Effects of Nigella Sativa (Black seeds) Supplementation on Plasma Lipid Profile in Human Subjects - A Review

Article ID: e021221198487 Pages: 10

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Abstract

Dyslipidemia is the major risk factor for Atherosclerotic Cardiovascular Disease (ASCVD), cerebrovascular disease, and Peripheral Artery Disease (PAD). It is characterized by higher plasma concentrations of Total Cholesterol (TC), Low-density Lipoprotein-cholesterol (LDL-c), apolipoprotein B (apoB), Very Low-density Lipoprotein-cholesterol (VLDL-c), Triglycerides (TGs) and low levels of high-density lipoprotein-cholesterol (HDL-c). Herbal medicines are preferred by many across the globe particularly to manage chronic conditions such as dyslipidemia, hypertension, type 2 diabetes, cancer, and plenty of others. Nigella sativa (black seeds or black cumin seeds) is a miracle herb employed within the management of many sicknesses for centuries. Hence, this review focuses on the ameliorative effects of N. sativa on the plasma lipid concentrations of human subjects. Numerous Randomized Controlled Clinical Trials (RCTs) and different clinical studies demonstrated that N. sativa possesses potential anti-dyslipidemic activity. The patients with dyslipidemia may well be benefited by using N. sativa along with healthy lifestyle changes and statin and other antihyperlipidemic medications as adjuvant therapy if needed.

Keywords: Nigella sativa, black seeds, kalonji, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, thymoquinone, nigellone.

Graphical Abstract

[1]
Presta, V.; Tocci, G.; Volpe, M. Excess of dyslipidemia in low income countries: The case of Colombia in the PURE study. Int. J. Cardiol., 2019, 290, 152-153.
[http://dx.doi.org/10.1016/j.ijcard.2018.11.105] [PMID: 31126735]
[2]
Cicero, A.F.G.; Landolfo, M.; Ventura, F.; Borghi, C. Current pharmacotherapeutic options for primary dyslipidemia in adults. Expert Opin. Pharmacother., 2019, 20(10), 1277-1288.
[http://dx.doi.org/10.1080/14656566.2019.1604687] [PMID: 31059312]
[3]
Taghizadeh, E.; Esfehani, R.J.; Sahebkar, A.; Parizadeh, S.M.; Rostami, D.; Mirinezhad, M.; Poursheikhani, A.; Mobarhan, M.G.; Pasdar, A. Familial combined hyperlipidemia: An overview of the underlying molecular mechanisms and therapeutic strategies. IUBMB Life, 2019, 71(9), 1221-1229.
[http://dx.doi.org/10.1002/iub.2073] [PMID: 31271707]
[4]
Vodnala, D.; Rubenfire, M.; Brook, R.D. Secondary causes of dyslipidemia. Am. J. Cardiol., 2012, 110(6), 823-825.
[http://dx.doi.org/10.1016/j.amjcard.2012.04.062] [PMID: 22658245]
[5]
Mahmoud, I.; Sulaiman, N. Dyslipidaemia prevalence and associated risk factors in the United Arab Emirates: A population-based study. BMJ Open, 2019, 9(11), e031969.
[http://dx.doi.org/10.1136/bmjopen-2019-031969] [PMID: 31699740]
[6]
Grundy, S.M.; Stone, N.J.; Bailey, A.L.; Beam, C.; Birtcher, K.K.; Blumenthal, R.S.; Braun, L.T.; de Ferranti, S.; Faiella-Tommasino, J.; Forman, D.E.; Goldberg, R.; Heidenreich, P.A.; Hlatky, M.A.; Jones, D.W.; Lloyd-Jones, D.; Lopez-Pajares, N.; Ndumele, C.E.; Orringer, C.E.; Peralta, C.A.; Saseen, J.J.; Smith, S.C.Jr; Sperling, L.; Virani, S.S.; Yeboah, J. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: A report of the American college of cardiology/American heart association task force on clinical practice guidelines. J. Am. Coll. Cardiol., 2019, 73(24), e285-e350.
[http://dx.doi.org/10.1016/j.jacc.2018.11.003] [PMID: 30423393]
[7]
Mach, F.; Baigent, C.; Catapano, A.L.; Koskinas, K.C.; Casula, M.; Badimon, L.; Chapman, M.J.; De Backer, G.G.; Delgado, V.; Ference, B.A.; Graham, I.M.; Halliday, A.; Landmesser, U.; Mihaylova, B.; Pedersen, T.R.; Riccardi, G.; Richter, D.J.; Sabatine, M.S.; Taskinen, M.R.; Tokgozoglu, L.; Wiklund, O. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Eur. Heart J., 2020, 41(1), 111-188.
[http://dx.doi.org/10.1093/eurheartj/ehz455] [PMID: 31504418]
[8]
Balasubramanian, R.; Maideen, N.M.P. HMG-CoA reductase inhibitors (statins) and their drug interactions involving CYP enzymes, P-glycoprotein and OATP transporters-an overview. Curr. Drug Metab., 2021, 22(5), 328-341.
[http://dx.doi.org/10.2174/1389200222666210114122729] [PMID: 33459228]
[9]
Zodda, D.; Giammona, R.; Schifilliti, S. Treatment strategy for dyslipidemia in cardiovascular disease prevention: Focus on old and new drugs. Pharmacy (Basel), 2018, 6(1), 10.
[http://dx.doi.org/10.3390/pharmacy6010010] [PMID: 29361723]
[10]
Bartlomiejczyk, M.A.; Penson, P.; Banach, M. Worldwide dyslipidemia guidelines. Curr. Cardiovasc. Risk Rep., 2019, 13(2), 2.
[http://dx.doi.org/10.1007/s12170-019-0597-x]
[11]
Maideen, N.M.; Balasubramanian, R.; Ramanathan, S. Nigella sativa (Black seeds), a potential herb for the pharmacotherapeutic management of hypertension-a review. Curr. Cardiol. Rev., 2020, 17(4), e230421187786.
[http://dx.doi.org/10.2174/1573403X16666201110125906] [PMID: 33172379]
[12]
Maideen, N.M.P. Antidiabetic activity of Nigella sativa (black seeds) and its active constituent (thymoquinone): A review of human and experimental animal studies. Chonnam Med. J., 2021, 57(3), 169-175.
[http://dx.doi.org/10.4068/cmj.2021.57.3.169] [PMID: 34621636]
[13]
Dehkordi, F.R.; Kamkhah, A.F. Antihypertensive effect of Nigella sativa seed extract in patients with mild hypertension. Fundam. Clin. Pharmacol., 2008, 22(4), 447-452.
[http://dx.doi.org/10.1111/j.1472-8206.2008.00607.x] [PMID: 18705755]
[14]
Ibraheim, Z.Z. Effect of Nigella sativa seeds and total oil on some blood parameters in female volunteers. Saudi Pharm. J., 2002, 10, 54-59.
[15]
Bamosa, A.O.; Basil, A.; Sowayan, A.A.; Sowayan, S.A. Effect of oral ingestion of Nigella sativa seeds on some blood parameters. Saudi Pharm. J., 1997, 2(2-3), 126-129.
[16]
Bilal, A.; Masud, T.; Uppal, A.M. BS5-5 Black seed (Nigella sativa) regulates glucose, insulin level and lipid profile in patients with type 2 diabetes. Diabetes Res. Clin. Pract., 2008, 79, S19-S20.
[http://dx.doi.org/10.1016/S0168-8227(08)70696-X]
[17]
Najmi, A.; Nasiruddin, M.; Khan, R.A.; Haque, S.F. Effect of Nigella sativa oil on various clinical and biochemical parameters of insulin resistance syndrome. Int. J. Diabetes Dev. Ctries., 2008, 28(1), 11-14.
[http://dx.doi.org/10.4103/0973-3930.41980] [PMID: 19902033]
[18]
Qidwai, W.; Hamza, H.B.; 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.
[http://dx.doi.org/10.1089/acm.2008.0367] [PMID: 19500003]
[19]
Bhatti, I.U.; Rehman, F.U.; Khan, M.A.; Marwat, S.K. Effect of prophetic medicine kalonji (Nigella sativa L.) on lipid profile of human beings: An in vivo approach. World Appl. Sci. J., 2009, 6(8), 1053-1057.
[20]
Datau, E.A.; Wardhana, ; Surachmanto, E.E.; Pandelaki, K.; Langi, J.A.; Fias, Efficacy of Nigella sativa on serum free testosterone and metabolic disturbances in central obese male. Acta Med. Indones., 2010, 42(3), 130-134.
[PMID: 20724766]
[21]
Amini, M.; Fallah Huseini, H.; Mohtashami, R.; Sadeqhi, Z.; Ghamarchehre, M.A. Hypolipidemic effects of Nigella sativa L. seeds oil in healthy volunteers: A randomized, double-blind, placebo- controlled clinical trial. J. Med. Plants, 2011, 10(40), 133-138.
[22]
Tasawar, Z.; Siraj, Z.; Ahmad, N.; Lashari, M.H. The effects of Nigella sativa (kalonji) on lipid profile in patients with stable coronary artery disease in Multan, Pakistan. Pak. J. Nutr., 2011, 10, 162-167.
[http://dx.doi.org/10.3923/pjn.2011.162.167]
[23]
Sabzghabaee, A.M.; 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. Arh., 2012, 66(3), 198-200.
[http://dx.doi.org/10.5455/medarh.2012.66.198-200] [PMID: 22822623]
[24]
Kaatabi, H.; Bamosa, A.O.; Lebda, F.M.; Al Elq, A.H.; Al-Sultan, A.I. Favorable impact of Nigella sativa seeds on lipid profile in type 2 diabetic patients. J. Family Community Med., 2012, 19(3), 155-161.
[http://dx.doi.org/10.4103/2230-8229.102311] [PMID: 23230380]
[25]
Memon, A.R.; Shah, S.S.; Memon, A.R.; Naqvi, S.H. Effect of combination of Nigella sativa and Trigonella foenum-graecum with glibenclamide on serum triglyceride, HDL and creatinine levels in type-2 diabetes mellitus patients. Pak. J. Pharmacol., 2012, 29(1), 1-6.
[26]
Shah, A.S.; Khan, G.M.; Badshah, A.; Shah, S.U.; Shah, K.U.; Mirza, S.A.; Khan, K.A. Nigella sativa provides protection against metabolic syndrome. Afr. J. Biotechnol., 2012, 11(48), 10919-10925.
[http://dx.doi.org/10.5897/AJB12.890]
[27]
Najmi, A.H.; Nasiruddin, M.O.; Khan, R.A.; Haque, S.F. Therapeutic effect of Nigella sativa in patients of poor glycemic control. Asian J. Pharm. Clin. Res., 2012, 5(3), 224-228.
[28]
Hosseini, M.S.; Mirkarimi, S.A.; Amini, M.; Mohtashami, R.; Kianbakht, S. Huseini H.F. Effects of Nigella sativa L. seed oil in type II diabetic Patients: A randomized, double-blind, placebo- controlled clinical trial. J. Med. Plants, 2013, 12(47), 93-99.
[29]
Najmi, A.H.; Nasiruddin, M.O.; Khan, R.A.; Haque, S.F. Indigenous herbal product Nigella sativa proved effective as an antihypertensive in metabolic syndrome. Asian J. Pharm. Clin. Res., 2013, 6(1), 61-64.
[30]
Bin Sayeed, M.S.; Asaduzzaman, M.; Morshed, H.; Hossain, M.M.; Kadir, M.F.; Rahman, M.R. The effect of Nigella sativa Linn. seed on memory, attention and cognition in healthy human volunteers. J. Ethnopharmacol., 2013, 148(3), 780-786.
[http://dx.doi.org/10.1016/j.jep.2013.05.004] [PMID: 23707331]
[31]
Bashar, T.; Misbahuddin, M.; Hossain, M.A. A double-blind, randomize, placebo-control trial to evaluate the effect of Nigella sativa on palmar arsenical keratosis patients. Bangladesh J. Pharmacol., 2014, 9(1), 15-21.
[http://dx.doi.org/10.3329/bjp.v9i1.17167]
[32]
Moeen-ud-din, H.; Murad, S.; Fatima, A. Placebo controlled study on comparison of effects of Nigella sativa and nicotinic acid along with low fat diet and physical exercise on LDL-cholesterol and HDL-cholesterol. Pak. J. Med. Health Sci., 2014, 8, 306-309.
[33]
Fatima, A.; Shad, M.N.; Asrar, A.; Murad, S. Effects of Nigella sativa on HDL-c & body weight. Pak. J. Med. Health Sci., 2014, 8(1), 122-124.
[34]
Farzaneh, E.; Nia, F.R.; Mehrtash, M.; Mirmoeini, F.S.; 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.
[PMID: 24627749]
[35]
Ahmad Alobaidi, A.H. Effect of Nigella sativa and Allium sativum coadminstered with simvastatin in dyslipidemia patients: A prospective, randomized, double-blind trial. Antiinflamm. Antiallergy Agents Med. Chem., 2014, 13(1), 68-74.
[http://dx.doi.org/10.2174/18715230113129990013] [PMID: 23848231]
[36]
Ibrahim, R.M.; Hamdan, N.S.; Ismail, M.; Saini, S.M.; Abd Rashid, S.N.; Abd Latiff, L.; Mahmud, R. Protective effects of Nigella sativa on metabolic syndrome in menopausal women. Adv. Pharm. Bull., 2014, 4(1), 29-33.
[http://dx.doi.org/10.5681/apb.2014.005] [PMID: 24409406]
[37]
Ibrahim, R.M.; Hamdan, N.S.; Mahmud, R.; Imam, M.U.; Saini, S.M.; Rashid, S.N.; Abd Ghafar, S.A.; Latiff, L.A.; Ismail, M. A randomised controlled trial on hypolipidemic effects of Nigella sativa seeds powder in menopausal women. J. Transl. Med., 2014, 12(1), 82.
[http://dx.doi.org/10.1186/1479-5876-12-82] [PMID: 24685020]
[38]
Latiff, L.A.; Parhizkar, S.; Dollah, M.A.; Hassan, S.T. Alternative supplement for enhancement of reproductive health and metabolic profile among perimenopausal women: A novel role of Nigella sativa. Iran. J. Basic Med. Sci., 2014, 17(12), 980-985.
[PMID: 25859301]
[39]
Mirmiran, P.; Hosseinpour-Niazi, S.; Hedayati, M.; Azizi, F. Effect of Nigella sativa oil extract on lipid profiles in type 2 diabetic patients: A randomized, double blind, placebo-controlled clinical trial. Iraninan J. Endocrinol. Metabol., 2015, 16(6), 411-418.
[40]
Amin, F.; Islam, N.; Anila, N.; Gilani, A.H. 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., 2015, 23(2), 165-174.
[http://dx.doi.org/10.1016/j.ctim.2015.01.008] [PMID: 25847554]
[41]
Heshmati, J.; Namazi, N.; Memarzadeh, M.R.; Taghizadeh, M.; Kolahdooz, F. Nigella sativa oil affects glucose metabolism and lipid concentrations in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial. Food Res. Int., 2015, 70, 87-93.
[http://dx.doi.org/10.1016/j.foodres.2015.01.030]
[42]
Mahdavi, R.; Namazi, N.; Alizadeh, M.; Farajnia, S. Effects of Nigella sativa oil with a low-calorie diet on cardiometabolic risk factors in obese women: A randomized controlled clinical trial. Food Funct., 2015, 6(6), 2041-2048.
[http://dx.doi.org/10.1039/C5FO00316D] [PMID: 26029855]
[43]
Niaz, K.; Qudoos, A.; Fatima, A.; Murad, S. Placebo-controlled study on comparison of two herbal hypolipidemic agents. J. Drug Deliv. Ther., 2016, 6(1), 7-10.
[http://dx.doi.org/10.22270/jddt.v6i1.1168]
[44]
Mohtashami, A.; Mahaki, B.; Azadbakht, L.; Entezari, M.H. Effects of bread with Nigella sativa on lipid profiles, apolipoproteins and inflammatory factor in metabolic syndrome patients. Clin. Nutr. Res., 2016, 5(2), 89-95.
[http://dx.doi.org/10.7762/cnr.2016.5.2.89] [PMID: 27152298]
[45]
Badar, A.; Kaatabi, H.; Bamosa, A.; 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., 2017, 37(1), 56-63.
[http://dx.doi.org/10.5144/0256-4947.2017.56] [PMID: 28151458]
[46]
Farhangi, M.A.; Dehghan, P.; Tajmiri, S. Powdered black cumin seeds strongly improves serum lipids, atherogenic index of plasma and modulates anthropometric features in patients with Hashimoto’s thyroiditis. Lipids Health Dis., 2018, 17(1), 59.
[http://dx.doi.org/10.1186/s12944-018-0704-x] [PMID: 29587770]
[47]
Khonche, A.; Huseini, H.F.; Gholamian, M.; Mohtashami, R.; Nabati, F.; Kianbakht, S. 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., 2019, 234, 106-111.
[http://dx.doi.org/10.1016/j.jep.2019.01.009] [PMID: 30639231]
[48]
Pelegrin, S.; Galtier, F.; Chalançon, A.; Gagnol, J.P.; Barbanel, A.M.; Pélissier, Y.; Larroque, M.; Lepape, S.; Faucanié, M.; Gabillaud, I.; Petit, P.; Chevassus, H. Effects of Nigella sativa seeds (black cumin) on insulin secretion and lipid profile: A pilot study in healthy volunteers. Br. J. Clin. Pharmacol., 2019, 85(7), 1607-1611.
[http://dx.doi.org/10.1111/bcp.13922] [PMID: 30875097]
[49]
Rashidmayvan, M.; Mohammadshahi, M.; Seyedian, S.S.; Haghighizadeh, M.H. The effect of Nigella sativa oil on serum levels of inflammatory markers, liver enzymes, lipid profile, insulin and fasting blood sugar in patients with non-alcoholic fatty liver. J. Diabetes Metab. Disord., 2019, 18(2), 453-459.
[http://dx.doi.org/10.1007/s40200-019-00439-6] [PMID: 31890671]
[50]
Darand, M.; Darabi, Z.; Yari, Z.; Hedayati, M.; Shahrbaf, M.A.; Khoncheh, A.; Hosseini-Ahangar, B.; Alavian, S.M.; Hekmatdoost, A. The effects of black seed supplementation on cardiovascular risk factors in patients with nonalcoholic fatty liver disease: A randomized, double-blind, placebo-controlled clinical trial. Phytother. Res., 2019, 33(9), 2369-2377.
[http://dx.doi.org/10.1002/ptr.6424] [PMID: 31293021]
[51]
Ghorbani, A; Zarvandi, M; Rakhshandeh, H. A randomized controlled trial of a herbal compound for improving metabolic parameters in diabetic patients with uncontrolled dyslipidemia. Endocr. Metab. Immune Disord. Drug Targets, 2019, 19(7), 1075-1082.
[http://dx.doi.org/10.2174/1871530319666190206213420] [PMID: 30727929]
[52]
Elfouly, A.E.; Ismail, M.A.; Kamal, H.M.; Ahmed, S.A.; Fiala, L.E. A randomized controlled trial measuring the effect of Nigella sativa extract on lipid profile in adult patients with dyslipidemia attending family practice clinic, Suez Canal university hospital, Egypt. Pharm Innov J, 2019, 8(7), 262-267.
[53]
Shari, FH; Ramadhan, HH; Mohammed, RN; Al Bahadily, DC Hypolipidemic and antioxidant effects of Fenugreek-Nigella sativa combination on diabetic patients in Iraq. Sys. Rev. Pharm., 2020, 11(6), 911-915.
[54]
Farhangi, M.A.; Tajmiri, S. The effects of powdered black cumin seeds on markers of oxidative stress, intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in patients with Hashimoto’s thyroiditis. Clin. Nutr. ESPEN, 2020, 37, 207-212.
[http://dx.doi.org/10.1016/j.clnesp.2020.02.015] [PMID: 32359745]
[55]
Hadi, S.; Daryabeygi-Khotbehsara, R.; Mirmiran, P.; McVicar, J.; Hadi, V.; Soleimani, D.; Askari, G. Effect of Nigella sativa oil extract on cardiometabolic risk factors in type 2 diabetes: A randomized, double-blind, placebo-controlled clinical trial. Phytother. Res., 2021, 35(7), 3747-3755.
[http://dx.doi.org/10.1002/ptr.6990] [PMID: 34142392]
[56]
Jangjo-Borazjani, S.; Dastgheib, M.; Kiyamarsi, E.; Jamshidi, R.; Rahmati-Ahmadabad, S.; Helalizadeh, M.; Iraji, R.; Cornish, S.M.; Mohammadi-Darestani, S.; Khojasteh, Z.; Azarbayjani, M.A. Effects of resistance training and Nigella sativa on type 2 diabetes: implications for metabolic markers, low-grade inflammation and liver enzyme production. Arch. Physiol. Biochem., 2021, 1-9.
[http://dx.doi.org/10.1080/13813455.2021.1886117] [PMID: 33612031]
[57]
Safi, S.; Razmpoosh, E.; Fallahzadeh, H.; Mazaheri, M.; Abdollahi, N.; Nazari, M.; Nadjarzadeh, A.; Salehi-Abargouei, A. The effect of Nigella sativa on appetite, anthropometric and body composition indices among overweight and obese women: A crossover, double-blind, placebo-controlled, randomized clinical trial. Complement. Ther. Med., 2021, 57, 102653.
[http://dx.doi.org/10.1016/j.ctim.2020.102653] [PMID: 33370571]
[58]
Razmpoosh, E.; Safi, S.; Nadjarzadeh, A.; Fallahzadeh, H.; Abdollahi, N.; Mazaheri, M.; Nazari, M.; Salehi-Abargouei, A. The effect of Nigella sativa supplementation on cardiovascular risk factors in obese and overweight women: A crossover, double-blind, placebo-controlled randomized clinical trial. Eur. J. Nutr., 2021, 60(4), 1863-1874.
[http://dx.doi.org/10.1007/s00394-020-02374-2] [PMID: 32876804]
[59]
Maideen, N.M. Clinically important and pharmacologically relevant drug interactions with alcohol. Am J Res Med Sci., 2019, 6(1)
[http://dx.doi.org/10.5455/ajrms.20190602042343]