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Cancer: An Odyssey Part 3: Oxygen Therapy, The Mighty Achilles


"Friends, have we never been in danger before this... did I not keep my nerve, and use my wits to find a way out for us? Now I say by hook or crook this peril too shall be something that we remember.”

— Odysseus, The Odyssey

I invariable get the question from everyone who I talk to: “so, is your father on chemotherapy, radiation or getting surgery?”

The answer, of course, is no.

Depending on the person's point of view, is always followed up by judgement, with the assumption that we are resigned his death for declining conventional treatment, or interest, which is followed up by the series of questions which amount to: “well, what are you doing?”

As we move forward in our series, let's discuss how to appropriately answer that.

In Part 1, we discussed the fundamental flaws in the paradigm of how the medical field views cancer. Conversely, by using a functional medicine approach, the key is to work on the cause, not the effect!

In Part 2, we dove deeper into the science regarding the metabolic advantages of fasting, caloric restriction and the ketogenic diet, particularly with respect to improving substrate in both the healthy and cancerous cells.

Just as the wise Odysseus used his wits to overcome his perils, overcoming cancer requires a combination of knowledge and experience that we shall explore further here. Now, throughout the rest of this series, we will be using individual heroes from the Trojan War to act as metaphors for the individual therapies.

As such, it makes sense to begin with the Achilles, who was the mightiest hero, but so headstrong and prideful, that he was just as likely to do harm, as he was to help.

“Sing, O Goddess, the ruinous wrath of Achilles, son of Peleus, the terrible curse that brought unnumbered woes to the Achaeans and hurled to Hades so many heroic souls...”

— Homer, The Iliad

The perfect analog for the great Achilles is oxygen bio-therapy.

While the production of free radicals, hydrogen peroxide (H2O2) in particular, causes damage that initiates both the development and progression of cancer [1, 2], hydrogen peroxide also plays a role in the induction of apoptosis (programmed cell suicide) in cancer cells selectively [3, 4].

In fact, the upregulation of free radicals, or reactive oxygen species (ROS), is a common mechanism used in chemotherapy drugs [5]. Moreover, supplemental oxygen is currently used as an adjunct to improve the outcome of conventional treatments [6, 7].

Now, there are a number of modalities which can used to but among the most researched is hyperbaric oxygen therapy [6, 8, 9, 10]. In addition to its increased production of ROS and related apoptosis, hyperoxic therapy has the ability to increase plasma oxygen levels, with subsequent downregulation of hypoxia-inducible factor-α (HIF-1α) and vascular endothelial growth factor (VEGF), thus limiting the tumors ability to proliferate and metastasize [6, 10].

Moreover, while it is currently thought of as complementary to conventional methods, such as chemotherapy and radiation, some research indicated it may even be more beneficial [10]!

But, while oxygen biotherapy is exciting by itself, it is the research being done when used in conjunction with a ketogenic diet that appears the most promising. By starving the cancer cells of glucose and introducing excess oxygen, this combination therapy reverses both of the metabolic adaptions cancer cells have adopted. In turn, they particularly sensitive to the increased free radical production, while the healthy cells are protected [11, 12].

As we previously established in Part 2, the concurrent administration of a ketogenic diet provides for a unique metabolic state which makes the cancer cells more susceptible to this oxidative stress, while protecting the healthy mitochondria [13].

Similar to Achilles, these free radicals are a force to be reckoned with, which while they can be self-destructive, if channeled properly, they can lead the pack in defeating the enemy!

Regarding other methods, interestingly, a number of herbs and vitamins, commonly thought of as antioxidants, can actually induce the production of hydrogen peroxide and other free radicals, including garlic [14], cayenne [15], turmeric/curcumin [16, 17] and high dose vitamin C [18, 19].

Moreover, in vitro data found hydrogen peroxide produced by oxidation of high dose vitamin C had an equivalent induction of cell death when compared to exogenous hydrogen peroxide therapy, with a particular selective preference for cancerous cells [20]!

Unfortunately, given my father is still dealing with his broken hip, hyperbaric oxygen and intravenous vitamin C are not options. However, oral exogenous hydrogen peroxide has made for an excellent substitute. Additionally, we had previous experience using it in his recovery from a mini-stroke induced by an occlusion following a severe tooth infection.

Just as a teaser to Part 4, let's discuss one more set of herbs we are currently using that also have the potential to induce apoptosis through increased free radical production. Two of the herbs in the Essiac tea preparation contain anthraquinones, which have shown efficacy at destroying cancer cells [21, 22] and whose derivatives are even currently being used as a form of chemotherapy [23, 24].

Now, this is only a fraction of the potential benefits of that particular therapy, but we will save the rest of the juicy stuff until next time. So make sure to stay tuned for Part 4. In the meantime, if you are interested in some more information on hyperoxic therapy Travis Christofferson discusses quite a bit of Dr. Dominic D'Agostino's research in his incredible book, Tripping Over The Truth.

While it is commonly thought that cancer cells are practically immortal, that is operating from the assumption that we will honor the metabolic agreement entered into when the cancer cells first developed and continue to provide the cancer with excess dietary carbohydrates and sugars, while allowing hypoxia to occur. But by implementing a calorie restricted ketogenic diet with hyperoxic therapy, we can hopefully initiate the changes necessary to defeat the beast!

“Fool, prate not to me about covenants. There can be no covenants between men and lions, wolves and lambs can never be of one mind, but hate each other out and out and through. Therefore there can be no understanding between you and me, nor may there be any covenants between us, till one or other shall fall”

— Achilles, The Iliad

References:

1) Lisanti, M. P., Martinez-Outschoorn, U.E., Lin, Z., Pavlides, S., Whitaker-Menezes, D., Pestell, R.G., Howell, A. & Sotgia, F. (2011). Hydrogen peroxide fuels aging, inflammation, cancer metabolism & metastasis: The seed & soil also needs “fertilizer.” Cell Cycle. Vol. 10(15):2440–2449.

2) Strzelczyk, J.K. & Wiczkowski, A. (2012). Oxidative damage & carcinogenesis. Contemp Oncol. Vol. 16(3):230–233.

3) López-Lázaro, M. (2007). Dual role of hydrogen peroxide in cancer: Possible relevance to cancer chemoprevention & therapy. Cancer Lett. Vol. 252(1):1-8.

4) Jeong, C.H. & Joo, S.H. (2016). Downregulation of reactive oxygen species in apoptosis. J Cancer Prev. Vol. 21(1):13–20.

5) Liou, G.Y. & Storz, P. (2010). Reactive oxygen species in cancer. Free Radic Res. Vol. 44(5):10.

6) Moen, I. & Stuhr, L.E.B. (2012). Hyperbaric oxygen therapy & cancer: A review. Targ Oncol. Vol. 7(4), 233–242.

7) Hatfield, S. M., Kjaergaard, J., Lukashev, D., Schreiber, T.H., Belikoff, B., Abbott, R., Sethumadhavan, S., Philbrook, P., Ko, K., Cannici, R., Thayer, M., Rodig, S., Kutok, J.L., Jackson, E.K., Karger, B., Podack, E.R., Ohta, A. & Sitkovsky, M.V. (2015). Immunological mechanisms of the antitumor effects of supplemental oxygenation. Sci Transl Med. Vol. 7(277):277ra30.

8) Lindenschmidt, R.C., Margaretten, N., Griesemer, R.A. & Witschi, H.P. (1986). Modification of lung tumor growth by hyperoxia. Carcinogenesis. Vol. 7(9):1581-1586.

9) Daruwalla, J. & Christophi, C. (2006). Hyperbaric oxygen therapy for malignancy: A review. World J Surg. Vol. 30(12):2112-2131.

10) Raa, A., Stansberg, C., Steen, V.M., Bjerkvig, R., Reed, R.K. & Stuhr, L.E. (2007). Hyperoxia retards growth & induces apoptosis & loss of glands & blood vessels in DMBA-induced rat mammary tumors. BMC Cancer. Vol. 7:23.

11) Poff, A.M., Ari, C., Seyfried, T.N. & D’Agostino, D.P. (2013). The ketogenic diet & hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer. PLoS ONE. Vol. 8(6):e65522:9 pp.

12) Poff, A.M., Ward, N., Seyfried, T.N., Arnold, P. & D’Agostino, D.P. (2015). Non-toxic metabolic management of metastatic cancer in VM mice: Novel combination of ketogenic diet, ketone supplementation & hyperbaric oxygen therapy. PLoS ONE. Vol. 10(6):e0127407.

13) Allen, B.G., Bhatia, S.K., Anderson, C.M., Eichenberger-Gilmore, J.M., Sibenaller, Z.A., Mapuskar, K.A., Schoenfeld, J.D., Buatti, J.M., Spitz, D.R. & Fath, M.A. (2014). Ketogenic diets as an adjuvant cancer therapy: History & potential mechanism. Redox Biol. Vol. 2:963–970.

14) Schäfer, G. & Kaschula, C.H. (2014). The immunomodulation & anti-inflammatory effects of garlic organosulfur compounds in cancer chemoprevention. Anticancer Agents Med Chem. Vol. 14(2):233–240.

15) Oyagbemi, A.A, Saba, A.B. & Azeez, O.I. (2010). Capsaicin: A novel chemopreventive molecule & its underlying molecular mechanisms of action. Indian J Cancer. Vol. 47(1):53-58. 16) Tuorkey, M.J. (2014). Curcumin a potent cancer preventive agent: Mechanisms of cancer cell killing. Interv Med Appl Sci. Vol. 6(4):139-146.

17) Papież, M.A., Krzyściak, W., Szade, K., Bukowska-Straková, K., Kozakowska, M., Hajduk, K., Bystrowska, B., Dulak, J. & Jozkowicz, A. (2016). Curcumin enhances the cytogenotoxic effect of etoposide in leukemia cells through induction of reactive oxygen species. Drug Des Dev Ther. Vol. 10:557-570.

18) González, M.J., Rosario-Pérez, G., Guzmán, A.M., Miranda-Massari, J.R., Duconge, J., Lavergne, J., Fernandez, N., Ortiz, N., Quintero, A., Mikirova, N., Riordan, N.H., Ricart, C.M. & Ricart, C.M. (2010). Mitochondria, energy & cancer: The relationship with ascorbic acid. J Orthomol Med. Vol. 25(1):29-38.

19) Park, S. (2013). The effects of high concentrations of vitamin C on cancer cells. Nutrients. Vol. 5(9):3496–3505.

20) Chen, Q., Espey, M.G., Krishna, M.C., Mitchell, J.B., Corpe, C.P., Buettner, G.R., Shacter, E. & Levine, M. (2005). Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Nat Acad Sci USA. Vol. 102(38):13604-13609.

21) Su Y.T., Chang, H.L. Shyue, S.K. & Hsu, S.L. (2005). Emodin induces apoptosis in human lung adenocarcinoma cells through a reactive oxygen species-dependent mitochondrial signaling pathway.Biochem Pharmacol. 2005 Jul 15;70(2):229-241.

22) Xie, M.J., Ma, Y.H., Miao, L., Wang, Y,, Wang, H.Z., Xing, Y.Y., Xi, T. & Lu, Y.Y. (2014). Emodin-provoked oxidative stress induces apoptosis in human colon cancer HCT116 cells through a p53-mitochondrial apoptotic pathway.Asian Pac J Cancer Prev. Vol. 15(13):5201-5205.

23) Shaaban, S., Negm, A., Ibrahim, E.E. & Elrazak, A. A. (2014). Chemotherapeutic agents for the treatment of h Carcinoma: Efficacy & mode of action. Oncol Rev. Vol. 8(1):246.

24) Vanajothi R. & Srinivasan P. (2016). An anthraquinone derivative from Luffa acutangula induces apoptosis in human lung cancer cell line NCI-H460 through p53-dependent pathway. J Recept Signal Transduct Res. Vol. 36(3):292-302.

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