Is Nigella sativa an Effective Bodyweight Lowering Agent and a Mitigator of Obesity Risk? A Literature Review

Introduction

Obesity is a major health-threatening condition. It affects about 1.9 billion people in the year 2016 worldwide, and its incidence continues to increase exponentially. The prevalence of overweight and obesity has increased by four folds from the year 1975 to the year 2016 in both adults and children, according to the World Health Organization report.¹ The main concern about the increasing prevalence of obesity is that obesity is a risk factor for all-cause mortality and a predisposing factor for diabetes mellitus, hypertension, ischemic heart disease, stroke, and cancer.² One of the proposed theories for the explanation of the high incidence of obesity is the contemporary modifications of the modern lifestyle; people tend to rely in their nourishment on the highly processed food, which is rich in sugar and fat, and ignore the healthy ingredients of nature, which provide fibers, vitamins, and antioxidants.³ Many natural products, which were frequently consumed by human in old ages, are found to be rich in antioxidants and provide numerous protective effects against multiple diseases, among which are the black seeds.⁴ The black seed is a medicinal plant known generically as Nigella sativa Linn and it belongs to the family of Ranunculaceae. It is composed of fixed oil, proteins, alkaloids, saponin and essential oil. The main constituents of the essential oil are thymoquinone in addition to other fatty acids, such as palmitoleic acid, palmitic acid, arachic acid, and linoleic acid.⁵ It is commonly used as a food herb and flavoring in the countries of the Middle East, India, and Iran. Furthermore, it is considered a natural remedy for multiple purposes, such as cough, asthma, stomach ache, vomiting, allergy, and eczema.⁶ Currently, the therapeutic effects of Nigella sativa (NS) are supported by accumulating evidence in the literature from extensive research work.⁷ Both experimental and clinical studies showed reproducible preferable effects of long-term supplementation of NS such as antioxidation and anti-inflammation.⁸ Not only this but also the intake of NS culminates in specific and favorable modulations of cardiac structure and function,^9,10 vascular growth and regeneration,^11,12 and immunoregulatory effects.¹³ NS in multiple studies demonstrated favorable modifications of the glucose and lipid metabolism in diabetic patients.¹⁴ However, less attention was given to the direct effect of NS on bodyweight and BMI. Few systematic reviews and meta-analyses are available in the literature, which discussed the effect of NS as an anti-obesity agent in human clinical trials. However, these systematic reviews included either numerous metabolic parameters in the discussion, missed some negative studies, excluded animal studies, or included multiple herbs besides NS.^15–17 On the other hand, these reviews did not discuss the mechanisms of the anti-obesity effect of NS, particularly in regard to the bodyweight lowering effect. Therefore, in the present review, we aim to analyse and evaluate the effect of NS supplementation on the bodyweight and anthropometric values in both human and animal studies. Moreover, we aim to explore the reported mechanisms of NS weight-lowering effect if present.

Methods

We searched the following databases: PubMed and Web of Science using the following terms: Nigella sativa or black seed and bodyweight, or anthropometric measures, waist-circumference, or appetite with no time restriction. PubMed search first yielded 170 articles and Web of Science yielded 281 articles. We excluded reviews and included only research articles, clinical trials, systematic reviews and meta-analyses. After meticulous review, we included studies that used NS supplementation as a crude substance, either powdered, oil or extract. Studies that used thymoquinone only – which is the active ingredient of NS– were excluded. We also excluded the studies that used NS in combination with other drugs or other natural products and did not show the sole effect of NS in any of the tested groups. The selected clinical trials and experimental studies were then evaluated using CONSORT checklist for herbal medicine and ARRIVE 2, respectively. The final number of included studies was 14 clinical trials, and 5 animal experimental studies (Figure 1).

Figure 1 Flow diagram for the process of article selection. Abbreviations: NS, Nigella sativa; WoS, Web of science.

Results

We have reviewed 14 clinical trials and 5 animal studies for understanding and evaluating the effect of long-term administration of NS on bodyweight. Most of the clinical studies include both male and female participants (8 studies), while 5 includes women only and one study includes men only. The targeted populations were diverse but all shared metabolic derangements such as diabetic patients, prediabetics, patients with autoimmune hypothyroidism, patients with non-alcoholic fatty liver or obese and overweight individuals. All the included studies employed an oral administration of NS capsules that either contain NS-powder or oil. Ten out of the 14 clinical studies revealed significant effect of NS on bodyweight, BMI, and waist circumference, and the effect was more consistent with the use of NS-oil (Table 1). The experimental studies were mostly on rats (4 studies) and one on mice. Two of the animal studies were on male rats, one used both male and female rats, one used ovariectomised female rats, and one used female mice. The preparations of NS used in the experimental studies were either NS-oil, petroleum ether extract, or aqueous extract of NS-powder. The duration of NS feeding ranges from 6 to 12 weeks. Four out of 5 animal studies showed a significant effect of NS intake on the weight gain of the growing animals (Table 2).

Table 1 Clinical Trials That Tested the Effect of Nigella sativa (NS) on the Anthropometric Data. The Studies are Presented in a Descending Chronological Order

Table 2 Experimental Studies That Tested the Effect of Nigella sativa (NS) on Bodyweight

The mechanisms of the weight reduction effect of NS were investigated by some authors, and the proposed mechanisms include induction of anorexia, reduction of intestinal glucose absorption, reduction of insulin secretion and increase in adiponectin level (Table 3).

Table 3 Clinical Trials and Experimental Studies That Explore the Mechanisms of Nigella sativa (NS) Effect on Bodyweight and Anthropometric Data

Discussion

In this review, we aimed to evaluate the bodyweight reduction effect of NS and explore the possible underlying mechanisms of this effect. Most of the analysed studies, whether clinical trials or experimental studies, revealed that NS administration in the form of NS-oil or powdered capsules for 6–12 weeks can culminate in bodyweight reduction as well as enhancement of BMI, waist, and hip circumference. We observed that studies that utilized NS-oil in doses of 1–3g/day for 6–12 weeks showed more pronounced effect on the bodyweight and the other anthropometric parameters than those which employed NS-powder of equivalent doses. This might be related to the difference in the composition of these two preparations for NS. NS-oil has higher concentrations of fatty acids, such as linoleic acid, linolenic acid, and palmitic acid in addition to a higher concentration of thymoquinone.^38,39 Dalle et al demonstrated different composition and concentration of multiple specific active compounds, such as thymoquinone, multiple fatty acids, catechin, rutin and gallic acid when they used different methods and solvents for the extraction of NS.⁵ Therefore, higher NS-powder or extract doses might be needed to induce the bodyweight-lowering effect of NS, and this can explain why Al Asoom³³ who utilized 800 mg/Kg dose of powdered NS failed to demonstrate weight lowering effect in rats, while Meddah et al³⁵ who adopted 2g/Kg for rats showed a significant reduction of rat weight gain. In addition, the responsiveness of the targeted subjects in each of the included clinical trials might also be different, because those subjects suffer from different aspects of metabolic derangements; Some are healthy obese and overweight, but others are diabetics or patients with fatty liver or Hashimoto’s hypothyroidism.

Furthermore, we believe that the weight-lowering effect of NS is a positive therapeutic effect and not a sign of toxicity based on the findings of multiple studies that showed an improvement of liver enzymes when diabetic patients or patients of fatty liver were treated by NS.^23,24 In addition, Le et al compared the acute effect of NS to Dimethyl sulfoxide (DMSO) on isolated hepatocytes and found no toxic effect of NS.³⁶ Furthermore, the acute administration of high doses of NS-oil whether orally or intraperitoneally up to 28.8 mL/kg of bodyweight showed no signs of toxicity. Similarly, the oral administration of 6g/kg methanol extract of NS for 14 days showed no change in the activity of hepatic enzymes in histological preparation. NS-oil or thymoquinone exerted protective effect against the toxicity induced by cyclophosphamide.⁴⁰ Thymoquinone also demonstrated in multiple studies a protective effect against the toxicity of chemotherapy in multiple types of cancer.⁴¹

Most of the analysed studies in this review reported the statistical significance and the safety of the weight-lowering effect of NS. However, one might argue the clinical significance of NS weight-lowering effect, but we can further illustrate that NS-weight lowering effect is also clinically significant based on the relatively large effect size of 0.6 for NS bodyweight-lowering and 0.4 for waist circumference reduction as reported by Safi et al¹⁸ as well as the frequently and repeatedly demonstrated metabolic effect of NS on lowering blood lipids including triglycerides, total cholesterol, LDL, blood glucose and HbA1C and the positive influence on HDL and insulin resistance.^23,29 In the study performed by Mostafa et al,¹⁹ NS administration for 12 weeks was superior to metformin or diet restriction in modifying total cholesterol, LDL, and triglycerides. Moreover, the clinical significance of NS-weight lowering effect can also be augmented by lifestyle modifications such as caloric restriction and exercise training because evidence has been shown that the combined NS administration and lifestyle changes yielded better effect than each of these interventions separately.^27,42

Mechanisms of NS-Induced Bodyweight Reduction

Most of the retrieved literature reflecting the weight reduction effect of NS lacks the explanation and the evidence of the exact mechanism of this effect. Some studies proposed an anorexic effect of NS and aimed to estimate the food intake or appetite modifications. Mahdavi et al,²⁶ Farhangi et al,²⁵ and Safi et al¹⁸ failed to demonstrate any difference in the total caloric intake of their NS-treated subjects compared to the control group, albeit Safi et al showed a reduction in appetite sensation using a visual scale of appetite before and after meals. On the other hand, Le et al³⁶ showed a significant reduction in food intake by rats fed with NS compared to control rats. Despite these efforts to estimate the caloric intake or the changes in the appetite, there is a lack of exploration of the appetite regulation pathways and the influence of multiple peptides on the satiety and hunger centers of the hypothalamus.⁴³ Few studies only, such as Moustafa et al²³ and Le et al,³⁶ showed a reduction in insulin secretion, and Mahdavi et al³⁷ demonstrated an increase in adiponectin. However, more mediators and peptides in the pathway of appetite and energy balance need to be explored. Meddah et al³⁵ showed an in vitro dose-dependent inhibition of intestinal glucose transport by NS. Similarly, Dalli et al,⁵ using different methods for NS extraction, also demonstrated an inhibition of intestinal glucose absorption by three different preparations of NS with a range of inhibition equals to 24.82–60.12%.

Limitations

The current review might be limited by the number of databases that were explored for related literature. In addition, the populations studied in the included articles were diverse in multiple metabolic diseases that might skew the interpretation of the effect of NS on bodyweight in healthy obese and overweight subjects.

Conclusion

The current review showed that the administration of about 1–3 g/day of NS for 6–12 weeks can culminate in a reduction of the bodyweight and other anthropometric indices. It further showed the advancement in the NS-related research particularly in the field of metabolic derangement. About two decades ago, NS-reported studies focused mainly on the effect of NS on diabetic metabolic profiles such as hyperglycemia, HbA1c and insulin resistance. Later, the studies started to explore the possible prophylactic influence of NS through recruiting prediabetic and healthy obese and overweight individuals and reflect explicitly on the direct effect of NS on the bodyweight and anthropometric data as primary outcomes.

In this review, we found that NS-oil might be superior to other NS-preparations in regard to the weight-lowering effect, and the doses used in all the reported clinical and experimental studies are safe and provide positive metabolic modifications that can minimize the hazards of obesity such as lowering the lipid profile and liver enzymes.

Therefore, NS can be recommended for bodyweight reduction along with lifestyle modifications in the form of diet restriction and high physical activity. Nevertheless, identification of the best preparation of NS for the induction of the weight-lowering effect is needed as well as the identification of the main active ingredients responsible for this effect. Moreover, large prospective clinical trials are also required to explore the efficacy and safety of NS on bodyweight in different age groups, such as children and adolescents. Finally, experimental work that focused on unveiling the exact mechanisms of NS bodyweight-lowering effect is still needed, which might open new paths for extra-therapeutic applications of NS.