Natural Medicine Update

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.

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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.

I had a very pleasant follow-up conversation with a patient the other day. When I picked up the phone, I was greeted with, “Hello Dr. Colicci. I just read your blog!” What a wonderful surprise. I guess I never really expected anyone to read it. This patient was happy to see another A type blogging. She expressed some frustration with keeping to the regime, and I assured her that she is not alone. This blog is dedicated to her….

Very often we hear patients voice their struggles with keeping on track with the diet. Do I advocate the Blood Type Diet? You bet I do! Do I find it the easiest thing in the world to do? Not always! That’s right, I said it! I will be the first person to admit that there are times that I really do miss those avoids, and boy oh boy is it ever a struggle to force myself to eat fish… Growing up, my mother (who happens to be an amazing cook) fed us well. She was always health conscience and kept herself well read when it came to nutrition. She used to own a fish market. Suffice to say, growing up around it made me not want to eat it. I think she now gets amused when she sees me eating it. I stopped by her house this evening on my way home from the clinic, and there it was beautifully placed in a dish waiting for me….COD!!!! Thanks Mom…..

So what is the key to success? I know that there are many answers to this question, as we all have our individual vices. My answer has a few simple points. First and most important, you need to believe in what it is that you are doing. The resistant grip loosens when both your heart and mind agree that something just “feels” right.

Second, try not to look at it as if you are dieting. In reality, it is so much more than that. It is more like a healthy lifestyle that incorporates healthy choices. You are not punishing yourself, but actually giving your body gifts every day. The better you take care of it, the better it takes care of you. I think this is why the BTD has sustained the test of fad diets.

Third, and I owe this one to the man himself, don’t spend so much time concentrating on what you can’t eat, rather concentrate on what you can eat. This probably seems like a play on words, but trust me, if you do this, it is so much easier!

The last issue I want to concentrate on is breakfast. Everyone asks me what I eat for breakfast, so I guess it is an important struggle point. My advice on breakfast is this: If you can eat it any other time of the day, you can eat it for breakfast. I am not sure exactly how foods got categorized as items that you only eat in the morning, but we need to break the mind set here. Don’t be surprised if you stop by the clinic in the morning and see me eating my cod…. :-)

Natalie