Nigella sativa (Black Seed)

Metadata

Key Constituents

Note on composition variability: The fixed oil content of the seed ranges from 32-40%, while the volatile (essential) oil content is 0.4-0.45%. Thymoquinone content varies substantially depending on geographic origin, cultivation conditions, extraction method, and storage. Commercial products show wide variation in thymoquinone content (3.08-809.4 mg per 100 g product), making standardization a critical issue for clinical use. [Source: PMC4387228; PMC5633670; PMC9460610]

Approved Indications

Commission E (Germany)

• No Commission E monograph exists for Nigella sativa
• The Commission E evaluation period (1978-1994) did not cover Nigella sativa, which was not a traditional German phytomedicine
• Black seed’s primary traditional use base is in Islamic/Middle Eastern and South Asian medicine systems, not in the central European phytotherapy tradition

ESCOP Monograph

• No ESCOP monograph for Nigella sativa
• ESCOP focuses primarily on European medicinal plants with established clinical use in EU member states

EMA/HMPC

• No EMA/HMPC monograph or community herbal monograph has been published for Nigella sativa
• The plant has not been submitted for assessment under either the “well-established use” or “traditional use” pathways
• This regulatory gap means there are no officially harmonized European therapeutic indications, posology guidelines, or safety assessments for Nigella sativa

Agreement/Disagreement Between Bodies

• Complete regulatory absence — unlike herbs such as garlic, hawthorn, or olive leaf, Nigella sativa has no formal monograph from any major European phytotherapy regulatory body
• This is primarily a cultural-geographic gap: Nigella sativa is deeply rooted in Islamic medicine (Tibb-e-Nabawi), Unani medicine, and Ayurveda, but was never part of the central/northern European herbal tradition that forms the basis for Commission E, ESCOP, and EMA/HMPC assessments
• The clinical evidence base has grown substantially since 2010, with multiple meta-analyses now available, but has not yet been submitted for formal European regulatory evaluation
• In the United States, the FDA recognizes Nigella sativa as GRAS (Generally Recognized As Safe) for food use, but this does not constitute a therapeutic endorsement
• The WHO has included Nigella sativa in some regional pharmacopoeias (particularly Eastern Mediterranean), but no WHO monograph of the same caliber as those for garlic or ginkgo has been published
• Implication for clinical use: Without formal monographs, there are no regulatory-endorsed dosing guidelines, standardization requirements, or quality criteria for therapeutic Nigella sativa preparations in Europe or North America

Conditions Treated

Primary (Emerging Clinical Evidence)

Hypertension

• Multiple RCTs demonstrate modest reductions in both systolic and diastolic blood pressure
• Meta-analytic evidence (Sahebkar et al. 2016, 11 RCTs, n=860): SBP reduction of -3.26 mmHg (95% CI: -5.10, -1.42) and DBP reduction of -2.80 mmHg (95% CI: -4.28, -1.32) compared to control
• Updated meta-analysis (Hadi et al. 2023): SBP -3.06 mmHg (95% CI: -3.89 to -2.22, p < 0.001) and DBP -2.69 mmHg (95% CI: -3.72, -1.66, p < 0.001)
• Effect sizes are statistically significant but clinically modest — comparable to garlic and inferior to pharmaceutical antihypertensives
• Powder form may have slightly greater BP-lowering effect than oil form

Dyslipidemia

• Consistent evidence for reductions in total cholesterol and LDL-cholesterol
• Sahebkar et al. 2016 meta-analysis: total cholesterol reduction of -15.65 mg/dL (95% CI: -24.67, -6.63, p=0.001); LDL-cholesterol significantly reduced; no significant effect on HDL-C
• Updated 2024 meta-analysis found more pronounced effects: TC (SMD: -1.78, p < 0.001), TG (SMD: -1.27, p < 0.001), LDL-C (SMD: -2.45, p < 0.001), with a modest increase in HDL-C (SMD: 0.79, p < 0.001)
• Seed oil may have greater effects on TC and LDL-C than seed powder; seed powder may be more effective for raising HDL-C

Secondary

Type 2 Diabetes and Glycemic Control

• Meta-analysis of 16 RCTs: fasting blood glucose reduction of -21.43 mg/dL and HbA1c reduction of -0.44%
• An updated meta-analysis of 30 studies confirmed significant benefits on FBG and HbA1c
• Subgroup analysis suggests: effects on FBG more pronounced with duration >8 weeks; HbA1c, HOMA-IR, and LDL more improved at doses >1 g/day, with oil form potentially more effective
• No significant effects on postprandial glucose, fasting insulin, or HOMA-IR in some analyses [Source: pubmed.ncbi.nlm.nih.gov/29154069/; pubmed.ncbi.nlm.nih.gov/36034891/]

Metabolic Syndrome

• Nigella sativa supplementation has shown improvements in multiple components of metabolic syndrome simultaneously: blood pressure, lipids, fasting glucose, and body weight
• One comparative study found Nigella sativa improved lipid panel and significantly suppressed inflammation in obese prediabetic subjects, with effects comparable to lifestyle modification
• Body weight and BMI reductions have been observed in several trials, though effect sizes are modest [Source: pubmed.ncbi.nlm.nih.gov/25125023/; pubmed.ncbi.nlm.nih.gov/34006388/]

Anti-inflammatory Effects

• Meta-analysis of RCTs in patients with metabolic syndrome found that Nigella sativa supplementation improved oxidative stress and inflammatory markers
• Reductions in C-reactive protein (CRP) and other inflammatory biomarkers have been documented [Source: pubmed.ncbi.nlm.nih.gov/37859312/]

Traditional Use

Islamic and Prophetic Medicine (Tibb-e-Nabawi)

• Nigella sativa holds a unique position in Islamic medicine, referenced in the Hadith (sayings of the Prophet Muhammad): “Use this black seed; for indeed it contains a cure for every disease except death” (Sahih al-Bukhari)
• Known as “Habbatus Sauda” (the black seed) or “Habbatul Barakah” (the seed of blessing)
• Used in Prophetic medicine for a wide range of ailments including digestive complaints, respiratory conditions, fever, headache, toothache, and general wellness
• This religious endorsement has driven centuries of widespread use across the Islamic world and remains a significant motivator for modern research

Unani Medicine

• Classified as a “hot and dry” drug in Unani pharmacology
• Known as “Shoneez” or “Kalonji” in the Unani system
• Used for liver disorders, digestive complaints, respiratory disease, joint pain, and skin conditions
• Avicenna’s “Canon of Medicine” (11th century) describes black seed as stimulating the body’s energy and aiding recovery from fatigue and dispiritedness [Source: researchgate.net/publication/304578667]

Ayurveda

• Used in the Indian traditional medicine system for digestive complaints, bronchial disorders, and skin diseases
• Known as “Kalonji” or “Krishna Jeeraka”
• Applied as a carminative, stimulant, and diuretic
• Used in traditional preparations for amenorrhea, dysmenorrhea, and as a galactagogue

Middle Eastern and North African Traditional Use

• Seeds used as a spice (particularly in bread and cheese) and as medicine for bronchitis, asthma, rheumatism, and related inflammatory diseases
• Topical application of seed oil for dermatological conditions
• Used as anthelmintic, analgesic, and appetite stimulant [Source: PMC3642442]

Mechanism of Action

Thymoquinone (TQ), the principal bioactive compound in Nigella sativa, exerts cardiovascular-relevant effects through multiple intersecting pharmacological pathways.

Antioxidant Activity

• Thymoquinone acts as a potent free radical scavenger, reducing reactive oxygen species (ROS) levels in vascular tissue
• TQ is metabolized in vivo by cellular reductases: one-electron reduction yields semiquinone (pro-oxidant), while two-electron reduction yields thymohydroquinone (potent antioxidant)
• Activation of the Nrf2/HO-1 (nuclear factor erythroid 2-related factor 2 / heme oxygenase-1) pathway — a master regulator of antioxidant defense
• Elevated HO-1 activity improves cardiac redox status and reduces angiotensin II-induced oxidative stress
• Protection of nitric oxide (NO) from oxidative degradation, thereby increasing NO bioavailability and promoting vasodilation [Source: PMC4387230; PMC8762160]

Anti-inflammatory Pathways

• Inhibition of nuclear factor kappa-B (NF-kB) signaling — a central mediator of inflammatory gene expression
• Reduced production of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6)
• Modulation of cyclooxygenase-2 (COX-2) activity
• Activation of PI3K/AKT signaling pathway with downstream anti-inflammatory effects
• Net effect: reduced vascular inflammation, which contributes to both acute blood pressure lowering and long-term vascular protection [Source: sciencedirect.com/science/article/pii/S0753332221002778]

Calcium Channel Blockade

• Nigella sativa volatile oil and thymoquinone induce smooth muscle relaxation by blocking voltage-operated Ca2+ channels
• This leads to dilatation of blood vessels and contributes directly to blood pressure reduction
• Mechanism is analogous to pharmaceutical calcium channel blockers (e.g., amlodipine), though considerably weaker on a dose-for-dose basis [Source: pubmed.ncbi.nlm.nih.gov/8270171/]

ACE Inhibition and Renin-Angiotensin System Modulation

• Nigella sativa supplementation has been associated with decreased angiotensin-converting enzyme (ACE) activity
• Thymoquinone ameliorates angiotensin II-induced hypertension in animal models, attenuating both the vasoconstrictor and pro-inflammatory effects of angiotensin II
• Jaarin et al. (2015) demonstrated that Nigella sativa oil administration in L-NAME-induced hypertensive rats increased cardiac heme oxygenase-1 activity, which in turn reduced angiotensin II-induced NADPH oxidase-mediated oxidative stress [Source: pubmed.ncbi.nlm.nih.gov/30269105/; PMC4642492]

Nitric Oxide Enhancement

• Thymoquinone increases endothelial nitric oxide synthase (eNOS) cascade activation and NO synthesis in endothelial cells
• Nigella sativa seed oil has been shown to halt the loss of plasma NO in animal models of hypertension
• Improved NO bioavailability is a key mechanism for both acute vasodilation and long-term endothelial function preservation [Source: PMC6263230]

Cholinergic and Serotonergic Modulation

• Thymoquinone-induced cardiovascular depressant effects are significantly antagonized by atropine (muscarinic blocker) and cyproheptadine (serotonin antagonist)
• This suggests involvement of both cholinergic and serotonergic pathways in the heart rate-lowering and hypotensive effects [Source: pubmed.ncbi.nlm.nih.gov/8270171/]

Metabolic Mechanisms

• Thymoquinone activates AMPK (AMP-activated protein kinase), leading to enhanced glucose uptake in peripheral tissues
• Inhibition of hepatic gluconeogenesis
• Enhancement of insulin sensitivity
• Inhibition of HMG-CoA reductase (lipid-lowering mechanism shared with statins, though much weaker)

Summary of Cardiovascular Mechanism Profile

Clinical Evidence Summary

Meta-Analyses

Comprehensive GRADE-Assessed Meta-Analysis (2025)

[Source: pubmed.ncbi.nlm.nih.gov/40714301/]

Blood Pressure Meta-Analyses

Sahebkar et al. 2016 (J Hypertens)

[Source: pubmed.ncbi.nlm.nih.gov/27512971/]

Hadi et al. 2023 (Phytother Res)

[Source: pubmed.ncbi.nlm.nih.gov/37341696/]

Lipid Meta-Analyses

Sahebkar et al. 2016 (Pharmacol Res)

[Source: pubmed.ncbi.nlm.nih.gov/26875640/]

Updated Lipid Meta-Analysis (2024)

[Source: pubmed.ncbi.nlm.nih.gov/38777430/]

Glycemic Control Meta-Analyses

Heshmati et al. 2022 (Front Nutr)

[Source: pubmed.ncbi.nlm.nih.gov/36034891/]

Key Individual RCTs

Blood Pressure Trials

[Source: pubmed.ncbi.nlm.nih.gov/18705755/; pubmed.ncbi.nlm.nih.gov/23436437/; pubmed.ncbi.nlm.nih.gov/29348380/]

Lipid and Metabolic Trials

[Source: PMC5633670; pubmed.ncbi.nlm.nih.gov/29154069/]

Overview of Systematic Reviews

Tavakoly et al. (2023, Front Nutr) published an umbrella review of systematic reviews and meta-analyses on Nigella sativa health outcomes, evaluating the totality of meta-analytic evidence. The overview found suggestive to convincing evidence for effects on fasting blood glucose, HbA1c, total cholesterol, and LDL-cholesterol, with weaker evidence for blood pressure and HDL-cholesterol effects. The authors noted that most individual meta-analyses were limited by moderate to high heterogeneity and potential publication bias in smaller studies. [Source: PMC10086143]

Evidence Limitations

• Heterogeneity: Studies use different preparations (seed powder, cold-pressed oil, ethanol extract, supercritical CO2 extract), doses (200-4,600 mg/day), and durations (1-48 weeks)
• Sample sizes: Most individual RCTs have n=30-120 participants; few large-scale trials exist
• Standardization: Thymoquinone content varies enormously between commercial products (3-810 mg/100 g); many studies do not report thymoquinone content of the intervention
• Geographic concentration: Most trials originate from Middle Eastern and South Asian countries (Iran, Saudi Arabia, Egypt, Pakistan, Indonesia), raising questions about generalizability
• Short duration: Most trials are 4-12 weeks; virtually no long-term (>1 year) cardiovascular outcome data
• Hard endpoints absent: No trials have evaluated cardiovascular mortality, myocardial infarction, stroke, or other hard clinical endpoints
• Comparison with standard therapy: Very few head-to-head trials against established pharmaceuticals

Safety Profile

General Safety Assessment

• Nigella sativa is FDA GRAS (Generally Recognized As Safe) for food use
• Clinical trials report the supplement is generally safe at doses up to 3 g/day for up to 3 months
• No serious adverse events have been reported in published clinical trials
• The safety profile at higher doses or longer durations is not well characterized

Adverse Effects

• Gastrointestinal: Epigastric pain, nausea, bloating, diarrhea, and vomiting — the most commonly reported side effects, generally mild and self-limiting
• General: Occasional reports of weakness and minor weight loss
• Dermatological: Allergic contact dermatitis reported with topical application of pure black seed oil; rare cases of erythema multiforme
• Hepatic: Rare elevation of liver enzymes, particularly at high doses — clinical significance uncertain
• Metabolic: Potential for hypoglycemia, especially when combined with antidiabetic medications

Contraindications

• Pregnancy (high doses): Animal studies suggest potential uterotonic effects at high doses; insufficient human safety data in pregnancy. Food-level quantities are likely safe, but therapeutic doses should be avoided
• Known hypersensitivity to Nigella sativa or Ranunculaceae family members
• Pre-operative patients: Consider discontinuation 2 weeks before surgery due to potential antiplatelet and hypoglycemic effects
• Severe hepatic impairment: Insufficient safety data; caution warranted given rare hepatotoxicity reports

Drug Interactions

[Source: pubmed.ncbi.nlm.nih.gov/35921950/; onlinelibrary.wiley.com/doi/10.1155/2013/953520; academia.edu/114286049]

Pregnancy and Lactation

• Pregnancy Category C — Animal studies have shown some concern at high doses; insufficient human data
• Traditional use in pregnancy exists in some cultures, but at food-level quantities, not therapeutic doses
• High-dose supplementation should be avoided during pregnancy due to potential uterotonic effects
• Lactation: Insufficient data; traditionally used as a galactagogue in some cultures, but safety not established by modern standards

Clinical Dosage

Dosage Considerations

• Standardization is critical: Products should specify thymoquinone content; target approximately 10-30 mg thymoquinone per day based on clinical trial interventions
• Onset: Effects on blood pressure and lipids are gradual, typically requiring 4-8 weeks of consistent supplementation
• Duration: Minimum 8 weeks for blood pressure effects; 12 weeks or longer for optimal lipid and glycemic effects
• Formulation matters: Seed oil and seed powder have different pharmacokinetic profiles and may have different efficacy for different endpoints (oil better for lipids; powder potentially better for BP)
• Timing: Usually taken with meals to improve tolerance and reduce GI side effects
• Blood pressure monitoring recommended when initiating supplementation, especially in patients on antihypertensive medications
• Blood glucose monitoring recommended in diabetic patients, particularly those on insulin or sulfonylureas

Sources

Meta-Analyses and Systematic Reviews

• Comprehensive GRADE-assessed systematic review and dose-response meta-analysis of 82 RCTs. Pharmacol Res. 2025. [PubMed: 40714301]
• Sahebkar A et al. A systematic review and meta-analysis of randomized controlled trials investigating the effects of supplementation with Nigella sativa (black seed) on blood pressure. J Hypertens. 2016;34(11):2127-2135. [PubMed: 27512971]
• Hadi A et al. Antihypertensive effects of Nigella sativa supplementation: An updated systematic review and meta-analysis of randomized controlled trials. Phytother Res. 2023;37(9):3848-3860. [PubMed: 37341696]
• Sahebkar A et al. Nigella sativa (black seed) effects on plasma lipid concentrations in humans: A systematic review and meta-analysis of randomized placebo-controlled trials. Pharmacol Res. 2016;106:37-50. [PubMed: 26875640]
• Updated lipid meta-analysis. Complement Ther Med. 2024. [PubMed: 38777430]
• Heshmati J et al. Nigella sativa supplementation improves cardiometabolic indicators in population with prediabetes and type 2 diabetes mellitus. Front Nutr. 2022;9:977756. [PubMed: 36034891]
• Daryabeygi-Khotbehsara R et al. Nigella sativa improves glucose homeostasis and serum lipids in type 2 diabetes: A systematic review and meta-analysis. Complement Ther Med. 2017;35:6-13. [PubMed: 29154069]
• Tavakoly R et al. Nigella sativa and health outcomes: An overview of systematic reviews and meta-analyses. Front Nutr. 2023;10:1107750. [PMC: 10086143]
• Namazi N et al. The effect of Nigella sativa supplementation on glycemic status in adults: An updated systematic review and meta-analysis of randomized controlled trials. Complement Ther Clin Pract. 2024. [ScienceDirect: S1098882324000790]
• Gholamnezhad Z et al. Effects of black seed (Nigella sativa L.) on cardiometabolic indices in type 2 diabetic patients: A systematic review and meta-analysis of RCTs. Complement Ther Clin Pract. 2025. [ScienceDirect: S0965229925000494]
• Mohtashami R et al. Effect of Nigella sativa Intake on Oxidative Stress and Inflammation in Patients with Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-analysis. Phytother Res. 2023. [PubMed: 37859312]

Key Individual RCTs

• Dehkordi FR, Kamkhah AF. Antihypertensive effect of Nigella sativa seed extract in patients with mild hypertension. Fundam Clin Pharmacol. 2008;22(4):447-452. [PubMed: 18705755]
• Fallah Huseini H et al. Blood pressure lowering effect of Nigella sativa L. seed oil in healthy volunteers: a randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2013;27(12):1849-1853. [PubMed: 23436437]
• Rizka A et al. Effect of Nigella sativa Seed Extract for Hypertension in Elderly. Acta Med Indones. 2017;49(4):307-313. [PubMed: 29348380]
• Bamosa AO et al. Effect of Nigella sativa seeds on the glycemic control of patients with type 2 diabetes mellitus. Indian J Physiol Pharmacol. 2010;54(4):344-354.
• Kaatabi H et al. Nigella sativa improves glycemic control and ameliorates oxidative stress in patients with type 2 diabetes mellitus. PLoS One. 2015;10(2):e0113486. [PubMed: 25706772]

Pharmacological and Mechanistic Studies

• El-Tahir KE, Bakeet DM. The black seed Nigella sativa — a mine for multi-drug therapy. J Taibah Univ Med Sci. 2006;1(1):1-19.
• Al-Ali A et al. The cardiovascular actions of the volatile oil of the black seed (Nigella sativa) in rats: elucidation of the mechanism of action. Gen Pharmacol. 1993;24(5):1123-1131. [PubMed: 8270171]
• Jaarin K et al. Mechanisms of the antihypertensive effects of Nigella sativa oil in L-NAME-induced hypertensive rats. Clinics. 2015;70(11):751-757. [PMC: 4642492]
• Hosseini SM et al. The standardized extract of Nigella sativa and its major ingredient, thymoquinone, ameliorates angiotensin II-induced hypertension in rats. J Basic Clin Physiol Pharmacol. 2018;30(1):51-58. [PubMed: 30269105]
• Darakhshan S et al. Thymoquinone and its therapeutic potentials. Pharmacol Res. 2015;95-96:138-158. [PMC: 4387230]
• Woo CC et al. Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol. 2012;83(4):443-451.

Drug Interaction Studies

• Alshammari TM et al. Potential food-drug interaction risk of thymoquinone with warfarin. Chem Biol Interact. 2022;365:110087. [PubMed: 35921950]
• Al-Jenoobi FI et al. Effects of Nigella sativa and Lepidium sativum on cyclosporine pharmacokinetics. Biomed Res Int. 2013;2013:953520.
• Qiu HQ et al. Herbal drug interaction and its implication: Inhibitory effect of Nigella sativa on Human CYP3A4, CYP3A5, CYP2C9 and CYP3A7.

Review Articles

• Ahmad A et al. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed. 2013;3(5):337-352. [PMC: 3642442]
• Bin Sayeed MS et al. Review on Clinical Trials of Black Seed (Nigella sativa) and Its Active Constituent, Thymoquinone. J Pharmacopuncture. 2017;20(3):179-193. [PMC: 5633670]
• Nyulas KI et al. The Use of Nigella sativa in Cardiometabolic Diseases. Biomedicines. 2024;12(2):405.
• Kooshki A et al. Nigella sativa: A Comprehensive Review of Its Therapeutic Potential, Pharmacological Properties, and Clinical Applications. Int J Mol Sci. 2024;25(24):13410. [PubMed: 39769174]
• Leong XF et al. Nigella sativa and Its Protective Role in Oxidative Stress and Hypertension. Evid Based Complement Alternat Med. 2013;2013:120732. [PMC: 3606739]

Connections

• Compare with Garlic for another herb with modest antihypertensive and lipid-lowering effects and CYP450 interaction concerns
• Compare with Hawthorn for a more established cardiovascular phytomedicine with European regulatory recognition
• Compare with Olive Leaf for another herb with ACE-inhibitory activity and emerging antihypertensive evidence but limited regulatory status
• Compare with Fenugreek for another herb from the Ayurvedic/Islamic medicine tradition with hypoglycemic and lipid-lowering effects
• See Berberine for a plant-derived compound with stronger evidence for lipid and glycemic control
• The regulatory gap for Nigella sativa (no Commission E, ESCOP, or EMA monograph) contrasts sharply with well-established cardiovascular herbs like garlic and hawthorn, and illustrates how cultural-geographic traditions shape European phytotherapy recognition