Study: Inhibition of histone-deacetylase activity by short-chain fatty acids and some polyphenol metabolites formed in the colon.
Authors: Waldecker M, Kautenburger T, Daumann H, Busch C, Schrenk D.
Journal: Food Chemistry and Environmental Toxicology, University of Kaiserslautern, D-67663 Kaiserslautern, Germany.
Colorectal cancer is the most abundant cause of cancer mortality in the Western world. Nutrition and the microbial flora are considered to have a marked influence on the risk of colorectal cancer, the formation of butyrate and other short-chain fatty acids (SCFAs) possibly playing a major role as chemopreventive products of microbial fermentation in the colon.
Abstract: This study investigated the effects of a number of short chain fatty acids, to include butyrate, as well as a number of phenolic SCFA and trans-cinnamic acid derivatives formed during the intestinal degradation of polyphenolic constituents of fruits and vegetables on global histone deacetylase (HDAC) activity in nuclear extracts from colon carcinoma cell cultures. Inhibition of HDAC activity, e.g., by butyrate, is related to a suppression of malignant transformation and a stimulation of apoptosis of precancerous colonic cells. In nuclear extracts from HT-29 human colon carcinoma cells, butyrate was found to be the most potent HDAC inhibitor (IC(50)=0.09 mM), while other SCFAs such as propionate were less potent. In the same assay, p-coumaric acid (IC(50)=0.19 mM), 3-(4-OH-phenyl)-propionate (IC(50)=0.62 mM) and caffeic acid (IC(50)=0.85 mM) were the most potent HDAC inhibitors among the polyphenol metabolites tested.
Butyrate was also the most potent HDAC inhibitor in a whole-cell HeLa Mad 38-based reporter gene assay, while all polyphenol metabolites and all other SCFAs tested were much less potent; some were completely inactive. The findings suggest that butyrate plays an outstanding role as endogenous HDAC inhibitor in the colon, and that other SCFAs and HDAC-inhibitory polyphenol metabolites present in the colon seem to play a much smaller role, probably because of their limited levels, their marked cytotoxicity and/or their limited intracellular availability.
Commentary: Butyric acid is notably found in rancid butter, aged cheeses, and has an unpleasant odor and acrid taste, with a sweetish aftertaste. The glyceride of butyric acid makes up 3% to 4% of butter. When butter goes rancid, butyric acid is liberated from the glyceride by hydrolysis leading to the unpleasant odor. It is an important member of the fatty acid sub-group called short chain fatty acids.
Butyric acid supports the health and healing of cells in the small and large intestine. Many research studies, like the one above, have demonstrated that butyric acid impedes the ability of cancer cells to proliferate in the colon, and therefore is protective of colon cancer. Butyric acid changes the structure of chromatin through its effects on posttranslational modifications, key modifications being acetylation and phosphorylation of the nuclear histones. These enzymes remove an acetyl group from histones, which allows histones to bind DNA and inhibit gene transcription. HDAC inhibitors disrupt the cell cycle and/or induce apoptosis via de-repression of genes such as P21 and BAX, and cancer cells appear to be more sensitive than non-transformed cells HDAC inhibitory compounds.
Butyric acid can also modify the differentiation state of cells, and in the case of cancerous colonic cells overcomes their resistance to normal programmed death. Thus, the activities of this fermentation product of dietary fiber may contribute substantially to the decreased incidence of bowel cancer that has been associated with fiber intake. Adverse butyrate effects occur in normal and neoplastic colonic cells. In normal cells, butyrate induces proliferation at the crypt base, while inhibiting proliferation at the crypt surface. In neoplastic cells, butyrate inhibits DNA synthesis and arrests cell growth in the G1 phase of the cell cycle.
Butyric Acid is a key ingredient in Intrinsa. This product is designed to support stomach, small intestine, and colon health using three well-researched ingredients. Usable by all ABO blood types and GenoTypes.
STUDY: Testing reveals scores of substances in study volunteers
JOURNAL: Environmental Working Group
AUTHORS: Jane Houlihan
ABSTRACT: When scientists sampled Andrea Martin’s blood and urine to see what toxins she’d picked up from the world around her, she got a surprise. “I had 95 chemical contaminants in my little body. And it was very mind blowing,” said Martin. The test results indicate that we all pick up tiny amounts of an astounding number of chemicals that are known to be dangerous in larger doses.
COMMENTARY: Martin and eight others were tested by Mt. Sinai School of Medicine in New York and an advocacy organization called the Environmental Working Group.
On average, the nine participants had traces of 53 chemicals known to cause cancer in human or animal tests. In addition, they had an average of 62 chemicals toxic to the brain or nervous system, plus 55 associated with birth defects.
The scientists did not find any single substance in amounts the government describes as unhealthy, but said the sheer number of chemicals was unnerving, especially given the uncertainty about the health effects of trace amounts.
"This is irrefutable proof that humans carry in their bodies scores of industrial contaminants, most of which didn’t exist 75 years ago,” said Jane Houlihan, co-author of the study.
Scientists have found chemicals called pthalates, which are known to cause birth defects in animals, in many personal care items like makeup, hairspray, soap and also plastic food wrap.
Other chemicals found in the participants’ bodies target the nervous system, including: Acetone in nail polish synthetic fragrances in perfume and soap, poisons in weed killers and bug sprays, perchloral ethyline in dry cleaners, zylene in paint which can also cause organ damage.
For those intent on avoiding even traces of toxic chemicals, the study’s authors suggest eating organic produce, minimizing fatty foods since chemicals concentrate in body fat, minimizing the use of beauty products, avoiding stain removers and avoiding seafood known to be high in mercury.
These precautions may be more hassle than many care to deal with, but the scientists in charge of the study say it is amazing how many potentially toxic chemicals get in our bodies.
Well, it has been way too long since my last blog. Busy, busy, busy…
I am sure you have read in Dr. D.’s blogs, things are changing a bit at the clinic. The new conference consultation room is working out wonderfully. We now have a huge white board in the room. One of the principles of Naturopathic Medicine is Docere, which means Doctor as Teacher. Those of you that have visited the clinic have noticed the student interns that are a part of your consultation team. They are there to learn. What I think this white board represents is that patients are there to learn also, and we are ready to teach them. What an amazing concept! How many visits to the doctor have you experienced an educational lesson in medicine and nutritional as it applies to you personally?
I have begun working on a clinic newsletter for patients. We hope to have the first issue finished before spring. Also, we have a new addition to the clinic staff. Barbara has joined us as receptionist. She has just about finished her first week with us. She is doing a great job as she learns the ropes. It is clear already what a wonderful part of the team she is. You may have also noticed or spoke with Carol at the clinic. Carol is the General Manager at North American Pharmacal. She has been giving us a hand at the clinic, as well as helping familiarize Barbara with the day to day clinic operations. (What a gem! Thanks Carol :-) )
Once the new book came out, I began to pester Dr. D. about writing the new Genotype SWAMI software. Maybe even before the book came out. ;-) He has been writing his numerous lines of code, and has been showing me the progress as it is made. First, I can’t believe how fast he is able to create a program of this magnitude. Second, this program is more than I could have ever dreamed possible! I don’t know how he does it, but boy oh boy am I glad he does! I can hardly wait to begin using this amazing tool with clinic patients!
Yesterday, Dr. D’Adamo gave a lecture in reference to the GenoType Diet. Although he and I have frequent conversations about it, especially when determining the type for the clinic patients, it was the first time I have been able to witness him lecturing about it in its entirety and in public. For those of you that have ever had the opportunity to personally witness Dr. D. lecturing, I am sure you will concur. What an amazing speaker. The dynamic energy that he expels is so capturing. He is not a lullaby lecturer. The lecture was very well received, and I think all the attendees got quite a bit from the Q&A session.
After the lecture, the clinic spent some time genotyping the attendees. I really enjoyed seeing the looks of anticipation involved as people waited to be told their genotype. It is somewhat similar to watching a child unwrap a birthday present. Very much like the exciting anticipation I see on the BTD forums. I can’t wait for the book to hit the shelves so that I can start blogging about it, but I guess we all need to wait in anticipation.
Martha was kind enough to take time out of her busy schedule to organize a yoga class for the clinic and NAP staff. We had our first session this past Wednesday. Although being familiar with yoga, it was the first class I have ever attended and it was amazing! Amy, our instructor, was wonderful. The next morning, to my surprise, I was so sore. I exercise 3-4 times per week, and I was not expecting to feel quite that way. Don’t get me wrong; it was the good kind of sore that lets you know that you did something. The thing I liked best about it was that I was sore in those hard to train muscle areas, and I did not have to lift a single weight.
How many of us adopt healthy lifestyles, to include diet and exercise, in order to improve the quality of our lives? If you could change your genetic destiny or the genetic destiny of your future lineage by the implementation of this type of lifestyle, would you try?
There is something to be said about the power found in knowledge and Dr. D’Adamo has done it again. He spent countless hours gathering research and pecking at his keyboard to put that power of knowledge into your hands. In just 4 short weeks, The GenoType Diet will be available….
For all of you devote BTD’ers, have no fear, The Blood Type Diet has not been abandoned. On the contrary, Dr. D’Adamo has taken the BTD and used it as the foundation of The GenoType Diet. The BTD set the bar on nutrition and individuality, and the GTD takes it even further using an individualized approach to nutrition with consideration to its affects on our genetic individuality. Talk about breaking it down to the nuts and bolts. What a concept! This may sound complicated, but as only Dr. D’Adamo can do, the book is written in an amazingly clear and concise way. You do not need a PhD in Molecular Biology to understand these concepts. I promise… Using your blood type, family medical history, and simple body measurements, you will fall into one of the six GenoTypes. I can’t wait for everyone to get their hands on this book!
I also wanted to mention that I have had some technical difficulties with my clinic email as of late. If you have sent me an email, and have failed to receive a response, rest assured that I am not ignoring you. :-) Just give the clinic a call to follow-up with your questions or comments.