Natural COX-2 inhibitors

I found heaps of very useful information in Dr. Roberto Benelli (an Italian urologist)’s books on prostate cancer and curcumin. To be honest, it’s hard to decide where to begin. Today’s chosen topic: natural COX-2 inhibitors. I have written a bit about this enzyme, COX-2, which is an independent signal of a poor outcome in MM (see my Ellagic Acid Part II post). For comparison purposes, I added a list of natural NF-kB inhibitors, too. I copied both lists from Dr. Benelli’s book titled L’Inibizione delle Vie di Segnale Cellulare: il €˜Curcumin,’ published in 2006. (Co-author: Marco Gavazzi.)

Four compounds are on both lists–curcumin, EGCG, quercetin and resveratrol–which is good to know. My most interesting new discovery: holy basil (Ocimum sanctum), is a COX-2 inhibitor. Needless to say, I am adding holy basil to my future research list. Here are the lists:

Natural COX-2 inhibitors: holy basil, berberine , curcumin, EGCG, ginger, common hop, fish oil, oregano, quercetin, resveratrol, rosemary, Chinese skullcap, vitamins A, E

Natural NF-kB inhibitors: allicin, curcumin, EGCG, genistein, gingko biloba, melatonin, quercetin, resveratrol, silymarin, sulphoraphane, vitamins A, C, E

I looked up the items I didn’t recognize on Wikipedia: berberine is a plant alkaloid present in herbs such as berberis (barberry) and goldenseal; Chinese skullcap is also know as Scutellaria baicalensis, which is on my list of substances to be studied because, guess what?, one of its components has anti-MM effects (antiproliferative and apoptotic effects) in vitro. Yippee. I will post that information soon. Let’s see, what else? Silymarin is extracted from milk thistle, and sulphorophane is a well-known anti-cancer compound found in cruciferous vegetables €”broccoli, etc. Allicin, of course, is extracted from garlic, and genistein from soy.

I would like to take this opportunity to thank Dr. Benelli publicly for his kindness in sending me these books. La ringrazio davvero tanto!

Hiss!

Priscilla and Puzzola have been telling me for the past few days that they resent the fact that I have written a post (“Balls!”) only about my male cat, Piccolo. They feel left out. Quite right. I apologized to both of them, and immediately began writing Priscilla’s story.

In the month of June, 2005, it would have been a Friday afternoon, I was supposed to go pick up my X-ray results at the lab. Since it wasn’t urgent and I didn’t feel like going out (it was very hot, I recall), I decided to wait until Saturday morning so that my husband could go with me. But in mid afternoon, I decided for some odd reason that I HAD to go pick up those X-rays. So off I went.

On the way home, as I was driving up our street, I noticed something tiny and furry dash under a parked car. A kitten, for sure. I stopped and found two tiny abandoned kittens under that car. The poor little dears were starving and meowing after and following every single cat in sight, desperately seeking their mother. The one who turned out to be our Priscilla began following a large tomcat, who was none too pleased and took off like a shot across the fields. My heart melted. I brought the kittens food and water. They gobbled up the food, but didn’t let me come within a few feet of them.

With the help of my neighbours, I finally managed to catch them, one at a time. The blasted little things bit me viciously to the point of drawing blood, but I didn’t let go, and carried them over to our back yard. We decided to keep them out there until they trusted us enough to let us handle them. The following day, I noticed that one of them had a tick on its head. I called my vet immediately. Unfortunately she was on sick leave, so I spoke with her substitute, who told me not to worry, that ticks are harmless. I was still worried, but, being unable to examine either kitten more closely, there was not much else I could do. At the time, I didn’t know that ticks can suck all the blood out of a kitten.

A few days later, one of my kittens was dead. I still get emotional when I think about it. Could I have saved her? Well, at least I managed to save the surviving sibling. I had to chase her all the way into my neighbour’s yard to catch her, and once again, in spite of being weakened by the ticks, she bit me savagely. We adopted this tiny feisty tiger-striped kitten and named her Priscilla. Priscilla still has a wild side. She growls and hisses when we pick her up. She LIKES to be picked up, but hisses anyway. What we have to do is flip her over on her back, and she will happily and quietly stay in our arms for hours.Priscilla 2006

In retrospect, we should have named her Vandal. She ignores expensive cat scratchers but prefers to sharpen her claws on the rugs and furniture (my irreplaceable Sardinian bridal rug is a prime example). But then she will climb onto my chest whenever I am lying down, and drape herself around my neck, purring madly and turning her head this way and that so that I can give her a proper scratch. Irresistible. And she used to retrieve wine corks, just like Piccolo (still) retrieves balls. Sadly, she won’t do that anymore.

She is madly in love with my father (can’t blame her). The poor man has no peace when he and my mother are visiting us. Priscilla is always on top of him, purring ecstatically into his beard, and drooling with passion all over his chest (yes, a literal drool). If I go lie on my parents’ bed when they aren’t here, Priscilla will get on top of me, but she isn’t fooled. She wants my father.

She gets along very well with our other two cats. She and Piccolo have bonded quite nicely. They sleep together on our bed and play (very roughly at times) a lot. Puzzola, our queen, looks on. It’s our own private circus. And we love it.

Ellagic Acid and MM, Part II

Finally, the second instalment of my more complicated post. There will be a few more instalments, because one long post would be too overwhelming. I am a bit overwhelmed, too, I must say. There is a lot of information to be digested. For an overview of ellagic acid, see this Sloan Kettering page: http://tinyurl.com/2z33t5

Back to us. I have a listserv friend who takes a million supplements. His attitude is that cancer is cancer. Period. He has done a lot of research on MM and cancer in general, and has kept his cancer smouldering,” that is, inactive, for more than 12 years using only alternative treatments. Needless to say, I have a lot of respect for him. One of his A-list supplements is ellagic acid. I have not come across any studies specifically linking ellagic acid, or ellagitannins (the difference is explained below), to MM, but its anti-cancer properties are well-established, at least in vitro and in vivo €”cells, rats and mice. I would like to mention that the University of Oslo is currently conducting a clinical trial on ellagic acid and other substances (quercetin, selenium, garlic extract, EGCG, etc.) for follicular lymphoma, Stage III/IV; see http://tinyurl.com/2q72ja This is the only clinical trial testing ellagic acid at present. Too bad.

The lack of human clinical studies does not discourage me. Ellagic acid is on my to-try list of supplements. This polyphenol can be found in raspberries and in berries in general, and also in pomegranates, walnuts and pecans. It has antioxidant, antibacterial and antiviral properties (aha!), and has been found to cause apoptosis of cancer cells (aha, again!). From what I have read, plants produce ellagic acid to ward off microbiological infection and pests such as aphids, which I find very appropriate since what is MM if not a pest?! According to the U.S. Department of Agriculture (http://tinyurl.com/2p9ms6): Plants produce ellagic acid and glucose to form ellagitannins, water-soluble compounds that are easier for people to absorb in their diets. This means small amounts of ellagitannins may be more effective in the human diet than large doses of ellagic acid. See also the Washington Red Raspberry Commission report (http://tinyurl.com/3xnq9v), which provides information on the best variety of raspberry in terms of ellagic acid content: the Meeker variety. The report also tells us the following: Ellagic acid acts as a scavenger to €˜bind’ cancer-causing chemicals, making them inactive. It inhibits the ability of other chemicals to cause mutations in bacteria. In addition, ellagic acid from red raspberries prevents binding of carcinogens to DNA, and reduces the incidence of cancer in cultured human cells exposed to carcinogens. How about that?! Keep in mind unripe raspberries/lamponithat this information is based on cells. Still…! The report also provides links to more than 100 references : http://tinyurl.com/2wru6y I haven’t checked all of them yet, but the interesting part for me was that the list goes back to the 1960s. Therefore, the cancer-ellagic acid studies are as old as I am. Almost! At any rate, this is a very useful website, with heaps of useful information about raspberries. Ohio State University (http://tinyurl.com/2tjpnq) published a study on the ellagic acid content of various berries, which concludes that the highest content of ellagic acid, at least in the Ohio plants, is in the leaves, not the fruit. It is also high in the seeds or in the unripe fruit (see the photo I took this morning of a few of my still unripe raspberries).

Synergism between natural compounds. I recently read a fascinating 2005 abstract (http://tinyurl.com/28w747) on the synergistic interactions between polyphenols, specifically ellagic acid, quercetin and resveratrol, added to human leukaemia cells (MOLT-4): Results indicate that the anticarcinogenic potential of foods containing polyphenols may not be based on the effects of individual compounds, but may involve a synergistic enhancement of the anticancer effects. Well, well. A 2004 study (http://tinyurl.com/29s5lr) informs us that phytochemicals extracted from plants, including ellagic acid, resveratrol and curcumin have been shown to suppress cancer cell proliferation, inhibit growth factor signaling pathways, induce apoptosis, inhibit NF-κB, AP-1 and JAK-STAT activation pathways, inhibit angiogenesis, suppress the expression of anti-apoptotic proteins, inhibit cyclooxygenase-2. By the way, the last item, i.e. cyclooxygenase-2, is the infamous COX-2 enzyme, which is an independent predictor of poor outcome in MM (see: http://tinyurl.com/2lvw9t). After reading these studies, my first thought was: put these compounds together in a bioavailable form, and cancer cells will have nowhere to hide. Of course, only human trials will show which compounds work well together and which do not. In the meantime, this summer, I will certainly be eating a lot of raspberries! Okay, that’s enough for today! I need a nap! 😉

My Curcumin Protocol (Afterthought)

I should have emphasized the following point more forcefully: before taking curcumin, or any other substance for that matter, I think it’s a good idea to speak with your healthcare provider, even if you are NOT doing chemotherapy. In January of 2006, my husband and I took the curcumin-MM studies to my former haematologist (who retired in August) and discussed the matter with him. At the time, he was suggesting that I do two cycles of Velcade, then an autologous SCT (stem cell transplant) in the summer of 2006. Happily, none of that ever came to pass, thanks to curcumin.

His reactions during that January meeting gave me the distinct impression that he was sceptical, but he did tell me to go ahead with the initial eight-week curcumin protocol. However, he added that I would have to start chemo if curcumin did not work. At the time, I said, “sure, okay.” Of course, curcumin DID work, and, as a result, my surprised (I think!) haematologist informed me that he had started sprinkling turmeric over his food. But the point is, I didn’t start taking curcumin without informing my doctor. I should add that I felt (feel!) so strongly about curcumin that I would have followed the eight-week protocol even if he had advised me against it. I can be stubborn at times! But the bottom line is: I feel that it is best to be open with our doctors, even if we think they will disapprove.

Of course, nobody can predict the long-term effects of curcumin and the other substances that I am taking or plan to take. So, while I am cheerfully (and stubbornly!) confident that I will remain stable on my protocol, only time will tell.

My Curcumin Protocol (Continued)

Since posting my protocol, I have received a few questions that I would like to address. Yes, it’s true, I HAVE done a lot of research on curcumin, but the more I do, the more I discover there is to do!, which is a very good thing, of course. As Mahatma Gandhi said, Live as if you were to die tomorrow. Learn as if you were to live forever.

One of the questions concerns why a curcumin-taker should build up slowly to eight grams (or more, actually; I know a few people who take 10-12 grams). As with any substance except perhaps for water, I think it’s a good idea to see how our body reacts to it. What if you began growing a second nose or something? Seriously, though, it’s merely a precaution. I personally have had no bad reactions to curcumin, even when I went up to nine grams of powder at one point last year. But a few people have reported diarrhea, which perhaps can be taken care of by cutting back on fiber intake (an MD Anderson nurse suggestion), and one person developed some kidney trouble, which may (or may not) have been caused by curcumin, even though Prof. Aggarwal replied that curcumin has a protective effect on the kidneys. And, in fact, I have never read of curcumin affecting the kidneys. But, hey, you never know, we are all different and react differently to the exact same thing. So, for those reasons, I think it’s best to err on the side of caution and build up to eight grams slowly.

A listserv friend, who plans to start taking curcumin soon, wrote about having chronic pain and headaches. I don’t recall if I have written anything about headaches on my blog, but this is what happened to me. I used to have horrendous headaches almost daily. I think they might have been caused by my very high blood viscosity (that seems to be one of my main MM symptoms), which essentially means that I have thick blood. Well, curcumin is a natural blood-thinner. Not long after I began taking curcumin, my headaches stopped. Gone. Poof! Just like that. I still get occasional mild headaches, probably because my blood viscosity is still on the high side, but nothing like those terribly painful pre-curcumin ones. I hope curcumin will take care of my friend’s headaches, too.

Another potential benefit: arthritic pain. Through Prof. Aggarwal, I met an Italian urologist who works in a Tuscan hospital. A wonderful man. He just sent me three books that he has written on curcumin and prostate cancer. Fascinating, well-written and containing historical and etymological information, which always makes me as happy as a little kid opening birthday presents. There is also some very useful information on curcumin bioavailability, so I will soon be posting a few comments on that issue. At any rate, he told me that he takes curcumin for his arthritis. And that rang a bell. Before I took curcumin (and I know I posted a few words on this topic, but it doesn’t hurt to reiterate a point, sometimes), I had a difficult time walking up the stairs in my house. I had to go up slowly, and pause now and again. My knees hurt and made scary creaky noises. I now dart up my stairs like an adolescent mountain goat. No problem whatsoever. No more creaky noises, no more pain. Another stupid thing: I used to have to sit on a step stool in order to put laundry inside my washing machine €”in Italy, we have front loaders €”because it hurt me to kneel down. I now can kneel with no problem, and pick up things from the floor (like cat bowls) without any trouble. There are studies on curcumin and arthritis, I have discovered. I am not surprised.

There is no denying that I am obsessed with curcumin. But with good reason. Curcumin is keeping me stable AND giving me many side benefits, including, as I have reported elsewhere, a substantial decrease in cholesterol, which is almost normal now (yippee!) for the first time in years. I checked as far back as 1999: it was 73 mg/dL HIGHER then. Plus, I am mentally more alert. I actually remember things now. I used to be such a scatterbrain: I would write notes to remember things and then forget where I put them. Check out the studies on curcumin and Alzheimer’s disease. Curcumin may prevent AD, which comes as no surprise to me. The AD-curcumin topic would merit a post of its own.

I have no doubt that I am doing myself a lot of good (some, perhaps most, of it completely unexpected) by taking curcumin.

And now for an amusing ending. A listserv friend (thank you!) recently posted this YouTube link to a funny Tom Rush video. Have a look at it when you have time, and have yourself a giggle! And, by the way, if you have a joke or a funny link, please send it to me. Thanks! http://www.youtube.com/watch?v=9yN-6PbqAPM

My Curcumin Protocol

Here it is, finally. I have been procrastinating about posting the protocol on my blog, even though I have written it out in countless private e-mails, mainly because I felt I should add a disclaimer, and, to be honest, I didn’t want to do that. The only reason I decided I needed to put a disclaimer here is because I have seen other alternative cancer treatment blogs do it. So, first, let’s get the disclaimer out of the way: my blog presents information based on my own experience and research. I do NOT intend to tell others what to do, or to become a substitute for anybody’s healthcare provider. I am not a doctor, just a researcher who has come up with a protocol that so far has worked to keep my MM stable. I cannot be held responsible for any adverse effects resulting from the application of the information contained in my blog. So, for instance, if curcumin gives you a bit of diarrhea, don’t say I didn’t warn you! (see my Warnings Page).

Phew. Now that the disclaimer is out of the way, let’s get down to business. This is the protocol that I followed last January, based on what I read etc. (I am still on eight grams of curcumin a day). I followed the initial protocol for eight weeks, then had blood tests repeated:

Week One: one gram of curcumin

Week Two: two grams of curcumin

Week Three: four grams of curcumin

Week Four (and thereafter): eight grams of curcumin

1. I will NOT recommend any specific curcumin brands. For one thing, I live in Italy, so my experience with U.S. brands is rather limited. For another, I do not want to sponsor any particular brand. Truth be told, I do not have a favourite brand. However, make sure your curcumin contains at least 95 % curcuminoids. Anything less than that is apparently useless.

2. Curcumin with or without bioperine (from black pepper)? That is an issue that I am still thinking about and researching. My capsules do contain bioperine, which apparently increase bioavailability. And it is true that my IgG count plus other markers have improved. So it’s up to you to decide.

3. Divide your curcumin intake into two or three doses a day, if possible. I am considering another experiment (for the fall): dividing my curcumin intake into four doses in order to keep curcumin in my bloodstream in a more constant manner. But I haven’t tried that yet, so I don’t know if it works. For now, I am sticking to the twice a day protocol.

4. If possible, take curcumin on an empty stomach. If your stomach rumbles, and you would prefer to take it with food, please leave me a comment or write me an e-mail, and I will get back to you with some advice. And please let me know if you experience any weird side effects, so I can post them on my Warnings Page.

5. Other curcumin-takers and I take our curcumin with some sort of fat, as follows: flaxseed oil or fish oil capsules. Curcumin has poor bioavailability (see my Bioavailability Page), so until researchers come up with a more bioavailable formula, we will simply have to rely on our own research and the experience of others. Based on that experience etc., it appears to be best to take curcumin WITH some sort of oil capsule, so it will be better absorbed.

6. Since January, I have been taking quercetin about 15 minutes before curcumin. See my page on quercetin for more details. I now take one gram of quercetin a day.

7. Before taking curcumin, check with your healthcare provider, especially if you are doing chemotherapy. Also, check my Warnings Page, I repeat. Some folks should NOT take it, as a precaution.

8. Last but not least, have blood tests done before and after you try the initial eight-week protocol. Otherwise, how will you know that curcumin works for you? 🙂 And please keep me posted! Thank you!

Artificial Food Additives and Our Health

Supermarket food looks so bright, colourful and healthy-looking, right? Well, that brightly coloured food is not healthful at all, according to recent studies carried out in the United Kingdom. And when you think about it, it makes total sense: blue and pink cake icing? Hello? There’s no question that those colours are attractive (I confess to having eaten blue supermarket cupcakes in the past), but hardly natural. And last year (ok, ok, another confession, just last week, too!) I tried the freshly-made pesto sauce from our local supermarket. It maintained its lovely healthy-looking greenness even after a couple of days spent in my fridge. When I make my own pesto sauce, it immediately turns brown no matter how quickly I cover it with olive oil. 😉 Well, duuuuh!, the supermarket pesto is full of artificial colours, Margaret. And have you ever wondered why ground beef remains bright RED for hours/days/centuries? When my husband and I grind our own beef, it goes brown almost instantly. What’s the difference between the store-bought meat and ours? Gee, let me guess. And if you want to be really scared, have a look at this Consumer Affairs’ report about carbon monoxide allowed in U.S. meat packaging to keep meat red and fresh-looking: http://tinyurl.com/23y3tm

Yellow dye, or tartrazine, derives from coal tar, see http://tinyurl.com/2x35vj, where you will also find a list of foods containing this dye. Can tar be considered food? Right, I thought not. Do you want brilliant yellow food? Well, simply add a natural colouring agent to it. For instance, the easiest way to have a lovely bright yellow frittata is to add some turmeric. Ok, before I get too carried away, let’s have a look at the UK studies, which inspired me to write this piece in the first place.

On May 8, BBC News (see: http://tinyurl.com/2vulgo) reported about a study by the University of Southampton concerning the effect of food additives on children. This study apparently confirms the findings of a previous one (known as the Isle of Wight study: http://tinyurl.com/32dlky) that linked food additives to children’s temper tantrums, hyperactivity, sleep disorders, allergic reactions (asthma and rashes, e.g.) and poor concentration. The University of Southampton researchers gave certain additives €”tartrazine (E102), ponceau 4R (E124), sunset yellow (E110), carmoisine (E122), quinoline yellow (E104) and allura red AC (E129) €”to three-year-olds and eight-to-nine year olds, in the amounts that an average child would consume on a daily basis. The study findings have not yet been published, but preliminary results have raised so many concerns that a few supermarkets have already banned the use of these additives as well as of aspartame, hydrogenated fats and flavour enhancers (such as monosodium glutamate): ASDA (the third-biggest supermarket chain in the UK) and Marks & Spencer, see http://tinyurl.com/36fb2n

Of course, it’s not just children who are being affected. We adults are victims of this artificial crap, too. I used to love eating brightly coloured chocolate covered peanuts (no brand names! 😉 ). After reading these reports…well, you can imagine how I would end this sentence !

Ellagic Acid and MM, Part I

I read about ellagic acid and its anti-cancer effects about three years ago. And that is why I brought back to Italy a couple of half dead shoots from my parents’ enormous raspberry bush in the States. Those shoots not only survived, but THRIVED in my back yard. I guess they like their new home in Florence. Every spring, there are new shoots all over the yard. But the best part is that we have raspberries from the end of May until October. And raspberries are full of ellagic acid, which will be discussed in Part II. Poldo

Yesterday afternoon I took a break from work and walked around our back yard, checking all my herbs and flowers. I stopped to take a closer look at the still unripe fruit on my raspberry plant and felt something tap my foot. Something warm and furry. I looked down, a bit startled, and saw the front part of my neighbours’ cat sticking out from under the bush. This handsome long-haired male cat looked so adorable that I rushed to get my camera. So here is Poldo, escaping from the heat under my raspberry bush.

Antioxidants and Chemotherapy

A listserv friend recently wrote a post about a study titled Impact of antioxidant supplementation on chemotherapeutic efficacy: A systematic review of the evidence from randomized controlled trials, published in Cancer Treatment Reviews in January 2007. With the help of an Italian friend (grazie mille!), I managed to gain access to the full study, not just the abstract (which is available at: http://tinyurl.com/24xm2u). It is estimated that between 13 and 87 % of all cancer patients take antioxidant supplements. Significant numbers. Yet many MM patients have told me that their doctors warned them, sometimes quite strongly!, against taking any supplements while doing chemotherapy, based on the myth that supplements could interfere with and even diminish treatment efficacy. Well, perhaps this 2007 study will debunk the myth once and for all.

This group of researchers went through electronic databases and looked at the randomized, controlled clinical trials that reported survival and/or tumor response 19 trials met the inclusion criteria. Antioxidants evaluated were: glutathione (7), melatonin (4), vitamin A (2), an antioxidant mixture (2), vitamin C (1), N-acetylcysteine (1), vitamin E (1) and ellagic acid (1). Subjects of most studies had advanced or relapsed disease. A total of 1554 patients were evaluated. Most of the 845 trials were excluded for a variety of reasons–because they were not controlled trials, because antioxidants were not given together with chemotherapy, etc.

An aside: since ellagic acid is on my June list, I was interested to read that prostate cancer patients taking ellagic acid had significantly decreased neutropenia over patients taking a placebo (33 versus 75 %). Those patients also lived longer and had a better response to treatment. Another interesting bit of news is that all studies reported similar or less neurotoxicity in the antioxidant group than the control group.

The study concludes that patients taking antioxidants during chemotherapy had increased survival, increased tumour responses and fewer toxic side effects. The researchers hope that their data will pave the way to larger studies on the concurrent use of antioxidants with chemotherapy. However, even though this study examined only a small sample of clinical trials, I believe its findings are significant enough to make dubious doctors change their minds on supplements. About time.