Quercetin, WNT Signaling Pathways and Myeloma

After reading the Delano Report a few months ago, I decided to test quercetin. For details (and a link to the report), please see my April 20th blog post titled Protocol, Spelled Out. What is quercetin? It’s a flavonoid found mainly in apples, onions, berries, cauliflower and nuts. It has significant anti-inflammatory and antioxidant properties. From Wikipedia: Quercetin may have positive effects in combating or helping to prevent cancer, prostatitis, heart disease, cataracts, allergies/inflammations, and respiratory diseases such as bronchitis and asthma. In fact, last August I bought a couple of bottles of quercetin for my asthma but hadn’t yet opened them. Until I read the Delano Report, that is. Then my interest in quercetin went way beyond asthma! An aside: I can report that my asthma is officially GONE. I still take one puff of my cortisone inhaler before going to bed, but that is merely a precaution.

MM and WNT. For the following section on WNT signaling pathways, I am greatly indebted to Stephen Martin, Ph.D., of the Grouppe Kurosawa. Without his posts, I might not have done any research on this topic. Last year, he wrote that WNT signaling is elevated in many cancers, including MM. Researchers have discovered that aberrant WNT signaling causes MM cells to proliferate and grow, as these studies show: http://tinyurl.com/2rorm6 and http://tinyurl.com/2yp3yc A Dutch study is currently looking into the WNT-MM connection, see: http://tinyurl.com/2ex6tp These signaling genes seem to be in every single type of cancer, from colorectal to oral cancer. For a detailed explanation on how they affect different types of cancer, see this important 2000 study: http://tinyurl.com/2jrw3p

What IS the WNT signaling pathway? In a nutshell, it is a complex network of proteins involved in many development processes (cell-to-cell communication during embyrogenesis). However, it can also influence cancer growth, as I mentioned. The more scientifically-minded can check out a Stanford University WNT Homepage containing a ton of information on the WNT gene: http://tinyurl.com/27fnaj What is relevant to my research, however, is that this pathway is consistently active in MM and causes cell proliferation and growth. Not a good thing! And guess what? Quercetin inhibits it. An April 2007 Blood study examines acute lymphoblastic leukaemia (ALL), not MM, that is true, but what is significant is that quercetin inhibits the WNT signaling pathway and causes the ALL cells to self-destruct: http://tinyurl.com/2m5w2d More evidence can be seen in a second study printed in the same edition of Blood : http://tinyurl.com/3d34vm Again, ALL cells self-destructed when treated with quercetin. Does this mean that it would have the same effect on MM cells? I haven’t found any studies on quercetin and MM, specifically…yet. But I have the feeling the answer is a resounding Yes!

My own observations. I have noticed two big changes since I began taking quercetin capsules more than a couple of months ago. One is that my rosacea (also known as curse of the Celts !) has gotten much better. I hadn’t connected this improvement to the quercetin, but recently I came to wonder: what else could it be? The other is that my peripheral neuropathy has gone completely. It had partially returned last fall (2006), though nothing like what I experienced in the pre-curcumin period (2005). Again, it’s impossible for me to say if the two things are related to my quercetin intake. Just a suspicion on my part. Of course, NOT to be discounted is the recent drop in my IgG count!

A note on quercetin from Wikipedia: Foods rich in quercetin include apples, tea (Camellia sinensis), onions (higher concentrations of quercetin occur in the outermost rings), red grapes, citrus fruits, broccoli & other leafy green vegetables, cherries, and a number of berries including raspberry, bog whortleberry (158 mg/kg, fresh weight), lingonberry (74 and 146 mg/kg), cranberry (83 and 121 mg/kg), chokeberry (89 mg/kg), sweet rowan (85 mg/kg), rowanberry (63 mg/kg), sea buckthorn berry (62 mg/kg), crowberry (53 and 56 mg/kg), and the fruit of the prickly pear cactus. A study by the University of Queensland, Australia, has also indicated the presence of quercetin in varieties of honey, including honey derived from eucalyptus and tea tree flowers.

This is just a first instalment. My research on quercetin continues. There is a lot to uncover, yet.

Curcumin Cuts Faulty Phone Lines

I used to be a professional translator, which is a big help when I try to make sense of what frequently looks like gobbledygook in scientific/medical articles. However, I didn’t need any translating skills to read Terri Michell’s clear report on the anti-cancer effects of curcumin (see link here on my homepage). Thanks to her, I became interested in kinases, which, she writes, are like phone lines that run right into the DNA of cancer cells, carrying grow signals. Easy! Compare that to the Wikipedia definition: in biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific target molecules (substrates); the process is termed phosphorylation. Uh huh. Right.

Terri Mitchell reports that there are over 2000 known protein kinases. Curcumin inhibits several of them, an ability it shares with other phytochemicals including silymarin (from milk thistle), apigenin (from parsley and celery), hypericin (commonly known as St. John’s wort) and EGCG (from green tea), just to mention a few. As far as MM is concerned, a kinase called IKK plays an important role in the activation of NF-kB, a crucial transcription factor (inhibited by curcumin) that I have discussed in previous posts. And the name of an IKK inhibitor? Yes, curcumin again! See this 2003 “Blood” study: http://tinyurl.com/ypc7o7

When curcumin is used to cut kinase phone lines, some types of cancer cells stop growing. Of utmost interest to us MMers is that curcumin causes MM cells to self-destruct (through a process called apoptosis). Poof!, and they are gone. Like magic…(said like a true Harry Potter fan)…There are hundreds, perhaps thousands, of online studies concerning kinases and curcumin. It would be impossible to list or read them all. There are also thousands of studies on kinase inhibitors and cancer: a hot topic, clearly.

Back to Terri Mitchell, who ends her report with these remarks: The actions of curcumin have been the subject of presentations at major meetings on cancer research, and the object of study by researchers at the most prestigious universities in the world. If curcumin were a drug, it would be hailed as one of the best all-around cancer drugs ever invented. As it is, it’s a phytochemical with impeccable credentials, thousands of years of use behind it, and a very small price tag. No wonder a host of drug companies want to imitate it.

Barni Rose

Rosa Barni, Giardino dell'Orticultura, aprile 2007This morning we went to a large flower fair in my favourite historical garden in Florence, “Il Giardino dell’Orticultura,” which was created in the 19th century by the Tuscan Society of Horticulture. It is an oasis of peace and beauty, and contains a spectacular tepidarium which was built in 1880. I tried to take a few photos of it, but there were too many people in my way. However, I did get a good shot of some of the Barni roses (see photo). The Barni family is famous worldwide for its beautiful roses, of which many are copyrighted. We bought a rose called “William Shakespeare” for our back garden. We also bought a few cranberry plants. Fancy that, cranberries in Italy! If they survive, I will post a photo of them, too!

Goodbye, Myeloma Man

The sun is shining in Florence this morning, but it doesn’t look very bright to me out there. I woke up to the sad and upsetting news that Hans Yeager, known to us MMers also as Myeloma Man, passed away on April 1. I still have a hard time believing it. I immediately went to his website only to discover that it is gone. I had meant to read every word of it some day soon. Too late now. It is with deep regret that I will remove the link from my blog.

His wife wrote a very touching account of his last hours; it was posted on one of the MM listservs. No point in repeating the details, here, but Hans was a fighter right up to the end. A brave man.

My most recent and, as it turned out, last exchange with Hans happened in mid March, right after he had gotten out of the hospital. He had just gotten home, and was about to take a shower. He wrote that he would get in touch with me as soon as he felt better, and I replied with a Get Well Soon e-mail. His last words to me were Look forward to conversing with you. Unfortunately, that will no longer be possible.

Germ Killer

One of the bothersome aspects about having MM or SM or even MGUS is that we are more exposed to illness than healthy people with fully functioning immune systems. What happens is that our abnormal plasma cells, or myeloma cells, produce too much of one completely useless kind of antibody, called an M-protein, which doesn’t help kill bacteria and germs, leaving us susceptible to infections. My main problem seems to be my lungs. If I get a cold, it usually goes into my chest, and even my daily intake of curcumin has not made me invincible. I sometimes have to take antibiotics. No big deal, of course, compared what most MMers go through. However, since I refuse to become a hermit or live under a glass dome like an antique teddy bear, my most recent minor complaint has given me the incentive to look up things we can do to prevent colds and the flu. I will skip the more obvious ones, such as: eat well, sleep enough, drink plenty of water, get some exercise, fresh air, laugh, avoid stress, don’t smoke and don’t drink alcohol. I will list only the suggestions that particularly struck me.

1. Common sense tells us to wash our hands whenever we come into contact with potentially contaminated objects. Germs can live on staplers, doorknobs and computer keyboards for hours, and in some cases, I have read, even weeks. Years ago I watched an Oprah show on germs. Tests were performed in various public areas, and I will never forget that flesh-eating bacteria, or necrotizing fasciitis, were found on the handlebars of shopping carts. Yikes. So, while shopping in a supermarket, wear disposable gloves.

2. Flu and cold germs can enter our bodies through the mouth, nose and eyes. Did you know about the eyes? I didn’t.

3. Don’t sneeze or cough into your hand. Cough or sneeze into the open air (if nobody is within a mile of you), into a tissue or into your sleeve. Otherwise, you risk spreading germs to anything you touch.

4. My father-in-law told me about an Italian folk remedy that I haven’t tried it personally (yet). Before you leave home on an errand that will put you in contact with a germ-filled crowd (supermarket, bus etc.), stick a couple of garlic cloves up your nose and leave them there for a few minutes or several hours (just kidding!). Hey, this is no laughing matter. However, do remember to fish them out of your nose before you leave the house. 😉 This simple act will apparently enhance your immune system and protect you from outside germs. After all, fresh garlic protects us from many types of fungi and bacteria, including the infamous Heliobacter pylori. And we all know that fresh garlic and onions are good for us when we get sick, so why NOT put some garlic up our nose? Besides, another possible effect is that germy people would be less likely to crowd around you if you smell heavily of garlic. Let’s not underestimate the many powers of garlic. 😉

5. Last but not least are turmeric and curcumin. Ayurvedic medicine prescribes turmeric for the treatment of common colds, coughs, sore throats, and upper respiratory disorders. Curcumin has antibacterial, antiviral, antiseptic and anti-inflammatory properties, and is also a mild expectorant. And finally, I read that turmeric is known as kringhna in Sanskrit, which means germ killer. 🙂

Protocol, Spelled Out

I began my curcumin capsule experiment on January 23, 2007, according to my notes. In order not to swallow a million pills at the same time, I divided my dose: one in the morning, one in the afternoon, away from meals. A few months ago, I read the Delano Report (http://tinyurl.com/yyucfp), which examines the possibility that quercetin, a flavonoid found in apples, onions, red grapes, citrus fruits, broccoli and so on, inhibits the sulfotransferase enzymes that render curcumin relatively inactive in the small intestine. I decided to add quercetin to my intake. I took two grams of quercetin about 15-30 minutes before swallowing the curcumin capsules. Each dose consisted of: one gram of quercetin and then four grams of curcumin with bioperine. However, if for some reason I wasn’t at home in the morning or afternoon, I would take one BIG dose once a day, for a total of: two grams of quercetin and eight grams of curcumin. With all those capsules, it was like having a small meal, practically!

On February 12, in order to enhance curcumin bioavailability, I added fish oil capsules, which are very expensive over here. I ran out of fish oil capsules in mid March, and decided to substitute them with black cumin oil (Nigella Sativa) capsules, which contain 500 mg of black cumin oil each. A total of two grams a day. I will be writing about black cumin oil soon, so keep posted. I took the fish oil or black cumin oil capsules at the same time as the curcumin. I also occasionally took some folic acid (starting on February 23) and a multivitamin with iron, but not every day. My main supplement intake was: quercetin, fish oil (later, black cumin oil) and curcumin.

Confession of stupidity. My most recent pet peeve concerns the words serving size written in VERY small print on supplement bottles. My January-April 2007 capsule experiment was not my first experiment with capsules. I had tested them for two months back in September-November 2006, to be precise. However, I hadn’t noticed the tiny print on the back label, which added the information “Serving Size Two Capsules.” There was no mention of per serving on the front label. The front label on my bottle of curcumin capsules reports the following: Turmeric Extract, Curcumin C3 Complex with Bioperine, 1,160 mg. That is IT, apart from minor information such as brand name and number of capsules. So for two months I inadvertently took a half dose of curcumin, four grams instead of my usual eight grams. By the time I discovered my mistake, I had been on four grams of curcumin a day for two whole months! Yikes. Did I feel stupid? Oh yes, indeed! And my blood tests in November 2006 reflected the halving of my daily intake: my IgG count jumped from 26.3 g/L to 32.5 g/L. I immediately switched back to eight grams of curcumin powder taken with a fat. My January 2007 tests were stable, and some MM markers had actually improved. Not my IgG count, though, which had remained at 32.5 g/L. However, it takes much more than that to discourage me (eternal optimist). This simply proved that four grams of curcumin is NOT enough to keep MM down, and I needed more time to give it another good whacking. In January I decided to try curcumin capsules again, this time the full EIGHT grams! Sorry, this is long and perhaps overly detailed, but I thought I should explain what happened. Besides, confessions of stupidity are good lessons in humility. Or so I hope! Yesterday I was just too overwhelmed with happiness to write out a full report. So, a final word of advice: before taking any supplement, check the small print on the back label! Front labels can be SO misleading. Live and learn but best to learn from the mistakes of others. 😉

When yesterday I wrote about not having been careful about my diet during the Xmas holidays, I should have explained that my biggest downfall were my Xmas cookies. Every year, I make HUGE batches of cookies for friends and family, following wonderful U.S. recipes chock-full of butter (REAL butter, never use margarine!) and chocolate and white or brown sugar. Last Xmas, in an attempt to be more health-conscious, I experimented with oatmeal spice cookies to which I also added turmeric. They were yummy (lovely bright yellow colour, too!), even though I know they will never replace my famous chocolate chip ones! Thing is, I had to TRY them first to make sure they were good enough to be given as presents. Right? 🙂

Curcumin Capsule Results

I just received my most recent (early April) blood test results. Premise: after hearing from other curcumin-takers that capsules worked well, I decided to give them a whirl (see my Bioavailability of Curcumin page for information on how I previously took curcumin). So I have been taking curcumin with bioperine capsules for more than two months. Well, well. The capsule results are better than I expected. In January 2007, my IgG count had gone up to 32.5 g/L, from a September 2006 low of 26,3 g/L. Quite a scary jump! I was not discouraged, though. These fluctuations can happen, and this particular one was my own fault (I didn’t pay too much attention to my diet over the Xmas holidays, etc.). Anyway, according to my April results, my IgG count has gone back down to 28,8 g/L, and there has been no change in my other immunoglobulin counts. That’s the first good bit of news.

Comparing my main MM markers in my January 2007 and April 2007 tests: Creatinine is down from 0.9 to 0.7 mg/dL, within normal range; Calcium is stable, within normal range; LDH is down from 168 to 139 U/L, within normal range; Total protein is down from 9,1 to 8,6 g/dL (the latter value coincides with the high end of the normal range, yippee!); B2M is down from 1,8 to 1,5 mg/dL, within normal range; CRP is within normal range (my hospital lab doesn’t give an exact CRP number, only reports that CRP is < 9,0 mg/L); Albumin is still within normal range, stable at 49.5 %. My cholesterol and triglyceride levels have taken another tumble, so I am very pleased about that, too. So, very good results. Have I forgotten anything? Please let me know. I will soon be posting the exact protocol that I have been following since January. But first I want to look over my notes and rejoice a bit with my family. It’s a gorgeous sunny day in Florence, Italy!

Nanocurcumin?

This morning I came across a very interesting bit of news. A group of researchers from the Johns Hopkins University School of Medicine and the University of Delhi have created a nano-encapsulated form of curcumin €”nanocurcumin! €”which can be readily dispersed in aqueous media. This might overcome the problem of curcumin’s poor systemic bioavailability. It has already been tested in vitro on pancreatic cancer cells and has showed the same degree of effectiveness as regular curcumin, such as inhibition of NF-kB and downregulation of IL-6. Indeed, according to preliminary tests, pancreatic cancer cells lapped up this new form of curcumin more eagerly than regular curcumin. Nanocurcumin was also given to mice, and no ill effects were reported. See http://tinyurl.com/3x23gk for more information. Good news!

April Flu

I must have picked up a stupid little flu bug at my doctor’s office last week. So I won’t be posting for a few days, but do stay tuned, because this has given me an incentive to finish my post on GERMS! 😉

Fractured English

Discovering that laughter helps boost the immune system and get our natural killer cells in motion has meant that I have been spending some time looking through the funny books that I have in my library. Has anybody read Richard Lederer’s “Anguished English” series? Well, if not, then off you go to the library or bookstore to get yourself a copy. You won’t regret it. I was just skimming through Lederer’s Fractured English, when I came upon the chapter devoted to English abroad. Since I used to translate from Italian to English and vice versa (still do, on occasion), I picked an example Lederer took from the brochure of an Italian hotel in the Dolomites area: Standing among savage scenery, the hotel offers stupendous revelations. There is a French widow in every room. We can offer you a commodious chamber, with balcony imminent to a romantic gorge. We hope you want to drop in. In the close village you can buy jolly memorials for when you pass away.

I always read hotel room instructions. I found a brilliant one in a hotel in Milan: in case of fire, please warm the manager. 🙂