The Linus Pauling - Mayo Clinic controversy involving vitamin C and cancer tests

Nutrition Health Review, Wntr, 1995 by Steve Austin, Cathy Hitchcock

Several vitamins and minerals called antioxidants protect the body against a form of cellular damage linked with cancer. Each of these vitamin and mineral antioxidants, including vitamin C, appears to provide some protection against cancer. Vitamin C is also known to protect animals from cancer.(1)(3) It is now relatively well accepted that vitamin C protects humans from stomach cancer.(4)(6) Many researchers believe other cancer risks are also reduced by higher-than-normal vitamin C intake.(7)

Vitamin C affects the immune system, which must be functioning well to combat cancer. White blood cells (WBCs), the immune system's primary fighting force, contain the vitamin. Reviews of the research show that WBCs taken from cancer patients have less vitamin C than do WBCs from healthy people.(8)

Treating cancer with vitamin C has been a controversial issue since Linus Pauling, the Nobel Prize-winning scientist, began to advocate it years ago. Working with a Scottish surgeon, Ewan Cameron, Pauling decided to investigate the possibility that vitamin C might help patients who already have cancer.(10) One hundred terminal cancer patients were given 10 grams of vitamin C daily (2.5 grams four times per day) and followed until death. They lived an average of 210 days, compared with hospital records of 1,000 "matched controls" (similar patients) who averaged only 50 days. A follow-up showed an even wider gap between the vitamin C and control groups.(11)

The rest of the research community was concerned about these results, in part because the 1,000 control patients received no placebo.(12) In other words, the patients taking the vitamin might have lived longer because they believed the therapy might have helped them.(*) Ironically, while conventional medicine has very little interest in psychological intervention in cancer treatment, medical doctors feel no qualms about using the argument that placebo effect, a psychological intervention, might extend life significantly.

The Mayo Clinic attempted to test Cameron and Pauling's results. The Mayo Clinic paper, which did have a placebo-control group, reported that vitamin C did not help.(13) Linus Pauling protested that the two trials weren't equivalent because most of the Mayo Clinic patients had had chemotherapy, while his patients had not. This distinction might be important because chemotherapy impairs the immune system; and, as mentioned earlier, one way in which vitamin C might help cancer patients is by boosting immune function. Theoretically, a damaged immune system might not be able to take advantage of supplemental vitamin C.

In response, the Mayo Clinic proceeded to do another study testing vitamin C. This time they used patients who had had no chemotherapy.(14) The researchers said that this trial was ethical because "there is no known form of chemotherapy for colorectal cancer that has been demonstrated to produce substantive palliative benefit or extension of survival."(15) For this reason, the second Mayo Clinic study was limited to colon cancer patients. Once again, the researchers claimed that vitamin C was useless.

But careful examination of the second Mayo Clinic study shows that Pauling's hypothesis was never tested. Pauling said that terminal cancer patients fed vitamin C until death would live substantially longer. In the Mayo study, as soon as the cancer progressed, patients were taken off vitamin C. The researchers claimed that it was unethical to keep them on the therapy because it wasn't working. In fact, there was no way to know whether the vitamin C was "working" unless patients were kept on it until they died. Keep in mind that these were terminal patients to begin with. Pauling and Cameron had never said that the vitamin was curative (though a couple of their patients actually lived for many years); rather, they claimed only that terminal patients taking C until they died lived longer on average.

There was another irony in the stance taken by the Mayo Clinic team. While it was "inhumane" to keep patients on vitamin C,(16) an inexpensive and harmless supplement, many of these patients were subsequently given fluorouracil, the very form of chemotherapy that had been proven repeatedly to be ineffectual and toxic in the treatment of colon cancer. Recall that the uselessness of chemo was the initial ethical justification for putting terminal colon cancer patients on a regimen that did not include chemo. Although the transparency of the clinic researchers' bias has been discussed in relatively obscure alternative sources,(17) it has not been picked up by the media or by conventional medical journals.

A separate criticism of the second Mayo Clinic trial also has some merit: The control group may also have been taking vitamin C. All of the colon cancer patients were told that vitamin C was being tested to see if it would help them. They were also told that they might not be getting the real vitamin C; their pill might be just a placebo. Under these circumstances, who would be so compliant as to not sneak a little vitamin C on the side? Such a surreptitious change would obviously invalidate the outcome. A very limited investigation was made to rule out this possibility (only six placebo-taking patients were checked, and they were checked at only one point in time). Vitamin C excreted in urine reflects oral intake; patients were considered not to be taking clandestine vitamin C if their urine contained 550 milligrams of vitamin C per day or less -- vastly more than the average person will excrete under normal circumstances. It seems inconceivable that the Mayo researchers didn't know that fact. Even at the 500 milligram level, one of the six patients exceeded the limit, strongly suggesting that he or she was "cheating," as most thinking people would do under the circumstances. To restate the implications, patients in the placebo group could have been taking vitamin C; and the test the researchers used to rule that out was faulty.