Cancer and Metastasis Reviews

, Volume 29, Issue 3, pp 543–552 | Cite as

Lipid replacement therapy: a nutraceutical approach for reducing cancer-associated fatigue and the adverse effects of cancer therapy while restoring mitochondrial function

  • Garth L. Nicolson


Cancer-associated fatigue is one of the most common symptoms in all forms and stages of cancer, yet scant attention is usually given to patients who have symptomatic complaints of fatigue. Cancer-associated fatigue is also associated with cellular oxidative stress, and during cancer therapy, excess drug-induced oxidative stress can limit therapeutic effectiveness and cause a number of side effects, including fatigue, nausea, vomiting, and more serious adverse effects. Cancer-associated fatigue and the chronic adverse effects of cancer therapy can be reduced by lipid replacement therapy using membrane lipids along with antioxidants and enzymatic cofactors, such as coenzyme Q10, given as food supplements. Administering these nutraceutical supplements can reduce oxidative membrane damage and restore mitochondrial and other cellular functions. Recent clinical trials using cancer and non-cancer patients with chronic fatigue have shown the benefits of lipid replacement therapy in reducing fatigue and restoring mitochondrial electron transport function.


Oxidative stress Alkylating agents Mitochondria Coenzyme Q10 Lipid peroxidation Electron transport chain Antioxidants Membranes Membrane lipids Fatigue 


Conflict of interest

The author has no financial interest in any products discussed in this contribution.


  1. 1.
    Hofman, M., Ryan, J. L., Figueroa-Moseley, C. D., et al. (2007). Cancer-related fatigue: The scale of the problem. The Oncologist, 12, 4–10.PubMedCrossRefGoogle Scholar
  2. 2.
    Brown, L. F., & Kroenke, K. (2009). Cancer-related fatigue and its association with depression and anxiety: A systematic review. Psychosomatics, 50, 440–447.PubMedCrossRefGoogle Scholar
  3. 3.
    Prue, G., Rankin, J., Allen, J., et al. (2006). Cancer-related fatigue: A critical appraisal. European Journal of Cancer, 42, 846–863.PubMedCrossRefGoogle Scholar
  4. 4.
    Curt, G. A., Breitbart, W., Cella, D., et al. (2000). Impact of cancer-related fatigue on the lives of patients: New findings from the Fatigue Coalition. The Oncologist, 5, 353–360.PubMedCrossRefGoogle Scholar
  5. 5.
    Respini, D., Jacobsen, P. B., Thors, C., et al. (2003). The prevalence and correlates of fatigue in older cancer patients. Critical Reviews in Oncology/Hematology, 47, 273–279.PubMedCrossRefGoogle Scholar
  6. 6.
    Sood, A., & Moynihan, T. J. (2005). Cancer-related fatigue: An update. Current Oncology Reports, 7, 277–282.PubMedCrossRefGoogle Scholar
  7. 7.
    Arnold, L. M. (2008). Understanding fatigue in major depressive disorder and other medical disorders. Psychosomatics, 49, 185–190.PubMedCrossRefGoogle Scholar
  8. 8.
    Bender, C. M., Engberg, S. J., Donovan, H. S., et al. (2008). Symptom clusters in adults with chronic health problems and cancer as a comorbidity. Oncology Nursing Forum, 35, E1–E11.PubMedCrossRefGoogle Scholar
  9. 9.
    Smets, E. M. A., Garssen, B., Cull, A., et al. (1996). Applications of the Multidimensional Fatigue Inventory (MFI-20) in cancer patients receiving radiotherapy. British Journal of Cancer, 73, 241–245.PubMedGoogle Scholar
  10. 10.
    Stone, P., Hardy, J., Huddart, R., et al. (2000). Fatigue in patients with prostate cancer receiving hormone therapy. European Journal of Cancer, 36, 1134–1141.PubMedCrossRefGoogle Scholar
  11. 11.
    Cella, D., Davis, K., Breitbart, W., et al. (2001). Cancer-related fatigue: Prevalence of proposed diagnostic criteria in a United States sample of cancer survivors. Journal of Clinical Oncology, 19, 3385–3391.PubMedGoogle Scholar
  12. 12.
    Ahlberg, K., Ekman, T., Gaston-Johansson, F., & Mock, V. (2003). Assessment and management of cancer-related fatigue in adults. The Lancet, 362(9384), 640–650.CrossRefGoogle Scholar
  13. 13.
    Gutstein, H. B. (2001). The biological basis for fatigue. Cancer, 92, 1678–1683.PubMedCrossRefGoogle Scholar
  14. 14.
    Manzullo, E. F., & Escalante, C. P. (2002). Research into fatigue. Hematology/Oncology Clinics of North America, 16, 619–628.PubMedCrossRefGoogle Scholar
  15. 15.
    Given, B., Given, C., Azzouz, F., & Stommel, M. (2001). Physical functioning of elderly cancer patients prior to diagnosis and following initial treatment. Nursing Research, 50, 222–232.PubMedCrossRefGoogle Scholar
  16. 16.
    Vogelzang, N., Breitbart, W., Cella, D., et al. (1997). Patient caregiver and oncologist perceptions of cancer-related fatigue: Results of a tripart assessment survey. Seminars in Hematology, 34(Suppl 2), 4–12.PubMedGoogle Scholar
  17. 17.
    Liu, L., Marler, M. R., Parker, B. A., et al. (2005). The relationship between fatigue and light exposure during chemotherapy. Supportive Care in Cancer, 13, 1010–1017.PubMedCrossRefGoogle Scholar
  18. 18.
    Marrow, G. R. (2007). Cancer-related fatigue: Causes, consequences and management. The Oncologist, 12(suppl 1), 1–3.CrossRefGoogle Scholar
  19. 19.
    Morrison, J. D. (1980). Fatigue as a presenting complaint in family practice. The Journal of Family Practice, 10, 795–801.PubMedGoogle Scholar
  20. 20.
    Kroenke, K., Wood, D. R., Mangelsdorff, A. D., et al. (1988). Chronic fatigue in primary care. Prevalence, patient characteristics, and outcome. JAMA, 260, 929–934.PubMedCrossRefGoogle Scholar
  21. 21.
    McDonald, E., David, A. S., Pelosi, A. J., & Mann, A. H. (1993). Chronic fatigue in primary care attendees. Psychological Medicine, 23, 987–998.PubMedCrossRefGoogle Scholar
  22. 22.
    Kehrer, J. P. (1993). Free radicals and mediators of tissue injury and disease. Critical Reviews in Toxicology, 23, 21–48.PubMedCrossRefGoogle Scholar
  23. 23.
    Halliwell, B. (1996). Oxidative stress, nutrition and health. Free Radical Research, 25, 57–74.PubMedCrossRefGoogle Scholar
  24. 24.
    Dreher, D., & Junod, A. F. (1996). Role of oxygen free radicals in cancer development. European Journal of Cancer, 32A, 30–38.PubMedCrossRefGoogle Scholar
  25. 25.
    Abidi, S., & Ali, A. (1999). Role of oxygen free radicals in the pathogenesis and etiology of cancer. Cancer Letters, 142, 1–9.CrossRefGoogle Scholar
  26. 26.
    Stadtman, E. (2002). Introduction to serial reviews on oxidatively modified proteins in aging and disease. Free Radical Biology & Medicine, 32, 789.CrossRefGoogle Scholar
  27. 27.
    Marnett, L. J. (2000). Oxyradicals and DNA damage. Carcinogenesis, 21, 361–370.PubMedCrossRefGoogle Scholar
  28. 28.
    Bartsch, H., & Nair, J. (2004). Oxidative stress and lipid peroxidation-driven DNA-lesions in inflammation driven carcinogenesis. Cancer Detection and Prevention, 28, 385–391.PubMedCrossRefGoogle Scholar
  29. 29.
    Castro, L., & Freeman, B. A. (2001). Reactive oxygen species in human health and disease. Nutrition, 17, 295–307.CrossRefGoogle Scholar
  30. 30.
    Johnson, T. M., Yu, Z. X., Ferrans, V. J., et al. (1996). Reactive oxygen species are downstream mediators of p53-dependent apoptosis. Proceedings of the National Academy of Science USA, 93, 11848–11852.CrossRefGoogle Scholar
  31. 31.
    Ghaffari, S. (2008). Oxidative stress in the regulation of normal and neoplastic hematopoiesis. Antioxidation and Redox Signaling, 10, 1923–1940.CrossRefGoogle Scholar
  32. 32.
    Maes, M. (2009). Inflammatory and oxidative and nitrosative stress pathways underpinning chronic fatigue, somatization and psychosomatic symptoms. Current Opinions in Psychiatry, 22, 75–83.CrossRefGoogle Scholar
  33. 33.
    Maes, M., & Twisk, F. N. (2009). Why myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may kill you: Disorders in the inflammatory and oxidative and nitrosative stress (IO&NS) pathways may explain cardiovascular disorders in ME/CFS. Neuro Endocrinology Letters, 30, 677–693.PubMedGoogle Scholar
  34. 34.
    Barber, D. A., & Harris, S. R. (1994). Oxygen free radicals and antioxidants: A review. American Pharmacology, 34, 26–35.Google Scholar
  35. 35.
    Sun, Y. (1990). Free radicals, antioxidant enzymes and carcinogenesis. Free Radical Biology & Medicine, 8, 583–599.CrossRefGoogle Scholar
  36. 36.
    Fridovich, I. (1995). Superoxide radical and superoxide dismutases. Annual Review of Biochemistry, 64, 97–112.PubMedCrossRefGoogle Scholar
  37. 37.
    Seifried, H. E., McDonald, S. S., Anderson, D. E., et al. (2003). The antioxidant conundrum in cancer. Cancer Research, 61, 4295–4298.Google Scholar
  38. 38.
    Jagetia, G. C., Rajanikant, G. K., Rao, S. K., et al. (2003). Alteration in the glutathione, glutathione peroxidase, superoxide dismutase and lipid peroxidation by ascorbic acid in the skin of mice exposed to fractionated gamma radiation. Clinica Chimica Acta, 332, 111–121.CrossRefGoogle Scholar
  39. 39.
    Schwartz, J. L. (1996). The dual roles of nutrients as antioxidants and prooxidants: Their effects on tumor cell growth. The Journal of Nutrition, 126, 1221S–1227S.PubMedGoogle Scholar
  40. 40.
    Aeschbach, R., Loliger, J., Scott, B. C., et al. (1994). Antioxidant actions of thymol, carvacrol, 6-gingerol, zingerone and hydroxytyrosol. Food Chemistry and Toxicology, 32, 31–36.CrossRefGoogle Scholar
  41. 41.
    Tanaka, T. (1994). Cancer chemoprevention by natural products. Oncology Reports, 1, 1139–1155.Google Scholar
  42. 42.
    Prasad, K. N., Cole, W. C., Kumar, B., et al. (2001). Scientific rationale for using high-dose multiple micronutrients as an adjunct to standard and experimental cancer therapies. Journal of the American College of Nutrition, 20, 450S–453S.PubMedGoogle Scholar
  43. 43.
    Toyokuni, S., Okamoto, K., Yodio, J., et al. (1995). Persistent oxidative stress in cancer. FEBS Letters, 358, 1–3.PubMedCrossRefGoogle Scholar
  44. 44.
    Ray, G., Batra, S., Shukla, N. K., et al. (2000). Lipid peroxidation, free radical production and antioxidant status in breast cancer. Breast Cancer Research and Treatment, 59, 163–170.PubMedCrossRefGoogle Scholar
  45. 45.
    Brown, N. S., & Bicknell, R. (2001). Hypoxia and oxidative stress in breast cancer. Oxidative stress: Its effects on the growth, metastatic potential and response to therapy of breast cancer. Breast Cancer Research, 3, 323–327.PubMedCrossRefGoogle Scholar
  46. 46.
    Klaunig, J. E., & Kamendulis, L. M. (2004). The role of oxidative stress in carcinogenesis. Annual Review of Pharmacology and Toxicology, 44, 239–267.PubMedCrossRefGoogle Scholar
  47. 47.
    Tas, F., Hansel, H., Belce, A., et al. (2005). Oxidative stress in breast cancer. Medical Oncology, 22, 11–15.PubMedCrossRefGoogle Scholar
  48. 48.
    Kang, D. H. (2002). Oxidative stress, DNA damage and breast cancer. AACN Clinical Issues, 13, 540–549.PubMedCrossRefGoogle Scholar
  49. 49.
    Sikka, S. C. (2003). Role of oxidative stress response elements and antioxidants in prostate cancer pathobiology and chemoprevention—a mechanistic approach. Current Medicinal Chemistry, 10, 2679–2692.PubMedCrossRefGoogle Scholar
  50. 50.
    Aydin, A., Arsova-Sarafinovska, Z., Sayal, A., et al. (2006). Oxidative stress and antioxidant status in non-metastatic prostate cancer and benign prostate hyperplasia. Clinical Biochemistry, 39, 176–179.PubMedCrossRefGoogle Scholar
  51. 51.
    Otamiri, T., & Sjodahl, R. (1989). Increased lipid peroxidation in malignant tissues of patients with colorectal cancer. Cancer, 64, 422–425.PubMedCrossRefGoogle Scholar
  52. 52.
    Oxdemirler, G., Pabucçoglu, H., Bulut, T., et al. (1989). Increased lipoperoxide levels and antioxidant system in colorectal cancer. Journal of Cancer Research and Clinical Oncology, 124, 555–559.Google Scholar
  53. 53.
    Asal, N. R., Risser, D. R., Kadamani, S., et al. (1990). Risk factors in renal cell carcinoma. I. Methodology, demographics, tobacco beverage use and obesity. Cancer Detection and Prevention, 11, 359–377.Google Scholar
  54. 54.
    Gago-Dominguez, M., Castelao, J. E., Yuan, J. M., et al. (2002). Lipid peroxidation: A novel and unifying concept of the etiology of renal cell carcinoma. Cancer Causes & Control, 13, 287–293.CrossRefGoogle Scholar
  55. 55.
    Manoharan, S., Kolanjiappan, K., Suresh, K., et al. (2005). Lipid peroxidation and antioxidants status in patients with oral squamous cell carcinoma. The Indian Journal of Medical Research, 122, 529–534.PubMedGoogle Scholar
  56. 56.
    Seril, D. N., Liao, J., Yang, G. Y., et al. (2003). Oxidative stress and ulcerative colitis-associated carcinogenesis: Studies in humans and animal models. Carcinogenesis, 34, 353–362.CrossRefGoogle Scholar
  57. 57.
    Batcioglu, K., Mehmet, N., Ozturk, I. C., et al. (2006). Lipid peroxidation and antioxidant status in stomach cancer. Cancer Investigation, 24, 18–21.PubMedCrossRefGoogle Scholar
  58. 58.
    Jaruga, P., Zastawny, T. H., Skokowski, J., et al. (1992). Oxidative DNA base damage and antioxidant enzyme activities in human lung cancer. FEBS Letters, 341, 59–64.CrossRefGoogle Scholar
  59. 59.
    Conklin, K. A. (2004). Chemotherapy-associated oxidative stress: Impact on chemotherapeutic effectiveness. Integrated Cancer Therapies, 3, 294–300.CrossRefGoogle Scholar
  60. 60.
    Nicolson, G. L., & Conklin, K. A. (2008). Reversing mitochondrial dysfunction, fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy. Clinical & Experimental Metastasis, 25, 161–169.CrossRefGoogle Scholar
  61. 61.
    Conklin, K. A. (2000). Dietary antioxidants during cancer chemotherapy: Impact on chemotherapeutic effectiveness and development of side effects. Nutrition and Cancer, 37, 1–18.PubMedCrossRefGoogle Scholar
  62. 62.
    Betteridge, D. J. (2000). What is oxidative stress? Metabolism, 49(suppl 1), 3–8.PubMedCrossRefGoogle Scholar
  63. 63.
    Hauptlorenz, S., Esterbauer, H., Moll, W., et al. (1985). Effects of the lipid peroxidation product 4-hydroxynonenal and related aldehydes on proliferation and viability of cultured Ehrlich ascites tumor cells. Biochemical Pharmacology, 34, 3803–3809.PubMedCrossRefGoogle Scholar
  64. 64.
    Gonzalez, M. J. (1992). Lipid peroxidation and tumor growth: An inverse relationship. Medical Hypotheses, 38, 106–110.PubMedCrossRefGoogle Scholar
  65. 65.
    Schackelford, R. E., Kaufmann, W. K., & Paules, R. S. (2000). Oxidative stress and cell cycle checkpoint function. Free Radical Biology & Medicine, 28, 1387–1404.CrossRefGoogle Scholar
  66. 66.
    Balin, A. K., Goodman, D. B. P., Rasmussen, H., et al. (1978). Oxygen-sensitive stages of the cell cycle of human diploid cells. The Journal of Cell Biology, 78, 390–400.PubMedCrossRefGoogle Scholar
  67. 67.
    Kurata, S. (2000). Selective activation of p38 MAPK cascade and mitotic arrest caused by low level oxidative stress. The Journal of Biological Chemistry, 275, 23413–23416.PubMedCrossRefGoogle Scholar
  68. 68.
    Wei, Q., Frazier, M. L., & Levin, B. (2000). DNA repair: A double edge sword. Journal of the National Cancer Institute, 92, 440–441.PubMedCrossRefGoogle Scholar
  69. 69.
    Fojo, T. (2001). Cancer, DNA repair mechanisms, and resistance to chemotherapy. Journal of the National Cancer Institute, 93, 1434–1436.PubMedCrossRefGoogle Scholar
  70. 70.
    Zhen, W., Link, C. J., O'Connor, P. M., et al. (1992). Increased gene-specific repair of cisplatin interstrand cross-links in cisplatin-resistant human ovarian cancer cell lines. Molecular and Cellular Biology, 12, 3689–3698.PubMedGoogle Scholar
  71. 71.
    Lee, Y.-J., & Shacter, E. (1999). Oxidative stress inhibits apoptosis in human lymphoma cells. The Journal of Biological Chemistry, 274, 19792–19798.PubMedCrossRefGoogle Scholar
  72. 72.
    Shacter, E., Williams, J. A., Hinson, R. M., et al. (2000). Oxidative stress interferes with cancer chemotherapy: Inhibition of lymphoma cell apoptosis and phagocytosis. Blood, 96, 307–313.PubMedGoogle Scholar
  73. 73.
    Hampton, M. B., Fadeel, B., & Orrenius, S. (1998). Redox regulation of the caspases during apoptosis. Annals of the New York Academy of Sciences, 854, 328–335.PubMedCrossRefGoogle Scholar
  74. 74.
    Chandra, J., Samali, A., & Orrenius, S. (2000). Triggering and modulation of apoptosis by oxidative stress. Free Radical Biology & Medicine, 29, 323–333.CrossRefGoogle Scholar
  75. 75.
    Greenberger, J. S., Kagan, V. E., Pearce, L., et al. (2001). Modulation of redox signal transduction pathways in the treatment of cancer. Antioxidants Redox Signaling, 3, 347–359.PubMedCrossRefGoogle Scholar
  76. 76.
    Feinendegen, L. E., Pollycove, M., & Neumann, R. D. (2007). Whole-body responses to low-level radiation exposure: New concepts in mammalian radiobiology. Experimental Hematology, 35, 37–46.PubMedCrossRefGoogle Scholar
  77. 77.
    Epperly, M. W., Gretton, J. E., Sikora, C. A., et al. (2003). Mitochondrial localization of superoxide dismutase is required for decreasing radiation-induced cellular damage. Radiation Research, 160, 568–578.PubMedCrossRefGoogle Scholar
  78. 78.
    Sabbarova, I., & Kanai, A. (2007). Targeted delivery of radioprotective agents to mitochondria. Molecular Interventions, 8, 295–302.Google Scholar
  79. 79.
    Leach, J. K., Black, S. M., Schmidt-Ullrich, R. K., & Mikkelsen, R. B. (2002). Activation of constitutive nitric-oxide synthase activity is an early signaling event induced by ionizing radiation. The Journal of Biological Chemistry, 277, 15400–15406.PubMedCrossRefGoogle Scholar
  80. 80.
    Conklin, K. A. (2005). Coenzyme Q10 for prevention of anthracycline-induced cardiotoxicity. Integrated Cancer Therapies, 4, 110–130.CrossRefGoogle Scholar
  81. 81.
    Lehninger, A. L. (1951). Phosphorylation coupled to oxidation of dihydrodiphosphopyridine nucleotide. The Journal of Biological Chemistry, 190, 345–359.PubMedGoogle Scholar
  82. 82.
    Rasmussen, U. F., & Rasmussen, H. N. (1985). The NADH oxidase system (external) of muscle mitochondria and its role in the oxidation of cytoplasmic NADH. The Biochemical Journal, 229, 632–641.Google Scholar
  83. 83.
    Nohl, H. (1987). Demonstration of the existence of an organo-specific NADH dehydrogenase in heart mitochondria. European Journal of Biochemistry, 169, 585–591.PubMedCrossRefGoogle Scholar
  84. 84.
    Davies, K. J. A., & Doroshow, J. H. (1986). Redox cycling of anthracyclines by cardiac mitochondria. I. Anthracycline radical formation by NADH dehydrogenase. Journal of Biological Chemistry, 261, 3060–3067.PubMedGoogle Scholar
  85. 85.
    Doroshow, J. H., & Davies, K. J. A. (1986). Redox cycling of anthracyclines by cardiac mitochondria. II. Formation of superoxide anion, hydrogen peroxide, and hydroxyl radical. The Journal of Biological Chemistry, 261, 3068–3074.PubMedGoogle Scholar
  86. 86.
    Gille, L., & Nohl, H. (1997). Analyses of the molecular mechanism of adriamycin-induced cardiotoxicity. Free Radical Biology & Medicine, 23, 775–782.CrossRefGoogle Scholar
  87. 87.
    Eaton, S., Skinner, R., Hale, J. P., et al. (2000). Plasma coenzyme Q10 in children and adolescents undergoing doxorubicin therapy. Clinica Chimica Acta, 302, 1–9.CrossRefGoogle Scholar
  88. 88.
    Karlsson, J., Folkers, K., Astrom, H., et al. (1986). Effect of adriamycin on heart and skeletal muscle coenzyme Q10 (CoQ10) in man. In K. Folkers & Y. Yamamura (Eds.), Biomedical and clinical aspects of coenzyme Q (Vol. 5, pp. 241–245). Amsterdam: Elsevier.Google Scholar
  89. 89.
    Papadopoulou, L. C., & Tsiftsoglou, A. S. (1996). Effects of hemin on apoptosis, suppression of cytochrome C oxidase gene expression, and bone-marrow toxicity induced by doxorubicin. Biochemical Pharmacology, 52, 713–722.PubMedCrossRefGoogle Scholar
  90. 90.
    Palmeira, C. M., Serrano, J., Kuehl, D. W., et al. (1997). Preferential oxidation of cardiac mitochondrial DNA following acute intoxication with doxorubicin. Biochimica et Biophysica Acta, 1321, 101–106.PubMedCrossRefGoogle Scholar
  91. 91.
    Brizel, D. M. (2007). Pharmacologic approaches to radiation protection. Journal of Clinical Oncology, 25, 4084–4089.PubMedCrossRefGoogle Scholar
  92. 92.
    Domae, N., Sawada, H., Matsuyama, E., et al. (1981). Cardiomyopathy and other chronic toxic effects induced in rabbits by doxorubicin and possible prevention by coenzyme Q10. Cancer Treatment Reports, 65, 79–91.PubMedGoogle Scholar
  93. 93.
    Usui, T., Ishikura, H., Izumi, Y., et al. (1982). Possible prevention from the progression of cardiotoxicity in adriamycin-treated rabbits by coenzyme Q10. Toxicology Letters, 12, 75–82.PubMedCrossRefGoogle Scholar
  94. 94.
    Judy, W. V., Hall, J. H., Dugan, W., et al. (1984). Coenzyme Q10 reduction of adriamycin cardiotoxicity. In K. Folkers & Y. Yamamura (Eds.), Biomedical and clinical aspects of coenzyme Q (Vol. 4, pp. 231–241). Amsterdam: North-Holland Biomedical.Google Scholar
  95. 95.
    Cortes, E. P., Gupta, M., Chou, C., et al. (1978). Adriamycin cardiotoxicity: early detection by systolic time interval and possible prevention by coenzyme Q10. Cancer Treatment Reports, 62, 887–891.PubMedGoogle Scholar
  96. 96.
    Buckingham, R., Fitt, J., & Sitzia, J. (1997). Patients’ experience of chemotherapy: Side-effects of carboplatin in the treatment of carcinoma of the ovary. European Journal of Cancer Care, 6, 59–71.PubMedCrossRefGoogle Scholar
  97. 97.
    Iarussi, D., Auricchio, U., Agretto, A., et al. (1994). Protective effect of coenzyme Q10 on anthracyclines cardiotoxicity: Control study in children with acute lymphoblastic leukemia and non-Hodgkin lymphoma. Molecular Aspects of Medicine, 15, S207–S212.PubMedCrossRefGoogle Scholar
  98. 98.
    Loke, Y. K., Price, D., Derry, S., et al. (2006). Case reports of suspected adverse drug reactions—systematic literature survey of follow-up. British Medical Journal, 232, 335–339.CrossRefGoogle Scholar
  99. 99.
    Von Roenn, J. H., & Paice, J. A. (2005). Control of common, non-pain cancer symptoms. Seminars in Oncology, 32, 200–210.CrossRefGoogle Scholar
  100. 100.
    Borneman, T., Piper, B. F., Sun, V. C., et al. (2007). Implementing the fatigue guidelines at one NCCN member institution: Process and outcomes. Journal of the National Comprehensive Cancer Network, 5, 1092–1101.PubMedGoogle Scholar
  101. 101.
    Escalante, C. P., Kallen, M. A., Valdres, R. U., et al. (2010). Outcomes of a cancer-related fatigue clinic in a comprehensive cancer center. Journal of Pain and Symptom Management, 39, 691–701.PubMedCrossRefGoogle Scholar
  102. 102.
    Ryan, J. L., Carroll, J. K., Ryan, E. P., et al. (2007). Mechanisms of cancer-related fatigue. The Oncologist, 12(Suppl. 1), 22–34.PubMedCrossRefGoogle Scholar
  103. 103.
    Mustian, K. M., Morrow, G. R., Carroll, J. K., et al. (2007). Integrative nonpharmacological behavioral interventions for the management of cancer-related fatigue. The Oncologist, 12(Suppl. 1), 52–67.PubMedCrossRefGoogle Scholar
  104. 104.
    Watson, T., & Mock, V. (2004). Exercise as an intervention for cancer-related fatigue. Physical Therapy, 84, 736–743.PubMedGoogle Scholar
  105. 105.
    Zee, P. C., & Acoli-Isreal, S. (2009). Does effective management of sleep disorders reduce cancer-related fatigue? Drugs, 69(Suppl. 2), 29–41.PubMedCrossRefGoogle Scholar
  106. 106.
    Milton, O., Richardson, A., Sharpe, M., et al. (2008). A systematic review and meta-analysis of the pharmacological treatment of cancer-related fatigue. Journal of the National Cancer Institute, 100, 1–12.Google Scholar
  107. 107.
    Levy, M. (2008). Cancer fatigue: A review for psychiatrists. General Hospital Psychiatry, 30, 233–244.PubMedCrossRefGoogle Scholar
  108. 108.
    Nicolson, G. L. (2003). Lipid replacement as an adjunct to therapy for chronic fatigue, anti-aging and restoration of mitochondrial function. Journal of the American Nutraceutical Association, 6(3), 22–28.Google Scholar
  109. 109.
    Agadjanyan, M., Vasilevko, V., Ghochikyan, A., et al. (2003). Nutritional supplement (NTFactor) restores mitochondrial function and reduces moderately severe fatigue in aged subjects. Journal of Chronic Fatigue Syndrome, 11(3), 23–26.CrossRefGoogle Scholar
  110. 110.
    Nicolson, G. L. (2005). Lipid replacement/antioxidant therapy as an adjunct supplement to reduce the adverse effects of cancer therapy and restore mitochondrial function. Pathology Oncology Research, 11, 139–144.PubMedCrossRefGoogle Scholar
  111. 111.
    Wei, Y. H., & Lee, H. C. (2002). Oxidative stress, mitochondrial DNA mutation and impairment of antioxidant enzymes in aging. Experimental Biology and Medicine, 227, 671–682.PubMedGoogle Scholar
  112. 112.
    Huang, H., & Manton, K. G. (2004). The role of oxidative damage in mitochondria during aging: A review. Frontiers in Bioscience, 9, 1100–1117.PubMedCrossRefGoogle Scholar
  113. 113.
    Logan, A. C., & Wong, C. (2001). Chronic fatigue syndrome: Oxidative stress and dietary modifications. Alternative Medicine Review, 6, 450–459.PubMedGoogle Scholar
  114. 114.
    Manuel, y, Keenoy, B., Moorkens, G., Vertommen, J., & De Leeuw, I. (2001). Antioxidant status and lipoprotein peroxidation in chronic fatigue syndrome. Life Science, 68, 2037–2049.CrossRefGoogle Scholar
  115. 115.
    Richards, R. S., Roberts, T. K., McGregor, N. R., et al. (2000). Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome. Redox Reports, 5, 35–41.Google Scholar
  116. 116.
    Felle, S., Mecocci, P., Fano, G., et al. (2000). Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome. Free Radical Biology & Medicine, 29, 1252–1259.CrossRefGoogle Scholar
  117. 117.
    Dianzani, M. U. (1993). Lipid peroxidation and cancer. Critical Reviews in Oncology/Hematology, 15, 125–147.PubMedCrossRefGoogle Scholar
  118. 118.
    Pall, M. L. (2000). Elevated, sustained peroxynitrite levels as the cause of chronic fatigue syndrome. Medical Hypotheses, 54, 115–125.PubMedCrossRefGoogle Scholar
  119. 119.
    Nicolson, G. L., Poste, G., & Ji, T. (1977). Dynamic aspects of cell membrane organization. Cell Surface Reviews, 3, 1–73.Google Scholar
  120. 120.
    Subczynski, W. K., & Wisniewska, A. (2000). Physical properties of lipid bilayer membranes: Relevance to membrane biological functions. Acta Biochimica Polonica, 47, 613–625.PubMedGoogle Scholar
  121. 121.
    Radi, R., Rodriguez, M., Castro, L., et al. (1994). Inhibition of mitochondrial electronic transport by peroxynitrite. Archives of Biochemistry and Biophysics, 308, 89–95.PubMedCrossRefGoogle Scholar
  122. 122.
    Kanno, T., Sato, E. E., Muranaka, S., et al. (2004). Oxidative stress underlies the mechanism for Ca(2+)-induced permeability transition of mitochondria. Free Radical Research, 38, 27–35.PubMedCrossRefGoogle Scholar
  123. 123.
    Nicolson, G. L., & Ellithrope, R. (2006). Lipid replacement and antioxidant nutritional therapy for restoring mitochondrial function and reducing fatigue in chronic fatigue syndrome and other fatiguing illnesses. Journal of Chronic Fatigue Syndrome, 13(1), 57–68.CrossRefGoogle Scholar
  124. 124.
    Ellithorpe, R. R., Settineri, R., & Nicolson, G. L. (2003). Reduction of fatigue by use of a dietary supplement containing glycophospholipids. Journal of the American Nutraceutical Association, 6(1), 23–28.Google Scholar
  125. 125.
    Mansbach, C. M., & Dowell, R. (2000). Effect of increasing lipid loads on the ability of the endoplasmic reticulum to transport lipid to the Golgi. Journal of Lipid Research, 41, 605–612.PubMedGoogle Scholar
  126. 126.
    Seidman, M., Khan, M. J., Tang, W. X., et al. (2002). Influence of lecithin on mitochondrial DNA and age-related hearing loss. Otolaryngology - Head and Neck Surgery, 127, 138–144.PubMedCrossRefGoogle Scholar
  127. 127.
    Piper, B. F., Linsey, A. M., & Dodd, M. J. (1987). Fatigue mechanism in cancer. Oncology Nursing Forum, 14, 17–23.PubMedGoogle Scholar
  128. 128.
    Nicolson, G. L., Ellithorpe, R. R., Ayson-Mitchell, C., et al. (2010). Lipid replacement therapy with a glycophospholipid–antioxidant–vitamin formulation significantly reduces fatigue within one week. Journal of the American Nutraceutical Association, 13(1), 11–15.Google Scholar
  129. 129.
    Colodny, L., Lynch, K., Farber, C., et al. (2000). Results of a study to evaluate the use of Propax to reduce adverse effects of chemotherapy. Journal of the American Nutraceutical Association, 2(1), 17–25.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.The Institute for Molecular MedicineHuntington BeachUSA
  2. 2.Department of Molecular PathologyThe Institute for Molecular MedicineS. Laguna BeachUSA

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