Life Extension Magazine February 2008
Coenzyme Q10 and Cancer
Enhancing Treatment Outcomes and Improving Chemotherapy Tolerability
By Julius Goepp, MD
Few lay people understand that one of the reasons chemotherapy does not cure more cancers is that its inherent toxicity limits the dosage that can be administered. What this means is that even if the cancer is slowly being eradicated by the chemo drugs, the damage inflicted on healthy cells can be so severe that chemotherapy must be discontinued. A common side effect cancer victims face is chemotherapy-induced immune suppression that leaves patients susceptible to life-threatening infections.
Fortunately, research suggests that coenzyme Q10 (CoQ10) can offer critical support for those challenged with cancer, including improving the tolerability of chemotherapy and lessening its adverse impact on immune function. In addition, tantalizing evidence suggests that CoQ10 may help chemotherapy drugs more effectively battle cancer via several fascinating mechanisms. Here, we’ll explore CoQ10’s importance in combating cancer.
Coenzyme Q10 Basics
Best known in medicine today for its vital contributions to heart and brain health,1 exciting new discoveries point to broad and novel roles for CoQ10 as a “chemoprotectant” with tremendous promise as an adjuvant therapy in cancer treatment.2-5
Early recognition of CoQ10’s potential as a cellular protectant came from the oncology laboratory of researchers studying the toxic effects of a potent chemotherapy drug, adriamycin (doxorubicin).6 Adriamycin is in the anthracycline class that kills cancer cells by damaging their DNA. At the high doses used in cancer treatment, however, adriamycin also interferes with mitochondria in healthy cells,7 causing damage to heart muscle that limits the drug’s usefulness and safety. Remarkably, when researchers treated laboratory rats first with CoQ10 and then with adriamycin, they found survival rates of 80-86%, compared with just 36-42% in animals receiving the drug alone without the supplement.6
Italian researchers confirmed this effect in a particularly vulnerable group of human patients—children with cancer.8 One group of children with leukemia or lymphoma received chemotherapy with anthra-cycline drugs plus CoQ10, while the other group was treated without the supplement. The researchers studied the children’s heart function using echocardiography, a means of directly viewing the beating heart and its structures with ultrasound. Under the punishing effects of the drugs, all children suffered some loss of cardiac function, but those in the CoQ10-supplemented group showed significantly less impairment than those in the drug-only group. The treating physicians concluded that their data demonstrated “a protective effect of CoQ10 on cardiac function during therapy.”
Inflammation, Oxidative Stress, and Genetic Damage – The Deadly Cycle
To understand the fundamental role that CoQ10 can play in cancer prevention and management, it’s important to recognize the intimate relationships between oxidant damage, inflammation, and the processes that initiate and promote cancer growth. Throughout life, a build-up of free radical damaged components occurs within cells, particularly during times of severe oxidant stress, such as disease and injury.9
Tissue damaged by free radicals triggers a protective inflammatory response through the release of chemical signals called cytokines and chemokines. Beneficial at first and in controlled amounts, these “mediators of inflammation” eventually produce new tissue damage. With time, this inflammation-induced cycle of destruction contributes to DNA damage.9
Cancer can occur when at least two conditions are met.10 First, DNA must become sufficiently damaged that a cell loses control of its own growth-regulating mechanisms (this process is called initiation of cancer). The next step, promotion, can occur when “cross-talk” between normal immune cells patrolling for cancerous cells becomes garbled by the chemical storm produced by inflammation.11 This disruption in cellular communication can allow tumor cells to proliferate. Finally, reactive oxygen species interfere with fundamental cellular controls that normally cause the programmed cell death of cancerous cells in the process known as apoptosis.11,12 By interfering with apoptosis, inflammatory cytokines render cancer cells resistant not only to natural control mechanisms but even to cancer-killing chemotherapy drugs.
CoQ10 and Cancer
Cancer is both the result and a significant cause of free-radical damage related to inflammation. A growing awareness of this critical and intimate association has led scientists to explore ways of controlling cancer growth by limiting free-radical damage. This line of thinking is a result not only of our progress in understanding how cancer develops, but also of our struggle to control the disastrous effects of chemotherapy drugs on healthy tissues. Given its strong performance as a tissue-protecting antioxidant molecule that promotes cardiovascular and brain health, it’s not surprising that cutting-edge medical researchers turned to CoQ10 as a possible means of preventing chemotherapy-related damage. What might be more surprising is that this versatile nutrient seems to actually improve the cancer-killing impact of the chemotherapy drugs themselves!
CoQ10 became part of the oncologist’s arsenal three decades ago when animal studies demonstrated how it could protect against the burst of free-radical release resulting from adriamycin treatment of various cancers.6,13 Within a year of its first use in that setting, however, alert scientists began to notice that CoQ10 was having an independent beneficial effect—it was helping to energize immune system cells that had been suppressed by cancer, restoring their ability to fight back by attacking the cancer cells themselves (remember that the immune system is a powerful defense against cancer metastasis).14-16 This “immunostimulatory” effect was demonstrated by Japanese researchers when they used carcinogenic chemicals to produce colon cancer in rats, followed by treatment with CoQ10 or other immunostimulants.17 As expected, none of the immune-stimulating treatments alone prevented colon cancer from developing—but all of them significantly reduced the number of tumors and also prevented their invasion of other tissues.
As CoQ10 began to be used to reduce the side effects of chemotherapy, alert scientists from the Institute for Biomedical Research at the University of Texas, Austin, began to assemble data on cancer survival rates in humans; by 1993, they found that over the preceding 25 years, patients with a number of cancer and blood-related conditions showed “striking” responses to therapy with CoQ10.18 Enhanced immune function was shown in other studies examined by this group of researchers, and they were able to document a total of 10 cases of unexpected survival of cancer patients treated with CoQ10 supplements. In the dramatically understated words of the lead investigator, “these results now justify systematic protocols.”
Several years later, the first fruits of such protocols began to be evident. The same Texas research group reported in 1997 on blood levels of CoQ10 in 116 cancer patients.19 Among breast cancer patients, 39% had CoQ10 levels below 0.6 mcg/mL; among healthy people in the same study only 25% had levels this low, a significant difference. (Healthy people taking CoQ10 supplements strive for CoQ10 blood levels of 2-3 mcg/mL, which demonstrates how severely deficient these breast cancer patients were who averaged only 0.6 mcg/mL.) In patients with multiple myeloma, as many as 53% of patients had low CoQ10 levels.
Other preliminary studies reported that CoQ10 might inhibit some of the tumor-associated cytokines that contribute to cancer proliferation.20 Carefully designed experimental studies soon followed, which provided more solid evidence of how CoQ10 might improve cancer survival independently of its proven ability to mitigate the devastating effects of chemotherapy.
Recognizing that CoQ10 achieves some of its protective effects by quenching chemotherapy-induced free-radical damage in mitochondria,7 biochemical researchers at the Post Graduate Institute of Basic Medical Sciences in Madras, India, looked for ways to protect mitochondrial function in cancer patients even before chemotherapy was begun.21 They took this approach because cancer results in markedly abnormal energy management, in which production of the vital cellular energy molecule adenosine triphosphate (ATP) is diminished. Without sufficient ATP, patients develop cachexia, the classic wasting we associate with cancer and other chronic illnesses. The Madras researchers wondered if protecting healthy cell mitochondrial ATP production lines with “energy-modulating” vitamins including CoQ10 could liberate more energy, giving cancer victims more resources to fight and control the cancer itself. To make this determination, the scientists induced mammary (breast) cancer in laboratory rats using a powerful chemical carcinogen. They then treated the animals with a combination comprising riboflavin, niacin, and CoQ10, or no supplement (controls) for 28 days. The mitochondria of the untreated cancer-bearing animals showed significantly decreased activity of the enzyme systems vital to extraction of energy and production of ATP, as was expected. Rats supplemented with the “energy-modulating” vitamins, however, showed restoration of those enzyme activities, making more energy available to the animals. This study was one of the first to show beneficial effects of CoQ10 in managing cancer independently of reducing chemotherapy side effects.
For researchers at the prestigious National Cancer Center Research Institute in Tokyo, those findings triggered another intriguing line of study. If CoQ10 reduced mitochondrial injury and improved the antioxidant status of the cell, could the ubiquitous nutrient actually prevent cancers from arising and proliferating? To find out, the scientists induced colon cancer in laboratory rats using a potent toxin called azoxymethane.22 The animals were fed either an unsupplemented control diet, or a diet containing low and medium doses of CoQ10, beginning just one day before the first dose of the carcinogen and continuing for four weeks. The researchers then sought evidence of early cancerous changes similar to those physicians look for during a colonoscopy, such as abnormal crypts. The results were remarkable—supplemented animals had reductions in abnormal crypts by up to nearly one-third compared with control animals. Perhaps even more strikingly, the abnormal crypts in supplemented animals contained significantly fewer abnormal cells than in the control group, suggesting that even when cancer did arise under this powerful stimulus, CoQ10 held it in check. Finally, in the supplemented animals, the number of crypts producing abnormal mucus (another early sign of colon cancer) was reduced to less than half that found in unsupplemented animals. The report concluded that “CoQ10 may be an effective chemopreventive agent against colon carcinogenesis.”
Back at the Department of Medical Biochemistry in Madras, researchers sought ways to prevent cancer cells from proliferating once formed. Given the tremendous odds in favor of DNA damage over a lifetime and the body’s natural ability to find and kill cancer cells with normal immunity, this strategy of “secondary prevention” is one that is being widely explored. In this case, the researchers studied the combination of CoQ10 and tamoxifen, a potent chemotherapy drug with its own antioxidant effects but significant side effects when given alone.10 They induced mammary carcinomas (breast cancers) in laboratory rats, and then treated them with various combinations of CoQ10 and tamoxifen. As expected, in control animals that received no therapy, antioxidant capacity dropped precipitously as their tumors developed. Supplemented animals, however, saw their antioxidant activities significantly restored, with inhibition of progression of their cancers.
The same research group then investigated a combination of riboflavin, niacin, and CoQ10, again in combination with tamoxifen in laboratory rats with chemically induced breast cancers.23 This time they took a much closer molecular look at the events inside a tumor cell, and at the effects of the antioxidants on those events. After inducing breast malignancies in female rats, the researchers supplemented most of the animals with the CoQ10-containing combination, studying oxidation products and enzyme activities within the cancer cells. Astonishingly, the supplements restored levels of all antioxidant systems in the cells to nearly normal values! And it wasn’t just a numbers game: antitumor activity was enhanced through increased production of tumor-suppressor genes—natural proteins that prevent aberrant cellular proliferation.