Black Seed 1000 mg by Madre Nature

POSSIBLY INEFFECTIVE

• Hyperlipidemia. Clinical research suggests that alpha-linolenic acid does not lower lipid levels in adults with hyperlipidemia. Details: A meta-analysis of 20 small clinical trials in patients with hyperlipidemia shows that taking foods or supplements containing alpha-linolenic acid does not reduce lipid levels when compared with control (104256). The findings from this analysis are limited by the heterogeneity of the alpha-linolenic acid supplementation regimens and patient populations.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atherosclerosis. Some research suggests that increasing dietary alpha-linolenic acid intake may decrease atherosclerosis. Details: Epidemiological research in White adults has found that high dietary intake of linolenic acid is associated with reduced calcified atherosclerotic plaques in the coronary arteries. Most dietary linolenic acid is alpha-linolenic acid (only a small fraction is gamma-linolenic acid). For every gram of linolenic acid consumed, risk of coronary artery calcification appears to decrease by 62% (12990). The effects of linolenic acid intake in other populations are unclear.
• Atopic dermatitis (eczema). Although there is interest in using oral alpha-linolenic acid (ALA) for atopic dermatitis, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Attention deficit-hyperactivity disorder (ADHD). It is unclear if alpha-linolenic acid is beneficial in patients with ADHD. Details: Small clinical trials show that taking alpha-linolenic acid does not improve symptoms of previously untreated ADHD in children aged 6-16 years. Taking alpha-linolenic acid 1 gram daily for 8 weeks, or taking a combination of alpha-linolenic acid 60 mg, linoleic acid 240 mg, mineral oil 95 mg, and alpha-tocopherol 5 mg twice daily for 7 weeks does not affect ADHD symptom scores when compared with placebo (100660,100661). However, these studies might have been inadequately powered to detect a difference between groups.
• Cancer. It is unclear if increased dietary intake of alpha-linolenic acid affects mortality in patients with cancer. Details: A large meta-analysis of prospective, observational studies has found that high dietary intake of alpha-linolenic acid is associated with a 6% increased risk of mortality from cancer when compared with low dietary intake of alpha-linolenic acid (106661).
• Cardiovascular disease (CVD). Population research has found that increased dietary intake of alpha-linolenic acid may have some benefit for CVD, but results from clinical research are generally less positive. Details: A large meta-analysis of prospective, observational studies has found that high dietary intake of alpha-linolenic acid is associated with an 8% or 11% reduced risk of mortality from CVD or coronary heart disease (CHD), respectively, when compared with low dietary intake of alpha-linolenic acid. A dose-response analysis and meta-analysis show that a 1-gram increase in daily dietary intake is associated with a 5% reduction in CVD mortality (106661,107741). Other population research has found that consumption of 1-2 grams of dietary alpha-linolenic acid daily is associated with a reduced risk of a first myocardial infarction (MI) by as much as 59% in both males and females (7152,7156). The risk of fatal ischemic heart disease is reduced by 65% in females (7153). In patients who have had a previous MI, following a Mediterranean diet rich in alpha-linolenic acid (1.2-1.6 grams daily) and low in saturated fat and cholesterol for 27 months appears to reduce the risk for a second MI by 73% and the risk for death from any cause by 70% when compared to the standard postinfarction diet (7150). Overall, increasing dietary intake of alpha-linolenic acid by 1-1.2 grams daily appears to reduce the risk of fatal coronary heart disease by 20% in people with no history of heart disease and by 20% or more in people with existing heart disease (12978,91403). However, clinical research has not supported these findings. A meta-analysis of a small number of low to moderate quality clinical studies shows that higher intake of alpha-linolenic acid has little to no benefit for primary prevention of CVD, and does not reduce all-cause mortality, CVD mortality, or CHD events. Any reductions in CVD mortality, arrhythmias, or CHD events in individual trials are very small (103955). This may be due in part to the difficulty in separating the effects of alpha-linolenic acid from those of other dietary, lifestyle, or drug interventions (12917). Some research suggests alpha-linolenic acid has a greater effect on coronary heart disease when intake of fish oils is low (12989).
• Chronic obstructive pulmonary disease (COPD). Although there is interest in using oral alpha-linolenic acid (ALA) for COPD, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Cognitive function. It is unclear if oral alpha-linolenic acid improves cognitive function in healthy adults.
• Crohn disease. Although there is interest in using oral alpha-linolenic acid (ALA) for Crohn disease, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Crohn disease. Although there is interest in using oral alpha-linolenic acid (ALA) for Crohn disease, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Depression. It is unclear if oral alpha-linolenic acid is beneficial in patients with depression. Details: Clinical research in patients aged 60-80 years who have had a myocardial infarction shows that consuming margarine containing alpha-linolenic acid 2 grams daily for 40 months does not reduce symptoms of depression when compared with placebo margarine (104978).
• Diabetes. It is unclear if oral alpha-linolenic acid is beneficial in patients with diabetes. Details: Epidemiological research involving overweight and obese individuals has found that eating at least 1.69 grams alpha-linolenic acid daily is associated with a 45% to 47% reduced risk of developing type 2 diabetes when compared with eating only 0.73 grams daily. However, higher intake of alpha-linolenic acid does not appear to be associated with a reduced risk of diabetes in people who are not overweight (101025). In patients with diabetes, epidemiological research shows that lower intake of alpha-linolenic acid is associated with an increased risk of diabetic nephropathy (101024). However, a meta-analysis of clinical research in adults with diabetes who are stable on oral antidiabetic medications shows that adding alpha-linolenic acid 1.5-7.4 grams daily, in the form of flaxseed oil, walnuts, or chia seeds, to a regular diet for 2-12 months does not improve glycemic control when compared with placebo (98002).
• Influenza. Although there is interest in using oral alpha-linolenic acid (ALA) for influenza, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Hypertension. Some research suggests that increasing dietary alpha-linolenic acid may decrease the risk of hypertension. Details: Epidemiological research has found that high dietary intake of linolenic acid is associated with a reduced risk of hypertension in White adults. Most dietary linolenic acid is alpha-linolenic acid (only a small fraction is gamma-linolenic acid). Eating a diet high in linolenic acid seems to reduce the risk of hypertension by about 33% (12991). The effects of linolenic acid intake in other populations are unclear.
• Kidney transplant. Observational research suggests that alpha-linolenic acid is not beneficial after a kidney transplant, and may actually increase the risk of mortality. Details: Epidemiological research has found that dietary intake of alpha-linolenic acid is not associated with improved graft function in kidney transplant. However, kidney transplant recipients in the highest tertile of alpha-linolenic acid intake appear to have a 2.2-fold increased risk of death from any cause when compared with those in the lowest tertile of dietary intake (98003). It is not clear whether this difference is specifically due to alpha-linolenic acid intake or to total fat intake.
• Migraine headache. Although there is interest in using oral alpha-linolenic acid (ALA) for migraine headache, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Multiple sclerosis. Although there is interest in using oral alpha-linolenic acid (ALA) for MS, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Overall mortality. It is unclear if increased dietary intake of alpha-linolenic acid affects all-cause mortality. Details: A large meta-analysis of prospective, observational studies has found that high dietary intake of alpha-linolenic acid is associated with a 10% reduced risk of all-cause mortality when compared with low dietary intake of alpha-linolenic acid. A dose-response analysis shows that a 1-gram increase in daily dietary intake is associated with a 5% reduction in overall mortality (106661). However, a meta-analysis of 250,000 individuals did not find an association between dietary alpha-linolenic acid intake and all-cause mortality (107741). The validity of this finding is limited by the use of dietary surveys to assess intake and the heterogeneity of the included studies.
• Prostate cancer. There is contradictory evidence about the role of alpha-linolenic acid in prostate cancer. Details: Some epidemiologic research suggests that high dietary intake of alpha-linolenic acid is associated with an increased risk for prostate cancer (1337,2558,7823,7147,12978). Other research suggests high intake or serum levels of alpha-linolenic acid is not associated with increased levels of prostate specific antigen (PSA) or the overall risk of prostate cancer (12961,15736,91402). However, it might increase the risk of advanced prostate cancer (12961). The best evidence to date, which comes from a meta-analysis of five prospective population studies, suggests that increasing intake of alpha-linolenic acid by 0.5 grams daily is associated with a modest 1% reduction in the risk of prostate cancer. However, this analysis is dominated by a single study. A meta-analysis of results from nine prospective population studies suggests that a 0.1% increase in blood levels of alpha-linolenic acid is not associated with prostate cancer risk (90677). Reasons for the discrepancies are not entirely clear, but the source of alpha-linolenic acid appears to be important. Alpha-linolenic acid from dairy and meat sources has been positively associated with prostate cancer. Alpha-linolenic acid from plant sources, such as flaxseed, may not affect prostate cancer risk (12909).
• Pneumonia. It is unclear if dietary alpha-linolenic acid reduces the risk for pneumonia. Details: Epidemiological research has found that increasing dietary alpha-linolenic acid consumption is associated with a reduced risk of community-acquired pneumonia (13760).
• Psoriasis. Although there is interest in using oral alpha-linolenic acid (ALA) for psoriasis, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Respiratory tract infections. It is unclear if oral alpha-linolenic acid is beneficial for reducing the incidence of respiratory tract infections in children. Details: Preliminary clinical research in children aged 3-4 years shows that taking alpha-linolenic acid 855 mg, in combination with linoleic acid 596 mg daily from November through February in 2 consecutive years, might reduce the number of recurrent respiratory infections when compared with placebo (10785).
• Rheumatoid arthritis (RA). It is unclear if oral alpha-linolenic acid is beneficial in patients with RA. Details: Preliminary clinical research shows that taking an alpha-linolenic acid-rich oil (flaxseed oil) for 3 months does not improve symptoms or laboratory parameters of RA when compared with baseline or with a linoleic acid-rich oil (safflower oil) (5898).
• Systemic lupus erythematosus (SLE). Although there is interest in using oral alpha-linolenic acid (ALA) for SLE, there is insufficient reliable information about the clinical effects of ALA for this condition.
• Ulcerative colitis. Although there is interest in using oral alpha-linolenic acid (ALA) for ulcerative colitis, there is insufficient reliable information about the clinical effects of ALA for this condition. More evidence is needed to rate alpha-linolenic acid for these uses.

(Read more about ALPHA-LINOLENIC ACID (ALA))

POSSIBLY EFFECTIVE

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

INSUFFICIENT RELIABLE EVIDENCE to RATE

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

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POSSIBLY INEFFECTIVE

• Cardiovascular disease (CVD). Most research suggests that increasing dietary intake of omega-6 fatty acids does not reduce the risk of CVD. Details: A meta-analysis including 19 low-quality randomized controlled trials that followed patients for 1-8 years shows that higher intake of omega-6 fatty acids for at least 12 months does not reduce the risk of primary or secondary CVD events, coronary heart disease (CHD) events, stroke, or all-cause or CVD mortality when compared with a lower intake. The intake of omega-6 fatty acids ranged from 0.8% to 20.6% of energy (99973). Population research conducted over about 7.3 years has also found that baseline red blood cell omega-6 fatty acid levels are not associated with CVD events, CHD events, ischemic strokes, CVD deaths, or all-cause mortality (99974), and red blood cell omega-6 fatty acid levels do not differ between people with or without coronary artery disease in patients hospitalized for coronary angiography (96918). However, some research suggests that individual omega-6 fatty acids may have differing effects in the body. One population study has found that increased levels of shorter chain omega-6 fatty acids in red blood cells, including linoleic acid, gamma linolenic acid, and dihomo-gamma linolenic acid, are associated with a reduced risk of CVD mortality. Higher levels of the longer chain omega-6 fatty acids adrenic acid and docosapentaenoic acid are associated with a moderately increased risk of overall mortality in these patients (96918). Higher quality studies are needed to confirm these findings.
• Child development. Most research suggests that supplementing infant formula with arachidonic acid, an omega-6 fatty acid, and docosahexaenoic acid (DHA), an omega-3 fatty acid, does not improve infant or child development. Details: Meta-analyses of clinical research show that inclusion of arachidonic acid in infant formula at levels of up to 0.84% of fatty acids, in addition to DHA, for 2-12 months does not improve visual or neurodevelopmental outcomes in preterm or full-term infants up to 18 months of age (96919,96920). Also, giving infants DHA- and arachidonic acid-supplemented formula during infancy does not appear to improve neurodevelopment by the age of 6 years (92503).
• Hyperlipidemia. Increasing dietary intake of omega-6 fatty acids does not seem to lower plasma cholesterol or triglyceride levels. Details: A meta-analysis of clinical research shows that increasing intake of omega-6 fatty acids, specifically linoleic acid or gamma-linolenic acid, by replacing dietary saturated or monounsaturated fatty acids modestly reduces levels of total cholesterol. However, the clinical significance is unclear. Also, increasing intake of omega-6 fatty acids does not seem to affect levels of high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, or triglycerides (99973).
• Multiple sclerosis (MS). Most research suggests that taking omega-6 fatty acids is not beneficial for MS. Details: A meta-analysis of the available literature shows that taking omega-6 fatty acids, mainly as linoleic acid, does not seem to prevent disease progression in relapsing-remitting MS patients or chronic progressive MS patients at 24 months (107318).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if increased dietary omega-6 fatty acid intake is beneficial for preventing age-related cognitive decline. Details: Population research has found that the highest blood levels of omega-6 fatty acids during middle age are associated with the best overall cognitive functioning 13 years later when compared with lower intakes (99979). In addition, the highest tertile of omega-6 fatty acid intake in older adults, at least 8.8 mg per kcal daily, is inversely associated with having low cognitive performance. However, the same pattern was observed for the highest tertile of omega-3 fatty acids, and the omega-6 to omega-3 fatty acid ratio in the diet had no overall association with cognitive performance (103308).
• Attention deficit-hyperactivity disorder (ADHD). Oral omega-6 fatty acids have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: Preliminary clinical research shows that taking a combination of omega-3 and omega-6 fatty acids twice daily for 3-6 months does not improve symptoms of ADHD in most children when compared with placebo, although it may improve ADHD symptoms in a subgroup of children with ADHD inattentive subtype plus comorbid neurodevelopmental disorders (65864).
• Blepharitis. It is unclear if oral omega-6 fatty acids are beneficial for blepharitis. Details: One preliminary clinical study in patients with Meibomian gland dysfunction shows that taking a specific product (Medilar, Fidia Oftal Bausch & Lomb Pharmaceuticals), which contains the omega-6 fatty acids linoleic acid 28.5 mg and gamma-linolenic acid 15 mg, once daily for 180 days in combination with eyelid hygiene can improve cloudiness from eye secretions and gland obstruction when compared with baseline (66665). However, the lack of a control group limits the validity of these results. Population research involving postmenopausal adults has also found that moderate dietary intake of omega-6 fatty acids is associated with a reduced risk of developing Meibomian gland dysfunction. However, high intake was not associated with a reduced risk in these patients, and the protective effect of omega-6 fatty acids, if any, in the general population is unclear (99978). Higher quality research is needed to confirm these results.
• Cancer. It is unclear if increased dietary intake of omega-6 fatty acids is beneficial for cancer prevention. Details: In a meta-analysis of clinical research, increasing intake of dietary omega-6 fatty acids does not seem to reduce cancer risk or mortality. However, the included research is of low quality (107005). Also, a meta-analysis of population research has found that dietary intake of omega-6 fatty acids is not associated with cancer risk. However, high blood levels of omega-6 fatty acids were associated with an 8% reduced risk of cancer when compared to low blood levels, with breast cancer carrying the strongest association. Each 5% increase in blood levels of omega-6 fatty acids was associated with a 2% decreased cancer risk (107006). These results should be interpreted with caution, since factors other than omega-6 fatty acid intake, such as alcohol intake or overall diet, may affect blood levels of omega-6 fatty acids (100516).
• Developmental coordination disorder (DCD). Oral omega-6 fatty acids have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: Preliminary clinical research shows that taking a combination of omega-6 and omega-3 fatty acids for 3 months can improve reading, spelling, and behavior, but not motor skills, when compared with placebo in children with DCD (13748).
• Diabetes. It is unclear if higher dietary or supplemental intake of omega-6 fatty acids is associated with a reduced risk of diabetes. Details: Population research has found that the highest blood levels of the omega-6 fatty acid linoleic acid are associated with a 43% reduced risk of developing diabetes over a period of 5-42 years when compared with the lowest blood levels. Blood levels of another omega-6 fatty acid, arachidonic acid, do not seem to be linked to diabetes risk (96914). These results should be interpreted with caution, since factors other than omega-6 fatty acid intake, such as alcohol intake or overall diet, may affect blood levels of omega-6 fatty acids (100516). In addition, a meta-analysis of low-quality clinical research does not support any benefit of omega-6 fatty acids in the prevention or treatment of type 2 diabetes (101504).
• Diarrhea. It is unclear if formula supplemented with arachidonic acid is beneficial for diarrhea prevention in infancy. Details: Preliminary clinical research shows that infant formula supplemented with arachidonic acid 34 mg/100 kcal and docosahexaenoic (DHA) acid, an omega-3 fatty acid, 17 mg/100 kcal (Enfamil Premium 1 and Enfamil Premium 2, Mead Johnson Nutrition) can reduce the incidence of diarrhea in the first year of life when compared with non-supplemented infant formula (92505).
• Dry eye. It is unclear if dietary intake of omega-6 fatty acids is beneficial for dry eye prevention. Details: Population research has found that higher intake of dietary omega-6 fatty acids is not associated with a reduced risk of dry eye after menopause (99978).
• Hypertension. It is unclear if dietary intake of omega-6 fatty acids is beneficial for blood pressure reduction. Details: Population research has found that higher dietary intake of omega-6 fatty acids, especially linoleic acid, is inversely associated with the odds of hypertension in non-diabetic individuals. However, in patients with diabetes, higher intake of omega-6 fatty acids is associated with an increased odds of hypertension (99975).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if dietary intake of omega-6 fatty acids is beneficial for NAFLD prevention. Details: Cross-sectional population research is mixed with respect to dietary intake of omega-6 fatty acids in patients with NAFLD when compared with healthy controls. One large cross-sectional study based on data from the National Health and Nutrition Examination Survey (NHANES) between 2007-2014 has found that consuming omega-6 fatty acids at a dose of at least 250 mg/kg daily is associated with an 82% reduced risk of having NAFLD when compared with consuming less than 121.3 mg/kg daily (107002).
• Obesity. It is unclear if oral omega-6 fatty acids are beneficial for reducing cholesterol or triglyceride levels in adults with obesity. Details: In individuals with abdominal obesity, a small clinical trial shows that taking linoleic acid 15 grams (females) or 20 grams (males) (Pharmatech AS) daily for 7 weeks from safflower oil has modest beneficial effects on levels of low-density lipoprotein (LDL)-, high-density lipoprotein (HDL)-, and total cholesterol when compared with baseline or taking fish oil. However, there was no effect on triglyceride levels (107003).
• Photoreactive keratectomy. Oral omega-6 fatty acids have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: Preliminary clinical research in patients who have undergone photoreactive keratectomy shows that taking a tablet containing the omega-6 fatty acids linoleic acid and gamma-linolenic acid, as well as beta-carotene, B vitamins, and trace minerals, daily for 30 days can improve tear production and eye healing when compared with a control group (66679).
• Respiratory tract infections. It is unclear if supplementing infant formula with arachidonic acid is beneficial for preventing respiratory tract infections. Details: Preliminary clinical research shows that infant formula supplemented with arachidonic acid 34 mg/100 kcal and docosahexaenoic acid (an omega-3 fatty acid) 17 mg/100 kcal (Enfamil Premium 1 and Enfamil Premium 2, Mead Johnson Nutrition) can reduce the incidence of respiratory illness in the first year of life when compared with non-supplemented infant formula (92505). More evidence is needed to rate omega-6 fatty acids for these uses.

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LIKELY SAFE ...when used orally in amounts typically found in foods (7141,7142,7144). There is insufficient reliable information available about the safety of alpha-linolenic acid when used in larger, medicinal amounts.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts typically found in foods (7141,7142,7145). There is insufficient reliable information available about the safety of alpha-linolenic acid during pregnancy and lactation when used in larger, medicinal amounts; avoid using.

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

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

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

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

LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when used orally in amounts found in foods. Dietary intake in amounts of 5% to 10% of daily calories are appropriate according to the Dietary Reference Intake (DRI) Acceptable Macronutrient Distribution Range (AMDR) (23723). There is insufficient reliable information available about the safety of omega-6 fatty acids when used orally in medicinal amounts.

CHILDREN: LIKELY SAFE
when consumed by children over the age of 12 months as part of the diet in amounts between 5% to 10% of daily calories according to the Dietary Reference Intake (DRI) Acceptable Macronutrient Distribution Range (AMDR) (23723).

PREGNANCY AND LACTATION: LIKELY SAFE
when consumed as part of the diet in amounts between 5% and 10% of daily calories according to the Dietary Reference Intake (DRI) Acceptable Macronutrient Distribution Range (AMDR) (23723).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when high amounts of omega-6 fatty acids are consumed in the diet. Population research suggests that the highest maternal intakes of omega-6 fatty acids (15.2-47.6 grams or 137-428 kcal daily) during pregnancy is associated with a 2.4-times greater odds of giving birth to an infant below the 10th percentile for birth weight when compared with the lowest maternal intakes (0.4-5.7 grams daily) (96913). In addition, population research in women with a history of atopy suggests that the highest blood levels of omega-6 fatty acids during the second trimester is associated with an increased odds of having a child develop atopic dermatitis by age 4-6 years when compared with the lowest intakes (103309). There is insufficient reliable information available about supplemental omega-6 fatty acids; avoid using.

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

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

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

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

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

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

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

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

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

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

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

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

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(Read more about OMEGA-6 FATTY ACIDS)

General ...Orally, alpha-linolenic acid from dietary sources is well tolerated when used in the diet as a replacement for other sources of fat, such as saturated fats.
Serious Adverse Effects (Rare):
Orally: There is some concern that high dietary intake of alpha-linolenic acid might increase the risk for prostate cancer, although research is conflicting.

Oncologic ...Epidemiologic research suggests that high dietary intake of alpha-linolenic acid might increase risk for prostate cancer (1337,2558,7823,7147,12978). Other research suggests high intake or serum levels of alpha-linolenic acid does not increase the overall risk of prostate cancer (12961,15736); however, it might increase the risk of advanced prostate cancer (12961). Association with prostate cancer appears to depend on the sources of alpha-linolenic acid. Dairy and meat sources has been positively associated with prostate cancer, whereas plant sources, such as flaxseed, don't seem to affect prostate cancer risk (12909). According to a clinical trial, intake of alpha-linolenic acid does not appear to increase levels of prostate specific antigen (PSA) (91402). Also, longer-chain omega-3 fatty acids in fish oils are associated with a decreased risk of total and advanced prostate cancer (12961).

Other ...Alpha-linolenic acid is a type of fat, containing 9 kilocalories/gram, and may result in weight gain if consumed in excess. Patients should be advised that it's best to substitute alpha-linolenic acid in the diet for other sources of fat, such as saturated fats.

(Read more about ALPHA-LINOLENIC ACID (ALA))

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

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

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

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

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

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

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

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General ...Orally, consuming omega-6 fatty acids in amounts found in foods is well tolerated.

Cardiovascular ...Dietary intake of the omega-6 fatty acid linoleic acid in amounts of 5% to 10% of daily calories is appropriate according to the Dietary Reference Intake (DRI) Acceptable Macronutrient Distribution Range (AMDR) (23723). However, higher intake levels, especially when compared with omega-3 fatty acid intake, might be detrimental. For example, a higher ratio of dietary omega-6 to omega-3 fatty acids is thought to increase the risk of cardiovascular disease compared to a lower ratio (66678). However, the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism, the Council on Cardiovascular Nursing, and the Council on Epidemiology and Prevention, suggest that reduction of omega-6 fatty acids in the diet is unlikely to be beneficial for the cardiovascular system if replaced with saturated or trans-fatty acids (66692). Population research has found that higher intake of omega-6 fatty acids might be associated with hypertension and increased levels of plasma homocysteine, a risk factor for cardiovascular disease and atherosclerosis (65498,66640,66642).

Musculoskeletal ...In epidemiological research, increased intake of omega-6 fatty acids was associated with elevated risk of fracture in the elderly (66662).

Neurologic/CNS ...In epidemiological research, an increased dietary ratio of omega-6 fatty acids to omega-3 fatty acids has been associated with an elevated risk of having a sleep disorder (107001).

Oncologic ...Some population research has found that high omega-6 fatty acid intake or blood levels are associated with an increased risk for cancer, including breast cancer and prostate cancer (3508,7824,66660,66664,66729).

Psychiatric ...In epidemiological research, adolescents with attention-deficit hyperactivity disorder (ADHD) had higher levels of omega-6 and lower levels of omega-3 fatty acids in red blood cells (48200). The role of omega-6 fatty acids in ADHD is unclear; it is possible that the low levels of omega-3 fatty acids and essential fatty acids in general may be playing a role. Also, higher levels of some omega-6 fatty acids in the body are associated with greater depressive symptomology and neuroticism (65815,66659). Higher concentrations of some omega-6 fatty acids in red blood cells of patients with schizophrenia are correlated with positive schizotypal trait measures in healthy adults (66635). This may be related to increased intake of omega-6 fatty acids in the diet of patients with schizophrenia (96916).

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