What is betulinic acid? Betulinic acid is a plant substance found particularly in large quantities in birch bark. The natural acid is a so-called pentacyclic triterpenoid, which researchers have found to be a powerful antioxidant that is thought to have antibacterial, antiviral and anti-inflammatory properties. In addition, it has been found to protect tissues in the body and could have cancer-inhibiting effects. For now, studies showing this have been conducted mainly on mice and not humans. A body cell is supposed to destroy itself (apoptosis) when irreparable DNA damage has occurred in it. In cancer cells, the natural system that causes apoptosis of a cell is disturbed so that the controlled breakdown of the cell does not occur, and a mutated cell can continue to divide. Betulinic acid has been shown to block the enzyme topoisomerase, which stimulates apoptosis.   Effect of betulinic acid  Since the 1980s, much research has been done on the effects of betulinic acid. Those studies have now shown that betulinic acid can be used to treat various types of cancer, including breast, liver, stomach, prostate, lung and cervical cancer. But betulinic acid does not only have cancer-inhibiting effects. Several studies have also shown that betulinic acid can help treat colon inflammation and Crohn's disease because the acid is a powerful antioxidant and reduces the oxidative stress that causes damage and ignition in the body thus decreases. There is also strong evidence that betulinic acid can help lower blood sugar levels and thus may be a good natural medicine for people with type 2 diabetes or pre-diabetes. A processed substance from birch bark may serve as the basis for new cancer drugs. The substance, betulinic acid, mainly harms cancer cells and, unlike chemotherapy, has little effect on healthy cells. So states researcher Lisette Potze in her dissertation. Betulin prevents mice and insects from gnawing on trees. Via a simple chemical operation, it can be converted into betulinic acid. That betulinic acid may have an effect on cancer was already known, but how the substance targets cancer cells was unclear. Potze unraveled that mechanism. To do so, she used cultured cells, which she administered a dose of betulinic acid. She then examined which chemical processes in the cell change as a result of the substance. Potze discovered that betulinic acid affects mitochondria, the cell's "power plants. The power plants consist partly of membranes made up of fats. These can be saturated or unsaturated. Unsaturated fats keep the membrane flexible. However, if the fats are saturated, the membrane stiffens, which can lead to leaks and ultimately kill the cell. "Normally an enzyme in the cell causes fats to be unsaturated, but this enzyme is inhibited by betulinic acid," Potze says. What's nice about betulinic acid is that it mainly affects cancer cells and leaves healthy cells alone. Healthy cells get fats mainly from external sources such as food. These are mostly unsaturated. But cancer cells mainly produce their own saturated fats to enable rapid cell division. This makes them much more dependent on the enzyme than healthy cells, Potze says. "It's as if the cancer cells are addicted to the enzyme that you take away from them. Tricky Trouble with the betulinic acid is that it is not soluble in water. Meanwhile, a Belgian professor has found a solution to that by binding the betulinic acid to cholesterol and then dissolving it in an oil at high temperature. Scientific publications Publications on the betulinic acid studies appeared in the various renowned scientific journals: Betulinic acid, article on the action of betulinic acid to kill cancer cells. Appeared in Cell Death and Disease. Betulinic acid has strong cell-killing activity in vitro (i.e. in plastic culture dishes) on the cells of all common cancers, while healthy cells are actually quite resistant to the substance. Published in the journal Cancer Letters. Betulinic acid acts through a special mechanism of tumor cell death, which is independent of certain molecules in the classical mechanism of apoptosis (programmed cell death). As a result, it also kills cancer cells that are resistant to other chemotherapeutics. Published in the journal Apoptosis. Betulinic acid is highly capable in vivo, in experiments in mice, of greatly slowing the growth of tumors, such that the survival of the mice is greatly increased. Importantly, no toxic side effects could be found in the mice. For this study, the betulinic acid was first incorporated into fat globules (liposomes), because it can then reach the tumor - after injection - through the bloodstream. Published in the journal Anticancer Drugs. Recently, the important discovery has been made that betulinic acid acts on the fat metabolism of cells. As a result of their great need for new building blocks, cancer cells have a different fat metabolism and fat composition than healthy cells and are therefore much more sensitive than healthy cells to the substance. In cancer cells, betulinic acid alters the lipid composition of the membrane of the cell's very important energy factories (the mitochondria), causing the mitochondria no longer work properly and the cancer cell dies. Thereby, the research on betulinic acid has exposed an Achilles' heel of the cancer cell, on which the cancer can be attacked, without being able to escape the attack. Lisette Potze received her PhD in November 2015 for this research on 'Mechanisms of Betulinic acid-induced cell death'. Her research may lead to the development of new drugs to treat cancer. The Volkskrant paid attention to this research.  Betulinic acid (Betulin Acid) studies Betulinic acid research title:'Inventory of the anti-cancer efficacy of the plant-derived compound Betunic acid and clarification of the mechanisms underlying its induction of tumor-specific apoptosis'. Betulinic Acid-induced Tumor Killing'. Follow-up study: 'Applicability and mechanisms of Betulinic Acid-induced cell death'. Conducted at the Academic Medical Center Amsterdam, Department of Laboratory of Experimental Oncology and Radiobiololy (LEXOR) CEMM, under the direction of Professor Jan-Paul Medema. Dissertations: Franziska Müllauer, 'Betulinic Acid Induced Tumor Killing', 2011 Lisette Potze, 'Mechanisms of Betulinic acid-induced cell death', 2015