Dr. Ron’s Research Review – November 8, 2017

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This week’s research review focuses on Coenzyme Q10, Riboflavin and Niacin (CoRN) for breast cancer.

Eighty-four breast cancer patients were randomized to receive a daily supplement of 100 mg co-enzyme Q10, 10 mg riboflavin and 50 mg niacin (CoRN), one dosage per d along with 10 mg tamoxifen twice per d. A significant increase in poly(ADP-ribose) polymerase levels and disappearance of RASSF1A DNA methylation patterns were found in patients treated with supplement therapy along with tamoxifen compared to untreated breast cancer patients and tamoxifen alone-treated patients. An increase in DNA repair enzymes and disappearance of DNA methylation patterns attributes to reduction in tumour burden and may suggest good prognosis and efficacy of the treatment. (Premkumar et al., 2008b)
In the present study, 84 breast cancer patients were randomized to receive a daily supplement of CoQ(10) 100 mg, riboflavin 10 mg and niacin 50 mg (CoRN), one dosage per day along with tamoxifen (TAM) 10 mg twice a day. Serum pro-angiogenic levels were elevated in untreated breast cancer patients (Group II) and their levels were found to be reduced in breast cancer patients undergoing TAM therapy for more than 1 year (Group III). When these group III breast cancer patients were supplemented with CoRN for 45 days (Group IV) and 90 days (Group V) along with TAM, a further significant reduction in pro-angiogenic marker levels were observed. Supplementing CoRN to breast cancer patients has found to decrease the levels of pro-angiogenic factors and increase the levels of anti-angiogenic factors. A reduction in pro-angiogenic marker levels attributes to reduction in tumour burden and may suggest good prognosis and efficacy of the treatment, and might even offer protection from cancer metastases and recurrence. (Premkumar et al., 2008a)
A study was undertaken to find if co-administration of CoQ(10), Niacin and Riboflavin along with TAM could augment the antioxidant (AO) status in postmenopausal women with breast cancer. The vitamin supplementation with Tamoxifen was given for a period of 90 days. Enhanced oxidative stress as evidenced by increased lipids and lipid peroxides with decreased AO levels in untreated breast cancer patients was observed. Adjuvant TAM-treated group had a limited impact on the increased oxidative stress with decreased AO status. Severe hypertriglycerdemia was observed in TAM-treated group when compared to untreated and control subjects. Combinatorial therapy (CT) of CoQ(10), Niacin and Riboflavin along with TAM decreased the oxidative stress and increased the AO status. (Yuvaraj et al., 2008)
In the present study, 84 breast cancer patients were randomized to receive a daily supplement of 100 mg coenzyme Q10 (CoQ10), 10 mg riboflavin and 50 mg niacin (CoRN) one dosage per day along with 10 mg tamoxifen (TAM) twice a day. Serum CEA and CA 15-3 levels were elevated in untreated breast cancer patients (group II) and their tumour marker levels significantly reduced upon tamoxifen therapy for more than 1 year (group III). Group III patients supplemented with CoRN for 45 d (group IV) and 90 d (group V) along with tamoxifen significantly reduced CEA and CA 15-3 levels. This study suggests supplementing CoRN to breast cancer patients along with tamoxifen reduces the serum tumour marker level and thereby reduce the risk of cancer recurrence and metastases. (Premkumar et al., 2007)
A study combined 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. The vitamin supplementation with tamoxifen was given for a period of 90 days. 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. (Yuvaraj et al., 2007)

Dr. Ron


 

Articles

Effect of coenzyme Q10, riboflavin and niacin on serum CEA and CA 15-3 levels in breast cancer patients undergoing tamoxifen therapy.
            (Premkumar et al., 2007a) Download
In breast cancer patients, it is not the primary tumour, but its metastases at distant sites that are the main cause of death. Circulating breast cancer tumour markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA 15-3) are reliable indicators of impending relapse, in which an increasing tumour marker level is associated with a very likelihood of developing recurrence. In the present study, 84 breast cancer patients were randomized to receive a daily supplement of 100 mg coenzyme Q10 (CoQ10), 10 mg riboflavin and 50 mg niacin (CoRN) one dosage per day along with 10 mg tamoxifen (TAM) twice a day. Serum CEA and CA 15-3 levels were elevated in untreated breast cancer patients (group II) and their tumour marker levels significantly reduced upon tamoxifen therapy for more than 1 year (group III). Group III patients supplemented with CoRN for 45 d (group IV) and 90 d (group V) along with tamoxifen significantly reduced CEA and CA 15-3 levels. This study suggests supplementing CoRN to breast cancer patients along with tamoxifen reduces the serum tumour marker level and thereby reduce the risk of cancer recurrence and metastases.

Serum cytokine levels of interleukin-1beta, -6, -8, tumour necrosis factor-alpha and vascular endothelial growth factor in breast cancer patients treated with tamoxifen and supplemented with co-enzyme Q(10), riboflavin and niacin.
            (Premkumar et al., 2007b) Download
The prognostic significance of supplementing co-enzyme Q(10) (CoQ(10)), riboflavin and niacin (CoRN) along with tamoxifen to breast cancer patients was evaluated by measuring the serum cytokine levels of interleukin (IL)-1beta, IL-6, IL-8, tumour necrosis factor alpha (TNF-alpha) and vascular endothelial growth factor. In the present study, 84 breast cancer patients were randomized to receive a daily supplement of CoQ(10) 100 mg, riboflavin 10 mg and niacin 50 mg, one dosage per day along with tamoxifen 10 mg twice a day. Serum cytokine levels were elevated in untreated breast cancer patients (Group II) and significantly reduced after tamoxifen therapy for more than 1 year (Group III). When group III breast cancer patients were supplemented with CoRN for 45 days (Group IV) and 90 days (Group V) along with tamoxifen, a significant reduction in cytokine levels were observed (P < 0.05). Such a decrease in serum cytokine levels after CoRN supplementation in breast cancer patients may suggest good prognosis and efficacy of the treatment, and might even offer protection from metastases and recurrence of cancer.

Anti-angiogenic potential of CoenzymeQ10, riboflavin and niacin in breast cancer patients undergoing tamoxifen therapy.
            (Premkumar et al., 2008a) Download
Tumour angiogenesis is a complex mechanism consisting of multi-step events including secretion or activation of angiogenic factors by tumour cells, activation of proteolytic enzymes, proliferation, migration and differentiation of endothelial cells. Both primary and metastatic tumours in the breast are dependent on angiogenesis. In the present study, 84 breast cancer patients were randomized to receive a daily supplement of CoQ(10) 100 mg, riboflavin 10 mg and niacin 50 mg (CoRN), one dosage per day along with tamoxifen (TAM) 10 mg twice a day. Serum pro-angiogenic levels were elevated in untreated breast cancer patients (Group II) and their levels were found to be reduced in breast cancer patients undergoing TAM therapy for more than 1 year (Group III). When these group III breast cancer patients were supplemented with CoRN for 45 days (Group IV) and 90 days (Group V) along with TAM, a further significant reduction in pro-angiogenic marker levels were observed. Supplementing CoRN to breast cancer patients has found to decrease the levels of pro-angiogenic factors and increase the levels of anti-angiogenic factors. A reduction in pro-angiogenic marker levels attributes to reduction in tumour burden and may suggest good prognosis and efficacy of the treatment, and might even offer protection from cancer metastases and recurrence.

Co-enzyme Q10, riboflavin and niacin supplementation on alteration of DNA repair enzyme and DNA methylation in breast cancer patients undergoing tamoxifen therapy.
            (Premkumar et al., 2008b) Download
In the present study, eighty-four breast cancer patients were randomized to receive a daily supplement of 100 mg co-enzyme Q10, 10 mg riboflavin and 50 mg niacin (CoRN), one dosage per d along with 10 mg tamoxifen twice per d. A significant increase in poly(ADP-ribose) polymerase levels and disappearance of RASSF1A DNA methylation patterns were found in patients treated with supplement therapy along with tamoxifen compared to untreated breast cancer patients and tamoxifen alone-treated patients. An increase in DNA repair enzymes and disappearance of DNA methylation patterns attributes to reduction in tumour burden and may suggest good prognosis and efficacy of the treatment.

Ameliorating effect of coenzyme Q10, riboflavin and niacin in tamoxifen-treated postmenopausal breast cancer patients with special reference to lipids and lipoproteins.
            (Yuvaraj et al., 2007) Download
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.

Augmented antioxidant status in Tamoxifen treated postmenopausal women with breast cancer on co-administration with Coenzyme Q10, Niacin and Riboflavin.
            (Yuvaraj et al., 2008) Download
BACKGROUND:  Reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide (H(2)O(2)), hydroxyl radical have been implicated in pathogenesis of various diseases including cancer and metastasis. Tamoxifen (TAM) is a non-steroidal anti-estrogen drug most widely used as an adjuvant hormonal therapy in breast cancer. TAM also has estrogenic activity on liver and endometrium causing severe oxidative stress and hypertriglycerdemia. Coenzyme Q(10) (CoQ(10)), Niacin and Riboflavin are well-known potent antioxidants and protective agents against many diseases including cancer. In this context, this study was undertaken to find if co-administration of CoQ(10), Niacin and Riboflavin along with TAM could augment the antioxidant (AO) status in postmenopausal women with breast cancer. 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 lipids, lipid peroxides and various circulating enzymatic and non-enzymatic antioxidants were estimated in 78 untreated, sole TAM treated and combinatorial treated group along with 46 age- and sex-matched controls. RESULTS:  Enhanced oxidative stress as evidenced by increased lipids and lipid peroxides with decreased AO levels in untreated breast cancer patients was observed. Adjuvant TAM-treated group had a limited impact on the increased oxidative stress with decreased AO status. Severe hypertriglycerdemia was observed in TAM-treated group when compared to untreated and control subjects. Combinatorial therapy (CT) of CoQ(10), Niacin and Riboflavin along with TAM decreased the oxidative stress and increased the AO status. CONCLUSION:  The antioxidant defense system is compromised in breast cancer patients. There is a shift in the oxidant / antioxidant balance in favor of lipid peroxidation (LPO), which could lead to tumour promotion observed in the disease. CT of CoQ(10), Niacin and Riboflavin along with TAM significantly increased the AO status, while decreasing lipid and lipid peroxides. The results suggest the necessity of therapeutic co-administration of antioxidants along with conventional drug to such patients. However, due to limited number of cases included in this study, more studies may be required to substantiate the results and arrive at a definitive conclusion, in terms of safety and efficacy of adding an AO therapy in treatment of breast cancer.

 

 

References

Premkumar, VG, et al. (2007a), ‘Effect of coenzyme Q10, riboflavin and niacin on serum CEA and CA 15-3 levels in breast cancer patients undergoing tamoxifen therapy.’, Biol Pharm Bull, 30 (2), 367-70. PubMed: 17268082
——— (2007b), ‘Serum cytokine levels of interleukin-1beta, -6, -8, tumour necrosis factor-alpha and vascular endothelial growth factor in breast cancer patients treated with tamoxifen and supplemented with co-enzyme Q(10), riboflavin and niacin.’, Basic Clin Pharmacol Toxicol, 100 (6), 387-91. PubMed: 17516992
Premkumar, VG, et al. (2008a), ‘Anti-angiogenic potential of CoenzymeQ10, riboflavin and niacin in breast cancer patients undergoing tamoxifen therapy.’, Vascul Pharmacol, 48 (4-6), 191-201. PubMed: 18407793
Premkumar, VG, et al. (2008b), ‘Co-enzyme Q10, riboflavin and niacin supplementation on alteration of DNA repair enzyme and DNA methylation in breast cancer patients undergoing tamoxifen therapy.’, Br J Nutr, 100 (6), 1179-82. PubMed: 18377693
Yuvaraj, S, et al. (2007), ‘Ameliorating effect of coenzyme Q10, riboflavin and niacin in tamoxifen-treated postmenopausal breast cancer patients with special reference to lipids and lipoproteins.’, Clin Biochem, 40 (9-10), 623-28. PubMed: 17425952
——— (2008), ‘Augmented antioxidant status in Tamoxifen treated postmenopausal women with breast cancer on co-administration with Coenzyme Q10, Niacin and Riboflavin.’, Cancer Chemother Pharmacol, 61 (6), 933-41. PubMed: 17668211