[Guest post written by John Leavitt, Ph.D., Nerac, Inc., Tolland, CT.]
During my daily work for pharmaceutical and biotech clients, I am continuously learning about developments resulting from my research at the Linus Pauling Institute of Science and Medicine in Palo Alto, CA in the 1980s. Likewise, I am regularly coming into contact with new medically related developments focusing on vitamin C, an interest of Linus Pauling in those years.
With regard to our research on human plastins, a gene family of proteins that we discovered, cloned, and characterized at the Pauling Institute, it has recently been reported that plastin (PLS3) is a marker of carcinoma cells circulating in the blood (for example Yokobori, et al.). Our hypothesis was that when this protein was inappropriately expressed in cells from solid tissues, as it is in many tumor types, (e.g. carcinomas, fibrosarcomas, etc.) these potential tumor cells become more like blood cells in that they are able to live and replicate in an anchorage-independent state, an essential property of metastatic tumor cells. It is metastasis that kills us when we get cancer. Thus plastins, discovered and characterized at the Pauling Institute, may turn out to be the “holy grail” of cancer research.
I often run across new information on the medical importance of vitamin C without looking for it. Back in the 1980s, we would receive an annual shipment of loose vitamin C from Hoffmann-La Roche, Inc. as a way of saying thank you to Dr. Pauling for his advocacy of the merits of vitamin C. We received no funding from Hoffmann-La Roche though. One year I recall that two dignitaries from the company visited us. Dr. Pauling, with me and several others, walked our visitors to lunch a few blocks down El Camino Real in Palo Alto to my favorite restaurant, the Captain’s Cabin.
Afterward, while walking back to the Institute, one of the guests asked Dr. Pauling if he thought the perceived benefits of vitamin C were due to the placebo effect. I was amused because I too had said something ill-advised like that to Dr. Pauling in my first few months at the Institute. I mentioned to him that I had a vitamin C-resistant cold to which he replied, “You’re not taking enough!” and told me that he takes 18 grams a day. No doubt he had calculated this number based on the amount of vitamin C that animals produce within themselves every day. He would stir 18 grams into a large glass of water and imbibe the glass with no great rush.
A few months ago I heard a physician state in the national media that taking supplemental vitamins is a waste of money. This bold assertion reminded me of the announcement of the discovery of cold fusion and another premature announcement of the discovery of a cure for AIDS. The progress of science is slow but relentless, like the new developments with plastins fifteen years after I left LPISM’s labs.
On October 31, 2013, Kim, et al. at Seoul National University in South Korea published their findings on a new strain of experimental mice. The researchers knocked out the mouse gene encoding the enzyme L-gulono-γ-lactone oxidase, known as gulo for short. This is the gene that is missing in humans and that keeps us from synthesizing our own vitamin C, unlike nearly all other animals. An extreme lack of vitamin C in our diet can lead to scurvy, caused by aberrant expression of collagen in our connective tissues because of starvation of vitamin C in our diet. In these mice the lack of this gene caused “vitamin C insufficiency” in an animal model – a model that can now be used to learn more about the importance of vitamin C.
As these mice matured they expressed known blood markers of liver damage. This damage, called fibrosis, is basically the scarring of the liver, sort of like the scarring of the skin that is caused by certain types of skin damage. Concomitantly, as the mice aged, reactive oxygen species (ROS) and lipid peroxides increased in the liver, as did activated hepatic stellate cells, which deposited abnormal collagen fibriles on the basement membrane of functional liver cells. There is a wealth of evidence that elevated ROS in the lungs, liver, and kidneys is associated with pulmonary, hepatic, and renal fibrosis. Elevated vitamin C in these tissues will quench ROS.
Currently in the United States, there are no drugs approved to treat any of these forms of fibrosis. Fortunately, Intermune’s drug, pirfenidone, is close to approval for treatment of pulmonary fibrosis and has already been approved in Canada, Europe, and Japan. This drug reduces ROS and inhibits other key targets that are suspected of playing a role in the development of fibrosis. So who is to say that supplementing your diet with vitamin C is of no consequence? It is certainly not toxic in any way. Oh, by the way, pulmonary fibrosis is worse than cancer – it kills you in three to five years once diagnosed. You basically die of asphyxiation.
In the last week I stumbled upon another interesting paper on the effects of vitamin C on humans. A 2011 paper by Juraschek, et al. at Johns Hopkins University Medical School reported the results of a significant meta-analysis (a systematic review of multiple clinical trials) of 13 randomized clinical trials involving 556 patients who took a median dose of 500 mg of vitamin C per day. (I take a full gram)
The purpose of the study was to examine the effects of vitamin C supplementation on uric acid levels in the blood. Elevated uric acid levels in the blood causes gout, because saturation of blood with uric acid causes urate crystals to form in the synovial fluids of joints (e.g. crystal arthritis). Drugs that lower uric acid in the blood are used to treat gout because lowering uric acid causes the urate crystals to dissolve to ameliorate the arthritic pain.
Admittedly gout is not as bad as cancer. But another systematic clinical review of multiple trials on humans published in 2012 by Lottmann, et al. at the IGES Institut GmBH in Germany has shown clearly that having gout is associated with both all-cause mortality and, in particular, cardiovascular mortality. So what could be worse than death by gout?
I think I will keep taking vitamin C.