According to the American Brain Tumor Association, primary brain tumors occur at a rate of 12.8 per 100,000 people.  Although people of any age can develop a brain tumor, the problem seems to be most common in children ages 3 to 12 and in adults ages 40 to 70. A recent US study showed that total coffee and tea consumption was inversely associated with risk of glioma, and experimental studies showed that caffeine can slow the invasive growth of glioblastoma. Glioma is a broad category of brain and spinal cord tumors that come from glial cells, the main brain cells that can develop into tumors. The symptoms, prognosis, and treatment of a malignant glioma depend on the person’s age, the exact type of tumor, and the location of the tumor within the brain.  These tumors tend to grow and infiltrate into the normal brain tissue, which makes surgical removal very difficult and complicates treatment. The European Prospective Investigation into Cancer and Nutrition (EPIC) examined the relation between coffee and tea intake and the risk of glioma and meninglioma in a large European group study. The study included more than 410,000 men and women between the ages of 25 and 70 from France, the Netherlands, Italy, Spain, Great Britain, Greece, Denmark, Norway, Sweden and Germany.  The participants were recruited between 1991 and 2000.  During this time they were told to keep track of the amount of tea and coffee that they consumed. The research team discovered that drinking 100 milliliters (mL) or 0.4 cups per day and above lowered the risk of gliomas by 34%.  The association was slightly stronger in men than in women. Dr. John S. Yu, director of the Brain Tumor Center of Excellence at Cedars-Sinai Medical Center in Los Angeles, described this study as “striking.”  He goes on to say, “If we had a drug for any disease that could demonstrate a risk reduction of 34% that would be considered a great drug.  That degree of risk reduction is very strong.” Dr. Jonathan Friedman, director of the Texas Brain and Spine Institute at Texas A&M Health Science Center College of Medicine in Bryan, agrees with Yu that these findings are “surprising”. Friedman exclaims, “However, the mechanism by which coffee is protective is completely unknown.  While the caffeine itself might be important, some of the other common components of coffee or tea might also be relevant, such as natural antioxidants.” Another study showed that caffeine could slow the invasive growth of glioblastoma in various vitro assays by inhibiting inositol 1,4,5 trisphosphate receptor subtype 3-mediated calcium release. Calcium signaling is very important in many signaling processes in cancer cell proliferation and motility.  An important consequence of the intracellular signaling is an increase in intracellular calcium concentration, which is well known to be a critical signal for gene expression motility, differentiation, and survival. Caffeine, a well-known activator of ryanodine receptor (RyR), has been reported to display anticancer effects.  Caffeine and its analogues have diverse effects on pain, Alzheimer’s disease, asthma, cancer, diabetes, and Parkinson’s disease. Current studies have shown that caffeine inhibits metastasis in a mouse mammary tumor model and UV-induced skin cancer in nude mice. Caffeine has been known to induce the release of calcium from the intracellular stores by opening RyR’s, especially in muscle cells and cardiac myocytes. To translate the results from the in vitro experiments they examined the effect of caffeine on brain slices and in in vitro animal models, in which local microenvironment could compromise the effect of caffeine. They took mouse brain slices in culture, placed 1 μLof Dil-labeled U178MG cells in hippocampal region after 6 days in culture and examined the radial progression of these cells to neighboring regions 5 days after placement.  They found that the invasion of Dil-labeled U178MG cells were significantly lower in the brain slices that were treated with various concentrations of caffeine compared with the untreated slices.  It was also found that mice supplied with caffeine containing drinking water showed a significantly reduced tumor mass compared with control mice after implantation. In another study, gene and protein expression patterns resulting from caffeine treatment showed that metastasis suppression may be associated with up-regulation of mRNA expression of multiple extracellular matrix genes.  This suggested that caffeine or other methylxanthine derivatives may improve the clinical outcome in patients prior to and following the diagnosis of metastatic diseases, and could potentially reduce the morbidity and mortality associated with disseminated tumors. Caffeine, a methylxanthine, is one of the most commonly used drugs in the world. Epidemiological evidence indicates that heavy caffeine consumption is negatively related to cancer related mortality. Caffeine and other methylxanines have also been shown to inhibit tumor cell invasiveness and experimental metastasis.  The anti-metastatic effects of caffeine may be related to a decrease in homing rate of primary tumor cells to distant target organs by multiple mechanisms, including by blocking the accessibility of the basement membrane to the tumor cells by suppressing cell adhesion to components of extracellular matrix (ECM), or by inhibiting complementary binding of tumor cells to endothelial cells.  Furthermore, caffeine can inhibit tumor cell growth and induce substantial differentiation in HL-60 cells. Caffeine has multiple biochemical activities.  It inhibits phosphodiesterase activities, alters intracellular calcium mobilization, inhibits phosphatidylinositol-3-kinase (P13K) activity, and antagonizes adenosine receptors.  These activities may all contribute to the modulation of the metastatic process that has previously been attributed to caffeine. In this study, mice were given doses of caffeine that were equivalent to six to seven cups of coffee per day.  They found that exposure to caffeine significantly lowered metastasis size.  These observations suggested that caffeine suppresses the formation of metastases, either by inhibiting extravasation and/or preventing the conversion of dormant cells to proliferative lesions. These findings are very important and should trigger future experiments about the therapeutic potential for caffeine to treat cancer.  Friedman stressed, “Additional studies will be required to confirm these findings and to identify the basis for the correlation.” “And as for the specific protective impact of caffeine, this finding follows other recent research that demonstrated that coffee drinking is associated with a lower risk for breast cancer as well,” Yu exclaimed.  “But even taken together, it has not yet been established whether or not this is directly causative – (in other words, whether) drinking caffeine directly reduces disease risk – or whether this is actually about an association between other factors concerning the type of people who drink a certain amount of coffee and risk reduction.  More research is needed to figure that out.” In the meantime drink on! Ashley To read more about this topic, go to the original studies listed below: Coffee and tea intake and risk of brain tumors in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study Caffeine-Mediated Inhibition of Calcium Release Channel Inositol 1,4,5-Trisphosphate Receptor Subtype 3 Blocks Glioblastoma Invasion and Extends Survival Caffeine suppresses metastasis in transgenic mouse model: a prototype molecule for prophylaxis of metastasis