September 2014 Issue

Nigella Sativa
By Megan Tempest, RD
Today’s Dietitian
Vol. 16 No. 9 P. 64

Research suggests this ancient medicinal plant may have present-day uses for a variety of conditions.

If you’ve never heard of Nigella sativa (also known as black seed or black cumin), you’re not alone. Despite centuries of use as a traditional, alternative medicine, Nigella sativa is off the radar of mainstream conventional medicine. Yet this ancient plant deserves some attention from health care professionals. Several animal studies and some human studies suggest that Nigella sativa potentially could treat common diseases and conditions typically addressed with pharmaceutical drugs.

This article provides a brief history of Nigella sativa, highlights recent studies that have examined its role in health promotion and disease prevention, and discusses whether dietitians should apply the data to daily practice.

What It Is
A member of the botanical family Ranunculaceae, the Nigella sativa seed is derived from a ripe fruit that grows abundantly in Eastern Europe, the Middle East, and western Asia. These small black seeds historically have been used in food and cooking preparations and for more than 2,000 years as a folk medicine to treat ailments ranging from headaches to parasitic infections. Reports suggest Nigella sativa was discovered in King Tut’s tomb.1,2

Today, Nigella sativa supplements are available online and in health food stores under the name black seed and usually are sold in capsules of crushed black seed or softgels of black seed oil. The supplements are marketed to support overall health and well-being and to treat specific ailments such as asthma, allergies, flu, joint pain, and gastrointestinal problems.2

Compelling Research
On the heels of much animal research, published results from human studies have emerged exploring Nigella sativa’s role as an effective complementary and alternative medicine. Here’s a review of some of the most recent research.

Hypertension
Nigella sativa has demonstrated antioxidant, hypotensive, calcium channel blockade, and diuretic effects that function to lower blood pressure.3

Its vasorelaxant effect was the focus of a double-blind, randomized, placebo-controlled clinical trial of 70 healthy individuals between the ages of 34 and 63 with systolic blood pressure ranging from 110 to 140 mm Hg and diastolic blood pressure from 60 to 90 mm Hg. (The American Heart Association defines the optimal range for blood pressure as below 120/80 mm Hg.)4

Published in the December 2013 issue of Phytotherapy Research, the results suggested that an oral intake of 5 mL of Nigella sativa oil for eight weeks significantly lowered systolic and diastolic blood pressures without any apparent adverse effects.4

Hyperlipidemia
When taken as an oral supplement, Nigella sativa has shown potential in improving dyslipidemia. Results of a four-week clinical trial suggested that supplemental Nigella sativa lowered total cholesterol by 5%, LDL cholesterol by 8%, and triglyceride levels by 17%.5

A two-month randomized trial of menopausal women with hyperlipidemia, published in the March issue of the Journal of Translational Medicine, associated the intake of a Nigella sativa supplement with a 27% reduction in LDL cholesterol, a 22% decrease in triglycerides, and a 16% decline in total cholesterol. Researchers noted a slight but statistically insignificant improvement in HDL cholesterol levels.

Furthermore, the researchers observed that when the women stopped taking the supplement, their lipid profiles reverted to pretreatment levels.6

One theory behind the slight HDL-boosting effects of Nigella sativa is that it stimulates apolipoprotein A-I gene expression, which is the primary component of cardioprotective HDL cholesterol.7

An analysis of overweight sedentary women published in the February issue of the International Journal of Preventive Medicine showed that eight weeks of Nigella sativa supplementation combined with aerobic activity had a synergistic effect in improving serum lipid profiles.8 Researchers saw a 5% decrease in total cholesterol, an 8% reduction in triglycerides, a 5% drop in LDL cholesterol, and a 6% rise in HDL cholesterol.

In a 12-week study published in September 2012 in the Journal of Family Community Medicine, researchers compared the effects of three different doses of Nigella sativa supplements (1, 2, and 3 g/day) on the lipid profiles of 94 individuals with type 2 diabetes. Patients who took 2 g/day had significantly greater reductions in total cholesterol (up to 15%), LDL cholesterol (up to 17%), triglycerides (up to 22%) and increases in HDL cholesterol (up to 6%) compared with those who took 1 g/day. However, researchers didn’t see a significantly greater benefit in those who took 3 g/day.9

Margaret Wertheim, MS, RD, CD, a private practice dietitian in Madison, Wisconsin, knows about the research linking Nigella sativa to improved serum lipid profiles but isn’t yet convinced she should recommend it to clients with hyperlipidemia. “Research has shown decreases in LDL and triglycerides, but the decrease is mild,” she says. “Since there are effective dietary strategies, I would try those first to reduce high LDL/triglycerides.”

Of course, diet and exercise modifications are widely accepted as safe and effective methods of improving lipid profiles, but the extent to which Nigella sativa may work in tandem with or in comparison to these methods still is relatively unknown.

Cancer Treatment
Researchers who have studied the medicinal plant in vitro have found that thymoquinone, the predominant bioactive constituent in Nigella sativa, can induce apoptosis (cell death) and slow cancer cell metastasis in breast cancer, glioblastoma, melanoma, squamous cell carcinoma, certain forms of lymphoma, cervical cancer, osteosarcoma, and lymphoblastic leukemia.10-17 Thymoquinone analogs have been shown to inhibit pancreatic cancer cell proliferation in vitro and enhance cancer cell sensitivity to chemotherapy,18 and results of a recent in vitro study showed that Nigella sativa seed extract and seed oil significantly reduced human lung cancer cell viability.19 Nonetheless, because these are in vitro studies, more research is needed to determine the anticancer effects.

Diabetes
One study suggested oral Nigella sativa supplementation could improve blood glucose control among patients with type 2 diabetes.20 Results of a recent animal study suggested that Nigella sativa supplements can help lower blood glucose levels and improve serum lipid profiles, demonstrating its potential as a functional food to treat diabetes and its associated comorbidities.21

In addition, researchers investigated the hypoglycemic effects of Nigella sativa in a study of menopausal women. They reported that 1 g/day of encapsulated Nigella sativa seed powder taken for two months correlated with a significant decrease in fasting blood glucose levels and improvement in serum lipid profiles compared with placebo.22

Cognitive Function
Following animal studies demonstrating a possible link between Nigella sativa and improved brain function, human studies are further establishing this relationship. A study of 40 healthy elderly patients showed that 1 g/day of Nigella sativa enhanced memory, cognition, and attention without adverse side effects. Based on these findings, the researchers emphasized the need for further research in Nigella sativa’s role in preventing or slowing the progression of Alzheimer’s disease.23

Liver Health
A study published in the April 2013 issue of the World Journal of Gastroenterology found an association between hepatoprotection and Nigella sativa in individuals with hepatitis C. Researchers concluded that 1,350 mg/day of Nigella sativa was tolerable, safe, and decreased viral load among participants. Moreover, this dose was found to improve oxidative stress, clinical condition, and glycemic control among diabetes patients with hepatitis C.24

Rheumatoid Arthritis
The beneficial, immune-modulating effects of Nigella sativa were the focus of a recent study on individuals suffering from rheumatoid arthritis. Among a group of 40 female rheumatoid arthritis patients, a 500-mg dose of Nigella sativa oil capsules twice daily was associated with a decrease in disease activity and symptoms of swollen joints and morning stiffness, suggesting Nigella sativa may be an affordable potential adjuvant therapy for rheumatoid arthritis treatment.25

Allergies
A prospective, double-blind, placebo-controlled trial investigated the anti-inflammatory effects of Nigella sativa on patients with allergic rhinitis. The results suggested it may reduce common symptoms such as nasal itching and congestion, runny nose, and sneezing. The researchers noted that this supplement could be considered a treatment for allergic rhinitis when the side effects of common allergy drugs must be avoided.26

Counseling Patients
The scientific evidence behind Nigella sativa’s health-promoting effects may pique dietitians’ interests. However, in the absence of further research and clinical trials to establish appropriate use and safe therapeutic doses, it may be premature for RDs and other health care professionals to recommend this supplement to treat specific medical conditions.

“Some of the most promising evidence for Nigella sativa appears to be for reducing allergy symptoms, and it could be a supplement recommended by RDs for this use,” Wertheim says. Acknowledging that the safety research on black seed is limited, she believes Nigella sativa does appear to be safe, “especially given that recommended supplemental doses are similar to amounts used as a culinary spice.” Research has shown that toxicity has occurred in rats that were given high doses; otherwise, adverse effects are reportedly rare.27,28 Regardless, Wertheim recommends pregnant and nursing women avoid using the supplement because of the lack of sufficient testing.

Julia Zumpano, RD, LD, a clinical dietitian in the department of preventive cardiology at the Cleveland Clinic, suggests dietitians use caution regarding Nigella sativa and all herbal supplements. “They aren’t regulated; therefore, it’s unknown if the dosage provided is accurate and effective.” Instead, she recommends all clients and patients be advised to check with their physician before taking any supplements since they can interact with current medications, other supplements, or medical conditions.

— Megan Tempest, RD, is a freelance writer based in Boulder County, Colorado.

References
1. Shabana A, El-Menyar A, Asim M, Al-Azzeh H, Al Thani H. Cardiovascular benefits of black cumin (Nigella Sativa). Cardiovasc Toxicol. 2013;13(1):9-21.

2. Black seed. WebMD website. http://www.webmd.com/vitamins-supplements/ingredientmono-901-BLACK SEED.aspx?activeIngredientId=901&activeIngredientName=BLACK SEED. Accessed June 24, 2014.

3. Leong XF, Rais Mustafa M, Jaarin K. Nigella sativa and its protective role in oxidative stress and hypertension. Evid Based Complement Alternat Med. 2013;2013:120732.

4. Fallah Huseini H, Amini M, Mohtashami R, 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.

5. Sabzghabaee AM, Dianatkhah M, Sarrafzadegan N, Asgary S, Ghannadi A. Clinical evaluation of Nigella sativa seeds for the treatment of hyperlipidemia: a randomized, placebo controlled clinical trial. Med Arch. 2012;66(3):198-200.

6. Ibrahim RM, Hamdan NS, Mahmud R, et al. A randomised controlled trial on hypolipidemic effects of Nigella Sativa seeds powder in menopausal women. J Transl Med. 2014;12:82.

7. Haas MJ, Onstead-Haas LM, Naem E, Wong NC, Mooradian AD. Induction of apolipoprotein A-I gene expression by black seed (Nigella sativa) extracts [published online March 17, 2014]. Pharm Biol.

8. Farzaneh E, Nia FR, Mehrtash M, Mirmoeini FS, Jalilvand M. The effects of 8-week Nigella sativa supplementation and aerobic training on lipid profile and VO2 max in sedentary overweight females. Int J Prev Med. 2014;5(2):210-216.

9. Kaatabi H, Bamosa AO, Lebda FM, Al Elq AH, Al-Sultan AI. Favorable impact of Nigella sativa seeds on lipid profile in type 2 diabetic patients. J Family Community Med. 2012;19(3):155-161.

10. Rajput S, Kumar BN, Dey KK, Pal I, Parekh A, Mandal M. Molecular targeting of Akt by thymoquinone promotes G(1) arrest through translation inhibition of cyclin D1 and induces apoptosis in breast cancer cells. Life Sci. 2013;93(21):783-790.

11. Racoma IO, Meisen WH, Wang QE, Kaur B, Wani AA. Thymoquinone inhibits autophagy and induces cathepsin-mediated, caspase-independent cell death in glioblastoma cells. PLoS One. 2013;8(9):e72882.

12. Salim LZ, Mohan S, Othman R, et al. Thymoquinone induces mitochondria-mediated apoptosis in acute lymphoblastic leukaemia in vitro. Molecules. 2013;18(9):11219-11240.

13. Ahmad I, Muneer KM, Tamimi IA, Chang ME, Ata MO, Yusuf N. Thymoquinone suppresses metastasis of melanoma cells by inhibition of NLRP3 inflammasome. Toxicol Appl Pharmacol. 2013;270(1):70-76.

14. Hussain AR, Uddin S, Ahmed M, Al-Dayel F, Bavi PP, Al-Kuraya KS. Phosphorylated IκBα predicts poor prognosis in activated B-cell lymphoma and its inhibition with thymoquinone induces apoptosis via ROS release. PLoS One. 2013;8(3):e60540.

15. Hasan TN, Shafi G, Syed NA, et al. Methanolic extract of Nigella sativa seed inhibits SiHa human cervical cancer cell proliferation through apoptosis. Nat Prod Commun. 2013;8(2):213-216.

16. Peng L, Liu A, Shen Y, et al. Antitumor and anti-angiogenesis effects of thymoquinone on osteosarcoma through the NF-κB pathway. Oncol Rep. 2013;29(2):571-578.

17. Das S, Dey KK, Dey G, et al. Antineoplastic and apoptotic potential of traditional medicines thymoquinone and diosgenin in squamous cell carcinoma. PLoS One. 2012;7(10):e46641.

18. Yusufi M, Banerjee S, Mohammad M, et al. Synthesis, characterization and anti-tumor activity of novel thymoquinone analogs against pancreatic cancer. Bioorg Med Chem Lett. 2013;23(10):3101-3104.

19. Al-Sheddi ES, Farshori NN, Al-Oqail MM, Musarrat J, Al-Khedhairy AA, Siddiqui MA. Cytotoxicity of Nigella sativa seed oil and extract against human lung cancer cell line. Asian Pac J Cancer Prev. 2014;15(2):983-987.

20. Bamosa AO, Kaatabi H, Lebdaa FM, Elq AM, Al-Sultanb A. 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.

21. Sultan MT, Butt MS, Karim R, et al. Nigella sativa fixed and essential oil supplementation modulates hyperglycemia and allied complications in streptozotocin-induced diabetes mellitus. Evid Based Complement Alternat Med. 2014;2014:826380. doi:10.1155/2014/826380

22. Ibrahim RM, Hamdan NS, Ismail M, et al. Protective effects of nigella sativa on metabolic syndrome in menopausal women. Adv Pharm Bull. 2014;4(1):29-33.

23. Bin 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.

24. Barakat EM, El Wakeel LM, Hagag RS. Effects of Nigella sativa on outcome of hepatitis C in Egypt. World J Gastroenterol. 2013;19(16):2529-2536.

25. Gheita 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.

26. Nikakhlagh S, Rahim F, Aryani FH, Syahpoush A, Brougerdnya MG, Saki N. Herbal treatment of allergic rhinitis: the use of Nigella sativa. Am J Otolaryngol. 2011;32(5):402-407.

27. Badary OA, Al-Shabanah OA, Nagi MN, Al-Rikabi AC, Elmazar MM. Inhibition of beno(a)pyrene-induced forestomach carcinogenesis in mice by thymoquinone. Eur J Cancer Prev.1999;8(5):435-440.

28. Nigella sativa. Memorial Sloan Kettering Cancer Center website. http://www.mskcc.org/cancer-care/herb/nigella-sativa. Last updated May 1, 2013. Accessed July 14, 2014.