In my November 22nd post, I mentioned a newly published MD Anderson study, co-authored by Prof. Aggarwal (abstract: http://tinyurl.com/35w4mn). Thanks to Sherlock (grazie mille!), I was able to read the full study, which I have read but must read again, as it is filled with so many significant details etc. My original post turned out to be too long, so I will divide it into chapters, at least two.

Titled Bioavailability of Curcumin: Problems and Promises, the study was published in the November 14th issue of Molecular Pharmaceutics. It begins with an overview of curcumin, which, as we know by now, has been shown to exhibit antioxidant, anti-inflammatory, antimicrobial, and anticarcinogenic activities. Additionally, the hepato- and nephro-protective, thrombosis supressing, myocardial infarction protective, hypoglycemic, and antirheumatic effects of curcumin are also well established. Even at high doses, up to 12 grams a day, curcumin is well tolerated. I know I have written all this before, but I think it’s good to go over known information sometimes.

Curcumin’s main problem, as we (again!) know, is bioavailability: studies over the past three decades related to absorption, distribution, metabolism and excretion of curcumin have revealed poor absorption and rapid metabolism of curcumin that severely curtails its bioavailability. The serum levels of curcumin are extremely low. Let us keep in mind, though, that the UK Phase I Clinical Trial of Oral Curcumin (full study: http://tinyurl.com/32kwok), which tested regular curcumin (C3 Complex without bioperine) on patients with advanced colorectal cancer, ends with the following statement: The findings of the study presented here lead us to conclude that the systemic pharmacological properties of a daily dose of 3.6 g of curcumin are suitable for its evaluation in the prevention of malignancies at sites other than the gastrointestinal tract. 3.6 grams. Very little, compared to the 8 grams that I am taking. This Phase I clinical trial in fact showed that consumption of 3.6 g of curcumin daily generates detectable levels of parent compound and conjugates in plasma and urine, where the parent compound was curcumin, of course. The study contains headache-causing (for a non-scientific brain!) amounts of details, but, unless I am much mistaken, a few are lacking, which I would be curious to know, for instance: 1. what time of day was curcumin taken by the patients and 2. did they take it on a full or empty stomach?

Speaking of time of day, as I was reading through the description of all the studies cited by the MD Anderson team, a BIG question popped into my head. Relevant or not, here it is. Remember my November 11th post on circadian rhythms, in particular the part about human versus rat testing? Well, here’s a memory refresher: Despite this evidence of variation, drug research is almost always done during daylight hours, when the humans leading the studies are awake and alert. And in the animal testing stage, it’s almost always done with mice and rats, which are nocturnal €”the middle of our day is the middle of their night. This can lead to gross misestimations of the effectiveness and toxicity of a drug intended for humans. My question: could circadian rhythms possibly affect the curcumin testing being conducted on mice and rats? And what about the curcumin testing on humans? What if these tests were conducted at different times of the day and night? Would there be differences in the results? My feeling is that there would be. Take a look at this sentence in the MD Anderson study: the serum levels of curcumin in rats and in human are not directly comparable. Hmmm. Well, okay, that makes sense on all sorts of levels, of course, even though I enjoy a bite of cheese probably as much as a mouse does 😉 , BUT could this divergence also be due, at least in part, to daylight testing on nocturnal animals? Another point. We don’t know what time of day or under what circumstances the human subjects in these trials took their dose of curcumin. And, for instance, we are informed that some folks developed diarrhea but others didn’t. Did both groups take curcumin at the same time? All this information would indeed be interesting to have. Okay, I realize that I’m in over my head here, and that my suspicions may turn out to be irrelevant rubbish. I must read the MD Anderson study again, and look up all the studies, one by one (yeah, that’s likely to happen… 😉 ). Ok, enough about circadian rhythms.

The MD Anderson researchers point out that the issue of curcumin levels found in body tissues has been relatively ignored. Interesting, I thought. One of the few studies dealing with body tissues dates to 1980 (abstract: http://tinyurl.com/3a93ko). I quote from the MD Anderson study: after oral administration of 400 mg of curcumin to rats only traces of unchanged drug were found in the liver and kidney. At 30 min, 90% of curcumin was found in the stomach and small intestine, but only 1% was present at 24 h. The team points out also that Although many curcumin analogues are found to show improved biological activity over curcumin, specific evaluations of structural analogues and/or derivatives of curcumin to show improved tissue and plasma distribution are lacking. More studies are needed!

There is lots more, including mentions of substances we can take to enhance the bioavailability of curcumin and novel bioavailability methods, some of which I have mentioned in previous posts. But this post is getting to be too long, so I will stop here for now. In chapter two, I will discuss glucuronidation! 😉

Last night I told Stefano about the Science Daily article and the paragraph that I quoted in my blog post yesterday, the one about the three to four year survival statistic, which is such hogwash (my opinion). He quoted a sonnet about statistics written by the Roman satirical poet Trilussa (real name: Carlo Alberto Salustri, 1871-1950). This morning I looked it up and thought it contained some interesting material, so here it is (my curcumin bioavailability post is ready, I will post it tomorrow). Trilussa’s sonnet, by the way, is not written in standard Italian but in the dialect of Rome (for which this dialect poet is famous, in fact). I will provide a rough translation, don’t worry!

Sai ched’è la statistica? E’ ‘na cosa

che serve pe’ fa’ un conto in generale

de la gente che nasce, che sta male,

che more, che va in carcere e che sposa.

.

Ma pe’ me la statistica curiosa

è dove c’entra la percentuale,

pe’ via che, lì, la media è sempre eguale

puro co’ la persona bisognosa.

.

Me spiego, da li conti che se fanno

seconno le statistiche d’adesso

risurta che te tocca un pollo all’anno:

.

e, se nun entra ne le spese tue,

t’entra ne la statistica lo stesso

perché c’è un antro che se ne magna due.

This translates roughly (If I made a mistake, please correct me!) as: You know what statistics is? It’s something you use to make a general count of the people who were born, who get ill, who die, who go to jail, who get married. But for me the peculiar statistic is the one dealing with percentages, because then the mean always remain the same for everyone, even for someone who has nothing. Let me explain, from the way they count in statistics nowadays, it appears that you eat one chicken per year: and, even if you can’t afford to buy a chicken, you are part of the statistic anyway, because there is someone else who eats two chickens.”

I am not a statistician, far from it, but if my interpretation is correct, according to statistics if one person doesn’t eat a chicken but another eats two chickens, as in the example, that doesn’t mean that they have eaten one chicken apiece, which would be absurd. It simply means that ON AVERAGE the two people in question have eaten a chicken. “What’s the difference?, the end result is still the same,” you might argue, “that is, one of the two went hungry.” Okay, we’d have to ask an expert to deal with this issue any further. My point is another, though, and it’s not to demean the importance of statistics, which must take no notice of the individual in order to describe an entire population (etc.).

Trilussa’s assessment, in my opinion, has a lot of relevance for cancer patients. If I am still alive ten years or more (eh!!!) after my diagnosis, that three to four year Science Daily sentence is completely irrelevant…as far as I am concerned, naturalmente. So while I understand why we need statistics blablabla, I also think that survival percentages in particular can really freak out newly diagnosed patients. Unnecessarily so, in some cases. A few years ago, when I was still MGUS, I read heaps of statistics concerning myeloma and wasn’t too thrilled, to put it mildly. Who would be? But now I understand that there are simply too many variables in a population of cancer patients: age, stage of disease, even attitude (and now, as we just found out, HORMONE STRESS LEVELS!), etc. So I focus on the individual. Oh, and in this case, that would be yours truly, I suppose! 😉 My final bit of advice: ignore survival statistics and focus on your own healing!

Thanks to my fantastic friend Sherlock 😉 , I received a (complete) copy of the recently-published MD Anderson study on the bioavailability of curcumin, the one I mentioned yesterday in my EF24 post. I have been working on it off and on today but still have some figuring out to do. I should be able to post part of my interpretation tomorrow.

In the meantime, I would like to mention that Beth’s Myeloma Blog and Laughing Plasma Cells have reports on a new study on stress hormones and their effects (not good ones, as was to be expected…) on multiple myeloma. You can go to their blogs (see links on the right-hand side of your monitor) and also to this link, which will take you straight to the Science Daily story: http://tinyurl.com/2fd9ty I would like to highlight this paragraph: “In this latest study, the researchers looked at a different type of cancer €” multiple myeloma. One of several types of cancers of the blood, multiple myeloma strikes nearly 20,000 Americans each year, killing at least half that many annually. Patients diagnosed with this disease normally survive only three to four years with conventional treatments.” Well, thinking about those three to four years will certainly help lower our stress hormone levels…

All joshing aside, this study does give us even more of an incentive to get rid of the stress in our lives and laugh ourselves silly at least twice a day…if possible, of course. Interesting read. And it reminded me that I really must put together a post on how stress affects our IL-6 levels. Wait, it’s dinnertime ALREADY?!!! How did THAT happen??? Stress, stress, stress! Gasp! 😉 Okay, off I go, silly me, see y’all tomorrow!

This is my post number 200! WOW! 🙂 But, even more incredible, according to my blog stats, my blog readers have left me 457 comments. Thank you all so so much.

Thanks also for all the private and public get well wishes. In fact, I feel much better today, and the positive thing about this bug is that it attacked my stomach, not my lungs (my weak spot). And that means: no antibiotics! Yippee! So I am back to doing research today. And laundry. 🙁

Blog readers’ questions. Laughing Plasma Cells (hi!), the vaccine I had was the inactive type. I made sure of that. In fact, on Tuesday I obliged my long-suffering 😉 GP to read the entire list of ingredients on the box before I let him administer the vaccine. I also wanted to make sure it contained no mercury, in accordance with recent European regulations. It didn’t. I had the vaccine.

Sue’s question: I have not heard about the yucca studies (sounds interesting). I have instead heard about Turmericforce, made by “New Chapter,” but it has such a low percentage of curcuminoids that I cannot say if it would work or not, even at a high dosage. I would like to add that I do like New Chapter and am going to try its Zyflamend and Scutellaria Baicalensis. Let’s see, I have tried both curcumin capsules AND powder (mixed in fat). Not sure if I can say which works better at this point. The only thing I CAN say for sure is that curcumin capsules withOUT bioperine didn’t work for me. That doesn’t mean that they won’t work for other folks, of course, since we all react differently to the same exact substance. Curcumin capsules WITH bioperine kept me stable. So, you ask a tough question. Don (Myeloma Hope blog, see link on this page) took thalidomide, then curcumin, then adopted the very tempting (to me) kitchen sink approach. You might go to his blog and ask him the same question. If only I had all the answers…!!! Some day…perhaps!

My blog reader Donna wrote me a private message, telling me I could share her good news, which is that her numbers have improved. She writes: “My IgG went from 637 to 669, IgA from 23 to 26, and IgM from 12 to 13! Although these are not drastic changes, at least they are going in the right direction…for a change!” She has added super Bio-Curcumin and quercetin to her intake this month. Go, Donna! 🙂

Important note for UK chocoholics. Dora informed me of a new product called Choxi (you can google it for more info) made by the Queen’s chocolatiers (how about that?). It’s been flying off the shelves, but she informed me that you can order it directly from the manufacturers, too. Thanks, Dora. I’ll be looking for some Italian Choxi…

Curcumin bioavailability is a huge issue, which seems to be in the forefront of research on curcumin. Prof. Aggarwal, head of the curcumin research team at MD Anderson in Texas, recently co-authored a study (abstract: http://tinyurl.com/35w4mn) published in Molecular Pharmaceutics (November 2007) on this very topic. The abstract tells us that Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). I will probably, at some point, be able to read the full study, and will provide a full report here. I hope, soon.

Before I go on, I should mention that the proposal that my friend Ana and I become curcumin lab mice has failed. The fantastic Italian urologist who uses and studies and writes about curcumin told me it would be quite impossible. I knew it would be difficult, but doesn’t the saying go “if you don’t try, you will never know”? Precisely. So I tried. Well, that chapter is closed for now, at any rate.

Curcumin EF24 analogue. The same doctor told me about EF24, the above-mentioned synthetic analogue. According to a study published in 2005 in Anticancer Drugs (abstract: http://tinyurl.com/3acjyc), EF24 was found to be effective against breast and prostate cancer cells. Effective against, meaning EF24 induced apoptosis in those cells. Apoptosis! Yeah! Thanks again to my friend Sherlock (grazie!), I was able to read the full study. Nearly 100 curcumin analogues were studied and tested for their anticancer and anti-angiogenesis properties. EF24 emerged as the most active one. Compared to regular curcumin, EF24 showed a 2- to 10-fold increase in cytotoxic activity. According to the study, it effectively penetrates and induces apoptosis in cultured human breast and prostate cancer cells.

A more recent study, published in September 2007 in the Journal of Biological Chemistry, examines the anticancer effect of EF24 on cisplatin-resistant human ovarian cancer cells. It induces G2/M arrest and apoptosis in those cells, as you can read in the abstract: http://tinyurl.com/2csz63. It increases the levels of the tumour-suppressing protein p53. The acronym mentioned in the title, PTEN, is a gene that is essential for the creation of a tumour-suppressing protein. By the way, if you ever have to look up a gene and its functions, here’s a good place to start, methinks: http://tinyurl.com/2y9yea This link will take you to information specifically about the PTEN gene, but you can do searches on any other types of genes, such as p53. Anyway, the point is that EF24 increased the activity of PTEN.

I didn’t find any studies on EF24 and myeloma. Too bad. In the next few days, I will check out two more recent curcumin analogues and see if they have been tested against myeloma cells.

Well, so much for doing research or much of anything else today. Yesterday after work I went to get vaccinated against the flu, and by early evening I had developed a terrific headache. Then I became nauseous…and will let you imagine the rest. Mamma mia! Suffice it to say that I still felt icky enough to call my doctor this morning, thinking that I could have had a reaction to the vaccine, but he told me it sounded more like a viral thingie that is going around Florence and should last no more than 24 hours. Oh well, no biggie, then. I might have picked up this bug at Careggi hospital on Monday. Or perhaps even before then…drat, I hope it won’t interfere with my test results.

Anyway, even though by now (midday) I do feel better, I am going to stay in bed and watch movies and documentaries until Stefano gets home from work. Speaking of staying in bed, this morning three of my nursing cats were lying on me: Piccolo (all eight kilos of him!) on my chest, with his paws wrapped around my neck, purring loudly and batting his eyes reassuringly at me; little Peekaboo just behind him, purring on my abdomen, and Priscilla asleep on my legs. Now that would have been a great photo! But of course there was nobody here to take it.

Anyway, tomorrow I will be fine. This is just a little bug.

 Long day at work today, so I am pooped. Too pooped to be of any use whatsoever to the blog. Tomorrow I WILL finish and post at least one of my research pieces, though.

Thanks for the surgical mask suggestions. I don’t like to call attention to myself in public, but I might try that as an experiment IF my friend Ana wears one, too (se va bene a te, va bene pure a me!).

I must remember never ever to go to Careggi Hospital on a Monday. I arrived at 7 a.m., and there were already 85 people in line in front of me. Had I arrived at 8 a.m., that number would have risen to 140. But today waiting in line took forever. The nurses were very slow for some reason. It usually goes much faster. I got so sleepy that I even had to stop reading my P.J. Wodehouse (the Jeeves series!). Yawn!

The Careggi waiting hall, located in a building called “La Piastra” for some unknown reason (it means “slab” or “plate,” as in “iron plate” not “dinner plate”), is quite large, and there usually are enough seats for everyone. Problem is, unless you are a special case” (pregnant, e.g.), you are lumped in with everyone else. If my immune system weren’t compromised I wouldn’t mind, of course. But I am very aware of GERMS. I always choose my seat carefully, and if I hear the slightest sneeze or cough nearby, I stop breathing and move away. This morning the waiting room was filled with people with horrific colds and evident cases of bronchitis, coughing and snorting and blowing their noses and sneezing all over the place. All of this, right into their hands. Sigh!

Last night I should have had a proper meal with vegetables and fruit. But we had Sunday lunch at my in-laws’ and overate. Since a bunch of my girlfriends were coming over to play cards after dinner, I ended up making brownies (ah yes, brownies with SUGAR, from a Martha Stewart recipe!) and eating a few of those for dinner. With a glass of MILK! Oh, bad bad girl! I bet my glucose test result will be sky high. At any rate, it will be interesting to see if NOT eating properly the night before having blood tests will make any difference. 😉

Today is my Dad’s 80th birthday. I figured that having my blood tests done on his birthday would bring me excellent luck! HAPPY BIRTHDAY, DAD! AUGURI, BABBO! Ti voglio tanto bene! 🙂

Today is Bence Jones Day…for ME, I mean. Bence Jones is a typical multiple myeloma monitoring test. But before I get into the nitty-gritty, I would like to mention that this morning I actually looked up Dr. Henry Bence Jones, an English physician and chemist who, in 1845 or thereabouts (some websites say 1847), discovered the existence of the proteins that bear his name. His name is also associated with the first recorded case of multiple myeloma in history, which I thought was a fascinating little historical fact. And he was a friend of Charles Darwin. Oh, but I digress!

Anybody who has ever taken this test (everyone with MGUS or SMM or MM, for sure!) knows what this test entails, but here’s a quick and not overly detailed explanation for those who haven’t. The test measures the presence and quantity of the Bence Jones proteins, which are small abnormal monoclonal proteins (free light chains) made by plasma cells. Now, proteins, generally speaking, are too large to be passed by the kidneys, but these little buggers are small enough to pass easily and quickly from the blood into the urine. When our blood contains too many of these proteins, our efficient bodies filter them out via the kidneys. I should note that during this passage they can damage the kidneys. Not good. Earlier today I read different statistics showing that these proteins are present in 40 to 80 % of myeloma patients. Healthy people don’t have a Bence Jones problem, of course.

In sum, the Bence Jones test is an important one. I have it done twice a year or so, and so far the test has been negative (and I plan to keep it that way!). I should mention that this test is not painful at all (it’s not a bone marrow biopsy, ouch!), but it IS a bit of a drag, especially for women. Every time we pay a visit to the bathroom in a 24-hour period, we have to collect the sample in a large container. Oh, plus, the collected liquid needs to be refrigerated. Since I refuse to keep my urine in the fridge next to our milk and vegetables (!), I bought a cooler that I use for this purpose ONLY. Okay, I have mentioned the word urine enough for one day. Tomorrow morning EARLY I am having my blood tests done at Careggi hospital and should have the results in two weeks or so. My next experiment begins tomorrow or the day after tomorrow. I will post about it in the next few days, once I have it all written down. Of course, my eight grams of curcumin will still be in the picture, but probably in capsule form.

It’s been a long day, so this will be brief. On my way home from teaching, I stopped at the organic supermarket located near my neighbourhood in Florence (there are two of these supermarkets, actually, in addition to various health food stores not too shabby for a city with only about 400,000 inhabitants, eh?) and bought some gluten-free organic pasta. I decided to try out three different pasta brands. My first step in the direction of my 2008 gluten-free test. 😉

I have a follow-up to my toxic wrappings piece. It always thrills me to bits to find that things we use everyday without thinking twice could be killing us slowly perhaps but steadily. Indeedie! I recently became a member of Cancer Compass, and now receive its weekly newsletter. This week’s featured article just happens to be on, you guessed it!, the toxic chemicals contained in plastic products and even in the lining of food cans (drat, that means I will no longer be able to use organic cooked and canned beans! Major bummer, I will have to go back to the old time-consuming system of boiling beans for hours). There are toxic chemicals in CDs, DVDs, medical equipment and BABY BOTTLES. Baby bottles!?! Words simply fail me. Okay, to be honest, I am not THAT surprised sigh! My blog reader Cathy is sooo right. Use glass, avoid plastic. Period. You can read the Cancer Compass article here: http://tinyurl.com/2ogblf I did a quick check and found thousands of online references to the possible and real cancer connections of the main chemical discussed in the article, i.e., bisphenol-A. It’s been linked to breast and ovarian cancers, prostate cancer well, you get the picture. It’s one of those estrogen-mimickers that I discussed in my Curcumin and Pesticides Page, by the way. And, quelle surprise, Bisphenol-A is produced in massive quantities: six billion pounds a year. As usual, profit is the name of the game, no matter what the toxic consequences for us.

Well, thank goodness for gluten-free organic pasta, I guess.

To end this piece on a cheerier note, for the first time ever! my tall dark brilliant sweet and handsome husband left me a blog comment today. I just wanted to mention how thrilled I am. Un bacione! 🙂

Lots of people, perhaps most people!, associate specific songs with important moments in their lives. You see this happen all the time in movies: first dance, first kiss, first driving lesson, first camping trip, first stubbed toe, first whatever. Songs played at weddings are a typical example. Well, Stefano and I don’t have a specific song. Of course, we both LOVE music, from classical to jazz and so on, but our love story is not tied to any particular song. I do have, however, a specific song tied to a specific moment in my life: when I learned what MGUS really meant the potential consequences

At some point in 2003 my GP finally gave me a gentle but detailed explanation concerning the monoclonal component that had showed up in my bloodstream since 1999, informing me that my still-benign MGUS could some day progress to a malignant incurable cancer.

Malignant. Incurable. Cancer.

Well, I remember being very calm and collected when I received this lovely bit of news in his office. I asked him a few questions, took his written request for me to have a check-up at the Hematology Center at Careggi Hospital in Florence, thanked him as usual and left. I got into my car, turned on the radio, and burst into tears (I still get emotional when I think back to that moment). Just then, though, the radio station began playing a song by Cat Stevens called Father and Son. I began listening to the lyrics and stopped crying. I later read that it was a song about lonely childhoods and the Russian Revolution (not the Myeloma Revolution), but never matter. Here are the relevant, to me, lyrics (I took out several lines, e.g. find a girl, settle down etc.):

Father: It’s not time to make a change, Just relax, take it easy. There’s so much you have to know. I know that it’s not easy, To be calm when you’ve found something going on. But take your time, think a lot, Why, think of everything you’ve got. For you will still be here tomorrow, but your dreams may not. It’s not time to make a change, Just sit down, take it slowly. There’s so much you have to go through. Son: All the times that I cried, keeping all the things I knew inside, It’s hard, but it’s harder to ignore it.

I remember thinking that this song contained a lot of sound advice: take your time, think a lot, just sit down, think of everything you’ve got, it’s hard but it’s harder to ignore it, etc. The right song came along at the moment I needed it, and I remembered this little fact yesterday while listening to another Cat Stevens’ song on the same radio station.

This song helped me through a tough time. I won’t forget that. Take it slowly but don’t ignore it.

Back to my research, now!