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Orthomolecular Medicine News Service, July 30, 2013

Vitamin C and Cancer:
The Naked Mole-Rat Connection

by Steve Hickey, PhD

(OMNS July 30, 2013) Naked mole-rats are highly resistant to cancer despite their living much longer than other small rodents. While laboratory mice generally live less than three years and often die of cancer, mole-rats can live up to 30 years yet tumours are rare. Researchers recently claimed that they had found an explanation.[1] It appears that naked mole-rats have a very strong tissue matrix based on a long-chain biomolecule called hyaluronic acid (hyaluronan). Supplement users may recognise this molecule from its wide use in reversing arthritis along with other glycosaminoglycans such as glucosamine and chondroitin. These supplements are used to regrow and reinforce damaged cartilage and other connective tissues. Similarly, hyaluronic acid helps mole-rats strengthen their tissues for tunnelling through soil and they have a particularly large version of the molecule. An enzyme called hyaluronidase breaks down hyaluronic acid. This and related enzymes work slowly in mole-rats which allows hyaluronic acid to accumulate in their tissues.

Hyaluronic Acid Inhibits Cancer

The abundance of hyaluronic acid in mole-rats strengthens the surrounding tissues, challenging their invasion by cancer cells. Tiny tumours have difficultly growing larger and spreading, both locally and to distant sites (metastases). In addition, hyaluronic acid acts as a signal inhibiting the growth of cancer cells. Naked mole-rat cells are seemingly far more responsive to the signal, making them even less likely to form a spreading cancer. This research "breakthrough" was recently reported in Nature, one of the world's leading scientific journals, and quickly picked up by the international media.[1] The study supports orthomolecular medicine since hyaluronic acid, available as a supplement in health food stores, is a natural molecule found in the body. So why are we somewhat less than impressed?

Vitamin C Prevents Spread of Cancer

The recent paper on cancer in mole-rats confirms and reinforces earlier findings. Going back to 1966, surgeon and orthomolecular doctor Ewan Cameron published a book on hyaluronidase and cancer which is now an expensive collector's item.[2] Over 30 years ago Ewan Cameron and Linus Pauling provided an updated explanation of how high doses of vitamin C prevent the spread of tumors.[3,4] They suggested that cells are restrained from proliferating by the highly viscous nature of hyaluronic acid and other glycosaminoglycans. In order to spread, cancer cells must escape from this restriction by breaking down these molecules in their local tissues.

Cameron and Pauling had previously described the importance of hyaluronidase and enzymes that break down hyaluronic acid.[5] They explained how cancer cells released hyaluronidase and other tissue breakdown enzymes. As they put it "the only difference between neoplasia and normal cell proliferation is the persistence of hyaluronidase release in the former."[3] They suggested that vitamin C blocked the breakdown of hyaluronic acid. In other words, Cameron and Pauling pre-empted the recent study by several decades. Some may be reminded of the description of Linus Pauling being consistently 20 years ahead of other scientists.[6]

Over the past decade it was shown that vitamin C inhibits hyaluronidase and related breakdown enzymes.[7,8] Once again this is not a new finding as it was determined by Edmond Reppert and colleagues back in 1951.[9] The recent mole-rat study is a confirmation of the core ideas of Cameron, Pauling, and others. It supports an important anticancer mechanism of high-dose vitamin C. Over the last several decades, additional ways that vitamin C attacks cancer have been established.[10-13]


Although we welcome the recent mole-rat paper, our enthusiasm is tempered by the lack of references to the far earlier work of Pauling, Cameron, and other orthomolecular researchers. The paper presents old ideas as new. Orthomolecular medicine should not be ignored when its findings are confirmed. Vitamin C provides an effective basis for the safe treatment of cancer, an important implication that the recent paper and the worldwide media coverage failed to mention.


1. Tian X, Azpurua J, Hine C. Vaidya A, Myakishev-Rempel M, Ablaeva J, Mao Z, Nevo E. Gorbunova V. Seluanov A. (2013) High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat, Nature, Jun 19, doi: 10.1038/nature12234.

2. Cameron E. (1966) Hyaluronidase and Cancer, Pergamon Press.

3. Cameron E. and Pauling L. (1973) Ascorbic acid and the glycosaminoglycans: an orthomolecular approach to cancer and other diseases. Oncology, 27, 181-192.

4. Cameron E, Pauling L, Leibovitz B. (1979) Ascorbic acid and cancer: a review, Cancer Res., 39(3), 663-681.

5. Gonzlez MJ, Miranda-Massari JR, Mora EM, Guzmn A, Riordan NH, Riordan HD, Casciari JJ, Jackson JA, Romn-Franco A. (2005) Orthomolecular oncology review: ascorbic acid and cancer 25 years later, Integr Cancer Ther., 4(1), 32-44.

6. Roberts H. (2004) Vitamin C, Linus Pauling was right all along. A doctor's opinion, Medical News Today, Aug 17.

7. Okorukwu ON, Vercruysse KP. (2003) Effects of ascorbic acid and analogs on the activity of testicular hyaluronidase and hyaluronan lyase on hyaluronan, J Enzyme Inhib Med Chem., 18(4), 377-382.

8. Spickenreither M, Braun S, Bernhardt G, Dove S, Buschauer A. (2006) Novel 6-O-acylated vitamin C derivatives as hyaluronidase inhibitors with selectivity for bacterial lyases, Bioorg Med Chem Lett., 16(20), 5313-5316.

9. Reppert E, Donegan J, Hines LE. (1951) Ascorbic acid and the hyaluronidase hyaluronic acid reaction, Exp Biol Med., 77(2), 318-320.

10. Hickey S (2013) Antioxidants may prevent cancer and some may even cure it.

11. OMNS (2011) Intravenous vitamin C as cancer therapy.

12. OMNS (2010) Cancer and vitamin C: Evidence-based censorship.

13. OMNS (2008) Vitamin C slows cancer down. And, doctors say, can reverse it as well.

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Editorial Review Board:

Ian Brighthope, M.D. (Australia)
Ralph K. Campbell, M.D. (USA)
Carolyn Dean, M.D., N.D. (USA)
Damien Downing, M.D. (United Kingdom)
Dean Elledge, D.D.S., M.S. (USA)
Michael Ellis, M.D. (Australia)
Martin P. Gallagher, M.D., D.C. (USA)
Michael Gonzalez, D.Sc., Ph.D. (Puerto Rico)
William B. Grant, Ph.D. (USA)
Steve Hickey, Ph.D. (United Kingdom)
Michael Janson, M.D. (USA)
Robert E. Jenkins, D.C. (USA)
Bo H. Jonsson, M.D., Ph.D. (Sweden)
Peter H. Lauda, M.D. (Austria)
Thomas Levy, M.D., J.D. (USA)
Stuart Lindsey, Pharm.D. (USA)
Jorge R. Miranda-Massari, Pharm.D. (Puerto Rico)
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Erik Paterson, M.D. (Canada)
W. Todd Penberthy, Ph.D. (USA)
Gert E. Schuitemaker, Ph.D. (Netherlands)
Robert G. Smith, Ph.D. (USA)
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