TRIBUTYRIN: A NEW CANCER DRUG
The Spring 1998 Cancer Chronicles
© 1998 by Ralph W. Moss, Ph.D.
NOTE: Reports that Tributyrin is being used in some German clinics prompted the following investigation.
Butyric acid (BA) is a substance that was isolated in 1869 from butter. It constitutes 4 to 5 percent by weight of ordinary cow's butter. Butyric acid is used industrially as an ingredient in the manufacture of some liqueurs, syrups, and candies. It can also be created synthetically through the fermenation of various carbohydrates.
Unlikely as it may seem, butyric acid and its derivatives are also being seriously considered around the world as potential anticancer agents. The reason for this is that butyric acid has a well documented ability to do what few such agents can do: it is "a potent antineoplastic agent with a well-documented differentiation activity on a wide variety of tumor cells" (Gillet, R. Cancer Chemother Pharmacol 1998;41:252).
Why is this important? Many agents can kill cancer cells, a process called cytotoxicity. Even better are those agents that can induce a malignant cell to kill itselfin which scientists call apoptosis.
But butyric acid (as well as a few other substances) have the unusual ability to induce many kinds of cancer cells to start on the road back to normality. The main problem with BA as a drug is that it is rapidly metabolized and cleared from the human body by our very efficient detoxification system.
So, in order to keep it in the body longer, scientists in many countries and laboratories are working on a strategy of giving patients BA's "prodrug," a triglyceride they call "tributyrin." Tributyrin is a modification that eventually turns into butyric acid inside the human body. Administering BA in this way keeps it around longer and able to work its magic on cancer cells.
And, indeed, just as the theory predicted, in test tube studies it increased the effectiveness of BA by three to four times. I repeat that it doesn't directly kill cancer cells but helps them mature into normal cellswhich is even better. This work is being done at the U.S. National Cancer Institute.
Another strategy involving tributyrin is to combine it with a substance known as retinoic acid, a variety of vitamin A. This combination is also a very promising approach although this work has also only taken place in the test tube (Chen, X and Breitman, TR. Cancer Res 1994;54:3494). NCI scientists have found that combining tributyrin with retinoic acid may be a better, more long-lasting treatment for a number of different kinds of cancer, includiong acute promyelocytic leukemia (Breitman, TR, et al. Semin Hematol 1994 Oct;31(4 Suppl 5):18-25). When tributyrin is given along with RA it reduces the requirements of RA by ten-fold.
Tributyrin by itself seems to provide little value in the prevention of colon cancer in some experimental rat models (Deschner EE, et al. Cancer Lett. 1990 Jun 30; 52;79) However, French scientists are working on new derivatives of butyric acid that get over the short metabolic half-life of the original butyric acid (Gillet, R. Cancer Chemother Pharmacol 1998;41:252).
Tributyrin is similar in some ways to phenylacetate and phenylbutyrate, precursors of Burzynski's antineoplastons (Newmark HL, Young CW, Butyrate and phenylacetate as differentiating agents: practical problems and opportunities. J Cell Biochem Suppl 1995;22:247-253).