Ameliorating effect of coenzyme Q10, riboflavin and niacin in tamoxifen-treated postmenopausal breast cancer patients with special reference to lipids and lipoproteins

https://doi.org/10.1016/j.clinbiochem.2007.02.003Get rights and content

Abstract

Objectives:

Tamoxifen (TAM), a non-steroidal anti-estrogen that is widely used in adjuvant therapy for all stages of breast carcinomas and in chemoprevention of high-risk group. The hepatic estrogenic effect of TAM induces hypertriglyceridemia by reduced activity of lipolytic enzymes (LPL) on triglycerides. Coenzyme Q10 (Co Q10), riboflavin and niacin are proved to be potent antioxidant and protective agents against many diseases including cancer and cardiovascular diseases (CVD). In this context, the objective of the study is to find the effect of the combined modality of Co Q10 (100 mg), riboflavin (10 mg) and niacin (50 mg) with TAM (10 mg twice a day) on serum lipids and lipoprotein levels in postmenopausal women with breast cancer.

Design and methods:

The vitamin supplementation with tamoxifen was given for a period of 90 days. Blood samples were collected at the base line, 45th and 90th day during the course of treatment. Plasma total cholesterol (TC), free cholesterol (FC), ester cholesterol (EC), phospholipids (PL), triglycerides (TGL), free fatty acids (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and very low density cholesterol (VLDL-C) were estimated in 78 untreated, only TAM-treated and combinatorialy treated group along with 46 age- and sex-matched controls.

Results:

Serum TGL and VLDL-C (p < 0.001) were found to be significantly elevated and LDL-C (p < 0.01), significantly reduced among TAM-treated patients as compared to the untreated breast cancer subjects. All the lipids and lipoprotein levels were found to be significantly altered in the untreated breast cancer patients when compared to their normal counterparts. All the lipid and lipoprotein abnormalities were reverted back to near normal levels on 90 days of treatment on combinatorial therapy.

Conclusion:

The study figures the altered lipid and lipoprotein levels in the untreated and TAM-treated breast cancer patients. On combination therapy with Co Q10, riboflavin and niacin, it counteracts the tamoxifen-induced hyperlipidemia to normal levels.

Introduction

Breast cancer is the most common malignancy comprising 18% of all cancers in women [1]. The introduction of tamoxifen (TAM), a non-steroidal anti-estrogen in the early 1970s represented a landmark in the treatment of breast cancer [2]. Since 1990, death rates from breast cancer have decreased by over 25%, and this is at least partly due to adjuvant treatment with TAM [3]. Apart from its use in adjuvant treatment protocol, TAM has also shown to reduce the risk of contralateral breast cancers in carriers of BRCA 1 or BRCA 2 genes and in advance metastatic breast cancers [4], [5]. The anti-tumor activity of TAM is largely believed to be due to its occupation of intracellular estrogen receptor sites in the target tissues and blocking the action of biologically active estrogen and estradiol [6].

Tamoxifen's effect on plasma lipids and lipoproteins, one of our earlier studies along with others has indicated that TAM increases VLDL-C levels resulting in hypertriglyceridemia [7], [8]. High TGL levels are proved to be independent and statistically significant risk factor for the development of cardiovascular complications [9]. Hence, this study is concentrated on reducing this contraindication of sole TAM treatment with Co Q10 (100 mg), niacin (50 mg) and riboflavin (10 mg), since combination of these vitamins could exert a profound influence on the fat-splitting enzymes that may titer the hypertriglyceridemic effect of TAM.

Co Q10 is a lipid-soluble benzoquionone found in all tissues and membranes. Co Q10 is particularly high in the inner mitochondrial membrane, where it functions as an electron carrier in oxidative phosphorylation. Co Q10 is an endogenously synthesized lipid-soluble anti-oxidant and protects membrane phospholipids and serum LDL-C from lipid peroxidation [10]. In the recent years, there is a growing body of evidence on protective role of Co Q10 in cardiovascular diseases (CVD) and cancer [11], [12], [13].

Riboflavin (vitamin B2) a water soluble vitamin in its active coenzyme forms such as flavin mononucleotide (FMN+) and flavin adenine dinucleotide (FAD+), participates in redox processes involving one- and two-electron transition and in non-redox reactions such as photo-repair of thymidine dimers in photo-damaged DNA and the dehydration of non-activated organic substrates [14]. Niacin (nicotinic acid, Vitamin B3) a water-soluble vitamin, serves as a precursor of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). Both NAD and NADP can be reduced to NADH and NADPH, respectively and these coenzymes participate in oxidation–reduction reactions catalyzed by dehyrogenase and oxidoreductase enzymes. The NAD/NADP-linked enzyme systems are involved in virtually every aspect of metabolic processes. Currently, niacin is one of the premier lipid lowering agents available to treat various CVD, with its first clinical utility, which dates back to 1954 [15]. In this context, efforts were undertaken to understand the benevolent role of Co Q10, riboflavin and niacin on TAM-instigated lipid and lipoprotein abnormalities in postmenopausal breast cancer women.

Section snippets

Selection of patients

Seventy eight consecutively treated postmenopausal with resectable breast cancer were recruited from the Department of Medical Oncology, Government Royapettah Hospital, Chennai, India, through their physicians according to the process approved by the institutional human ethical review board. Informed consent was obtained from all the subjects with due explanation before entering into the study. The patient's characteristics are given in Table 1. Age: younger than 70 years with potentially

Results

The values of plasma lipid levels are indicated in Table 2. The levels of all the lipid parameters were significantly altered in Group II (p < 0.01), when compared to control Group I subjects. The levels of total cholesterol (TC), free fatty acids (FAA) and phospholipids (PL) were reduced in TAM-treated Group III patients as compared to Group II subjects, however, it was not statistically significant, whereas the triglycerides (TG) levels were significantly increased in the Group III subjects (p < 

Discussion

In the last 30 years, TAM has been shown to be effective not just as an adjuvant therapy after surgery, chemo or radiation therapy in early and advanced breast cancer cases, but also in chemoprevention in high-risk pre- and postmenopausal women. Some results of aromatase (enzyme responsible for synthesis of estrogen) inhibitors have been shown to be encouraging in postmenopausal women; however, they have contraindicated results in premenopausal women with functioning ovaries [20]. These

Acknowledgments

The authors whole-heartedly thank Kaneka Corp., Japan, for its philanthropic gift of coenzyme Q10 samples and Madras Pharmaceuticals for the niacin and riboflavin samples. The technical expertise provided by Dr. K. Rengaswamy and Dr. AL. Arun Kumar of Appaswamy Hospital and Isotope Diagnostic Center, Chennai, is greatly acknowledged.

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