SUBJECT: The long story of Roc’s inquiry into vitamin C to cure cancer.
1. See also my research poster #175 on vitamin C to treat superficial bladder carcinoma.
2. Here is why a new oral vitamin C may be able to treat cancer. Regular vitamin C tablets only increase serum levels to about 80 micromolar, first discovered by me, Roc Ordman, in 1994. To achieve that level, you take 500 mg, twice a day. But the new liposome vitamin C, developed around 2010, permits much higher absorption levels, perhaps to levels high enough to kill cancer, which becomes possible at levels in the serum above 1mM. And here is where it can be ordered.
How much is useful to take? We (Science paper author Jihye Yun ) injected vitamin C via IP to mice because it was challenging to do tail vein injection daily. If we could do IV, we would not need to give 4 g/kg vitamin C to mice. It seems that vitamin C is safe even 0.5 g/kg IV injection in human (clinical trial phase I). As long as it is safe, I don't see the issue of giving lots of vitamin C.
3. Science articles about how vitamin C may cure a particular type of colon cancer led me to write experts about the mechanism: Roc wrote: Linus Pauling is finally being redeemed. The cover of Science magazine, 11 Dec 2015, has a banner Vitamin C and cancer cell metabolism! The articles explain how vitamin C kills cancer cells - which most physicians denied as they reproduced Pauling's work incorrectly, using oral but not iv vitamin C. Perhaps this will help me get funding for the American Cancer Society proposal I submit in April.
But a fine colleague responded that the Science story only discussed a particular set of colon cancer cells, with vitamin C working by a particular mechanism. He wrote, “This is good, However, there are some real problems in their mechanism. They totally ignored H2O2. Their small molecules they naively call antioxidants react with H2O2 directly with rate constants that can explain all their data. So? Be careful.” Vitamin C is likely to work on many forms of cancer through other mechanisms.
4. Free radicals (ROS) generated in the mitochondrion trigger an anti-aging mechanism. I feared that taking vitamin C might block this beneficial action of ROS. But experts assure me that is not the case. Metformin is an anti-diabetes drug that has wonderful benefits preventing chronic disease. Ever since the news about Meformin as a possible "anti-aging" medication, I have been concerned that its benefit is caused by ROS in the mitochondrion. Since free radicals are blocked by vitamin C, might this make vitamin C supplements harmful to health?
ANSWER 1: Dear Roc, In the review I only tried to address the question as to whether mitochondrial dysfunction (via ROS or not) is causal to aging. And it doesn't look like it. ANSWER 2: I'm familiar with metformin, I even use it in studies from time to time. The "hormetic ROS" hypothesis is only one of several potential mechanisms of action for metformin, and actually one of my least favorite likely mechanisms of action. Metformin can also trigger the mitochondrial unfolded protein response (mtUPR) which makes the cell actively remove damaged proteins from the mitochondria, and model animals with activated mtUPRs tend to have extended lifespans. ANSWER 3: Mice with a mitochondrially targetted version of the antioxidant enzyme catalase (mCAT mice) live about 25% longer than control mice, suggesting that mitochondrial ROS can also be detrimental. Below are 3 top sites of faculty working on mitochondrial function.
ref site 1.(diagram of mitochondrial stress).....ref site 2.(catalase mice).......ref site 3.
Does vitamin C get transported into mitochondria? Almost assuredly yes.
Might this be why vitamin C is beneficial in preventing ROS damage in many bodily systems, but would be hazardous for mitochondrial health? Possibly, but in my experience these answers are rarely so simple. Some tissues rely on ROS for signaling, while others lack damage control and struggle with ROS burdens. Also keep in mind that mitochondria contain more metal ions than any other organelle, so ascorbate might actually act as a source for free radicals in that context. In truth, I think people ascribe more effects to ROS than are actually casual for effects. I always worry because I can find 100 studies that say one thing and 100 that say the exact opposite, unfortunately. Still vitamin C is much safer as a compound to study than N-acetylcysteine (NAC) which is highly overused and subject to all sort of metabolic alterations than have nothing to do with ROS - yet it's the most used antioxidant in research today!