Today I would like to continue quoting a message sent to me by one of my blog readers (the same who is quoted in my October 19th post) because I think it is tremendously important to understand what happens to curcumin once we swallow it. Not a simple matter, but my blog reader (thank you!!!) makes the process seem simple by using simple terms. Here goes:

The starting point to understanding the central issue of low bioavailability is to realize that curcumin is insoluble in water at pH of 7 and below. Therefore, in the stomach, where the curcumin first encounters body fluids, it remains insoluble because the stomach fluids are acidic. Once the stomach contents enter the small intestine they are changed to alkaline pH by the bile and other digestive fluids that are injected there. Curcumin is soluble in alkaline aqueous solutions at a pH of 7.4 and above and would dissolve in the small intestine. Then the curcumin molecules that are present only when a solution exists can enter the capillaries of the hepatic venous system that serves the stomach and the large and small intestines. Prior to solution, curcumin exists as small crystals or clumps of crystals that cannot pass through the tiny pores in the capillary walls–only molecules of curcumin can–thus the importance of having the curcumin in solution. However, it is found that in the stomach the curcumin is rapidly conjugated to curcumin glucoronide and curcumin sulfate, neither of which show any biological activity with the cells, as does curcumin. As a result, a considerably smaller part of the total ingested curcumin enters the small intestine, ready to be dissolved there. But some does dissolve and gets through the venous capillaries and then proceeds through the hepatic portal vein directly to the liver, where it undergoes “first pass metabolism” wherein more of the curcumin is converted to biologically inactive metabolites. All these hurdles must be surmounted before the curcumin gets a chance to circulate to the rest of the body to organs that might use it beneficially. The end result is that the measurable level of curcumin in the blood serum peaks very soon after a small two mg dose is given and only reaches a very low peak concentration.

Now consider the implications of these results for a person who takes that two gram dose of plain curcumin twice a day, approximately ten hours apart. Within the first hour after dosing, he sees a slight rise in his serum curcumin concentration, which blip then disappears within three hours, leaving nothing to supply to the tissues for the next seven hours. Then the same blip occurs after the second dose is taken, and some curcumin level exists for another three hours. So for about six hours total time there is some curcumin getting to the tissues and nothing for the other eighteen hours of the day. When developing a dosing amount and frequency for a medicine it is the objective to obtain an overlap between dose concentration peaks, so that there is drug available to the tissues for the entire 24 hours, even though the concentration changes as the drug is metabolized and excreted. It will be at the highest concentration shortly after taking a dose and will be at its lowest concentration shortly before taking the next dose. Two grams per day of plain curcumin simply will not give that desired overlap, and even curcumin with Bioperine will not do it either, because it also disappears within five hours. Only a much larger dose of curcumin taken together with Bioperine (or other means of enhancing bioavailability) is likely to achieve a continuous level of curcumin in the serum, though with peaks and valleys.

I hadn’t thought of the implications of curcumin crystals versus molecules before reading this message. A few things began to click in my brain. As I recall, my friend Don (see my October 25th post) takes curcumin at least three times a day. I try to take it twice a day, except on the days when I teach when it is difficult for me to do so. On those days, I usually take it in one big dose, all eight grams of it, when I get home in the afternoon. Now I realize that is probably NOT a good idea, and I will make some changes in my schedule so I always have a morning dose, too. The idea of keeping, or trying to keep, curcumin in the serum with overlapping doses makes total sense to me. After all, when we have a horrendous headache, don’t we take Tylenol or whatnot every four to six hours?

I was sort of dared to post my fuzzy puffin dot photos, so here goes! Enjoy! 😉

My MMA list friend is back from Venice, where she also experienced the thrill of high tide in St. Mark’s Square yesterday. Not much fun, but she was a good sport about it. She also returned with a cold and a cough, poor dear. Unfortunately, it rained during most of her stay. Bummer. Apart from those two things, though, she loved (how could she NOT???) and was overwhelmed by Venice. She told me that at one point she ran into a tourist who told her that she would be in Venice for just five hours and then would be leaving for another city on her tour group’s itinerary. I was appalled. Why bother going to Venice if you only have five hours? Just to be able to say: been there, done that? Well, five hours is better than nothing at all, I suppose…

Isn’t it just THE BEST to read great news first thing in the morning while you are sipping your cappuccino (or whatnot)? That is what happened to me today. I had a message from my friend Don waiting in my e-mail box, telling me to rush to his blog and check out his news. Well, well, it turns out that his most recent tests are very good if not excellent!, see: http://myelomahope.blogspot.com/2007/10/excellent-test-results.html Congratulations, Don! I will drink a sip or two of red wine in your honour this evening at dinner! 🙂

I have something else to celebrate. Yesterday morning my parents landed safe and sound in Boston. I am not celebrating their departure from Florence, of course, since it will be some time before I see them again (I hope, not TOO long!), but I do celebrate their safe arrival back home!

This has nothing to do with celebrations, but I wanted to mention that I tried a slightly different method of taking curcumin this morning: as usual, I dissolved four grams of curcumin powder in a bit of melted butter, then added melted dark chocolate. No milk, no cream. Well, the flavour of course was more intense compared to the milk drink, and the consistency was that of a rather liquid pudding, the kind that cooks might consider to be a failure 😉 , but it was certainly palatable. I forgot to take a photo.

Speaking of photos, yesterday I went to a friend’s website (a professional photographer) where I practically drooled over all his amazing photos of puffins. In response to my glowing fan letter, he suggested that Stefano and I go to Skokholm, a small island nature reserve off the south-west coast of Pembrokeshire, Wales. He also suggested a couple of other places. Last night, Stefano and I talked briefly about going to the UK for a week this summer, early summer, which is the best time of year to view puffins. This summer!?! That would be one of my dreams come true. You see, I am puffin-mad. Absolutely, completely mad! (No idea why, really, except I think these little birds are the funniest creatures I have ever clapped my eyes on.) Stefano is almost as obsessed as I am. Two years ago, we spent part of our U.S. summer holiday in Maine mainly to see puffins (Eastern Egg Rock, and off the coast of Acadia), but we arrived late in the breeding season, and most of these fantastic birds had left for the Atlantic. We managed to “see” a few, but they were nowhere near our tour boat so all that our photos show (when completely enlarged) are tiny fuzzy dots with an itsy bitsy dash of orange (the beak!)…very disappointing. Too embarassing to upload those photos here! 😉 I told Stefano back then that I wanted to travel to Wales to see one of the puffin colonies there. So 2008 may turn out to be our puffin year. Yes!

After days of rain and gloom, it’s finally what I consider to be a perfect fall day in Florence (earlier this afternoon I took the above photo, which shows part of the view we have from an upstairs window): a bit sunny, a bit cloudy, a bit windy, a bit chilly. Earlier this morning I went to the greengrocer’s to buy some salad, broccoli and fruit, and admired the leaves turning red and yellow. Not as spectacular as the New England fall (I was born in Massachusetts, and spent several years there, off and on), but pretty enough for me. Yes, it’s a very good day. For many reasons 🙂

I have an exciting announcement for all curcumin-takers with MGUS, SMM or MM! Please go to the Beating-Myeloma website (http://beating-myeloma.org/) and fill out the form for the Curcumin Patient Study! (See my September 7th post for a bit more information on this informal patient study).

Once you reach the B-M homepage, you will find the CPS listed under Patient Studies, on the left-hand side of your screen. Click on that link, and follow the directions. It’s easy. Only we have access to our data, so we can add updates whenever we get new test results and so on.

For some reason, today I had to scroll down the page to view the list of those (eight of us curcumin-takers) who have already filled in the form. So if you see a blank page, just scroll!

Anyway, in order to participate in the CPS, you must be a B-M member. If you are not, please sign up first (it’s free). As a member, you can also sign up for the forum/listserv, where discussions range from alternative to conventional and complementary myeloma treatments. It’s a very very very friendly group of myeloma patients (all stages) and MM patient caregivers, so I urge you to join.

If you are not a myeloma patient or are merely curious about curcumin and wish to view the study results, please click on this link: http://beating-myeloma.org/patient-study-results/

As David (the founder and owner of the B-M website) wrote in a post to the MMA listserv yesterday, this is not a rigorous trial but a collection or snapshot of mmers who take curcumin often along with conventional therapies like thal/dex or velcade. Experiences range from MGUS diagnosis changing to smoldering and IgG diagnosis in complete remission experiencing improving numbers…

While this is not a formal myeloma clinical trial, if enough of us participate we may gain some interesting and potentially important information about curcumin. So, whether your experience with curcumin has been positive or negative, please fill out the form. The more, the merrier!

My MMA list friend left yesterday morning for Venice. She will be back in Florence on Thursday. I would have loved to have accompanied her since I haven’t been to Venice in years, but I am teaching this week, oh well. Anyway, she is a truly wonderful person, and I feel as though we have known each other for decades instead of just a few days. Her visit has turned out to be a complete joy and has also been an eye-opener in many ways. I should mention that she is a professional therapist, and a very good one at that!, and perhaps that is why I find myself telling her things that even my closest friends don’t know. How does THAT happen??? Oh, and the funny thing is, she frequently doesn’t even have to ask me any questions. Words just start pouring out of my mouth. That’s never happened to me.

Today I want to write about one of those eye-opening discussions: feelings. Feelings, she said, are so rarely discussed on the myeloma listservs. I had never really considered that aspect of the myeloma puzzle. But she’s right: listserv members discuss treatments and symptoms and pain and so on, so why do we not discuss feelings on more than an occasional basis? The simple answer is, because it’s hard.

After giving the matter some thought, I have come to recognize that, when I do research, it is as though I am doing this for SOMEONE ELSE, not for me. I am not the myeloma patient when I don my researcher outfit. I become detached. Does this make any sense?

Perhaps my friend is right. Perhaps I keep my mind busy doing research so that I won’t have to deal with any feelings about myeloma. Even my blog, now that I think about it, may just be another way to avoid feeling. In my daily life I rarely think about myeloma, even when I take my curcumin twice a day. Sure, I visualize the malignant cells, but I probably don’t make the connection: those cells are PART OF ME. In fact, when I visualize them, they are outside my body. They have always been big slow hairy (no idea why I think of them as hairy!) stupid monsters that I slash and kill with my sword. Outside my body

This is a tough subject, and I am certainly not equipped to go into much, if any, depth, but it is also an interesting and perhaps very important one. My friend has given me lots of food for thought. At one point, she asked me if I had ever felt angry or if I ever feel angry, obviously in connection with myeloma. Angry? No, I answered immediately. How about sad, she asked? No, not at all. And fear? Well, yes, sometimes I do get scared, I admitted. Well, so what do you FEEL?, she insisted. I answered: I feel determined. But determination isn’t a feeling, she pointed out. It isn’t? Darn it, she is right. Merriam Webster defines determination as the firm or fixed intention to achieve a desired end. There is no emotion attached to determination (or is there?). So am I not allowing myself to have emotions about myeloma? But I DO have emotions, my brain protests. No, no I don’t, let’s be honest, not where myeloma is concerned. I have very few emotions surrounding myeloma. Of course, I strongly feel for and empathize with other suffering myeloma patients, but if I try to feel something for myself, I feel nothing. No fear, no anger, no sadness, no depression.

Final question for the day: are my cheerful attitude and quirky sense of humor simply a mask (in the sense of a Pirandellian mask)? I don’t think so, since I have been this way all my life, but I don’t know for certain. I have no definite answers, except that perhaps denial, if that is what it is, gives us a way of coping and trying to function on a daily basis. Perhaps it is not necessarily a bad thing…

Well, that’s it for now. Yesterday I discovered something new, so I have some research to do. 😉

When I signed up for two of the myeloma listservs more than a year ago, I met many wonderful people. Among them is a friend with MGUS, a curcumin-taker, who arrived Thursday in Rome. This is her first trip to Europe! She arrived in Florence yesterday and is staying with us. We hadn’t actually met until yesterday. Anyway, this is very very exciting!

After doing some sightseeing this morning, we returned home where I prepared my first curcumin mixture, my butter/curcumin/hot chocolate milk concoction. She tasted it and pronounced it very good. She was surprised. She thought it would taste terrible. She just told me, and I quote: “it tasted like pure chocolate, there was no aftertaste of curcumin.” I am quite pleased. 🙂

Anyway, we are busy, so I will stop here. More soon!

A blog reader recently sent me a fascinating message concerning the bioavailability of curcumin and his own experiments with curcumin. Since I believe that it is essential for us to be aware of what happens to curcumin once we swallow it, I would like to reprint parts of his message (divided into brief chapters). Here follow a few suggestions on how to dissolve curcumin powder. Some of these methods have been discussed on previous occasions:

I verified that curcumin will not dissolve in plain water, although if curcumin is added to water and then boiled it appears to dissolve. However, upon closer examination following cooling of the mixture it turns out that the clumps of curcumin crystals from the capsule were broken up by the agitation of the water and a suspension of fine crystals or tiny clumps of crystals was formed and its color and opaqueness suggested a solution existed. But then after time the suspended particles settled out, leaving essentially clear water and curcumin solids at the bottom. No curcumin actually dissolved.

Curcumin will rapidly dissolve in ethanol (ethyl alcohol) and in glycerine, which is a sugar alcohol, edible and sweet tasting. However, these two solutions will be digested differently than curcumin dissolved in the true oils, and are not the preferred way to get curcumin, in my opinion, as will be explained later.

But it is quite easy to dissolve curcumin in various edible oils. For example, curcumin from a 900 mg capsule would readily dissolve in one teaspoon (or 4 grams) of each of the following oils, with only a small amount of mixing: omega-3 fish oil, flax seed oil (which is another omega-3 oil), olive oil, canola oil, and clarified and warmed butter. In addition, curcumin from a 900 mg capsule would readily dissolve in one melted dark chocolate truffle, weighing 18.3 grams and containing 8 grams of fat.

Curcumin dissolved in the warmed butter and chocolate present some interesting possibilities in taking your curcumin. For instance, I spread the teaspoon of cooled but still softened butter/curcumin mix on a piece of toast and it was very delicious and just a little tangy. How about pancakes, French toast? Also, the melted chocolate/curcumin mix was poured into a flat saucer and hardened in the refrigerator, then cut up into small rectangles that could be saved and then later popped into the mouth and swallowed whole, without even chewing. Needless to say, the chocolate mix was very delicious while in the mouth.

All of the oils with dissolved curcumin can be readily swallowed by the teaspoonful and vary somewhat in their taste and palatability and feel in the mouth. I very much prefer the fish oil, because it is virtually tasteless and easy to swallow. I use Carlson’s Very Finest Liquid Fish Oil and buy it in 500 ml bottles, a case of 8 bottles at a time from Lucky Vitamins, Vitacost, or whoever has the best price at the time. Once opened, the bottle is kept in the refrigerator to prevent oxidation and development of a poor taste.

When my curcumin, which I buy from Swanson’s Vitamins, was mixed in all six of the above fats and other two fluids I noticed that there were tiny little residual grains of hard stuff that did not dissolve, like sand. But they could be crushed up with the back of a spoon into finer particles, which still did not dissolve. This affects the palatability somewhat when the mix is taken by the spoonful, because you feel these small granules in the mouth. This gritty stuff may be unique to the Swanson’s curcumin, which is the standard 95% curcuminoids blend of curcumin and the other two curcuminoids. But maybe that remaining 5% is stuff that the Curcuma longa plant makes that is not soluble in any of the tested oils and alcohols. But I never even noticed the gritty stuff when eating my curcumin/butter toast or chocumin chip.

My own observations: like my blog reader, I have been stumped by the sand-like grains that don’t dissolve. Since I use the C3 Complex Sabinsa curcumin, grittiness would appear to be a common feature of curcumin. I too tried crushing the gritty bits with a spoon, but soon realized that it was pointless. As my blog reader suggests, however, these grainy formations do NOT occur when warm butter is used. Dissolving curcumin in warm butter has another benefit: you can skip the double cream and use milk instead (fewer calories!), if you plan to drink the mixture. First, dissolve the curcumin in a bit of warm butter, not much at all, then slowly add the hot chocolate milk. Photo number 1 (above) demonstrates that curcumin dissolves perfectly in butter. No gritty remains. The second photo (here on the left) shows the end result, after the addition of hot chocolate milk. Both photos are a bit out of focus, I apologize. The second one doesn’t clearly show that the dissolved curcumin sort of floats on top, similar to what happens when you add a bit of oil to a glass of water. But I assure you that that is the case. By the way, in recent days I have been putting less chocolate into the mixture, which I find more palatable, oddly enough.

My concern about making chocolate lozenges would be curcumin degeneration. Heated up, then cooled in the fridge would that alter the healing properties of curcumin? No idea.

As for my reader’s suggestion to spread curcumin on French toast etc., my friend Don (see the link to his blog, Myeloma Hope, on the right-hand side of my homepage) tried adding curcumin to his morning oatmeal. Well, why not? I would dissolve the curcumin in a bit of butter first, then add it to the oatmeal. Since I love oatmeal, I may try that some day.

I never thought I would tire of eating chocolate. Ever. Chocolate has always been as crucial to me as the sun is to flowers, Chocolat is one of my favourite movies in the world (of course, it helps that Johnny Depp is one of the protagonists, and I adore Juliette Binoche), and as soon as I was old enough to handle hot ovens on my own I taught myself how to make and bake chocolate desserts. The words Margaret and Chocolate have always been synonymous…

A true and proud chocoholic. Until two days ago.

After two weeks or so on the chocolate/double cream/curcumin drink, twice a day, I am getting sick of chocolate. Sick of CHOCOLATE??? Moi??? Impossible! My own father didn’t believe me when I gave him the news this morning. He thought I was kidding, But Margaret, come on, it’s CHOCOLATE!

Sadly though, it is true. If you were to offer me a slice of chocolate cake now, I would say no, thanks. Nope, not even a slice of Chocolate Devil’s Food Cake or of that scrumptious heavenly flourless chocolate cake that I make and that nobody can resist.

From what I have read and been told, the exact same thing happens to those who work in chocolate factories. I always thought that would be a great job, because new employees are frequently given access to as much chocolate as they want. Now I know why: they get sick of it after a while!

Of course, this won’t stop me from preparing and drinking this chocolate mixture until I have my next set of tests. I can be quite stubborn. The moment I have my tests, though, no more chocolate for at least two months!

Writing this post reminded me that some time ago I came across a Chocoholic Page, which has some great quotes. Here are a few: “1. There’s nothing better than a good friend, except a good friend with CHOCOLATE; 2. I never met a chocolate I didn’t like; 3. A guy found a bottle in the ocean and opened it. Out popped a genie who said he would grant the guy three wishes. The guy wished for a million dollars, and poof! there were a million dollars. Then he wished for a convertible, and poof! there was a convertible [I would like to note that wishing for a convertible AFTER wishing for a million dollars was perhaps not a very smart move ]. And then, he wished he could be irresistible to all women… poof! he turned into a box of chocolates [hehe]; 4. A day without chocolate is a day without Sunshine; 5. Note of Advice: put “eat chocolate” at the top of your list of things to do today. That way, at least you’ll get one thing done; 6. Research tells us that fourteen of any ten individuals like chocolate.” Hehe, I like that last one.

Ok, I needed a break from molecules and genes and virus delivery systems. So today I looked up some fun stuff. These are supposedly real phone calls received by real computer help desks. If Stefano weren’t a computer genius, able to solve all of my computer woes, I might well be one of the customers on this list! Hehe.

Tech support: What kind of computer do you have? Customer: A white one…

Tech support: Click on the “my computer” icon on to the left of the screen. Customer: Your left or my left?

Customer: Hi, good afternoon, I can’t print. Every time I try, it says ‘Can’t find printer.’ I’ve even lifted the printer and placed it in front of the monitor, but the computer still says he can’t find it…

Customer: I have problems printing in red…Tech support: Do you have a colour printer? Customer: Aaaah…….thank you.

Tech support: What’s on your monitor now, ma’am? Customer: A teddy bear my boyfriend bought for me.

Customer: My keyboard is not working anymore. Tech support: Are you sure it’s plugged into the computer? Customer: No. I can’t get behind the computer. Tech support: Pick up your keyboard and walk ten paces back. Customer: OK. Tech support: Did the keyboard come with you? Customer: Yes. Tech support: That means the keyboard is not plugged in. Is there another keyboard? Customer: Yes, there’s another one here. Ah…that one does work…

Customer: Can’t get on the Internet. Tech support: Are you sure you used the right password? Customer: Yes, I’m sure. I saw my colleague do it. Tech support: Can you tell me what the password was? Customer: Five stars.

Tech support: What anti-virus program do you use? Customer: Netscape. Tech support: That’s not an anti-virus program. Customer: Oh, sorry…Internet Explorer.

Customer: I have a huge problem. A friend has placed a screen saver on my computer, but every time I move the mouse, it disappears.

Tech support: How may I help you? Customer: I’m writing my first e-mail. Tech support: OK, and what seems to be the problem? Customer: Well, I have the letter ‘a’ in the address, but how do I get the circle around it?

A customer called the Canon help desk with a problem with her printer. Tech support: Are you running it under windows? Customer: “No, my desk is next to the door, but that is a good point. The man sitting in the cubicle next to me is under a window, and his printer is working fine.”

And last but not least…

Tech support: Okay Colin, let’s press the control and escape keys at the same time. That brings up a task list in the middle of the screen. Now type the letter “P ” to bring up the Program Manager.

Customer: I don’t have a “P.”

Tech support: On your keyboard, Colin.

Customer: What do you mean?

Tech support: “P”…..on your keyboard, Colin.

Customer: I’M NOT GOING TO DO THAT!!!

Well, it seems that I may stand corrected. In my October 8th post on CD40, I mentioned my doubts concerning the possible use of a modified cold virus delivery system for myeloma patients, but yesterday morning I read a few items that, hmmm, may have changed my mind. I will proceed in order.

All plasma cells express CD40, but that is not the case with all myeloma cells. According to a 1994 French Blood study (see: http://tinyurl.com/ywcyv4), two-thirds of myeloma patients express CD40. That means that one-third are CD40-. By the way, in case you had any doubt concerning the importance of CD40 for myeloma, read this excerpt: …patients with progressive myeloma present a high level of CD40 expression.

Regardless of whether your myeloma expresses CD40 or not, though, the important concept contained in a 2002 Blood study (see: http://tinyurl.com/ytv929) is that we should be able to stimulate our immune systems to react against the malignant cells if we are able to deliver a transgenic (genetically modified, basically) form of CD40L (= CD40 ligand or CD154) to either type of myeloma cells, whether it has CD40 on its surface or not. The study ends: because our results show that the interaction with CD40 antigen on tumor cells is neither universal nor required for the immune enhancement mediated by transgenic CD40L, the molecule may be of therapeutic value in both CD40+ and CD40- forms of the disease. So all bases are covered. Excellent.

Now, if we connect this study with the modified cold virus theory, we may have a delivery system, a system that is being tested in clinical trials for other types of cancer right now. I am getting to the good part, hold on.

I did research for and wrote this post after reading two very interesting Ph.D. thesis abstracts (Baylor University). The first, dated February 2007 (abstract: http://tinyurl.com/yqwr6l), is titled Anti-tumor properties of CD40 ligand when delivered as a transgene by the conditional replicative oncolytic adenovirus AdEH to breast cancer cells (try saying that out loud without stopping to take a breath!). The abstract informs us that a potential limitation of CD40L therapy is systemic toxicity. The good news, however, is that this toxicity can apparently be overcome by using an adenovirus, which is essentially a virus that causes upper respiratory tract infections.

Ahhh, a modified cold virus, perhaps? 😉

I have requested authorization to read the full text of the second Ph.D. thesis, dated March 2007 and titled: Growth inhibition of human multiple myeloma cells by a conditional-replicative, oncolytic adenovirus armed with the CD154 (CD40-ligand) transgene (abstract: http://tinyurl.com/25dsdk). The abstract informs us that for targeted delivery of CD40L, we have constructed a conditional-replicative adenoviral for delivery of the CD40L transgene (AdEHCD40L). So here we have a sort of Federal Express delivery van, that is, an adenoviral delivery system. The van is supposed to deliver a “lethal package,” that is, a genetically modified form of CD40L, called AdEHCD40L, to its CD40 “customer” located on the surface of myeloma cells. The delivered transgene, our FedEx package, then inhibits the growth of CD40+ human myeloma cell lines. Simply put, adenovirus plus modified CD40L equals no myeloma cell growth.

I admit that I am becoming a bit obsessed with these darned molecules. When I was a child, many many years ago!, I used to spend hours putting puzzles together. The more complicated and the more pieces there were, the better. Well, this molecule business is like a big virtual puzzle. Every day I seem to come upon a new piece of the puzzle. I will, however, stop before my brain melts.

Not yet, though!