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The following article is published by the Brewer Science Library. Single copies of the article may be printed for the reader's personal research and study. Reproduction in any other manner, format or location is expressly prohibited.


BUTYRIC  ACID (butyrate) &  CANCER  RESEARCH:

 

Butyric acid is a natural substance that is found in butter.  Butyrate is a short chain fatty acid (SCFA) that is formed in the colon when colonocytes act on undigested fiber in the colon.   These short chain fatty acids that are formed stimulate the bifidobacterium in the large intestine.  Many positive health results can occur, including an increase in the body’s immune response.  

Previous research with butyric acid, and derivatives of butyric acid, has demonstrated that it is a potent anti-neoplastic agent.  A search on PubMed will bring up hundreds of cancer research abstracts that mention butyric acid (several are listed at the end of this article).  The action of butyric acid against many kinds of cancer cells is primarily through differentiation, not apoptosis (cellular self-suicide).   Differentiation is the process that has the action of “taming” cancer cells, and causing them to behave more normally.  Another natural substance that acts in this way in the body is IP6.     One of the problems with using butyric acid as a cancer agent is that it is rapidly metabolized and removed from the body. 

The specific mechanism of action of sodium butyrate with cancer cells is its action as a histone deacetylase inhibitor (HDAC), which is associated with repression of genes that are activated in cancer cells.  Growth inhibition and differentiation of the cancer cells are the result. 

TRIBUTYRIN:  A BUTYRATE ANALOG
In order to overcome this problem, various analogs have been created.  One of them is called Tributyrin, which did demonstrate in test tube studies three to four times the effectiveness of butric acid.    A brief  two page discussion of this analog can be found on the Cancer Chronicles website of Ralph Moss in a 1998 article titled, Tributyrin:  A New Cancer Drug, found at:   (www.ralphmoss.com/html/tributyrin.shtml)

More recent research on Tributyrin was reported in the Journal of Nutrition. 2001; 131;1839-1843, (link at:  www.jn.nutrition.org/cgi/content/abstract/131/6/1839).  This test tube research was carried out on human colon cancer cells to determine the effects of Tributyrin on growth, differentiation and vitamin D receptor expression.  Interestingly, the researchers concluded that at least part of the beneficial results demonstrating  differentiation and reduced cancer growth was due to the upregulation of the vitamin D receptor by Tributyrin.   Research over the last several years has discovered that Vitamin D has not only a protective effect against the development of several cancers, such as colon, breast and prostate, but also has an anti-proliferative effect against cancer cells that are already established.  (Link to Vitamin D and cancer:  posted here when Vitamin D article is done).

SYNERGISM  of  ARTEMISININ and  BUTRIC  ACID:
Dr. Narendra P. Singh, and Dr. Henry C. Lai, the University of Washington artemisinin researchers,  conducted test tube research to determine if a combination of butyric acid and an artemisinin analog (dihydroartemisinin, DHA) would increase the effectiveness of these compounds against cancer cells.   At 24 hours the test tube results with DHA alone demonstrated a 40% reduction in cancer cells.  At 24 hours the test tube results with sodium butyrate alone yielded a 32% reduction in cancer cells.   The combination of both DHA and sodium butyrate yielded a 100% reduction in cancer cells at 24 hours.  Their research article, Synergistic Cytotoxicity of Artemisinin and Sodium Butyrate on Human Cancer Cells, was published in 2005 in Anticancer Research 25: 4325-4332. 
 
These interesting research results have been the basis for many cancer patients deciding to add natural supplements of butyric acid to their nutritional protocols that contain artemisinin.  The research conducted was in test tubes, not in humans, so although butyric acid is a natural, non-toxic substance, no one knows exactly how much might be needed orally to have a significant effect. 

One website (www.herbological.com/herblog/?cat=6)  commented that the plasma levels that would be needed to approximate the above experiments would be 1.0 millmolar, and that would require 10,000 mg a day (10 grams).   It was also mentioned that in brain tumors more has been used, even up to 20 grams a day.  That would require about 16 caps a day for the 10 grams and 30 for the 20 grams. 

Since butyrate is a completely natural substance and non-toxic, this article mentions that the main side effect would be body odor.  It is possible that some people might develop diarrhea from such a high dose, and it would always be best to start with a low dose, as suggested on the label, or perhaps even lower, and gradually work up to a higher dosage.  Although it is a non-toxic substance, it does beneficially change the bowel bacteria, which could result in some of the bad bacteria, like candida, dying off in large numbers, which could cause diarrhea.   

Natural supplements of butyric acid are available from:  

  1. ButyrEn, from Allergy Research Group, is an enteric-coated tablet of the calcium and magnesium salts of butyric acid, providing 815 mg of butyrate and 100 mg of both calcium and magnesium (100 tabs/bottle; retails for $15.60).  The enteric coating is designed to provide delayed release in the intestinal tract.    The manufacturer’s suggested dosage as a dietary supplement, is to take 1 or 2 tablets three times daily with meals, or as directed by a healthcare practitioner.   Allergy Research products are widely available on the internet and also from most health food stores.
  2. Sodium Butyrate, from Body Bio, is a capsulated product.   The following website offers it for sale and has  two pages that answers many of the common questions about it:  www.bodybio.com/main/products/sodiumbutyrate_qa.htm
  3. Sodium Butyrate in capsules (600 mg per cap, 100 caps/bottle; $12.99) is also available from Holley Pharmaceuticals (www.holleypharma.com), who is a supplier of GMP certified artemisinin.  Their toll-free phone number is 1-866-846-5539, and the phone number outside of the U.S. is 714-871-7070. 

BUTYRATE  and  HYALURONIC  ACID  (HA):
In searching PubMed for information on butyric acid and cancer, information about a unique combination of hyaluronic-acid butyric esters was found that demonstrated some efficacy against some cancers.  Hyaluronic acid is a natural substance that is the primary constituent of the extracellular matrix in the human body.  Cancer cells have an overexpressed membrane receptor (CD44) that is associated with tumor progression.  Compounds that are combined with HA get carried to these CD44 receptors more specifically.  For more information about HA and HA compounds that can inhibit cancer, go to this link:    (www.                             )

 

2007 NEWS:  BUTYRATE-SUGAR COMBINATION  MOLECULE CAUSES CANCER CELL DEATH:
The study of sugar molecules, or glycolipids, has become a continually enlarging field of study in the last decade as scientists became aware of their potential against cancer cells.  It has been known for the last two decades that butyrate has a normalizing effect on cancer cells, through its actions in modulating the expression of genes in the cancer cell.  Researchers have combined it with various substances in order to not only take advantage of its cancer growth inhibiting characteristics, but also in order to find another substance that will enable it to be even more effective at inhibiting cancer growth.   It appears that Johns Hopkins University researchers may have done that.  Their innovative discovery has been reported in the December 2006 journal Chemistry and Biology.  They have developed a combination molecule consisting of butyrate with the sugar molecule, N-acetyl-D-mannosamine, abbreivated as ManNAc, that has demonstrated significant cancer cell death in test tube studies.  Other combinations that were tested by the researchers showed some initial halting of the cancer cell growth in lab dishes, but within fifteen days the cancer growth had resumed.  In contrast, the cancer cells treated with the hybrid molecule containing both the butyrate and ManNAc, had all died within fifteen days.  This hybrid molecule easily penetrates the cell membrane and is then split apart by enzymes within the cell.  The ManNAc is then turned into a different sugar molecule called sialic acid that provides anti-cancer activity in the cell, while the butyrate activates the genes that slow down cancer growth.     When the two compounds were used separately, but concurrently, the cells did not undergo apoptosis.   It is only the chemically combined hybrid that has demonstrated the powerful anti-cancer effects.  The next research step is to start animal studies with the compound.  Since both of the compounds are natural, the researchers do not expect the hybrid molecule to negatively affect healthy cells.  Although human studies are a long way off, this initial breakthrough appears to offer a new, relatively non-toxic strategy against cancer cell growth. 

DOCTORS  UTILIZING  ARTEMISININ  COMPOUNDS:
Although there certainly are physicians and nutritional consultants who are guiding people on the use of artemisinin, and butyrate compounds, there is no list of them that can be found.  One option might be to consult the American College for Advancement in Medicine, (ACAM list of doctors: 1-888-439-6891 or www.acam.org/dr_search/) who do alternative therapies, usually IV therapies for chelation.  They might also be familiar with artemisinin and/or other nutritional support protocols for cancer.   

SOME BUTRIC ACID RESEARCH ABSTRACTS & ARTICLES OF INTEREST:

The histone deacetylase inhibitor sodium butyrate induces breast cancer cell apoptosis through diverse cytotoxic actions including glutathione depletion and oxidative stress; International Journal of Oncology, 2004 Dec; 25(6): 1701-11.

Bcl-2 expression regulates sodium butyrate-induced apoptosis in human MCF-7 breast cancer cells; Cell Growth Differ; 1996 Mar; 7(3):311-8. 

Anti-cancer effects of butyrate:  use of micro-array technology to investigate mechanisms; Proceedings of the Nutrition Society (2003), 62, 197-115.

Butyrate Therapy for Poorly Differentiated Breast Cancer;  Life Sciences & Biotechnology Update, Dec, 2000.  

Augmentation of Sodium Butyrate-induced Apoptosis by Phosphatidylinositol 3’-Kinase Inhibition in the KM20 Human Colon Cancer Cell Line, Clinical Cancer Research Vol 8, 1940-1947,  June 2002.

Short-chain fatty acid-hexosamine cancer prodrugs:  The sugar matters!  Drugs of the Future, 2006, ISSN 0377-8282.

Butyrate-Induced Apoptosis in Prostate Cancer Cell Lines, Defense Technical Information Center, Aug 2001.

Leptin counteracts sodium butyrate-induced apoptosis in human colon cancer HT-29 cells via Nfkappa-B signaling, J. Biol. Chem, 10.1074/jbc.M312999200, Jan, 2004.

Valproic acid and butyrate induce apoptosis in human cancer cells through inhibition of gene expression of Akt/protein kinase B, Molecular Cancer, 2006, 5:71.

A novel role of sodium butyrate in cancer-associated aromatase promoter I.3 and II by disrupting a transcriptional complex in breast adipose fibroblasts, J. Biol. Chem, 10.1074/jbc.M508498200, Nov, 2005.      

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This article was originally published by the Brewer Science Library. Photocopying or reproduction is strictly prohibited without permission from the publisher.

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