Oregon State UniversitySpecial Collections & Archives Research Center
Vitamin C and Cancer: A Personal Perspective
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Contrary to what our many critics may think, the idea that vitamin C (ascorbic acid) might have some therapeutic value in cancer, has a perfectly respectable scientific background. In my own case, it evolved from a whole series of arguments progressively developed over many years.

As we all know, the cancer cell has two behavioral characteristics, namely relentless proliferation and remorseless invasion. Almost all cancer research, directed towards evolving new treatment strategies, has concentrated on finding methods of destroying proliferating cells. And, of course, it is quite wrong to imagine that this approach has failed. We have radiation therapy, very effective in many forms of cancer, and a whole armory of cytotoxic chemotherapeutic drugs capable of killing proliferating cancer cells. However, as we all know, their use is limited because they also destroy all proliferating normal cells. In passing, it is interesting to note that the oncologists, who are our bitterest critics, do not possess a single specific anti-cancer drug in their cupboards.

For many years I have felt almost alone in suggesting an alternate way of controlling the cancer cell, by devising methods of disarming its other property, namely invasiveness. Invasiveness is quite unique to the cancer cell, therefore any treatment strategy along these lines would be quite specific for cancer, leaving all normal cells unharmed. Furthermore, invasiveness, the ability to infiltrate, ulcerate, and destroy adjacent tissues including the ability to form distant metastases themselves invasive, is the dangerous and ultimately lethal property of the malignant cell. Inhibit invasiveness, and the cancer cell becomes harmless.

To inhibit invasiveness requires an understanding of the underlying mechanism. Compressing many years of personal work, I may simply say that it is due to the continuous release of the enzyme hyaluronidase from the malignant cell, depolymerizing and hydrolyzing the glycosaminoglycans and proteoglycans that form the viscous ground substance that binds all tissue components together (1).

Tumor cell hyaluronidase may be inhibited by preparing antisera, and Soviet investigators have reported some success in tumor-bearing animals using this route. One may inhibit hyaluronidase by pharmacological methods, but the compounds known to be active are all fairly toxic and interfere in many enzyme systems. To me, the most promising route could be the one labeled "natural" or "physiological."

Way back in the early 1950's, Dr. David Glick, late of Stanford University, discovered that there exists in the tissue and plasma of all animal species, including man, a substance he labeled Physiological Hyaluronidase Inhibitor or PHI. Moreover, this plasma fraction occupies a fairly narrow, low range in healthy individuals, but rises appreciably in all cancer patients though not always to the same extent (2). Dr. Glick's main interest was in discovering a diagnostic laboratory test for cancer, and when he found that elevated levels were found in a number of acute infections and other cell-proliferative illnesses, he promptly lost interest (3).

Spontaneous regression of advanced human cancers have been documented on many hundreds of occasions usually following massive bacterial infections, classically erisypelas. I postulated that massive invasion of the tissues by hyaluronidase-producing streptococci, as in erisypelas, would swamp the circulation with depolymerization by-products including PHI raised to such a high level that the tumor would be permanently suppressed. Finding a safe method of permanently raising PHI to a very high level could lead to a cancer cure. These arguments and the supporting evidence are given at length in my 1966 book (1).

Ground substance glycosaminoglycan is a very high molecular weight polymer of the repeating disaccharide unit (Glucuronic Acid-N-Acetyl Glucosamine). After my book was published, some Australian workers led by Peter Ghosh discovered that PHI was a glycoprotein of which the carbohydrate moiety was a tetrasacharide of ground substance origin, but changed in some subtle way to give it its specific inhibitory activity (5). Glucuronic acid is the intermediate in the biosynthesis of ascorbic acid from glucose. Douglas Rotman, a young American and I, indicated in 1971 that PHI was simply the basic tetrasachharide in which one or both glucuronic acid units had become replaced by its near chemical relative, ascorbic acid (6).

This led to the seemingly absurd conclusion that simple, safe, common vitamin C might have some therapeutic value against such a bafflingly complex disease as cancer. I say absurd, because until then the only use of vitamin C in my hospital was as a placebo sleeping tablet. I can therefore understand why the medical profession is still skeptical about our work. I cannot understand the open hostility expressed in some quarters.

The proposal gains some support from the oft-repeated finding that cancer patients are almost invariably depleted of vitamin C (references in 7) and high in PHI (2). My strategy was to prescribe vitamin C in the hope of boosting PHI to the maximum possible extent.