IL-17 and medical day: stability!

Well, the answer to yesterday’s question is as follows: yes, we can. Curcumin inhibits IL-17. Figures, huh? There are three (possibly more) studies that mention the IL-17-inhibiting role of curcumin. The abstracts can be viewed here: http://tinyurl.com/2rn3jy (a 2003 study), http://tinyurl.com/ynvkdj (a 2005 study). Thanks to Sherlock, I read the full study of the third abstract, a 2004 study published in “Cellular Signaling” and titled, get this: “Interleukin-17 signal transduction pathways implicated in inducing matrix metalloproteinase-3, -13 and aggrecanase-1 genes in articular chondrocytes” (see abstract: http://tinyurl.com/2lfy7t).

All these studies tell us that curcumin inhibits IL-17. Simple as that.

Haematologist appointment. Stefano and I went to see my haematologist at noon today. I asked her outright to classify me. She said that I am definitely not MGUS, no way. My IgGs are too high, and let’s not forget the 40% bone marrow biopsy result (from last year). So it’s official: I’m "smouldering," which means, among other things: "to exist in a state of suppressed activity." Heh. She examined my tests more in detail and pronounced me stable. Stable as a rock. So, all good news.

I asked her what the half-life of a myeloma cell is. She replied that it depends on a variety of factors, such as the type of myeloma and its proliferation rate. It can be calculated using cells from a BMB. She told me that a myeloma cell can live up to several months. MONTHS? Drat, now I am almost sorry I asked!

She confirmed that I am taking the correct amount of vitamin D. She also told me NOT to stop taking curcumin when I get a cold or an infection of any sort. Even though it inhibits NF-kB, she said that stopping cold turkey (odd expression, that one, when you think of it) is not a good thing. Good to know.

Let’s see. I am going down my list of questions and scribbles right now, not necessarily in order of importance. Oh, speaking of importance, this is exciting: I gave her the myeloma stem cell study (she had read the abstract, not the full study) and the DMAPT study, and she is going to find out about the DMAPT trial that should be starting soon in the UK to see if I qualify for it. She is going to contact the researchers that she knows personally. I am at a loss for words. Can’t wait to hear back from her. Gulp!

She is going to push the lab technicians to get more details on my “old” bone marrow samples, which would be fantastic. And, last but not least, she is going to try to attend the upcoming presentation in Calenzano, where I will be giving a brief speech. She is leaving for a conference in Turkey that evening, so it’s iffy. Even if she isn’t able to make it, however, she is sending five people from her lab to the presentation. Five? Fabulous.

Last but not least. For the first time, she wrote that I am stable "perhaps" due to curcumin. And that I should continue with the same treatment. (When my GP read those two sentences this afternoon, he got very excited.)

As we stood up to leave at the end of the visit, she asked me to explain why there are cases of myeloma in India, if curcumin is so effective. I answered that there are only a handful of cases compared to the Western world, and besides, I managed to add with a straight face, those folks undoubtedly didn’t use turmeric in their diet. My husband let out a snort, and she gave me a big smile and shooed us out of her office.  Hehe. I love my haematologist. Good sense of humour.

Yes, today was a good day.

Sherlock RULES!!!

Sherlock got her test results today. These are her pre-Biocurcumax results, by the way. Mine will be ready next week (we have different hematologists, so some of our tests are different, that’s the reason for my "delay," even though we got tested on the same day, i.e. the 8th of January). She authorized me to publish some of her more important values, but a little while ago we discussed the matter by phone and decided to wait until I get my results.

After we hung up, though, I decided, oh whatever, I just cannot wait until next week! I’m simply bursting with joy!!! So here are just a few details, and I will publish more of ’em next week after I get my results.

First, a bit of background: 1. she had never taken curcumin before and 2. she tested curcumin (C3 Complex) with bioperine capsules. I don’t remember every single detail about how she took the curcumin capsules, but, as I recall, she melted them in hot milk, adding a bit of chocolate to improve the taste. I will post more specifics next week.

Okay, now for a few numbers: her IgG decreased from 34.8 to 28,5 g/L (normal range: 7-16 g/L). That’s an 18% decrease from her previous tests (29th of October 2007). Nothing to sneeze at, for sure! This is her first IgG decrease since February of 2007; indeed, percentage-wise, she told me, it’s the biggest decrease she has had since 2002! Fantabulous!

Her M-spike went from 2,62 down to 2,24. It is now the lowest it has ever been since she started testing it in 2005.

She is absolutely thrilled, as you can imagine, and so am I, needless to say. When we spoke, I could hear the joy in her voice. Evvai, Sherlock! Sei grande!

My blog finally makes its debut…inside a castle!

This morning, due to an unexpected meeting, I had no time to reread the second part of yesterday’s post, which I won’t be posting until tomorrow or the next day. I would like instead to post about this morning’s meeting.

Background: almost exactly a month ago, I was asked by an Italian urologist (and blog reader), Dr. Roberto Benelli, to talk briefly about my experience with curcumin and my blog at the upcoming official presentation of his new book on curcumin and prostate cancer. I hesitated back then, because of fear of speaking in public. But after meeting with Dr. Benelli and one of the book presentation sponsors earlier today, I accepted. My little speech won’t last long, just ten minutes or so (that was one big thing that convinced me!).

This book presentation is actually going to be a sort of mini-conference, with brief presentations given mainly by local urologists, but also by a well-known oncologist from Florence and two molecular scientists. These scientists, one from Genoa, the other from Munich, will be talking about their work on breast cancer and curcumin. Anyway, the principal aim of this meeting is to present curcumin and suggest how it could be used in a medical setting. Dr. Benelli will present his new book, of course, and also give a separate presentation on the history of curcumin, its use in traditional Ayurvedic medicine and its potential applications in oncology today. I will definitely invite my GP and my haematologist.

It’s an open meeting, by the way. Here are the details, therefore, mainly for those blog readers who live in Tuscany: the meeting will be held in the castle of Calenzano (yes, a real castle! I am beginning to feel like a debutante  !), on March 8, 2008, at 10 a.m. To be more precise, it will be held in the Auditorium del Castello di Calenzano, Calenzano Alto (Firenze). The title of the meeting is “Modulazione del fattore NF-kB e prospettive terapeutiche.” My friend Sherlock will attend the meeting and plans to tape it in mp3, which I will try to post on my blog, at least some parts of it. If possible! Of course, the meeting will be in Italian, so hey, why put off studying this beautiful language? Sign up for some Italian classes today! 

Seriously, though, this should be very very interesting. If you are able to attend, please make sure you introduce yourself to me. I’d be happy to meet any blog readers! Ci vediamo l’8 marzo, spero!

MD Anderson Curcumin Myeloma Clinical Trial Results: Preliminary Comments

First, a blog notice: yesterday I sort of updated my "Curcumin in the News" and "Italian Curcumin References" links. My New Year’s Resolution number 2861 (!) is to keep these links a bit more updated, and the same goes for some of my more sadly neglected blog pages, such as the recipe one.

I was waiting to read the full MD Anderson report before discussing the curcumin-myeloma trial results here, but Chris’ comment on yesterday’s post, on top of all the private messages I have received to this regard, made me decide this morning to go ahead and write a post even though, I repeat, I don’t have ALL the facts and numbers. I will certainly have more to say on the topic as soon as I read the full study, which hasn’t been published yet. In the meantime, for what it’s worth, here goes!

Oh, before proceeding, though, I wanted to mention that you can view Prof. Aggarwal’s ASH presentation on the International Myeloma Foundation’s website: http://tinyurl.com/yw4m7y One important thing he points out is that, even when as little as TWO grams of curcumin were administered to some of the myeloma patients in the clinical trial, after four weeks a downregulation of the evil (I added the "evil" part) transcription factor NF-kappaB was observed. After 24 weeks, no NF-kappaB could be detected in some of these patients. Not even a glimpse. And they were taking only two grams. How about that?

Prof. Aggarwal also says that cancer treatment requires the inhibition of more than a single pathway, which makes curcumin an ideal agent since it inhibits several different pathways involved in cancer progression. A key sentence: “Although this study was very interesting and we did find the downregulation of various markers for cancer in MM pts, no objective responses were noted. So, in the future, I think that it would be interesting to combine curcumin with some of the existing treatments.”

A few introductory comments of my own: we know from the huge number of studies published on curcumin that this biologically active compound has extraordinary anticancer properties in vitro. Frequently, however, extraordinary properties do not work as well, or indeed at all!, when applied in vivo. It’s one thing to inject curcumin directly into some cancerous cell cultures, quite another for us to swallow a capsule or pill and hope that eventually our myeloma cells will be blasted by enough active curcumin. As we know, when taken orally, most of the swallowed curcumin gets transformed into (probably) less powerful, perhaps even useless metabolites (first-pass metabolism etc.). The issue of bioavailability pops up, again.

So the big question is: how do we get enough still-active curcumin delivered right smack into our cancerous cells? Eh. Still working on that!

ASH abstract. Thanks to the kindness of someone who sent me the abstract presented by the MD Anderson curcumin myeloma trial researchers at the American Society of Hematology (ASH) meeting held in December 2007, I was able to read some of the preliminary clinical trial data. Jan 15 UPDATE: here is the link to the abstract: http://tinyurl.com/26mjb7

The abstract tells us that the MD Anderson clinical trial (which is still recruiting patients, by the way) consisted of 29 myeloma patients with asymptomatic, relapsed/refractory, or plateau phase disease. They took curcumin capsules without bioperine, 2, 4, 6, 8, or 12 grams/day in two divided doses, OR curcumin capsules with bioperine, 10 grams, again twice a day. The abstract tells us that “At least 6 pts are enrolled at each dose level; 3 on the curcumin arm and 3 on the curcumin + bioperine arm.” Conclusions: “Of the 29 evaluable pts treated so far, no objective responses have been seen. Twelve pts continued treatment for more than 12 weeks and 5 (1 patient at 4 grams, 2 pts at 6 grams, and 2 pts at 8 grams dose levels) completed one year of treatment with stable disease.”

Key words: “stable disease.” These patients remained STABLE. My glass is half full, not half empty. Always. 

Most of the people with whom I have corresponded privately have focused on the “disappointing” trial results, that is, not one of these myeloma patients experienced a decrease in her/his myeloma markers. But that is precisely what I expected since my own results from my capsule experiments have been similar. So I am not disappointed. Not at all. Sure, it would have been great to see a decrease at least in one patient since I (myself) did experience a fluky IgG decrease in September of 2006 that may or may not be ascribed to my curcumin capsules with bioperine intake (update: my parents pointed out to me that the way I worded this last sentence makes it seem as though my September 2006 IgG decrease has been my ONLY decrease to date. That is not the case, of course. I have experienced decreases  while taking curcumin powder. So I thought I should clarify that I was referring to capsules here). I say "fluky" because at the time, pre-blog era, I wasn’t keeping good records on my intake, and when, months later, I repeated the capsule with bioperine experiment my results were stable, that is, there was no decrease. Hmmm.

Well, anyway, in my view, the following trial results are even more important than disease stability (which is important enough!): “Oral administration of curcumin significantly downregulated the constitutive activation of NF-kB (at 3 months a median reduction of 77%, p<0.0001) and STAT3 (69%, p<0.001), and suppressed COX2 (66%, p<0.0001) expression in most of the pts at each of the monthly time points.”

Check out those percentages! Accipicchia! Excellent! This means that curcumin is able to inhibit all the overly active transcription factors that make myeloma cells proliferate…and this happened IN VIVO! That is, in spite of its low oral bioavailability, curcumin was still able to inhibit these bothersome pathways in myeloma patients. In vitro translates to in vivo. That result is not at all disappointing but very very exciting. To me, at least. Oh, I can’t wait to read the full report.

Curcumin won’t cure myeloma (or perhaps it could, but it would have to be injected directly into each cell, I am afraid…), but if it can keep me and others, I hope!, stable or even decrease my/our counts until someone finds a way to exterminate the cancerous STEM cells (DMAPT trial, where art thou?), well, that’s fine by me. As Earl (Beth’s blog reader, see yesterday’s post) wisely declares, “always believe you can do it…if you think you can, you can…if you think you can’t, you can’t.”

I think I can.

Blood Tests and A Good Story

Sherlock and I had our blood tests done today up at the main hospital in Florence, as usual. My cocoa mass/curcumin powder, Scutellaria baicalensis and Zyflamend experiment has officially ended. Funny thing is, I just realized that I am going to miss my powder concoction at the end of the day! Oh well. I get these test results back on January 31st, which is rather late, but that’s because I also got tested for celiac disease, a test that requires special consideration.

Today the BioCurcumax experiment officially begins. BioCurcumax is, allegedly, a more bioavailable form of curcumin manufactured by an Indian company called Arjuna (you can read a bit more about it on my Bioavailability page). It’s basically curcumin mixed with essential oil of turmeric (curcumin mixed with a fat). We shall see!

Anyway, this morning, in between dodging the coughs and sneezes of others while waiting to have our blood drawn, Sherlock and I discussed exactly HOW we would conduct this experiment. We decided the following: I will take it in two doses of 4 grams each, whereas she will take it in one big gulp. We decided it would be interesting to take it in different ways rather than the exact same way, which was our other option. We will continue to take quercetin, but I will switch to the capsule form.

Today we start with 4 grams of BioCurcumax. Tomorrow, 6 grams. On Thursday we will go up to the full 8-gram dose, which we will take until early March, then we will have blood tests repeated.

So, as things stand today, this will be my protocol for the next couple of months:

Quercetin capsules with bromelain: 1.5 grams, 10 minutes before taking curcumin.

BioCurcumax capsules: 8 grams, divided into two doses, on a empty stomach.

Vitamin D drops, cholecalciferol, oil-based preparation: 2500 IU per week.

Freshly ground flaxseeds added to my food.

A multivitamin on occasion, with mostly B vitamins.

As time goes on, I may make a few minor changes. If that happens, I will post about it here. The main difference between my intake and Sherlock’s is, as I mentioned, that she will take the daily dose all at once. She will also continue to take vitamin C, which I do not take except as part of an occasional multivitamin. That’s it, for now.

A good story. Beth told me about one her blog readers, Earl, who is treating his precancerous prostate condition with…well, go see for yourselves: http://tinyurl.com/3dfc8g My hat’s off to you, Earl! 

Curcumin Dreams And Culinary Tips

I am about to begin poring over a handful of studies on general bioavailability (sigh), but I am a bit sleepy this morning and my coffee hasn’t kicked in yet, so I thought I would share a few recent odd discoveries with y’all.

Dreaming background: I have only on extremely rare occasions in the past been able to remember my dreams. At times I might wake up with a start after a particularly bad nightmare, but I would remember very few details. And if anybody asked me right then and there what the nightmare was about, I would be hard put to answer. This has changed in recent times, it would seem.

I don’t remember exactly WHEN I became aware of this new phenomenon, but I now remember my early morning dreams. I mean, EVERY single one! I now I wake up with a sort of clear “dream movie” in my brain. I remember details, colours, language spoken (I dream in at least two languages!) and so on. How long has this been going on? I am not sure, but my best estimate is: for about a month.

Another point. I think that most people would be able to relate to the following: even when you wake up remembering a dream clearly, this memory starts fading straight away, and if you don’t tell someone or write things down immediately, you will forget everything, no matter how hard you may try to recapture the moment later on in the day. Well, right now I can remember the dream I had before waking up…more than two hours ago, although, yes, the images are beginning to fade.

Only yesterday did I think of a possible connection between remembering dreams and my sublingually-absorbed curcumin mixture.

Could curcumin be affecting parts of my brain that are normally not “awake”? Could that be possible? Is there any other explanation? Are there any brain cell experts among us who could clarify this point, or tell me that I am simply…dreaming things?

Culinary Tips: yesterday I read a Science Daily article on boiling broccoli (see: http://tinyurl.com/3xzq59). Since you can go read the article for yourself, I won’t go into any details, but, in two words, a just published Italian (YEAH!) study has shown that some cooking methods actually seem to increase the release of certain nutrients contained in vegetables, which is contrary to conventional wisdom. I did know that cooked tomatoes have a higher content of lycopene compared to their raw counterpart, but broccoli? Apparently, if you steam (NOT boil, mind you) broccoli, you increase “its content of glucosinolates, a group of plant compounds touted for their cancer-fighting abilities.” How about that? I am very glad to learn this, since Stefano and I love steamed broccoli, which we eat the Italian way, almost as a hot salad, adding extra virgin olive oil, raw chopped garlic, lemon juice and a bit of salt.

Another titbit I read yesterday, and that someone actually told me about during the Xmas holidays, is that crushing garlic before cooking with it reduces the loss of its healthful properties. I found a February 2007 Science Daily article on this: http://tinyurl.com/2zu9v3 If you cook garlic whole, you lose a lot of the healthful compounds. But if you crush or even chop it before cooking, you release an enzyme called alliinase “that catalyzes the formation of allicin, which then breaks down to form a variety of healthful organosulfur compounds.” Crush garlic and then wait at least ten minutes before cooking with it, to give this enzyme enough time to work.

This is not a new discovery, eh. A study reported in 1998 (see: http://tinyurl.com/27hh3f) showed that garlic loses its anti-cancer characteristics if roasted for 45 minutes or cooked even just for one minute (!) in a microwave oven. But the good news is that “Garlic’s anti-cancer activity was retained, however, if the herb was first chopped or crushed and allowed to stand for 10 minutes before being heated. In the case of roasted whole garlic, anti-cancer activity was partially retained if the top of the bulb was sliced off prior to heating.”

Interesting stuff. Since I eat a lot of garlic, from now on I will crush it, just as my favourite British chef Jamie Oliver ("easy peasy!") does. Okay, back to my bioavailability studies. If I find some pearls of wisdom, I will be sure to report them here…tomorrow!

Curcumin and Angiogenesis

Again, happy holidays to everyone! I have been busy busy busy, not with research but with family and holiday-related engagements. But I did have time this morning to take a quick look at a study dealing with curcumin and angiogenesis, and will attempt to present some of its findings. Quickly, since I have some folks downstairs waiting for me to join them for a card game, hehe!

A blog reader (thank you!) recently sent me the link to an article (see: http://tinyurl.com/36aaem) about a study (see abstract: http://tinyurl.com/ysyq4y)  published in the October 24 2007 issue of the “Journal of Cellular Physiology.” The study is titled “Opposing effects of curcuminoids on serum stimulated and unstimulated angiogenic response.” In a nutshell, a group of researchers from the University of Kerala, India, discovered that curcumin promotes the formation of blood vessels in HEALTHY cells. This may not sound so amazing, but it really IS, when you think about it, because their finding confirms the fact that curcumin has the ability to distinguish between healthy and cancerous cells. Curcumin provides a supply of blood to normal cells whenever they need it but cuts off that same supply to nasty cancer cells. This may appear to be contradictory, but the Kerala researchers, as we will see, may have found an explanation. And their finding may be important not only for the treatment of cancer but also of ischemic conditions where there is a shortage in blood supply and, consequently, of oxygen.

The Kerala study (the full text was sent to me by another blog reader, thanks!) begins with an explanation of angiogenesis, which “is the formation of new blood vessels from preexisting vessels. […] Physiologically, it plays an important role in wound healing and ovulation. Nevertheless, uncontrolled angiogenesis results in many pathological conditions.” Indeed!

Curcumin applied to wounds caused by radiation has strong healing properties. An interesting aside: while I was doing research for this part of the post, I came upon a 2007 study (http://tinyurl.com/2ahqmg)  showing that curcumin has both radioprotective AND radiosensitizing properties. How about THAT? So curcumin will protect our healthy cells from the harmful effects of radiation while enhancing the murderous effects of radiation on cancer cells. At the exact same time! Extraordinary. That is why it might be very useful in the radiotherapy treatment of cancer, the study suggests. Well, I already knew about the radioprotective effects of curcumin, and now in fact I am not at all nervous about having my annual skeletal exam, but not the radiosensitizing effects. Curcumin never ceases to amaze me!

A 1999 study (see abstract: http://tinyurl.com/2fs5bw) showed that curcumin both when taken orally and applied topically improved wound healing in diabetic rats and mice.

The above-mentioned Kerala researchers point out that it seemed contradictory for curcumin to have wound healing properties when it is also has these anti-angiogenic properties. So they focused on the cellular microenvironment to see if it had “any effect on the angiogenic potential of curcuminoids.” Well, it does. This was a difficult, very technical study for me to read (the abstract will give you an idea…), but the following is more or less clear: curcuminoids stimulated the expression of proangiogenic factors when there was no extracellular stimulation (of an angiogenic response) by serum or proangiogenic growth factors, whereas, in the presence of those stimuli, curcuminoids appeared to be anti-angiogenic. Okay, perhaps this is not clear at all, now that I reread it! Well, basically, depending on the presence or absence of serum or certain growth factors, curcuminoids help normal cells live happily ever after, but they can also kill cancer cells by cutting off their blood supply.

This study gives us another example of the wonderful dual nature of curcumin, able to distinguish between the good and the bad guys. Yeah!

My Cocoa Mass And Curcumin Recipe In English And Italian

Yesterday I went to see my family doctor, who was absolutely thrilled to see my most recent test results. Almost as thrilled as he was to get a big bag of my Xmas cookies, hehe. And some Slitti chocolate. Oh, I just have to fly my own kite for a second: he told me that MY cookies are the best he has EVER had. Ever!  Anyway, he wrote down my chococumin recipe and also asked if I had posted about it on my blog. Since I couldn’t remember the exact date and am too lazy to look it up, I decided to post the recipe again. It’s not even a real recipe, since I don’t measure anything!

Anyway, here goes (I will translate this into Italian, too, see following paragraph): I use one and a half or two small squares of cocoa mass, or 100% chocolate (not cocoa powder, mind you). Cocoa mass looks like a regular chocolate bar, and you don’t need but a small bit. I melt it over very low heat, but you could use a double boiler, if you prefer. I add a couple of heaping teaspoonfuls of dark organic honey, otherwise it’s too bitter to swallow, in my opinion. As soon as these two ingredients have melted (be careful not to burn the mixture, as I have done a couple of times in the past!), I take the pan off the stove and add two grams of quercetin powder and my eight grams of C3 Complex curcumin powder. Stir quickly and eat the mixture even more quickly since it has a tendency to harden. Important note: I put small blobs of it under my tongue, where there are a TON of blood vessels. My idea is to get the dissolved curcumin into the bloodstream without much ado. It would seem that this approach works, which is why I am SO curious to see my next test results.

Ricetta in italiano: prendere un quadratino e mezzo oppure due (dipende dalla grandezza; ad esempio, se è pasta di cacao Slitti ne basta uno e mezzo; se è Domori ce ne vogliono due) di pasta di cacao. Mi raccomando, che non sia cacao in polvere (non so perché, ma mi dà l’idea che funzionerebbe peggio), ma pasta di cacao, che assomiglia alle tavolette di cioccolato normali. Praticamente si tratta di cioccolato al 100%, senza zucchero insomma. Aggiungere due cucchiaini da té stracolmi di miele biologico, il più scuro possibile (tipo, castagno). Scioglierlo a fuoco bassissimo oppure a bagnomaria. Attenzione a non bruciarlo sennò fa veramente schifo (lo so per esperienza, eheh!). Aggiungere due grammi di quercetina in polvere e otto grammi di curcumina, sempre in polvere. Io uso la curcumina C3 Complex. Una volta sciolto e mescolato il tutto, ne metto un po’ sotto la lingua e lo faccio sciogliere piano piano. L’idea è che da lì entra velocemente in circolo nel sangue senza passare per lo stomaco e l’intestino dove viene aggredito in malo modo da diversi enzimi. Ultima cosa: siccome questa specie di pastone cioccolatoso si indurisce rapidamente, bisogna mangiarlo velocemente e, soprattutto, mentre è caldo.

Back to English. I am busily finishing research for a post and have other errands to run. Busy days, these! I apologize to those who have sent me messages and who are not receiving a reply. I do read every single message, but I probably won’t get to answering any of ’em until Sunday or so. Ok, off I go! Poof!