The remarkable clinical versitility of Nigella sativa

by Max Langen

OMNS (June 1, 2023) Nigella sativa, also called black cumin, is one of the most important medicinal plants. Its seeds (sometimes called "black seeds") have been used for thousands of years as a spice and condiment, and in several traditional medicine systems to treat a wide range of diseases. This plant is described and acknowledged in ancient medical and religious literature. The Bible mentions Nigella sativa as "Curative black seed," and it is also known as prophetic medicine, since Prophet Muhammad, the founder of Islam, referred to it as "cure for every disease except death." It was mentioned in Chinese and Indian traditional medicine and was also described in traditional Arab and Islamic medicine. [1-3]

The biochemical content of nigella sativa seeds includes oils (30-40%), essential oils including thymoquinone, nigellidine, and PUFAs, and many other proteins (~25%), minerals, fatty acids, alkaloids, sterols (alpha-hederine), phenolics, flavonoids, and saponins. Recent clinical studies have shown that seeds of nigella sativa and their major compounds including thymoquinone have strong immunomodulatory, anti-inflammatory, anti-oxidant, antiviral, antibacterial, antimalarial, antifungal, antihistaminic, anticancer, antidiabetic, anti-epileptic, anti-asthmatic, anti-allergic, antitussive, anticoagulant, analgesic, cardioprotective, hepatoprotective, gastroprotective and neuroprotective effects, among others. [1-3]

Nigella sativa has shown in several studies to be highly effective for the prevention and treatment of Covid-19, massively reducing severe outcomes and mortality. Many could still be alive had this therapy not been widely ignored. Also, the combination of nigella sativa and vitamin D has shown to be remarkably effective in the clearance of a viral infection.

Before looking more closely at those impressive results from studies on Covid-19, here are short summaries of what recent clinical studies have shown about the healing effects of nigella sativa for other conditions, including other infectious diseases. As of April 2023, there are more than 1900 scientific publications on nigella sativa. More than 90 randomized controlled trials (RCTs) and meta-analyses of RCTs have been published to date that tested the effectiveness of nigella sativa for various diseases and health outcomes, with a large majority of them showing clear benefits. This evidence suggests that nigella sativa could be used as an effective (adjuvant) treatment to improve many conditions. RCTs, often placebo-controlled, or meta-analyses of RCTs have shown that nigella sativa, often administered as capsules with 1000 or 2000 mg of nigella sativa seed oil, or pharmaceutical powder of the seeds (and sometimes given in other forms, for example as pure, non-powdered nigella sativa seeds or as topical ointment/gel application) can effectively:

• reduce hypertension by lowering both systolic and diastolic blood pressure. [4]
• support achieving and maintaining a healthy weight in overweight individuals by helping to moderately reduce weight and body mass index. [5]
• treat metabolic syndrome, by reducing body mass index, waist circumference and body fat percentage, fasting glucose and lipid levels. The combination of nigella sativa + turmeric was even more effective. [6]
• improve glucose status in patients with type 2 diabetes, by decreasing fasting plasma glucose, postprandial glucose and long term glucose (HbA1c) levels. [7] In patients with prediabetes, it reduces glycemic and anthropometric parameters just as effectively as the drug metformin. [8]
• decrease blood lipid levels, including total cholesterol, very low density cholesterol, LDL cholesterol and triglycerides for individuals with excessive levels. [9]
• treat nonalcoholic fatty liver disease by improving the grades of liver steatosis, injury and fatty liver. Various liver and cholesterol parameters improved. [10,11]
• increase total antioxidant capacity and reduce oxidative stress. [12]
• reduce inflammatory processes (especially hs-CRP and TNF-alpha), suggesting that it decreases chronic inflammation. [12] Of note, chronic low-grade inflammatory processes are important causes of most diseases and conditions including cancer.
• improve cardiovascular health and therefore reduce the risk of cardiovascular diseases via many different mechanisms (incl. reduction of hypertension, cholesterol and body weight, glucose regulation, reduction of silent inflammation and oxidative stress etc.) In patients at increased risk of cardiovascular disease, it also improved flow-mediated dilation, the level of nitric oxide, and lowered mean arterial pressure and heart rate, [13,14] suggesting that it can greatly stabilize the health of the cardiovascular system.
• improve kidney parameters, suggesting that it may help maintain or increase health of the kidneys. [9] In patients with (advanced) chronic kidney disease (stage 3 or 4) due to diabetic nephropathy, it reduced blood glucose and improved kidney parameters incl. serum creatinine and glomerular filtration rate etc. suggesting that it may stop the progression of kidney disease or even help reverse it. [15] An additional study confirmed that patients with advanced kidney disease greatly improve by nigella sativa. The addition of nigella sativa to the treatment protocol caused a "marked improvement" in clinical features and kidney parameters. [16]
• dissolve kidney stones. In the nigella sativa group, 44% of patients excreted their kidney stones completely, and in a further 52% the size of the stones was reduced. In the placebo group, only 15% excreted their stones, 12% had a reduction of stone size, and 15% even had an increase of stone size. [17] This suggests nigella sativa may also prevent kidney stone formation.
• improve Hashimoto thyroiditis, which is one of the most common autoimmune diseases. TSH, antibodies against the thyroid and vascular endothelial growth factor decreased, while the thyroid hormone T3 level increased, suggesting that it helps reverse the disease, strengthens the health of the thyroid and may also be an effective treatment for autoimmune diseases in general. [18] As will be shown below, nigella sativa has already shown to be effective for several autoimmune conditions: rheumatoid arthritis, ulcerative colitis, psoriasis, vitiligo and asthma.
• decrease the severity of rheumatoid arthritis. Swollen joints and morning stiffness were also reduced. [19]
• reduce stool frequency in patients with ulcerative colitis. [20]
• improve psoriasis. Both oral and gel administration of nigella sativa were effective in most patients and led to improvements after several weeks of treatment. However, the combination of both oral and gel administration led to the best outcomes. 55% of psoriasis patients who received this combination achieved a good response. Further, 30% even had an excellent response or achieved a complete cure. Of note, if the treatment was stopped, the condition returned in some patients, indicating that it may be helpful for these patients to continue the treatment. [21]
• treat vitiligo (patchy skin pigmentation). Nigella sativa (as a gel application) was more effective than fish oil in reducing the vitiligo area scoring index. [22]
• treat hand eczema. Nigella sativa (as gel application) was just as effective as the drug betamethasone, reducing the severity of hand eczema and increasing quality of life in the affected patients. [23]
• treat dermatitis. Nigella sativa reduced the symptoms and signs of occupational contact dermatitis like eczematous lesions. In many patients, dermatitis improved or disappeared completely. Of note, oral capsules were more effective than topical administration. [24]
• treat acne vulgaris (as gel application). After 2 months, the acne disability index had declined by 64% in the Nigella sativa group, compared with 5% in the placebo group. [25]
• reduce symptoms of asthma (shortness of breath, night time waking, interference with activity), reduce rescue treatment and inhaler use, rating of asthma control, and improve lung function measured as forced expiratory volume at 1 second (FEV1). [26]
• treat impaired lung function in chemical war victims. Nigella sativa (as boiled extract) improved pulmonary function, chest wheezing and all other respiratory symptoms. The need to use inhalers and drugs decreased, suggesting that it may at least partially substitute for drugs. [27]
• treat allergic conditions, including allergic rhinitis, by reducing runny nose, nasal congestion, sneezing attacks, nasal itching, turbinate hypertrophy etc. in affected patients. [28,29]
• reduce knee osteoarthritis symptoms and pain. [30] Nigella sativa (as gel/oil application) was more effective in relieving pain (51% reduction) than the common pharmaceutical pain reliever diclofenac (14% reduction). [31]
• improve symptoms of menopausal women (in combination with another herbal medication: Vitex agnus-castus). Psychosocial, physical and vasomotor (hot flashes) symptoms decreased. [33]
• treat polycystic ovary syndrome. It was effective in the treatment of menstrual irregularities in women with PCOS. [34]
• stabilize/increase mood, calmness and cognition, and decrease anxiety. [35]
• treat major depressive disorder. In the intervention group that received the antidepressant sertraline + Nigella sativa capsules, the depression scores declined more than in the control group that only received sertraline + placebo. [36]
• increase attention and memory, suggesting that it may help prevent cognitive decline and dementia. [37]
• treat epilepsy in patients resistant to conventional anti-epileptic drugs. Administration of the aqueous extract of Nigella sativa or high dose thymoquinone (one of its main active ingredients) reduced the frequency of epileptic seizures. [38,39]
• improve nasal dryness, obstruction and crusting (as intranasal application) in older people suffering from nasal mucosa symptoms. [40]
• improve oral submucous fibrosis. Burning sensation decreased by 80% after continuous application of nigella sativa. Mouth opening was also reduced. [41]
• treat alveolar osteitis/dry socket (painful inflammation following tooth extraction). Nigella sativa (as oil and powder) was a more effective dressing material than a commonly used commercial dressing. Those who received this treatment had immediate and complete pain relief and required less repeated visits. [42]
• improve recovery of oral cavity ulcers or traumatic ulcers. [43]
• treat gingivitis. Nigella sativa oil reduced the gingival index score, inflammation, and pathogenic (streptococcus) bacteria. By decreasing biofilm formation and disrupting the colonization of such bacteria, it may help reduce the progression of periodontal diseases. It was as effective as chlorhexidine, suggesting that nigella sativa could be an alternative to chemical mouthwashes. [44]
• treat insomnia. Nigella sativa restored restful sleep in patients with sleep issues. [45]
• improve irritable bowel syndrome after some weeks of continuous intake. Severity of the disease symptoms, abdominal distention and the impact of the condition on daily life decreased, and defecation improved. [46]
• reduce urinary incontinence (in older women). [47]
• improve semen quality (sperm count, motility, morphology, volume etc.) in infertile men, suggesting that it may help reverse infertility and increase pregnancy rates. [48]
• treat female infertility by improving reproductive parameters including the number of ovarian follicles and reducing oxidative stress and may therefore help reverse female infertility and increase pregnancy rates. [49]
• increase volume of breastmilk in breastfeeding mothers. [50]
• treat (chronic) rhinosinusitis. Nigella sativa (as nasal drops) reduced the congestion, pain, numbness, pressure, fullness and bad breath in patients with chronic rhinosinusitis. [51]
• treat arsenic poisoning in patients with palmar arsenical keratosis. Nigella sativa reduced the body arsenic load, which led to an improvement of arsenical keratosis. Therefore, it might also support detoxification of other toxic metals. [52]
• improve immune health. Nigella sativa (1 g of seed oil per day) has an immunopotentiating effect, increasing total lymphocyte count, CD3+ and CD4+ cells, suggesting that it reduces the risk of infectious diseases. [53]
• prevent side effects of toxic cancer therapies: Nigella sativa (as a gel application) reduced the incidence and severity of phlebitis (inflammation of veins), a common complication of intravenous chemotherapy. [54] As a mouth rinse it decreased the severity of chemotherapy-induced oral mucositis. Erythema, ulceration and pain were reduced. Therefore, it enabled those patients to consume normal food. [55] Nigella sativa (as a gel application) reduced the risk of developing acute radiation dermatitis in breast cancer patients treated with radiotherapy. [56] Nigella sativa also reduced the risk of developing febrile neutropenia (FN), a dangerous complication of chemotherapy. Chemotherapy harms the immune system and often leads to a reduction of immune cells (neutrophil granulocytes). 5 grams of nigella sativa seeds per day greatly reduced the risk of developing a chemotherapy-induced FN, inhibiting the harm done to the immune system and reducing by almost 90% severe or deadly (viral, bacterial, fungal) infections. [57]
• treat hepatitis C infections by attenuating viral load. 50% of hepatitis C patients treated with (a relatively low dose of) nigella sativa had a decrease in the quantitative viral load and 17% even became seronegative. [58] A higher dose might have been even more effective. Of note, another study also showed that hepatitis can be treated more effectively by adding nigella sativa and vitamin C to conventional therapy. [59]
• treat vaginitis caused by a candida albicans infection. Standard therapy + nigella sativa was more effective in reducing several symptoms and signs of candida-induced vaginitis compared with standard therapy + placebo. [60]
• eradicate helicobacter pylori infections (bacteria), which are among the leading causes of gastric cancer. Resistance of helicobacter towards pharmaceutical drugs has recently increased alarmingly. Eradication of helicobacter occurred in almost 60% of patients who were treated with high dose nigella sativa + honey. [61] Double-blind RCTs confirmed that patients who received standard therapy + nigella sativa achieved a greater eradication. [62,63]
• treat staphylococcal skin infections. In neonates with staphylococcal skin infections, it was similarly effective as the antibacterial drug mupirocin. [64]
• inhibit bacterial wound infections caused by staphylococcus aureus. A lab study with samples obtained from cases of wound infections in a hospital showed that high dose thymoquinone may inhibit s. aureus and therefore prevent/treat such wound infections. [65]
• inhibit MRSA (methicillin resistant staphylococcus aureus), which is one of the deadliest bacterial infections often acquired in a hospital. Nigella sativa (in high concentrations in a preclinical study) was shown to have inhibitory effects against MRSA. [66] It also had inhibitory effects against vancomycin resistant staphylococcus aureus (VRSA). [67]
• accelerate the recovery of acute respiratory infections overall (flu/cold etc.). Patients with an acute respiratory infection who received nigella sativa had a greater chance of becoming symptom-free after only 4 days. [68] A combination of nigella sativa oil + echinacea extract + garlic powder + panax ginseng extract + vitamin C + zinc cut the duration of a common cold in half (4 vs. 8 days of median recovery time). [69]

Treating Covid-19

Nigella sativa not only prevented Covid-19 in many people, but also accelerated the recovery and greatly reduced the development of severe symptoms or death in patients with Covid-19. [3] Several compounds of nigella sativa, including thymoquinone, nigellidine and alpha-hederin have proven antiviral and anti-inflammatory effects. Thymoquinone can inhibit the main protease in SARS-CoV-2, causing a "strong anti-SARS-CoV-2 activity." [70]

A prospective prophylaxis study with 376 participants has shown that daily consumption of 40 mg/kg of nigella sativa seeds (= 3000 mg per day for a 75 kg person) reduced the risk of developing a symptomatic case of Covid-19 by more than 60%. Of note, the results of this study were available in Jan 2021. [71] A widespread recommendation to use nigella sativa would therefore have been an effective way to limit the pandemic and reduce the incidence of symptomatic infections in the population.

In a recent RCT with hospitalized Covid-19 patients, the treated group received standard therapy and 80 mg/kg/day of encapsulated nigella sativa seeds plus 1 g/kg/day of honey. [72] The results showed that the treated group had significantly faster viral clearance and recovery. In fact, those who received NS + honey recovered almost twice as fast. Overall, the patients in the treated group had a 82% lower risk of death compared with the control group. Importantly, these striking results of this high quality study were available in Nov. 2020, during the first year of the pandemic. [73]

Therefore, by 2020 it was clear that this treatment could reduce the fatality rate of hospitalized Covid-19 patients by 80%. Since then, millions of Covid-19 patients have died, but many of these deaths could have been easily prevented, not only with nigella sativa and honey, but also with other natural and orthomolecular treatment protocols that have shown to be similarly effective in reducing mortality of Covid-patients. [74,75]

Importantly, earlier treatment with nigella sativa can even prevent the progression and development of severe stages of Covid-19. A recent RCT showed that, if treatment with nigella sativa is started early in the disease course, shortly after symptoms begin, serious complications (and therefore hospitalization etc.) can be strongly reduced. Among those patients who only received the standard treatment, 17% developed a severe case. However, among those who received nigella sativa seeds for a duration of 2 weeks, only 1% developed severe symptoms, a 93% reduction. The results of this RCT were published in Jan 2021. [76]

A recent RCT confirmed that daily treatment with 1000 mg of nigella sativa seed oil (in capsules) improves recovery from Covid-19. The patients in the intervention group (standard therapy + nigella sativa) recovered significantly faster from Covid-symptoms than those in the control group (who only received standard therapy). The intervention group had a 75% lower risk of requiring hospitalization. [77]

In another RCT, Covid-19 outpatients were divided into four groups:

Group 1 received standard therapy + nigella sativa capsules, group 2 received standard therapy + vitamin D, group 3 received standard therapy + a combination of both nigella sativa and vitamin D and group 4 received only standard therapy (control group). The results showed that while viral clearance and symptom recovery occurred faster in groups 1 and 2 compared with the control group, the combination group that received both nigella sativa + vitamin D had the most impressive results with regard to recovery of the disease. The authors noted the remarkably fast viral clearance and reduction of many symptoms in this combination group and recommended this treatment for Covid-patients. [78] It is therefore highly likely that nigella sativa + vitamin D may also be a very effective treatment combination for other (infectious) diseases. They may have synergistic effects.

The evidence clearly shows: Had nigella sativa been used widely to treat Covid-19, many lives could have been saved. Unfortunately, however, governments around the world chose to recommend (or enforce) an experimental prophylactic drug, which caused massive numbers of serious adverse events and injuries [79] and led to significant excess mortality. [80] Analyses from various countries clearly showed that the higher the uptake of this experimental drug in 2021, the stronger the increase in excess deaths in 2022. Extensive mortality analyses by many scientists indicate that these drugs caused the deaths of 6.5 to 13 million people worldwide. [81]

Even before the roll-out of those experimental drugs, many people died from side effects of typical conventional medicine. Prescription drugs are one of the leading causes of death in Europe and in the United States of America. [82] Orthomolecular or natural medicine has been shown to be highly effective for many conditions and diseases, suggesting that most of these deaths from conventional drugs could easily be prevented by more widespread use of natural treatment approaches. Of course, each individual's situation is different and may require different treatment approaches. Health issues should always be discussed with an orthomolecular or natural health care provider who can offer medical advice and help finding the best natural (or natural + conventional) treatment for an individual.

Many nigella sativa products are available and not all of them are high quality. When choosing nigella sativa capsules (rather than consuming the raw seeds in sufficient amounts), one should make sure that the seed oil is cold-pressed, to ensure that the capsules contain the seeds' effective compounds. The color of the oil needs to be golden and a bitter smell/taste should prevail. A lighter yellow color would be a negative sign, which indicates that too many of the compounds have been removed during the processing.

References:

1. Ahmad MF, Ahmad FA, Ashraf SA, et al. (2021) An updated knowledge of Black seed (Nigella sativa Linn.): Review of phytochemical constituents and pharmacological properties. J Herb Med. 25:100404. https://pubmed.ncbi.nlm.nih.gov/32983848

2. Ijaz H, Tulain UR, Qureshi J, et al. (2017) Review: Nigella sativa (Prophetic Medicine): A Review. Pak J Pharm Sci. 30:229-234. https://pubmed.ncbi.nlm.nih.gov/28603137

3. Maideen NMP (2020) Prophetic Medicine-Nigella Sativa (Black cumin seeds) - Potential herb for COVID-19? J Pharmacopuncture. 23:62-70. https://pubmed.ncbi.nlm.nih.gov/32685234

4. Sahebkar A, Soranna D, Liu X, et al. (2016) 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. 34:2127-2135. https://pubmed.ncbi.nlm.nih.gov/27512971

5. Mousavi SM, Sheikhi A, Varkaneh HK, et al. (2018) Effect of Nigella sativa supplementation on obesity indices: A systematic review and meta-analysis of randomized controlled trials. Complement Ther Med. 38:48-57. https://pubmed.ncbi.nlm.nih.gov/29857879

6. Amin F, Islam N, Anila N, Gilani AH. (2015) Clinical efficacy of the co-administration of Turmeric and Black seeds (Kalongi) in metabolic syndrome - a double blind randomized controlled trial - TAK-MetS trial. Complement Ther Med. 23:165-174. https://pubmed.ncbi.nlm.nih.gov/25847554

7. Askari G, Rouhani MH, Ghaedi E, et al. (2019) Effect of Nigella sativa (black seed) supplementation on glycemic control: A systematic review and meta-analysis of clinical trials. Phytother Res. 33:1341-1352. https://pubmed.ncbi.nlm.nih.gov/30873688

8. Mostafa TM, Hegazy SK, Elnaidany SS, et al. (2021) Nigella sativa as a promising intervention for metabolic and inflammatory disorders in obese prediabetic subjects: A comparative study of Nigella sativa versus both lifestyle modification and metformin. J Diabetes Complications 35:107947. https://pubmed.ncbi.nlm.nih.gov/34006388

9. Razmpoosh E, Safi S, Abdollahi N, et al. (2020) The effect of Nigella sativa on the measures of liver and kidney parameters: A systematic review and meta-analysis of randomized-controlled trials. Pharmacol Res. 156:104767. https://pubmed.ncbi.nlm.nih.gov/32201245

10. Tang G, Zhang L, Tao J, Wei Z. (2021) Effect of Nigella sativa in the treatment of nonalcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials. Phytother Res. 35:4183-4193. https://pubmed.ncbi.nlm.nih.gov/33728708

11. Khonche A, Huseini HF, Gholamian M, et al. (2019) Standardized Nigella sativa seed oil ameliorates hepatic steatosis, aminotransferase and lipid levels in non-alcoholic fatty liver disease: A randomized, double-blind and placebo-controlled clinical trial. J Ethnopharmacol. 234:106-111. https://pubmed.ncbi.nlm.nih.gov/30639231

12. Montazeri RS, Fatahi S, Sohouli MH, et al. (2021) The effect of nigella sativa on biomarkers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials. J Food Biochem. 45:e13625. https://pubmed.ncbi.nlm.nih.gov/33559935

13. Emamat H, Mousavi SH, Kargar Shouraki J, et al. (2022) The effect of Nigella sativa oil on vascular dysfunction assessed by flow-mediated dilation and vascular-related biomarkers in subject with cardiovascular disease risk factors: A randomized controlled trial. Phytother Res. 36:2236-2245. https://pubmed.ncbi.nlm.nih.gov/35412685

14. Badar A, Kaatabi H, Bamosa A, (2017) Al-Elq A, Abou-Hozaifa B, Lebda F, Alkhadra A, Al-Almaie S. Effect of Nigella sativa supplementation over a one-year period on lipid levels, blood pressure and heart rate in type-2 diabetic patients receiving oral hypoglycemic agents: nonrandomized clinical trial. Ann Saudi Med. 37:56-63. https://pubmed.ncbi.nlm.nih.gov/28151458

15. Ansari ZM, Nasiruddin M, Khan RA, Haque SF (2017) Protective role of Nigella sativa in diabetic nephropathy: A randomized clinical trial. Saudi J Kidney Dis Transpl. 28:9-14. https://pubmed.ncbi.nlm.nih.gov/28098097

16. Alam MA, Nasiruddin M, Haque SF, Khan RA. (2020) Evaluation of safety and efficacy profile of Nigella sativa oil as an add-on therapy, in addition to alpha-keto analogue of essential amino acids in patients with chronic kidney disease. Saudi J Kidney Dis Transpl. 31:21-31. https://pubmed.ncbi.nlm.nih.gov/32129194

17. Ardakani Movaghati MR, Yousefi M, Saghebi SA, et al. (2019) Efficacy of black seed (Nigella sativa L.) on kidney stone dissolution: A randomized, double-blind, placebo-controlled, clinical trial. Phytother Res. 33:1404-1412. https://pubmed.ncbi.nlm.nih.gov/30873671

18. Farhangi MA, Dehghan P, Tajmiri S, Abbasi MM. (20106) The effects of Nigella sativa on thyroid function, serum Vascular Endothelial Growth Factor (VEGF) - 1, Nesfatin-1 and anthropometric features in patients with Hashimoto's thyroiditis: a randomized controlled trial. BMC Complement Altern Med. 16:471. https://pubmed.ncbi.nlm.nih.gov/27852303

19. Gheita TA, Kenawy SA. (2012) Effectiveness of Nigella sativa oil in the management of rheumatoid arthritis patients: a placebo controlled study. Phytother Res. 26:1246-8. https://pubmed.ncbi.nlm.nih.gov/22162258

20. Nikkhah-Bodaghi M, Darabi Z, Agah S, Hekmatdoost A. (2019) The effects of Nigella sativa on quality of life, disease activity index, and some of inflammatory and oxidative stress factors in patients with ulcerative colitis. Phytother Res. 33:1027-1032. https://pubmed.ncbi.nlm.nih.gov/30666747

21. Ahmed Jawad H, Ibraheem Azhar Y, Al-Hamdi Khalil I (2014) Evaluation of efficacy, safety and antioxidant effect of Nigella sativa in patients with psoriasis: A randomized clinical trial. Journal of Clinical and Experimental Investigations. 5:186-193. https://un.uobasrah.edu.iq/papers/4104.pdf

22. Ghorbanibirgani A, Khalili A, Rokhafrooz D. (2014) Comparing Nigella sativa Oil and Fish Oil in Treatment of Vitiligo. Iran Red Crescent Med J. 16:e4515. https://pubmed.ncbi.nlm.nih.gov/25068060

23. Yousefi M, Barikbin B, Kamalinejad M, et al. (2013) Comparison of therapeutic effect of topical Nigella with Betamethasone and Eucerin in hand eczema. J Eur Acad Dermatol Venereol. 27:1498-1504. https://pubmed.ncbi.nlm.nih.gov/23198836

24. Saad A, Besher S, Ammar N, Emam, H (2001) Therapeutic effects of Nigella Sativa on occupational contact dermatitis. Central European J Occ and Env Med. 7:26-38. https://www.researchgate.net/profile/Amal-Saad-Hussein/publication/230838076_THERAPEUTIC_EFFECTS_OF_NIGELLA_SATIVA_ON_OCCUPATIONAL_CONTACT_DERMATITIS/links/0912f5051cf358aed8000000/THERAPEUTIC-EFFECTS-OF-NIGELLA-SATIVA-ON-OCCUPATIONAL-CONTACT-DERMATITIS.p

25. Soleymani S, Zargaran A, Farzaei MH, et al. (2020) The effect of a hydrogel made by Nigella sativa L. on acne vulgaris: A randomized double-blind clinical trial. Phytother Res. 34:3052-3062. https://pubmed.ncbi.nlm.nih.gov/32548864

26. Han A, Shi D. (2021) The efficacy of Nigella sativa supplementation for asthma control: a meta-analysis of randomized controlled studies. Postepy Dermatol Alergol. 38:561-565. https://pubmed.ncbi.nlm.nih.gov/34658694

27. Boskabady MH, Farhadi J. (2008) The possible prophylactic effect of Nigella sativa seed aqueous extract on respiratory symptoms and pulmonary function tests on chemical war victims: a randomized, double-blind, placebo-controlled trial. J Altern Complement Med. 14:1137-1144. https://pubmed.ncbi.nlm.nih.gov/18991514

28. Nikakhlagh S, Rahim F, Aryani FH, et al. (2011) Herbal treatment of allergic rhinitis: the use of Nigella sativa. Am J Otolaryngol. 32:402-407. https://pubmed.ncbi.nlm.nih.gov/20947211

29. Kalus U, Pruss A, Bystron J, et al. (2003) Effect of Nigella sativa (black seed) on subjective feeling in patients with allergic diseases. Phytother Res. 17:1209-1214. https://pubmed.ncbi.nlm.nih.gov/14669258

30. Huseini HF, Mohtashami R, Sadeghzadeh E, et al. (2022) Efficacy and safety of oral Nigella sativa oil for symptomatic treatment of knee osteoarthritis: A double-blind, randomized, placebo-controlled clinical trial. Complement Ther Clin Pract. 49:101666. https://pubmed.ncbi.nlm.nih.gov/36150238

31. Azizi F, Ghorat F, Rakhshani MH, Rad M (2019) Comparison of the effect of topical use of Nigella Sativa oil and diclofenac gel on osteoarthritis pain in older people: A randomized, double-blind, clinical trial. J Herb Med. 16:100529. https://www.sciencedirect.com/science/article/abs/pii/S2210803319300053

32. Huseini HF, Kianbakht S, Mirshamsi MH, Zarch AB. (2016) Effectiveness of Topical Nigella sativa Seed Oil in the Treatment of Cyclic Mastalgia: A Randomized, Triple-Blind, Active, and Placebo-Controlled Clinical Trial. Planta Med. 82:285-288. https://pubmed.ncbi.nlm.nih.gov/26584456

33. Molaie M, Darvishi B, Jafari Azar Z, et al. (2019) Effects of a combination of Nigella sativa and Vitex agnus-castus with citalopram on healthy menopausal women with hot flashes: results from a subpopulation analysis. Gynecol Endocrinol. 35:58-61. https://pubmed.ncbi.nlm.nih.gov/30129806

34. Naeimi SA, Tansaz M, Hajimehdipoor H, Saber S (2020) Comparing the Effect of Nigella sativa oil Soft Gel and Placebo on Oligomenorrhea, Amenorrhea and Laboratory Characteristics in Patients with Polycystic Ovarian Syndrome, a Randomized Clinical Trial. Res J Pharmacogn. (RJP) 7:49-58. https://www.rjpharmacognosy.ir/article_99289_f5613bb45b6fb6dd8a7a2a9b5f7857a1.pdf

35. Bin Sayeed MS, Shams T, Fahim Hossain S, et al. (2014) Nigella sativa L. seeds modulate mood, anxiety and cognition in healthy adolescent males. J Ethnopharmacol. 152:156-162. https://pubmed.ncbi.nlm.nih.gov/24412554

36. Zadeh AR, Eghbal AF, Mirghazanfari SM, et al. (2022) Nigella sativa extract in the treatment of depression and serum Brain-Derived Neurotrophic Factor (BDNF) levels. J Res Med Sci. 27:28. https://pubmed.ncbi.nlm.nih.gov/35548175

37. Bin Sayeed MS, Asaduzzaman M, Morshed H, et al. (2013) The effect of Nigella sativa Linn. seed on memory, attention and cognition in healthy human volunteers. J Ethnopharmacol. 148:780-786. https://pubmed.ncbi.nlm.nih.gov/23707331

38. Akhondian J, Parsa A, Rakhshande H. (2007) The effect of Nigella sativa L. (black cumin seed) on intractable pediatric seizures. Med Sci Monit. 13:CR555-9. 4 https://pubmed.ncbi.nlm.nih.gov/18049435

39. Akhondian J, Kianifar H, Raoofziaee M, et al. (2011) The effect of thymoquinone on intractable pediatric seizures (pilot study). Epilepsy Res. 93:39-43. https://pubmed.ncbi.nlm.nih.gov/21112742

40. Oysu C, Tosun A, Yilmaz HB, et al. (2014) Topical Nigella Sativa for nasal symptoms in elderly. Auris Nasus Larynx. 41:269-272. https://pubmed.ncbi.nlm.nih.gov/24398317

41. Pipalia PR, Annigeri RG, Mehta R. (2016) Clinicobiochemical evaluation of turmeric with black pepper and nigella sativa in management of oral submucous fibrosis-a double-blind, randomized preliminary study. Oral Surg Oral Med Oral Pathol Oral Radiol. 122:705-712. https://pubmed.ncbi.nlm.nih.gov/27720650

42. Khan ZA, Prabhu N, Ahmed N, et al. (2022) A Comparative Study on Alvogyl and a Mixture of Black Seed Oil and Powder for Alveolar Osteitis: A Randomized Double-Blind Controlled Clinical Trial. Int J Clin Pract. 2022:7756226. https://pubmed.ncbi.nlm.nih.gov/35685605

43. Sadat Afraz E, Kazemi S, Ghaneei F, et al. (2022) The Healing Effects of Nigella sativa Gel on Oral Traumatic Ulcer. Int J BioLife Sci. 1:118. https://www.jobiost.com/article_162053.html

44. Rahman I, Mohammed A, AlSheddi MA, et al. (2023) Nigella sativa oil as a treatment for gingivitis: A randomized active-control trial. Asian Pac J Trop Med. 16:129-1138. https://www.apjtm.org/text.asp?2023/16/3/129/372290

45. Mohan ME, Thomas JV, Mohan MC, et al. (2023) A proprietary black cumin oil extract (Nigella sativa) (BlaQmax(r)) modulates stress-sleep-immunity axis safely: Randomized double-blind placebo-controlled study. Front Nutr. 10:1152680. https://pubmed.ncbi.nlm.nih.gov/37139438

46. Alavinejad P, Aghadhani M, Bakhtiari N, et al. (2023) Evaluation of total black seed (Nigella sativa) extract efficacy in patients with irritable bowel syndrome - pilot study. Eur. Chem. Bull. 12:997-1006. https://www.eurchembull.com/uploads/paper/85fcfba8ff6ae017bd08ff7823739390.pdf

47. Alizadeh A, Mohammah-Alizadeh-Charandabi S, Khodaie L, Mirghafourvand M. (2023) Effect of Nigella sativa L. seed oil on urinary incontinence and quality of life in menopausal women: A triple-blind randomized controlled trial. Phytother Res. 37:2012-2023. https://pubmed.ncbi.nlm.nih.gov/36640148

48. Kolahdooz M, Nasri S, Modarres SZ, et al. (2014) Effects of Nigella sativa L. seed oil on abnormal semen quality in infertile men: a randomized, double-blind, placebo-controlled clinical trial. Phytomedicine. 21:901-905. https://pubmed.ncbi.nlm.nih.gov/24680621

49. Amalia A, Hendarto H, Mustika A, Susanti I (2022) Effects of Nigella Sativa on Female Infertility: A Systematic Review. Proc 6th Int Conf Med Health Inform. May 2022, 234-237. https://dl.acm.org/doi/abs/10.1145/3545729.3545776

50. Zakaria R, Astuti SCD (2022) The Effect of Black Cumin (Nigella Sativa) on Breastfeeding Mothers. J Info Kesehatan 20:29-40. https://jurnal.poltekeskupang.ac.id/index.php/infokes/article/view/627/437

51. Nemati S, Masroorchehr M, Elahi H, et al. (2021) Effects of Nigella sativa Extract on Chronic Rhinosinusitis: A Randomized Double Blind Study. Indian J Otolaryngol Head Neck Surg. 73:455-460. https://pubmed.ncbi.nlm.nih.gov/34722227

52. Bashar T, Misbahuddin M, Hossain MA. (2014) A double-blind, randomize, placebo-control trial to evaluate the effect of Nigella sativa on palmar arsenical keratosis patients. Bangladesh J Pharmacol. 9:15-21. http://www.bdpsjournal.org/index.php/bjp/article/view/188/611

53. Salem A, Bamosa A, Alam M, et al. (2021) Effect of Nigella sativa on general health and immune system in young healthy volunteers; a randomized, placebo-controlled, double-blinded clinical trial. F1000Research 10:1199 https://f1000research.com/articles/10-1199

54. Behnamfar N, Parsa Yekta Z, Mojab F, Kazem Naeini SM. (2019) The effect of nigella sativa oil on the prevention of phlebitis induced by chemotherapy: a clinical trial. Biomedicine (Taipei). 9:20. https://pubmed.ncbi.nlm.nih.gov/31453801

55. Hussain SA, Mohammed Ameen HA, Mohammed MO, et al. (2019) Nigella sativa Oil Mouth Rinse Improves Chemotherapy-Induced Oral Mucositis in Patients with Acute Myeloid Leukemia. Biomed Res Int. 2019:3619357. https://pubmed.ncbi.nlm.nih.gov/31781612

56. Rafati M, Ghasemi A, Saeedi M, et al. (2019) Nigella sativa L. for prevention of acute radiation dermatitis in breast cancer: A randomized, double-blind, placebo-controlled, clinical trial. Complement Ther Med. 47:102205. https://pubmed.ncbi.nlm.nih.gov/31780017

57. Mousa HFM, Abd-El-Fatah NK, Darwish OA, et al. (2017) Effect of Nigella sativa seed administration on prevention of febrile neutropenia during chemotherapy among children with brain tumors. Childs Nerv Syst. 33:793-800. https://pubmed.ncbi.nlm.nih.gov/28349493

58. Barakat EM, El Wakeel LM, Hagag RS. (2013) Effects of Nigella sativa on outcome of hepatitis C in Egypt. World J Gastroenterol. 19:2529-2536. https://pubmed.ncbi.nlm.nih.gov/23674855

59. Ahmed S, Zahoor A, Ibrahim M, et al. (2020) Enhanced Efficacy of Direct-Acting Antivirals in Hepatitis C Patients by Coadministration of Black Cumin and Ascorbate as Antioxidant Adjuvants. Oxid Med Cell Longev. 2020:7087921. https://pubmed.ncbi.nlm.nih.gov/32566096

60. Adiban Fard F, Tork Zahrani S, Akbarzadeh Bagheban A, Mojab F. (2015) Therapeutic Effects of Nigella Sativa Linn (Black Cumin) on Candida albicans Vaginitis. Arch Clin Infect Dis. 10:e22991. https://brieflands.com/articles/archcid-20960.pdf

61. Hashem-Dabaghian F, Agah S, Taghavi-Shirazi M, Ghobadi A. (2016) Combination of Nigella sativa and Honey in Eradication of Gastric Helicobacter pylori Infection. Iran Red Crescent Med J. 18:e23771. https://pubmed.ncbi.nlm.nih.gov/28191328

62. Alizadeh-Naini M, Yousefnejad H, Hejazi N. (2020) The beneficial health effects of Nigella sativa on Helicobacter pylori eradication, dyspepsia symptoms, and quality of life in infected patients: A pilot study. Phytother Res. 34:1367-1376. https://pubmed.ncbi.nlm.nih.gov/31916648

63. Mohtashami R, Huseini HF, Heydari M, et al. (2015) Efficacy and safety of honey based formulation of Nigella sativa seed oil in functional dyspepsia: A double blind randomized controlled clinical trial. J Ethnopharmacol. 175:147-52. https://pubmed.ncbi.nlm.nih.gov/26386381

64. Babu B, Rao P, Suman E, Udayalaxmi J (2023) A Study of Antibacterial Effect of Nigella Sativa Seed Extracts on Bacterial Isolates from Cases of Wound Infection. Infect Disord Drug Targets. 2023 Apr 3. Online ahead of print. https://pubmed.ncbi.nlm.nih.gov/37016531

65. Rafati S, Niakan M, Naseri M. (2014) Anti-microbial effect of Nigella sativa seed extract against staphylococcal skin Infection. Med J Islam Repub Iran. 28:42. https://pubmed.ncbi.nlm.nih.gov/25405108

66. Hannan A, Saleem S, Chaudhary S, et al. (2008) Anti bacterial activity of Nigella sativa against clinical isolates of methicillin resistant Staphylococcus aureus. J Ayub Med Coll Abbottabad. 20:72-74. https://pubmed.ncbi.nlm.nih.gov/19610522

67. Liaqat F, Sheikh AA, Nazir J, et al. (2015) Report-Isolation identification and control of vancomycin resistant Staphylococcus aureus. Pak J Pharm Sci. 28:997-1004. https://pubmed.ncbi.nlm.nih.gov/26004734

68. Elango A, Rao LN, Sugumar P, Radhakrishnan A. (2022) Evaluation of Clinical Efficacy and Safety of Nigella Sativa Seed Oil added to Standard Treatment in Uncomplicated Respiratory Infection - A Randomised, Open Labelled, and Parallel Arm Study. Special Issue - COVID-19 & Other Communicable Diseases 91-97. https://medical.advancedresearchpublications.com/index.php/Journal-CommunicableDiseases/article/view/815/702

69. Yakoot M, Salem A. (2011) Efficacy and safety of a multiherbal formula with vitamin C and zinc (Immumax) in the management of the common cold. Int J Gen Med. 4:45-51. https://pubmed.ncbi.nlm.nih.gov/21403792

70. Abdallah HM, El-Halawany AM, Darwish KM, et al. (2022) Bio-Guided Isolation of SARS-CoV-2 Main Protease Inhibitors from Medicinal Plants: In Vitro Assay and Molecular Dynamics. Plants (Basel) 11:1914. https://pubmed.ncbi.nlm.nih.gov/35893619

71. Al-Haidari KAA, Faiq TAN, Ghareeb OA (2021) Preventive value of black seed in people at risk of infection with COVID-19. Pak J Med Health Sci. 15:384-387. https://pjmhsonline.com/2021/jan/384.pdf

72. Ashraf S, Ashraf S, Ashraf M, et al. (2023) DOCTORS LOUNGE consortium.(2023) Honey and Nigella sativa against COVID-19 in Pakistan (HNS-COVID-PK): A multicenter placebo-controlled randomized clinical trial. Phytother Res. 37:627-644. https://pubmed.ncbi.nlm.nih.gov/36420866

73. Ashraf S, Ashraf S, Ashraf M, et al. (2020) Honey and Nigella sativa against COVID-19 in Pakistan (HNS-COVID-PK): A multi-center placebo-controlled randomized clinical trial. medRxiv preprint, Nov 2020. https://www.medrxiv.org/content/10.1101/2020.10.30.20217364v4.full.pdf

74. Leal-Martínez F, Abarca-Bernal L, García-Pérez A, et al. (2022) Effect of a Nutritional Support System to Increase Survival and Reduce Mortality in Patients with COVID-19 in Stage III and Comorbidities: A Blinded Randomized Controlled Clinical Trial. Int J Environ Res Public Health. 19:1172. https://pubmed.ncbi.nlm.nih.gov/35162195

75. Langen M (2023) Millions of avoidable deaths from COVID-19. Orthomolecular Medicine News Service. http://orthomolecular.org/resources/omns/v19n16.shtml

76. Al-Haidari KAA, Faiq TN, Ghareeb OA (2021) Clinical trial of black seeds against covid - 19 in Kirkuk city/Iraq. Indian J Foren Med Toxicol 15:3393-3399. https://www.revistaamplamente.com/index.php/ijfmt/article/view/15825

77. Koshak AE, Koshak EA, Mobeireek AF, et al. (2021) Nigella sativa for the treatment of COVID-19: An open-label randomized controlled clinical trial. Complement Ther Med. 61:102769. https://pubmed.ncbi.nlm.nih.gov/34407441

78. Said SA, Abdulbaset A, El-Kholy AA, et al. (2022) The effect of Nigella sativa and vitamin D3 supplementation on the clinical outcome in COVID-19 patients: A randomized controlled clinical trial. Front Pharmacol. 13:1011522. https://pubmed.ncbi.nlm.nih.gov/36425571

79. Fraiman J, Erviti J, Jones M, et al. (2022) Serious adverse events of special interest following mRNA COVID-19 vaccination in randomized trials in adults. Vaccine. 40:5798-5805. https://pubmed.ncbi.nlm.nih.gov/36055877

80. Aarstad, J.; Kvitastein, O.A. Is there a Link between the 2021 COVID-19 Vaccination Uptake in Europe and 2022 Excess All-Cause Mortality?. Asian Pac J Health Sci. 10:25-30. https://hvlopen.brage.unit.no/hvlopen-xmlui/bitstream/handle/11250/3062560/Aarstad.pdf

81. Rancourt DG, Baudin M, Hickey J, Mercier J (2023) Age-stratified COVID-19 vaccine-dose fatality rate for Israel and Australia. Correlation Research in the Public Interest. https://correlation-canada.org/report-age-stratified-covid-19-vaccine-dose-fatality-rate-for-israel-and-australia

82. Gøtzsche PC. (2014) Our prescription drugs kill us in large numbers. Pol Arch Med Wewn. 124:628-634. https://pubmed.ncbi.nlm.nih.gov/25355584

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