I was awarded my Ph.D. from the University of Toronto, which means that I receive its (paper edition) magazine four times a year. Excellent magazine, I would like to add. At any rate, in the autumn 2007 issue I came across a bit of not-so-stunning (I suppose) information in an article titled A Bad Wrap. Scary stuff…

I quote: “A study led by two University of Toronto chemists has shown that potentially harmful chemicals commonly applied to food wrappers can make their way into the bloodstream. Earlier research has found that perfluorinated chemicals can migrate from wrappers into food. The new study by environmental chemists Scott Mabury and Jessica D’eon establishes that the wrappers are a potential souce of these chemicals in human blood. Professor Mabury, chair of the Dept of chemistry, and D’eon, a doctoral student, fed the chemicals to rats, whose blood was monitored daily. The chemicals appeared in the rodents’ bloodstream within four hours, which suggests a similar process could occur in humans. Researchers have not yet determined the impact of the chemicals on human health, but Mabury says the findings suggest more research is warranted. €˜I think our results do indicate that a broader look is necessary,’ he says, €˜especially when it comes to the potential for toxicity.’ ‘I think (regulators) have made three assumptions, says Mabury, ‘that the chemicals wouldn’t move off paper into food, they wouldn’t become available to the body and the body wouldn’t process them. They were wrong on all three counts.”

How about that? Ahhh, when I think back on all my university years spent eating chocolate bars and wrapped fast food whatnot ! Yikes!

Last week I came across and had just enough time to glance at an interesting article on the effectiveness of chemotherapy drugs administered at different times of the day when my computer crashed. (Don’t you hate it when that happens?) I lost the page reference and so far haven’t been able to find it again. Sigh. The gist, however, was that malignant cells are more susceptible to certain chemo drugs at different times of day. The reason I found this idea fascinating is because I wonder if it applies to curcumin and other non toxic substances. Well, why wouldn’t it? I clearly remember Prof. Aggarwal telling me that the best time to take curcumin is early in the morning. He didn’t say why, but I will ask him again, and I will see if I can come up with an answer on my own (not today, though, I have run out of time!). Also, one of my blog readers takes some of her supplements, I forget the details, late at night when cancer cells may be more vulnerable. I confess that this sounded a bit nuts to diffident and sceptical me when I first read about it, but is now beginning to make sense.

So even though this topic wasn’t on my to-be-researched-in-a-hurry list and I meant to post on an entirely different issue today, I woke up thinking that I would like to take a quick poke at it. It’s a grim day in Florence, so we are staying inside, a perfect day to do research. Well, truth be told, I should be straightening up the house, blablabla but that can wait. 😉

The first reference I found this morning was a well-written article in the online magazine Slate. I confess that this was the first time I’d ever heard the term circadian rhythm, no, not even in connection with jet lag, which is a typical example of disruption of our internal clock. The “Slate” article wasn’t the same one that I lost last week but it covers similar points, i.e. the best time of day to take a given medication” (see: http://tinyurl.com/267jrs). Even something that we imbibe almost without thinking, i.e. aspirin, is best taken in the evening, when it will do “less damage to the stomach lining” than in the morning. Did you know that? I didn’t.

The article continues: 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. How about that for a shocker? What if certain toxic or undesirable side effects from drugs, perhaps even from curcumin itself (some of my correspondents have reported diarrhea and stomach upsets, for instance), could be AVOIDED simply by modifying our supplement/drug-taking schedules? Why, that is absolutely BRILLIANT! And WHY doesn’t the FDA focus on such crucial issues? Well, the “Slate” article provides the obvious answer to that question: money!

I quote again from the article, a good easy read, I highly recommend it: Modern drug development generally assumes that the body maintains a stable internal state. To that end, many prescription drugs are designed to be taken in equal amounts at regular intervals to keep a patient’s drug levels steady. The problem is that a growing body of research suggests that our bodies are not constant. Instead, nearly every physiological process oscillates with our internal circadian rhythms. The body’s temperature, immune function, and hormone levels all partly depend on whether it’s night or day, or sometime in between. Meanwhile, many diseases also have daily rhythms, with symptoms more severe at certain times. The body’s sensitivity to time of day means that a drug proven safe to take in the morning may not be safe at night, or that a dose that works at 8 p.m. may be too small at 8 a.m. This would seem to support my friend Ana’s feeling that she should take her curcumin dose once a day instead of twice a day. Perhaps her circadian rhythm is telling her something. Okay, that sounds completely unscientific, but please read the above-mentioned article before jumping to conclusions.

I had the time this morning to find a couple of related and interesting studies. The first one, see full text: http://tinyurl.com/2anhv6, published in “Cancer Research” in 2003, is titled The Days and Nights of Cancer Cells. Need I say more? The second study, see full text: http://tinyurl.com/yp76f3, published in “Cancer Research” in 1977 (1977!), examines how leukaemic mice reacted to the administration of cyclophosphamide (Cytoxan) and 1-f3-D-anabinofuranosylcytosine (ara-C, for short)…at different times of day. It turns out that giving these drugs at different times of day produced different effects in terms of animal weight, toxic reactions and survival. For example, more mice (94% compared to 44%!) survived when Cytoxan was given to them in the late afternoon/early evening, leading to the conclusion that the optimal time to administer cyclophosphamide is around the transition from rest to activity (between 5 p.m. and 8 p.m. for mice kept in light from 6 a.m. to 6 p.m., alternating with 12 hr of darkness). For ara-C, however, the best time was 8 AM. For both drugs taken together, apparently the best time was 11 AM: after 75 days, in fact, 28% of the mice treated with both drugs at 11 AM were still alive. The study also tells us that drug toxicity was affected by circadian rhythms: mice that received Cytoxan in the evening had significantly fewer toxic reactions than those on the morning schedule, for instance.

In conclusion, and speaking of mice (poor dears!), I wish research would focus on important matters such as these instead of developing mutant mice that aren’t afraid of cats (did you hear THAT bit of recent news? A few days ago, it made the Italian national news, for crying out loud talk about research money going down the bloody drain ! Ahhh, che pazienza che ci vuole!!!).

I recently read a study with a very long title, The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the nuclear factor kappaB pathway in Chang Liver cells (!), published in the “European Journal of Pharmacology” in February of 2007. The abstract can be seen here: http://tinyurl.com/26yy5q I was able to read the full study thanks to a friend (grazie, Sherlock!). As usual, I would be more than happy to forward the study upon request.

First, what are Chang liver cells? The online Dictionary of Cell and Molecular Biology tells us that these liver cells are derived from non-malignant human tissue. Now, I don’t want to get involved in a detailed explanation concerning inducible nitric oxide synthase, or iNOS, which is beyond my purpose here, anyway (phew!!!). Let it suffice to say that iNOS is linked to inflammation, and anything that inhibits it is good news. We already know about COX-2 (see my “Ellagic Acid” and “Natural COX-2 Inhibitors” Pages for more info) and CRP, and of course the ubiquitous NF-kappaB. Ah yes, and kaempferol is a natural flavonoid found in tea, broccoli, grapefruit and other plant sources. On with the study, then.

On page 222 we read that Reactive C-protein (CRP) is an acute phase protein produced by hepatocytes whose serum elevation is considered as indicator of chronic inflammation and whose interaction with endothelial cells may be the mechanistic link between CRP and atherosclerosis [ ]. It is known that IL-6 induces CRP through a mechanism involving NF-κB [ ], but no study has until now documented potential effects of flavonoids on CRP expression in liver cells. Hepatocytes, by the way, are liver cells (for the more scientifically-minded, epithelial cells found in the liver that, among other things, have the function of helping to detoxify our blood).

Both quercetin and kaempferol reduce iNOS and COX-2: The present study indicates that both flavones reduce iNOS protein level in activated Chang Liver cells and that kaempferol was a slightly more potent inhibitor at low concentrations. COX-2 protein level was also reduced [ ] And, most importantly for our purpose, i.e., identifying substances that reduce CRP levels naturally: Our data show that both quercetin and kaempferol significantly reduce CRP protein level in liver cells and that this inhibition is concentration-dependent [ ]. SIGNIFICANTLY REDUCE? Well, I have been putting quercetin powder in my curcumin/chocolate mixture for other reasons (see my Bioavailability page for more information), but I am very pleased to discover that it may also be reducing my CRP levels.

The study ends: In summary, the present study indicates that the modulation of iNOS, COX-2 and CRP by quercetin or kaempferol may contribute to the anti-inflammatory effects of these two structurally similar flavonoids in the liver, via mechanisms likely to involve blockade of NF-κB activation. Sounds good to me!

Important aside. After reading this study, I must post a warning: at very high doses, quercetin MAY have some genotoxic effects, see http://tinyurl.com/2lzaw6. The words to keep in mind are may and very high doses. Low doses of quercetin are okay, and I have confirmed this elsewhere (see for instance: http://tinyurl.com/2uvbzt). I have been taking a maximum of two grams per day. Not much, so I am not in the least concerned and will continue to take my daily dose, but it reminds me that caution is the name of the game, as the saying goes. So, do your research…first!

Today I received an e-mail from a U.S. blog reader who would like, if possible!, to have curcumin capsules from two different sources tested by a laboratory. More specifically, he would like to have the capsules analyzed for volume/quality of curcumin and the quality/identity of other ingredients. Does anybody know where in the U.S. he might have this performed? Thanks!

Another blog reader pointed out (please read the comment she left me on yesterday’s post) that myeloma patients are currently discussing the possible connection between myeloma and celiac disease on the Cancer Compass message board. This is not the first time I have read about this connection, and I really hope my friend Paul will have time to post a comment about it. Another item goes on my to-be-researched-soon list! Here is the direct link to the celiac disease myeloma discussion: http://tinyurl.com/2cvftx Coincidentally, just the other day I became a member of the Cancer Compass website and now receive its newsletter! Well, well.

I would also like to point out Art’s experiment with a self-made curcumin patch, which you can read about in the comment section of my November 1st post. Thank you, Art!

I didn’t have time to do any research today. ARGH! I have two half-finished posts on the back burner that I should finish in the next couple of days, though. Oh, and I just couldn’t resist uploading a photo taken last night of Peekaboo on the kitchen counter, even though it has nothing to do with the title of this post. But I couldn’t resist: she looks so adorably triumphant, indeed, a bit defiant (along the lines of: “No, no, no, I won’t, I won’t, I won’t get down, and you can’t MAKE me!”)! Hehe. Time for dinner!

Life has been relatively easy until now. This morning, as I was preparing breakfast for my four hungry cats, I looked up with unfocused eyes (before coffee!) and noticed something amiss: a pair of inquisitive blue eyes staring back at me and a flash of white. A second, more focused look confirmed that my five-month-old kitten has finally learned how to jump up onto the ledge overlooking the kitchen counter. Until this morning, only the other cats have been able to make that jump. She looked as surprised as I was, so this must have been her very FIRST jump! A major jump toward adultcathood, I would add. I darted upstairs as excited as a squirrel with a nut to tell Stefano about it. I walked into our bedroom as he was getting ready to go to work and said, as gravely as I could: Life as we have known it is over. Things will never be the same again. I didn’t fool him. He replied, grinning She jumped onto the ledge, right? I married a very smart guy (how the heck did he guess?)

Of course, this means that we may have kitten-prints all over my Xmas cookies! Drat. 😉

Second important event. The company where I teach English is conveniently located near a farm cooperative that has wonderfully fresh organic vegetables. I frequently shop there before returning home. Well, yesterday I saw some pomegranates for sale. I had never eaten a pomegranate, imagine that!, so I bought one, which we ate after dinner last night. We really liked it, and I can see that the seeds would taste fabulous in a salad. Pomegranates, by the way, are full of ellagic acid. Good stuff!

Okay, I am working on a couple of research posts so I will get back to them now, but I just thought I would share two rather significant moments of my life with you: my kitten’s first big leap and eating my first pomegranate

Oh, wait, one more thing. A few more interesting comments have been added to my November 1st post, so please have a look at them if you are interested in the issue of curcumin bioavailability. The lecithin idea is compelling, but I still have to have a closer look at it. One thing: I will not eat uncooked egg yolks. I also went to and read the transdermal link that Art provided. Hmmm, also interesting. I think JHope already brought up the patch possibility. Well, thanks, everyone!

I tried to do some research and answer e-mails when I got home from teaching this afternoon, but my brain is fried. I can’t put two thoughts together. So I decided to get off the computer for what’s left of the afternoon. No point in pushing it. But first, I wanted to post this recent photo of my second youngest kitty, Priscilla. Since she is my parents’ favourite, the apple of their eye, this photo is for you, Mom and Dad! And, to be honest, right now I feel exactly like my sleeping green-eyed darling! Zzzzzzzzzzz! Well, tomorrow is another day…research can wait. Ok, time for my curculate!

Oh, before I go, though, I received a Google Alert for Scutellaria baicalensis (see my Scutellaria baicalensis page on the right for more info) that might be of interest to anyone suffering from gastrointestinal distress caused by ritonavir: http://tinyurl.com/3adof8

I have invented a new dish called “curcustrone.” 😉 Background of the “invention”: the other day I made a huge pot of minestrone, a very rich Italian vegetable soup with beans. Yummy, if I do say so myself. I use all sorts of vegetables, a few herbs and two kinds of beans (Italian cannellini and bortolotti).

Stefano and I like our minestrone mixed up in a blender because the tastes become more homogeneous, which explains why you cannot see any bits of carrot or potatoes or rosemary or spinach or sage floating on the top (photo on the bottom right). So what does minestrone have to do with curcustrone? Well, today, since I had to have a late lunch and didn’t have enough time to make my curculate (chocolate and curcumin) mixture, plus, to be honest, I was starving, I went ahead and mixed my curcumin and quercetin powders in a bit of olive oil (top left photo, before mixing), heated up a bowl of minestrone, and mixed it all together (bottom photo, showing the minestrone on top of the curcumin oil and beginning to turn orange). This time, I did remember to take a few photos. Not the best photos I have ever taken, but they give an idea of what this concoction looked like. I admit that it tasted a bit odd, but it was still very palatable, and it was a nice change from curculate. A good solution (I hope!) for when I don’t have much time to spare.

Well, I have been a bit lazy this long holiday weekend. Lazy in terms of doing my research and answering e-mails (sorry!), mainly. But today was such a glorious day that Stefano and I went on a nice walk up through the hills behind our street. The last time we walked up there was when it snowed in Florence…two years ago! Shameful. At any rate, we finally had to turn back and go home because of the icy slippery roads. I confess that I am one of those odd creatures that adores cold weather and simply goes bonkers over snow…

We live in a very nice neighbourhood of row houses built in the late 1920s and surrounded by hills, cypresses and trees of all sorts, olive groves and fields. It feels as though we live in the country, but we are just a few minutes away from a main busline that takes us downtown in about 20 minutes. It’s a wonderful area. Here are a couple of the photos I took earlier today. The top one shows a view of an olive grove and, if you look very closely, you can make out a bit of Florence in the background. The second photo is a view of the road we…climbed. Here we were about halfway up, or halfway down, depending on which way your back was turned. 😉

Blog reader notes. For my UK readers: please reply here or to me privately if you have an answer to Dora’s question (see my Curcumin Curcumin Curcumin! post). Thank you! And Val, I think he recommends curcumin with bioperine capsules, but am not 100% sure. I will ask him and let you know.

My MMA list friend left for Sorrento this morning. From there, she will visit Naples, the Amalfi Coast and Pompeii. She will be back in Florence on Tuesday. She planned this short trip, I think, in order to leave Stefano and yours truly alone for the long weekend. Very thoughtful of her! We don’t have anything romantic planned YET, but we will definitely do SOMETHING! After all, it is not too hard to be romantic in Tuscany…!

Back to my post title. I finally had the time to read, carefully, the comments on my October 28th post. WOW! Thank you, everyone. The comments were so out of the ordinary that I decided to write an entire post about them. Proceeding in order, more or less:

Eileen. Interesting abstract on the transfollicular delivery system, thank you. Well, well. Food for thought. Yes, the problem is how to avoid looking like a circus clown. Some time ago, I tried dabbing curcumin on my rosacea, which made me look as though someone had thrown bright orange paint in my face (the Sabinsa curcumin has an orange hue). This effect lasted for a few days, no matter how much I scrubbed my face. So I gave up on that plan, even though my rosacea did improve somewhat.

A perhaps (perhaps not!) related matter is that I have noticed that my tongue turns bright orange after I drink my curcumin powder mixture. I feel certain that my tongue delivers at least some curcumin to my malignant cells (even if that is not the case, I will continue to believe it until someone tells me otherwise). Not that I am an expert of Ayurveda or Chinese traditional medicine, but I do know that the tongue is very important and, after all, many conventional and alternative remedies have to be dissolved on or under the tongue. Ok, that’s beyond the point, here.

JHope’s comment: I have no idea! Anyone else?

Snezhi’s suggestion that we could make our own nasal sprays is also very interesting. I confess I do not have the know-how, but I would have no problem spraying curcumin up my nose, and I say this seriously, even though it might sound facetious. And hey, how about the nose hair follicles (see Eileen’s comment)? There you go, more food for thought…

Don: thirty-four GRAMS of curcumin??? At times I have gone up to almost 10 grams. Never beyond that. I cannot imagine taking more than 12, which is the most that, as far as I know, has been tested in Phase I clinical trials on healthy subjects. Perhaps there is more recent info on that, though. One word of caution: we do not know the long-term effects of such high doses (as the lab rats in Eileen’s household are taking). If I were on such a high dose, I would have all sorts of tests run every couple of months, perhaps even once a month, if possible. Speaking of taking massive amounts of curcumin, please read Wally’s brilliant comment carefully. If we can manage to make curcumin more bioavailable, we don’t have to take huge doses. Makes a lot of sense to me.

The matter of doses brings me to my friend Ana’s comment. She has just begun taking curcumin (e vai!!! 🙂 ), and has decided to take it in one large dose instead of two or three. Well, until quite recently, that’s precisely how I took it, whether it was powder mixed with a fat or curcumin with bioperine capsules. My counts remained stable and even decreased. So I say, whatever works for you, your markers and your daily routine…go for it!

Speaking of Ana, she and I have already discussed the idea of offering ourselves as lab rats to a doctor here in Tuscany who is doing a lot of research on curcumin, which he is using (successfully) with his prostate cancer patients. I haven’t talked about it here because I don’t know if it’s even feasible. But it’s well worth a try, perhaps two. I am going to get in touch with this doctor soon, perhaps even this weekend, to ask if he has access to a laboratory, and, if so, if he would be willing to set up a tiny trial testing Ana and me as well as our willing husbands (two healthy subjects). I may be able to get another Florentine friend with MGUS involved, too. I can provide the necessary curcumin powder or capsules, since I have plenty of both. My idea is that we could ingest different amounts of curcumin in different ways and at different times of the day, and then have our blood tested, obviously at different intervals etc. I will also approach my haematologist in Florence about this. Fingers crossed.

Wally is so right: we need this data. Soon. Now.

I haven’t had time to do any blogging in the past few days. No time for any research, no time to answer e-mails (for which I apologize!) or blog comments, etc. My to-do list is getting longer and longer. YIKES! I have simply been ignoring it. 😉 I have been busy, busy, busy, but away from my computer. I have spent a lot of time with my MMA list friend (fun!) as well as preparing my classes and teaching.

Tomorrow is a big Catholic holiday, called Ognissanti in Italian (All Saints’ Day in English, I think), and then we have a long holiday weekend, which I plan to spend with Stefano and also doing some research…finally! In the meantime, since today I again have no time to write a serious post, I just wanted to wish everyone a Happy Halloween! (P.S. The kitty in the photo is REAL: it’s my five-month-old Peekaboo! And no, even though it’s hard to believe, I didn’t put her there, I just set up my Halloween puppets, showed her how interesting that broomstick was, and she sat right behind ’em…my perfect photogenic model! Of course, a split second after I took this photo, she started chewing on the broomstick…) 🙂