Protective role of Nigella sativa in diabetic nephropathy: A randomized clinical trial

Zafar Masood Ansari; Mohammad Nasiruddin; Rahat Ali Khan; Shahzad Faizul Haque

doi:10.4103/1319-2442.198093

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ORIGINAL ARTICLE

Year : 2017 | Volume : 28 | Issue : 1 | Page : 9-14

Protective role of Nigella sativa in diabetic nephropathy: A randomized clinical trial

Zafar Masood Ansari¹, Mohammad Nasiruddin¹, Rahat Ali Khan¹, Shahzad Faizul Haque²
¹ Department of Pharmacology, J. N. Medical College and Hospital, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
² Department of Medicine, J. N. Medical College and Hospital, Aligarh Muslim University, Aligarh, Uttar Pradesh, India

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Date of Web Publication

12-Jan-2017

Abstract

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 prospective, comparative, and open-label study. Patients were randomized 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.

How to cite this article:
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;28:9-14

How to cite this URL:
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 [serial online] 2017 [cited 2021 Jun 21];28:9-14. Available from: https://www.sjkdt.org/text.asp?2017/28/1/9/198093

Introduction

Chronic kidney disease (CKD) and diabetes mellitus (DM) are major public health problems and both have worldwide distribution. Diabetic nephropathy is the most common cause for the development of CKD. Approximately, 30% of patients with DM have diabetic nephropathy, and with the growing number of DM patients and aging population, there is likely a parallel increase in CKD incidence. According to the International Diabetes Federation Diabetes Atlas 2014, the number of patients with DM in India (currently around 66.8 million) is expected to rise to 101.2 million by 2030 unless urgent preventive measures are taken.^[1] The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative guidelines^[2] defined CKD as kidney damage or glomerular filtration rate (GFR) <60 mL/min/1.73 m^[2] for three months or more, irrespective of cause. According to Screening and Early Evaluation of Kidney disease-India cohort study, the prevalence of CKD was approximately 17.2% with ~6% have CKD Stage 3 or worse.^[3] The financial load of renal replacement therapy (RRT) is augmented with increasing prevalence of CKD, end-stage renal disease (ESRD), and CKD-related cardiovascular disease, and it is assessed that around 100,000 new patients of ESRD require RRT annually in India.^[4] In the body, nitrogenous metabolic waste products can be reduced with ingestion of low-protein diet (0.6 g/kg BW/day) and very low-protein diet (0.3 g/kg BW/day) while maintaining sufficient nutritional status. Hence, secondary problems such as metabolic acidosis, metabolic bone disease, and insulin resistance as well as proteinuria and deterioration of renal function are reduced.^{[5] ,[6]}

Nigella sativa has a long history as a diversely beneficial herb. For more than 3000 years ago, people have used the black seed to cure numerous ailments and to maintain and improve general health. The nephroprotective activity of

N. sativa has been reported previously by many authors in both clinical^[7] and experimental^{[8] ,[9]} studies. N. sativa has antidiabetic and renoprotective effects in patients of type 2 DM.^[10] A randomized clinical trial established that N. sativa oil has anti-inflammatory properties and improved kidney function, blood glucose level, HbA^[1]c level, and liver function.^[11]

N. sativa oil contains fixed and essential oils. Fixed oil contains mainly linoleic acid, oleic acid, palmitic acid, and stearic acid. Thymoquinone, cymene, and carvone are main components of essential oil. Thymoquinone is the main active component which has multiple beneficial properties. The use of N. sativa oil in association with a lowor very low-protein diet permits a decreased ingestion of nitrogen while avoiding the deleterious outcomes of inappropriate intake of dietary protein and malnourishment because it contains a high amount of unsaturated fatty acids.^[12] The antioxidant and anti-inflammatory activities of N. sativa are considered the key factors accountable for its renoprotective and hepatoprotective effects.^[13] In spite of association between N. sativa and its renoprotective activity, there is no clinical study reported in patients with diabetic nephropathy. N. sativa has been used in diabetic and hypertensive patients previously. Therefore, the aim of this study was to assess the efficacy and safety of N. sativa oil supplementation in patients of diabetic nephropathy.

Materials and Methods

This prospective comparative study was conducted in patients of CKD due to diabetic nephropathy attending a renal clinic or admitted in inpatient department of a tertiary care center of North India from March 2014 to March 2015. The study was carried out in accordance with the Declaration of Helsinki (1964) and its revised form (2008). It was a prospective, randomized, parallel group, and open-label study which was approved by the Institutional Ethics Committee. This study is also enlisted with Clinical Trials Registry-India (CTRI) with a registration number CTRI/2015/01/005371. All the patients gave written and informed consent voluntary for the study. The diagnosis of CKD due to diabetic nephropathy was made on the basis of detailed medical history, physical examination, and investigations (blood glucose level and kidney function test).

Patients with CKD (Stage 3 and 4) due to diabetic nephropathy aged 20-60 years, either sex were included in the study. Pregnant females, patients on dialysis, terminally sick and immunocompromised, or patients having severe renal pathology such as malignancy were excluded from the study.

Out of 68 evaluated patients, 63 patients completed the study. Five patients [3 of Group 1 (control) and 2 of Group 2 (test)] failed to complete the study. Included patients were randomized into two groups with the help of random allocation software in a ratio of 1:1. After final diagnosis, applying exclusion and inclusion criteria, patients were enrolled in the study. Patients of Group 1 (Control) received conservative management (insulin, torsemide, telmisartan, iron, calcium, Vitamin D3, and erythropoietin) of diabetic nephropathy, whereas patients of Group 2 (test) received conservative management along with N. sativa oil (2.5 mL, per orally, once daily) ([Figure 1]). Both groups received treatment for 12 weeks. N. sativa oil of 100% purity was used in the study which was commercially available and purchased from the local market under the brand name "Kalonji oil" from Mohammedia Products, Hyderabad, India (a GMP certified company).

Figure 1. Shows recruitment, allocation, and follow-up of participants.

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All the enrolled patients were regularly followed up, and blood glucose level, kidney function test, hemogram, and serum electrolytes were done at 0, 6, and 12 weeks of treatment.

All adverse drug events detected by the investigator or reported by the patients were recorded on standard adverse drug reaction (ADR) reporting form of Central Drugs Standard Control Organisation at each visit. Naranjo Scale^[14] and Modified Hartwig and Siegel Scale^[15] were used for causality and severity assessment, respectively. A physical examination including assessment of vital signs was done at the start of the study and on following visits. Additional routine laboratory tests such as liver function test, electrocardiogram, and chest X-ray were performed whenever necessary.

Statistical Analysis

The values were expressed as a mean ± standard deviation. Statistical significance between pre- and post-treatment values in each group was calculated using Student's paired t test, whereas statistical significance between the groups was calculated with the help of unpaired t-test. P <0.05 was considered statistically significant. The data were analyzed with the help of Statistical Package for the Social Sciences (SPSS) software version 20.0 (SPSS Inc, Chicago, IL, USA).

Results

Group 1 included 31 patients with a mean age of 48.09 years (range 20-60 years), whereas Group 2 included 32 patients with a mean age of 53.27 years (range 20-60 years). The distribution of patients was almost similar among the groups. There was neither mortality nor need for dialysis in either group during the follow-up period. Eighteen patients were in CKD Stage 3 (11 and 7 in Group 1 and 2, respectively) and 45 patients in CKD stage 4 (20 and 25 in Group 1 and 2, respectively).

The signs and symptoms at the start of the treatment were similar in the two groups and consisted of anorexia, weakness, nausea, vomiting, weight loss, pruritus, edema, oliguria, and anemia. The clinical features improved gradually and progressively in both the groups after 12 weeks of treatment, but this was more apparent in N. sativa oil-treated group.

Various biochemical parameters and clinical features were improved gradually and progresssively in both the groups of diabetic nephropathy, but N. sativa oil-treated group (Group 2) showed a greater improvement. Both the groups showed a significant increase (P <0.001) in hemoglobin level with Group 2 also showing significant change (P <0.05) in comparison to Group 1. Blood urea was decreased in both groups, but the change was significant (P <0.001) in Group 2 only after 12 weeks of treatment. Serum creatinine decreased significantly (P <0.001) in Group 2. Furthermore, Group 2 showed a significant change (P <0.05) in comparison to Group 1 at 12 weeks. Fasting blood glucose was decreased significantly in Group 1 (P <0.05) and Group 2 (P <0.001). The change in postprandial blood glucose was also significant in Group 1 (P <0.01) and Group 2 (P <0.001), but these improvements in blood glucose were more marked in the N. sativa oiltreated group (Group 2). Total urinary volume was improved significantly (P <0.001) in both groups, but it was more prominent in Group 2 after 12 weeks of treatment. There was a significant rise in total urinary protein level in Group 1 (P <0.05) and Group 2 (P <0.001), and Group 2 also showed a significant change (P <0.01) compare to Group 1 at the end of the study. GFR was significantly improved in Group 2 (P <0.001), and this change was also significant (P <0.01) in comparison to Group 1 at 12 weeks. Serum electrolytes were improved but within a normal physiological range in both the groups ([Table 1]).

Table 1. Shows hemoglobin percent, renal function test, blood glucose level, and serum electrolytes in
control (Group 1) and test (Group 2) groups before and after 12 weeks of treatment.

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According to Modified Hartwig and Siegel Scale, the ADRs were mild (no hospitalization, no change of therapy, and no additional treatment) in the test group. No adverse event was of acute onset (within 60 min). On Naranjo Scale, the ADRs were possible (Score = 1-4) in two cases and probable (Score = 5-8) in one case with Group 2 ([Table 2]).

Table 2. Shows ADRs in test group.

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Discussion

Conservative management can play a key role to obviate CKD and to avert its progression toward ESRD. It delays the progressive decline of renal functions in diabetic nephropathy and offers only symptomatic relief. Hence, novel modalities of treatment are being explored which can halt injury to nephron, delay the progress of ESRD from diabetic nephropathy, and is cost effective. Due to steep increase in the prevalence of DM globally, more and more patients are suffering from diabetic nephropathy as a major cause of CKD. In India, CKD due to diabetic nephropathy is a major burden for both economy and health. In India, more than 100,000 new patients need RRT per annum.^[16] Only 10% of Indian ESRD patients receive any form of RRT due to inadequate resources and high cost. The cost of continuous ambulatory peritoneal dialysis is $600 per month, whereas hemodialysis costs $300. The cost of renal transplant is $8900 in the 1^st year, which decreases later to $3000 per annum. Among the RRT options, renal transplant is the preferred choice for being economical and offers improved quality of life, but still, only a fraction of Indians suffering from CKD of various etiologies can afford it.^[16]

The results of the present clinical study revealed that N. sativa oil enhanced the glycemic control and improved renal functions in patients with diabetic nephropathy. It has a strong antidiabetic property established by previous clinical studies.^{[17] ,[18]} This property is thought to be due to N. sativa oil's effect on reducing peripheral insulin resistance and elevating β-cell function.^[18] N. sativa supplementation improves renal and hepatic functions along with glucose homeostasis in patients with diabetic nephropathy.^[7] CKD and cardiovascular disorders are characterized by systemic inflammation and raised inflammatory markers. N. sativa and honey mixture decreased the levels of inflammatory markers and improved lipid profile.^[19] Another study also proved that N. sativa supplementation was useful in the treatment of metabolic syndrome. Blood sugar, blood pressure, total cholesterol, and triglyceride levels were decreased. Hence, it might be useful in CKD due to prolonged and uncontrolled diabetes and hypertension.^[20] Thymoquinone, the main active constituent of N. sativa oil, reduces the serum levels of inflammatory makers such as tumor necrosis factor-α and interleukin-1.^[21] It has a strong antioxidant property.^[22] The strong antioxidant and anti-inflammatory activities of N. sativa are considered the key factors for its nephroprotective effect.^[10] Due to its strong antidiabetic, antioxidant, anti-inflammatory, nephroprotective, and antihypertensive activity, N. sativa oil can be used as a natural adjuvant in the management of diabetic nephropathy.

In our study, N. sativa oil at the dose of 2.5 mL (per. orally, once daily) showed beneficial effects in Stage 3 and 4 of CKD due to diabetic nephropathy.

The results in our study are in congruence with those reported previously. Hence, conservative management along with N. sativa oil supplementation produces improvement in biochemical parameters as well as clinical features and safe in patients of diabetic nephropathy. Further studies will help to better understand the role of N. sativa in improving renal functions. Thus, we suggest that molecular level studies are needed to confirm its broad-spectrum effects not only on diabetic nephropathy but also on various diseases, in which N. sativa is traditionally used as palliative to cure these diseases.

Conclusion

N. sativa oil has the potential to be used as a natural adjuvant to conservative treatment in the management of diabetic nephropathy. As N. sativa has very low cost and side effects, the cost-benefit ratio will be in favor of using it, if its usefulness is proved by further studies. Therefore, add-on therapy of N. sativa oil boosted the therapeutic advantage of conservative management in patients of diabetic nephropathy.

Acknowledgment

This research work received no specific fund from any agency in the public, commercial, or not-for-profit sectors.

Conflict of interest: None declared.

References

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Correspondence Address:
Zafar Masood Ansari
Department of Pharmacology, J. N. Medical College and Hospital, Aligarh Muslim University, Aligarh, Uttar Pradesh
India