Meta-analysis Finds Black Cumin Beneficial for Glucose Homeostasis and Serum Lipids; Confirms Potential as Adjunct Therapy for Type 2 Diabetes
Black cumin (BC; Nigella sativa, Ranunculaceae) seed, a food and traditional medicine native to South and Southwest Asia and widely cultivated in the Middle East and North Africa, has drawn strong research interest. An appetite stimulant, bronchodilator, diuretic, antibacterial, liver tonic, and analgesic, it is used for type 2 diabetes (T2D), liver and kidney problems, hypertension, cardiovascular diseases, digestive ailments, diarrhea and dysentery, cancer, skin ailments, infections, rheumatism, headaches, and asthma and bronchitis. Human trials have investigated its seed oil or powder in T2D, rheumatoid arthritis, and hypertension. Animal studies report hypoglycemic and hypolipidemic effects in T2D models. Systematic reviews and meta-analyses have reported promising results on metabolic parameters, but none have previously assessed its pooled effects on glycemia and serum lipids. This lack of evidence precludes the American Diabetes Association from listing BC as a primary option (Level A) for T2D management.
The authors conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A database search for human trials of BC’s effects on glycemia and serum lipids up to February 2017 located 292 non-duplicate reports. Titles and abstracts were screened for relevance; 275 were excluded. To meet criteria, trials had to be of interventions using BC seed oil or powder in patients with T2D, report relevant outcome measures of glycemia (fasting blood sugar [FBS], glycated hemoglobin [HbA1c], etc.) and/or serum lipids profile (triglycerides [TG], cholesterol, etc.), and compare BC with placebo or standard treatment. Excluded were animal studies, those studies lacking an interventional approach, those lacking pre- and post-intervention desired outcomes and any duplicates. Of 17 full-text articles considered, eight were not trials and two were in languages other than English or Persian. Their exclusion left seven for review and analysis. These included 255 patients in active arms; 250 in controls. Three studies were conducted in Iran; three, Saudi Arabia; and one, India. Duration was two to 12 months. Four investigated BC seed powder at dosages from 0.5-2.0 g/day; three used seed oil at doses from 1-5 mL/d. All used a parallel design.
Risk of publication bias for each outcome was assessed via Egger’s test. No significant risk was found for FBS, total cholesterol (TC), TG, high-density lipoprotein cholesterol (HDL-c), or low-density lipoprotein cholesterol (LDL-c). However, there was significant publication bias risk for HbA1c (P = 0.01).
Pooled effects of trials reporting outcomes of interest are shown in forest plots. For glycemic results, five trials saw significant reductions in FBS with BC powder or oil (weighted mean difference [WMD], −17.84 mg/dL; 95% confidence interval [CI], −21.19 to −14.49; P < 0.001). No heterogeneity was found (I2 = 28.5%; P = 0.23). Five studies had pooled decreases in HbA1c with either form of BC (WMD, −0.71%; 95% CI, −1.04 to −0.39; P < 0.001). There was significant evidence of heterogeneity (I2 = 89.3%; P < 0.001). For FBS and HbA1c, sensitivity analysis found that omitting one study significantly changed pooled effect size. Excluding it left a WMD for FBS of −16.89 mg/dL (95% CI, −22.42 to −11.33; P < 0.001); for HbA1c, WMD was −0.61% (95% CI, −0.93 to −0.29; P < 0.001).
Mechanisms of action for BC’s significant benefits on glycemia in T2D are posited to include amelioration of pancreatic β-cells and the resultantly increased insulin secretion, reduced liver gluconeogenesis, and induced insulin sensitivity in peripheral tissue. BC compounds thymoquinone, dithymoquinone, linoleic acid, and oleic acid are credited, although research in this area is limited. Both BC powder and oil were seen to maintain significant decreases in FBS and HbA1c for more than a year. This meta-analysis found BC’s effects on HbA1c equal to those of dipeptidyl peptidase-4 (DPP-4) inhibitors.
Four studies reported significant decreases in TC from baseline with BC (WMD, −22.99 mg/dL; 95% CI, −32.16 to −13.83; P < 0.001). Heterogeneity was not seen (I2 = 31.9%; P = 0.22). Subgroup analyses found greater reductions in TC with oil over powder, but studies with oil showed moderate heterogeneity. Five studies assessed BC’s effect on plasma TG. WMD was −6.80 mg/dL (95% CI, −33.59 to 19.99; P = 0.61). Heterogeneity was significant (I2 = 89.5%; P < 0.001). Subgroup analyses showed that BC oil significantly reduced TG (WMD, −14.8 mg/dL; 95% CI, −23.1 to −6.5; P < 0.001), but BC powder significantly raised it (WMD, 29.4 mg/dL; 95% CI, 16.9-42.0; P < 0.001). There was significant heterogeneity in powder studies (I2 = 71.2%; P = 0.06) but not in those using oil (I2 = 0.0%; P = 0.48). Pooled effects of five studies reporting HDL-c were nonsignificant (WMD, 0.37 mg/dL; 95% CI, −1.59 to 2.33; P = 0.71), with no heterogeneity (I2 = 0.0%; P = 0.52). For LDL-c, five trials showed a significant drop (WMD, −22.38 mg/dL; 95% CI, −33.60 to −11.15; P < 0.001). Heterogeneity was seen (I2 = 80.0%; P < 0.01). Subgroup analyses found that both forms of BC reduced LDL-c, but studies of each type were heterogeneous (oil, I2 = 76.7%, P = 0.01; powder, I2 = 91.1%, P = 0.001). Sensitivity analysis found that no single study significantly affected pooled effects on TC, TG, HDL-c, or LDL-c.
BC’s effects on lipid levels are thought to be due to its antioxidant activity. An agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ), it reduces lipid peroxidation, promotes hepatic uptake of LDL-c, and inhibits cholesterol synthesis. Lipid profiles in healthy people also have been found in meta-analyses to improve with BC supplementation. The lack of BC powder effect on TG levels in this meta-analysis may be due to insufficient dosage, since patients with T2D tend to have significantly higher TG than healthy people. This does not explain the observed different effects of oil vs. powder on TG, perhaps related to preparation processes. While standard statin doses reduce LDL-c more than BC, evidence suggests that further reductions in LDL-c after statin therapy reduce all-cause mortality among patients with T2D, pointing to a complementary role for BC. Mild, “barely reported” adverse events (there is some reporting of mild gastrointestinal problems) make BC even more promising in managing T2D.
Daryabeygi-Khotbehsara R, Golzarand M, Ghaffari MP, Djafarian K. Nigella sativa improves glucose homeostasis and serum lipids in type 2 diabetes: a systematic review and meta-analysis. Complement Ther Med. December 2017;35:6-13.