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*Coenzyme Q10 & Breast Cancer Connection

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*The Co-Q10 - Cancer Connection

Coenzyme Q10 (Co-Q10) is a powerful antioxidant that boosts the heart's ability to endure stress and supports mitochondria—cellular structures that produce energy from food. Recent research suggests that low Co-Q10 levels are linked to certain cancers. One U.S. study compared 27 women with normal Pap smears with 75 women with cervical cancer and its precursor—cervical intraepithelial neoplasia. Women with cervical cancer and neoplasia had lower concentrations of cervical/vaginal cell Co-Q10 and vitamin E (alpha-tocopherol) compared to women with normal Pap smears.¹ In another study, 200 French women with malignant and nonmalignant breast tumors were found to have reduced amounts of Co-Q10 in the blood despite normal concentrations of vitamin E, another antioxidant.² A study of 21 Turkish women who underwent radical mastectomies for breast cancer found lower levels of Co-Q10 within the breast tumor compared to the normal surrounding tissue. Four of the women had no detectable amounts of Co-Q10 in the tumor or nearby tissue.³ No placebo-controlled studies have validated the effectiveness of Co-Q10 alone in preventing or treating cancer.⁴ But in light of a recent clinical study showing Co-Q10 supplementation protects immune cells from DNA damage,⁵ this anti-oxidant merits further study.

Anthony Almada is a nutritional and exercise biochemist and has collaborated on more than 50 university-based clinical trials. He is the co-founder of EAS and founder and chief scientific officer of IMAGINutrition.

This section is maintained by Frank M. Painter, D.C.
Send all comments or additions to:   Frankp@chiro.org

References

1. Mikhail MS, et al. Coenzyme Q10 and a-tocopherol concentrations in cervical intraepithelial neoplasia and cervix cancer. Obstet Gynecol 2001;97: (Abstract)3S.

2. Jolliet P, et al. Plasma coenzyme Q10 concentrations in breast cancer: prognosis and therapeutic consequences. Fund Clin Pharmacol 1997;11: (Abstract)176.

3. Portakal O, et al. Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. Clin Biochem 2000;33:279-84.

4. Lockwood K, et al. Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10. Biochem Biophys Res Commun 1994;199:504-8.

5. Tomasetti M, et al. In vivo supplementation with coenzyme Q10 enhances the recovery of human lymphocytes from oxidative DNA damage. FASEBJ 2001 Apr 6 (published online before print).

Progress on Therapy of Breast Cancer with Vitamin Q10 and the Regression of Metastases

FROM:   Biochem Biophys Res Commun 1995 (Jul 6);   212 (1):   172–177 Lockwood K, Moesgaard S, Yamamoto T, Folkers K Pharma Nord, Vejle, Denmark Over 35 years, data and knowledge have internationally evolved from biochemical, biomedical and clinical research on vitamin Q10 (coenzyme Q10; CoQ10) and cancer, which led in 1993 to overt complete regression of the tumors in two cases of breast cancer. Continuing this research, three additional breast cancer patients also underwent a conventional protocol of therapy which included a daily oral dosage of 390 mg of vitamin Q10 (Bio-Quinone of Pharma Nord) during the complete trials over 3-5 years. The numerous metastases in the liver of a 44-year-old patient "disappeared," and no signs of metastases were found elsewhere. A 49-year-old patient, on a dosage of 390 mg of vitamin Q10, revealed no signs of tumor in the pleural cavity after six months, and her condition was excellent. A 75-year-old patient with carcinoma in one breast, after lumpectomy and 390 mg of CoQ10, showed no cancer in the tumor bed or metastases. Control blood levels of CoQ10 of 0.83-0.97 and of 0.62 micrograms/ml increased to 3.34-3.64 and to 3.77 micrograms/ml, respectively, on therapy with CoQ10 for patients A-MRH and EEL.

Partial and Complete Regression of Breast Cancer in Patients in Relation to Dosage of Coenzyme Q10

FROM:   Biochem Biophys Res Commun 1994 (Mar 30);   199 (3):   1504–1508 Lockwood K, Moesgaard S, Folkers K Pharma Nord, Vejle, Denmark Relationships of nutrition and vitamins to the genesis and prevention of cancer are increasingly evident. In a clinical protocol, 32 patients having -"high-risk"- breast cancer were treated with antioxidants, fatty acids, and 90 mg. of CoQ10. Six of the 32 patients showed partial tumor regression. In one of these 6 cases, the dosage of CoQ10 was increased to 390 mg. In one month, the tumor was no longer palpable and in another month, mammography confirmed the absence of tumor. Encouraged, another case having a verified breast tumor, after non-radical surgery and with verified residual tumor in the tumor bed was then treated with 300 mg. CoQ10. After 3 months, the patient was in excellent clinical condition and there was no residual tumor tissue. The bioenergetic activity of CoQ10, expressed as hematological or immunological activity, may be the dominant but not the sole molecular mechanism causing the regression of breast cancer.

Relevance of the Biosynthesis of Coenzyme Q10 and of the Four Bases of DNA as a Rationale for the Molecular Causes of Cancer

FROM:   Biochem Biophys Res Commun 1996 (Jul 16);   224 (2):   358–361 Folkers K Institute for Biomedical Research, University of Texas at Austin 78712, USA In the human, coenzyme Q10 (vitamin Q10) is biosynthesized from tyrosine through a cascade of eight aromatic precursors. These precursors indispensably require eight vitamins, which are tetrahydrobiopterin, vitamins B6, C, B2, B12, folic acid, niacin, and pantothenic acid as their coenzymes. Three of these eight vitamins (the coenzyme B6, and the coenzymes niacin and folic acid) are indispensable in the biosynthesis of the four bases (thymidine, guanine, adenine, and cytosine) of DNA. One or more of the three vitamins required for DNA are known to cause abnormal pairing of the four bases, which can then result in mutations and the diversity of cancer. The coenzyme B6, required for the conversion of tyrosine to p-hydroxybenzoic acid, is the first coenzyme required in the cascade of precursors. A deficiency of the coenzyme B6 can cause dysfunctions, prior to the formation of vitamin Q10, to DNA. Former data on blood levels of Q10 and new data herein on blood levels of B6, measured as EDTA, in cancer patients established deficiencies of Q10 and B6 in cancer. This complete biochemistry relating to biosyntheses of Q10 and the DNA bases is a rationale for the therapy of cancer with Q10 and other entities in this biochemistry.

Coenzyme Q10 Concentrations and Antioxidant Status in Tissues of Breast Cancer Patients

FROM:   Clin Biochem 2000 (Jun);   33 (4):   279–284 Portakal O, Ozkaya O, Erden Inal M, Bozan B, Kosan M, Sayek I Department of Biochemistry, The Medical School of Osmangazi University, Eskisehir, Turkey. portakal@ada.net.tr OBJECTIVES:   An increasing amount of experimental and epidemiological evidence implicates the involvement of oxygen derived radicals in the pathogenesis of cancer development. Oxygen derived radicals are able to cause damage to membranes, mitochondria, and macromolecules including proteins, lipids and DNA. Accumulation of DNA damages has been suggested to contribute to carcinogenesis. It would, therefore, be advantageous to pinpoint the effects of oxygen derived radicals in cancer development. DESIGN AND METHODS:   In the present study, we investigated the relationship between oxidative stress and breast cancer development in tissue level. Breast cancer is the most common malignant disease in Western women. Twenty-one breast cancer patients, who underwent radical mastectomy and diagnosed with infiltrative ductal carcinoma, were used in the study. We determined coenzyme Q10 (Q) concentrations, antioxidant enzyme activities (mitochondrial and total superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase), and malondialdehyde (MDA) levels in tumor and surrounding tumor-free tissues. RESULTS:   Q concentrations in tumor tissues significantly decreased as compared to the surrounding normal tissues (p < 0.001). Higher MDA levels were observed in tumor tissues than noncancerous tissues (p < 0.001). The activities of MnSOD, total SOD, GSH-Px and catalase in tumor tissues significantly increased (p < 0.001) compared to the controls. CONCLUSIONS:   These findings may support that reactive oxygen species increased in malignant cells, and may cause overexpression of antioxidant enzymes and the consumption of coenzyme Q10. Increased antioxidant enzyme activities may be related with the susceptibility of cells to carcinogenic agents and the response of tumor cells to the chemotherapeutic agents. Administration of coenzyme Q10 by nutrition may induce the protective effect of coenzyme Q10 on breast tissue.

 

Recent Progress in Treatment and Secondary Prevention of Breast Cancer With Supplements

Steve Austin, N.D.

 

Abstract

This article discusses five naturally occurring agents that are currently being studied to evaluate their potential in the treatment and/or secondary prevention of breast cancer. Preliminary data have been published suggesting that high dose coenzyme Q10 may have anti-cancer activity in women with node-positive breast cancer. Low serum levels of dehydroepiandrosterone associate with increased risk of premenopausal breast cancer, but a reduced risk of postmenopausal breast cancer. The clinical implications remain unclear. Melatonin has antiestrogenic and antioxidant activity. Preliminary research suggests that high-dose melatonin may have anti-cancer activity particularly in women with estrogen receptor-positive breast cancer. Preliminary data show that vitamin D analogues and possibly vitamin D itself have anti-cancer activity in relation to human breast cancer. Blinded research using yeast-based selenium suggests powerful anti-cancer activity, though it does not yet appear that the protection extends to reduction in breast cancer risk specifically. (Alt Med Rev 1997;2(1):4-11)

Introduction

Small reductions in American breast cancer mortality rates are finally appearing after many decades showing no progress. Early detection may indirectly be the leading cause of these limited gains, but advances in allopathic treatment may also be partially responsible.¹ Nonetheless, in American women breast cancer remains both the most common invasive cancer and the second leading cause of cancer deaths.²

Many women choose to augment or in some cases replace parts of allopathic treatment with natural medicine. In the case of nutritional intervention for the purpose of secondary prevention, our basic understanding of the relationship between diet and breast cancer has not changed significantly in the last few years and has been reviewed elsewhere.³ However, the picture is changing regarding the use of certain natural substances in the treatment of breast cancer. The purpose of this review is to describe these recent changes. Research regarding the relationship between breast cancer prevention or treatment and most standard nutritional antioxidants (vitamins E, C, and beta-carotene) and medicinal herbs (such as the Hoxsey formula) will not be included in this review.

Coenzyme Q 10 (CoQ10) as a Treatment for Breast Cancer

Three preliminary reports by the same research group have recently concluded that coenzyme Q10 may play a role in the treatment and secondary prevention of breast cancer. All three have serious methodological shortcomings.

In 1994, Danish and American workers reported on the previously unpublished results⁴ of treating 32 node-positive breast cancer patients for 18 months with a protocol of supplements plus conventional allopathic treatment.⁵ The protocol included 2850 mg vitamin C, 2,500 IU vitamin E, 32.5 IU ß-carotene (presumably synthetic), 387 mcg selenium, 1.2 g gamma-linolenic acid, 3.5 g omega-3 fatty acids from fish oil, 90 mg CoQ10 and a low-dose multi-vitamin/mineral per day. Only some of the 32 had evidence of metastatic disease at the start of the study but specifics were not given. It's remarkable that better data were not provided, as the staging of breast cancer is critical to prognosis, and expected prognoses are essential to the evaluation of the outcome of this study.

All 32 patients survived the 18 months. None showed further evidence of distal metastasis. As most node-positive patients would be expected to both survive and be metastasis-free after such a brief period, the chance of 18 months of metastasis-free survival in a group of 32 node-positive patients even without supplemental intervention is unclear without more staging detail and statistical analysis; neither was fully provided.

If many of the 32 patients actually had metastatic disease (stage IV), then a lack of progression after 18 months would be impressive indeed. By not listing how many patients were stage IV, proper evaluation of this study becomes impossible.

The authors reported no weight loss and a "reduced use of pain killers." However, stage II and III patients (some of whom were included in this study) would not be expected to lose weight and most do not take analgesics unless done so postsurgically. The use of postsurgical analgesics would naturally decline even in the absence of nutritional intervention. Again, the statements made by the authors cannot be properly evaluated.

Six of the 32 showed evidence of "partial remission." However, patients were also treated with tamoxifen and/or chemotherapy. The possibility of 18-month partial remissions from conventional treatment is quite real given the small sample size. As for typical stage II and III patients, most become temporarily disease-free as a result of conventional allopathic treatment, making "partial remission" resulting from the use of the supplements impossible to evaluate for such patients; they should already be in total remission.

Increased natural killer cell and total lymphocyte counts were recorded between months 3 and 12 of the intervention, but no baseline was provided. Thus, the increases in killer cell and lymphocyte count could have been due to cessation of chemotherapy.

Six cases were described more fully. One patient with bony metastases showed no progression of disease-an 18 month outcome which might have resulted from the tamoxifen she was taking. Another patient had pleural metastases which disappeared from her chest film, but she had also been treated with chemotherapy. Reports of the disappearance of local residual tumor and decrease in the size of recurrence to skin overlying the breast in two other patients were accompanied with no details about allopathic treatment. Another patient who did not have metastatic disease was in "excellent clinical condition" throughout the 18 months, but such an outcome is common in the absence of the supplement protocol. The sixth case suffered a local recurrence during the intervention. Thus the outcome of this preliminary study proves very little.

A later report of the same trial describes two-year follow up.⁶ At that time, all patients were still alive and evidence of further metastatic spread was not found. The authors report that six of the 32 were expected to be deceased at two years, but without staging information, this figure cannot be verified.

Higher dose CoQ10 were used in two of the 32 patients. In one case, after two years at 90 mg, the dose of CoQ10 was increased to 390 mg. Local recurrence apparently disappeared after one month on high-dose CoQ10. This case appears to be unverified, however, because apparent clinical recurrences need to be confirmed by biopsy; in this case the evidence of appearance and disappearance seem to have come from physical exam and mammography alone.

Another patient was given 300 mg of CoQ10. After four months, there was apparent disappearance of residual carcinoma not removed by the original surgery. Again, however, the evidence was from physical and mammographic findings apparently not confirmed by biopsy.

Like the initial report, the two-year follow-up claims tumor regression in "six" of the 32 patients. Two of the six cases of regression were discussed in the second report in more detail. However, neither is among the six discussed in the original report, suggesting that two of the original cases of regression must have suffered a relapse, though this is not stated. The second report goes on to review the data showing increased immune function in humans resulting from CoQ10 supplementation⁷ and decreased blood levels of CoQ10 in cancer patients.⁸

A third report has more recently been published by the same group, describing three additional patients treated with 390 mg of CoQ10 for 3-5 years.⁹ In one patient, multiple liver metastases disappeared after 11 months of high-dose CoQ10 administration. While the details are not completely clear, it seems that the disappearance of liver metastases did not happen during or shortly after chemotherapy, suggesting that the CoQ10 may have been responsible for the remarkable remission. This case is complicated by the fact that the diagnosis was apparently mislabeled "invasive intraductal" carcinoma (now called ductal carcinoma in situ [DCIS]). DCIS is by definition not invasive and does not progress directly to metastatic disease. Possibly, the patient had invasive ductal carcinoma, and the diagnosis was improperly stated.

In the second of the three cases, fluid in the right pleural cavity associated with proven metastasis disappeared during three years of CoQ10 administration (90 mg for one year and 390 for the last two years). In the absence of CoQ10, this durable remission would be extremely unlikely, even if chemotherapy or tamoxifen had been used.

The third patient described had lumpectomy with involved margins followed by mastectomy. While she remained disease-free during 39 months of CoQ10 therapy, no rationale is provided as to why this outcome would be unexpected in the absence of CoQ10. Many node-positive patients are disease-free at 39 months.

Most importantly in the evaluation of the last report, it is unclear whether the final three cases were consecutive or were selected because these patients fared particularly well. If the latter is true, then this report, as interesting as it is, would not tell us the likelihood that massive doses of CoQ10 would help late-stage patients.

While troubled by omissions and lack of important data in all three reports, I have nonetheless begun to suggest high-dose CoQ10 as part of the protocol I use with node-positive breast cancer patients with high risk of recurrence. A lack of serious CoQ10 toxicity, the hope of a therapeutic effect with CoQ10, and a lack of curative allopathic treatments for late-stage patients combines to form my rationale. Other doctors of natural medicine have done the same, but to date it appears that none of us has followed these patients long enough to evaluate the possible effects. While the preliminary results look both interesting and encouraging, the real effects of using high-dose CoQ10 in the treatment of breast cancer remain unknown.

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