Gholamnezhad Z, Havakhah S, Boskabady MH. Preclinical and clinical effects of Nigella sativa and its constituent, thymoquinone: a review. J Ethnopharmacol. June 2016;190:372-386.
Black cumin (Nigella sativa, Ranunculaceae) has been used traditionally and clinically to treat several diseases and conditions, including infertility, fever, cough, bronchitis, asthma, migraine, diabetes, rheumatism, and hypertension. The seeds reportedly have antidiabetic, anticancer, anti-inflammatory, immunomodulatory, antioxidant, antimicrobial, analgesic, spasmolytic, bronchodilatory, and hepatoprotective properties. Although black cumin has been the subject of many reviews, none of them have focused on its clinical effects. These authors sought to provide a comprehensive report of clinical studies on black cumin and some of its constituents. The beneficial effects of black cumin have been attributed to its prominent constituents such as nigellicine, nigellidine, thymoquinone (TQ), dithymoquinone, thymol, and carvacrol; most of its biological activities are related to its essential oil components, mainly TQ.1
The authors searched for studies in PubMed, Science Direct, Scopus, and Google Scholar that took place between 1979 and 2015, using the terms N. sativa, its constituents, its clinical effects, and various disorders.
Inflammation is a main characteristic of many chronic and acute diseases. The authors listed ten studies (seven clinical studies and three in vitro studies) that reported on the anti-inflammatory and immunomodulatory effects of black cumin and its constituents. In a placebo-controlled, crossover study,2 the investigators examined the anti-inflammatory effect of black cumin oil in patients with rheumatoid arthritis. The 40 patients received placebo capsules twice daily for one month and then consumed black cumin seed oil capsules (500 mg twice daily) for one month. After treatment, white blood cell count, disease activity score, number of swollen joints, and duration of morning stiffness significantly decreased compared with baseline and with the placebo intervention. However, the authors of the review still suggest "more RCT [randomized, controlled trials] and N. sativa supplementation is needed for the plant to be used as an inexpensive potential adjuvant biological therapy in inflammatory disorders."
The effect of black cumin oil was compared with that of fish oil on vitiligo (an autoimmune skin disorder) lesions in a well-designed, randomized, double-blind clinical trial.3 Fifty-two patients were divided into two equal groups and applied oil twice daily on their lesions for six months. Both oils reduced the size of the lesions, but black cumin oil was more effective than fish oil. No significant adverse effects were reported. Because of the study's limitations, including uncontrollable factors such as patient nutrition, which could influence skin lesions, the results cannot be generalized.
In well-designed in vitro studies, the lipid-soluble components of black cumin potentiated T-cell-mediated immunity and its water-soluble components affected B-cell-mediated immunity.
"All these studies showed that both lipid- and water-soluble fractions of N. sativa are potent and safe immunomodulatory agents and could be recommended as prophylactic and therapeutic adjuvants in immune system diseases," write the review authors.
Studies of the effects of black cumin essential oil against various bacteria resistant to a number of antibiotics were identified. The oil's potent dose-dependent antibacterial activity was more pronounced against Gram-positive than Gram-negative bacteria. In a clinical study,4 the effects of ethanolic extracts of black cumin, ginger (Zingiber officinale, Zingiberaceae), and their mixture were evaluated in patients with hepatitis C. The extracts of black cumin seed and ginger decreased the viral load and altered liver function in those patients. Noting that the identified studies demonstrated that black cumin seed extract and oil are potent antimicrobial agents, the review authors state, "Isolation and the formulation of new antimicrobial components from this herb should be carried out in the future, and more clinical trials should be designated before marketing."
Antitumor effects of TQ and ethanolic and aqueous black cumin extracts were shown in eight listed in vitro studies. Cytotoxic and apoptotic effects on human cell lines, including lung cancer, breast cancer, renal adenocarcinoma, colon cancer, osteosarcoma, and cervical squamous carcinoma, were observed; "however, more clinical trials are needed to recommend N. sativa derivatives as potential anticancer products," note the authors.
The effects of black cumin on metabolic disorders (including diabetes mellitus, hyperlipidemia, and metabolic syndrome) and on renal health were evaluated in 15 listed studies. In patients with type 2 diabetes mellitus, improvements were seen in fasting blood glucose, insulin resistance, glycosylated hemoglobin, and two-hour postprandial blood glucose levels after treatment with black cumin seed or oil. In studies of patients with hyperlipidemia, treatment with black cumin lowered total cholesterol, low-density lipoprotein cholesterol, and triglycerides. A well-designed, randomized, double-blind, placebo-controlled, two-arm, parallel study with a large number of patients with psoriasis5 showed a synergic effect of black cumin seed oil and garlic (Allium sativum, Amaryllidaceae) oil in improving dyslipidemia. Combination of the two herbs with simvastatin, a pharmaceutical statin drug, significantly improved lipid profiles more than simvastatin did alone. Although the identified studies reported positive effects of black cumin seed on glycemic control and lipid profile, the differences in the dose and type of plant extract, dietary intake, physical activity level, baseline biochemical profile, duration of study, type of disease, ethnicity of the patients, and genotype could have affected the results, suggest the review authors.
In a study investigating the protective effect of black cumin against methotrexate-induced hepatotoxicity in 40 children newly diagnosed with acute lymphoblastic leukemia,6 a nonsignificant increase was observed in markers of liver damage in those consuming black cumin oil for one week after each methotrexate dose. The increase in those markers in patients treated with placebo was significant, resulting in a significant between-group difference. "These results demonstrated the anti-hepatotoxic effect of N. sativa oil," conclude the review authors.
The effects of black cumin on aging and memory and the effects of TQ on epilepsy were reported in several studies. Bin Sayeed et al. reported that black cumin supplementation could prevent or slow down the complications of Alzheimer's disease.7 In a double-blind, crossover, clinical study,8 the investigators reported a reduction in the frequency of seizures after a four-week adjuvant therapy of TQ compared with baseline and with placebo.
Reports of cardiovascular effects of black cumin, suggested to be due to TQ, polyphenols, flavonoids, and unsaturated fatty acids of the plant, are mixed. Dehkordi and Kamkhah9 showed that a two-month supplementation with black cumin seed extract in patients with mild hypertension led to significantly reduced levels of both systolic and diastolic blood pressure compared with baseline. In a long-term, randomized, double-blind trial of 73 adults,10 Qidwai et al. found favorable effects of powdered black cumin seed capsules on lipid and blood sugar levels, blood pressure, and body weight; however, the results were not statistically significant because of the small sample size.
The respiratory effects of black cumin reported in the studies include a preventive effect on asthma and a prophylactic effect on respiratory disorders. Boskabady et al.11 concluded that the use of black cumin extract led to improvement in all asthma symptoms in the study patients. A randomized, double-blind, placebo-controlled trial examining the prophylactic effect of a two-month daily intake of a black cumin seed aqueous extract in chemical war victims reported significant improvements in all respiratory symptoms, chest wheezing, and pulmonary function test values, with no adverse effects.12 "Taking into account the bronchodilatory as well as anti-inflammatory effects of TQ and its high content in the plant oil, it was found to be responsible for those effects," the review authors write.
A two-month supplementation with a daily intake of 5 mL black cumin oil significantly improved the sperm count, motility, morphology, semen volume, pH, and round cells in infertile men compared with placebo, without any adverse effects.13 The review authors suggest that "the antioxidant activity of TQ, vitamin E, selenium, and unsaturated fatty acid contents of the N. sativa oil may be responsible for this effect of the plant."
Confounding factors and limitations of the studies reviewed here make data interpretation difficult, say the authors. Limitations include the failure to explain the design of placebo or control groups, to include baseline biochemical profiles, to identify the active constituent and the phytochemical assessment and formulation of the applied agents, to mention the type of randomization, and to control the patients' diet. Some study results are limited by small sample sizes and short durations.
Although the findings of this review support the traditional use of black cumin, the authors state that "more precise clinical studies regarding the effect of N. sativa and its constituents on various diseases are needed to ensure their exact clinical efficacy as well as the mechanisms of each effect."
1Woo CC, Kumar AP, Sethi G, Tan KH. Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol. 2012;83(4):443-451.
2Gheita TA, Kenawy SA. Effectiveness of Nigella sativa oil in the management of rheumatoid arthritis patients: a placebo controlled study. Phytother Res. 2012;26(8):1246-1248.
3Ghorbanibirgani A, Khalili A, Rokhafrooz D. Comparing Nigella sativa oil and fish oil in treatment of vitiligo. Iran Red Crescent Med J. 2014;16(6):e4515. doi: 10.5812/ircmj.4515.
4Abdel-Moneim A, Morsy BM, Mahmoud AM, Abo-Seif MA, Zanaty MI. Beneficial therapeutic effects of Nigella sativa and/or Zingiber officinale in HCV patients in Egypt. EXCLI J. 2013;12:943-955.
5Ahmad Alobaidi AH. Effect of Nigella sativa and Allium sativum coadminstered [sic] with simvastatin in dyslipidemia patients: a prospective, randomized, double-blind trial. Antiinflamm Antiallergy Agents Med Chem. 2014;13(1):68-74.
6Hagag AA, Elaal AMA, Elsheik A, Elzamarany EA. Protective effect of Nigella sativa oil against methotrexate induced hepatotoxicity in children with acute lymphoblastic leukemia. J Leuk (Los Angel). 2013;1(4):123. doi: 10.4172/2329-6917.1000123.
7Bin Sayeed MS, Asaduzzaman M, Morshed H, Hossain MM, Kadir MF, Rahman MR. The effect of Nigella sativa Linn. seed on memory, attention and cognition in healthy human volunteers. J Ethnopharmacol. 2013;148(3):780-786.
8Akhondian J, Kianifar H, Raoofziaee M, Moayedpour A, Toosi MB, Khajedaluee M. The effect of thymoquinone on intractable pediatric seizures (pilot study). Epilepsy Res. 2011;93(1):39-43.
9Dehkordi FR, Kamkhah AF. Antihypertensive effect of Nigella sativa seed extract in patients with mild hypertension. Fundam Clin Pharmacol. 2008;22(4):447-452.
10Qidwai W, Hamza HB, Qureshi R, Gilani A. Effectiveness, safety, and tolerability of powdered Nigella sativa (kalonji) seed in capsules on serum lipid levels, blood sugar, blood pressure, and body weight in adults: results of a randomized, double-blind controlled trial. J Altern Complement Med. 2009;15(6):639-644.
11Boskabady MH, Javan H, Sajady M, Rakhshandeh H. The possible prophylactic effect of Nigella sativa seed extract in asthmatic patients. Fundam Clin Pharmacol. 2007;21(5):559-566.
12Boskabady MH, Farhadi J. 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. 2008;14(9):1137-1144.13Kolahdooz M, Nasri S, Modarres SZ, Kianbakht S, Huseini HF. Effects of Nigella sativa L. seed oil on abnormal semen quality in infertile men: a randomized, double-blind, placebo-controlled clinical trial. Phytomedicine. 2014;21(6):901-905.