 Vitamin C is no stranger to controversy, as evidenced by the fact that it took 40 years between when citrus fruits were shown to cure scurvy in the 1700s and the widespread implementation of this practice to save lives. Is it possible we're in the midst of a similar 40-year lag with research in the mid-70s purporting to show that terminal cancer patients treated with vitamin C lived four times longer, and sometimes 20 times longer? Researchers at the venerable Mayo Clinic decided to put it to the test, and they failed to show any benefit. The survival curves for both groups of patients were essentially identical. In fact, the one success story, a guy with end-stage pancreatic cancer who had shown no response to any previous attempts at chemo, but started improving, was still alive five years later, was one of the patients who got the sugar pill placebo. It was official. Vitamin C didn't work. The apparently positive results reported previously, read the accompanying National Cancer Institute editorial, almost certainly resulted from systematic bias in terms of which historic controls were chosen to compare with the treatment group. Linus Pauling disagreed, arguing that the prior chemotherapy in nearly all the Mayo Clinic study patients may have negated the effect of the vitamin C. If the vitamin C works by boosting your immune system, and your immune system is first destroyed by chemo, the thinking goes, well no wonder it didn't work. In the original vitamin C study, only four out of the hundred patients had ever received chemo. The Mayo Clinic researchers were skeptical, but Pauling had a legendary reputation in science for being right about all sorts of things. So one might do worse, perhaps, than rely at least partly on Pauling's awesome intuition. And so a second randomized double-blind placebo-controlled study was performed on patients with advanced cancer, but this time, who had no prior chemotherapy. And again, it was a spectacular failure. No measurable response. The cancer in the vitamin C group progressed just as rapidly, and the patients on the placebo sugar pills lived just as long. In fact, if anything, the sugar pill group lived longer. Two years, everyone in the vitamin C group was dead, but there were still a few survivors in the placebo group that made it out at least past three. And so they concluded high-dose vitamin C therapies not effective against advanced cancer, regardless of whether the patient has had prior chemotherapy or not. Because the Mayo clinics were taken as definitive, the medical community concluded that vitamin C was useless. However, in the Mayo Clinic studies, they gave the vitamin C orally in supplements, not intravenously through the vein. In retrospect, the root of administration may have been key. In the original study, they started out infusing 10 grams of vitamin C a day intravenously, where both the Mayo Clinic studies, designed to replicate the protocol, they just gave people vitamin C supplements to take orally, just sent them home to swallow 20 capsules a day. Same dose, but 10 grams given orally is not the same thing as 10 grams given IV, but they could be excused because this wasn't discovered until decades later. It turns out vitamin C concentrations in our bloodstream is tightly controlled, such that if you tried to swallow more, then you'd get like eating five servings of fruits and veggies, your body cuts down on the absorption in the intestine. For example, if you go from eating 200 milligrams a day to eating 10 times more, 2,500 milligrams, the level in your bloodstream only goes up 3 mg per liter, or quart of blood. In contrast, because intravenous injection bypasses the intestinal absorption system, it can result in super high blood concentrations, as in like 1 or 200 times the level in the bloodstream you can achieve just taking vitamin C orally, no matter how much you take. So maybe that explains why the original studies seem so promising, but the follow-up studies were so disappointing. This raises the controversial question of a re-evaluation of vitamin C in cancer treatment. Researchers responded to the challenge and took up the mantle, and we'll see what they found next.