Maybe Linus Pauling was on to something after all. Decades ago the Nobel Prize–winning chemist was relegated to the fringes of medicine after championing the idea that vitamin C could combat a host of illnesses, including cancer. Now, a study published online today in Science reports that vitamin C can kill tumor cells that carry a common cancer-causing mutation and—in mice—can curb the growth of tumors with the mutation. If the findings hold up in people, researchers may have found a way to treat a large swath of tumors that has lacked effective drugs. "This [could] be one answer to the question everybody's striving for," says molecular biologist Channing Der of the University of North Carolina, Chapel Hill, one of many researchers trying to target cancers with the mutation. The study is also gratifying for the handful of researchers pursuing vitamin C, or ascorbic acid, as a cancer drug. Maybe people will finally pay attention," says vitamin C researcher Mark Levine of the National Institute of Diabetes and Digestive and Kidney Diseases.
In 1971, Pauling began collaborating with a Scottish physician who had reported success treating cancer patients with vitamin C. But the failure of two clinical trials of vitamin C pills, conducted in the late 1970s and early 1980s at the Mayo Clinic in Rochester, Minnesota, dampened enthusiasm for Pauling’s idea. Studies by Levine’s group later suggested that the vitamin must be given intravenously to reach doses high enough to kill cancer cells. A few small trials in the past 5 years—for pancreatic and ovarian cancer—hinted that IV vitamin C treatment combined with chemotherapy can extend cancer survival. But doubters were not swayed. "The atmosphere was poisoned" by the earlier failures, Levine says. A few years ago, Jihye Yun, then a graduate student at Johns Hopkins University in Baltimore, Maryland, found that colon cancer cells whose growth is driven by mutations in the gene KRAS or a less commonly mutated gene, BRAF, make unusually large amounts of a protein that transports glucose across the cell membrane.
The transporter, GLUT1, supplies the cells with the high levels of glucose they need to survive. GLUT1 also transports the oxidized form of vitamin C, dehydroascorbic acid (DHA), into the cell, bad news for cancer cells, because Yun found that DHA can deplete a cell’s supply of a chemical that sops up free radicals. Because free radicals can harm a cell in various ways, the finding suggested “a vulnerability” if the cells were flooded with DHA, says Lewis Cantley at Weill Cornell Medicine in New York City, where Yun is now a postdoc. Cantley’s lab and collaborators found that large doses of vitamin C did indeed kill cultured colon cancer cells with BRAF or KRAS mutations by raising free radical levels, which in turn inactivate an enzyme needed to metabolize glucose, depriving the cells of energy. Then they gave daily high dose injections—equivalent to a person eating 300 oranges—to mice engineered to develop KRAS-driven colon tumors. The mice developed fewer and smaller colon tumors compared with control mice.
Cantley hopes to soon start clinical trials that will select cancer patients based on KRAS or BRAF mutations and possibly GLUT1 status. His group’s new study "tells you who should get the drug and who shouldn't," he says. Cancer geneticist Bert Vogelstein of Johns Hopkins University, in whose lab Yun noticed the GLUT1 connection, is excited about vitamin C therapy, not only as a possible treatment for KRAS-mutated colon tumors, which make up about 40% of all colon cancers, but also for pancreatic cancer, a typically lethal cancer driven by KRAS. “No KRAS-targeted therapeutics have emerged despite decades of effort and hundreds of millions of dollars [spent] by both industry and academia,” Vogelstein says. Others caution that the effects seen in mice may not hold up in humans. But because high dose vitamin C is already known to be safe, says cancer researcher Vuk Stambolic of the University of Toronto in Canada, oncologists “can quickly move forward in the clinic." One drawback is that patients will have to come into a clinic for vitamin C infusions, ideally every few days for months, because vitamin C seems to take that long to kill cancer cells, Levine notes.
But Cantley says it may be possible to make an oral formulation that reaches high doses in the blood—which may be one way to get companies interested in sponsoring trials. Spread the Word to By Sharing this Article. This Hidden Threat Is Making Pets Sick All Over the Country Boycott This Unethical Pet Food Brand, Riddled With Lies and False Claims Most Dogs Hate This - How to Turn It Into a Pampering Session Instead of Dread Sailors Considered These Gypsy Cats Good Luck - Are You Lucky Enough to Own One? Your Guide to Avoiding and Treating the Top 5 Genetic Diseases Visit the Pet Video Library Long-acting anticoagulants, called LAACs, are the most common type of mouse and rat poisoning in use today. Typical active ingredients in these products include brodifacoum, diphacinone, warfarin, and bromadiolone, among others. Most of these products contain green dye so humans can recognize them quickly. But since dogs and cats have poor color vision, the pellets may look like dry pet food.
When ingested by an animal, anticoagulant agents block the synthesis of vitamin K, an essential component for normal blood clotting. This reduces production of certain clotting factors. There is no effect on clotting factors already in circulation in the bloodstream, which is why there is a lag time between ingestion of the poison and bleeding problems. The eventual result, however, is spontaneous and uncontrolled bleeding, which leads to death. Causes and Types of Anticoagulant Poisoning The most common cause of anticoagulant poisoning in pets is ingestion of rodent poison. Dogs and cats who go outdoors frequently are at risk for encountering the poison in a neighbor’s yard, in an alleyway, or in a trash bag. Pets that chase and kill rodents can also be at risk. Keep in mind that even if rats or mice aren’t a problem where you live, rodent poison may also be used for other animals such as opossums, raccoons, or squirrels. Another cause of anticoagulant poisoning is the accidental ingestion of human medications, for example, heparin, which is used to treat certain blood clotting disorders.
Common anticoagulant chemicals found in rat and mouse poisons include warfarin, hydroxycoumadin, brodifacoum, bromadiolone, pindone, diphacinone, diphenadione, and chlorohacinone. Products containing warfarin and hydroxycoumarin are cumulative poisons, meaning they require multiple feedings over several days to kill a rodent. The other listed anticoagulants are deadlier and are intended to kill rodents in a single dose. Rodenticides containing brodifacoum and bromadiolone, for example, are from 50 to 200 times more toxic than those containing warfarin or hydroxycoumarin. Symptoms in Dogs and Cats When a dog or cat ingests an LAAC, it usually takes 3 to 5 days before signs of poisoning become obvious. In cases of chronic exposure, however, symptoms can appear sooner. Common symptoms are signs of internal bleeding or blood clotting issues. They include lethargy, exercise intolerance, coughing, and difficulty breathing due to bleeding into the lungs, a swollen abdomen from accumulation of blood, weakness, and pale gums.
There can also be vomiting or diarrhea (sometimes bloody), bleeding from the rectum, spontaneous nosebleeds, and bruising that appears suddenly without trauma. Other symptoms can include bloody urine, swollen joints, loss of appetite, and bleeding gums or other bleeding in the oral cavity. Signs of bleeding in more than one location are a definite clue there’s a problem with blood clotting. My very first case of LAAC poisoning was in a Husky who was brought in with ruptured blood vessels in her sclera, which are the white parts of the eyes. When I looked at her beautiful blue eyes, all of the area around the blue was flaming red instead of white, and looked really scary. When I checked her gums, they were very pale, and she also had petechial hemorrhages that looked like tiny speckles all over her mouth. They were actually hundreds of broken blood vessels just under the mucus membranes. The skin on the dog’s belly was also starting to show some bruising. With signs of bleeding in more than one location on her body, I knew there could be a problem with blood clotting caused by anticoagulant toxicosis.
If you suspect your pet has ingested rodent bait or another product containing an anticoagulant, you’ll need to give a thorough history of his health and recent activities to your veterinarian. A chemical blood profile, complete blood count, and urinalysis will be performed. Your vet will also check the time it takes for your pet’s blood to clot to determine the severity of the poisoning. The PTT (partial thromboplastin time) test looks at intrinsic pathways. The PT (prothrombin time) test measures extrinsic pathways. If both pathways show disruption, rat poison is the most likely cause. If you have a sample of the suspected poison, you should take that with you to your veterinarian's office. Samples of your dog’s stool and/or vomit may also be helpful. Treatment for Anticoagulant Poisoning If your pet has just ingested the poison, the veterinary staff will likely attempt to induce vomiting, and certain agents will be administered to prevent the poison from entering your dog’s or cat’s system.
If an animal is suffering from significant blood loss from spontaneous bleeding caused by anticoagulants, he or she will receive fresh whole blood or a frozen plasma transfusion, and require hospitalization. The antidote to anticoagulant poisoning is vitamin K. It is started by injection in life-threatening situations. When the patient is stabilized, oral tablets are prescribed. Veterinary-strength vitamin K is a 25 mg tablet, which is actually 5 times the strength of the oral human prescription dose. Vitamin K1 is the form of vitamin K that’s used for therapeutic purposes. It’s a natural form of vitamin K found in plants and is absorbed nutritionally. Vitamin K3 might seem like an inexpensive way to treat a pet with rat poisoning at home, but vitamin K3 is sometimes toxic and can lead to red blood cell destruction. Inexpensive, over-the-counter vitamin K3 pills are not acceptable antidotes, and I don’t recommend that you try them. Vitamin K1 is absorbed early in the GI tract and concentrates directly in the liver where it is most needed.
Only vitamin K1 should be considered as the antidote for anticoagulant rodenticide poisoning. Since there are different classes of anticoagulant rodenticides and they remain in the animal’s body for different periods of time up to several weeks, it can really be difficult to determine when to discontinue vitamin K therapy. Common practice is to give the therapy for a couple of weeks, discontinue it, and then run the PT test after 48 hours. If the poison remains in the animal’s system, the PT test results will be abnormal but the bleeding will not have restarted yet. The PT test results tell your veterinarian whether or not additional vitamin K therapy is needed. When the PT test has returned to normal, you know it’s safe to discontinue therapy. It’s extremely important, after vitamin K therapy is discontinued, to return for the PT recheck as scheduled, because just an extra day or two will allow internal bleeding to recur if your animal hasn’t had enough therapy. While anticoagulant rodenticide poisoning can threaten the life of your pet, there is at least an antidote readily available (vitamin K).
Other types of mouse and rat poison have no known antidote at this time, including Vitamin D Analogs (Quintox, Rampage, Rat-B-Gone, and Mouse-B-Gone), bromethalin (Fast Kill), strychnine (gopher bait), and zinc phosphide in gopher bait such as Moletox. I’m sad that these really scary rodenticides are available on the market, because there’s no hope for animals that accidently ingest them. What if My Pet Eats a Poisoned Rodent? If your dog or cat eats a rat that has gorged on a fast-acting anticoagulant rodenticide, there is certainly cause for concern. A rat with a big appetite can eat enough poison to kill 20 rats before he starts to feel sick. If your pet eats that rat, all the poison will be transferred right up the food chain to your pet. Fortunately, most rats don’t overeat or gorge themselves to this degree, and animals that are secondarily poisoned by eating a poisoned rat usually depend heavily on rats as their main food source. Probably none of you listening or reading here today are allowing your pet to free-range hunt in your front or backyard or other property.