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Orthomolecular Medicine News Service, September 17, 2024

Nutritional Pharmacology and Cancer: A Comprehensive Review

Juan Manuel Martinez, M.D.

Introduction

Intravenous (IV) and oral nutritional pharmacology represents a rapidly evolving field within oncology, offering potential therapeutic benefits by delivering high concentrations of nutrients and pharmacological agents directly to patients. The integration of IV nutritional strategies into cancer management aims to mitigate the side effects of conventional treatments, enhance immune function, and potentially exhibit direct anti-cancer effects.

Compassion in Cancer Treatment: A Broader Perspective

Compassion in cancer treatment goes beyond standard clinical care to include a profound sensitivity to the emotional, psychological, and physical suffering of patients. It is an integral part of patient-centered care, especially in the context of serious illnesses like cancer, where patients often experience not just physical pain but also emotional and existential distress.

Compassionate care involves recognizing and addressing these multiple dimensions of suffering. It encourages healthcare providers to engage with patients on a deeper level, understanding their fears, concerns, and hopes. In practice, this means offering emotional support, facilitating open communication about treatment options and outcomes, and ensuring that patients feel respected and valued throughout their care journey.

From a nutripharmacological perspective, compassion also manifests in the personalized care plans that consider the unique nutritional and pharmacological needs of each patient. This might include customizing IV nutritional therapies to not only support the body's physical health but also to enhance the patient's overall well-being, reduce treatment-related side effects, and improve quality of life.

In integrative oncology, compassion might be reflected in the use of supportive therapies that address both the physical and emotional aspects of cancer treatment. For instance, alongside conventional cancer treatments, patients might receive nutritional counseling, stress management techniques, and therapies aimed at improving mental health, such as mindfulness and relaxation exercises. These complementary approaches can significantly improve the patient's experience and outcomes, making compassion a cornerstone of holistic cancer care.

Vitamin C and Cancer

High-dose intravenous vitamin C (IVC) has garnered significant interest in cancer therapy. Early studies demonstrated that pharmacologic doses of ascorbate could selectively induce cytotoxicity in cancer cells without harming normal cells. This selective cytotoxicity is primarily attributed to the production of hydrogen peroxide in the extracellular space surrounding tumor cells, which is lethal to cancer cells but not to normal cells due to their higher antioxidant capacity [1]. Clinical investigations have shown that high-dose IVC can improve the quality of life and reduce chemotherapy side effects in cancer patients [2]. Recent research supports these findings, highlighting IVC's potential as a promising multi-targeting agent in cancer treatment. Böttger et al. (2021) demonstrated the efficacy of high-dose IVC in targeting multiple cancer pathways, establishing it as a potent anti-cancer agent [3].

The idea that vitamin C could play a critical role in cancer therapy is not new. Over 60 years ago, William J. McCormick, M.D., proposed that deficient collagen formation, due to vitamin C deficiency, is a key factor in various conditions, including cancer [4]. McCormick hypothesized that nutritional vitamin C deficiency might underlie collagen diseases and, subsequently, cancer. His theory laid the groundwork for later studies, including those by Linus Pauling and Ewan Cameron, who explored high-dose vitamin C for cancer treatment. This historical perspective adds depth to our understanding of vitamin C's potential in modern oncology.

Pharmaco-Nutrients and Immuno-Nutrients in Cancer

The concept of pharmaco-nutrients and immuno-nutrients has gained significant attention in cancer treatment, forming part of an integrative approach aimed at enhancing therapeutic outcomes. These nutrients, administered at pharmacological doses, exert effects beyond their basic nutritional roles, particularly in modulating the immune system and bolstering the body's resilience against cancer.

Pharmaco-Nutrients in Cancer Therapy

Pharmaco-nutrients are nutrients administered in doses high enough to produce drug-like effects. Notable examples include:

1. Omega-3 Fatty Acids: Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have demonstrated anti-inflammatory and anti-cancer properties. These fatty acids inhibit the production of pro-inflammatory cytokines and reduce cancer cachexia risk by modulating inflammation-related pathways and preserving muscle mass [5].
2. Glutamine: This amino acid is critical in maintaining gut integrity and supporting immune function during cancer treatment. For patients undergoing chemotherapy, glutamine has been shown to reduce the incidence of mucositis and other gastrointestinal side effects, thereby improving overall nutritional status [6].
3. Curcumin: The active compound in turmeric, curcumin, exhibits anti-inflammatory, antioxidant, and anti-cancer properties. At pharmacological doses, curcumin can inhibit cancer cell proliferation, induce apoptosis, and enhance the efficacy of chemotherapy and radiotherapy [7].

Immuno-Nutrients in Cancer Therapy

Immuno-nutrients are specific nutrients that modulate the immune system, thereby improving the body's defense mechanisms against cancer:

1. Arginine: A conditionally essential amino acid, arginine enhances T-cell function, increases nitric oxide production, and improves wound healing. In the context of cancer, arginine supplementation supports immune function and enhances the response to immunotherapy [8].
2. Nucleotides: As the building blocks of DNA and RNA, nucleotides play a crucial role in immune function. Supplementation with nucleotides has been shown to enhance immune responses, improve gut health, and support recovery in cancer patients [9].
3. Vitamin D: Vitamin D is known for its immunomodulatory effects, which are crucial in cancer therapy. It enhances the pathogen-fighting capabilities of monocytes and macrophages while decreasing inflammation. Sufficient levels of vitamin D are associated with better outcomes in cancer patients, particularly in terms of survival and response to treatment [10].

Pleiotropic Effects of Pharmacological Intravenous Vitamin C in Oncology

Pharmacological intravenous vitamin C (IVC) has been increasingly studied in oncology for its pleiotropic effects-meaning it can exert multiple effects depending on the context, dosage, and specific cancer type. Understanding these effects is crucial to explaining the discrepancies in study outcomes, such as those between the Mayo Clinic's study and the pioneering work of Dr. Linus Pauling and Ewan Cameron.

1. Pro-Oxidant Activity: At pharmacological doses, IVC generates hydrogen peroxide in the extracellular fluid, selectively targeting cancer cells while sparing normal cells [11].
2. Immune Modulation: IVC has shown potential in modulating the immune system by enhancing the function of various immune cells, including T-cells and natural killer cells. This modulation can lead to improved immune surveillance and possibly better tumor control [12].
3. Collagen Synthesis: Vitamin C is crucial for collagen synthesis, which may help stabilize the extracellular matrix and potentially limit tumor invasion and metastasis [13].
4. Anti-Inflammatory Effects: IVC has demonstrated the ability to reduce inflammation, a common feature in the tumor microenvironment. By lowering pro-inflammatory cytokines, IVC may help create a less conducive environment for cancer progression [14].
5. Inhibition of Hypoxia-Inducible Factor (HIF-1): IVC may inhibit HIF-1, a key regulator in the cellular response to hypoxia, which is often upregulated in tumors. This inhibition can disrupt the metabolic flexibility of cancer cells and reduce their survival under low oxygen conditions [15].
6. Enhancing Chemotherapy and Radiotherapy: IVC has been shown to enhance the efficacy of conventional cancer treatments like chemotherapy and radiotherapy. It can increase the sensitivity of cancer cells to these treatments while protecting normal cells from their toxic effects, highlighting its role as an adjuvant therapy [16].

Critical Comparison: Mayo Clinic and Pauling & Cameron's Studies

The Mayo Clinic's study on terminal cancer patients failed to replicate the results achieved by Dr. Linus Pauling and Ewan Cameron, who claimed that high doses of vitamin C could extend the lives of these patients. The primary reasons for this discrepancy lie in the differences in experimental design and methodology between the two studies, particularly in the administration routes of vitamin C-oral versus intravenous (IV)-and the broader implications within orthomolecular medicine and nutripharmacology.

• Study Design: Pauling and Cameron conducted non-controlled studies, while the Mayo Clinic performed randomized, double-blind, placebo-controlled trials. This rigorous design minimizes bias and could explain the differences in outcomes [17].
• Bioavailability and Pharmacokinetics: A critical difference between the studies was the method of vitamin C administration. Oral administration of vitamin C, as used in the Mayo Clinic's study, is limited by the body's intestinal absorption mechanisms, which become saturated at relatively low doses. This limitation prevents oral vitamin C from achieving the high plasma concentrations possible with intravenous administration [18]. Intravenous vitamin C, on the other hand, bypasses the digestive system entirely, allowing it to directly enter the bloodstream and reach pharmacological concentrations that can be more than tenfold higher than what is possible with oral dosing [19]. This distinction is crucial in orthomolecular medicine, where achieving these higher blood levels is believed to be necessary for therapeutic effects, especially in cancer treatment.
• Pharmacological Effects of High-Dose IV Vitamin C: Within the field of nutripharmacology, IV vitamin C is recognized for its unique properties that differ from those seen with dietary or oral vitamin C. At high plasma concentrations, vitamin C can act as a pro-oxidant, generating hydrogen peroxide selectively in tumor tissues, which can lead to cancer cell death while sparing normal cells [20]. This pharmacological effect is not observed with oral administration due to its inability to reach such high plasma levels [21]. The Mayo Clinic's use of oral vitamin C, therefore, would not be expected to produce the same therapeutic outcomes as Pauling and Cameron's use of IV vitamin C.

Nutritional Interventions in Cancer Cachexia

Cancer cachexia, characterized by weight loss, muscle atrophy, and inflammation, remains a significant challenge in oncology. Nutritional interventions, including IV administration of omega-3 fatty acids, amino acids, and micronutrients, have shown promise in improving nutritional status and attenuating the progression of cachexia [22]. These interventions not only provide essential nutrients but also modulate inflammatory pathways, which play a critical role in the pathogenesis of cachexia [23].

Nutritional Support During Chemotherapy

Adjuvant chemotherapy often results in various late toxicities, including fatigue, gastrointestinal disturbances, and immunosuppression. Nutritional approaches, particularly IV supplementation, can support patients undergoing chemotherapy by reducing the severity of these side effects. For instance, IV administration of antioxidants, such as vitamin C and glutathione, has been studied for its potential to protect normal tissues from oxidative damage caused by chemotherapy [24].

Comparative Analysis of Nutritional Pharmacology and Traditional Pharmaceuticals in Cancer Care

The following table compares the roles of nutritional pharmacology, specifically intravenous vitamin C, with traditional pharmaceutical approaches in oncology.

Here is the comparative chart showing the outcomes (tumor regression, survival improvement, and quality of life improvement) for conventional cancer therapies alone (chemotherapy, radiotherapy, immunotherapy) versus these therapies combined with intravenous nutri-pharmacological therapy (IVC). The chart clearly illustrates the enhanced outcomes when IVC is included in the treatment regimen

• IHR Magazine discusses how intravenous vitamin C (IVC) therapy, when combined with chemotherapy, can enhance treatment efficacy. It suggests that vitamin C sensitizes cancer cells to chemotherapy, potentially reducing tumor progression and improving patient outcomes. IHR Magazine. "Effectiveness of Intravenous Vitamin C in Combination with Conventional Chemotherapy in Cancer Treatment."
• It refers to studies showing that IVC can improve tumor regression, survival rates, and overall quality of life, especially when used in combination with standard cancer treatments. Journal of Experimental & Clinical Cancer Research. "High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer." BioMed Central. Available at: Journal of Experimental & Clinical Cancer Research.
• The reference from the National Cancer Institute (NCI) highlights that IVC can achieve plasma concentrations significantly higher than oral administration, which might contribute to its ability to selectively kill cancer cells without harming normal cells. National Cancer Institute (NCI). "Intravenous High-Dose Vitamin C in Cancer Therapy." Available at: NCI.
• The reference from Cancer Ireland notes that IVC has shown potential in stabilizing disease and prolonging survival, particularly in advanced or refractory cancers when combined with chemotherapy. Cancer Ireland. "Intravenous Vitamin C Therapy." Available at: Cancer Ireland.

These findings highlight the potential of combining traditional cancer treatments with advanced therapies like IVC to achieve better clinical outcomes, although further research is needed to confirm long-term benefits.

Understanding Pleiotropic Effects and the Triage Theory

Pharmacological and Nutritional Targeting of Cancer Pathways

Recent advances in cancer biology have identified voltage-gated sodium channels as potential pharmacological targets in cancer treatment. Nutritional interventions, including specific micronutrients delivered intravenously, may inhibit these channels, thereby reducing cancer cell proliferation and metastasis [25]. This novel approach underscores the intersection of nutritional pharmacology and molecular oncology, providing a new avenue for cancer treatment [26].

Historical Background of Intravenous Vitamin C in Cancer Treatment

The concept of using high-dose vitamin C as a therapeutic agent dates back to the mid-20th century. In the 1950s, Dr. Frederick Klenner, a pioneer in the use of vitamin C, began utilizing high doses of intravenous vitamin C to treat a wide range of viral infections and chronic diseases [27]. Dr. Klenner's groundbreaking work demonstrated that large doses of vitamin C could effectively treat conditions such as polio, hepatitis, and encephalitis [28]. Although his work initially focused on infectious diseases, it laid the foundation for later investigations into the use of vitamin C in cancer treatment.

The turning point in cancer therapy came with the pioneering work of Dr. Linus Pauling and Dr. Ewan Cameron in the 1970s. Linus Pauling, a two-time Nobel laureate, and Ewan Cameron, a Scottish surgeon, hypothesized that high doses of vitamin C, administered intravenously, could inhibit the growth of cancer cells and improve the quality of life for cancer patients [29].

Pauling and Cameron's collaboration resulted in a series of studies that demonstrated prolonged survival in terminal cancer patients treated with high-dose vitamin C compared to those who received standard care. Their findings, published in several scientific journals, sparked considerable interest in the potential role of vitamin C in oncology. However, subsequent studies, particularly those conducted at the Mayo Clinic in the late 1970s, failed to replicate these results when vitamin C was administered orally [30]. This discrepancy was later attributed to differences in the administration route-intravenous vs. oral-and the pharmacokinetics of vitamin C.

The Work of Hugh Riordan and Michael Gonzalez

The legacy of Pauling and Cameron's work was carried forward by Dr. Hugh Riordan and his colleagues, including Dr. Michael Gonzalez, who further investigated the therapeutic potential of intravenous vitamin C (IVC) in cancer treatment. Dr. Riordan, an advocate of orthomolecular medicine-a form of complementary and alternative medicine that emphasizes the use of naturally occurring substances in optimal amounts-was instrumental in developing protocols for the safe and effective administration of IVC in cancer patients [31].

Dr. Riordan's research, conducted at the Riordan Clinic, provided compelling evidence that pharmacologic doses of vitamin C could exert cytotoxic effects on cancer cells while sparing normal cells [32]. This work was published extensively and has been widely cited in the fields of orthomolecular medicine and regenerative medicine [33]. Dr. Michael Gonzalez, a professor at the University of Puerto Rico, further expanded on this research, exploring the biochemical mechanisms underlying vitamin C's anti-cancer effects and its role in enhancing the efficacy of conventional therapies [34].

Recent Advances and Current Perspectives

In recent years, the scientific community has revisited the potential of IVC in oncology, with a growing body of evidence supporting its use as an adjunctive therapy. Researchers have focused on optimizing IVC protocols, understanding the pharmacodynamics of high-dose vitamin C, and elucidating its role in modulating oxidative stress and immune responses in cancer patients [35].

The concept of ortho-regenerative medicine has also emerged, building on the principles of orthomolecular medicine to incorporate regenerative techniques that support the body's natural healing processes [36]. IVC is now considered a key component of this approach, particularly in integrative oncology settings where it is used to enhance patient resilience and improve clinical outcomes [37].

Protocols of Metabolic Rehabilitation for Cancer

According to the protocols outlined by Dr. Juan Manuel Martínez Méndez, metabolic-mitochondrial rehabilitation for cancer requires an integrative and compassionate approach. These protocols aim to regulate and optimize all organic systems, selectively inducing apoptosis in cancer stem cells while generating positive pleiotropic effects, such as improving the quality of life, reducing oxidative stress, enhancing hepatic detoxification, and supporting overall cellular health. The protocols include high doses of sodium ascorbate (vitamin C), often exceeding 50 grams per infusion, combined with other therapies like alpha-lipoic acid, which together act as potent redox agents to combat oxidative stress in cancer patients.

The rehabilitation strategy also incorporates other therapies like bioresonance and magnetic field therapy, aimed at treating the patient holistically by addressing physical, emotional, and mental dimensions. The goal is to maximize the integral energy function of the body, leading to improved outcomes in the fight against cancer [38].

Conclusion

IV nutritional pharmacology presents a promising adjunct to conventional cancer therapies, offering benefits such as enhanced therapeutic efficacy, reduced toxicity, and improved patient outcomes. While more research is needed to fully understand the mechanisms and optimize protocols, current evidence supports the integration of these approaches in the comprehensive care of cancer patients. The history of intravenous vitamin C in cancer treatment is a testament to the persistence and innovation of researchers dedicated to exploring alternative and complementary therapies. From the early hypotheses of William J. McCormick, Pauling, Cameron, and Klenner to the contemporary work of Riordan and Gonzalez, IVC has evolved into a promising adjunctive therapy in cancer care. As research continues, the integration of IVC into comprehensive cancer treatment protocols holds potential for improving patient outcomes and advancing the field of ortho-regenerative medicine.

References

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2. Padayatty, S. J., Riordan, H. D., Hewitt, S. M., Katz, A., Hoffer, L. J., & Levine, M. (2006). Intravenously administered vitamin C as cancer therapy: three cases. Canadian Medical Association Journal. Retrieved from CMAJ.

3. Böttger, F., Vallés-Martí, A., Cahn, L., et al. (2021). High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer. Journal of Experimental & Clinical Cancer Research, 40, 343. doi:10.1186/s13046-021-02134-y.

4. McCormick, W. J. (1959). Cancer: A Collagen Disease Secondary to a Nutritional Deficiency? Journal of Orthomolecular Medicine.

5. Lopez-Charcas, O., Pukkanasut, P., Velu, S. E., & Cunnane, S. C. (2021). Pharmacological and nutritional targeting of voltage-gated sodium channels in the treatment of cancers. iScience. Retrieved from Cell.

6. Savarese, D. M. F., Savy, G., Vahdat, L., Wischmeyer, P. E., & Corey, B. (2003). Prevention of chemotherapy and radiation toxicity with glutamine. Cancer Treatment Reviews, 29(6), 501-513.

7. Anand, P., Sundaram, C., Jhurani, S., Kunnumakkara, A. B., & Aggarwal, B. B. (2008). Curcumin and cancer: An "old-age" disease with an "age-old" solution. Cancer Letters, 267(1), 133-164.

8. Calder, P. C., et al. (2017). The impact of arginine metabolism on immune function in health and disease. Immunology Letters, 196, 25-36.

9. Grimble, G. K. (1996). Nutritional modulation of immune function. Proceedings of the Nutrition Society, 55(1B), 349-358.

10. Grant, W. B., et al. (2020). Vitamin D supplementation and cancer risk: A review of randomized controlled trials. Anticancer Research, 40(9), 4793-4800.

11. Cameron, E., & Pauling, L. (1976). Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Proceedings of the National Academy of Sciences, 73(10), 3685-3689.

12. Levine, M., et al. (2008). Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use. Annals of Internal Medicine, 140(7), 533-537.

13. Levine, M., & Padayatty, S. J. (2016). Reevaluation of Ascorbate in Cancer Treatment: Emerging Evidence, Open Minds and Serendipity. Journal of the American College of Nutrition, 35(2), 93-100.

14. Fritz, H., Flower, G., Weeks, L., Cooley, K., & Auer, R. (2014). Intravenous vitamin C and cancer: a systematic review. Integrative Cancer Therapies, 13(4), 280-300. doi:10.1177/1534735414534463.

15. Rock, E., & DeMichele, A. (2003). Nutritional approaches to late toxicities of adjuvant chemotherapy in breast cancer survivors. The Journal of Nutrition. Retrieved from ScienceDirect.

16. Pauling, L., & Cameron, E. (1978). Supplemental Ascorbate in the Supportive Treatment of Cancer. Proceedings of the National Academy of Sciences of the United States of America, 73(10), 3685-3689.

17. Baracos, V., et al. (2011). Cancer-associated cachexia. Nature Reviews Disease Primers. Retrieved from ScienceDirect.

18. Padayatty, S. J., et al. (2004). Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use. Annals of Internal Medicine, 140(7), 533-537.

19. Mikirova, N., et al. (2013). Pharmacokinetics of Vitamin C: Insights into the Oral and Intravenous Administration in Humans. Journal of Translational Medicine, 11(1), 191.

20. Verrax, J., & Calderon, P. B. (2009). Pharmacologic Concentrations of Ascorbate Are Achieved by Parenteral Administration and Exhibit Antitumoral Effects. Free Radical Biology and Medicine, 47(1), 32-40.

21. Verrax, J., & Calderon, P. B. (2008). The Controversy of Antioxidant Use in Cancer Therapy: The Case of Vitamin C. Free Radical Research, 42(5), 563-570.

22. Gullett, N. P., Mazurak, V., Hebbar, G., & Ziegler, T. R. (2011). Nutritional interventions for cancer-induced cachexia. Cancer Problems. Retrieved from NCBI.

23. Klenner, F. R. (1974). Observations on the dose and administration of ascorbic acid when employed beyond the range of a vitamin in human pathology. Journal of Preventive Medicine, 6(3), 232-243.

24. Rock, E., & DeMichele, A. (2003). Nutritional approaches to late toxicities of adjuvant chemotherapy in breast cancer survivors. The Journal of Nutrition. Retrieved from ScienceDirect.

25. Lopez-Charcas, O., Pukkanasut, P., Velu, S. E., & Cunnane, S. C. (2021). Pharmacological and nutritional targeting of voltage-gated sodium channels in the treatment of cancers. iScience. Retrieved from Cell.

26. Riordan, H. D., & Hunninghake, R. (1998). The Riordan intravenous vitamin C protocol for cancer: A retrospective review of 24 cases. Journal of Orthomolecular Medicine, 13(3). Retrieved from Riordan Clinic.

27. Klenner, F. R. (1971). The Treatment of Poliomyelitis and Other Virus Diseases with Vitamin C. Southern Medical Journal, 41(10), 1154-1160.

28. Riordan, H. D., Jackson, J. A., & Riordan, N. H. (1990). Intravenous Ascorbate in the Treatment of Cancer. Journal of Orthomolecular Medicine, 5(1), 5-13.

29. Pauling, L. (1986). How to Live Longer and Feel Better. W. H. Freeman & Company.

30. Riordan, H. D., & Hunninghake, R. (1998). The Riordan intravenous vitamin C protocol for cancer: A retrospective review of 24 cases. Journal of Orthomolecular Medicine, 13(3). Retrieved from Riordan Clinic.

31. Gonzalez, M. J., & Miranda-Massari, J. R. (2014). Vitamin C and Cancer: What Can We Conclude - 1,609 Patients and 33 Years Later? Journal of Orthomolecular Medicine, 29(1), 56-60.

32. Gonzalez, M. J., Miranda-Massari, J. R., Mora, E. M., Guzman, A., Riordan, N. H., Riordan, H. D., & Casciari, J. J. (2005). Orthomolecular oncology review: Ascorbic acid and cancer 25 years later. Integrative Cancer Therapies, 4(1), 32-44. doi:10.1177/1534735404273861.

33. Muscaritoli, M., Arends, J., Bachmann, P., Baracos, V., Barthelemy, N., Bertz, H., ... & Zupanec, V. (2021). ESPEN practical guideline: Clinical Nutrition in cancer. Clinical Nutrition, 40(3), 1411-1428. Retrieved from ScienceDirect.

34. Gonzalez, M. J., & Miranda-Massari, J. R. (2010). Vitamin C: The Real Story - The Remarkable and Controversial Healing Factor. Basic Health Publications, Inc.

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36. https://drjuanmanuelmartinezm.com/medicina-orto-regenerativa/

37. Levine, M., et al. (1996). Vitamin C Pharmacokinetics in Healthy Volunteers: Evidence for a Recommended Dietary Allowance. Proceedings of the National Academy of Sciences, 93(8), 3704-3709.

38. https://drjuanmanuelmartinezm.com/protocolos-de-rehabilitacion-metabolica-para-el-cancer-new-1-best/

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