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Evidence-based Uses of Standardized Black Seed Oil

Black Seed Oil Black Seed Oil
EuroMedica
 
Longevity By Nature

Although public and industry awareness of the health/wellness benefits of black seed oil (BSO) has only gained traction in the last few years, this botanical ingredient has seen some very quick growth with an estimated global market size of $18 million in 2021, and expectations to expand at a CAGR (compound annual growth rate) of 7.2 percent from 2022 to 2028.1 Furthermore, research suggests that most of the therapeutic properties of BSO are attributed to its essential oil constituent, thymoquinone. This article will examine some of the research demonstrating the effectiveness of BSO standardized for its thymoquinone content.

Historical Background

Let’s begin with some historical background. Black cumin seed, or black seed for short (Nigella sativa) is a plant native to, and cultivated in, North Africa, Turkey and the Middle East. It has been used medicinally in the Middle East and Southeast Asia for more than 2,000 years,2,3 and has been used throughout the world medicinally and as a food seasoning for centuries. It is widely used in various traditional systems of medicine, such as ayurveda, unani and siddha. Black seeds are mentioned in the Bible as well as in the Koran. People think of black seeds as a holy plant created by God in order to relieve difficult medical conditions and in Arabic it used to be called “the blessing seed.” Greek pharmaco-botanist Dioscorides (40-90 CE) described the use of black seeds from a plant now thought to be N. sativa as a remedy for breathing difficulties, inflammatory conditions, skin ailments and parasites.4 Black seeds were also historically thought to be useful for the afterlife journey and were found in the tomb of Egyptian pharaohs.

Non-standardized BSO Studies

Before a discussion on BSO standardized for thymoquinone, we’ll review research on non-standardized BSO (which requires a higher dose than the standardized form).

• A meta-analysis5 of 13 studies found that 2-3 g/day of BSO helped significantly reduce body weight in participants who were healthy, overweight or obese, or had risk factors such as high cholesterol or mild hypertension.

• A randomized, double-blind, placebo-controlled clinical trial6 found that 2 g/day of BSO helped reduce body weight, blood pressure and blood glucose levels in people with coronary artery disease.

• A randomized, double-blind, placebo-controlled trial7 found that 2.5 mL BSO/day (~2.3 g) lowered systolic and diastolic blood pressure without any adverse effects in healthy volunteers.

• A randomized, double-blind, placebo-control clinical trial8 demonstrated that 2 g/day of BSO helped improve endothelial/arterial function and reduce oxidation in patients with coronary artery diseases.

• A randomized controlled trial9 found that 1,000 mg/day of BSO in capsules improved flow-mediated dilation and arterial-related biomarkers in subjects with cardiovascular disease risk factors.

• A randomized, double-blind, placebo-controlled clinical trial10 determined that 1,000 mg/day of BSO in capsules exerted beneficial effects on blood sugar control, serum lipid profile, blood pressure and body weight among people with type 2 diabetes.

• A randomized, double-blind, placebo-controlled clinical trial11 demonstrated that 1,000 mg/day of BSO in capsules provided cardiovascular protective effects in patients with type 2 diabetes, by improving the lipid profile and fasting blood sugar, C-reactive protein (inflammation marker) and lipid peroxidation.

• An open-label randomized clinical trial12 determined that 1,350 mg/day of BSO was comparable to metformin in lowering weight significantly, and in regard to effects on fasting insulin, cholesterol, triglycerides and other parameters.

• A double-blind, randomized, placebo-controlled clinical trial13 determined that 2.5 mL BSO/day (~2.3 g) reduced osteoarthritis symptoms and the required dose of acetaminophen in the knee osteoarthritis patients.

• An open-label randomized controlled clinical trial14 demonstrated that 1,000 mg/day of BSO in capsules was associated with faster recovery of symptoms than usual care alone for patients with mild COVID-19 infection.

• A randomized, double-blind, placebo-controlled trial15 found that 1,000 mg/day of BSO in capsules improved asthma control with a trend in pulmonary function improvement.

• A randomized, prospective, comparative and open-label study16 determined that 2.5 mL BSO/day (~2.3 g) reduced blood glucose, serum creatinine, blood urea and 24 h total urinary protein levels, while increasing glomerular filtration rate, 24 h total urinary volume and hemoglobin level in patients with chronic kidney disease due to diabetic nephropathy.

• A randomized, double-blind, placebo-controlled trial17 demonstrated that 5 mL BSO/day (~4.6 g) reduced dyspepsia severity and the rate of H. pylori infection in patients with functional dyspepsia.

The rest of this article will examine research on BSO standardized for its thymoquinone content, starting with an explanation about the full-spectrum BSO.

Full-spectrum

Although thymoquinone is certainly the primary active compound in BSO, research suggests that a full-spectrum BSO has the most value. The fact is that BSO has several key phytochemical compounds: thymoquinone, p-cymene, carvacrol, its fatty acid and free fatty acids (FFA). There are also numerous other compounds found in a full-spectrum oil, including sterols and saponins, novel lipid constituents and volatile oils of varying compositions.18 Essential phytochemicals such as phytosterols are important to mention due to their nutraceutical and medicinal benefits in lowering LDL cholesterol and total cholesterol levels.19 The major sterols identified in BSO are beta-sitosterol, campesterol, stigmasterol and 5-avenasterol.20,21 Tocopherols found in BSO and other plants’ oils are well recognized for their antioxidant potential.

Cold Press Vs. Extraction

What appears to work best in achieving a balanced and full-spectrum BSO is using freshly harvested black cumin seeds and a cold-pressed extraction. Using fresh seeds with cold-pressed extraction yields a standardized, full-spectrum oil with optimal ratios of all the bioactives found in black seeds. These precise ratios contribute to the synergistic effects available in BSO. Conversely, extractions that force high thymoquinone concentrations will often leave other beneficial compounds out or in low proportions, resulting in a narrow composition and thereby reduced therapeutic benefit.

Why Standardization Matters

Standardization matters in order to achieve a balance between thymoquinone and free fatty acids (FFA). Studies show that 3 percent thymoquinone combined with low FFA (less than 2 percent), (and other important bioactives at optimal levels) provides superior inflammatory-fighting potential compared to other BSO compositions. The bar graph above (see Figure 1) shows the effect of using a 3 percent thymoquinone standardized oil with low FFA compared to three different finished products from the market containing significantly lower levels of the active compound. Their effects were compared via an inflammation inhibition model using inhibition of NO production as an inflammatory marker. ThymoQuin BSO was used in this and the following studies to provide this preferred balance between thymoquinone and FFA.

Likewise, a study was conducted to evaluate the importance of standardization for the thymoquinone and FFA actives on the antifungal activity of several cold-pressed BSOs with varying concentrations of TQ and FFA. As shown in the bar graph (Figure 2) the growth of two opportunistic fungal skin pathogens, Malassezia furfur and an antibiotic-resistant strain of Candida albicans were most inhibited by a combination of high amounts of thymoquinone (3 percent) and low amounts of FFA fatty acids (2 percent).22

Bioavailability

In addition to a balance between thymoquinine and FFO, bioavailability is another key factor in achieving the therapeutic benefits of the compounds in BSO. In the case of ThymoQuin BSO, a method was developed to enhance the bioavailability and stability. The addition of minor amounts of sunflower derivatives has made a marked improvement in both as shown in study on mice in Figure 2. Note the small addition of the sunflower proprietary blend (SPB) and the considerable spike in bioavailability (orange line versus the green line).

Standardized BSO Studies – In-vitro

Mitochondria are the energy factories found in our cells. In-vitro research revealed that standardized BSO (ThymoQuin BSO) increased mitochondrial energy production and a combination of omega-3s and standardized BSO improved mitochondrial functionality and efficiency over either of the single ingredients. This benefit improves overall energy and may also help the body burn calories more efficiently and effectively. Both omega-3 and ThymoQuin BSO provide individual benefits, but the synergistic combination of both provided significantly better results.23 Likewise, another in-vitro study and mouse study24 also demonstrated that standardized BSO increased mitochondrial generation.

Standardized BSO Studies – Oral

High blood pressure is considered to be one of the leading causes of death in the Western world. As shown in the previous paragraphs, non-standardized BSO was shown to help reduce blood pressure in doses of at least 2 g/day. To determine if a reduced dose of 500 mg/day BSO standardized for 3 percent thymoquinone (ThymoQuin BSO) could also reduce blood pressure, a clinical trial25 was conducted with 20 healthy adults (average age 55 ± 13 years BMI avg 29.6 ± 14.2) with normal blood pressure. Following a three-week washout period, patients were given placebo treatment for a period of six weeks. Blood pressure was measured daily throughout the study. Results were that standardized BSO significantly decreased blood pressure—by 11.2 percent for systolic and by 12.2 percent for diastolic. Following the washout period and placebo treatment, blood pressure was slightly increased, and the treatment effects started diminishing. In conclusion, daily dosing with 3 percent thymoquinone (as ThymoQuin BSO) was successful in reducing blood pressure in healthy adults. This study also demonstrated that a standardized BSO was effective at one-quarter of the dose of non-standardized BSO for reducing blood pressure. Additionally, the initial reduction in blood pressure could be observed after only two days, as seen in the accompanying chart.

A four-week, placebo-controlled, double-blind study26 was conducted to evaluate the effect of 500 mg/day BSO standardized for 3 percent thymoquinone (ThymoQuin BSO) or placebo on upper-respiratory tract complaints (URTCs) and psychological mood state in 37 marathon and half-marathon runners. Subjective and objective measures were collected before and after supplementation. Subjects completed the profile of mood state (POMS) psychological assessment and a questionnaire style health log measuring health status and URTCs (subjective measures), as well as provided saliva samples and fecal samples for measurement of cortisol and microbiome balance, respectively (objective measures). Results were that subjects in the ThymoQuin supplementation group reported significantly fewer upper respiratory tract complaints (62 percent lower) and better overall well-being (11 percent improvement), as well as lower cortisol (44 percent less) and superior microbiome diversity (66 percent higher Streptococcus thermophilus, 8 percent higher microbiome composite score) compared to placebo. These results suggest that ThymoQuin BSO may improve immune system vigilance and overall well-being following the stress of endurance training and competition.

Standardized BSO Studies – Topical

In addition to oral supplementation with standardized BSO, there have also been studies demonstrating benefits with topical application.

Branded as B’utyQuin for cosmetic use, standardized BSO has been studied in-vitro to determine mechanisms related to mitochondrial biogenesis and revitalization. This has been followed by clinical research to establish the safety, compatibility and efficacy of B’utyQuin as a topical anti-aging cosmetic aid for human skin. A 28-day, single-center, randomized, blinded, placebo-controlled trial27 was conducted with 22 healthy male and female subjects, aged 35-65 years with all types of skin. Subjects received samples of topical creams, including the Active Cream with 3 percent standardized BSO oil as B’utyQuin, and a placebo cream. All subjects applied both B’utyQuin product and the placebo, one on each half of the face. Products were attributed for half-face applications (left/right) to the subjects in a randomized manner. Both creams were assessed using a variety of standard dermatological examination techniques and equipment. These evaluations determined the degree of change in skin firmness and elasticity (Cutometer), hydration (Corneometer), skin color and luminosity (Chromameter CR-400), and general skin appearance (standardized images VISIA-CA) over the course of the 28-day study. Results were:

• Active Cream was completely safe and compatible with all skin types of study participants.

• Active Cream improved skin firmness by 11.2 percent, compared to only 5.5 percent with the placebo cream.

• Active Cream increased skin elasticity by 6.8 percent, compared to only 1 percent with the placebo cream.

• Active Cream increased skin hydration by 22.2 percent from, compared to a 14.3 percent with the placebo cream.

• Active Cream increased skin luminosity 1.1 percent, compared to a 1.5 percent decrease with the placebo cream.

A blinded, controlled, single-center 28-day study28 was conducted to verify the efficacy, compatibility and safety of a cosmetic product with 5 percent B’utyQuin (Scalp Serum) and 2 percent free fatty acids. The study involved 10 male and female subjects, aged 18-65 years old (all skin types), with mild to moderate seborrhea of the scalp. Evaluation of changes in scalp condition, erythema, itchiness, oiliness, scaliness and flaking were compared to baseline (day 0). The subjects applied an amount necessary to cover the affected area with Scalp Serum daily, using a gentle massaging action. Primary endpoints of the study were efficacy of the Scalp Serum in improving symptoms of seborrheic dermatitis such as redness/erythema, itchiness, scaling/flaking and oiliness of the scalp. Secondary endpoints included scalp soothing properties, safety, compatibility and lack of side effects. Improvements were assessed via patient questionnaires, self-examination, dermatologist examination and standardized photography of the scalp. Results were that after 28 days of Scalp Serum application, there was a statistically significant 58.8 percent decrease in erythema (reddening) scores and a statistically significant 30 percent decrease in scaling scores for the Scalp Serum as compared to baseline. Although not quite statistically significant, scalp oiliness scores also decreased by 16.7 percent compared to baseline (day 0).

Combining Black Cumin Seed Oil With Other Nutraceuticals

There is also research demonstrating beneficial results when combining black cumin seed oil with other nutraceuticals. In one study,29 black cumin seed oil increased stem cell (MSC) proliferation and significantly reduces the inflammatory state, both alone and with vitamin D3. In another study,30 the combination of black cumin seed oil plus fish oils significantly decreased upper-374 respiratory tract complaints and improved psychological mood state following intense endurance 375 training and competition. In an article I’m writing for Vitamin Retailer (Natural Practitioner’s sister publication) later this year, I’ll go into more details about synergism with black seed oil and other nutraceuticals.

Conclusion

The interest in use of BSO oil is on a market growth trend. Its extensive history of use in different systems of traditional medicine is complemented by the modern research demonstrating effectiveness in modulating body weight, cardiovascular risk factors, blood glucose, inflammation, immune function and more. Standardized BSO oil (as ThymoQuin) has shown particular value, lowering blood pressure with only one-quarter of the dose of conventional BSO, and also improving immune system vigilance and overall well-being following the stress of endurance training and competition. In addition, standardized BSO (as B’utyQuin) has demonstrated effectiveness for improving skin firmness, elasticity, hydration and luminosity, as well as decreasing erythema scores scaling in seborrhea of the scalp.

References:

1 Black Seed Oil Market Size, Share & Trends Analysis Report By Product (Oil, Powder, Tablets, & Capsules, Soft Gel), By Application, By Region, And Segment Forecasts, 2022 – 2028. Grand View Research. Report ID: GVR-4-68039-941-5. 78 pages. Retrieved March 31, 2023 from www.grandviewresearch.com/industry-analysis/black-seed-oil-market-report.

2 Heiss AG, Stika HP, De Zorzi N, Jursa M. Nigella in the mirror of time: a brief attempt to draw a genus’ ethnohistorical portrait. Offa-Zeitschrift Berichte und Mitteilungen zur Urgeschichte Frubgeschichte und Mittelalteraarchaologie 2012;13:69/70:147-169.

3 Germer R. Handbuch der altagyptischen Heilpflanzen. Wiesbad, Germany: Otto Harrassowitz; 2008.

4 Beck LY. De Materia medica by Pedanius Dioscorides. Hildesheim, Germany: Olms-Weidman; 2005.

5 Mousavi SM, Sheikhi A, Varkaneh HK, Zarezadeh M, Rahmani J, Milajerdi A. Effect of Nigella sativa supplementation on obesity indices: a systematic review and meta-analysis of randomized controlled trials. Complement Ther Med. June 2018;38:48-57.

6 Tavakoli-Rouzbehani OM, Abbasnezhad M, Kheirouri S, Alizadeh M. Effects of Nigella sativa oil supplementation on selected metabolic parameters and anthropometric indices in patients with coronary artery disease: A randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2021 Jul;35(7):3988-3999.

7 Fallah Huseini H, Amini M, Mohtashami R, Ghamarchehre ME, Sadeqhi Z, Kianbakht S, Fallah Huseini A. Blood pressure lowering effect of Nigella sativa L. seed oil in healthy volunteers: a randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2013 Dec;27(12):1849-53.

8 Tavakoli-Rouzbehani OM, Abbasnezhad M, Kheirouri S, Alizadeh M. Efficacy of Nigella sativa oil on endothelial function and atherogenic indices in patients with coronary artery diseases: A randomized, double-blind, placebo-control clinical trial. Phytother Res. 2022 Dec;36(12):4516-4526.

9 Emamat H, Mousavi SH, Kargar Shouraki J, Hazrati E, Mirghazanfari SM, Samizadeh E, Hosseini M, Hadi V, Hadi S. 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. 2022 May;36(5):2236-2245.

10 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 Jul;35(7):3747-3755.

11 Kooshki A, Tofighiyan T, Rastgoo N, Rakhshani MH, Miri M. Effect of Nigella sativa oil supplement on risk factors for cardiovascular diseases in patients with type 2 diabetes mellitus. Phytother Res. 2020 Oct;34(10):2706-2711.

12 Moustafa HAM, El Wakeel LM, Halawa MR, Sabri NA, El-Bahy AZ, Singab AN. Effect of Nigella sativa oil versus metformin on glycemic control and biochemical parameters of newly diagnosed type 2 diabetes mellitus patients. Endocrine. 2019 Aug;65(2):286-294.

13 Huseini HF, Mohtashami R, Sadeghzadeh E, Shadmanfar S, Hashem-Dabaghian F, Kianbakht S. 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. 2022 Nov;49:101666.

14 Koshak AE, Koshak EA, Mobeireek AF, Badawi MA, Wali SO, Malibary HM, Atwah AF, Alhamdan MM, Almalki RA, Madani TA. Nigella sativa for the treatment of COVID-19: An open-label randomized controlled clinical trial. Complement Ther Med. 2021 Sep;61:102769.

15 Koshak A, Wei L, Koshak E, Wali S, Alamoudi O, Demerdash A, Qutub M, Pushparaj PN, Heinrich M. Nigella sativa Supplementation Improves Asthma Control and Biomarkers: A Randomized, Double-Blind, Placebo-Controlled Trial. Phytother Res. 2017 Mar;31(3):403-409.

16 Ansari ZM, Nasiruddin M, Khan RA, Haque SF. Protective role of Nigella sativa in diabetic nephropathy: A randomized clinical trial. Saudi J Kidney Dis Transpl. 2017 Jan-Feb;28(1):9-14.

17 Mohtashami R, Huseini HF, Heydari M, Amini M, Sadeqhi Z, Ghaznavi H, Mehrzadi S. Efficacy and safety of honey based formulation of Nigella sativa seed oil in functional dyspepsia: A double blind randomized controlled clinical trial. J Ethnopharmacol. 2015 Dec 4;175:147-52.

18 Botnick I, Xue W, Bar E, Iet al. Distribution of primary and specialized metabolites in Nigella sativa seeds, a spice with vast traditional and historical uses. Molecules. 2012 Aug 24; 17(9):10159-10177.

19 San Mauro-Martín I, Blumenfeld-Olivares JA, Garicano-Vilar E, et al. Di_erences in the e_ect of plant sterols on lipid metabolism in men and women. Topics Clin Nutr. 2018;33(1):31-34.

20 Matthaus B, Özcan MM. Fatty acids, tocopherol, and sterol contents of some Nigella species seed oil. Czech J Food Sci. 2011;29(2):145-150.

21 Cheikh-Rouhou S, Besbes S, Hentati B, et al. Nigella sativa L.: chemical composition and physicochemical characteristics of lipid fraction. Food Chemistry. 2007;101(2):673-681.

22 Ogen-Shtern N, Margarita Y, von Oppen-Bezalel L. Antimicrobial activity by a unique composition of cold pressed Nigella sativa seed (Black Cumin) Oil. Food Sci Nutr Res. 2021; 4(2): 1-9.

23 von Oppen-Bezalel L, Jurenka JS. Mitochondrial revitalization for skin rejuvenation by a proprietary, cold-pressed Nigella sativa seed (black cumin) oil standardized to 3 percent thymoquinone. SOFW7Days. 2022 June 08;147:1-7.

24 Licari M, Raffaelle M, Rosman ZF, et al. Beneficial effects of thymoquinone on metabolic function and fatty liver in a murine model of obesity. J Nutr Food Sci. 2019;9:751.

25 Bush B, Peña T, Bush R, et al. Effects of Standardized Black Seed Oil Cold Press Supplement Over A Six Week Period on Blood Pressure and Heart Rate in Healthy Patients: A Nonrandomized Clinical Trial. Food Sci Nutr Res. 2020; 3(1): 1-5.

26 Talbott SM, Talbott JA. Effect of ThymoQuin Black Cumin Seed Oil as a Natural Immune Modulator of Upper-Respiratory Tract . Complaints and Psychological Mood State. Unpublished, nd.

27 von Oppen-Bezalel L, Jurenka JS. Mitochondrial Revitalization for Skin Rejuvenation by a Proprietary, Cold-Pressed Nigella sativa Seed (Black Cumin) Oil Standardized to 3 percent Thymoquinone. Cosmetics & Toiletries. June 10, 2022. Retrieved March 31, 2023 from www.cosmeticsandtoiletries.com/cosmetic-ingredients/natural-sustainable/article/22236404/trinutra-20871-mitochondrial-revitalization-for-skin-rejuvenation-coldpressed-nigella-sativa-seed-oil-standardized-to-3-thymoquinone.

28 von Oppen-Bezalel L, Jurenka JS. Irritated, Itchy, Scaly, Seborrheic Scalp: Causes and Relief with a Proprietary, Cold-Pressed Nigella sativa (Black Seed) Oil Standardized to 3 percent Thymoquinone. SOFW Journal. July 8, 2022. Retrieved March 31, 2023 from www.sofw.com/en/sofw-journal/articles-en/48-personal-care/3101-irritated-itchy-scaly-seborrheic-scalp-causes-and-relief-with-a-proprietary-cold-pressed-nigella-sativa-black-seed-oil-standardized-to-3-thymoquinone.

29 Yuen K, Alex A, Raffaelle M, Shen H, et al. Beneficial effect of 3 percent Thymoquinone on stem cell-mediated improvement in immune system and anti-Inflammatory function. Journal of Food & Nutritional Sciences. 2021; 3(3): 63-74.

30 Talbott SM, Talbott JA. Black Cumin Seed Oil plus Fish Oil Combination Modulates Gut-Immune-Axis. Unpublished, nd.

Gene Bruno, MS, MHS, the provost for Huntington University of Health Sciences, is a nutritionist, herbalist, writer and educator. For more than 40 years he has educated and trained natural product retailers and health care professionals, has researched and formulated natural products for dozens of dietary supplement companies, and has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications. He can be reached at eugenejbruno@gmail.com.