Resp-Immune by North American Herb & Spice

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: A meta-analysis of 4 clinical studies shows that black seed reduces glycated hemoglobin (HbA1c) by 0.4%. However, analysis of 7 clinical studies suggests that black seed does not reduce fasting blood glucose (111503). One clinical study shows that taking black seed powder 1 gram twice daily for 3-12 months improves 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). Black seed has also been evaluated in combination with other ingredients. A moderate-sized clinical study in treatment-naïve adults newly diagnosed with type 2 diabetes shows that taking a combination product containing extracts of black seed 250 mg, cassia cinnamon, and ficin (NW Low-Glu) 4-5 times daily for 12 weeks reduces HbA1c by 0.6-0.8% and 2-hour postprandial glucose by 25-35 mg/dL when compared to baseline and is similarly effective to metformin. However, there were no notable improvements in fasting blood glucose, insulin resistance, or beta cell function (111710). It is unclear if these effects are due to black seed, other ingredients, or the combination.
• 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.
• Hyperlipidemia. Oral black seed seems to modestly improve serum lipids in patients with or without hyperlipidemia. Details: A meta-analysis of 24 moderate-quality, clinical studies in healthy adults and patients with various cardiometabolic conditions shows that taking black seed modestly reduces total cholesterol, LDL cholesterol, and triglycerides, and increases HDL cholesterol when compared with placebo or control (114813). Interpretation of findings is limited by significant heterogeneity in results which may be due to the inclusion of different patient populations, doses or types of black seed preparations, and treatment durations. Similarly, a meta-analysis of 5 clinical studies in adults with type 2 diabetes with or without hyperlipidemia shows that taking black seed reduces total cholesterol by 17 mg/dL, low-density lipoprotein (LDL) cholesterol by 11 mg/dL, and triglycerides by 12 mg/dL, but does not improve high-density (HDL) lipoprotein cholesterol, when compared with a control (111503). Additionally, 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%, 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 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).
• 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: Meta-analyses of results from 33 small clinical studies in patients with or without hypertension show that taking black seed powder 0.5-3 grams daily or black seed oil 0.1-4.2 grams daily for 4-16 weeks reduces both systolic and diastolic blood pressure by about 2-3 mmHg when compared with placebo (16437,94489,112242). Subgroup analysis suggests that black seed supplementation is most beneficial for durations of 8 weeks or less and in patients over 50 years old with a BMI of 25-30 kg/m2 (112242). 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 to baseline (96929).
• 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). 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 reduces the severity of some symptoms, including cough, diarrhea, fatigue, and pharyngitis, as well as the percentage of patients with viral positivity at day 7, when compared with 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. A meta-analysis of 3 studies in patients with COVID-19 shows that taking black seed 40-80 mg/kg for 13-14 days or 500 mg twice daily for 7 days reduces the odds of mortality by 78% relative to patients with COVID-19 who did not use black seed (112243). 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.
• 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. It is unclear if oral black seed oil is beneficial for patients with insomnia. Details: A small clinical study in healthy adults with self-reported sleep problems shows that taking a specific black seed oil extract product containing 5% thymoquinone (BlaQmax, Akay Natural Ingredients) 200 mg daily before bedtime for 90 days increases sleep quality, latency, duration, and efficiency and reduces sleep disturbances and daytime dysfunction when compared with placebo. Black seed oil also improves biomarkers of sleep as shown by increased salivary melatonin and decreased orexin A (112244).
• 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). Similarly, a very small, open-label, non-randomized intervention in patients with oral lichen planus shows that topical application of a mucoadhesive patch containing black seed extract 10% three times daily for 4 weeks is as effective as a triamcinolone acetonide 0.1% patch for reducing pain and burning intensity and lesion severity (114815). Both studies are limited by the lack of inclusion of a placebo-controlled group.
• Male infertility. It is unclear if oral black seed oil is beneficial for male infertility. 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).
• Meniere disease. It is unclear if oral black seed is beneficial for patients with Meniere disease. Details: A very small clinical study in adults with Meniere disease shows that taking black seed oil 1 gram daily for 3 months does not improve hearing threshold, tinnitus severity, or vertigo when compared with placebo (112245).
• 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 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 2-4 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 (96926,98815,111503). 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.
• Oral submucous fibrosis. It is unclear if oral black seed is beneficial for oral submucous fibrosis. Details: A small clinical study in patients with oral submucous fibrosis shows that taking black seed 1000 mg 3 times daily for 3 months increases mouth opening by 14%, cheek flexibility by 44%, tongue protrusion by 9%, and reduces burning sensations by 79% when compared to baseline, but not when compared with a combination product containing turmeric and black pepper (114880). The validity of this study is limited by the lack of a placebo 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.
• Polycystic ovary syndrome (PCOS). It is unclear if oral black seed is beneficial for PCOS. Details: A moderate-sized clinical study in adolescents with PCOS shows that taking black seed 1000 mg daily for 16 weeks reduces ovarian volume, testosterone and luteinizing hormone levels, hirsutism, and menstrual irregularities when compared with oral medroxyprogesterone 10 mg daily on menstrual cycle days 14 to 23 (114814). The validity of this study is limited by poor methodology, including results presented only using a per-protocol analysis.
• 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).
• Stress. It is unclear if oral black seed is beneficial for patients with stress. Details: A small clinical study in healthy adults with self-reported stress shows that taking a specific black seed oil extract product containing 5% thymoquinone (BlaQmax, Akay Natural Ingredients) 200 mg daily before bedtime for 90 days reduces measures of perceived stress and salivary cortisol levels when compared with placebo (112244).
• 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.

(Read more about BLACK SEED)

POSSIBLY EFFECTIVE

• Burns. Topical application of gauze containing honey seems to improve burn healing. Details: Honey applied directly in gauze applications seems to improve formation of granulation tissue and speed healing time in partial thickness burns. The benefits of honey appear to be comparable to topical antibiotics, including silver sulfadiazine and moisture permeable polyurethane dressing (OpSite) (395,396,397,398,399,14317,55175,55200,55204,55264)(91363,97696). In these studies, honey has been used under dressings or impregnated in gauze as needed for up to 12 weeks. The duration between changing of dressings or gauze has varied (395,396,397,398,399,55175,55200,55204,55264,91363). One small clinical study in adults with moderate burns shows that early surgical intervention with tangential excision and skin grafting appears to improve outcomes when compared with honey (7848). However, poor study design limits the reliability of these findings.
• Cough. Most studies show that oral honey reduces cough in children. It is unclear whether oral honey is beneficial for cough in adults. Details: Clinical research shows that taking honey 2.5-10 mL (0.5-2 teaspoons) at bedtime reduces nighttime cough frequency and severity and improves sleep when compared with placebo in children aged 2 years and older with upper respiratory tract infections (URTIs) (15910,55253,97693,103959). Honey also appears to be at least as effective as the cough suppressant dextromethorphan in typical over-the-counter doses (15910,17299,97693). The effects of honey on cough duration are not known (97693). One clinical study in children 1-5 years of age with URTIs and cough for up to 7 days shows that acacia honey is similarly effective to a honey-flavored placebo, given as 3 mL one hour before bedtime for 2 consecutive nights, for reducing cough frequency and severity and improving sleep (110003). However, this study may have been inadequately powered to detect a difference between groups. A meta-analysis of the available research suggests that honey does not improve cough in adults when compared with usual care (103959). However, due to the small number of available studies, the analysis might have been inadequately powered to detect a smaller magnitude of benefit. Some research in adults has also evaluated honey in combination with other ingredients. In adults with post-infectious cough of at least 3 weeks' duration, taking 25 grams of a paste in a warm water solution providing honey 20.8 grams and coffee 2.9 grams every 8 hours for one week reduces cough frequency by about 93% when compared with baseline. Those taking prednisolone experienced a cough reduction of 20% (91367). It is unclear if this effect is due to honey, coffee paste, or the combination.
• Diabetic foot ulcers. Topical honey seems to be beneficial for diabetic foot ulcers. Details: A meta-analysis of mainly lower quality clinical trials including 267-616 patients with diabetic foot ulcers shows that applying dressings impregnated with honey for 1-2 weeks shortens the wound debridement and healing time and increases the rate of wound healing by moderate to large amounts when compared with other dressings (101032). Individual clinical studies also show that using dressings impregnated with manuka honey (Medihoney Tulle Dressing) or beri honey decreases healing time for diabetic foot ulcers by 11-12 days and reduces the need for antibiotics when compared with saline-soaked gauze (19739,91364,97701).
• Dry eye. Specific manuka honey eyedrops seem to be modestly beneficial for improving symptoms of dry eye. Details: Most clinical research shows that specific honey products might be helpful for symptoms of dry eye (97694,97695,105231,105234). Preliminary clinical research shows that applying a specific manuka honey product (Optimel Manuka Plus Dry Eye Drops, Melcare Biomedical Pty Ltd) 2-3 times daily for 14 or 28 days reduces some, but not all, measures of eye discomfort (97694,105234). In patients with dry eye due to contact lenses, dry eye symptoms were reduced by about 18% when compared with baseline (97694). In patients with general mild dry eye symptoms, preliminary clinical research shows that symptoms were reduced by about 52% when compared with baseline (105234). These improvements were significant when compared with lubricant drops (97694,105234). Specific honey products also seem to be beneficial for dry eye associated with meibomian gland dysfunction. In these patients, preliminary clinical research shows that using Optimel Manuka Plus Eye Drops (Melcare, Biomedical Pty Ltd) or Optimel Antibacterial Manuka Eye Gel (Melcare Biomedical Pty Ltd) twice daily for 3 or 8 weeks along with warm compresses improves the function of the tear glands (97695,105231). In one study, 73% to 95% of participants using the honey products required less lubricant, compared with 48% of participants using warm compresses alone. However, the honey products did not improve bacterial counts, redness, or dryness (97695). In another study, eye dryness, lid margin, conjunctival redness, and meibomian gland function were modestly improved when compared with baseline. All improvements were statistically similar to the control group receiving a lubricant. However, patients using a lubricant did not experience an improvement in eye dryness when compared to baseline (105231).
• Herpes labialis (cold sores). Applying honey to cold sores may heal lesions 2-4 days faster than conventional therapies. Details: A meta-analysis of three clinical trials, including one relatively large study, in patients with herpes labialis shows that applying honey to lesions 4-5 times daily reduces lesion healing time by around 2 days, although it does not improve pain when compared with acyclovir 5% cream (108526). Also, a small crossover trial in patients with recurrent cold sores shows that applying medical grade honey three times daily to lesions at the onset of symptoms or blistering reduces lesion healing time by around 4 days and improves symptoms such as pain and itching when compared with conventional treatments, which ranged from prescription antivirals to herbal remedies and wound care products (108527).
• Herpetic gingivostomatitis. Slowly swallowing honey seems to be beneficial for herpetic gingivostomatitis treatment in children. Details: Clinical research in children aged 2-8 years with primary herpetic gingivostomatitis shows that use of a local honey 5 mL every 4 hours with slow swallowing, in combination with acyclovir 15 mg/kg five times daily for 7 days, results in the clearing of oral lesions 3 days faster when compared with acyclovir and a placebo syrup. Drooling and difficulties eating also improved faster, and pain and the need for analgesics were reduced. Fever and extra-oral lesions were not improved (101038).
• Oral mucositis. Rinsing the mouth with and then slowly swallowing honey seems to be beneficial for oral mucositis prevention or treatment, although most research is lower quality. Details: Although contradictory evidence exists (55219,91361), most research shows that honey may have some benefit in preventing or reducing symptoms of oral mucositis (16352,55133,55137,55202,55241,55245,55265,91368,97704,104562). A meta-analysis of eight trials shows that applying honey reduces the development of intolerable oral mucositis lesions by approximately 52%. Applying honey to lesions also appears to reduce pain associated with oral mucositis; however, the number of studies included in this latter analysis was small (101035). Another meta-analysis suggests that pure natural honey may be more effective than manuka honey or local honey for treating oral mucositis (101034). However, these analyses have significant quality issues. They included studies that did not fit inclusion criteria and omitted studies that did fit inclusion criteria (103967). The majority of these studies have had patients rinse with and then slowly swallow up to 20 mL honey three times or more daily, usually before radiation therapy, 15 minutes after radiation therapy, and 6 hours after radiation therapy or at bedtime. Some studies have used honey topically or as ice chips or lozenges (16352,55133,55137,55202,55219,55241,55265,91361,97704,101034)(101035,104562). Also, rinsing the mouth and swallowing a paste of honey or honey and coffee 10 mL every 3 hours for one week has been used (91368). Preliminary clinical research in patients undergoing chemoradiation and using conventional treatments shows that a combination of licorice powder 5 grams mixed in honey and applied twice daily along with oral licorice powder 500 mg twice daily for 6 weeks also seems to reduce the risk of oral mucositis and severe symptoms when compared with conventional treatments alone (104562). However, it is not clear whether any benefit in this study is due to honey, licorice, or the combination. In pediatric intensive care patients aged 2-16 years, preliminary clinical research shows that applying a local honey, 1-1.5 grams/kg in two divided doses, with a spoon to the inside of the mouth, teeth, lips, and tongue, reduces the severity and development of oral mucositis when compared with using chlorhexidine. However, honey was not as effective as topical vitamin E (101036).
• Rosacea. Topical honey seems to be beneficial for rosacea. Details: Clinical research in adults shows that applying a 90% medical-grade kanuka honey (Honevo) with glycerin to affected areas twice daily for 8 weeks and washed off after 30-60 minutes is more effective than Cetomacrogol, an emollient, for improving symptoms of rosacea. Approximately twice as many patients responded to the honey product when compared with Cetomacrogol cream (97699).
• Wound healing. Topical honey seems to improve the healing of various types of wounds, although the optimal formulation and application regimen remains unclear. Details: Several small clinical trials and case reports describe the use of honey or honey-impregnated dressings for various types of wounds, including post-surgical wounds, chronic leg ulcers, abscesses, burns, abrasions, lacerations, and skin graft donor sites. Honey seems to improve granulation and epithelialization, reduce odors and purulent exudate, help clean the wound, increase eradication of infection, reduce pain, and decrease time to healing (7847,7849,14317,16354,16355,16357,16358,16360,16362,16369)(16372,16374,55109,55130,55144). Meta-analyses of clinical research show that applying honey reduces healing time of partial thickness burns by 4.7 days when compared with conventional dressing and about 5 days when compared with silver sulfadiazine. Honey also appears to improve healing time for postoperative wounds when compared with antiseptic washes followed by gauze (55264). In some reports, wounds healed with honey after failing previous treatments (16369,16371). Honey applied directly to wounds appears to be comparable to hydrogels such as carboxymethylcellulose, povidone iodine, and hypochlorite solutions (16355,16358,16360,16376,55235). Honey dressings also appear to be comparable to hydrocolloid dressings, paraffin gauze, nanocrystalline silver, and saline-soaked gauze (16358,16360,16372,55101). However, poor study design limits the reliability of some of these findings. Trials cannot be directly compared due to variation in wound type and severity, patient characteristics, honey type and processing, dressing techniques, treatment duration, and concomitant use of antibiotics. Adequate blinding is also difficult to achieve due to the distinctive properties and smell of honey (16360). Many of the clinical trials used manuka honey, which is derived from the nectar of Leptospermum scoparium and is gamma irradiated to inactivate bacterial spores (16355,16357,16362,16369,16371). Other trials used unprocessed honey (16358,16372). Honey dressings are typically changed every 24-48 hours, although in some cases dressings are changed only twice weekly (16355,16362,16372,16374,55101,55130,55235). In children aged 2 months to 14 years, honey soaked gauze has been packed into wounds twice daily until closure (16376). When used directly, unprocessed honey or manuka honey 15-30 mL has been applied and covered with sterile gauze and bandages or a polyurethane dressing. When applied directly, honey is typically used every 12-48 hours, although in some cases it has been used only once weekly (16354,16358,16369,16372,16376,55144).

POSSIBLY INEFFECTIVE

• Acne. Topical honey does not seem to be beneficial for acne. Details: Clinical research in adolescents and adults 16 years of age and older shows that applying a 90% medical-grade kanuka honey (Honevo) with glycerine to the face twice daily after using an antibacterial soap does not improve facial acne when compared with antibacterial soap alone (97700).
• Hyperlipidemia. Oral honey does not seem to improve lipid levels in patients with hyperlipidemia. Details: A meta-analysis of 15 small clinical studies in patients with hyperlipidemia shows that taking honey 20-75 grams daily for up to 4 months does not reduce total cholesterol, low-density lipoprotein (LDL) cholesterol, or triglyceride levels when compared with control (108533).
• Rhinosinusitis. Intranasal honey does not seem to be beneficial for improving symptoms of chronic rhinosinusitis. Details: A small clinical study in adults who have undergone maximal medical and surgical treatment for allergic fungal rhinosinusitis shows that using 2 mL of an intranasal spray containing honey 50% in saline once daily at night for 30 days does not reduce symptoms when compared with usual treatment (55216). Manuka honey nasal spray also does not seem to work better than saline spray in adults with chronic rhinosinusitis. A small clinical study shows that manuka honey 10% (Medihoney, Derma Sciences) in saline sinus irrigation twice daily for 30 days is no more effective than saline irrigation for reducing overall symptoms (97705). Additionally, a small clinical study in patients with recalcitrant chronic rhinosinusitis shows that using manuka honey 16.5% twice daily augmented with 1.3 mg/mL methylglyoxal sinonasal rinses for 14 days is no better than taking targeted oral antibiotics and performing normal saline rinses twice daily (103969). However, this study was not adequately powered to detect a difference between treatment groups. Additional research is needed to determine if honey-containing nasal sprays are beneficial in circumstances with limited access to antibiotics or nasal steroids, or in patients with high immunoglobulin E (IgE) levels (55216,97705). Intranasal honey has also been evaluated in patients recovering from surgery for rhinosinusitis. A small clinical study in adults with chronic rhinosinusitis who have undergone endoscopic sinus surgery shows that applying 2 mL of Tualang honey to the nasal dressing, which remains in place for one week, results in similar improvements in symptoms when compared with a triamcinolone-containing dressing at 7, 14, and 28 days after surgery. However, at 3 months after surgery, triamcinolone seems to provide further improvement in rhinosinusitis symptoms and surgical recovery when compared with honey (108529).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). It is unclear if oral honey is beneficial for hay fever. Details: Preliminary clinical research shows that consuming honey one tablespoon (20 grams) daily, in addition to standard treatment, does not improve allergy symptoms (14319). Other preliminary clinical research shows that ingesting honey 1 gram/kg daily for 4 weeks, in addition to taking loratadine 10 mg daily, may improve allergic symptoms during treatment and for up to 4 weeks following cessation of treatment. However, it's not clear if this improvement is significant when compared with loratadine alone (91360).
• Alveolar osteitis. It is unclear if oral honey is beneficial for alveolar osteitis. Details: A small, low-quality clinical study in patients with alveolar osteitis after dental surgery shows that applying gauze soaked in 2 mL of honey, 3 times over 10 days, improves healing, pain, and formation of granulation tissue when compared with baseline (103961).
• Asthma. Oral honey has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One preliminary clinical study shows that taking a combination of honey and black seed modestly improves measures of lung function when compared with baseline in patients with moderate to severe asthma. However, another preliminary clinical study using this combination did not show improvement on all measures. Both studies were small and may not have been adequately powered to detect a difference in outcomes (105228). Other preliminary clinical research shows that taking a combination of honey and celery seed modestly improves some measures of lung function when compared with baseline (105228). It is unclear whether any benefit is due to honey, the other ingredient, or the combinations. Additionally, the validity of these studies is limited by the lack of a comparator group.
• Athletic performance. Although there is interest in using oral honey to improve athletic performance, there is insufficient reliable information about the clinical effects of honey for this purpose.
• Atopic dermatitis (eczema). It is unclear if topical honey is beneficial for atopic dermatitis. Details:In patients with bilateral atopic dermatitis, a small preliminary clinical trial shows that topical application of manuka honey to one site overnight for 7 days improves lesions when compared to baseline (105239). The validity of this finding is limited by the lack of a placebo comparator group.
• Blepharitis. It is unclear if topical honey is beneficial for blepharitis. Details: A small clinical study in patients with blepharitis shows that applying MGO Manuka Honey microemulsion (Manuka Health New Zealand Ltd) eye cream to closed eyelids nightly for 3 months improves symptoms of dry eye and reduces ocular mites and bacterial load when compared with no intervention (103962). The validity of this finding is limited by the lack of a placebo comparator group.
• Cataracts. Although there is interest in using topical honey for cataracts, there is insufficient reliable information about the clinical effects of honey for this condition.
• Catheter-related infections. It is unclear if topical medical honey is beneficial for preventing catheter-related infections in patients on hemodialysis or in those with diabetes. Details: Preliminary clinical research shows that manuka honey (Medihoney, Medihoney Pty Ltd) applied three times weekly to the exit sites of tunneled, cuffed central venous hemodialysis catheters is as effective as mupirocin ointment in reducing the incidence of catheter-associated infection and bacteremia. It may also be associated with a lower rate of bacterial resistance than mupirocin (16361). A retrospective analysis also found that use of povidone iodine for dialysis catheter site care is associated with a 58% increased cumulative incidence rate of exit-site infections or peritonitis when compared with use of medical honey. Patients were followed from catheter insertion until catheter removal, transplant, death, or end of treatment (101039). However, well-designed clinical research shows that application of antibacterial honey (Medihoney Antibacterial Wound Gel, Comvita) 10 mg at the exit site along with standard care is no more effective than standard care alone for reducing dialysis-related infections (91362). It is unclear if honey reduces the risk of catheter-related infection in patients with diabetes. Some evidence shows that applying an antibacterial honey product approximately doubles the risk of infection and peritonitis in patients with diabetes when compared with no honey (91362). However, a large retrospective analysis found that exit-site application of honey was associated with a lower chance of peritoneal dialysis-related infection when compared with povidone iodine, even in patients with diabetes (101039).
• Chemotherapy-related fatigue. Oral honey has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with breast cancer and chemotherapy-related fatigue shows that taking a specific product (Jollab tonic beverage) containing honey, saffron, and rose water, as 20 mL three times daily for 4 weeks, reduces scores on a cancer fatigue scale when compared with placebo. Scores on a visual analog fatigue scale and on a fatigue severity scale were only improved when compared with baseline, not placebo (110001).
• Corneal opacity. Although there is interest in using topical honey for corneal opacity, there is insufficient reliable information about the clinical effects of honey for this purpose.
• Corneal ulceration. It is unclear if honey-containing ophthalmic drops are beneficial for corneal ulceration. Details: A small clinical study in patients with foreign body-induced corneal ulceration shows that applying ophthalmic drops containing honey into the affected eye every 6 hours for 14 days might speed up healing of corneal epithelial defect, but does not improve corneal infiltration, when compared with using ciprofloxacin eye drops. The honey in these drops was produced from the nectar of various ziziphus species (103968). The validity of this study is limited by its small size and short duration.
• Diabetes. It is unclear if oral honey is beneficial for diabetes. Details: In patients with type 2 diabetes, small clinical trials show that taking honey 50 grams or 1-2.5 grams/kg daily for 8 weeks increases glycated hemoglobin (HbA1c) levels by a small amount (55182,105235). However, lower doses of 5-25 grams daily for 16 weeks or 0.5 grams/kg daily for 12 weeks seem to have no effect on HbA1c and may modestly reduce levels when compared to baseline or no treatment (105230,105236). Also, although some research disagrees, taking honey does not seem to affect fasting levels of insulin or glucose, or measures of insulin resistance (105230,105235,105236). There is conflicting evidence regarding the effects of honey on lipid levels in patients with diabetes. Some preliminary clinical research shows that consuming honey 0.5-2.5 grams/kg daily modestly decreases total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides, and modestly increases high-density lipoprotein (HDL) cholesterol (55182,105230), while other research does not show any effect on plasma lipids (105236). In patients with type 1 diabetes, one clinical study shows that taking honey 0.5 mL/kg daily for 12 weeks decreases fasting blood glucose, total cholesterol, triglycerides, and LDL cholesterol when compared with control (55263).
• Diabetic neuropathy. It is unclear if oral honey is beneficial for diabetic neuropathy. Details: In patients with mild to moderate diabetic neuropathy who are taking antidiabetes medications and gabapentin, preliminary clinical research shows that taking honey 0.5 gram/kg daily in water for 3 months modestly reduces nerve pain and improves quality of life when compared with baseline. Nerve conduction was generally not affected (105230). The validity of this study is limited by the lack of an appropriate control group.
• Diarrhea. Small clinical studies suggest that oral honey is beneficial in children and infants with diarrhea. Details: One small clinical study in children and infants with gastroenteritis shows that adding honey to oral rehydration solution (ORS) at a concentration of 50 mL per liter ORS decreases the frequency of vomiting and diarrhea, and reduces recovery time when compared with ORS alone (55194). Other clinical research shows that adding honey to ORS at the same concentration reduces the duration of diarrhea by about 1.4 days when compared with standard ORS in infants and children with bacterial gastroenteritis, but not when all types of gastroenteritis are considered (55273). Another small clinical study in children hospitalized with acute diarrhea shows that taking 1.5-2 mL of honey every 6 hours for 5 days plus 5 mL of zinc gluconate syrup, providing 5 mg of elemental zinc, every 6 hours for 10 days reduces the duration of diarrhea by 6.5 hours and the duration of hospitalization by 24 hours when compared with zinc gluconate alone (108534).
• Dry mouth. It is unclear if oral honey is beneficial for dry mouth associated with intubation. Details: Preliminary clinical research in a small group of intubated adults in an intensive care unit shows that applying Indonesian honey 20 mL to all areas of the mouth with a brush and gauze swab twice daily for 3 days, in addition to standard oral care with 20 mL chlorhexidine gluconate 0.2%, improves overall oral health scores on a modified Beck Oral Assessment Scale when compared with chlorhexidine alone (110002).
• Dysmenorrhea. It is unclear if oral honey is beneficial for dysmenorrhea. Details: Preliminary clinical research shows that taking honey 1.2 mg/kg daily, starting on the 15th day of the menstrual cycle and continuing until the onset of menstruation, is comparable to mefenamic acid 250 mg every 6 hours for reducing pain associated with dysmenorrhea (97702).
• Gingivitis. It is unclear if chewing "leather" made from manuka honey is beneficial for gingivitis. Details: Preliminary clinical research shows that chewing "leather" made from manuka honey after meals for 21 days reduces plaque severity and the number of bleeding sites when compared to baseline in patients with gingivitis and plaque (55091).
• Hemorrhoids. Topical honey has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that applying a spoonful of a mixture containing equal volumes of honey, olive oil, and beeswax to the skin twice daily for up to 4 weeks reduces bleeding and itching when compared to baseline in patients with hemorrhoids (34100). It is not clear if these effects are due to honey, the other ingredients, or the combination.
• Genital herpes. It is unclear if topical honey is beneficial for genital herpes. Details: Preliminary clinical research shows that applying a gauze soaked with honey four times daily to the lesion until healing does not improves symptoms or healing time (55095).
• Impaired glucose tolerance (prediabetes). It is unclear if oral honey is beneficial for prediabetes. Details: Preliminary clinical research shows that taking honey does not improve glycemic control or lipid levels in patients with prediabetes. In one study, taking honey (Dutch Gold Honey) providing 50 grams of carbohydrates daily for 2 weeks does not improve these measures when compared with sucrose or corn syrup providing similar amounts of carbohydrates (105238). In another study, taking Malaysian Kelulut honey (Bayu Kelulut) 30 grams daily for 30 days was not beneficial (105237). The validity of these studies is limited by the lack of an appropriate control group.
• Leishmania lesions. It is unclear if topical honey is beneficial for leishmania lesions. Details: Some research shows that honey might prevent the healing of leishmania lesions. One preliminary clinical study shows that applying honey-soaked gauze onto leishmania lesions twice daily for 6 weeks in addition to receiving a glucantime injection reduces the proportion of patients with healed wounds by about 28% when compared with glucantime injection alone (55118).
• Male infertility. Intravaginal honey has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that applying 10 mL of a combination mixture containing various bee products intravaginally immediately before or after each coital act, beginning one day after the last menstruation and continuing for three menstrual cycles or until pregnancy, increases pregnancy rate from 3% to 8% when compared to standard intrauterine insemination in couples having difficulty getting pregnant due to male asthenozoospermia. However, since all unsuccessful couples were crossed over to the alternative treatment after 2 months, the causality of successful pregnancy is unclear. The mixture consisted of Egyptian bee honey 100 grams, royal jelly 3 grams, and bee bread 1 teaspoon, which was diluted in saline in a 1:1 ratio prior to application (55131).
• Malnutrition. It is unclear if oral honey is beneficial for malnutrition in children. Details: Preliminary clinical research in infants and children with a mean age of 11-13 months with protein-energy malnutrition (PEM) shows that honey improves weight and other biomarkers when compared to control. Honey 2 mL/kg diluted in water was used daily for 2 weeks in combination with conventional nutritional rehabilitation (55196,55210).
• Menopausal symptoms. It is unclear if oral honey is beneficial for metabolic control in postmenopausal individuals. Details: In postmenopausal individuals, preliminary clinical research shows that taking Tualang honey 20 grams daily for 4 months results in a slight increase in low-density lipoprotein (LDL) cholesterol and fasting blood sugar when compared with baseline. However, there were no statistically significant differences in lipid profile, glycemic control, or bone density when compared with low-dose hormone replacement therapy (105241). The validity of this study is limited by its short duration and lack of blinding.
• Necrotizing fasciitis. It is unclear if topical honey is beneficial for necrotizing fasciitis. Details: Preliminary clinical research has shown conflicting results with the use of honey, applied directly and covered with a dressing or applied as a honey-soaked gauze, given as an adjunct to antibiotics, for the treatment of Fournier's gangrene, a type of necrotizing fasciitis (55106,55293,55295,55315,91363).
• Obesity. It is unclear if oral honey is beneficial for metabolic control in adolescents with obesity. Details: Preliminary clinical research in obese prepubertal females on a calorie-reduced diet shows that consuming a wild flower and thyme honey product (Attiki) 15 grams daily for 6 months does not improve levels of glucose, insulin, or blood lipids when compared with a marmalade control (101037).
• Osteoarthritis. Oral honey has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults 40-85 years of age with knee osteoarthritis shows that taking a specific product (G-rup syrup, Yas Daru Pharmaceutical Co.) containing honey 150 mg/mL and ginger extract 100 mg/mL in a dose of 30 mL twice daily for 12 weeks reduces pain scores on a visual analog scale and improves scores on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) when compared with baseline. Total WOMAC scores decreased by about 7 in the active group and by 4 in the placebo group (110000). The validity of this finding is limited by the lack of statistical comparison to the placebo group. Additionally, it is unclear whether these changes would be considered clinically significant.
• Peptic ulcers. Although there is interest in using oral honey for peptic ulcers, there is insufficient reliable information about the clinical effects of honey for this condition.
• Postoperative pain. Several small clinical studies suggest that topical honey may reduce pain after tonsillectomy in children and adults. Details: A meta-analysis of low-quality clinical research in children 3 years and older immediately post-tonsillectomy shows that honey might reduce pain, analgesic use, and night-time awakening by a small to moderate amount in the week after surgery when compared with placebo or control. In these studies, honey was used in doses ranging from 4-15 mL every hour or once daily for 1-7 days (97703). A small observational cohort in adults post-tonsillectomy has found that applying honey 20 grams to the oral cavity for 5 minutes, 8 times daily for the first 5 days after surgery, is associated with reduced pain and bleeding when compared with usual treatment (103963). Another small clinical trial in adults post-tonsillectomy shows that gargling and then swallowing a solution containing 15 mL of honey mixed with 5 mL of water for two minutes every 6 hours for 10 days reduces pain and analgesic use when compared with placebo or no treatment (108530).
• Pressure ulcers. It is unclear if topical honey is beneficial for pressure ulcers in children. Details: Preliminary clinical research in critically ill children aged 2 months to 17 years shows that use of a manuka honey dressing reduces the median time to complete healing of pressure ulcers by approximately 2 days when compared with standard wound care. In addition, complete healing was about 1.9 times more likely in children given the honey dressing. However, there were no differences in the proportion of children with complete healing or treatment failure, or in the duration of stay in the ICU or hospital (105229).
• Pruritus. It is unclear if topical honey is beneficial for pruritus due to intertrigo. Details: Preliminary clinical research shows in adults with intertrigo that applying a honey cream (Medihoney Barrier Cream, Derma Sciences, Inc.) topically twice daily for 21 days reduces pruritus complaints when compared with zinc oxide ointment (55258).
• Radiation dermatitis. It is unclear if topical honey is beneficial for treating radiation dermatitis. Details: Clinical research shows that applying honey gauze (HoneySoft) once daily to radiation-induced skin wounds does not increase the speed of wound healing when compared with paraffin gauze in patients with severe radiation-induced dermatitis (55105).
• Radiation-induced esophagitis. It is unclear if topical honey is beneficial for radiation-induced esophagitis. Details: In patients with radiation esophagitis, preliminary clinical research shows that taking liquid manuka honey 10 mL or honey lozenges providing 10 mL of dehydrated manuka honey four times daily for 4 weeks does not improve pain on swallowing when compared with standard supportive care. However, only 14% of patients using liquid honey reported opioid use, compared with 37% of those given only supportive care (97698).
• Sinonasal polyposis. It is unclear if intranasal honey is beneficial in patients recovering from surgery for sinonasal polyposis. Details: A small clinical study in patients recovering from sinus surgery for nasal polyposis shows that intranasal irrigation with a diluted processed honey spray four times daily starting the day after surgery does not improve healing or reduce polyp recurrence when compared with normal saline irrigation (108528).
• Sunburn. Although there is interest in using topical honey for sunburn, there is insufficient reliable information about the clinical effects of honey for this purpose.
• Tooth extraction. It is unclear if topical honey is beneficial for wound healing after tooth extraction. Details: A small clinical study in children that had a tooth extraction shows that applying a thin layer of Iranian Kurdistan Mountains honey with a cotton swab and keeping the swab in place for 45 minutes seems to reduce wound size more rapidly when compared with using normal saline (103966). The validity of this finding is limited because a large percentage of study participants were excluded from the final analysis.
• Vaginal candidiasis. It is unclear if intravaginal honey is beneficial for vaginal candidiasis. Details: In patients with vulvovaginal candidiasis, preliminary clinical research shows that applying 5 grams of a vaginal gel containing honey 50% nightly for 8 days is as effective as the same amount of clotrimazole 1% cream for reducing burning and sensitivity and improving culture results. Honey also reduces vaginal discharge in almost twice as many patients as those using clotrimazole (105227). More evidence is needed to rate honey for these uses.

(Read more about HONEY)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Bronchitis. Although there has been interest in using inhaled juniper essential oil for bronchitis, there is insufficient reliable information about the clinical effects of juniper for this purpose.
• Cancer. Although there has been interest in using oral juniper for cancer, there is insufficient reliable information about the clinical effects of juniper for this purpose.
• Diabetes. Although there has been interest in using oral juniper for diabetes, there is insufficient reliable information about the clinical effects of juniper for this purpose.
• Dyspepsia. Although there has been interest in using oral juniper for dyspepsia, there is insufficient reliable information about the clinical effects of juniper for this purpose.
• Flatulence. Although there has been interest in using oral juniper for flatulence, there is insufficient reliable information about the clinical effects of juniper for this purpose.
• Gastroesophageal reflux disease (GERD). Although there has been interest in using oral juniper for GERD, there is insufficient reliable information about the clinical effects of juniper for this purpose.
• Kidney stones (nephrolithiasis). Although there has been interest in using oral juniper for nephrolithiasis, there is insufficient reliable information about the clinical effects of juniper for this purpose.
• Intestinal parasite infection. Although there has been interest in using oral juniper for intestinal parasite infection, there is insufficient reliable information about the clinical effects of juniper for this purpose.
• Rheumatoid arthritis (RA). Although there has been interest in using topical juniper for RA, there is insufficient reliable information about the clinical effects of juniper for this purpose.
• Urinary tract infections (UTIs). Although there has been interest in using oral juniper for UTIs, there is insufficient reliable information about the clinical effects of juniper for this purpose.
• Wound healing. Although there has been interest in using topical juniper for wound healing, there is insufficient reliable information about the clinical effects of juniper for this purpose. More evidence is needed to rate juniper for these uses.

(Read more about JUNIPER)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there has been interest in using topical oregano oil for acne, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Asthma. Although there has been interest in using oral oregano for asthma, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Bronchitis. Although there has been interest in using oral oregano for bronchitis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Canker sores. Although there has been interest in using topical oregano oil for canker sores, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Cough. Although there has been interest in using oral oregano for cough, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Dandruff. Although there has been interest in using topical oregano oil for dandruff, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Diabetes. Although there has been interest in using oral oregano for diabetes, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Dysmenorrhea. Although there has been interest in using oral oregano for dysmenorrhea, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Dyspepsia. Although there has been interest in using oral oregano for dyspepsia, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Gingivitis. Although there has been interest in using topical oregano oil for gingivitis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Headache. Although there has been interest in using topical oregano oil for headache, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Insect repellent. Although there has been interest in using topical oregano oil as an insect repellent, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Intestinal parasite infection. It is unclear if oral oregano is beneficial in patients with intestinal parasite infections. Details: In one small, uncontrolled study, taking a specific emulsified oregano leaf oil product (ADP, Biotics Research Corporation) 200 mg orally three times daily with meals for 6 weeks resulted in eradication of Blastocystis hominis, Entamoeba hartmanni, and Endolimax nana from the stool in 10 of 13 patients (6878). The clinical significance of this is unclear since the Centers for Disease Control (CDC) considers Entamoeba hartmanni and Endolimax nana to be non-pathogenic, while blastocystosis caused by Blastocystis hominis is usually self-limiting and does not require treatment.
• Pain (acute). Although there has been interest in using topical oregano oil for the relief of acute pain, including joint and muscle pain, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Psoriasis. Although there has been interest in using topical oregano oil for psoriasis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Rhinosinusitis. Although there has been interest in using oral oregano for rhinosinusitis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Seborrheic dermatitis. Although there has been interest in using topical oregano oil for seborrheic dermatitis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Tinea capitis. Although there has been interest in using topical oregano oil for tinea capitis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Tinea corporis. Although there has been interest in using topical oregano oil for tinea corporis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Tinea pedis. Although there has been interest in using topical oregano oil for tinea pedis, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Toothache. Although there has been interest in using topical oregano oil for toothache, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Upper respiratory tract infection (URTI). Although there has been interest in using oral oregano for URTIs, such as the common cold and influenza, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Urinary tract infections (UTIs). Although there has been interest in using oral oregano for UTIs, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Varicose veins. Although there has been interest in using topical oregano oil for varicose veins, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Warts. Although there has been interest in using topical oregano oil for warts, there is insufficient reliable information about the clinical effects of oregano for this purpose.
• Wound healing. It is unclear if topical oregano is beneficial for improving healing or preventing infections in people with skin wounds. Details: One small clinical trial shows that applying an ointment containing a 3% concentration of the water-soluble fraction of the oregano plant twice daily for 10-14 days after minor dermatological surgery might reduce infection rates and improve scar formation when compared with petrolatum ointment (67348). More evidence is needed to rate oregano for these uses.

(Read more about OREGANO)

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) or 3 grams daily for 3 months (114880). ...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), as a 30% gel twice daily for approximately 2 months (94483), or as a 10% solution in a patch to oral lesions 3 times daily for 4 weeks (114815).

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 and appropriately (13160,14319). Concerns about botulism pertain only to children under 12 months of age and not to adults (13160). ...when used topically and appropriately. A specific commercially available wound dressing containing manuka honey (Medihoney) is approved as a medical device by the US Food and Drug Administration (FDA) (16353,16355,16357,16362,16369,16371). Some evidence suggests other honey preparations can also be used safely when applied to the skin or used to rinse the mouth (395,396,397,398,399,7847,7849,13133,14317)(16358,16372,97704,101034,108530).

POSSIBLY SAFE ...when properly diluted honey is used intranasally. Manuka honey 16.5% solution has been used with apparent safety as a nasal rinse twice daily for 14 days (103969). ...when specific, medical-grade honey products are used in eye drops. A specific product (Optimel Manuka Plus Eye Drops, Melcare Biomedical Pty Ltd) has been used safely 2-3 times daily for up to 4 weeks (105231,105234).

LIKELY UNSAFE ...when honey produced from the nectar of rhododendrons is used orally. This type of honey contains grayanotoxins, which may lead to cardiovascular symptoms, such as arrhythmias, hypotension, chest pain, bradycardia, syncope, asystole, various types of heart block, and myocardial infarction (12220,55119,55122,55125,55126,55129,55141,55142,55157)(55163,55170,55171,55180,55183,55190,55224,55233,55234,55239)(55248,55260,55261,55280,55281).

CHILDREN: LIKELY SAFE
when used orally and appropriately, short-term in children at least 12 months of age (15910,17299,55210,55253,97693).

CHILDREN: POSSIBLY UNSAFE
when used orally in children less than 12 months of age. Ingestion of raw honey contaminated with Clostridium botulinum spores can cause botulism poisoning in infants under 12 months of age (13160,55067,55290,91359). This is not a danger for older children or adults. Medical-grade, sterilized honey has been used with apparent safety in the formula of premature newborns at doses of up to 15 grams daily for up to 2 weeks (97697).

PREGNANCY AND LACTATION: LIKELY SAFE
when consumed in food amounts. The concern about botulism pertains to children under 12 months of age and not to pregnant adults (13160). There is insufficient reliable information available about the safety of honey when used for medicinal purposes when pregnant or breast-feeding.

(Read more about HONEY)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Juniper, juniper berry, and juniper extract have Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when used topically on limited areas of skin (12230). ...when the oil is used by inhalation and appropriately as aromatherapy (7107). There is insufficient reliable information available about the safety of juniper when used orally in doses of less than 10 grams of berries or 100 mg of oil daily, short-term. Juniper oil and berry have a long history of traditional use (12,103759).

LIKELY UNSAFE ...when used orally in excessive amounts or long-term. Use of daily doses greater than 10 grams of juniper berries (about 60 berries) or 100 mg of juniper essential oil, or prolonged oral use longer than 4 weeks, have been reported to increase the risk of severe adverse effects such as convulsions or kidney damage (8,19,103759).

PREGNANCY: UNSAFE
when used orally. Juniper can increase uterine tone, interfere with fertility and implantation, and cause abortion (4,19).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about JUNIPER)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Oregano leaf and oil have Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of oregano when used orally in amounts greater than those found in food. There is also insufficient reliable information available about the safety of oregano when used topically. Oregano oil in concentrations of greater than 1% may be irritating when applied to mucous membranes (67348,88188).

PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts. Oregano is thought to have abortifacient and emmenagogue effects (19,7122,19104).

LACTATION:
There is insufficient reliable information available about the safety of oregano when used in medicinal amounts; avoid amounts greater than those found in food.

(Read more about OREGANO)

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 or decrease levels and 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). However, animal research shows that black seed decreases the maximum concentration of and total systemic exposure to phenytoin by 57% and 87%, respectively. This seems to be related to increased clearance and steady state volume of distribution (110905). This interaction has not been shown in humans.

PREDNISOLONE Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically black seed might reduce plasma levels and therapeutic effects of prednisolone.  Details In animal research, oral administration of a single dose of black seed oil 15 minutes prior to oral prednisolone decreases the prednisolone maximum plasma concentration by 65% and area under the curve by 25%(114811). 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.

SILDENAFIL (Viagra) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black seed might reduce plasma levels and the therapeutic effects of sildenafil.  Details Animal research shows that black seed reduces the total systemic exposure to sildenafil by 43% (110898). So far, this interaction has not been reported in humans.

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.

(Read more about BLACK SEED)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, honey may increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.  Details In vitro, honey inhibits platelet aggregation and increases the time to clotting (55222). Furthermore, animal research suggests that feeding mice large doses of honey for 12 days increases bleeding time when compared with no intervention (103964). However, these effects have not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, honey might decrease levels of drugs metabolized by CYP3A4, but research is conflicting.  Details Some clinical research shows that honey induces CYP3A4 (55116). However, other clinical studies found no effect on CYP3A4 activity (55208). Different honey preparations may have different effects on CYP3A4.

PHENYTOIN (Dilantin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, honey might increase levels of phenytoin.  Details In an animal model, the rate and extent of absorption of phenytoin was increased by honey (20352). This effect has not been reported in humans.

(Read more about HONEY)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking juniper berry with antidiabetes medications might cause additive hypoglycemia.  Details Animal research shows that juniper berry can lower blood glucose (4,10580,14907).

DIURETIC DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, juniper berry might increase the risk of adverse effects from diuretic drugs.  Details Juniper berry is thought to have mild diuretic effects (4,512).

LITHIUM Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, juniper berry might reduce lithium excretion and increase serum levels of lithium.  Details Juniper berry is thought to have mild diuretic effects (4,512).

(Read more about JUNIPER)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, oregano might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.  Details In vitro research shows that aristolochic acid isolated from oregano leaves has antithrombin activity (67164). It has also been reported that oregano oil inhibits arachidonic acid-induced, and ADP-induced, platelet aggregation (49445).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, oregano might increase the risk for hypoglycemia when taken with antidiabetes drugs.  Details In vitro and animal research shows that oregano extracts might lower blood glucose levels (67191,67204,110122).

(Read more about OREGANO)

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). One case report describes hepatotoxicity, kidney injury, and rhabdomyolysis occurring in an otherwise healthy 26-year-old male after taking black seed oil 1000 mg twice daily for 1 month. The patient was hospitalized for critical care management, including hemodialysis. After 52 days in the hospital, the patient had recovered and was discharged (114812).

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). Additionally, a case of acute kidney injury, rhabdomyolysis, and hepatotoxicity has been reported in an otherwise healthy 26-year-old male after taking black seed oil 1000 mg twice daily for 1 month. The patient was hospitalized for critical care management, including hemodialysis. . After 52 days in the hospital, the patient had recovered and was discharged (114812).

(Read more about BLACK SEED)

General ...Orally and topically, honey is generally well tolerated in those at least 1 year of age. When given intranasally or into the eyes, honey seems to be well tolerated. However, honey containing grayanotoxins, which are found in rhododendrons, is likely unsafe and should be avoided.
Most Common Adverse Effects:
Orally: Nausea, stomach pain, and vomiting.
Topically: Burning, pain, and stinging.
Intranasally: Burning and nausea.
Ocular: Stinging.
Serious Adverse Effects (Rare):
Orally: Case reports of botulism in infants have occurred. Anaphylaxis has been reported in sensitive individuals. Honey from the Black Sea coast of Turkey, which is derived from the nectar of rhododendrons, has caused respiratory depression, dizziness, sweating, weakness, bradycardia, atrioventricular (AV) block, hypotension, cardiac arrhythmias, and myocardial infarction within a few minutes to several hours after consumption.

Cardiovascular ...Honey from the Black Sea coast of Turkey has been linked with a unique form of poisoning. Honey from this region sometimes contains excessive concentrations of grayanotoxins from rhododendrons, which can cause bradycardia, atrioventricular (AV) block, cardiac arrhythmias, myocardial infarction, and hypotension within a few minutes to several hours after consumption (12220,55110,55126,55129,55238,55269,55270,55280). Fatalities have not been reported. Patients typically respond to fluids and reversal of cardiac conduction abnormalities with atropine.

Dermatologic ...Topically, the use of honey applied to wounds can cause local pain, stinging, and burning in about 5% of patients, some of whom stop treatment as a result (16356,16357,16358,16361,91362,97694,96595). Theoretically, honey may cause excessive drying of wounds, which could delay healing. This can be managed by application of saline packs as needed (7850).

Gastrointestinal ...Orally, honey may cause mild nausea, vomiting, and stomach ache (12220,55119,55190,55294,97693). Honey from the Black Sea coast of Turkey has been linked with a unique form of poisoning. Honey from this region sometimes contains excessive concentrations of grayanotoxins. These toxins can cause increased salivation, nausea, and vomiting within a few minutes to several hours after consumption (12220,55119,55190,55294). Intranasally, honey may cause nausea (55216).

Immunologic ...Orally, honey can cause allergic reactions, including anaphylaxis (6,11,108531,108532). These reactions may be due to various components of the honey, including the honey itself, pollen, or bee secretions (91370). When used topically, local allergic reactions have been reported in people with pre-existing atopy (16356,55118). Allergic contact dermatitis related to honey enriched with propolis has been reported (91365).

Neurologic/CNS ...Orally, honey may cause nervousness, insomnia, and hyperactivity in children (91366,97693). Honey from the Black Sea coast of Turkey has been linked with a unique form of poisoning. Honey from this region sometimes contains excessive concentrations of grayanotoxins, which can cause dizziness, sweating, and weakness within a few minutes to several hours after consumption (12220,55110,55119,55296).

Ocular/Otic ...When used in eye drops, transient stinging has been reported rarely (105231,105234).

Pulmonary/Respiratory ...When used intranasally, a burning sensation of the nasal passages has been reported (55216). Honey from the Black Sea coast of Turkey, which sometimes contains excessive concentrations of grayanotoxins, can cause respiratory depression within a few minutes to several hours after consumption (12220,55110,55119,55296).

Other ...Some honey is contaminated with Clostridium botulinum spores, which poses a risk to infants (6,11,13160,55067,55290,91359). Botulinum spores can proliferate in the intestines of infants and cause botulism poisoning (55112). However, this is not a concern for older children and adults.

(Read more about HONEY)

General ...Orally and topically, juniper seems to be generally well tolerated when used short-term in low doses. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Topically: Allergies, skin irritation.

Dermatologic ...Topically, juniper can cause skin irritation. Signs of topical poisoning include burning, erythema, inflammation with blisters, and edema (4). Repeated exposure to the juniper pollen can cause occupational allergies that affect the skin (6). In a case report, a 62-year-old woman developed burn-like blistering lesions after carrying juniper in close contact to her skin. Concurrent sun exposure was thought to worsen the skin irritation caused by juniper (103756).

Genitourinary ...Orally, large amounts of the juniper berry can cause purplish urine (4).

Pulmonary/Respiratory ...Repeated exposure to the juniper pollen can cause occupational allergies that affect the respiratory tract (6).

(Read more about JUNIPER)

General ...Orally, oregano is well tolerated when used in amounts typically found in foods. There is currently a limited amount of information available about the safety of oregano when used in larger amounts as medicine.
Most Common Adverse Effects:
Orally: Gastrointestinal upset.
Topically: Dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Systemic allergic reactions, including anaphylaxis, in sensitive individuals.

Dermatologic ...Oregano has been reported to cause allergic contact dermatitis (46902). Topically, oregano oil in concentrations of greater than 1% has been reported to cause irritation when applied to mucous membranes (67348,88188).

Gastrointestinal ...Orally, large amounts of oregano can cause gastrointestinal upset. Concentrated, non-emulsified oil of oregano can cause localized irritation of the gastrointestinal tract (6878).

Immunologic ...Systemic allergic reactions have been reported with oregano. A 45-year-old male developed pruritus, respiratory difficulty, hypotension, swelling of the lips and tongue, and facial edema after ingesting pizza seasoned with oregano. He had 2 similar episodes after ingesting foods seasoned with thyme, another member of the Lamiaceae family. He did not react to similar foods without the seasoning, and he had positive skin tests to plants of the Lamiaceae family (3705).

(Read more about OREGANO)