Primary & Secondary Hyperlipidemia: How to Treat? Volume 2 - Issue 2

Shah Murad*¹, Fasiha Fatima², Sana Tufail³, A Qudoos⁴, Seema⁵, Abdul Ghaffar⁶ and Jamila Shah⁷

• ¹Department of Pharmacology, Islamabad Medical & Dental College, Pakistan
• ²AP Biochemistry, KIMS Karachi, Pakistan
• ³Department of Pharmacology, Shaikhzaid Medical College, Pakistan
• ⁴Department of Pharmacology, HBS Medical and Dental College, Pakistan
• ⁵Department of Gynaecology, National Medical Centre, Pakistan
• ⁶CWO, Islamabad Medical and Dental College, Pakistan
• ⁷Department of Psychology, Bahria University, Pakistan

Received: December 02 2019;   Published: December 13, 2019

*Corresponding author: Shah Murad, Department of Pharmacology, Islamabad Medical & Dental College, Pakistan

DOI: 10.32474/ANOAJ.2019.02.000134

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Abstract

Highly altered Body Mass Index (BMI) and hypertension are independent and reversible determinants for coronary artery disease. Hypolipidemia can prevent hyperlipidemic patients to be victim of coronary artery disease. This study was conducted to compare hypolipidemic effects of Niacin and Jujube fruit in primary as well as secondary hyperlipidemic patients. Study was conducted from November 2015 to February 2016 at Jinnah Hospital Lahore, Pakistan. Sixty participants were enrolled of both gender male and female hyperlipidemic patients age range from 20 to 70 years. Written and explained consent was taken from all patients. They were divided in two groups. Group-I was advised to take two grams Niacin in divided doses for the period of two months. Group-II was advised to take 500 grams of fruit Jujube daily for the period of two months. Their baseline LDL and HDL cholesterol was determined by conventional method of measuring Lipid Profile. After two months therapy, their post treatment lipid profile was measured and mean values with ± SEM were analyzed biostatistically. Group-I which was on Niacin their LDL cholesterol decreased significantly and HDL cholesterol was increased significantly. In group-II patients LDL cholesterol was decreased significantly but HDL increase was not significant with p-value of >0.05. It was concluded from the research work that Niacin is potent in lowering LDL and increasing HDL cholesterol, while Jujube has significant effect as LDL cholesterol lowering agent, but it does not increase HDL cholesterol significantly.

Introduction

If used regularly, allopathy related hypolipidemic drugs are very effective for the treatment of primary or secondary hyperlipidemia. They do not only decrease the level of plasma lipids, but they do reduce risk of coronary artery disease leading to other problems concerned with vital organs of human body. Commonly hypolipidemic agents are used in prevention of ischemia, myocardial infarction, vascular diseases in periphery, congestive cardiac failure, cardiac arrhythmias [1]. Recommended medications for treatment of dyslipidemia include Statins, Fibric acids, Niacin, and Resins. But unfortunately, all these agents have potential to cause unwanted effects in human body making low compliance [2]. Vitamin B-3 which is also known as niacin when given in sufficient hypolipidemic doses i.e. more than two grams per day it causes partial inhibition of release of free fatty acids from adipose tissue, and increased lipoprotein lipase activity, which may increase the rate of Chylomicrons triglyceride removal from plasma. Niacin decreases the rate of hepatic synthesis of VLDL and LDL by formation of apoproteins (proteins carrying free lipids in plasma) which are integral part of low-density lipoprotein and very low-density lipoprotein’s structure [3]. Many of the herbs have been proved to reduce plasma lipids in human body. Jujubes or Ziziphus jujube, commonly called BAIR in urdu, punjabi, pothoharee, hazarvi, siraiki, and hindi languages in Pakistan and India. These jujubes have hypolipidemic, hypotensive as well as hypoglycemic effects [4]. Jujube fruit is flavorful and contain considerable amount of phenolic compounds like caffeic acid, chlorogenic acid, garlic acid, and protocatechuic acid [5]. These polyphenolic componds are capable of interacting with free radicals formed in human body in many biotransformatory reactions. This will decrease oxidative stress in human body. Hepatoprotective features of jujubes are proved in many research studies. Many researchers supported presence of biochemical compounds present in this fruit, which protect hepatocytes to be damaged by free radicals [6]. Some studies evaluated the effect of Jujubes fruit in controlling dyslipidemia in obese young hyperlipidemic patients. A placebo-controlled study trial on eighty-six obese hyperlipidemic young adults age range from 12 to 18 years proved its effects on plasma lipids, labeling this fruit as hypolipidemic. It was observed by researchers that fruit was well tolerated, tasty for the hyperlipidemic patients which normalized lipid profile parameters in these patients [7]. Effects of its hydro-alcoholic extract on peripheral blood vessels, monocytes, neutrophils and lymphocytes is proved in many phase-II and phase-III drug’s safety trials. Fruit reduced monocytes and neutrophils and increased lymphocytes [8]. Jujubes powder was formed by drying and grinding it then used in obese patients with high plasma lipid levels. It reduced all parameters of lipid profile except increase in high density lipoprotein cholesterol. In this research study fruit did not show any harmful effect on liver functions measured by alanine transaminase and aspartate transaminase [9].

Patients and Method

Study type/Duration/Place: This research work was parallel comparison of two medicinal agents conducted from November 2015 to February 2016.

a. Sample Size: Sixty hyperlipidemic patients were selected from Jinnah Hospital Lahore-Pakistan to compare hypolipidemic effects of Niacin and commonly used fruit in winter season in Pakistan i.e. Jujube (Bair in urdu).

b. Inclusion Criteria: Both male and female patients suffering from primary or secondary hyperlipidemia were selected. The age limit for patients was 20 to 70 years.

c. Exclusion Criteria: Alcoholic addictive patients, cigarette smokers, habitual to enjoy sedentary life, with impaired liver or renal functions were excluded from the research study.

d. Consent: Written/approved/well explained consent was taken from all participants.

e. Method: Baseline Lipid Profile was determined in Biochemistry lab of the Hospital. Serum cholesterol was estimated by enzymatic method using kit Cat. No: 303113050 by Eli Tech Diagnostic, France. Serum HDL-cholesterol was determined by using kit Cat No: 303210040 by Elli Tech Diagnostic, France. Chylomicrons, low density lipoprotein and very low-density lipoprotein are specially precipitated with phosphotungstic acid and magnesium ions can then be removed by centrifugation, while high density lipoproteins remain in the supernatant. Cholesterol included in this phase is measured by an enzymatic method. LDL-cholesterol was calculated according to Friedwald formula (3) i.e.; LDL= TC- (TG/5+ HDL-C).

f. Patients Grouping: Patients were divided in two groups, 30 patients in each group. Group-I was on Tab. Niacin 2 grams daily in three divided doses. Group-II was on Jujube 500 grams daily in three divided times to eat. They were advised to take this fruit for two months.

g. Statistical Analysis: Mean values ± SEM were taken for statistical analysis using SPSS version 26 (2015). Paired ‘t’ test was applied to get significance changes in parameters before and after treatment. P-value >0.05 was considered as nonsignificant change, p-value <0.01 was considered as significant and p-value <0.001 was considered as highly significant change in the tested parameter.

Results

With two months therapy by Niacin LDL-cholesterol in 27 hyperlipidemic patients reduced 29.2 mg/dl and HDL increase in this group was mg/dl. Three patients withdrew from the study work in this group due to non-compliance of Niacin i.e. it produced flushing, urticaria and heat perception. All these effects produced by Niacin were not its adverse effects, but it was production of prostaglandin D-2 which caused vasodilatation leading to these effects. In group-2 (n = 30) two months therapy by Jujubes reduced LDL-cholesterol from 198.82±2.17 mg/dl to 190.91±1.73 mg/dl, which is 7.9 mg/dl change in the parameter. HDL-cholesterol in this group increased from 38.6±2.19 mg/dl to 41.9±2.97 mg/dl, which is 3.3 mg/dl change in the parameter. Biostatistically it is nonsignificant change in the tested parameter of lipid profile (Table 1).

Discussion

When we study pathogenesis of atherosclerotic plaque formation in system circulation is simple to understand in hyperlipidemic patients. When there is too much concentration of plasma lipids, especially LDL-cholesterol, there are chances of LDL oxidation due to presence of free radicals, which make macrophages to attach with these oxidized LDL particles. This process is initiative step for development of atherogenesis, causing CAD. Hypolipidemic drugs decrease chances of LDL particles available for oxidation, so prevent CAD. Niacin is commonly used drug which inhibit lipoprotein lipase activity, so lesser formation of free fatty acids will be available which are main sources of TG-rich lipoproteins (VLDL) formation. Lesser amount of VLDL lead to lesser synthesis of LDL particles which are rich in cholesterol. In our results Niacin 2 grams daily intake for two months decreased LDL-cholesterol about 13.9 % which is highly significant changes. HDL-cholesterol in this group increased about 16.2 % which is again highly significant change. ZQ Zhu and W Cao [10,11] proved same results when they used 2 grams of Niacin in 66 hyperlipidemic patients, but [12] observed lesser effects of Niacin on HDL cholesterol, i.e. only 4.4 % increase in HDL cholesterol. [13] explained different mechanisms of hypolipidemic response of Nicotinic acid on persons with different genetic code. One of the favorable mechanisms for patients with CAD they described is fibrinolytic activity of Niacin. In our results Jujube fruit decreased LDL cholesterol is 7.9 mg/dl, which is significant change in the parameter. HDL cholesterol is not increased significantly in our results with p-value of >0.05. Tan H and Tripathi M [14,15] observed same reason of Jujube on LDL and HDL-cholesterol, which augment our results. Tschesche R [16] observed more effects of Jujube as we observed in low density lipoprotein cholesterol. Um S [17] proved that LDL cholesterol is much decreased as compared to our results. KB Kang [18] observed too less effects of Jujube fruit in 5 hyperlipidemic patients. This difference in two studies are obviously due to their small sample size, i.e. they tried herb only on five hyperlipidemic patients, while we tried in 30 hyperlipidemic patients.

Conclusion

After completion of the research work, it was concluded that Niacin has more potential to reduce LDL-cholesterol and increase HDL-cholesterol than flavorful fruit Jujubes. Jujubes has some potential to reduce LDL-cholesterol, but this fruit do not increase HDL-cholesterol when analyzed statistically.

References

1. Bruckert E, Labreuche J, Amarenco P (2010) Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis. Atherosclerosis 210(2): 353-361.
2. Jau FF, Lyme UI, Fauo KT, Panic ML (2010) Guidelines for Niacin Therapy for the Treatment of Elevated Lipoprotein a (Lpa). Thrombophelia 12(5): 222-227.
3. Duggal JK, Singh M, Attri N, Singh PP, Ahmed N, et al. (2010) Effect of niacin therapy on cardiovascular outcomes in patients with coronary artery disease. Journal of cardiovascular pharmacology and therapeutics 15(2): 158-166.
4. Reza Afrisham, Mohammad Aberomand, Mohammad Ali Ghaffari, Amir Siahpoosh, Mostafa Jamalan (2015) Inhibitory Effect of Heracleum persicum and Ziziphus jujuba on Activity of Alpha-Amylase. Journal of Botany Pp 1-8.
5. Anbarasi Balakrishnan, Parimala Devi Balasubramaniyam, Senthil Kumar Natesan (2012) Antipyretic Activity of Zizyphus jujuba lam Leaves. Journal of Advanced Scientific Research 3(3): 40-42.
6. Daneshmand F, Zare Zardini H, Tolueinia B, Hasani Z, Ghanbari T (2010) Crude Extract from Ziziphus Jujuba Fruits, a Weapon against Pediatric Infectious Disease. Iranian Journal of Pediatric Hematology Oncology 3(1): 216-221.
7. Louay Labban (2013) Effect of Zizyphus jujuba on serum lipid profile and some anthropometric measurements. Clinical Nutrition 1(3): 49-55.
8. Malik A, Kuliev ZA, Akhmedov Yu A, Vdovin AD, Abdullaev ND (1997) Proanthocyanidins of Ziziphus jujuba. Chemistry of Natural Compounds 33: 165-173.
9. Ganachari MS, Shiv Kumar, Bhat K G (2004) Effect of Ziziphus jujuba leaves extract on phagocytosis by human neutrophils. J Natural Rem 4(1): 47-51.
10. Zhu ZQ, Chen JW, Hu TX, Zhu DY (2011) Niacin affects HDL-cholesterol and LDL cholesterol. Phytochemistry 22: 1667-72.
11. W Cao BN, Wang H, Gao MT, Fan JB (2011) Vitamin B-3 or Niacin for prevention of coronary artery disease. Plant Pharmacol 61: 703-7.
12. WB Yao, H Wang, Peko L, GC Zhou, Lama Cai (2011) Niacin is important for healthy heart. Science of Pharmacol 10(1): 122-7.
13. Hung PJ, Wang J, Li LT, Dan Y (2011) Vitamin B-3 for Atherosclerosis and its prevention. J Food Chem 10(1): 21-4.
14. Tan NH, Fan HG, Zhou J (2007) Jujube Is Hypolipidemic Herb. Chem. Rev 106:840-45.
15. Tripathi M, Pandey MB, Jha RN, Pandey VB, Tripathi PN et al. (2001) Cyclopeptide alkaloids from Zizyphus jujuba. Fitoterapia 72(5): 507-510.
16. Tschesche R, Khokhar I, Wilhelm H, Eckhardt G, Jubanine A, et al. (2010) Alkaloids from Ziziphus jujuba have antioxidant characteristics. Phytochemistry 15: 541-2.
17. Um S, Choi TJ, Kim H, Kim BY, Kim SH, et al. (2013) Hypolipidemic effects of Z Jujube. J Org Chem 78: 321-29.
18. KB Kang, JJ You, LL mumpycal, ST Simon Z (2014) Jujube is effective to reduce oxidation burden. Phytochemistry 22(4): 222-5.