function. Details: Clinical research in a small group of adolescent males shows that taking crushed black seed 500 mg daily for 4 weeks improves some measures of short-term or long-term recall when compared with placebo (96915). Other clinical research in a small group of middle-aged men shows that taking black seed 500 mg twice daily for 9 weeks improves some measures of memory, attention, and cognitive function when compared with placebo (96928). The improvements in both studies appear to be modest, so the clinical significance is unclear.
• Constipation. Although there is interest in using oral black seed for constipation, there is insufficient reliable information about the clinical effects of black seed for this condition.
• Contraception. Although there is interest in using oral black seed for contraception, there is insufficient reliable information about the clinical effects of black seed for this purpose.
• Coronavirus disease 2019 (COVID-19). It is unclear if oral black seed is beneficial for patients with COVID-19. Details: Preliminary clinical research in patients with mild COVID-19 shows that taking black seed oil (Marnys Cuminmar) 500 mg twice daily for 10 days results in recovery by day 14, defined as freedom of symptoms lasting three days, in 62% of patients, compared with 36% of those patients not given black seed oil. Also, the duration to recovery was reduced by 1.6 days (110267). Also, preliminary clinical research in patients with mild to moderate COVID-19 shows that taking black seed (Baraka, Pharco Pharmaceuticals, Cairo, Egypt) 900 mg twice daily for 14 days modestly reduced the severity of some symptoms, including cough, diarrhea, fatigue, and pharyngitis, as well as the percent patients with viral positivity at day 7, when compared to standard care alone. Similar findings occurred when black seed was taken with vitamin D3 (Davalindi, Medical Union Pharma, Cairo, Egypt) 2,000 IU daily (110265). These studies are limited by a lack of placebo and blinding. In contrast to these findings, clinical research in patients with mild or asymptomatic COVID-19 does not show that taking black seed for 10 days has beneficial effects on symptoms or inflammatory markers when compared with charcoal as control. The black seed form in this study varied between whole seeds and powder, as well as the number (two to nine) of capsules taken in divided doses daily (110271). Black seed oil has also been investigated in combination with other compounds. Preliminary clinical research in patients with moderate to severe COVID-19 given standard care shows that taking black seed powder 80 mg/kg daily in combination with raw honey 1 gram/kg daily for 13 days reduces the time to alleviate symptoms by approximately 50%, and the time to clear virus by about 35%, when compared with placebo capsules and no honey. In patients with moderate symptoms, 63.6% had resumed normal activity within 6 days when compared with 10.9% of those taking placebo. In patients with severe symptoms, 50% were discharged from hospital by day 6 compared with 2.8% of those taking placebo, and the mortality rate was reduced by approximately 79% (110261). It is not clear if any beneficial effects are due to black seed, honey, or the combination.
• Diarrhea. Although there is interest in using oral black seed for diarrhea, there is insufficient reliable information about the clinical effects of black seed for this condition.
• Dysmenorrhea. It is unclear if topical black seed oil reduces menstrual pain. Details: Clinical research shows that topical application of black seed oil (Barij Essence Company) 1-2 drops to the fontanel lobe of the head each night for up to 8 days, starting three days before menstruation, for three menstrual cycles modestly reduces menstrual pain when compared with olive oil (104662). It is unclear if any benefits are clinically significant.
• Dyspepsia. Oral black seed oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking a 1:1:1 mixture of a black seed oil, honey, and water orally for 2 months improves overall symptoms of dyspepsia by approximately 43%, compared to only 10% in the placebo group (94487).
• Epilepsy. It is unclear if oral black seed is beneficial for patients with epilepsy. Details: Some preliminary clinical research in children aged 13 months to 13 years with epilepsy shows that taking black seed extract 40 mg/kg every 8 hours for 4 weeks reduces the frequency of seizures in 65% of, compared to only 20% of patients taking placebo (36180). Other preliminary clinical research in children 2-16 years of age with epilepsy shows that taking black seed oil 40-80 mg/kg daily does not reduce seizure frequency or severity when compared with placebo (94491). It is possible that there is a constituent found in the extract, and absent in the oil, that is responsible for any anti-seizure effects of black seed.
• Gingivitis. It is unclear if topical black seed is beneficial for patients with gingivitis. Details: In patients with moderate to severe gingivitis, preliminary clinical research shows that topical application of black seed extract for three days reduces gingival swelling and redness by a moderate amount, and plaque by a small amount, when compared to baseline. However, it is less effective than scaling and root planing (104664).
• Hemorrhoids. Although there is interest in using oral black seed for hemorrhoids, there is insufficient reliable information about the clinical effects of black seed for this condition.
• Hepatitis C. It is unclear if oral black seed is beneficial for patients with hepatitis C. Details: Preliminary clinical research shows that taking black seed oil (Baraka, Pharco Pharmaceuticals) 450 mg three times daily for 3 months reduces hepatitis C viral load in 67% of patients, improves lower limb edema, and modestly increases total protein and albumin levels when compared to baseline; however, no improvement is seen in Child-Pugh score or other measures of liver function, including bilirubin, liver enzymes, or INR (95986). The validity of these findings is limited by the lack of a control group.
• HIV/AIDS. Although there is interest in using oral black seed for HIV/AIDS, there is insufficient reliable information about the clinical effects of black seed for this condition.
• Hyperlipidemia. It is unclear if oral black seed is beneficial for patients with hyperlipidemia. Details: Some preliminary clinical research shows that taking whole crushed black seed 1 gram twice daily or black seed powder 1 gram daily for 4-8 weeks reduces total cholesterol by 5% to 16%, low-density lipoprotein (LDL) cholesterol by 8% to 27%, and triglycerides by 17% to 22% when compared to baseline in these patients; these improvements are significantly greater than changes in the placebo group (18221,94484). The effect of black seed when used in combination with statins shows conflicting results. One clinical study shows that taking black seed powder 1 gram twice daily for 6 weeks does not decrease cholesterol levels when compared with statins alone in normocholesterolemic, borderline hypercholesterolemic, or hypercholesterolemic patients (36244). Other clinical research in adults with hypercholesterolemia shows that taking whole crushed black seed 500 mg, garlic oil 250 mg, and simvastatin 10 mg daily for 8 weeks produces a larger increase in high-density lipoprotein (HDL) cholesterol and a greater reduction in total cholesterol, LDL cholesterol, and triglycerides when compared with simvastatin 10 mg daily alone (95985). Reasons for these conflicting results may relate to the black seed dose or formulation and the cholesterol levels of the included patients at baseline. Taking whole crushed black seed 1 gram twice daily for 8 weeks in conjunction with aerobic training does not appear to improve LDL cholesterol, total cholesterol, or triglyceride levels when compared with aerobic training alone in females with hypercholesterolemia; however, it appears to modestly increase HDL cholesterol levels (95983).
• Impaired glucose tolerance (prediabetes). It is unclear if oral black seed oil is beneficial for patients with prediabetes. Details: Preliminary clinical research in obese patients with prediabetes shows that taking black seed oil (Baraka450; Pharco Pharmaceutical Company) 450 mg twice daily for 6 months improves most anthropometric, lipid, and glycemic parameters when compared with baseline. Also, most improvements are similar to changes following the use of metformin 500 mg twice daily or following a controlled diet and exercise regimen (110275).
• Influenza. Although there is interest in using oral black seed for influenza, there is insufficient reliable information about the clinical effects of black seed for this condition.
• Insomnia. Although there is interest in using oral black seed oil for insomnia, there is insufficient reliable information about the clinical effects of black seed oil for this condition.
• Lichen planus. It is unclear if topical black seed oil is beneficial for patients with oral lichen planus. Details: Clinical research in patients with oral lichen planus shows that topical application with cream containing black seed oil (Greenish Baraka black seed oil, Greenish India Pvt. Ltd., Chennai) 75% twice daily after meals for 45 days is as effective as gel containing clobetasol propionate 0.05% for reducing lesion size and burning severity (110263). This study is limited by the lack of inclusion of a placebo-controlled group.
• Menopausal symptoms. Oral black seed has only been evaluated in combination with other ingredients; its effect when used alone is unclear. It is unclear if topical black seed oil is beneficial for menopausal symptoms. Details: Preliminary clinical research in postmenopausal females shows that taking a combination of black seed and vitex agnus-castus daily for 8 weeks, in combination with citalopram 20 mg, improves vasomotor, psychosocial, and physical symptoms of menopause when compared with placebo and citalopram (100325). It is not clear if these effects are due to black seed, vitex agnus-castus, or the combination. Clinical research in postmenopausal females shows that topical application with 2-3 drops of black seed oil (Barij Essence Pharmaceutical Company, Kashan, Iran) on the lower abdomen twice daily for 8 weeks does not improve sexual function or quality of life related to menopause when compared with placebo (110262).
• Metabolic syndrome. It is unclear if oral black seed is beneficial for patients with metabolic syndrome. Details: Clinical research in patients with metabolic syndrome after menopause shows that taking black seed extract 500 mg daily for 8 weeks improves levels of fasting blood sugar by 23%, low-density lipoprotein (LDL) cholesterol by 12%, and triglycerides by 8% over baseline. These changes were significant when compared with placebo. However, taking black seed extract did not improve anthropometric measures when compared with placebo (101549). In addition, preliminary clinical research in patients with metabolic syndrome shows that taking a specific black seed oil product (Mohammedia Products, Hyderabad) 2.5 mL twice daily for 6 weeks decreases total cholesterol by 59%, LDL cholesterol by 50%, and fasting blood glucose by 58% over placebo (36262). The effects of this black seed oil product on other important parameters of metabolic syndrome, such as weight and blood pressure, were not reported in this study. In contrast, other clinical research shows that taking bread providing black seed powder 3 grams daily for 2 months does not have a significant effect on lipid profiles in patients with metabolic syndrome. Weight and waist circumference were not reported (104667).
• Methotrexate toxicity. It is unclear if oral black seed oil is beneficial for reducing toxicity associated with methotrexate treatment. Details: Preliminary clinical research shows that taking black seed oil (Baraka, Pharco Pharmaceuticals) 80 mg/kg orally in three divided doses daily for 1 week after each methotrexate dose prevents elevations in bilirubin and liver function enzymes when compared with placebo in children aged 4-13 years with acute lymphoblastic leukemia (95984).
• Nonalcoholic fatty liver disease (NAFLD). Research suggests that oral black seed or black seed oil modestly improves some metabolic and liver health parameters in patients with NAFLD. However, some studies are small, and research related to measures of steatosis, including liver biopsy and magnetic resonance imaging (MRI), is needed. Details: Clinical research in adults with NAFLD shows that taking black seed oil 2.5 mL twice daily for 3 months, or 1000 mg (Barij Essence Co., Iran) daily for 8 weeks, modestly increases high-density lipoprotein (HDL) cholesterol levels and reduces levels of liver function enzymes, low-density lipoprotein (LDL) cholesterol, and triglycerides when compared with placebo (100322,110282). These studies also show that taking black seed oil also modestly improves levels of fasting blood glucose (110282) and steatosis grade as measured by ultrasound (100322). In one study, both black seed oil capsule and placebo capsule also contained honey and water (100322). However, taking black seed oil does not seem to improve insulin levels (110282). The effect of black seed oil on blood pressure has also been investigated. Clinical research shows that taking black seed oil (Barij Black Seed Oil, Barij Essence Pharmaceutical Company, Kashan, Iran) 1000 mg daily for 8 weeks does not reduce systolic or diastolic blood pressure when compared with placebo (110274,110282). Black seed has also been investigated in small clinical trials in adults with NAFLD. One trial shows that taking black seed 2 grams daily for 12 weeks reduces glucose and insulin levels, improves measures of insulin sensitivity and resistance, and reduces hepatic steatosis percentage when compared with placebo. However, there was no improvement in fibrosis scores, steatosis grades, and levels of lipids and liver function enzymes (102061). Another trial shows that using the same dose of black seed powder results in large reductions in body weight and body mass index (BMI), as well as liver enzymes, when compared with placebo. Also, 57.1% of patients taking black seed had normal fatty liver grading on abdominal ultrasound, compared with 6% of those taking placebo (110268). The reasons for these disparate results are unclear. However, it is possible the studies were underpowered to detect differences in secondary outcomes. More research is needed using gold standard measures of steatosis, including liver biopsy and magnetic resonance imaging (MRI).
• Obesity. It is unclear if oral black seed is beneficial for increasing weight loss. Details: Meta-analyses of preliminary clinical research involving a total of 875 patients show that taking black seed oil 3-5 grams daily, black seed powder 0.1-3 grams daily, or black seed extract 100-200 mg daily for up to 13 weeks reduces body weight by about 2 kg and body mass index (BMI) by 0.85-1.2 kg/m2 when compared with placebo. It is unclear if these reductions are clinically significant. In addition, most studies in these meta-analyses do not involve patients with a BMI over 25 kg/m2 (96926,98815). Although some individual research shows that taking black seed powder 2 grams or black seed oil 3 grams daily for 8 weeks does not reduce BMI in overweight females who are also exercising or following a low-calorie diet (95983,96927), most individual studies show that black seed or black seed oil reduces body weight and waist circumference (95730,96927,104661,110269). One study shows that black seed has a moderate effect on weight loss, BMI, and waist circumference, and a small effect on total and visceral fat mass (104661). These studies have used black seed powder 1.5 grams twice daily for 3 months or black seed oil 2 or 3 grams daily for 8 weeks (95730,96927,104661). Reasons for the discrepancies may relate to concomitant use with dieting or exercise. It is unclear if taking black seed oil improves the lipid profile of individuals with a BMI of at least 25 kg/m2. One small clinical study shows that taking black seed oil 2 grams daily for 8 weeks has a small to moderate effect on levels of high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol when compared with placebo (104666). However, another study shows that although taking black seed oil 3 grams daily for 8 weeks reduces triglyceride levels more than placebo, there is no effect on HDL or LDL cholesterol levels (96927).
• Opioid withdrawal. It is unclear if oral black seed is beneficial for reducing symptoms of opioid withdrawal. Details: Preliminary clinical research shows that taking black seed powder 500 mg by mouth three times daily for 12 days decreases symptoms of opioid withdrawal by 70% to 77% when compared to baseline (36239). The validity of this finding is limited by the lack of a comparator group.
• Osteoarthritis. It is unclear if topical black seed oil is beneficial for knee osteoarthritis. Details: Preliminary clinical research shows that applying black seed oil 1 mL to the knee by massaging into the skin for 5 minutes three times daily for 3 weeks reduces pain when compared to baseline and produces a larger reduction in pain than acetaminophen 325 mg three times daily for 3 weeks (95981). Other clinical research shows that applying approximately 10 mL of black seed oil to the knees three times weekly for 1 month reduces pain severity when compared to baseline (98814). The validity of this finding is limited by the lack of a control group.
• Psoriasis. Although there is interest in using topical black seed for psoriasis, there is insufficient reliable information about the clinical effects of black seed for this condition.
• Radiation dermatitis. It is unclear if topical black seed is beneficial for preventing dermatitis caused by radiotherapy. Details: Clinical research in breast cancer patients undergoing radiation treatment shows that applying a gel containing black seed extract providing thymoquinone 0.01% twice daily delays the incidence of radiation dermatitis and the onset of moist desquamation by 2-6 days when compared with placebo gel. However, there was no effect on the quality of life related to skin condition (101557).
• Rheumatoid arthritis (RA). It is unclear if topical black seed is beneficial for RA. Details: Preliminary clinical research shows that taking a specific brand of black seed oil (Nigellar, Kahira Pharmaceutical and Chemical Industries Company) 500 mg twice daily for one month improves symptoms of RA, such as pain, morning stiffness, and disease severity, when compared with placebo in patients who are already taking methotrexate (94482).
• Senile rhinitis. It is unclear if topical black seed is beneficial for patients with senile rhinitis. Details: The elderly population is particularly susceptible to symptoms of nasal dryness and irritation due to a reduction in mucus production. Preliminary clinical research shows that black seed oil given as 3 sprays into each nostril three times daily for 2 weeks can modestly improve symptoms of nasal dryness, obstruction, and crusting in this population when compared with sodium chloride nasal spray; however, there is no improvement in burning, itching, or nasal mucociliary clearance (95988).
• Tonsillopharyngitis. Oral black seed has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that the combination of chanca piedra 50 mg and black seed 360 mg, taken orally three times daily for 7 days, may relieve pain in patients with tonsillopharyngitis when compared with placebo (36199).
• Ulcerative colitis. It is unclear if oral black seed is beneficial for patients with ulcerative colitis. Details: Preliminary clinical research in adults with mild to moderate ulcerative colitis shows that taking black seed powder 2000 mg daily for 6 weeks does not improve disease activity scores or symptoms of ulcerative colitis when compared with placebo (100323).
• Urinary incontinence. It is unclear if topical black seed oil is beneficial for patients with urinary incontinence. Details: Clinical research in postmenopausal females with urinary incontinence shows that topical application with 2-3 drops of black seed oil (Barij Essence Pharmaceutical Company, Kashan, Iran) on the lower abdomen twice daily for 8 weeks modestly improves symptoms of mixed urinary incontinence, as well as related quality of life, when compared to placebo. However, there was no beneficial effect of topical black seed oil on stress incontinence, urge incontinence, or severity of symptoms (110262).
• Vaginal candidiasis. Although there is interest in using intravaginal black seed for vaginal fungal infections, there is insufficient reliable information about the clinical effects of black seed for this condition.
• Vitiligo. It is unclear if topical black seed oil is beneficial for patients with vitiligo. Details: Preliminary clinical research in adults with vitiligo shows that applying a cream containing black seed oil to the skin twice daily for 6 months improves skin pigmentation. This cream induced repigmentation of 50% or more in around 44% of patients with facial or hand involvement and 88% of patients with genital region involvement (102064). The validity of these findings is limited by the lack of a comparator group. More evidence is needed to rate black seed for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. Applying dill seed extract to the skin may improve some measures of skin wrinkles, but the overall clinical benefit is small. One clinical study in women with age-related wrinkles around the eyes shows that applying 1% dill seed extract to the face twice daily for 3 months improves skin elasticity and firmness by up to 30%, as well as average wrinkle size by approximately 20%, compared with a placebo formulation. However, the dill formulation does not appear to reduce the number of wrinkles or total wrinkle size (99908).
• Dysmenorrhea. Preliminary clinical research shows that taking dill seed powder 3 grams in two divided doses daily for 3 days, beginning at the onset of pain and repeated over three consecutive menstrual cycles, reduces pain associated with dysmenorrhea by a moderate to large amount when compared with baseline. However, it does not improve other menstrual symptoms (101994). The validity of this finding is limited by the lack of a comparator group.
• Hyperlipidemia. Preliminary clinical research in hyperlipidemic patients with coronary artery disease shows that taking dill 650 mg orally twice daily for 6 weeks in addition to following a cholesterol-lowering diet does not improve levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglycerides (47790). In patients with type 2 diabetes, taking dill leaf powder 3 grams daily for 8 weeks lowers LDL cholesterol and total cholesterol, and increases HDL cholesterol when compared with placebo, but does not affect triglycerides (112061). In a meta-analysis of 7 trials, dill significantly reduced LDL cholesterol in a subgroup of patients over 50 years of age who took doses above 1000 mg daily for at least 8 weeks. The analysis did not find any effect on triglycerides, total cholesterol, or high-density lipoprotein (HDL) cholesterol (112062).
• Labor pain. Preliminary clinical research shows that consuming boiled and filtered dill seeds 10 grams once at the beginning of the active labor phase does not reduce labor pain when compared with routine care. However, the duration of each stage of labor was reduced by up to 50% and there was improvement in dilation and effacement (99907). When compared with oxytocin 10 IU at the beginning of the active phase of labor, taking boiled dill seeds 10 grams reduces the duration of the first stage of labor, but not the second or third stages. It also decreases the occurrence of severe anxiety, but does not improve labor pain, when compared with oxytocin (101993). More evidence is needed to rate dill for these uses.

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POSSIBLY EFFECTIVE

• Dysmenorrhea. Taking fennel oil or extract by mouth may reduce pain in patients with primary dysmenorrhea. This benefit may be similar to ibuprofen or mefenamic acid. Details: Two separate meta-analyses in patients with primary dysmenorrhea show that taking fennel oil or fennel extract for 1-6 menstrual cycles reduces dysmenorrhea pain when compared with placebo. Improvement in pain was similar when compared with ibuprofen or mefenamic acid. In the included studies, doses of fennel oil ranged from 3-30 drops every 4-8 hours, and doses of fennel extract ranged from 30-230 mg daily (104196,108972). However, most studies included in these meta-analyses were small and low-quality, and all studies were conducted in Iran. Higher quality studies in other geographic locations are needed to confirm these findings.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anxiety. Although there has been interest in using oral fennel for anxiety, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Bronchitis. Although there has been interest in using oral fennel for bronchitis, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Cancer. Although there has been interest in using oral fennel for cancer prevention, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Cholera. Although there has been interest in using oral fennel for cholera, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Colic. Small clinical studies suggest that oral fennel may reduce crying time in infants with colic. However, most research to date has evaluated fennel in combination with other ingredients. Details: A meta-analysis of three small clinical studies shows that giving fennel to infants with colic can reduce crying time by about 72 minutes daily when compared with placebo (97497). However, the studies included in this meta-analysis were at medium to high risk of bias, and the placebo response rate was high in all of the included studies. Additionally, two of the three studies evaluated combination products (16735,19715,49428). In the one study that used fennel alone, administering 5-20 mL of fennel seed oil 0.1% emulsion daily for one week led to colic relief in 65% of infants, compared with 24% of infants receiving placebo (49428). The other studies evaluated fennel in combination with lemon balm and German chamomile (ColiMil) or in combination with chamomile, vervain, licorice, and lemon balm (Calma-Bebi, Bonomelli). These combination products produced a response in 57% to 85% of infants, compared with 26% to 49% of infants receiving placebo (16735,19715).
• Constipation. Oral fennel has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small crossover trial in patients with constipation shows that drinking an herbal tea containing 3 grams of a combination of fennel, anise, elderberry, and senna daily for 5 days can decrease colonic transit time, increase the number of daily evacuations, and improve the perception of bowel function when compared with placebo (49494). Another small clinical study in elderly patients with constipation shows that drinking a specific tea (Smooth Move, Traditional Medicinals) containing fennel, senna, licorice, orange peel, cassia cinnamon, coriander, and ginger for 28 days can increase the number of bowel movements when compared to baseline (46196). The validity of this finding is limited by the lack of a comparator group. Additionally, a small clinical study in patients aged 60-65 years with functional constipation shows that taking a traditional Iranian combination product containing 5 grams each of fennel seed and rose flower, dissolved in water twice daily before meals for 4 weeks, improves constipation severity and stool consistency when compared with polyethylene glycol 10 grams. Improvements in constipation severity persisted in both groups 4 weeks after treatment completion (108973). However, polyethylene glycol is usually taken at a higher dose of 17 grams daily, limiting the validity of these findings.
• Cough. Although there has been interest in using oral fennel for cough, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Dementia. Although there has been interest in using oral fennel for dementia, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Diabetes. Although there has been interest in using oral fennel for diabetes, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Dyspepsia. Although there has been interest in using oral fennel for dyspepsia, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Flatulence. Although there has been interest in using oral fennel for flatulence, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Hirsutism. It is unclear if topical fennel is beneficial in patients with hirsutism. Details: A small clinical study in females with male pattern body hair due to unknown causes shows that applying a fennel 2% cream twice daily for 12 weeks can reduce hair diameter by approximately 19% when compared with placebo (49429).
• Insomnia. Although there has been interest in using oral fennel for insomnia, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Irritable bowel syndrome (IBS). Oral fennel has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in adults with either diarrhea- or constipation-predominant IBS shows that taking two capsules containing fennel essential oil 25 mg and curcumin 42 mg per capsule (CU-FEO, Alfa Wassermann S.p.A.) twice daily for 30 days improves overall ratings of abdominal pain, abdominal distention, and quality of life by 24% when compared with placebo (97422).
• Lactation. Although there has been interest in using oral fennel to stimulate breastmilk production, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Menopausal symptoms. Small clinical studies suggest that oral fennel oil or fennel seed powder may modestly improve menopausal symptoms. Details: One small clinical trial in adults with medium severity menopausal symptoms shows that taking fennel essential oil 60 mg daily for 8 weeks improves scores on the Menopause Rating Scale when compared with a sunflower oil placebo (97498). Another small clinical study in postmenopausal adults shows that taking fennel seed powder 2 grams daily for 8 weeks improves scores on the Kupperman Menopausal Index when compared with placebo (104198). Fennel has also been evaluated in combination with other ingredients. One small clinical study shows that taking a combination of fennel 120 mg, chamomile 1000 mg, and saffron 60 mg daily for 12 weeks reduces physical, psychological, and urogenital symptom scores on the Menopause Rating Scale when compared with placebo or lower doses of the combination (103628). Additionally, a moderate-sized clinical study in postmenopausal women conducted in Iran shows that taking combined fennel and valerian extract 500 mg twice daily for 8 weeks modestly improves self-reported scores for frequency and severity of hot flashes but does not improve sleep quality or duration of hot flashes when compared with placebo (112369). However, it is unclear if these benefits are due to fennel, other ingredients, or the combination.
• Nausea and vomiting. Although there has been interest in using oral fennel for nausea and vomiting, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Nocturnal enuresis. Although there has been interest in using oral fennel for nocturnal enuresis, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Osteoarthritis. It is unclear if oral fennel extract is beneficial in patients with knee osteoarthritis. Details: A small clinical trial in females with osteoarthritis of the knee shows that taking powdered fennel extract 800 mg daily for 2 weeks reduces pain and disability scores, but not stiffness, when compared with placebo (104199).
• Polycystic ovary syndrome (PCOS). It is unclear if oral fennel is beneficial in patients with PCOS. Details: A small clinical study in patients with PCOS shows that taking two fennel capsules, containing anethole 21-27 mg per capsule, daily along with a hypocaloric standard diet or a hypocaloric high-protein diet for 3 months does not reduce body weight or improve androgenic parameters such as testosterone levels, sex hormone-binding globulin levels, or free androgen index, when compared with these diets plus placebo (104197). Fennel has also been evaluated in combination with other ingredients. A clinical study in patients with oligomenorrhea due to PCOS shows that taking a traditional combination product (Aslagh) containing equivalent amounts of essential oils of fennel, wild carrot seeds, and Vitex agnus-castus fruit for 3 months, either alone or in combination with metformin, improves rates of menstrual bleeding and menstrual cyclicity similarly to metformin alone. All three groups experienced a significant improvement from baseline. Aslagh was taken as two, 500-mg capsules twice daily, except during menses; metformin was titrated over one week to a dose of 500 mg three times daily (108974). Additionally, a moderate-sized clinical study in patients with PCOS shows that taking fennel 60 mg and Elwendia persica 25 mg twice daily for 4 months modestly improves number of ovarian follicles and body mass index when compared with placebo; however, when compared to baseline, the combination also improves hirsutism scores and menstrual cycle duration and interval (112370). It is unclear if these effects are due to fennel, other ingredients, or the combination.
• Rheumatoid arthritis (RA). Although there has been interest in using oral fennel for RA, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Sexual desire. It is unclear if oral fennel is beneficial for improving sexual desire. Details: A small clinical study in postmenopausal adults shows that taking fennel seed powder 2 grams daily for 8 weeks does not improve scores on the Hurlbert Index of Sexual Desire when compared with placebo (104198).
• Sunburn. It is unclear if topical fennel emulsion is beneficial for preventing sunburn. Details: A small clinical study shows that applying a fennel 5% emulsion topically prior to ultraviolet (UV) exposure can reduce sunburn by 65% when compared with a control (49518).
• Upper respiratory tract infection (URTI). Although there has been interest in using oral fennel for upper respiratory tract infections, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Vaginal atrophy. It is unclear if intravaginal application of fennel cream is beneficial in patients with vaginal atrophy. Details: A small clinical study in postmenopausal adults shows that applying 5 grams of a fennel 5% cream to the vagina once daily for 8 weeks seems to reverse vaginal thinning, improve vaginal pH, and reduce symptoms of vaginal atrophy such as itching, dryness, and pain with intercourse when compared with placebo (92509). Patients in the fennel group also rated their sexual function to be improved when compared with those receiving placebo (97496). More evidence is needed to rate fennel for these uses.

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LIKELY SAFE ...when used orally in amounts found in foods (6).

POSSIBLY SAFE ...when black seed oil is used orally at doses of up to 5 mL or 5 grams daily for up to 12 weeks (36071,94486,96927,96929,98815,101550,102062,110269,110276). ...when a specific black seed oil formulation containing 5% thymoquinone (BlaQmax) is used in doses of 200 mg daily for 90 days (110264). ...when black seed powder is used orally at doses of up to 2 grams daily for up to 12 months (36239,36244,94478,94479,94485,96928,102061,110268,110271). ...when used topically and appropriately, short-term. There is some clinical evidence that black seed oil can be safely applied as an oil 2 times daily for up to 6 months or 3 times daily for up to 1 month (95981,98814,102064,110262) or as a 30% gel twice daily for approximately 2 months (94483).

CHILDREN: POSSIBLY SAFE
when black seed oil is used orally at doses of 40-80 mg/kg daily for 2-19 months in children ages 4-17 years old (36071,95984). However, the higher dose of 80 mg/kg daily has been associated with increased adverse effects such as gastrointestinal complaints when taken on an empty stomach (36071).

PREGNANCY: LIKELY UNSAFE
when used orally in amounts exceeding those found in food. Black seed may decrease or inhibit uterine contractions (241) and may have contraceptive activity (242).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about BLACK SEED)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Dill has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts (12). There is insufficient reliable information available about the safety of dill when used topically.

PREGNANCY: POSSIBLY UNSAFE
when used in medicinal amounts. Dill seed is used to stimulate menstrual flow (19). Theoretically, dill seed might adversely affect pregnancy.

LACTATION:
Insufficient reliable information available; avoid amounts greater than those found in foods.

(Read more about DILL)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Fennel has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when fennel essential oil or extract is used orally and appropriately, short-term. Twenty-five drops (about 1.25 mL) of fennel fruit extract standardized to fennel 2% essential oil has been safely used four times daily for 5 days (49422). Also, two 100 mg capsules each containing fennel 30% essential oil standardized to 71-90 mg of anethole has been safely used daily for 8 weeks (97498). Powdered fennel extract has been used with apparent safety at a dose of 800 mg daily for 2 weeks (104199). ...when creams containing fennel 2% to 5% are applied topically (49429,92509).

CHILDREN: POSSIBLY SAFE
when combination products containing fennel are used to treat colic in infants for up to one week. Studied products include up to 20 mL of a fennel seed oil emulsion; a specific product (ColiMil) containing fennel 164 mg, lemon balm 97 mg, and German chamomile 178 mg; and up to 450 mL of a specific tea (Calma-Bebi, Bonomelli) containing fennel, chamomile, vervain, licorice, and lemon balm (16735,19715,49428).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Observational research has found that regular use of fennel during pregnancy is associated with shortened gestation (100513).

LACTATION: POSSIBLY UNSAFE
when used orally. Case reports have linked consumption of an herbal tea containing extracts of fennel, licorice, anise, and goat's rue to neurotoxicity in two breast-feeding infants. The adverse effect was attributed to anethole, a constituent of fennel and anise (16744). However, levels of anethole were not measured in breastmilk, and the herbal tea was not tested for contaminants. Furthermore, other adverse effects related to use of fennel during lactation have not been reported. However, until more is known, avoid using.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black seed may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details In vitro and animal research suggests that black seed extract can inhibit platelet aggregation and clotting, and increase bleeding time (36029,36049,36100,108701). In addition, decreased platelet counts have occurred in a human case report and in animal research (104665).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking black seed with antidiabetes drugs might increase the risk of hypoglycemia.  Details Some clinical research (36262,94479,94485,101552,102062,110269,110276) and numerous animal studies (36037,36086,36150,36155,36214,110270) suggest that black seed, especially its constituent thymoquinone, can have hypoglycemic effects.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking black seed with antihypertensive drugs might increase the risk of hypotension.  Details Clinical research suggests that black seed powder and oil might reduce blood pressure by 2-3 mmHg (16437,94489). In animal research, black seed modestly reduces blood pressure and concomitant use of black seed and amlodipine (Norvasc) or metoprolol (Lopressor) increased the blood pressure lowering effects of these drugs (101559,108703).

CLOPIDOGREL (Plavix) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, black seed may increase the risk of bleeding if used with clopidogrel.  Details Animal research shows that taking black seed extract daily for 2 weeks prior to a single dose of clopidogrel increases maximum concentrations of clopidogrel by approximately 31% and modestly decreases oral clearance. Furthermore, bleeding time was increased by 12% (108701). This has not been shown in humans.

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use with drugs that have sedative properties may cause additive effects.  Details Animal research suggests that black seed may have CNS depressant effects (36064).

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically taking black seed might reduce the levels and clinical effects of cyclosporine.  Details In animal research, black seed extract decreased the maximal levels of cyclosporine in the blood by 35.5% (94474). This has not been shown in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black seed might increase levels of drugs metabolized by CYP2C9.  Details In vitro research suggests that thymoquinone, a constituent of black seed, can decrease the metabolism of phenytoin by a mechanism possibly related to the inhibition of CYP2C9 (110281). The effect of black seed on CYP2C9 is unclear. This has not been shown in humans.

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking black seed with diuretic drugs might increase potassium loss and the risk of hypokalemia.  Details Black seed extract has shown diuretic effects in animals, which could theoretically increase potassium loss (36026). This has not been shown in humans.

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black seed might interfere with immunosuppressive therapy.  Details Animal and in vitro studies suggest that black seed might stimulate immune function (36086,36137,36161). However, other animal studies suggest that black seed may suppress immune function (36085,36142).

PHENYTOIN (Dilantin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black seed might increase levels and adverse effects of phenytoin.  Details In vitro research suggests that thymoquinone, a constituent of black seed, can decrease the metabolism of phenytoin (110281). This effect may be due to inhibition of cytochrome P450 2C9 (CYP2C9). The effect of black seed on phenytoin metabolism is unclear. This has not been shown in humans.

SEROTONERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining serotonergic drugs with black seed might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders.  Details Animal research suggests that black seed can increase brain serotonin levels (36180,94488). In one case report, a 35-year-old man undergoing endoscopic surgery experienced immediate postoperative serotonin syndrome that was likely associated with the use of black seed oil 600 mg daily starting 4 days before surgery, and precipitated by the use of serotonergic pain medications, including fentanyl and oxycodone (101558). Monitor patients for signs of serotonin syndrome and other serotonergic side effects if using black seed with serotonergic drugs.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, black seed might increase levels of warfarin and increase the risk of bleeding.  Details In vitro research suggests that thymoquinone, a constituent of black seed, can decrease the metabolism of warfarin (110280). This effect may be due to inhibition of cytochrome P450 2C9 (CYP2C9). The effect of black seed on warfarin metabolism is unclear. This has not been shown in humans.

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dill extract might have additive effects with antidiabetes drugs and increase the risk of hypoglycemia. Animal research shows that dill extract can reduce blood sugar levels (47799,47817). Monitor blood glucose levels closely. Dose adjustments might be necessary.  Details Some antidiabetes drugs include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), and others.

(Read more about DILL)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fennel might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.  Details Animal research suggests that fennel oil has antithrombotic and antiplatelet effects (31415,49445).

CIPROFLOXACIN (Cipro) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, fennel might decrease the levels and clinical effects of ciprofloxacin.  Details Animal research shows that fennel reduces ciprofloxacin bioavailability by nearly 50%, possibly due to the metal cations such as calcium, iron, and magnesium contained in fennel. This study also found that fennel increased tissue distribution and slowed elimination of ciprofloxacin (6135).

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking large amounts of fennel might decrease the effects of contraceptive drugs due to competition for estrogen receptors.  Details Some constituents of fennel have estrogenic activity (11).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fennel might increase levels of drugs metabolized by CYP3A4.  Details In vitro research suggests that fennel inhibits CYP3A4 enzyme activity (38375,49468). This effect has not been reported in humans.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking large amounts of fennel might interfere with hormone replacement therapy due to competition for estrogen receptors.  Details Some constituents of fennel have estrogenic activity (11).

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking large amounts of fennel might decrease the antiestrogenic effect of tamoxifen.  Details Some constituents of fennel have estrogenic activity (11), which may interfere with the antiestrogenic activity of tamoxifen.

(Read more about FENNEL)

General ...Orally and topically, black seed seems to be well tolerated.
Most Common Adverse Effects:
Orally: Constipation, gastric burning or discomfort, nausea, and vomiting.

Dermatologic ...Orally, black seed can cause itching, but this adverse effect is rare (94481). It has also been reported to cause bullous drug eruption and maculopapular eruption (94480,100324). Topically, black seed and its oil have been reported to cause allergic contact dermatitis (36053,36296,36297,100324). Rarely, topical use of the oil has been reported to cause a rash related to drug reaction with eosinophilia and systemic symptoms (DRESS) (110277).

Gastrointestinal ...In a clinical trial, unspecified gastrointestinal complaints occurred in 20% of patients taking black seed oil orally (36071). Gastrointestinal complaints occurred rarely in another clinical trial; however, one patient in this study was hospitalized for nausea and vomiting thought to be associated with black seed oil (110267). Gastrointestinal adverse effects to black seed have included constipation (36180), burning sensation (94487), epigastric discomfort (94479), vomiting (94491), or mild nausea (94481,94489,94491,96927,96929). Gastrointestinal adverse effects to a specific black seed oil formulation containing 5% thymoquinone (BlaQmax) have included mild cases of bloating, burping and mild diarrhea (110264).

Genitourinary ...Orally, relatively severe menstrual bleeding has occurred in one clinical trial (104661).

Hepatic ...While intake of black seed has been associated with hepatotoxicity in some animal research, other animal research has not confirmed this finding (245,95982). Hepatotoxicity has not been reported in humans.

Immunologic ...Orally, black seed has been reported to cause bullous drug eruption and maculopapular eruption (94480,100324). Topically, black seed and its oil can cause allergic contact dermatitis (6,36053,36296,36297,100324,110266). One case of bullous drug eruption with skin detachment has been reported for a 54-year-old woman who used black seed oil orally. The eruptions resolved following treatment with clobetasol propionate 0.05%. Although this patient showed a positive skin prick test for undiluted black seed oil, the tests were negative when the oil was diluted to 10% and 1% (94480). A 28-year-old woman developed a rash following topical use of black seed oil. She was diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS), including enlarged lymph nodes, and required systemic corticosteroid treatment. This diagnosis was confirmed six months later following confirmation with a patch test (110277). In another case report, a 58-year-old woman developed eczematous lesions on the lower and upper eyelids after topical application of an oil containing black seed. This reaction was followed by the development of a diffuse maculopapular eruption after taking two oral capsules containing black seed oil. It is theorized that the topical application of black seed oil led to systemic sensitization prior to the use of oral black seed in this patient (100324).

Renal ...Orally, black seed might cause renal dysfunction. A case of acute renal failure thought to be related to use of black seed tablets 2-2.5 grams daily has been reported for a 62 year-old patient with diabetes (94477).

(Read more about BLACK SEED)

General ...Orally, dill is well tolerated when used in amounts commonly found in foods (4912). Dill seems to be well tolerated when used as medicine (12). However, a thorough evaluation of safety outcomes has not been conducted. Some people are allergic to dill (47751,47753).
Topically, photodermatosis is possible after contact with juice from freshly harvested plants (19). Dill can also cause contact dermatitis (19,47767,47773).

Dermatologic ...Topically, photodermatosis is possible after contact with juice from freshly harvested plants (19).

Immunologic ...Orally, there are case reports of individuals allergic to dill (47751,47753). In one case, symptoms, including swelling around the eyes, itching, rash, and chapped lips, occurred after a delay of 12 hours (47751). In another case, immediate symptoms of anaphylaxis, as well as vomiting and diarrhea, occurred following intake and inhalation of foods cooked with dill (47753).
Topically, dill has resulted in contact dermatitis (47767,47773).

(Read more about DILL)

General ...Orally and topically, fennel seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal discomfort, photosensitivity, and allergic reactions in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Seizures.

Dermatologic ...Advise patients to avoid excessive sunlight or ultraviolet light exposure while using fennel (19). Allergic reactions affecting the skin such as atopic dermatitis and photosensitivity may occur in patients who consume fennel (6178,49507).

Gastrointestinal ...Orally, fennel may cause gastrointestinal complaints, including nausea and vomiting (19146,104196).

Hematologic ...Methemoglobinemia has been reported in four infants following intoxication related to ingestion of a homemade fennel puree that may have been made from improperly stored fennel (49444).

Immunologic ...A case report describes an 11-year-old male who developed an allergy to fennel-containing toothpaste. Immediately after using the toothpaste, the patient experienced sneezing, coughing, itchy mouth, rhinorrhea, nasal congestion, wheezing, difficulty breathing, and palpitations, which resolved within 10 minutes of spitting out the toothpaste and rinsing the mouth. In challenge tests, the patient reacted to chewing fresh fennel root, but not ground fennel seeds (103822).

Neurologic/CNS ...Orally, fennel oil has been associated with tonic clonic and generalized seizures (12868). New-onset cluster headaches are reported in a 24-year-old female while using a toothpaste containing fennel and camphor for 3 months. The headaches resolved upon stopping the toothpaste (112368). It is unclear if this adverse effect can be attributed to fennel, camphor, or the combination.

Pulmonary/Respiratory ...Orally, fennel and fennel seed have been reported to cause bronchial asthma (49478).

(Read more about FENNEL)