BLACK CUMIN SEED

Black cumin seeds and oils containing Nigella Sativa are well research functional foods with anti-inflammatory and metabolic health actions. See also Nigella Sativa in the Supplements Library.

Thymoquinone is the major active ingredient of both nigella sativa and piperine supplements, though piperine is also studied. Limited by its absorption and penetration – bioavailability- there is a lack of evidence directly in cancer treatments during oncology. A single phase one trial in 2017 showed no measurable effects, though dose levels were low.

Mixed and varied evidence around reduction of inflammation processes related to IL-1b and IL-6. Or increases in the anti-inflammatory markers such as IL-10. But most likely benefits of nigella sativa / thymoquinone are in blood glucose and cholesterol health and probably more so in patients with some form of inflammatory disease. Some studies on metabolic syndrome and type two diabetes patients where more consistent postive effects are reported.

Clinical evidence does exist for kidney function protection from anti-inflammatory actions, and similar in wound healing support. A small phase II trial has shown some interesting anti-viral activities in reducing covid related symptoms ( see references), and larger meta-analysis confirm these trial results. These partly seem to show effects in activating healthy immune response.

EXAMPLES OF IMPROVED OUTCOMES

PRE-DIAGNOSIS OR PREVENTION

Highlighted Studies

NS supplementation significantly reduced the mRNA expressions and serum levels of IL-1β with medium-high effect sizes(d=-1.6). Significant reductions with large effect sizes were observed in the gene expression and serum levels of IL-6 (d=-1.8, d=-0.78, respectively) and Leptin (d=-1.9, d=-0.89, respectively; serum leptin. Despite the meaningful carryover effect for serum leptin, results remained significant following the first intervention period ...

N. sativa significantly improved fasting blood sugar , total-cholesterol (TC)..and LDL-cholesterol (LDL-c).. The overall effects for triglyceride (TG) and HDL-cholesterol (HDL-c) were insignificant. Subgroup analysis revealed significant reduction on TG with N. sativa seed oil , while <a cla...

..patients receiving N sativa seeds displayed a significant decrease in TC [total cholesterol], LDL-C and the calculated lipid ratios .. In addition, HDL-C was higher than baseline values in the N sativa group. These results confirm the lipid lowering and anti-atherogenic lipoprotein pattern activities of N sativa seeds previously observed in patients with stable coronary artery disease26 and in type 2 diabetic patients.20 Another study was conducted in patients with hypercholesterolemia....

N. sativa supplementation had beneficial effects on CRP, TNF-α, MDA, SOD, GPx, and TAC. Thus, Nigella sativa can be recommended as an adjuvant anti-oxidant agent and anti-inflammatory…In total, twenty trials consisting of 1086 participants were included in the meta-analysis. Findings from 20 RCTs included in the meta-analysis suggest that N. sativa supplementation could significantly reduce serum C-reactive protein (CRP) (SMD = − 2.28), tumour necrosis fac...

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TABLE OF REFERENCES

URL	Rating	Category	Highlight	Highlight 2	Dose mg/kg
https://pmc.ncbi.nlm.nih.gov/articles/PMC10086143/	3	Meta-analysis	This overview suggests that N. sativa has the potential to improve different clinical outcomes, such as blood glucose, inflammatory markers, oxidative stress factors, serum lipids, blood pressure, liver and kidney parameters, and even asthma indicators. However, there are certain limitations in reporting and methodological quality, and future studies should improve the administration process. In addition, the clinical efficacy of N. sativa needs to be confirmed in high-quality, large-sample RCTs	This overview suggests that N. sativa is beneficial for various clinical outcomes. However, there are certain limitations to reporting and methodological quality. The clinical efficacy of N. sativa requires confirmation in high-quality, large-sample, randomized controlled trials.
https://bmccomplementmedtherapies.biomedcentral.com/articles/10.1186/s12906-023-04226-y	3	Meta-analysis	NS supplementation significantly reduced the mRNA expressions(d=-0.68) and serum levels of IL-1β with medium-high effect ... Significant reductions with large effect sizes were observed in the gene expression and serum levels of IL-6 (d=-1.8, d=-0.78) and Leptin(d=-1.9, d=-0.89. Despite the meaningful carryover effect for serum leptin, results remained significant following the first intervention period... A significant but low effect size decrease in serum insulin was observed	daily supplementation of 2000 mg of NS oil after 2 periods of 8 weeks resulted in significant reductions in blood mRNA expression levels of obesity-related pro-inflammatory genes, including IL-6, IL-1β, and leptin. Serum levels of IL-6, IL-1β, leptin, and insulin were also significantly reduced but the changes in insulin levels are of minor clinical significance. As the changes in blood mRNA gene expressions of interested outcomes were with high effect sizes, these findings suggest that NS oil can be considered a beneficial supplemental therapy to help prevent and manage overweight and obesity,
https://magistralbr.caldic.com/storage/product-files/109632469.pdf	3	Meta-analysis	... significant reductive effects of N. sativa on fasting glucose was found (WMD: −15.18); this finding was affirmed in all subgroup analysis. N. sativa reduced HbA1C levels (WMD: −0.45), but it had no significant influence on insulin (WMD: 0.92) and HOMA-IR (WMD: −0.35)	Pooling 29 effect sizes, a significant reductive effects of N. sativa on fasting glucose was found (WMD: −15.18); this finding was affirmed in all subgroup analysis. N. sativa reduced HbA1C levels (WMD: −0.45), but it had no significant influence on insulin (WMD: 0.92) and HOMA-IR (WMD: −0.35). Subgroup analyses were applicable only for fasting glucose and insulin
https://europepmc.org/article/MED/37036558	3	Meta-analysis	N. sativa supplementation had beneficial effects on CRP, TNF-α, MDA, SOD, GPx, and TAC. .....1086 participants were included in the meta-analysis. Findings from 20 RCTs included in the meta-analysis suggest that N. sativa supplementation could significantly reduce serum C-reactive protein (CRP) (SMD = - 2.28)	.. tumour necrosis factor α (TNFα) (SMD = - 1.21), and malondialdehyde (MDA) (SMD = - 2.15) levels, and significantly improves total antioxidant capacity (TAC) (SMD = 2.28), glutathione peroxidase (SMD = 1.23) and superoxide dismutase (SOD) (SMD = 2.05) levels. However, no significant reduction was found in interleukin 6 (IL-6) levels
https://pmc.ncbi.nlm.nih.gov/articles/PMC9144779/	2	Human study	The exploratory analysis of effect T lymphocytes showed a significant increase in cytotoxic CD8+ T lymphocytes (p = 0.042) and helper CD4+ T lymphocytes (p = 0.042) with native/central memory phenotype (CD45RA+CCR7+), from baseline to day 14, in TQF arm as compared to placebo. This suggests that TQF supports the recovery of the immune system against SARS-CoV-2, which likely helps prevent the progression to severe SARS-CoV-2 ... We also posit that TQF might directly prevent the overall T cell exhaustion and promote SARS-CoV-2-specific T cell proliferation.	TQF led to a significantly faster decline in the total symptom burden (TSB) (p < 0.001), and a significant increase in cytotoxic CD8+ (p = 0.042) and helper CD4+ (p = 0.042) central memory T lymphocytes. TQF exhibited an in vitro inhibitory effect on the entry of five SARS-CoV-2 variants. TQF was well-tolerated. While the median time-to-SCR did not reach statistical significance; it was shorter in the TQF arm and preclinical/clinical signals of TQF activity across multiple endpoints were significant	1500mg BID
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5633670/	1.5	Human study, Meta-analysis	We found that the side effects of this herbal medicine did not appear serious, so it can be applied in clinical trials because most of its major effects have been shown to be beneficial. Some properties of NS, such as its hypoglycemic, hypolipidemic, and bronchodilatory properties, are sufficiently understood so that NS can be used for subsequent phases of clinical trials or for drug development	dyslipidemia is an important risk factor responsible for cardiovascular disease in patients with diabetes [109], so alleviation/elimination of lipid abnormalities is important in the prevention of the complications of diabetes [79]. Thus, keeping the lipid profile of diabetic patients in the normal range can improve their health status, and NS intake, in combination with anti-diabetics and statins or fibrates, can help diabetic patients to control both dyslipidemia and blood sugar. We also reported the results of 13 clinical trials that presented data on the hypoglycemic effect of NS, 8 of which included patients with insulin resistance. The results showed that the use of black seed could decrease the HbA1c (5 studies) and the PPBG (2 studies) levels significantly.
https://www.jcpjournal.org/journal/view.html?volume=25&number=3&spage=136	1	Meta-analysis	[Thymoquinone] has clearly established it as a multi-target inhibitor that exerts its chemopreventive and anticancer activities by inhibiting multiple pathways involved in tumorigenesis, tumor progression, and metastasis. It should be stressed here that none of these pathways are mutually exclusive. Often, they are inter-connected and overlapping. The cumulative effects lead to the potent inhibition of cancer cell growth and progression by TQ. ...TQ has been shown to inhibit the cellular machinery and molecular targets underlying almost all of the hallmarks of cancer. Thus, the ability of TQ to inhibit multiple signaling pathways involved in cancer growth and progression highly underscores its potential as an ideal candidate for adjuvant therapy....TQ can overcome resistance to various chemotherapeutic drugs and potentiate their efficacies while reducing their innate cytotoxicity	However, it should be noted that the efficacy of TQ alone or in combination therapies could be context-specific. For example, TQ treatment along with paclitaxel reduced the potency of paclitaxel as evidenced by an increase in IC50 values for paclitaxel in the combination regiment. TQ has been shown to antagonize the therapeutic efficacy of paclitaxel in breast cancer cell lines [163]. It is also of importance to note that although TQ-cisplatin combination treatment showed synergy in an in vitro oral squamous cell carcinoma model, it contrarily increased cytotoxicity to normal oral epithelial cells
https://jeccr.biomedcentral.com/articles/10.1186/1756-9966-29-87#Sec17	1	Lab study- adjunct	Using a mouse xenograft model we were able to demonstrate that combination of TQ and CDDP was well tolerated and significantly reduced tumor volume and tumor weight without additional toxicity to the mice. In the combination arms (TQ5 mg/kg/Cis 2.5 mg/kg) tumor volume was reduced by 59% and (TQ20 mg/kg/Cis 2.5 mg/kg) by 79% as compared to control which is consistent with in vitro data	In the mouse xenograft model TQ alone at 20 mg/kg was active. The combination of TQ and CDDP was more active than each agent alone. The combination of (20 mg/kg TQ and 2.5 mg/kg of CDDP) reduced tumor volume by 79% without additional toxicity to the mice. These results are very encouraging and consistent with our in vitro data and show that TQ and CDDP is an effective therapeutic combination in lung cancer.	5 or 20mg/ kg and as adjunct with Cisplatin
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272120/	1	Lab study	Thymoquinone inhibited the migration and invasion as well as the EMT in RCC cells in an autophagy‐dependent manner. To further explore the underlying mechanism, we detected the AMPK/mTOR signaling pathway. The results indicated that TQ inhibited the metastasis of RCC cells by inducing autophagy via AMPK/mTOR signaling pathway. Our findings provide a novel therapeutic strategy that aims at TQ‐induced autophagy in Renal cell carcinoma treatment	TQ exerted anti‐metastatic properties in RCC cell lines 786‐O and ACHN. In addition, these characteristics, including inhibiting migration, invasion and EMT, were mainly dependent on TQ‐induced autophagy. Furthermore, we revealed that the mechanism by which TQ‐induced autophagy inhibited the metastasis of RCC cells was regulated through the AMPK/mTOR pathway. These findings indicated the potential role of TQ‐induced autophagy in cancer treatment and suggested that combining TQ with autophagy inhibitors might enhance its cancer suppression effects.	20mg/kg every 3 days
https://www.mdpi.com/1467-3045/46/1/10	1		Based on the available literature and published studies, it can be concluded that TQ has potential for use in the treatment of CRC due to its broad antitumor activity. Also in its favor is its high safety profile, low toxicity to normal cells and lack of information on significant side effects. The results of co-treating cancer cells with TQ and chemotherapeutic agents used in clinical practice also appear promising. Not only can TQ support therapy due to its synergistic effect with chemotherapeutics, but its ability to improve the sensitivity of CRC cells to chemotherapeutics has also been observed, which is curious in the case of 5-FU, since resistance to 5-FU is currently one of the biggest challenges in CRC treatment. Thus, the use of thymoquinone in chemoprevention and as an adjuvant therapy for CRC seems justified	TQ exhibits anti-CRC activity by inducing a proapoptotic effect and inhibiting proliferation, primarily through its effect on the regulation of signaling pathways crucial for tumor progression and oxidative stress. TQ can be used synergistically with chemotherapeutic agents to enhance their anticancer effects and to influence the expression of signaling pathways and other genes important in cancer development. These data appear to be most relevant for co-treatment with 5-FU. We believe that TQ is a suitable candidate for consideration in the chemoprevention and adjuvant therapy for CRC, but further studies, including clinical trials, are needed
https://www.ijbs.com/v17p3456.htm	1	Lab study	Taken together, this study demonstrates that TQ could induce the overproduction of ROS and downregulation of MMP, as well as the impaired autophagic flux, to initiate the apoptosis of BC cells. As well, we prove TQ activates miR-877-5p/PD-L1 axis to inhibit the EMT procedure and invasion of BC cells, hence further inhibits the progression of bladder carcinoma. It can be concluded that, as a multi-effective phytomedicine discovered for decades, TQ could be used as a novel treatment strategy, or play an adjuvant role in the systemic therapy of human bladder carcinoma.	Furthermore, TQ is proved to block the fusion of autophagosomes and lysosomes, causing the accumulation of autophagosomes and subsequent cell apoptosis. In addition, TQ is also found to initiate the miR-877-5p/PD-L1 axis, which suppresses the epithelial mesenchymal transition (EMT) and invasion of bladder carcinoma cells. Taken together, TQ induces the apoptosis through upregulating ROS level and impairing autophagic flux, and inhibiting the EMT and cell invasion via activating the miR-877-5p/PD-L1 axis in bladder carcinoma cells.	15mg/kg of TQ every 3rd day
https://www.frontiersin.org/articles/10.3389/fphar.2023.1138265/full	1	Lab study- adjunct	In pancreatic cancer cells, Tthymoquione can promote apoptosis, inhibit migration, invasion, and metastasis, and enhance the sensitivity to GEM. The underlying mechanism may involve the regulation of ECM production through the TGFβ/Smad pathway, in which HIF-1α plays a key role.	Our data suggest that TQ may enhance GEM sensitivity by influencing pancreatic interstitial fibrosis. We found that TQ can affect key proteins of ECM production in vitro and in vivo, thereby affecting tumor cell invasion and GEM sensitivity. In addition, TQ modulated the expression of key proteins of the TGFβ/Smad pathway, suggesting that TQ regulates ECM production through this pathway. HIF-1α plays a key role in the above regulatory mechanisms.	20mg/kg orally
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466966/	1	Meta-analysis	Thymoquinone (TQ), the main bioactive component of Nigella sativa, has been found to exhibit anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Moreover, TQ can specifically sensitize tumor cells toward conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy) and simultaneously minimize therapy-associated toxic effects in normal cells	TQ interferes in the phosphorylation and subsequent activation of several upstream tyrosine kinases (e.g., MAPK, Akt, mTOR, PIP3) that are involved in tumor cell proliferation signaling pathways ....Transcriptional factors (e.g., Nrf2, NF-κB, and STAT-3), key players in various oncogenesis process, are other crucial molecular targets of TQ .....by regulating the activation of these transcription factors, TQ can counteract different tumorigenic processes including inflammation, cell proliferation, cell survival, angiogenesis, cell invasions, and metastasis
https://www.mdpi.com/2072-6643/13/6/1784	1	Meta-analysis	Mounting evidence support the potential benefits of functional foods or nutraceuticals for human health and diseases. Black cumin (Nigella sativa L.), a highly valued nutraceutical herb with a wide array of health benefits, has attracted growing interest from health-conscious individuals, the scientific community, and pharmaceutical industries. The pleiotropic pharmacological effects of black cumin, and its main bioactive component thymoquinone (TQ), have been manifested by their ability to attenuate oxidative stress and inflammation, and to promote immunity, cell survival, and energy metabolism, which underlie diverse health benefits, including protection against metabolic, cardiovascular, digestive, hepatic, renal, respiratory, reproductive, and neurological disorders, cancer, and so on. Furthermore, black cumin acts as an antidote, mitigating various toxicities and drug-induced side effects.	By virtue of its antioxidant potential, TQ, the major bioactive of black cumin, was identified to regulate diverse signaling systems in inhibiting cancer progression (Figure 4) [121]. For example, Shahin et al. reported that administration of seed extract (150, 250, and 350 mg/kg, p.o. daily for 12 days) and TQ (20 mg/kg, p.o., three alternative days/week for 12 days) exerted chemopreventive efficacy by improving antioxidant status (GSH, GST, GPx, and SOD), downregulating expressions of Bcl-2, c-fos, and PCNA and by inhibiting epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinase (ERK)1/2 signaling pathway [117]. In addition, TQ (20 and 100 mg/kg) was reported to inhibit eEF-2K expression and suppress tumor growth and progression in an orthotopic TNBC xenograft mouse model
https://www.frontiersin.org/files/Articles/409609/fphar-09-01294-HTML/image_m/fphar-09-01294-g004.jpg	1	Lab study	..Analysis of bone isolated from TQ treated mice indicated a reduction in number of osteolytic lesions and the expression of metastatic biomarkers. In conclusion, the results indicate that TQ primarily exerts its anti-metastatic effects by down-regulation of NF-κB regulated CXCR4 expression and thus has potential for the treatment of breast cancer.	Bone metastasis was found to be significantly suppressed in the TQ treated group, and the number of osteolytic lesions in the mandibles, femora, and tibiae were markedly decreased, as indicated by bioluminescence imaging. Western blot analysis of tumors obtained from the lung and brain also showed a decrease in the expression of CXCR4 and Ki67. In fact, upon TQ treatment, there was a marked reduction in thinning of bones, as evidenced by H&E staining. In addition, IHC analysis of lung, brain, and bone tumors revealed inhibition of CXCR4 expression	2 or 4mg/kg for 4 weeks
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0046641#s3	1	Lab study	The results demonstrate that thymoquinone and/or diosgenin have antiproliferative and apoptotic properties mediated through the caspase, JNK and Akt (Ser473) pathway in A431 and Hep2 squamous cell carcinoma cell lines. Combinations of the two drugs have synergistic effects and show potential in suppressing sarcoma 180–induced solid tumors. The findings may offer an alternative strategy for development of potential antineoplastic therapies against squamous cell carcinoma.	In combination, TQ and DG had synergistic effects, resulting in cell viability as low as 10%. In a mouse xenograft model, a combination of TQ and DG significantly (P<0.05) reduced tumor volume, mass and increased apoptosis. TQ and DG, alone and in combination, inhibit cell proliferation and induce apoptosis in squamous cell carcinoma. The combination of TQ and DG is a potential antineoplastic therapy in this common skin cancer.	10 and 20mg/kg or both - Nigella Sativa and Fenugreek extracts TQ and DG
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620515/	1	Lab study	Results obtained in the in vitro experiments were supported by in vivo results. Significant reduction (p < 0.05) in tumor size was observed in the group treated with the combination therapy. This combination also caused tumor regression in 60% of treated mice. Additionally, the combination therapy induced extensive necrosis in tumors and reduced the death rate to 0% compared with 20% observed in the negative control group. The high therapeutic efficiency of this combination is a direct result of activation of different anticancer mechanisms including angiogenesis inhibition, apoptosis induction, and shifting the immune response toward Th1 anticancer immune response.	A combination of TQ and piperine can work synergistically to inhibit breast cancer in vitro and in vivo. The combination acts mainly by apoptosis induction, inhibition of angiogenesis, and shifting the immune response toward Th1 anticancer response. TQ is the main inducer of caspase-dependent apoptosis in this combination. B
https://www.mdpi.com/1422-0067/24/12/9878	1	Lab study	...TNF-α-stimulated MDA-MB-231 cells were compared with MDA-MB-468 cells, the two cells were sensitive to TQ’s anti-chemokine and anti-metastatic effect in preventing cell migration. It was concluded from this investigation that genetically different cell lines may respond to TQ differently, as TQ targets CCL3 and CCL4 in MDA-MB-231 cells and CCL2 and CCL20 in MDA-MB-468 cells. Therefore, the results indicate that TQ may be recommended as a component of the therapeutic strategy for TNBC treatment. These outcomes stem from the compound’s capacity to suppress the chemokin	..CCL20 is involved in Breast Cancer lung and bone metastases, and higher levels of CCL20 expression are associated with poorer overall survival. CCL20 expression was higher in TNBC than non-TNBC status and AA with BC than in European American. Chemotherapy has been demonstrated to increase CCL20 expression, which promotes chemo-resistance and further suggests that CCL20 may play a role in therapeutic outcome. TQ dramatically reduced the mRNA and protein expressions in the current study and may offer exciting alternatives for treating and preventing TNBC, either alone or in combination with chemotherapy
https://www.frontiersin.org/articles/10.3389/fnut.2022.977756/full	1	Human study, Meta-analysis	The results of the present study have indicated that N. sativa may improve cardiometabolic parameters by ameliorating glucose homeostasis and alleviating dyslipidemia, inflammation, and oxidative stress in individuals with prediabetes and T2DM. Overall, our results suggest that N. sativa supplementation can be a potential adjuvant therapy in the management of prediabetes and T2DM. In the future, more well-designed clinical studies are guaranteed to shed light on these findings.	Our findings are also supported by the previous systematic reviews and meta-analyses demonstrating the hypoglycemic efficacy of N. sativa among various non-diabetic populations (57–59). Hallajzadeh et al. (58) reported the beneficial effects of N. sativa on FPG and HbA1c without any change in serum insulin levels. Moreover, N. sativa consumption had a significant lowering effect on FPG, HbA1c, and OGTT values in a study conducted by Askari et al. (57). N. sativa could preserve pancreatic β-cell integrity, enhance the quantity of islets, and consequently make a contribution to the pancreatic β-cells proliferation and decreasing insulin resistance in diabetic experimental models and clinical studies
https://www.sciencedirect.com/science/article/abs/pii/S0965229917302649	1	Meta-analysis, Human study	his meta-analysis demonstrated that N. sativa exerts beneficial effects on glucose homeostasis and serum lipids, confirming its potential as a part of adjunct therapy among patients with T2D. These healthy effects in conjunction with barely reported mild side effects most probably make N. sativa supplementation a suitable choice to managing the complications of diabetes, although further research is advised to recognize the long-term effects as well as reasonable doses of seed oil and powder	To the best of our knowledge, this is the first meta-analysis investigating the effectiveness of N. sativa in T2D. The study revealed promising findings for the improvement of glycemia and serum lipids in diabetes. Clinical and statistical significant reduction in FBS and HbA1c levels following N. sativa consumption with either forms provides strong evidence for incorporation of N. sativa as part of therapy in diabetes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9460610/	N/A	Absorption and dosage	The content of TQ in the samples varied considerably (Table 3) and ranged from 3 to 809 mg/100 g. TQ concentrations in black seed oil published thus far varied even more. Alkhatib et al. [3], who analyzed five different black seed oil samples, found TQ amounts between 140 and 1880 mg/100 g, which was comparable to the results presented here. The results reported by Aboul-Enein et al. [14] and Ghosheh et al. [16] were somewhat lower but still of the same order of magnitude (33 and 132 mg/100 mL; 53 mg/100 g,	Upon conversion to human dosage, the safe daily TQ dosage was calculated to be below 48.6 mg per adult [27]. In a Phase-I-Study, the safe use of 200 mg black seed oil formulation with 5% TQ (10 mg TQ in the daily dosage) was confirmed in 35 healthy volunteers over 90 days versus placebo (n = 35) [28]. Based on the data available, we suggest that sample 5 at a dose of 3.7 g or 4 mL (supposing a specific mass of 0.92 g/mL) per day containing 30 mg TQ may safely be employed in a putative clinical study over six weeks.