title: The risks and rewards of covariate adjustment in randomized trials: an assessment of 12 outcomes from 8 studies Toxicity effect of nigella sativa on the liver function of rats. Antihypertensive effect of Nigella sativa seed extract in patients with mild hypertension 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 Preliminary safety evaluation and biochemical efficacy of a Carum carvi extract: results from a randomized, triple-blind, and placebo-controlled clinical trial. Efficacy of a fixed peppermint oil/caraway oil combination in non-ulcer dyspepsia. Protective role of Nigella sativa in diabetic nephropathy: A randomized clinical trial. The effect of Nigella sativa Linn. seed on memory, attention and cognition in healthy human volunteers. Blood pressure lowering effect of Nigella sativa L. seed oil in healthy volunteers: a randomized, double-blind, placebo-controlled clinical trial. Effect of Nigella sativa seeds on the glycemic control of patients with type 2 diabetes mellitus. Effects of Nigella sativa on outcome of hepatitis C in Egypt. Nigella sativa oil with a calorie-restricted diet can improve biomarkers of systemic inflammation in obese women: A randomized double-blind, placebo-controlled clinical trial. Efficacy of black seed (Nigella sativa L.) on kidney stone dissolution: A randomized, double-blind, placebo-controlled, clinical trial. 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.
abstract: Background Adjustment for prognostic covariates can lead to increased power in the analysis of r and omized trials . However , adjusted analyses are not often performed in practice . Methods We used simulation to examine the impact of covariate adjustment on 12 outcomes from 8 studies across a range of therapeutic areas . We assessed ( 1 ) how large an increase in power can be expected in practice ; and ( 2 ) the impact of adjustment for covariates that are not prognostic . Results Adjustment for known prognostic covariates led to large increases in power for most outcomes . When power was set to 80 % based on an unadjusted analysis , covariate adjustment led to a median increase in power to 92.6 % across the 12 outcomes ( range 80.6 to 99.4 % ) . Power was increased to over 85 % for 8 of 12 outcomes , and to over 95 % for 5 of 12 outcomes . Conversely , the largest decrease in power from adjustment for covariates that were not prognostic was from 80 % to 78.5 % . Conclusions Adjustment for known prognostic covariates can lead to substantial increases in power , and should be routinely incorporated into the analysis of r and omized trials . The potential benefits of adjusting for a small number of possibly prognostic covariates in trials with moderate or large sample sizes far outweigh the risks of doing so , and so should also be considered PURPOSE The aim of this study was to determine the toxic effect of Nigella sativa powder on the liver function which was evaluated by measuring liver enzymes and through histopathological examination of liver tissue . METHODS Twenty four male Sprague Dawley rats were allotted r and omly to four groups including : control ( taking normal diet ) ; low dose ( supplemented with 0.01 g/kg/day Nigella sativa ) ; normal dose ( supplemented with 0.1 g/kg/day Nigella sativa ) and high dose ( supplemented with 1 g/kg/day Nigella sativa ) . All of supplements administered in powder form mixed with rats ' pellet for 28 days . To assess liver toxicity , liver enzymes measurement and histological study were done at the end of supplementation . RESULTS The finding revealed that there was no significant change in serum alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) between treatment groups . Histopathological study showed very minimal and mild changes in fatty degeneration in normal and high doses of Nigella sativa treated group . Inflammation and necrosis were absent . CONCLUSION The study showed that supplementation of Nigella sativa up to the dose of 1 g/kg supplemented for a period of 28 days result ed no changes in liver enzymes level and did not cause any toxicity effect on the liver function Hypertension ( HT ) is a lifestyle‐related disease and dietary modifications are effective for its management and prevention . We conducted a r and omized , double‐blind , placebo‐controlled trial to evaluate the efficacy of treatment with an oral Nigella sativa ( NS ) seed extract supplement in patients with mild HT . Subjects were r and omized into three groups : a placebo and two test groups that received 100 and 200 mg of NS extract twice a day . After 8 weeks , systolic blood pressure ( SBP ) values in both case groups were found to be significantly reduced when compared with the baseline values for each group . In addition , the decrease in SBP in the two case groups was statistically significant relative to the placebo group ( P < 0.05–0.01 ) . Meanwhile , diastolic blood pressure ( DBP ) values in the case groups were found to be significantly reduced from the baseline and a significant reduction was also observed in these groups ( P < 0.01 ) when compared with the placebo group . In addition , extract administration reduced both SBP and DBP in a dose‐dependent manner . Meanwhile , NS extract caused a significant decline in the level of total and low‐density‐lipoprotein (LDL)‐cholesterol relative to baseline data . No complications caused by NS were observed . The results suggest that the daily use of NS seed extract for 2 months may have a blood pressure‐lowering effect in patients with mild HT BACKGROUND Diabetic patients with hypertension and dyslipidemia are at a high risk of cardiovascular complications . OBJECTIVES To determine the effect of Nigella sativa supplementation on the lipid profile , mean arterial pressure , and heart rate in persons with type 2 diabetes on oral hypoglycemic agents ( OHA ) .  DESIGN Single-blind , nonr and omized . SETTING Diabetes clinic of a university hospital in Saudi Arabia . PATIENTS AND METHODS Type-2 diabetic patients were recruited by purposive sampling and assigned to treatment or control at the discretion of the investigator with the patient blinded to treatment . Before the intervention and every 3 months thereafter until the end of the treatment period , the following parameters were measured : triglycerides ( TG ) , total cholesterol ( TC ) , low density lipoprotein cholesterol ( LDL-C ) , high density lipoprotein cholesterol ( HDL-C ) , systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , mean arterial pressure ( MAP ) , heart rate ( HR ) , and body mass index ( BMI ) . Results at the baseline and each subsequent visit were compared between the two groups . MAIN OUTCOME MEASURE(S ) Lipid and cardiovascular parameters , and BMI . RESULTS Fifty-seven patients were assigned to receive N sativa 2 g daily for one year and 57 were assigned to receive an identical regimen of placebo , along with OHA . A significant decrease in HDL-C and increase in the TC/HDL-C and LDL-C/HDL-C ratios were seen in the control group . The N sativa group had a significant decline in TC , LDL-C , TC/HDL-C and LDL-C/HDL-C ratios , compared with the respective baseline data and the control group . HDL-C was significantly elevated in the N sativa group . The control group showed a significant elevation in MAP . The N sativa group had a significant reduction in SBP , DBP , MAP and HR and a significant decrease in DBP , MAP and HR as compared with the control group . CONCLUSION N sativa supplementation improves total cholesterol , mean arterial pressure and heart rate in type 2 diabetes patients on oral hypoglycemic agents .  LIMITATIONS There were 9 subjects in each group lost to follow up ; thus the sample size could not be maintained as per the sample size calculation . The study was nonr and omized and thus there was a possibility of allocation bias . ( Clinical trial registration number : CTRI/2013/06/003781 , Clinical Trial Registry of India ) Carum carvi L. ( Apiaceae ) is known as caraway , and its derivatives find wide medicinal use for health purpose s , including for gastrointestinal problems and obesity . Since there is inconsistency among the reports on the safety of this plant in humans , this research was aim ed at assessing the safety of a characterized caraway aqueous extract ( CAE ) in a r and omized , triple-blind , placebo-controlled study . Seventy , overweight and obese , healthy women were r and omly assigned into placebo ( n = 35 ) and plant extract ( n = 35 ) groups . Participants received either 30 ml/day of CAE or placebo . Subjects were examined at baseline and after 12 weeks for changes in heart rate , blood pressure , urine test , 25-item blood chemistries , and general health status . No significant changes of blood pressure , heart rate , urine specific gravity , and serum blood tests were observed between the two groups before and after treatment . However , in the complete blood count test , red blood cell levels were significantly ( p < 0.01 ) increased , and platelet distribution width was significantly decreased after the dietary CAE treatment , as compared with placebo . No negative changes were observed in the general health status of the two groups . This preliminary study suggests that the oral intake of CAE appears to be without any adverse effects at a dosage of 30 ml daily for a period of 12 weeks The efficacy and safety of the st and ardized herbal combination preparation of Enteroplant , consisting of peppermint oil ( 90 mg ) and caraway ( 50 mg ) in an enteric coated capsule , have been studied in a double-blind , placebo-controlled multicentre trial in patients with non-ulcer dyspepsia . A total of 45 patients were included in the trial after thorough physical and gastro-enterological examination . The primary outcome variables were the change in the intensity of pain and the global clinical impression ( Clinical Global Impression [ CGI ] , Item 2 ) , which were evaluated for 39 patients ( test preparation : 19 , placebo : 20 ) . After four weeks of treatment both target parameters were significantly improved for the group of patients treated with the peppermint oil/caraway oil combination compared to the placebo group ( p = 0.015 and 0.008 , respectively ) . Before the start of treatment all patients in the test preparation group reported moderate to severe pain , while by the end of the study 63.2 % of these patients were free of pain . The pain symptoms had improved in a total of 89.5 % of the patients in the active treatment group . After 4 weeks the Clinical Global Impressions were improved for 94.5 % of the patients treated with the peppermint oil/caraway oil combination . The trial medication was also superior to placebo with respect to pain frequency , medical prognosis , the severity of the disorder and the efficacy index ( CGI , Items 1 and 3 ) , which were adopted as secondary end-points for evaluation of efficacy . There were similarly favourable findings for the herbal combination , compared with placebo , with respect to the reduction of other gastrointestinal symptoms . The combination preparation was found to be excellently tolerated . There was a total of 7 adverse events ( test preparation : 4 , placebo : 3 ) , with a causal association with the treatment being ascribed in one case for the test preparation group and one case for the placebo group This study aims to evaluate efficacy and safety of Nigella sativa oil supplementation in patients with chronic kidney disease Stage 3 and 4 due to diabetic nephropathy . It was a prospect i ve , comparative , and open-label study . Patients were r and omized into two groups . Group 1 ( Control ) received conservative management of diabetic nephropathy , whereas Group 2 ( Test ) received N. sativa oil ( 2.5 mL , once daily and per orally ) along with conservative management for 12 weeks .  Blood glucose , hemogram , and kidney function test were done at 0 , 6 , and 12 weeks of treatment . Significance of differences between pre- and post-treatment values in each group was assessed using Student 's paired t-test and between the groups using unpaired t-test . We found a drop in blood glucose , serum creatinine , blood urea , and 24 h total urinary protein levels and a rise in glomerular filtration rate , 24 h total urinary volume , and hemoglobin level in the treatment group compared to the control group BACKGROUND Experimental evidence s have demonstrated that Nigella sativa Linn . seed ( NS ) has positive modulation effects on aged rats with memory impairments , prevents against hippocampal pyramidal cell loss and enhances consolidation of recall capability of stored information and spatial memory in rats .  NS has neuroprotective , nephroprotective , lung protective , cardioprotective , hepatoprotective activities as established by previous studies on animals . Several clinical trials with NS on human have also demonstrated beneficial effect . AIM OF THE STUDY The present study was design ed to investigate the effects of NS on memory , attention and cognition in healthy elderly volunteers . Furthermore , safety profile of NS was assessed during the nine-week study period . METHODS Forty elderly volunteers were recruited and divided r and omly into group A and group B -- each consisting of 20 volunteers . The treatment procedure for group A was 500 mg NS capsule twice daily for nine weeks and Group B received placebo instead of NS in the similar manner . All the volunteers were assessed for neuropsychological state and safety profile twice before treatment and after nine weeks . The neuropsychological tests were logical memory test , digit span test , Rey-Osterrieth complex figure test , letter cancellation test , trail making test and stroop test . Safety profile was assessed by measuring biochemical markers of Cardiac ( total cholesterol , triglycerides and high density lipoprotein cholesterol , very low density lipoprotein , low density lipoprotein cholesterol , creatine kinase-MB ) ; Liver ( aspartate aminotransferase , alanin aminotransferase , alkaline phosphatase , total protein , albumin , bilirubin ) and Kidney ( creatinine and blood urea nitrogen ) through using commercial kits . RESULTS There was significant difference ( p<0.05 ) in the score of logical memory test-I and II , total score of digit span , 30 min delayed-recall , percent score in Rey-Osterrieth complex figure test , time taken to complete letter cancellation test , time taken in trail making test-A and test-B , score in part C of stroop test due to ingestion of NS for nine weeks . There were not statistically significant changes ( p>0.05 ) in any of the biochemical markers of cardiac , liver , kidney function during this nine-week study period . CONCLUSIONS The current study demonstrates the role of NS in enhancing memory , attention and cognition . Therefore , whether NS could be considered as potential food supplement for preventing or slow progressing of Alzheimer disease needs further investigations . However , study with Alzheimer 's patients with large population size for longer period of time is recommended before using NS daily and extensive phytochemical investigations are recommended for novel drug discovery from NS for treating cognitive disorders Nigella sativa L. seeds ( N. sativa ) have been used as a traditional remedy for a wide range of diseases including hypertension . The present study was performed to explore the effects of N. sativa oil on blood pressure ( BP ) in healthy volunteers . In a double-blind , r and omized study , 70 healthy volunteers aged 34 to 63 years with systolic BP from 110 to 140 mmHg and diastolic BP from 60 to 90 mmHg were r and omly allocated to receive 2.5 mL N. sativa oil or placebo two times a day for 8 weeks . The systolic and diastolic BPs , body mass index and blood levels of aspartate transaminase , alanine transaminase , alkaline phosphatase , creatinine and blood urea nitrogen were determined at baseline and endpoint . Results showed that in N. sativa oil treated group the systolic and diastolic BPs decreased significantly compared with baseline and placebo group at the endpoint . Other parameters did not significantly change in both groups at the endpoint . No adverse effects were reported . In conclusion , oral daily administration of 5 mL N. sativa oil to healthy volunteers for 8 weeks lowers systolic and diastolic BPs without any adverse effects UNLABELLED Diabetes mellitus is a common chronic disease affecting millions of people world wide . St and ard treatment is failing to achieve required correction of blood glucose in many patients . Therefore , there is a need for investigating potential hypoglycemic drugs or herbs to improve glycemic control in diabetic patients .  Nigella sativa seeds were used as an adjuvant therapy in patients with diabetes mellitus type 2 added to their anti-diabetic medications . A total of 94 patient were recruited and divided r and omly into three dose groups . Capsules containing Nigella sativa were administered orally in a dose of 1 , 2 and 3 gm/day for three months . The effect of Nigella sativa on the glycemic control was assessed through measurement of fasting blood glucose ( FBG ) , blood glucose level 2 hours postpr and ially ( 2 hPG ) , and glycosylated hemoglobin ( HbA1c ) . Serum C-peptide and changes in body weight were also measured . Insulin resistance and beta-cell function were calculated usin the homeostatic model assessment ( HOMA2 ) . Nigella sativa at a dose of 2 gm/day caused significant reductions in FBG , 2hPG , and HbA1 without significant change in body weight . Fasting blood glucose was reduced by an average of 45 , 62 and 56 mg/dl at 4 , 8 and 12 weeks respectively . HbAlC was reduced by 1.52 % at the end of the 12 weeks of treatment ( P<0.0001 ) . Insulin resistance calculated by HOMA2 was reduced significantly ( P<0.01 ) , while B-cell function was increased ( P<0.02 ) at 12 weeks of treatment . The use of Nigella sativa in a dose of 1 gm/day also showed trends in improvement in all the measured parameters but it was not statistically significant from the baseline . However , no further increment in the beneficial response was observed with the 3 gm/day dose . The three doses of Nigella sativa used in the study did not adversely affect either renal functions or hepatic functions of the diabetic patients throughout the study period . IN CONCLUSION the results of this study indicate that a dose of 2 gm/ day of Nigella sativa might be a beneficial adjuvant to oral hypoglycemic agents in type 2 diabetic patients AIM To evaluate the safety , efficacy and tolerability of Nigella sativa ( N. sativa ) in patients with hepatitis C not eligible for interferon (IFN)-α . METHODS Thirty patients with hepatitis C virus ( HCV ) infection , who were not eligible for IFN/ribavirin therapy , were included in the present study . Inclusion criteria included : patients with HCV with or without cirrhosis , who had a contraindication to IFN-α therapy , or had refused or had a financial constraint to IFN-α therapy . Exclusion criteria included : patients on IFN-α therapy , infection with hepatitis B or hepatitis I virus , hepatocellular carcinoma , other malignancies , major severe illness , or treatment non-compliance . Various parameters , including clinical parameters , complete blood count , liver function , renal function , plasma glucose , total antioxidant capacity ( TAC ) , and polymerase chain reaction , were all assessed at baseline and at the end of the study . Clinical assessment included : hepato and /or splenomegaly , jaundice , palmar erythema , flapping tremors , spider naevi , lower-limb edema , and ascites . N. sativa was administered for three successive months at a dose of ( 450 mg three times daily ) . Clinical response and incidence of adverse drug reactions were assessed initially , periodically , and at the end of the study . RESULTS N. sativa administration significantly improved HCV viral load ( 380808.7 ± 610937 vs 147028.2 ± 475225.6 , P = 0.001 ) and TAC ( 1.35 ± 0.5 vs 1.612 ± 0.56 , P = 0.001 ) . After N. sativa administration , the following laboratory parameters improved : total protein ( 7.1 ± 0.7 vs 7.5 ± 0.8 , P = 0.001 ) , albumin ( 3.5 ± 0.87 vs 3.69 ± 0.91 , P = 0.008 ) , red blood cell count ( 4.13 ± 0.9 vs 4.3 ± 0.9 , P = 0.001 ) , and platelet count ( 167.7 ± 91.2 vs 198.5 ± 103 , P = 0.004 ) . Fasting blood glucose ( 104.03 ± 43.42 vs 92.1 ± 31.34 , P = 0.001 ) and postpr and ial blood glucose ( 143.67 ± 72.56 vs 112.1 ± 42.9 , P = 0.001 ) were significantly decreased in both diabetic and non-diabetic HCV patients . Patients with lower-limb edema decreased significantly from baseline compared with after treatment [ 16 ( 53.30 % ) vs 7 ( 23.30 % ) , P = 0.004 ] . Adverse drug reactions were unremarkable except for a few cases of epigastric pain and hypoglycemia that did not affect patient compliance . CONCLUSION N. sativa administration in patients with HCV was tolerable , safe , decreased viral load , and improved oxidative stress , clinical condition and glycemic control in diabetic patients BACKGROUND Inflammation is one of the primary mechanisms in the development of metabolic complications . Although anti-inflammatory characteristics of Nigella sativa ( NS ) have been indicated in animal models , clinical trials related to the effects of NS on inflammatory parameters are relatively scarce . OBJECTIVE The aim of the present study was to determine the effects of NS oil combined with a calorie-restricted diet on systemic inflammatory biomarkers in obese women . METHODS In this double-blind placebo-controlled r and omized clinical trial , 90 volunteer obese ( body mass index = 30 - 34.9 kg/m(2 ) ) women aged 25 - 50 years were recruited . Participants were r and omly divided into two groups , an intervention group ( n = 45 ) and a placebo group ( n = 45 ) . Each group received either : ( 1 ) a low-calorie diet with 3 g/day of NS oil or ( 2 ) a low-calorie diet with 3 g/day placebo for 8 weeks . RESULTS A total of 84 females ( intervention group = 43 ; placebo group = 41 ) completed the trial . Subjects in the intervention group did not report any side effects with the NS oil supplementation . NS oil decreased serum levels of tumor necrosis factor-alpha ( -40.8 % vs -16.1 % , P = .04 ) and high-sensitivity C-reactive protein ( -54.5 % vs -21.4 % , P = .01 ) compared to the placebo group . However , there were no significant changes in interleukin-6 levels ( -8.6 vs -2.4 % , P = .6 ) in the NS group compared to the placebo group . CONCLUSIONS NS oil supplementation combined with a calorie-restricted diet may modulate systemic inflammatory biomarkers in obese women . However , more studies are needed to clarify the efficacy of NS oil as an adjunct therapy to improve inflammatory parameters in obese subjects Pre clinical studies have shown beneficial effects of black seed ( Nigella sativa L. ) in the prevention and treatment of renal stones .  Hence , we design ed a study to evaluate the renal-stone-dissolving efficacy of black seed .  Sixty patients with renal stones were r and omly enrolled in two arms of a r and omized , triple-blind , placebo-controlled , clinical trial . The patients were treated by black seed capsules ( 500 mg ) or placebo two times per day for 10 weeks . Patients were assessed in terms of size of renal stones by using sonography before and after intervention . In the black seed group , 44.4 % of patients excreted their stones completely , and the size of the stones remained unchanged and decreased in 3.7 % and 51.8 % of patients , respectively . In contrast , in the placebo group , 15.3 % of the patients excreted their stones completely , 11.5 % had reduction in stone size , 15.3 % had increase in stone size , and 57.6 % had no change in their stone size . The difference in the mean size of renal stones after the study was significant between the two groups ( p < 0.05 ) . N. sativa L. , as compared with placebo , is demonstrated to have significant positive effects on disappearance or reduction of size of kidney stones OBJECTIVE The seed extracts from Nigella sativa is used by Unani physicians of traditional medicine ( Hakims or Tabibs ) and Ayurvedic practitioners ( Vaids ) in the treatment of several medical disorders including dyslipidemia , obesity , and hypertension . It is , therefore , important to prove or disprove the effectiveness , safety , and tolerability of powdered N. sativa ( Kalonji ) seed in capsules on serum lipid levels , blood sugar , blood pressure , and body weight in adults . DESIGN The study design was a r and omized , double-blind trial . SETTING S/LOCATION Conducted at Aga Khan University Hospital , Karachi , from February 2006 to January 2007 . SUBJECTS Half of the respondents received powdered N. sativa ( Kalonji ) seed in capsule and the rest received a placebo . INTERVENTION/ OUTCOME Baseline and after-intervention variables recorded were the following : body-mass index , waist-hip ratio , blood pressure , fasting blood sugar , serum lipids , serum alanine aminotransferase , and serum creatinine . RESULTS One hundred and twenty-three ( 123 ) patients were recruited . Sixty-four ( 64 ) and 59 patients were r and omized to the intervention and the control arms , respectively . Thirty-nine ( 39 ) patients in the intervention group and 34 in the control group completed the study . Favorable impact of powdered N. sativa ( Kalonji ) seed in capsule was noted on almost all variables , but results were not statistically significant because of small sample size . CONCLUSIONS Favorable impact of powdered N. sativa ( Kalonji ) seed in capsule was noted on almost all variables , but results were not statistically significant . A larger study with adequate sample size is recommended
target: Our data suggested that N.S supplementation had significant impacts on liver and kidney parameters leading to a decrease in ALP and BUN levels .
background: The aim of this systematic review and dose-response meta- analysis was to determine the effect of Nigella Sativa ( N.S ) supplementation on  liver and kidney parameters .