Single blind placebo-controlled study on hypolipidemic potential of drugs

Complications associated with high serum cholesterol levels include hypertension, CCF, cardiac arrhythmias, and cardiac arrest. To compare hypolipidemic potential of herb nigella sativa with allopathy-related hypolipidemic agent Fenofibrate, we conducted this research. It was single blind placebo-controlled study conducted at Ghurki trust teaching hospital, Lahore from February 2017 to July 2017. 75 diagnosed secondary hyperlipidemic patients were selected with age range from 20 to 70 years. Patients suffering from hypothyroidism, diabetes mellitus, any gastrointestinal upset, renal impairment, and any hepatic or cardiac disease.

Grouping: All patients were divided in three groups (group-A, group-B, group-C), 25 in each group. The study period was eight weeks. Twenty five patients of group-A were advised to take two grams of Kalonji, twice daily. Twenty five patients of group-B were advised to take Fenofibrate 40 mg tablets, BD ie; one after breakfast and one after dinner. Twenty five patients were provided placebo capsules, (containing grinded sorghum), taking one capsule after breakfast and another before going to bed. All participants were advised to take these medicines for eight weeks.

Method: Serum LDL-cholesterol was calculated by Friedwald formula1 (LDL-Cholesterol = Total Cholesterol-(Triglycerides/5 +HDL-Cholesterol). Data were expressed as the mean ± SD and “t” test was applied to determine statistical significance as the difference. A probability value of <0.05 was considered as non-significancant and P<0.001 was considered as highly significant change in the results when pre and post-treatment values were compared. After 8 weeks when results were compiled and analyzed statistically, it was observed that Kalonji reduced total cholesterol (TC), triglycerides (TG), and LDL-cholesterol highly significantly. HDL-cholesterol was increased in this group significantly with p-value <0.01. Fenofibrate decreased TC, TG, and LDL-cholesterol highly significantly with p-value <0.001, while increase in HDL-cholesterol was significant with p-value <0.01.

Conclusion: It was concluded from this study that hypolipidemic potential of herbal medication NIGELLA SATIVA is comparably same as hypolipidemic potential of allopathy related drug FENOFIBRATE when given in large amount (ie; 4 grams daily) for specific time.

Introduction

Hyperlipidemia (also known as high cholesterol) refers to several disorders that can result in too much fat (lipids) in the blood. These lipids can enter the walls of the arteries and increase the risk for developing hardening of the arteries, which could cause heart disease or stroke. Hyperlipidemia can be controlled with lifestyle changes and medication. Baptist Health is known for advanced, superior care for patients with heart conditions and the diagnosis, treatment and management of hyperlipidemia. You will appreciate timely appointments and a professional, friendly atmosphere where we take time to listen to your concerns. At Baptist Health, you have access to the region’s most comprehensive, multidisciplinary team of specialists and innovative therapies, including many available only through specialized clinical trials. In every way, we work to demonstrate the utmost in excellent care to those who trust us with their health. Hyperlipidemia is an umbrella term for those conditions characterized by an excessive amount of fats or lipids in the blood. From the practical point of view, for most patients hyperlipidemia is just the medical term for high cholesterol [1]. Conventional medicine has long advocated: high cholesterol causes heart disease – which represents the biggest killer in advanced countries. This has given rise to an entire industry of low-fat food products as well as cholesterol-lowering drugs, which are among the most widely prescribed medicines in the entire world! Unfortunately for this businesses, the connection is controversial at its best – and at worst, there’s no connection at all! In fact, in biological medicine we see both: the problem and the solution differently! Hyperlipidemia is essentially a disturbance of the body’s ability to metabolize fats. Conventional medicine describes the condition as an epidemic and thus an alarming danger for today’s society, and prescribes for almost every sufferer a category of drugs known as statins, which are now routinely given to men in the USA as a preventative measure – we have to know: they don’t even have high cholesterol! Free radicle formation in human body is normal, but there are chances of development of atherosclerotic plaques if these free radicles are interacted with high plasma lipids [2]. Atherosclerotic plaques are stuck with endothelial layer of coronary arteries leading to development of coronary artery disease (CAD) [3]. Hypertension, congestive cardiac failure (CCF), cardiac arrest, and cardiac arrhythmia are consequences of CAD [4].One of the factors causing CAD is abnormal plasma lipid levels [5]. For prevention of CAD, either blood lipids must be at normal levels (by administration of hypolipidemic drugs) or free radicle formation must be reduced (by use of antioxidant medications) [6]. In allopathy niacin, statins, fibrates and psyllium are used as hypolipidemic agents. Vitamin C, vitamin E, adenosine, lactoferrin and carotenoids are used as antioxidant drugs, which also reduce risk for developing CAD [7]. It is well known and established fact that Fenofibrate causes activation of peroxisome proliferator activated receptor α (PPARα), leading to increased lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of apoprotein C-III, which inhibits lipoprotein lipase [8]. This phenomenon will ultimately reduce formation of TG, and VLDL. Nigella sativa or Kalonji is being used as medicinal herb since pre-historical times. It contains carvacrol, nigellicine, polyunsaturated fatty acids, alphahederin, thymoquinone, mucilage, sterols, and migellamine [9]. Kalonji affects HMG-Co-A reductase leading to decreased formation of cholesterol in hepatocytes. This herb contain thymoquinone which inhibits lipid peroxidation in liposomes [10,11]. Alphahederin, thymoquinone, mucilage, sterols, and migellamine present in kalonji scavenge superoxide anion and hydroxyl radicles leading to decreased chances of LDL oxidation, and development of coronary artery disease [10-12].

Patients and Methods

Type of study

The research work was single blind placebo-controlled, conducted at Ghurki trust teaching Hospital, Lahore from February 2017 to July 2017.

Patients & Consent: Seventy five hyperlipidemic patients were selected for research work. Written consent was taken from all patients.

Inclusion Criteria: 75 diagnosed secondary hyperlipidemic patients were selected with age range from 20 to 70 years.

Exclusion Criteria: Exclusion criteria were hypothyroidism, diabetes mellitus, alcohol addictive patients, peptic ulcer, any gastrointestinal upset, renal impairment, and any hepatic or cardiac problem. GROUPING: All patients were divided in three groups (group-A, group-B, group-C), 25 in each group. Their baseline experimental data was taken and filed in specifically designed Performa, at start of taking medicine, like lipid profile, blood pressure and pulse rate. The study period was eight weeks. Twenty five patients of group-A were advised to take two grams of Kalonji, twice daily. Twenty five patients of group-B were advised to take Fenofibrate 40 mg tablets, BD ie; one after breakfast and one after dinner. Twenty five patients were provided placebo capsules, (containing grinded sorghum), taking one capsule after breakfast and another before going to bed. All participants were advised to take these medicines for eight weeks. They were also advised for 20 minutes brisk walk at morning or evening time. Patients were called every 2 weeks for follow up to check blood pressure, weight, pulse rate etc. Drug compliance to the regimen was monitored by interview and counseling at each clinical visits.

Method: Serum LDL-cholesterol was calculated by Friedwald formula13 (LDL-Cholesterol = Total Cholesterol-(Triglycerides/5 +HDL-Cholesterol).

Biostatistical Analysis: Data were expressed as the mean ± SD and “t” test was applied to determine statistical significance as the difference. A probability value of <0.05 was considered as non-significancant and P<0.001 was considered as highly significant change in the results when pre and post-treatment values were compared.

Results

When results were compiled and statistically analyzed by using SPSS, it was observed that Nigella sativa and fenofibrate decreased total-cholesterol, LDL-cholesterol, triglycerides highly significantly (p-value <0.001) and increased HDL-cholesterol significantly (p-value <0.01) as compared to placebo treatment. Results are summarized as:

Effects of KALONJI on lipid profile of 25 hyperlipidemic patients: TC at day-0 was 231.21±1.12 mg/dl which reduced to 200.90±3.11 mg/dl. The overall change in the parameter was 30.31 (P-value= <0.001). TG at day-0 was 178.90±3.01 mg/dl which reduced to 141.10±1.01 mg/dl. Change was 37.80 (P-value= <0.001). LDL-C at day-0 was 191.14±3.45 mg/dl which reduced to 159.40±2.98 mg/dl. Change was 31.74 (P-value= <0.01). HDL-C at day-0 was: 36.48±2.11 mg/dl which increased to 41.17±1.88 mg/dl. Incraese in the parameter was 4.69 (p-value = <0.01)

Effects of FENOFIBRATE on 25 hyperlipidemic patients: TC at day-0 was 240.92±2.21 mg/dl which reduced to 197.31±1.00 mg/dl. In mg/dl this change was 43.61 with P-value= <0.001. TG at day-0 was 204.31±1.26 mg/dl which reduced to 170.14±2.93 mg/dl. Reduction in mg/dl it was 34.17 (P-value= <0.001). LDL-C at day-0 was 197.77±3.91 mg/dl which reduced to 159.62±2.20 mg/dl. Over all change was 38.15 with P-value= <0.001. HDL-C at day-0 was 32.97±3.10 mg/dl which increased to 40.45±2.22 mg/dl. Increased in mg/dl it was 7.48 mg/l. P-value= <0.01.

Placebo Effects on 25 hyperlipidemic patients: TC at day-0 was 213.11±2.32 mg/dl which reduced to 210.10±2.91 mg/dl. P-value= >0.05. TG at day-0 was 170.00±3.01 mg/dl which reduced to 161.70±3.91 mg/dl with P-value= >0.05. LDL-C at day-0 was 163.104±1.45 mg/dl which reduced to 159.40±1.77 mg/dl (P-value= >0.05). HDL-C at day-0 was 31.12±1.01 mg/dl which increased to 31.69±2.00 mg/dl. P-value= >0.05

Discussion

If hyperlipidemia is suspected, we perform a physical examination and ask questions about symptoms. We then use advanced diagnostic procedures and technology to effectively diagnose, inform treatment and carefully monitor the condition. Common diagnostic procedures can include: Blood test: Blood tests check the levels of certain fats, cholesterol, sugar and protein in the blood that could indicate heart conditions. Nigella sativa and Fibrates are very good hypolipidemic agents which can be used alone or in combination. Changes in all parameters of 25 hyperlipidemic patients lipid profile (i.e.; serum cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol) were highly significant in two drug groups when they compared with placebo-controlled group, except change in serum total cholesterol in Nigella sativa group, which is significant with probability value <0.01. Our results regarding lipid lowering effects of Nigella sativa match with results of research work conducted by Fiju G et al14 match with research study conducted by , who did see reduction of serum total cholesterol 13.01 %, triglycerides 9.1 % and 17.89 %. HDL-cholesterol increased 23.62 %. Merghatt V et al15 proved highly significant changes in lipid parameters of hyperlipidemic rats when they used one teaspoon of Nigella sativa oil twice daily for 3 weeks. These results match with results of our work. Jimiyath CT et al 16 conducted research on hyperlipidemic patients and proved 12.76, 8 %, 15 % decrese in serum cholesterol, triglycerides, and LDL-cholesterol in 19 days when they used kalongi oil. They have explained marked protective action of Nigella sativa against ischemic reperfusion-induced gastric mucosal lesions, an effect that was mediated by suppression in the level of lipid peroxide and lactic dehydrogenase and an increase in those in glutathione and superoxide dismutase. The results of research work conducted by Rolkerr F17 do not match with our results who observed 10.11 %, 12.51 %, 12.45 % reduction in total cholesterol, triglycerides, and LDL-cholesterol when they used kalongi oil for two months in hyperlipidemic patients. This difference in results may be due to large difference in sample size of tested group individuals. Turnorj F, et al. 18 observed much higher quantity of reduction in LDL-Cholesterol (-30.11 %) when they used two spoons of Nigella sativa in 1000 hyperlipidemic patients for the period of 6 months. This difference is surely due to large sample size in their study and duration of research study. Our results are in contrast with research work results of Erovha E et al19 who observed (11 %) increase in HDL-cholesterol with use of Kalonji for 4 weeks in 19 patients suffering from hyperlipidemia. Qulath C et al20 describes more than six mechanism by which Kalonji affects blood lipids, Enterohepatic circulation inhibition is one of them. Askalth VV et al21 have emphasized not to combine seeds of kalonji with vitamin D and E, as absorption of these vitamins may be decreased leading to iatrogenic effects like SUPERINFECTIONS. Parjhat K et al 22, and Soghan MM, et al. 23 observed same effects of Kalonji as ours. Results of study by Rullt FD et al [24], and Wksort VB et al [25] support our results. In our results Fenofibrate decreased TC 43.61 mg/dl, TG 34.17 mg/dl, LDL-C 38.15 mg/dl, and increased HDL-C 7.48 mg/dl.

We acknowledge hospital management for all types of help to conduct this research.

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