IV therapy

The use of IV therapy with cancer patients may differ from taking supplements , vitamin in general patients.

Phytonutrient & Nutrition therapy is a form of treatment in which natural forms of medicaments such as,

Amino acids,

Fatty acids,

Vitamins,

Minerals

Antioxidants

The use of these IV therapies can be complemented with other on-going treatments. Getting nutrients from the core food groups are essential but commonly not taken sufficient enough.

Therefore, nutrients from natural sources such as curcumin, EGCG from green tea  which can be highly beneficial and there are many anti-cancer properties.

In addition, the use of adequate nutrient therapy also improves the patient’s nutrition plus immunity and in turn helps them to tolerate treatment better.

Treatments through IV therapy is a safer option as compared to the unnecessary use of chemical-based medicaments.

The side effects if any are much more manageable as compared to treatments such as chemotherapy or radiation for a cancer patient.

High dose Vitamin C

Vitamin C or Ascorbic acid is a natural water-soluble vitamin. It is an organic substance. Vitamin C is naturally found in citrus and other fruits, and in vegetables. Vitamin C cannot be produced or stored by humans and must be obtained in the diet.

Ascorbic acid is a potent reducing and antioxidant agent (electron donor) and cofactor of enzymes that functions in

  • Immune health as required for leucocytes function in fighting with infections
  • Detoxifying reactions by recycling each other with glutathione and reducing chemical toxicity to DNA and liver cells
  • Formation of collagen in fibrous tissue, teeth, bones, connective tissue, skin, and capillaries.
  • Synthesis of epinephrine and steroid hormones produced by adrenal gland
  • Tyrosine metabolism
  • Carnitine metabolism
  • Intestinal absorption of iron from diets

Vitamin C Deficiency and Oxidative Stress

Extensive literature demonstrates that cancer patients experience vitamin C deficiency correlated with reduced oral intake, inflammation, infection, physiological stress of disease processes, metabolic state of the malignancy and its effects on host metabolism and effects of treatments such as radiation, chemotherapy, and surgery.

Cancer patients experience increased oxidative stress and inflammation known to increase utilization of ascorbic acid. That increase in utilization correlates with low vitamin C blood levels in this group of patients.

Vitamin C is consumed during inflammation as it reduces free radical activity. When an antioxidant destroys a free radical, the antioxidant itself becomes oxidized.

Vitamin C deficiency interferes with collagen synthesis, catecholamine formation, prostaglandin metabolism, and cellular immunity.

Antioxidant resources must be restored in the body. When inflammation consumes vitamin C such that stores become low, the kidneys slow excretion so that vitamin C from dietary consumption can be retained. However, decreased excretion might not be well compensated oral intake during high levels of inflammation.

Vitamin C and cancer treatment

By the 1970s, Nobel Price winner Linus Pauling had already developed a strategy to use intravenous (IV) vitamin C in cancer patients. He treated patients with advanced cancer with high doses of vitamin C and reported a positive effect on survival.

Pharmacokinetic studies show that the way of administration makes a big difference as peak plasma vitamin C concentrations after intravenous administration are much higher (up to 70-fold) than after oral intake. Peak plasma concentrations also continue to increase when the intravenous dose of

vitamin C is increased, while peak plasma concentrations plateau even though oral doses are increased.

Linus Pauling suggested that 50 grams a day or more as high dose of vitamin C into the vein with slow drip would impact human cancer.

There are multiple hypotheses about the way vitamin C has anti-tumor effects. An important possible mechanism of action is that in pharmacological concentrations (especially after intravenous use). Ascorbate functions as a pro-oxidant and stimulates the formation of hydrogen peroxide (H2O2) from ascorbate via Fenton reaction with iron ions in extracellular space. Hydrogen peroxide can create reactive oxygen species (ROS),that directly have cytotoxic activity and induce apoptosis selectively in cancer cells. Healthy cells can neutralize H2O2 with catalase enzyme.

Another important hypothesis is that vitamin C can create important epigenetic changes due to its effect on 2-oxoglutarate-dependent dioxygenases, like histone and DNA demethylases. Vitamin C regulates embryonic stem cells differentiation and inhibit p53 induced replicative senescence.

Vitamin C has an important role in the immune system, as it stimulates the production and/or activation of immune cells, like T-lymphocytes and natural killer cells, that have a function in fighting against pathogens and cancer cells. Vitamin C is essential for synthesis of immunoglobulin. In preclinical studies investigators also show that vitamin C can have a synergistic effect with some types of chemo- and immunotherapy. High dose vitamin C IV is very supportive during chemotherapy, improving drug uptake and reducing resistance. High dose vitamin C reduces side effects of chemotherapy, radiotherapy so it can improves quality of life . High dose vitamin C can alter hyaluronidase activity that helps slowing the spread of cancer and can deplete copper level which inhibits angiogenesis.

High dose vitamin C IV can stabilize a majority of cancer cases, arresting growth and spread of tumors. Good results are seen in

  • Lymphoma
  • Non-small cell lung cancer
  • Cholangiocarcinoma
  • Breast cancer
  • Kidney cancer
  • Bladder cancer
  • Prostate cancer
  • Colon cancer

SIDE EFFECTS

Reported side effects of High dose vitamin C IV include nausea, dizziness, dry mouth, perspiration, and weakness. Suggestions for prevention of side effects include giving plenty of oral fluids before and during treatment.

 

SAFETY

Conditions for which screening is recommended for all dosage levels of vitamin C IV include glucose 6 phosphate dehydrogenase (G6PD) deficiency, iron and copper storage diseases, renal failure, history of kidney stones or oxaluria, and pregnancy or lactation.

Using of lower doses of vitamin C IV could be appropriate at the discretion of the clinician

No Vitamin C IV is given to patients with G6PD deficiency.

Use caution with oral vitamin C in G6PD deficiency.

Using of lower doses of vitamin C IV could be appropriate at the discretion of the clinician.

SUPPORTIVE TO HIGH DOSE VITAMIN C THERAPY

  • Hyperbaric oxygen therapy (HBOT)
  • Ketogenic diets
  • Oral vitamin K1/K2
  • Oral vitamin C 6-12 gm. /day
  • Selenium 200 mcg./day
  • Helixor M mistletoe 100-800 mg.
  • Quercetin
  • Grape seed extract
  • Biotin and Niacinamide
  • R-Alpha Lipoic acid

References

1.https://riordanclinic.org/research-study/vitamin-c-research-ivc-protocol/ 2.https://www.emedicinehealth.com/vitamin_c_high_dose_benefits_side_effects/article_em.htm#h igh-dose_vitamin_c_benefits 3.https://www.isom.ca/wp-content/uploads/2013/01/Oral-vs.-Intravenous-Vitamin-C-OMT- 2009.pdf 4.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927785/ Intravenous vitamin C in the supportive care of cancer patients: a review and rational approach E. Klimant, MD,* H. Wright, ND,D. Rubin, ND,D. Seely, ND MSc,and M. Markman, MD§

5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071214/ Systematic Review of Intravenous Ascorbate in Cancer Clinical TrialsGina Nauman,1 Javaughn Corey Gray,2 Rose Parkinson,2 Mark Levine,1 and Channing J. Paller2,*

6.https://journals.sagepub.com/doi/full/10.1177/1534735414534463?url_ver=Z39.88- 2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed Intravenous Vitamin C and Cancer: A Systematic Review 7.https://www.academia.edu/14219866/Intravenous_Vitamin_C_and_Cancer_A_Systematic_Revi ew 8. https://en.wikipedia.org/wiki/Intravenous_ascorbic_acid 9. Naturopathic oncology-An encyclopedic guide for patients& physicians 3rd edition; Dr.Neil Mckinney, BSsc,,ND; Vitamin C: p.147-151 10. https://www.semanticscholar.org/paper/Vitamin-C%3A-a-concentration-function-approach- yields-Levine-Padayatty/560fdaba6d9730b4f12027f191bad209f9daa591/figure/3

Alpha Lipoic Acid (ALA)

Alpha Lipoic Acid (ALA) is an antioxidant with acidic properties and that acts as an electron transporter to help balance and stimulate the function of vitamin C.

Therefore, the use of Alpha Lipoic Acid together with vitamin C increases the efficiency of vitamin C’s mechanism of action. In addition ALA also helps boost efficacy when  synergised with the function of both with vitamin E (Vitamin E) and coenzyme Q10 (Co-enzyme Q10). Therefore, ALA has been called a Universal Antioxidant (Vitamin Antioxidant), which is an important enzyme that helps in various metabolic systems.

The mechanism of action of ALA and vitamin B-complex is the transfer of electrons from inside the cell which help drive the metabolic system. This restores the metabolic mechanism and makes it work better. Apart from the above, ALA also helps get rid of the remaining lactic acid and also has the ability to capture heavy metals. This in turn assist with the reduction of the toxin levels in the body. Therefore, ALA and vitamin B-complex play important roles in promoting the body’s immunity, reducing the survival rate of cancer cells plus reducing the rate of cancer cell division.

The part from the metabolism of sugar, ALA is a catalyst for insulin to burn sugar better in individual cells. This is done by increasing activity of glucose to drive to the cells to burn well. This action enables the mitochondria to generate energy well, helping to reduce acidity, lactate production and increase the efficiency of cancer cells atrophy (fighting cancer at the root cause).

Curcumin

Concentrated turmeric extract (Curcumin) has the ability to help reduce inflammation, fight bacteria, boost antioxidant, reduce the accumulation of beta-amyloid proteins in the brain and reduce the blood sugar levels. Apart from fighting cancer, curcumin can also be used to treat leukemia Lymphoma, Breast Cancer, Ovarian Cancer, Gastrointestinal Cancer Urinary system cancer, lung cancer, brain cancer, bone cancer, tissue cancer in the head and neck.

It also helps to reduce side effects such as dermatitis from cancer treatment through radiotherapy also known as Radiation dermatitis. The use of concentrated turmeric extract through the intravenous route has been proven to be more effective in treating cancer than taking it orally. This is because concentrated turmeric extract is less absorbent in the digestive system. For Cancer treatments, Concentrated Turmeric Extract or Curcumin has the following properties:

  • stop the growth and spread of cancer cells
  • helping to Hinder the cell mutation
  • stop the increase of the number of cancer cells
  • reduce inflammation
  • stimulate the destruction of cancer cells (Apoptosis)
  • helps to inhibit the production of proteins that stimulate the growth of cancer cells
  • ability to help control the growth of cancer
  • inhibiting the creation of new blood vessels of cancer cells

Therefore, Curcumin can effectively reduce the spread of cancer cells (Metastasis), inhibits the growth of cancer in the protein growth stages. In cancer-resistant tissues, proteins are generated to stimulate the proliferation of abnormal cells. This is because the cells grows abnormally and turn cancerous. Curcumin inhibits proteins or inhibits protein receptors, which control the growth of cancer and can also be a form of targeted treatment which has zero effect on normal cells.

Quercetin

What is Quercetin?

Quercetin (3,5,7,3’,4’- pentahydroxy flavone) is a major flavonoid present abundantly in apples, red grapes, onions, raspberries, honey, cherries, citrus fruits and green leafy vegetables. Flavonoids are compounds with benefits on human health including antitumor and antioxidant activities. [1] Many flavonoids exert potent antitumor activity through induction of apoptosis and cell cycle arrest in several cancer cell lines. [2]

Why do people use Quercetin for cancer?

  • Given with Chemotherapy, quercetin helps to hold it inside cancer cells to overcome multi drug resistance MDR to effect a cure.
  • Restricts drug resistance by inhibition of heat shock protein HSP-70. Inhibition of heat shock proteins disrupts formation of complexes of mutant p53 and HSPs which would allow tumor cells to bypass normal cell cycle checkpoints.
  • Increases effectiveness of radiation and chemotherapy, especially doxorubicin, ribavirin and tamoxifen.
  • Blocks EGFR and reduces activity in the HER2 signal pathway
  • Enhance NK activity and is immune modulating.
  • Binds type II estrogen receptors in breast, colon, ovary, melanoma, leukemia and meningeal cancer cells, inhibiting growth.
  • Inhibits replication of RNA and DNA viruses.
  • Powerful antihistamine (can replace cimetidine in cancer therapy application).
  • Blocks tumor export of lactate resulting in drop in tumor pH and triggering pH dependent apoptosis.
  • Inhibits cancer cell invasion and metastasis.

How does Quercetin work?

Quercetin inhibits cell proliferation by causing apoptosis and/or cell cycle arrest (G2/M or G1) [3] [4].  It generates mild DNA damage and activates Chk2 kinase which plays a crucial role in p21 induction. Quercetin is also a strong antioxidant because it can chelate metals, scavenge oxygen free radicals and inhibit xanthine oxidase and lipid peroxidation. [5]

Does Quercetin work?

Numerous epidemiological studies have evaluated the possible relationship between the consumption of foods containing flavonoids and the risk of developing specific cancers. The analysis of data from 18 case-control studies (8585 cases with cancer and 9975 control subjects) revealed that a high consumption of flavonoids was associated with a statistically significant reduction of overall cancer risk.  These results suggest that consumption of foods rich in the flavonoids such as quercetin, may reduce the risk of developing cancer. [6]

Does Quercetin have side effects?

Side effects are extremely rare.

Some reactions that are rarely found- dull headache, nausea, or a general sick feeling.

Is Quercetin safe?

Quercetin is relatively nontoxic and is considered safe – orally in doses of 500 mg or less. [7]

Extreme doses are toxic to the kidneys.

What is the recommended dose of Quercetin?

Clinical trials have not established for optimal quercetin dose during or after cancer treatment.

Ref

[1] Lea et al 1993, Plaumann et al 1996 DiCarlo et al, 1999

[2][Wenzel et al, 2000

[3] Yang et al 2005; Lee et al 2006

[4] Choi et al 2001; Ong et al 2004, Beniston and Campo 2003

[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136711/

[6] http://www.webmedcentral.com/article_view/4264

[7] https://bcct.ngo/search-therapies/search-therapy-summaries/quercetin

[8] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561933/  

[9]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736626/

EGCG

EGCG is classified as a natural antioxidant, Green tea is more effective in strength when compared to vitamin C and vitamin E by 25-100 times. According to some research studies, the properties of green tea has Epigallocatechin gallate (EGCG) functions which boost the reduction of inflammation. It also has the ability to protect the cells from damage. It is also found that EGCG can help destroy cancer cells and stop the growth of cancer cells.

EGCG has powerful antioxidant properties that helps to prevent occurrences of diseases like atherosclerosis and especially coronary artery disease. EGCG is a weapon that helps fight “Oxidation” caused by the cells in the body reacting with oxygen that releases “free radicals”.

Research has found that Green tea can help reduce total cholesterol and at the same time increase the amount of good cholesterol (HDL). Catechins in turn can help prevent cancer by destroying cancer cells and stop the growth of cancer cells. Green tea has a positive medical effect on the following cancer treatments:

  • bladder cancer
  • breast cancer
  • ovarian cancer
  • colon rectal cancer
  • Oesophageal cancer
  • lung cancer
  • mild liver cancer
  • skin cancer
  • stomach cancer

Green tea also may help to control blood sugar levels and prevent the occurrence of one type of diabetes. It has the ability to delay the onset diabetes. It assist in controlling the glucose level in the body and bring it back to an equilibrium state.

Polyphenols in turn can help increase good bacteria in the intestines plus detoxify and eliminate toxins from the body. It can help to protect the liver from damages caused by toxins such as alcohol.

Epigenin

Apigenin in cancer therapy: anti-cancer effects

Apigenin is a common dietary flavonoid( 4′, 5, 7-Trihydroxyflavone), a major plant flavone, possessing antioxidant, anti- inflammatory, and anticancer properties affecting several molecular and cellular targets used to treat various human diseases.

Apigenin is present principally as glycosylated in significant amount in vegetables (parsley, celery, onions) fruits (oranges), herbs (chamomile, thyme, oregano, basil), and plant-based beverages (tea, beer, and wine).

Apigenin is also one of the active ingredients in Chinese medical herbs.

Figure 1. Structure and natural sour- ces of apigenin. Data from US Depar- tment of Agriculture (2011; https:// www.ars.usda.gov/ARSUserFiles/8040 0525/Data/Flav/Flav_R03.pdf).

Cancer is a disease caused by the abnormal proliferation and differentiation of cells and is governed by tumorigenic factors. Therefore, natural and edible small molecules such as flavones, which are thought to have remarkable physiological effects, low toxicities, and non-mutagenic properties in the human body, have gained more and more interest in anti-cancer agent development.

Extensive studies performed in patients and healthy individuals have shown apigenin to possess anticancer properties. Anticarcinogenic properties of apigenin occur through regulation of cellular response to oxidative stress and DNA damage, suppression of inflammation and angiogenesis, retardation of cell proliferation, and induction of autophagy and apoptosis. Recently apigenin was reported to show anti-cancer activities by stimulating and immune response.

During those processes, multiple signaling pathways and protein kinases are modulated by apigenin including PI3K/AKT, MAPK/ERK, JAK/STAT, NF-kB and Wnt/β-catenin.

 

Role of Apigenin in cancer prevention

In 1980s, Birt et al. first demonstrated the effective anti-mutagenic and anti-promotive properties of apigenin. The chemopreventive effect of apigenin was explored in at least dozen in vivo studies. This effect was attributed to the

suppression of the phosphoinositide 3-kinase (PI3K)/Akt/Forkhead box O-signaling pathway. Apigenin effectively suppressed prostate cancer, oral carcinogenesis, colon and UVB-induced skin cancer.

 

Induction of apoptosis

Apoptosis is the process of the programmed cell death. To date, apoptosis is induced by two core pathways extrinsic (death receptors) pathway and the intrinsic (mitochondrial) pathway. Apoptosis is a critical process that allows undesirable cells to be removed under physiological conditions. Avoiding apoptosis is one of the most important characteristic of cancer cells. Apigenin has been demonstrated to be and effective agent for triggering apoptosis via either the intrinsic or extrinsic pathway in human cancer cells.

In prostate cancer therapy, treatment of the androgen-refractory human prostate cancer cell lines resulted in apoptosis and a reduction in cell viability.

In human promyelocytic leukemia HL-60 cells, apigenin reduced the mitochondrial outer membrane potential, released cytochrome c from the mitochondria into the cytosol, induced procaspase-9 processing, and finally induced cell apoptosis through the intrinsic apoptotic pathway.

Apigenin also have effect on cell line of colorectal cancer, non-small cell lung cancer, skin cancer.

 

Modulation of cell cycle

Uncontrolled and rapid cell division is another hallmark of cancer. Apigenin inhibits cancer cell proliferation by modulating the cell cycle and blocking the cell phase at the G2/M or G0/G1 checkpoint.

In human colorectal carcinoma, apigenin treatment potently inhibited cell growth by inducing cell arrest at G2/M phase.

As in the human breast cancer cell line, cyclin A, cyclin B, and cyclin-dependent kinase-1 (CDK1) was suppressed by apigenin treatment.

In addition, in renal cell carcinoma cells, apigenin caused DNA damage in cells in a time- and dose-dependent manner and induced G2/M phase cell cycle arrest.

 

Induction of Autophagy

Autophagy, type 2 non-apoptotic cell death, is characterized by the sequestration of cytoplasmic

material into vacuoles for bulk degradation by lysosomal enzymes. Autophagy triggered by apigenin was first observed in erythroleukemia TF1 cells. Evidences have been presented that apigenin could induce autophagy which serves as tumor suppressive under different circumstances.

 

Inhibition of cancer cell migration and invasion

Malignant tumor cells are highly unstable and have the ability to metastasize and invade other tissue to form further lesions. The majority of patients in clinical practice do not die of primary disease but by varying degrees of tumor metastasis.

Presently, metastases, along with the development of chemoresistance and tumor relapse, are still the major barriers to effective treatment with cancer therapy.

In prostate, melanoma, lung, colorectal cancer cell lines, apigenin has been shown to inhibit cancer cell migration and invasion by modulating PI3K/AKT signaling pathway.

 

Induction of immune response

Cancer immunotherapy is a means of treating cancers by activating the patient’s own immune system. Avoiding destruction by the immune system is a crucial characteristic for carcinoma cells in overcoming human immune system surveillance.

Apigenin shows promise as a cancer immunotherapy agent by modulating PD1/ PD-L1 expression in cancer/T killer cells and by regulating the percentage of T killer and T regulatory cells.

 

Apigenin functions on cancer stem cells

Apigenin shows signifcant cell cytotoxicity selectively against various types of cancer cells with low or no toxicity to normal cells. Apigenin shows clear anti-cancer effects by inhibiting the self-renewal capacity of CSCs(cancer stem cells).

In human glioblastoma cell , head and neck squamous cells , and prostate cancer cell lines, apigenin show efficacy by down regulate the stem cell marker.

Signaling transduction modulation by apigenin in cancer therapy

1. PI3K/AKT/mTOR signaling pathway

2. MAPK/ERK signaling

3. NF κB signaling pathway

4. JAK/STAT signaling

5. Wnt/β catenin signaling

Apigenin has effect on several human cell lines in vitro and in vivo studies:

– Breast Cancer – Colon Cancer – Gastric Cancer – Liver Cancer – Lung Cancer – Pancreatic Cancer – Prostate Cancer – Skin Cancer – Cervical Cancer – Endometrial Cancer – Ovarian Cancer – Hematologic Cancer – Adrenocortical Carcinoma – Thyroid Cancer – Neuroblastoma – Bladder Cancer – Mesothelioma – Osteosarcoma

 

Safety and Possible side effect

Human exposure to apigenin occurs primarily through the consumption of chamomile and through its presence as a glycoside in many fruits and vegetables. These glycosides are efficiently hydrolyzed in vivo by bacterial enzymes in the human intestinal tract to the free flavonoids.

Foods rich in apigenin include apples, endive, beans, broccoli, celery, cherries, cloves, grapes, leeks, onions, barley, parsley and tomatoes, while plant-derived beverages containing apigenin include tea and wine.

References:

1. https://www.ncbi.nlm.nih.gov/pubmed/25738871 2. https://ntp.niehs.nih.gov/ntp/htdocs/chem_background/exsumpdf/apigenin_508.pdf 3. https://www.ncbi.nlm.nih.gov/pubmed/29593542 4. https://www.ncbi.nlm.nih.gov/pubmed/30875872 5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629766/ 6. https://www.ncbi.nlm.nih.gov/pubmed/18645020 7. https://www.ncbi.nlm.nih.gov/pubmed/29245972 8. http://www.bioscirep.org/content/39/5/BSR20190452 9. https://www.ncbi.nlm.nih.gov/pubmed/28260058 10. https://www.ncbi.nlm.nih.gov/pubmed/24067903 11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098219/ 12. https://www.nature.com/articles/s41420-018-0124-8 13. https://www.ncbi.nlm.nih.gov/pubmed/24922650 14. https://www.ncbi.nlm.nih.gov/pubmed/25654996 15. https://www.ncbi.nlm.nih.gov/pubmed/23697369 16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472148/ 17. https://www.jimmunol.org/content/198/1_Supplement/219.12 18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629076 19. https://www.ncbi.nlm.nih.gov/pubmed/30881359

20. https://www.ncbi.nlm.nih.gov/pubmed/29399439 21. https://www.ncbi.nlm.nih.gov/pubmed/29850614 22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5207605/ 23. http://www.apjtb.org/article.asp?issn=2221- 1691;year=2018;volume=8;issue=11;spage=519;epage=526;aulast=Ittiudomrak

Apigenin in cancer therapy: anti-cancer effects
Apigenin is a common dietary flavonoid( 4′, 5, 7-Trihydroxyflavone), a major plant flavone, possessing antioxidant, anti- inflammatory, and anticancer properties affecting several molecular and cellular targets used to treat various human diseases.
Apigenin is present principally as glycosylated in significant amount in vegetables (parsley, celery, onions) fruits (oranges), herbs (chamomile, thyme, oregano, basil), and plant-based beverages (tea, beer, and wine).
Apigenin is also one of the active ingredients in Chinese medical herbs.
Figure 1. Structure and natural sour- ces of apigenin. Data from US Depar- tment of Agriculture (2011; https:// www.ars.usda.gov/ARSUserFiles/8040 0525/Data/Flav/Flav_R03.pdf).
Cancer is a disease caused by the abnormal proliferation and differentiation of cells and is governed by tumorigenic factors. Therefore, natural and edible small molecules such as flavones, which are thought to have remarkable physiological effects, low toxicities, and non-mutagenic properties in the human body, have gained more and more interest in anti-cancer agent development.
Extensive studies performed in patients and healthy individuals have shown apigenin to possess anticancer properties. Anticarcinogenic properties of apigenin occur through regulation of cellular response to oxidative stress and DNA damage, suppression of inflammation and angiogenesis, retardation of cell proliferation, and induction of autophagy and apoptosis. Recently apigenin was reported to show anti-cancer activities by stimulating and immune response.
During those processes, multiple signaling pathways and protein kinases are modulated by apigenin including PI3K/AKT, MAPK/ERK, JAK/STAT, NF-kB and Wnt/β-catenin.
Role of Apigenin in cancer prevention
In 1980s, Birt et al. first demonstrated the effective anti-mutagenic and anti-promotive properties of apigenin. The chemopreventive effect of apigenin was explored in at least dozen in vivo studies. This effect was attributed to the
suppression of the phosphoinositide 3-kinase (PI3K)/Akt/Forkhead box O-signaling pathway. Apigenin effectively suppressed prostate cancer, oral carcinogenesis, colon and UVB-induced skin cancer.
Induction of apoptosis
Apoptosis is the process of the programmed cell death. To date, apoptosis is induced by two core pathways extrinsic (death receptors) pathway and the intrinsic (mitochondrial) pathway. Apoptosis is a critical process that allows undesirable cells to be removed under physiological conditions. Avoiding apoptosis is one of the most important characteristic of cancer cells. Apigenin has been demonstrated to be and effective agent for triggering apoptosis via either the intrinsic or extrinsic pathway in human cancer cells.
In prostate cancer therapy, treatment of the androgen-refractory human prostate cancer cell lines resulted in apoptosis and a reduction in cell viability.
In human promyelocytic leukemia HL-60 cells, apigenin reduced the mitochondrial outer membrane potential, released cytochrome c from the mitochondria into the cytosol, induced procaspase-9 processing, and finally induced cell apoptosis through the intrinsic apoptotic pathway.
Apigenin also have effect on cell line of colorectal cancer, non-small cell lung cancer, skin cancer.
Modulation of cell cycle
Uncontrolled and rapid cell division is another hallmark of cancer. Apigenin inhibits cancer cell proliferation by modulating the cell cycle and blocking the cell phase at the G2/M or G0/G1 checkpoint.
In human colorectal carcinoma, apigenin treatment potently inhibited cell growth by inducing cell arrest at G2/M phase.
As in the human breast cancer cell line, cyclin A, cyclin B, and cyclin-dependent kinase-1 (CDK1) was suppressed by apigenin treatment.
In addition, in renal cell carcinoma cells, apigenin caused DNA damage in cells in a time- and dose-dependent manner and induced G2/M phase cell cycle arrest.
Induction of Autophagy
Autophagy, type 2 non-apoptotic cell death, is characterized by the sequestration of cytoplasmic
material into vacuoles for bulk degradation by lysosomal enzymes. Autophagy triggered by apigenin was first observed in erythroleukemia TF1 cells. Evidences have been presented that apigenin could induce autophagy which serves as tumor suppressive under different circumstances.
Inhibition of cancer cell migration and invasion
Malignant tumor cells are highly unstable and have the ability to metastasize and invade other tissue to form further lesions. The majority of patients in clinical practice do not die of primary disease but by varying degrees of tumor metastasis.
Presently, metastases, along with the development of chemoresistance and tumor relapse, are still the major barriers to effective treatment with cancer therapy.
In prostate, melanoma, lung, colorectal cancer cell lines, apigenin has been shown to inhibit cancer cell migration and invasion by modulating PI3K/AKT signaling pathway.
Induction of immune response
Cancer immunotherapy is a means of treating cancers by activating the patient’s own immune system. Avoiding destruction by the immune system is a crucial characteristic for carcinoma cells in overcoming human immune system surveillance.
Apigenin shows promise as a cancer immunotherapy agent by modulating PD1/ PD-L1 expression in cancer/T killer cells and by regulating the percentage of T killer and T regulatory cells.
Apigenin functions on cancer stem cells
Apigenin shows signifcant cell cytotoxicity selectively against various types of cancer cells with low or no toxicity to normal cells. Apigenin shows clear anti-cancer effects by inhibiting the self-renewal capacity of CSCs(cancer stem cells).
In human glioblastoma cell , head and neck squamous cells , and prostate cancer cell lines, apigenin show efficacy by down regulate the stem cell marker.
Signaling transduction modulation by apigenin in cancer therapy
1. PI3K/AKT/mTOR signaling pathway
2. MAPK/ERK signaling
3. NF κB signaling pathway
4. JAK/STAT signaling
5. Wnt/β catenin signaling
Apigenin has effect on several human cell lines in vitro and in vivo studies:
– Breast Cancer – Colon Cancer – Gastric Cancer – Liver Cancer – Lung Cancer – Pancreatic Cancer – Prostate Cancer – Skin Cancer – Cervical Cancer – Endometrial Cancer – Ovarian Cancer – Hematologic Cancer – Adrenocortical Carcinoma – Thyroid Cancer – Neuroblastoma – Bladder Cancer – Mesothelioma – Osteosarcoma
Safety and Possible side effect
Human exposure to apigenin occurs primarily through the consumption of chamomile and through its presence as a glycoside in many fruits and vegetables. These glycosides are efficiently hydrolyzed in vivo by bacterial enzymes in the human intestinal tract to the free flavonoids.
Foods rich in apigenin include apples, endive, beans, broccoli, celery, cherries, cloves, grapes, leeks, onions, barley, parsley and tomatoes, while plant-derived beverages containing apigenin include tea and wine.

 

References:
1. https://www.ncbi.nlm.nih.gov/pubmed/25738871 2. https://ntp.niehs.nih.gov/ntp/htdocs/chem_background/exsumpdf/apigenin_508.pdf 3. https://www.ncbi.nlm.nih.gov/pubmed/29593542 4. https://www.ncbi.nlm.nih.gov/pubmed/30875872 5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629766/ 6. https://www.ncbi.nlm.nih.gov/pubmed/18645020 7. https://www.ncbi.nlm.nih.gov/pubmed/29245972 8. http://www.bioscirep.org/content/39/5/BSR20190452 9. https://www.ncbi.nlm.nih.gov/pubmed/28260058 10. https://www.ncbi.nlm.nih.gov/pubmed/24067903 11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098219/ 12. https://www.nature.com/articles/s41420-018-0124-8 13. https://www.ncbi.nlm.nih.gov/pubmed/24922650 14. https://www.ncbi.nlm.nih.gov/pubmed/25654996 15. https://www.ncbi.nlm.nih.gov/pubmed/23697369 16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472148/ 17. https://www.jimmunol.org/content/198/1_Supplement/219.12 18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629076 19. https://www.ncbi.nlm.nih.gov/pubmed/30881359
20. https://www.ncbi.nlm.nih.gov/pubmed/29399439 21. https://www.ncbi.nlm.nih.gov/pubmed/29850614 22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5207605/ 23. http://www.apjtb.org/article.asp?issn=2221- 1691;year=2018;volume=8;issue=11;spage=519;epage=526;aulast=Ittiudomrak

Ozone Therapy (MAH)

Ozone is one of several oxidative therapies used to modify the biochemistry of human body so that it strengthens the immune system as well as eliminates micro-organisms, cancer cells and neutralizes toxic chemicals.

Oxidative therapies mean that we take advantage of the fundamental way that the body works by enhancing oxidation. Oxidation-reduction, or redox reactions are how energy in the body is produced, many hormones and other products necessary for life are made and how the immune system kills cancer cells and unwanted microorganisms. It is the fundamental way that almost all of metabolism takes place. Without it, life would be impossible.

Any chemical reaction in which the oxidation numbers (oxidation states) of the atoms are changed is the definition of a redox reaction. Usually called, redox reactions, to shorten the term reduction-oxidation. It is the electron transfer system inside cells where the oxidation of glucose in the human body takes place to produce all the energy to live.

The formal definition of redox reactions is:

Oxidation – requires the loss of electrons or hydrogen OR the gain of oxygen resulting in the increase in the oxidation state.

Reduction – requires that there is a gain of electrons or hydrogen OR loss of oxygen resulting in a decrease in the oxidation state

Mechnism of action in ozonate major  autohemotherapy :

The most common form of medical ozone use is “MAH or Major autohemotherapy”. This procedure starting by taking about 200 ml of the patient’s blood to the closed system sterile glass bottle. The medical grade ozone generator administrate the ozone to activate  the blood , The interaction between blood component and ozone via both rapid oxidation spicies (ROS)  in rapid phase action and lipd peroxidation (LOP) in late phase action, we call all component of blood after reaction with blood ozanoid. The blood ozanoid can be dripping it back into a patient via  an intravascular route. The procedure take about30-40 minutes

The blood zonanoid administered intravenously results in an increase in the amount or concentration of oxygen in the blood and tissues, neutralizes toxins and kills unwanted cells, including cancer and microorganisms.  

Eliminates bacteria, viruses, fungi, yeast and protozoa (single cell organism-parasites):

Ozone disrupts the bacterial cell envelope membrane by oxidizing the phospholipids and lipoproteins that make up the cell membrane. With regards to fungi, ozone halts cell growth at certain stages.

When it comes to viruses, the ozone actually damages the viral membrane (capsid) as well as destroys the ability of the virus to reproduce. Since viruses invade healthy cells and edit the DNA so that the healthy cell now produces viruses, this means that these cells are destroyed and then replaced with healthy cells.

Enhancement of circulation: Another benefit of ozone which enhances circulation is that ozone oxidizes, or breaks up the plaque found in arteries, hence unclogging them and restoring blood flow.

Stimulation of oxygen metabolism: Ozone causes red blood cells to produce more of a chemical necessary for oxygen to leave the red blood cell and enter into the tissues, where it is needed.  This chemical is therefore vital in the whole circulation of the blood because without it, the oxygen would never reach its destination.

Ozone also activates the Krebs inside the mitochondria which is required to produce energy.  Energy in all biological systems is carried in a molecule called, ATP (adenosine tri-phosphate) Many other aspects of this process of energy production is stimulated by ozone as well as the increasing the cells ability to clean, or detoxify itself through an increase in glutathione, the main chemical compound used by the body to detoxify.  And finally, the production of prostacyclin, which prevents blood clotting as well as dilating the vessels so that more blood can be carried, is a result of ozone therapy.

Formation of peroxides: Ozone reacts with the unsaturated fatty acids in the cell membranes, and much like high dose vitamin C, produces different hydro peroxides, including H2O2, alkoxyl and peroxyl radicals, singlet oxygen, ozonides, carbonides, carbonyls, alkanes and alkenes.

Dissolution of malignant tumors: Ozone inhibits tumor metabolism and oxidizes the cell membrane of cancer cells so that they break open and die. Ozone also stimulates the production of citrulline, nitrite and nitrate by white blood cells called phagocytes, which also produce peroxides….all of these actions destroy tumors.

Activation of the immune system:  ozone causes a great increase in the production of interferon and tumor necrosis factor (TNF) and interleukin 2.  Then, interleukin 2 (IL-2) stimulates a whole host of immunological reactions necessary to recruit the white blood cells necessary to kill cancer cells. Interferon and TNF are also essential for a successful immune response to cancer cells.

Ozone is the one of Nrf2 activator :

The blood ozanoid can circulate to whole call and give the redox signelling to the cell via the nrf2, the important protein which is the master regulator of the total anti oxidant system that is available in all human cell.. The result after Nrf2 activation can feedback antioxidant property to restore and prevent mitochondria from environmental oxidative stress. So we can call the ozone therapy as the one of  Nrf2 activator and mitochondrial support  treatment.

Safty of Major auto hemotherapy :

  Ozone therapy is safe. Major Auto-Hemotherapy (MAH) was evaluated for safety in a study in 1980. After 5,579,238 MAH treatments conducted by 644 therapists on 384,775 patients,only 40 complaine of side effects (0.00001%). Millions of patients have received ozone therapy .

Possible side effect :

    As with all IV therapies, there is a risk of bruising, pain or swelling at the injection site. Some patients may also experience dizziness or light-headedness during the treatment. After treatment, fatigue, muscle aches and/or mild flu like symptoms may be experienced.

 

Reference and download paper :

  1. https://isco3.org/wp-content/uploads/2017/03/ISCO3-MET-00-01-MAHT-V1-03102016.pdf
  2. file:///C:/Users/user/AppData/Local/Packages/Microsoft.MicrosoftEdge_8wekyb3d8bbwe/TempState/Downloads/2045-9912-1-29%20(1).pdf
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674660/
  4. https://www.ncbi.nlm.nih.gov/pubmed/28623000
  5. file:///C:/Users/user/AppData/Local/Packages/Microsoft.MicrosoftEdge_8wekyb3d8bbwe/TempState/Downloads/7931849%20(1).pdf
  6. file:///C:/Users/user/AppData/Local/Packages/Microsoft.MicrosoftEdge_8wekyb3d8bbwe/TempState/Downloads/archcid-13-02-61320%20(1).pdf
  7. https://europepmc.org/articles/pmc3312702
  8. https://accedacris.ulpgc.es/bitstream/10553/41568/2/Medical%20Ozone.%20Raquel%20Cerpa.pdf

Photodynamic Therapy (PDT)

When one think about laser beam treatments, Photodynamic Therapy (PDT) would normally come to mind.  It uses light as a catalyst through a Photosensitizer that responds to the light. Let’s us explore a little more about this treatment and the benefits.

Many people would think that low intensity laser therapy might not be able to reach organs that are located deep in the body. However, the facts are as follow:

There are limitations in the use of laser that has the capability to treat the tissues that penetrates the skin. There might be a chance that the skin could burn during treatment.

Therefore, low intensity laser therapy could be the best option available as it is able to optimize treatment results through highly efficient amounts of exposure needed for each individual patient.

The organs or tissues respond to an increase of light makes it more efficient by using “Photosensitizer”. This technique is widely used in the treatment of cancer as it is able to destroy the cancer cells. This is because when the cancer cells are stimulated, the photoreceptor will react, which is the process that causes Apoptosis.

How it works

When the Photosensitizer is being use, the body will be exposure to the light. The cells becomes 2-3 times more sensitive when the exposure takes place. Currently, there are many photosensitizers that are being used. Some examples are as follow:

  • Chlorophyll will improve the function of red-light. When consumed orally, the chlorophyll will be present in the blood. When low level of red-light laser is used, it will improve the efficacy of the function of red light as chlorophyll is a catalyst.

Red-light laser can help alleviate pain or make the body more alert.  Chlorophyll in the form of liquid can be consumed and the laser treatment can be done by using either the red light or laser watch.

  • Curcumin is a substance found in turmeric, which helps improve the function of blue light in terms of sterilization and the reduction of inflammation.

Therefore, taking curcumin in conjunction with blue light during treatment has the ability to improve the sterilization of the blood. This combination is highly effective in managing a cold or improving one’s immunity.

  • St. John’s Wort Extract can help improve the function of yellow light. When taking St. John’s Wort Extract in combination with low level yellow light laser, the efficacy of the treatment for cases like depression will increase.
  • For cancer treatments, deep laser transmission is commonly used. Red light and infrared are the sources of light energy that can perpetrate deeper than other lights.

Therefore, Choline-B 6, the light catalyst that is suitable with the function of red light and Indocyanine Green (ICG), the photosensitizer that is suitable with the function of infrared are better options for an optimal result.

The combination mentioned above is commonly used for diagnostic in conventional medicine. They are non-poisonous and cause no side-effects to the body. In turn, they are highly sensitive and has the ability to detect cancerous and mutated cells.

The tissues effected by tumor will be dyed by the substances mentioned. The laser treatment will then take place thereafter. During treatment, the cancer cell will be destroyed whereas the normal cells will not be affected. This technique is an effective, non-poisonous, non-harmful approach to treating cancer.

IPT

Cancer cells needs a lot of sugar to survive. Therefore, with this knowledge we use insulin to manipulate and lure cancer cells. This treatment protocol combinations the use of insulin with low-dose chemotherapy. Many research studies have shown the increase in effectiveness of chemotherapy with the help of insulin in weakening the cancer cells. Insulin is a form of hormone that takes glucose into cells.  Cancer cells cannot use oxygen to burn consumed glucose for energy. In general, normal cells can generate 38 ATP of energy from 1 glucose molecule, while cancer cells only generate 2 ATP of glucose from 1 molecule.

Cancer cells require 19 times more sugar than normal cells on the surface. Therefore, cancer cells have insulin receptors. In insulin therapy, the mechanism of action works by adjusting itself to the environment around the cancer cells so that the cancer cells are ready to absorb the insulin.

In our treatment protocol, patients have to abstain from food for 6-12 hours before being undergoing the insulin therapy which consist of the controlled insulin injection. About 20-40 minutes after the injection, patients will be infused with a low dose of chemotherapy accordingly. The insulin injection given before the chemotherapy acts as a kind of homing device so that it enables the cancer cells to precisely absorb more of the  chemotherapy. The treatment must be done under the strict supervision of the physician.

This mechanism of action increases the effectiveness of the cancer treatment because the chemotherapy is able to fully engulf the cancer cells. The physician’s aim is to use only a small amounts of chemotherapy in order to reduce the side effects. This also allows the chemotherapy to be done more often while reducing the risk of damaging the normal cells in the body. The other positive side effect of the therapy is that it slows down any further cancerous cell growth without harming the immune system.

With the insulin therapy, the immune system will continue to work as before. Therefore, the therapy can still effectively protect the body better than using straight forward chemotherapy to fight the cancer due to its low-dose nature. The whole aim of this treatment is to make the chemotherapy change the growth process of the cancer cells and how the cells divide themselves to further multiply in the body. By doing so, it can assist in stopping the cell division or slowing it down.

However, this treatment does not fully destroy the cancer cells. In order to do so, this treatment must be done in conjunction with Immunotherapy. This is simply because the immune system can help to induce the condition that stimulates the process of cancer cells destruction, also known as Apoptosis plus boost cell metabolism. The metabolic system will allow cells to create more oxygen. When the oxygen condition improves, Mitochondria works well and the immune system will be much stronger. This process will inevitably cause the cancer cells to be destroyed.

Artesunate

Artesunate is a drug used in the treatment of Malaria. It is a natural extract and has many beneficial properties. It has been used in traditional Chinese medicine and oriental medicine for thousands of years, for the purpose of killing of parasites, detoxing and treating Malaria.

According to a study from the University of Washington, researchers found that Artesunate has specific effects on cancer cell destruction. This happens because it affects the iron in the body. Iron is a mineral that produces free radicals which causes Inflammation and helps cancer cells grow better.

Therefore, it makes Artesunate effective in eliminating cancer cells. It reacts with normal iron to convert it into an iron mineral that has a  destructive reaction towards cancer cells as they contains iron. The compound of the Normal cells in turn, do not consist of high iron content.

As mentioned above, this treatment is not toxic to normal cells.  Studies have shown that such as Artesunate, has the ability to destroy cancer cells up to 100 times more than normal cells and also found that cancer cells contain 34,000 times more iron than normal cells. Thus, the use of Artesunate for a targeted treatment of cancer cells can be highly effective and so far has a proven track record of positive outcomes in fighting cancer.

Amigdalin

Laetrile/ Amygdalin/ B17

Laetrile, also known as Amygdalin or B17, is an aromatic cyanogenic glucoside found in the pits of many fruits, in raw nuts, and in other plants such as bitter almonds, peach, plums, apple well as apricot and cherry seeds. Plants like lima beans, clover and sorghum also contain amygdalin. Although it is frequently called

vitamin B17 but it is not recognized as vitamin.

Laetrile is a partly man-made (synthetic) form of the natural substance amygdalin. Laetrile was isolated from apricot pits by Ernest Krebs, MD. In the 1920’s.

HOW VITAMIN B17 KILLS CANCER?

According to research conducted by Ernest T. Krebs Jr. Amygdalin (B17) itself is nontoxic but it produces poisonous substance Hydrogen Cyanide (HCN) which is decomposed by enzymes Beta- Glucosidase which found in very large quantities only at the cancer cells but not found anywhere else in the body.

B17 is made up of 2 parts glucose, 1 part Hydrogen Cyanide and 1 part Benzaldehyde (analgesic/painkiller).

One particular enzyme called Rhodanese found everywhere in the body except at the cancer cells.

The Rhodanese breaks the Hydrogen Cyanide and Benzaldehyde down into 2 by-products, Thiocyanate and Benzoic acid which are beneficial in nourishing healthy cells and forms the metabolic pool production for vitamin B12.

When the B17 comes into contact with cancer cells, there is no Rhodanese to break it down and neutralise it but instead, only the enzyme Beta-Glucosidase is present in very large quantities.

When B17 and Beta-Glucosidase come into contact with each other, a chemical reaction occurs and the Hydrogen Cyanide and Benzaldehyde combine synergistically to produce a poison which destroys and kills the cancer cells. This whole process is known as selective toxicity. Only the cancer cells are specifically targeted and destroyed.

Amygdalin (B17) is available as:

• an injection (intravenously)

• tablets

Taking Amygdalin as tablets has more side effects than having it as an injection such as nausea, vomiting, headache and dizziness

Avoid eating other foods containing amygdalin if you take Amygdalin as tablets. This may include foods like:

• raw almonds

• carrots

• celery

• apricots

• peaches

• bean sprouts

• beans – mung, lima, butter and other pulses

• nuts

• flax seed

• high doses of vitamin C

• crushed fruit stones or pips

These foods are safe to eat when you’re not taking Amygdalin because the levels of amygdalin in them are low.

Use with caution in patients who have liver problem.

 

REFERENCES

https://www.researchgate.net/publication/228673923_Vitamin_B17LaetrileAmygdalin_a_Review

https://www.sciencedirect.com/topics/neuroscience/amygdalin

https://en.wikipedia.org/wiki/Amygdalin

http://www.acanceresearch.com/cancer-research/review-on-pharmacological-activity-of- amygdalin.pdf

Laetrile; Naturopathic Oncology : An Encyclopedia Guide for patients and physicians, Dr.Neil Mckinney, BSc, ND; 3rd edition

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