Black Seed Oil: Understanding Thymoquinone Benefits and Side Effects

Gut health plays a critical role in overall well-being. A diet rich in diverse high-fiber foods, fermented foods, and foods rich in polyphenols, including herbs and spices, is instrumental in promoting gastrointestinal health.¹ However, it can be challenging to consistently include all necessary micro- and macronutrients through diet alone. In such cases, nutritional supplements offer a practical solution to bridge any nutrition gaps.   

Thymoquinone is the most abundant constituent of nigella sativa seeds, commonly known as black cumin. Although black cumin is traditionally used as a spice across different cultures, its health benefits as a dietary supplement have attracted the interest of researchers. This article explains thymoquinone’s health benefits and side effects, how it supports gut functions, and why you should consider including an advanced thymoquinone supplement in your diet. Use the links below to jump ahead to different topics on the page. 

What is Thymoquinone?

Thymoquinone, chemically known as 2-methyl-5-isopropyl-1, 4-benzoquinone, is a monoterpene molecule and the most prominent bioactive compound  in nigella sativa seeds. Although black cumin seeds contain other beneficial compounds such as terpenes, terpenoids, alkaloids, phytosterols, tocols, and polyphenols, the health benefits of the seeds are largely attributed to the presence of thymoquinone. Although thymoquinone and its derivatives account for the antioxidative properties of black seed oil, the overall antioxidative activity of the oil is increased by the presence of thymol isomers.²*

Thymoquinone Extraction from Black Seeds

The thymoquinone content in black cumin seeds increases steadily as the seeds mature, reaching peak levels around day 75 after fertilization. As the primary phytoconstituent of the seed, thymoquinone is abundant in the volatile oil fraction. Thus, the time of harvesting the seeds is a key determining factor of their thymoquinone content.   

The extraction method used to extract black seed oil plays a significant role in the total thymoquinone yield and the pharmacological properties of the seed oil. The following are different extraction methods used to obtainthe seed oil: 

• Cold press
• Supercritical fluid extraction
• Microwave-assisted extraction
• Hydrodistillation
• Enzymatic digestion
• Ultrasonication
• Pulse electric field

Although cold press extraction is the conventional method for extracting the seed oil, the thymoquinone concentration in oil extracted by cold press is found to be lower than that in oil extracted by supercritical fluid extraction(SFE). SFE has several benefits over traditional extraction methods, such as mild processing conditions and minimal risks of solvent contamination. Supercritical fluid extraction of black cumin seed oil allows for a higher-quality and purer thymoquinone extract. 

Pharmacological Properties of Thymoquinone

The antioxidative properties of thymoquinone and its ability to help maintain the body’s natural inflammatory response translate to various health benefits associated with black cumin seeds.* Thymoquinone exerts its antioxidative and immunomodulatory effects through various molecular pathways*, including:

1. Activation of cyclooxygenase-2 (COX-2)
2. Nuclear factor erythroid 2-related factor 2 (Nrf2)
3. Phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) 
4. Nuclear factor kappa-light-chain-enhancer of activated B (NF-Κβ)

The following table highlights the antioxidative and immunomodulatory effects of thymoquinone:

Thymoquinone’s Health Benefits and Side Effects

Thymoquinone’s pharmacological properties promote several health functions, including those of the brain, gut, heart, lungs, kidneys, liver, skin, and reproductive organs.* The following table summarizes the role of thymoquinone in protecting health functions against oxidative stress and adverse inflammatory responses:

Beyond the health benefits of thymoquinone covered above, accumulating evidence suggests^14,15 that it is a potent inhibitor of cellular proliferation and may induce apoptosis, or cell death, by modulating various cell signaling pathways.* 

Side Effects of Thymoquinone  

Culinary use of black cumin is considered safe for most individuals. In a clinical trial¹⁶, healthy volunteers who consumed 5 ml of Nigella sativa (NS) oil daily for eight weeks had no notable liver, kidney, or gastrointestinal side effects. Short-term usage (3 months) of NS oil and its constituents has not been linked to any adverse side effects. However, there is limited data on its prolonged usage.  

Is Thymoquinone Safe? 

The U.S. Food and Drug Administration categorizes Nigella sativa seeds and the extracted oil as Generally Recognized as Safe (GRAS). Clinical studies¹⁷ have observed no adverse or toxic effects of black seed oil, and it is overall well-tolerated. However, the thymoquinone content of the oil in the studies to date was not stated. Based on scientific literature, a daily thymoquinone intake of less than 48.6 mg may be considered safe for adults. 

Why Do You Need An Advanced Thymoquinone Supplement Formulation? 

Thymoquinone’s efficacy through oral intake is limited by its poor bioavailability and low absorption, primarily due to its hydrophobic nature and low solubility in water. These challenges can significantly reduce its effectiveness. However, advanced nutrients delivery systems in supplement formulations can overcome thymoquinone’s bioavailability and absorption challenges to help maximize its therapeutic potential.

Nanoparticle-based formulations have been found to have relatively higher bioavailability than unformulated thymoquinone. The movement of thymoquinone-loaded nanocarriers through the intestinal lymphatic system bypasses the initial digestion and metabolism, thus enhancing the relative bioavailability. 

Frequently Asked Questions About Thymoquinone Supplements

The following are some frequently asked questions (FAQs) about thymoquinone supplements: 

When should I include a thymoquinone supplement in my diet? 

Before considering taking a thymoquinone supplement, you should understand thymoquinone’s health benefits and side effects. Although thymoquinone has a well-established safety profile and promotes multiple health functions, it is always recommended to consult your healthcare provider before including a thymoquinone supplement in your diet. 

Can I take a thymoquinone supplement with prescription medications?

Thymoquinone can be potentially contraindicated with certain medications, such as blood thinners or renal medications. Consult with your healthcare provider before taking a thymoquinone supplement with prescription medications or any supplements that are a regular part of your routine.   

How do I determine the efficacy of a thymoquinone supplement?

The efficacy of a thymoquinone supplement is determined by its optimal absorption and bioavailability. An advanced formulation containing a blend of botanical extracts delivered through a nano-delivery system enables maximum absorption of the active nutrients. 

ThymoQuell® is an advanced thymoquinone supplement developed by Tesseract Medical Research to beneficially influence inflammatory response and oxidative stress in the gastrointestinal tract.* ThymoQuell® Plus contains our advanced thymoquinone along with a blend of botanical extracts — turmeric oil and four powerful terpenes – geraniol, borneol, nerol, and farnesol, to promote normal inflammatory responses in the gastrointestinal tract through enhanced nutritional support.* Both formulations are powered by Tesseract’s proprietary CyLoc® – DexKey® nutrient delivery nanotechnology for optimal absorption and solubility of the active nutrients.    

Citations:

¹Dingeo G, et al. Phytochemicals as modifiers of gut microbial communities. Food Funct. 2020;11(10):8444-8471. doi:10.1039/d0fo01483d

²Sakib R, et al. Antioxidant Properties of Thymoquinone, Thymohydroquinone and Black Cumin (Nigella sativa L.) Seed Oil…Antioxidants (Basel). 2023;12(3):607. doi:10.3390/antiox12030607

³Khaikin E, et al. Screening of thymoquinone content in commercial Nigella sativa products to identify a promising and safe study medication.” Nutrients vol. 14,17 3501. 25 Aug. 2022, doi:10.3390/nu14173501

⁴Khan MA, et al. Activities of Nigella sativa (black cumin). African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM vol. 8,5 Suppl (2011): 226-232. doi:10.4314/ajtcam.v8i5S.10

⁵Shaterzadeh-Yazdi, H, et al. Immunomodulatory . . . effects of thymoquinone.” Cardiovascular & Hematological Disorders Drug Targets vol. 18,1 (2018):52-60. doi:10.2174/1871529X18666180212114816

⁶Velagapudi R, et al. AMPK and SIRT1 activation contribute to inhibition of neuroinflammation by thymoquinone in BV2 microglia. Molecular and Cellular Biochemistry vol. 435,1-2 (2017):149-162. doi:10.1007/s11010-017-3064-3

⁷Shakeri F, et al. Gastrointestinal effects of Nigella sativa and its main constituent, thymoquinone: A review. Avicenna Journal of Phytomedicine vol. 6,1 (2016):9-20.

⁸Enayatfard L, et al. The standardized extract of Nigella sativa and its major ingredient, thymoquinone . . . in rats. Journal of Basic and Clinical Physiology and Pharmacology vol. 30,1 (2018):51-58. doi:10.1515/jbcpp-2018-0074

⁹ Majdalawieh AF, et al. Thymoquinone, a major constituent in Nigella sativa seeds…Eur J Pharmacol. 2021;909:174420. doi:10.1016/j.ejphar.2021.174420

¹⁰Abdelrazek HMA, et al. Black seed thymoquinone improved insulin secretion, hepatic glycogen storage, and oxidative stress in Streptozotocin-induced diabetic male Wistar rats. Oxidative Medicine and Cellular Longevity vol. 2018 8104165. 4 Mar. 2018, doi:10.1155/2018/8104165

¹¹Mosbah R, et al. Protective effect of Nigella sativa oil against acetamiprid induced reproductive toxicity in male rats. Drug and Chemical Toxicology vol. 41,2 (2018):206-212. doi:10.1080/01480545.2017.1337127

¹²Sarac G, et al. Effectiveness of topical Nigella sativa for vitiligo treatment. Dermatologic Therapy vol. 32,4 (2019): e12949. doi:10.1111/dth.12949

¹³Selçuk CT, et al. Evaluation of the effect of thymoquinone treatment on wound healing in a rat burn model. J Burn Care Res. 2013;34(5):e274-e281. doi:10.1097/BCR.0b013e31827a2be1

¹⁴Raut PK, et al. Thymoquinone induces oxidative stress-mediated apoptosis through downregulation of Jak2/STAT3 signaling pathway in human melanoma cells. Food Chem Toxicol. 2021;157:112604. doi:10.1016/j.fct.2021.112604

¹⁵He P, et al. Thymoquinone induces apoptosis and protective autophagy in gastric cancer cells by inhibiting the PI3K/Akt/mTOR pathway. Phytother Res. 2023;37(8):3467-3480. doi:10.1002/ptr.7820

^16,17Fallah Huseini H, et al. [E]ffect of Nigella sativa L. seed oil in healthy volunteers: a randomized, double-blind, placebo-controlled clinical trial. Phytotherapy Research : PTR vol. 27,12 (2013): 1849-53. doi:10.1002/ptr.4944