Thursday
September 28, 2023
Dr. rer. nat. Günther Stoll
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Relevance of micronutrients in oncological treatments
Abstract
Micronutrients are defined as essential dietary elements required to regulate a range of physiological functions necessary to maintain or restore health. In a rapidly growing number of observational as well as interventional clinical trials in oncological patients substances like intermediary metabolites (e.g. carnitine), phytochemicals (e.g. isoflavones, lycopene, mistletoe lectin), vitamins (ascorbate, cholecalciferol) and trace elements (zinc, and especially important selenium) showed clinical benefits like reduction of side-effects, improvement in immune response or improvement of clinical efficacy of the tumour-reductive therapy. The problem of randomized clinical trials (RCTs) as a clinical gold standard, however, is that they demonstrate the effect of individual substances or therapeutic measures, but cannot or can only poorly map interactions between biochemical substances via physiological networks. Recent publications show that such interactions may influence therapeutic success as well as the outcome of RCTs in synergistic or antagonistic ways. In this short presentation, this will be elaborated on two examples: the epigenetic regulation of metabolic pathways and the composition of the gut microbiome.
Selected publications of the author on this topic
Stoll, G.: Mikronährstoffe, Immunüberwachung und Immunseneszenz. Deutsche Zeitschrift für Onkologie 52: 101 – 108 (2020)
Stoll, G.: Arzneimittel vs. Nahrungsergänzungsmittel – Abgrenzung, Anwendung und juristische Fallstricke. Deutsche Zeitschrift für Onkologie 54: 78 – 85 (2022)
Stoll, G.: Selen in der Anti-Aging-Medizin. OM – Zs. f. Orthomol. Med. 20: 24 – 28 (2022)
Stoll, G.: Selen und das humane Mikrobiom. OM – Zs. f. Orthomol. Med. 21: 23 – 27 (2023)
Dr. rer. hum. Claudia Vollbracht
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Evidence on high-dose intravenous vitamin C in oncology: epigenetics, quality of life and chemotherapeutic potential
Vitamin C deficiency in oncology patients has been documented in many studies and becomes further intensified by treatment (surgery, radiation, chemotherapy, etc.) [1]. Vitamin C deficit correlates with a decrease in quality of life and poorer rates of survival (oxidative stress ↑, inflammation ↑, immunodeficiency, TET2 ↓, HIF ↑) [1-3].
Infusion treatment can rapidly correct vitamin C deficiencies and studies show significant improvement in quality of life – in particular, significant relief of fatigue, pain, poor appetite, sleep disturbances and depression [4-7]. In addition, vitamin C treatment shows less myelosuppression (leukopenia, anaemia, thrombocytopenia) [7] and a significant and clinically relevant increase in the lymphocyte count in lymphopenia [8].
Initial clinical trial data also show prolonged survival [6, 7, 9] or a trend towards this [5]. This is supported by experimental studies that describe a chemotherapeutic potential through high vitamin C concentrations. Vitamin C primarily acts on three vulnerabilities of many cancer cells: redox imbalance, epigenetic reprogramming and regulation of oxygen sensitivity [10]. Experimental studies observe a direct selective tumour cytotoxic effect through the formation of hydrogen peroxide (H2O2), a shift in the epigenetic profile towards tumour suppression (TET2 ↑, HIF ↓) and a decrease in metastasis-relevant processes (epithelial-mesenchymal transition (EMT) ↓, collagen ↑)[1, 10, 11].
- Carr, A.C. and J. Cook, Intravenous Vitamin C for Cancer Therapy – Identifying the Current Gaps in Our Knowledge. Front Physiol, 2018. 9: p. 1182.
- Mayland, C.R., M.I. Bennett, and K. Allan, Vitamin C deficiency in cancer patients. Palliat Med, 2005. 19(1): p. 17-20.
- Campbell, E.J., et al., Activation of the hypoxia pathway in breast cancer tissue and patient survival are inversely associated with tumor ascorbate levels. BMC Cancer, 2019. 19(1): p. 307.
- Carr, A.C., M.C. Vissers, and J.S. Cook, The effect of intravenous vitamin C on cancer- and chemotherapy-related fatigue and quality of life. Front Oncol, 2014. 4: p. 283.
- Ma, Y., et al., High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci Transl Med, 2014. 6(222): p. 222ra18.
- Ou, J., et al., A randomized phase II trial of best supportive care with or without hyperthermia and vitamin C for heavily pretreated, advanced, refractory non-small-cell lung cancer. J Adv Res, 2020. 24: p. 175-182.
- Ou, J., et al., A Retrospective Study of Gemcitabine and Carboplatin With or Without Intravenous Vitamin C on Patients With Advanced Triple-Negative Breast Cancer. Integr Cancer Ther, 2020. 19: p. 1534735419895591.
- Rodríguez, D.M., et al., Total lymphocyte count in cancer patients with lymphopenia treated with intravenous vitamin C: Results of an observational study. Translational Medicine Communications, 2017. 2(1): p. 3.
- Zhao, H., et al., The synergy of Vitamin C with decitabine activates TET2 in leukemic cells and significantly improves overall survival in elderly patients with acute myeloid leukemia. Leuk Res, 2018. 66: p. 1-7.
- Ngo, B., et al., Targeting cancer vulnerabilities with high-dose vitamin C. Nat Rev Cancer, 2019. 19(5): p. 271-282.
- Polireddy, K., et al., High Dose Parenteral Ascorbate Inhibited Pancreatic Cancer Growth and Metastasis: Mechanisms and a Phase I/IIa study. Sci Rep, 2017. 7(1): p. 17188.
Dr. med. Ilse E. Fleck-Václavik
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Mistletoe Therapy in Cancer Treatment to reduce cancer related fatigue
Cancer related fatigue (CRF) is a well-known issue for cancer patients, affecting a high percentage. Patients suffer not only from physical exhaustion but also from emotional and cognitive symptoms.
CRF is caused both by the disease itself and due to chemotherapy or other anticancer treatments. It can be an ongoing symptom for several years after treatment, reducing the patients´ quality of life.
The administration of subcutaneously injected mistletoe extracts (viscum album L.) can help patients in overcoming their fatigue and restoring their quality of life.
In the following two case reports the value of mistletoe therapy is shown both in the curative and in the palliative setting:
One female patient was diagnosed with breast cancer in 2007 at the age of 26 and had metastasis in the supra- and infraclavicular lymph nodes just 3 years later. Chemotherapy caused severe side-effects and cancer related fatigue. Under the therapy with mistletoe extracts she recovered quickly, being able to return to work. 11 years later she was diagnosed with a malignant breast tumor in the contralateral breast, shortly after having given birth to her daughter. Once more she had to undergo chemotherapy with severe symptoms of cancer related fatigue. Adapting her mistletoe therapy helped her to regain strength rapidly.
When there were no further options for conventional treatment, a male patient with metastatic anal cancer was also offered treatment with subcutaneous injections of mistletoe extract. Under a multimodal therapy with mistletoe extract, homeopathic remedies and the administration of a variation of micronutrients both his physical and mental condition improved. Despite an extremely poor prognosis, the patient survived for a surprisingly long time with a high quality of life.
Both case reports demonstrate the potential benefits of adapting mistletoe therapy to a variety of clinical situations, as well as the importance of paying attention to sometimes small hints to make an astonishing outcome possible.
Steve Ottersberg, MD
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CATEGORY OF FOCUS: Future of Integrative Oncology and Key Therapies Showing Promise in Improving Patient Outcomes
BACKGROUND:
The purpose of this presentation is to review case studies of cancer patients who are utilizing a ketogenic diet. The focus will be on the metabolic pathways epigenetically modulated by ketogenic diet, and the biomarkers associated with oxidative stress and how to optimize ketogenic diet to minimize DNA damage. Energy metabolism and mitochondrial function are altered as a hallmark of many tumor types. These alterations in energy metabolism and mitochondrial function allow cancer cells to evade programmed cell death that is mediated by mitochondrial ROS production. These metabolic alterations are associated with markers of DNA damage such as 8OHDG and Nrf2. In estrogen sensitive cancers, alterations in cytochrome activity and methylation of estradiol has been shown to lead directly to DNA damage from quinone metabolites of estrogen.
METHODS:
Case studies will be presented for patients with cancer diagnosis, that chose to utilize ketogenic diet. Patient data will include, single nucleotide polymorphism genotyping, CBC, CMP, LDH, urinary organic acid profiles, and critical cancer biomarkers.
Participants will learn from a biochemists perspective, the key gene polymorphisms associated with the major metabolic pathways, the critical biomarkers associated with ketogenic diet and how genetic polymorphisms may influence biomarker status, and strategies to optimize patient compliance and outcomes.
RESULTS:
The results of this clinical case review will provide clinicians with an understand of the linkage between genetic markers associated with energy metabolism and DNA damage, the biomarkers of energy metabolism and DNA damage and the result of clinical intervention based on a metabolic approach.
CONCLUSIONS:
With abundant evidence on ketogenic diet and improved survival, quality of life and improved efficacy of standard therapies, clinicians are largely untrained on the genetic and metabolic biomarkers for managing individualized treatments to optimize compliance and quality of life foe patients on ketogenic diet.
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