Integrative Cancer Treatment – Combination of Nutritional Ketosis and Hyperoxygenation Therapies


Dr. Santhosh John

Introduction

Cancer is a multifactorial disease, where various types of cancers exhibit varying mechanisms, pathways, genetic, and cellular defects. However, there are two phenomena that are common to almost all cancers, either causative and/or developmental, namely hypoxia and upregulated glycolysis.

Hypoxia, the absence of enough oxygen in the tissues, is a critical hallmark of solid tumors, which involves increased tumor survival, angiogenesis, glycolytic metabolism, metastasis, resistance to standard treatments and mortality rate. The presence of hypoxia in human tumors has been strongly demonstrated by histopathological study of vascular insufficiency, direct oxygen measurements in tumors, and by physiological imaging and mapping by clinicians and researchers.1,2

Glycolytic metabolism is a consistent feature of most tumor cells across all tissue types. In 1930, Otto Warburg (Nobel Laureate) observed that all cancers express high rates of fermentation, which cause cancers to rely heavily on glucose for energy.3 Mitochondrial defects, overexpression of glycolytic genes, and oncogenic mutations in the tumor microenvironment (TME) contribute to the increased glucose consumption by cancer cells.

Nutritional ketosis and hyper-oxygenation therapies are very effective, non-toxic interventions to target hypoxia and glycolysis.

Nutritional Ketosis

Ketosis is a metabolic condition of the body when it is deprived of carbohydrates, in which ketone bodies are the primary source of energy, instead of glucose. Cancer cells mainly rely on glucose for their energy and, at the same time, normal cells, including brain cells, can survive with ketone bodies in the absence of glucose. Thus, elimination of carbohydrates can slow down the tumor growth and progression.

Nutritional ketosis can limit the growth of the tumor, protects healthy cells from damage by chemotherapy or radiation, accelerates chemotherapeutic toxicity toward cancer cells, and lowers inflammation, which acts as a precursor to cancer.4-7 A dietary regimen called Ketogenic Diet (KD) and ketone supplements are efficient in producing nutritional ketosis in the system.

Ketogenic Diet

The KD is a high-fat, low-carbohydrate diet with adequate protein and calories originally developed in the 1920s as a treatment for intractable epilepsy. The traditional KD is a 4:1 formulation of fat content to carbohydrate plus protein. KD delivers 90% calories from fat, 8% from protein and only 2% from carbohydrate.

Studies in mice models with cerebral tumor and malignant gliomas showed ketosis, enhanced the survival rate and reduced the tumor growth and tumor energy metabolism. The inflammation and angiogenesis found in the TME [toxic metabolic encephalopathy] and the process of apoptosis are greatly influenced by ketosis, which results in the reduction of tumor growth. It is found that ketosis stimulates some complex interactions amongst a number of gene networks that regulate the important intracellular signalling cascades and cellular homeostatic mechanisms for tumor reduction in addition to lowering blood glucose.8-10 The above results are reobserved in the animal studies of prostate cancer, colon cancer, and gastric cancer.11-14 Ketosis potentiated the chemotherapy effects, concurrently healed the side effects of chemotherapy in normal cells.15

KD improved the quality of life in patients with advanced metastatic cancer and also improved cancer patients’ quality of sleep, emotional health, and mood.16,17

Ketone Supplementation

Therapeutically ketone supplements like 1, 3-butanediol or ketone esters are administered to elevate ketone bodies in the blood without the need of severe dietary restriction. These agents serve as ketogenic precursors and are either enzymatically cleaved or metabolized to produce ketones. Ketone supplements can be administered along with standard diet or with KD. Ketone supplements with KD offer more profound results.18

Hyperoxygenation Therapies

Hyperoxygenation therapies help to increase the O2 level of the TME to target hypoxia. Hyperbaric oxygen therapy and ozone therapy are studied by many researchers in regards to cancer due to its efficacy, safety, and wide usage in the health industry.

Hyperbaric oxygen therapy. Hyperbaric oxygen therapy (HBO2T) involves the administration of 100% oxygen at elevated pressure (greater than sea level). HBO2T increases plasma O2 saturation, which facilitates oxygen delivery to the tissues, independent of haemoglobin O2 saturation.

Numerous animal studies confirm the anti-proliferative effect of HBO2T. Both in vivo and in vitro study of murine osteosarcoma exposed to HBO2T, shows significant reduction in tumor volume, metastasis, proliferation, and mortality rate. When HBO2T combined with carboplatin, the chemotherapeutic effect was greatly accelerated.19 In rat model studies of mammary tumors and glioma, the HBO2T reduced the tumor growth, angiogenesis, and increased the apoptosis. Mesenchymal-to-epithelial transition, induced by HBO2T, reduced the aggressiveness of the tumor cells. Glycolysis, the signature cancer metabolism, has been shifted to oxidative phosphorylation, which results in tumor suppression.20-23

In a study of nineteen randomised control trials with 2286 patients, HBO2T elicited anti-proliferative effects, especially with head and neck and uterine cervix cancers.24 HBO2T enhanced the effects of 5-fluorouracil (5-FU) in a mice study with sarcoma,25 and also enhanced the chemotherapeutic effect of doxorubicin both in vitro and in vivo study of rat model metastatic lung cancer.26 HBO2T proved its strong anti-proliferative effect in mammary tumor as a stand-alone treatment in various animal studies.27-30 HBO2T with Radio Therapy (RT) has shown good result in patients with colon and rectal cancer.31 In vitro studies of leukemia and prostate cancers treated with HBO2T elicited profound anti-cancer properties along with improving the drug sensitivity.32-35

Intravenous ozone therapy. Ozone therapy refers to the process of administering ozone gas into the body to treat a disease or wound. Ozone is a colorless gas made up of three atoms of oxygen (O3). Ozone therapy can be comfortably administered in cancer due to its profound anti-cancer properties.

Human cell culture studies of lung, breast, uterine, colon tumors and neuroblastoma, when treated with O3, exhibited inhibition of tumor cells through apoptosis. O3 also potentiates the effect of 5-FU and chemotherapy drugs like cisplatin and etoposide.36,38,39 In vitro study of ovarian cancer, colon cancer, lung cancer and sarcoma, when treated with O3, decreased the tumor metastasis and proliferation, and increased the cytotoxicity of radiation, cisplatin and 5-FU.37,40,41 In a rabbit model study with metastatic squamous cell carcinoma, when treated with medical O3/O2 gas mixture intra peritoneally has shown complete disappearance of primary tumor along with prevention and/or remission of local and distant metastases.42

In addition, the potentiation of CT and RT by O3 could be of higher clinical relevance. Animal studies with rat model sarcoma and tongue cancer and mice model peritoneal cancer, when treated with adjuvant O3 therapy, report super anti-tumor effects along with greater survival rates.43-45

Some human clinical trials on O3 therapy in cancer shown fantastic results. Patients with pelvic tumor, head and neck tumors, non-small cell lung cancer treated with O3 with or without RT, showed good results, which includes improved quality of life, less aggressive tumor behavior, and fast tumor regression with minimal side effects of radiation.46-49

Combination of Nutritional Ketosis and Hyperoxygenation Therapies

Combining these therapies produces potent, synergistic anti-cancer effects by targeting several overlapping metabolic pathways that are critical to cancer progression and are especially prominent in metastatic cells.

In a mouse model study of metastatic tumor by Angela Poff, et al., (i) mice group treated with KD, (ii) mice group treated with KD and ketone supplements and (iii) mice group treated with KD, ketone supplements and hyperbaric oxygen therapy exhibited a 44.6%, 65.4% and 103.2% increase in mean survival time compared to controls (mice group fed with standard diet alone), respectively. Combination group has shown significant reduction in tumor burden and metastatic spread compared to other groups. This study strongly suggests that combining nutritional ketosis with HBO2T may be an effective non-toxic therapy for the treatment of metastatic cancer.50

Maurer GD, et al., who studied the utilization of ketone bodies by glioma cells, suggest that, along with nutritional ketosis, a co treatment – an antiangiogenic agent like hyperoxygenation therapy can potentiate the  anti-tumor effect by synergistic action.8 In a double blind control study, 54 critically ill cancer patients with 6 different metastatic tumors (liver cancer, colorectal cancer, kidney cancer, brain metastatic tumors, breast cancer, and lung cancer) were treated with the combination of KD and intravenous ozone therapy (IOT). After three months, an average of 58% reduction in the tumor size was recorded.51 This study continued with 31 patients for 180 days with an addition of HBO2T and several supplements after 90 days and resulted in 98.8% reduction in the tumor size, which warrants the development of non-toxic, non-invasive cancer treatment protocol with the substantial inclusion of above mentioned therapeutic components.

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Published June 17, 2023

About the Author

Dr. Santhosh John is Ayush Medical Officer (Naturopathy & Yoga) at Government Primary Health Centre, Gudalur, Theni District, Tamil Nadu, India. E-mail: manonehujeph@google.com, Mob: 0091 8668161009