White Paper: Continuous Oral Dosages Required to Kill Colon Cancer Stem Cells

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White Paper: Continuous Oral Dosages Required to Kill Colon Cancer Stem Cells

Post Number:#1  Post by ofonorow » Fri Oct 27, 2017 5:00 am

This is the draft our the Foundation White Paper https://vitamincfoundation.org/pdfs/CancerWhitePaper.pdf that assign oral dosages to the optimal numbers found in the landmark Sen, et. al. study Opposing effects of low versus high concentrations of water soluble vitamins/dietary ingredients Vitamin C and niacin on colon cancer stem cells (CSCs)
http://onlinelibrary.wiley.com/doi/10.1002/cbin.10830/full

Press release http://www.einpresswire.com/article/411975996/landmark-study-resolves-the-linus-pauling-and-arthur-robinson-vitamin-c-and-cancer-controversy-both-men-were-right

This is collected from earlier related posts
http://vitaminc.foundation/forum/viewtopic.php?f=3&t=13473
http://vitaminc.foundation/forum/viewtopic.php?f=3&t=13483
http://vitaminc.foundation/forum/viewtopic.php?f=3&t=13494

Oral Vitamin C Dosages Required to Achieve Cancer Stem Cell Destruction to Avoid Colon Cancer Stem Cell Proliferation.

For the first time in the history of science a group of researchers studied the optimal dosing of vitamin C with respect to the "seeds of cancer," i.e., colon cancer stem cells (CSCs). Sen, et. al., found that higher doses of vitamin C and Niacin, or vitamin B3, destroy cancer stem cells.

Published in the journal Cell Biology International, the landmark study investigated both low and high doses of vitamin C and Niacin on stem cells tumors of the intestine. Different dosages produced opposite effects. Note: Vitamin C was twice as effective as Niacin. We are not experts in Niacin blood concentrations, but note the late E. Hoffer, MD, PhD, prescribed equal dosages of vitamin C and Niacin to his cancer patients.


Abstract

Colorectal cancer is one of the global causes of cancer deaths. Cancer stem cells (CSCs) inside the tumour niche responsible for metastasis and relapses, and hence need to be targeted for cancer therapeutics. Although dietary fibre and lifestyle changes have been recommended as measures for colorectal cancer prevention, no such recommendations are available for using water soluble vitamins as prophylaxis measure for colorectal cancers. High dose of Vitamin C has been proven to selectively kill colon cancer cells having BRAF and KRAS mutations by inducing oxidative stress. In this study, we show for the first time the opposing effects of the low and high dose of Vitamin C and vitamin B3 on colon CSCs isolated from HT-29 and HCT-15 colorectal carcinoma cell lines. At small doses, both of these vitamins exerted a cell proliferative effect only on CSCs, while there was no change in the proliferation status of non-stem cancer cells and wild-type (WT) populations. On the other hand, the death effects induced by high doses of Vitamin C and B3 were of the order of 50–60% and ∼30% on CSCs from HT-29 and HCT15, respectively. Interestingly, the control fibroblast cell line (NIH3T3) was highly refractory all the tested concentrations of Vitamin C and B3, except for the highest dose – 10,000 μg of Vitamin C that induced only 15% of cell death. Hence, these results indicate the future scope of use of therapeutic doses of Vitamin C and B3 especially in patients with advanced colorectal cancer.


This research shows that when taking vitamin C to create a blood concentration of 5-25 micromole/L of vitamins C and B3, which is a low concentration, there is a process of active reproduction of stem cells tumors of the intestine. At high dosages (creating concentrations of 100 to 1,000 micromoles) these stem cells are destroyed.

New Study is Not A Threat to Oncology

There are two different types of cancer cells. Ordinary malignant cancer cells divide rapidly, making them susceptible to both chemotherapy and/or radiation therapy. The other type of cell, the "seeds" of cancer that spawn ordinary malignant cancer cells are called Cancer Stem Cells or CSCs in the literature. They divide too slowly for chemo or radiation to be effective. Because they survive, they soon spawn more aggressive ordinary malignant cells, thus the high recurrence rate for chemo/radiation.

This new research shows that both Vitamin C, and Niacin, in optimal concentrations - that can be achieved by around-the-clock oral dosing - kills the CSCs. So this doesn't affect the original business of oncology - people need to deal with the ordinary malignancy. However, if oncologists added the oral vitamin C/niacin protocol as a complementary treatment, they would be able to suppress the now very high recurrence rates and save their patient's lives.

This is the essence of the news in our press release
http://www.einpresswire.com/article/411 ... were-right

We Recommend Continuous Oral Vitamin C (and Niacin) Dosing for Cancer Patients

The Vitamin C Foundation nonprofit recommends, on the basis of the Indian Sen, et. al. landmark study, that all cancer patients be advised to supplement vitamin C in oral amounts that can achieve at least a 100 micromoles/liter concentration in their blood for as long as possible.

The major problem is that the kidney constantly reduces vitamin C concentrations to less than this amount steady state, e.g. 85 micromoles/liter, with a half-life of 30 minutes. Our initial estimates are that 1 gram or less of oral vitamin C daily creates the concentrations that promote CSC proliferation, and that 4 grams creates the minimum required 100 micromole/litter concentration, at least for a little while. Dosages up to 80 grams would be appropriate and safe.

Continuous Oral Dosing May Work Better than IV/C

The Vitamin C Foundation calculates that continuous oral supplemental oral intakes of vitamin C can achieve the study's reported cancer-lethal concentrations in the blood. The normal laboratory range for vitamin C in the USA is 0.4 mg/dl to 1.5 mg/dl, (23 to 85 μM/L). The Indian study results indicate that a 100 μM concentration (1.76 mg/dl) is the low end of the cancer-lethal range, or just above steady state (1.5 mg/dl). Sustaining this above-steady state blood level requires continuous vitamin C supplementation, as long advocated by vitamin C experts Steve Hickey and Hilary Roberts, PhDs. While intravenous vitamin C can exceed the 10,000 μM by 2.5 times (e.g. 440 mg/dl or 24,983.2 μM/L ) this is apparently suboptimal, may spur CSC proliferation, and it is difficult to keep people on constant intravenous vitamin C infusions.

The low range (5 to 25 μM) that promotes the growth of cancer stem cells equals a lab range of 0.08 to 0.44 mg/dl which is below normal and can easily be raised through regular vitamin C supplementation.

I Have Cancer, How Much Vitamin C Should I Take Based on The Sen, et. al. Test Tube Study?

On the basis of research conducted in New Zealand, (Krone/Ely) we believe that the minimum dosage to maintain a cancer-killing concentration is 1,000 mg every 2 hours.


A 1 g oral dose of AA can raise plasma AA to 130 µmol/L within an hour and such doses at intervals of about two hours throughout the day can maintain ~230 µmol AA/L
Cheryl A Krone, John A Ely, Journal of the New Zealand Medical Association, 23-August-2002, Vol 115 No 1160, Glycohaemoglobin and ascorbic acid)


This protocol requires a minimum daily dosage of 12,000 milligram (12 gram). Note: 8 hours of sleep requires a loading dose before bed, or timed release vitamin C. This minimum oral protocol maintains a 230 µM concentration, which is at the low-end of the optimum cancer killing range (100µM to 1,000µM )

There is an uninvestigated range, AA concentrations from 26 µM to 99 µM.

The low, CSC stimulating concentrations (<26µM) would be expected from taking 1,000 mg (1 gram) of vitamin C or less daily.

We calculate that without the short half-life, approximately 40,000 mg (40 grams) of Vitamin C daily would reach a maximum optimal concentration of 1,000 uM. But high levels of vitamin C do not remain in the blood. Because of the short 30-minute half-life, we believe that 80 grams of vitamin C would be safe, and achieve the 1,000 uM concentration, on average, over a longer duration.

Conclusion

Many factors can affect ascorbate (vitamin C) blood concentrations, including stress and illness, the type of vitamin C that is taken orally (e.g. ascorbic acid versus sodium ascorbate or liposomal vitamin C), the amount of sugar (glucose) in the diet, and the ability of the patient to consume high amounts of vitamin C, often called Bowel Tolerance.

We know from the work of biochemist Sherry Lewin, PhD (VITAMIN C: Its Biology and Medical Potential (1976)) that when vitamin C is administered at the same time carbohydrates are eaten, the vitamin breaks down in the intestinal tract, and less is absorbed into the blood stream. In contrast, when vitamin C is eaten with a protein, the amino acids chelate with the vitamin, protecting it during digestion, making the vitamin more bioavailable. There are many products on the market that offer both vitamin C and the amino acid lysine together.

Our recently published BIOAVAILABILITY OF VITAMIN C paper demonstrated the different rates of absorption between ascorbic acid, and the salt sodium ascorbate. Previously unknown, ascorbic acid entry into the blood stream is very rapid, probably through the stomach wall, and concentrations can exceed an IV/C, at least for a short time. On the other hand, sodium ascorbate enters the blood stream more slowly, more like a timed release, and probably travels down the GI Tract and is absorbed through the intestines. If not taken with protein, it is probable that more of the vitamin would break down and not be bioavailable in the form of sodium ascorbate, indicating that a higher dosage may be required.

Some people have low bowel tolerances, meaning they cannot achieve even the minimum daily protocol of 1 gram every 2 hours. Liposomal technology may be the answer because more vitamin C is absorbed when encapsulated in liposomes, and the liposomes persist 4 to 6 times longer in the blood stream. It is unknown whether the vitamin encased in a 150 nanometer liposome would have the same CSC killing effect. Sen reports on a study that found liposomes made from fat soluble vitamin C (ascorbyl palimate) were more potent than ordinary vitamin C injections in breast cancers.

Our advice at this point if you have cancer. Supplement vitamin C, at least 1 gram every 2 hours, no matter what other therapies you are on. (12,000 mg or 12 g per day_)

Higher doses, e.g. 2 or 4 grams every 3 to 4 hours would be even more optimal. 16,000 mg (16 g) to 24,000 mg (24 g) per day.

The highest dosages, up to 40 to 80 g per day should maintain the highest optimal CSC killing range. This confirms Dr. Robert's Cathcart, II, MD's clinical experience that the bowel tolerance range for cancer patients is a daily amount 15 g to 100 g (https://vitamincfoundation.org/FDAapproved/pdfs/Vitamin_C_Dosage_in_Disease.pdf)

While much higher dosages are being investigated intravenously (Drisko), the optimality of these dosage w/r to CSCs was not investigated by Sen.

References


1. Ma, Y., Sullivan, G. G., Schrick, E., Choi, I.-Y., He, Z., Lierman, J., … Chen, Q. (2013). A Convenient Method for Measuring Blood Ascorbate Concentrations in Patients Receiving High-Dose Intravenous Ascorbate. Journal of the American College of Nutrition, 32(3), 187–193. http://doi.org/10.1080/07315724.2013.791167

2. Bürzle M, Hediger MA. (2012). Functional and physiological role of vitamin C
transporters. Curr Top Membr, 70:357-75.

3. Corti A., Casini A. F., Pompella A. (2010). Cellular pathways for transport and efflux of ascorbate and dehydroascorbate. Archives of Biochemistry and Biophysics, 500(2):107–115. doi: 10.1016/j.abb.2010.05.014.

4. Szarka A, Lőrincz T. (2013). Cellular and intracellular transport of vitamin C. The physiologic aspects. Orv Heti, 154(42):1651-6. doi: 10.1556/OH.2013.29712.

5. Fonorow, O. (2015, June 15). Bioavailability of Vitamin C. Retrieved from http://vitaminc.foundation/forum/viewto ... =3&t=11944

6. Hickey, S., & Roberts, H. (2004). Ascorbate: The science of vitamin C. Morrisville, NC: Lulu.

7. Hickey, S., & Roberts, H. (2005). Ridiculous Dietary Allowance. Lulu.com.

8. Levine M., Conry-Cantilena C., Wang Y. (1996). Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci, 93(8):3704–3709.


9. Levine M, Padayatty SJ, Espey MG. (2011). Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries. Adv Nutr, 2:78–88.

10. Chen P., Stone J., Sullivan G., Drisko J. A., Chen Q. (2011). Anti-cancer effect of pharmacologic ascorbate and its interaction with supplementary parenteral glutathione in preclinical cancer models. Free Radical Biology and Medicine, 51(3):681–687. doi: 10.1016/j.freeradbiomed.2011.05.031.

11. Monti, D. A., Mitchell, E., Bazzan, A. J., Littman, S., Zabrecky, G., Yeo, C. J., … Levine, M. (2012). Phase I Evaluation of Intravenous Ascorbic Acid in Combination with Gemcitabine and Erlotinib in Patients with Metastatic Pancreatic Cancer. PLoS ONE, 7(1), e29794. http://doi.org/10.1371/journal.pone.0029794

12. Wang G, Yin T, Wang Y. (2016). In vitro and in vivo assessment of high-dose vitamin C against murine tumors. Exp Ther Med, (12):3058–3062.

13. Leekha A, Gurjar BS, Tyagi A, Rizvi MA, Verma AK. (2016). Vitamin C in synergism with cisplatin induces cell death in cervical cancer cells through altered redox cycling and p53 upregulation. J Cancer Res Clin Oncol, 142(12):2503-2514.

14. Baek MW, Cho HS, Kim SH, Kim WJ, Jung JY. (2017). Ascorbic Acid Induces Necrosis in Human Laryngeal Squamous Cell Carcinoma via ROS, PKC, and Calcium Signaling. J Cell Physiol, 232(2):417-425. doi: 10.1002/jcp.25438.


15. Campbell EJ, Vissers MC, Wohlrab C, Hicks KO, Strother RM, Bozonet SM, et al. (2016). Pharmacokinetic and anti-cancer properties of high dose ascorbate in solid tumours of ascorbate-dependent mice. Free Radic Biol Med, 99:451–62.10.1016/j.freeradbiomed.2016.08.027

16. FRAJESE, G. V., BENVENUTO, M., FANTINI, M., AMBROSIN, E., SACCHETTI, P., MASUELLI, L., … BEI, R. (2016). Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro. Oncology Letters, 11(6), 4224–4234. http://doi.org/10.3892/ol.2016.4506

17. Aguilera, O., Muñoz-Sagastibelza, M., Torrejón, B., Borrero-Palacios, A., del Puerto-Nevado, L., Martínez-Useros, J., … García-Foncillas, J. (2016). Vitamin C uncouples the Warburg metabolic switch in KRAS mutant colon cancer. Oncotarget, 7(30), 47954–47965. http://doi.org/10.18632/oncotarget.10087

18. Jung S-A, Lee D-H, Moon J-H, Hong S-W, Shin J-S, Hwang IY, et al. (2016). L-Ascorbic acid can abrogate SVCT2-dependent cetuximab resistance mediated by mutant KRAS in human colon cancer cells. Free Radic Biol Med, 95:200–8.10.1016/j.freeradbiomed.2016.03.009

19. Chung MK, Kim do H, Ahn YC, Choi JY, Kim EH, Son YI. (2016). Randomized Trial of Vitamin C/E Complex for Prevention of Radiation-Induced Xerostomia in Patients with Head and Neck Cancer. Otolaryngol Head Neck Surg, 155(3):423-30. doi: 10.1177/0194599816642418.

20. Zhao F, Wang YF, Song L, Jin JX, Zhang YQ, Gan HY, Yang KH. (2017). Synergistic Apoptotic Effect of D-Fraction From Grifola frondosa and Vitamin C on Hepatocellular Carcinoma SMMC-7721 Cells. Integr Cancer Ther, 16(2):205-214. doi: 10.1177/1534735416644674.

21. Parrow, N. L., Leshin, J. A., & Levine, M. (2013). Parenteral Ascorbate As a Cancer Therapeutic: A Reassessment Based on Pharmacokinetics. Antioxidants & Redox Signaling, 19(17), 2141–2156. http://doi.org/10.1089/ars.2013.5372

22. Cathcart R.F. (1981). Vitamin, C.; titrating to bowel tolerance, anascorbemia, and acute induced scurvy. Med. Hypotheses, 7:1359–1376. doi: 10.1016/0306-9877(81)90126-2.
Owen R. Fonorow, Orthomolecular Naturopath
My statements have not been evaluated by the Food and Drug Administration. Any product mentioned is not intended to diagnose, treat, cure or prevent any disease.”

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