Bioavailability of curcumin

There are several studies online about curcumin’s low bioavailability, which means that most of what we swallow goes directly into our gastrointestinal area and is expelled. Very little remains in the bloodstream about an hour or so after ingestion. However, it is possible that the small amount that does get absorbed is enough to induce apoptosis of the MM cells. Otherwise, curcumin wouldn’t have worked in my case.
 Curcumin is not soluble in water, but in fat. When dissolved in fat, curcumin will go directly into the lymphatic system. On the Grouppe Kurosawa website (www.grouppekurosawa.com) there is a lot of information on the bioavailability of curcumin, such as the following: The lymphatic system bathes all the cells in the body. It also bypasses the liver in what is called the first pass phenomenon. This means that more curcumin gets into the body to interact with cancer cells. Some more scientifically-minded MM listserv members have disputed this, writing that fats do not by-pass the liver. They travel from the stomach to the intestine, where they are digested, and the digestion products travel from there to the lymph, then to the blood, and then to all organs of the body, including the liver. But that’s fat. Curcumin isn’t fat.
 The fact remains that my Ig count decreased or remained stable on my coconut milk (fat)-curcumin powder drink. So, whatever the mechanism, some curcumin had and has to be reaching my malignant cells.
 For several months I mixed curcumin powder with a fat. I tried everything from coconut milk to flaxseed oil. The problem arose when I began feeling nauseous just at the smell of coconut milk heating up on the stove. That’s when I tried mixing curcumin powder with flaxseed oil. The taste was more than I could stand, but for a few weeks I managed to swallow this concoction, too. But then I joined the two main MM listservs. And began experimenting.

MMA Support mailing list and Acor MM listserv

In November of 2006, I joined the MMA Support mailing list. Later that month I joined the Acor MM listserv. I posted my curcumin experience on both lists, and began receiving dozens of private e-mails, mostly from people who wanted more information about curcumin, but some were from curcumin-takers. I learned a lot from them. Nobody mixed curcumin powder with a fat substance. I was the only one. And all had had positive results from curcumin. So I decided to test curcumin capsules with bioperine for a couple of months. I chose the same curcumin that is being used in the MD Anderson clinical trial, the C3 Complex made by the Sabinsa Corporation.
 I began my capsule experiment in January and expect to take my blood tests at the end of March 2007.
 Some curcumin-takers advised me to take curcumin capsules together with fish oil or flaxseed oil capsules. Aha, the fat needed for curcumin to be absorbed!
 A month or so ago, an Acor listserv subscriber posted a study called the Delano Report, which suggested that quercetin, a flavonoid found in apples, onions, red grapes, citrus fruits, broccoli and so on, would inhibit the sulfotransferase enzymes which render curcumin relatively inactive (for more information, see the Delano Report at: http://tinyurl.com/yyucfp ). As a result, I now take between 1 and 2 grams of quercetin 15 to 30 minutes before curcumin.

Bioavailability update. September 10 2007 post. A blog reader recently posted a comment, with an attached abstract, on this topic, which for obvious reasons is of utmost importance and interest to me and to anybody else who takes curcumin. The abstract (http://tinyurl.com/2t73w5) reports that the bioavailability of curcumin is enhanced with HEAT. Key sentence: We report here that the water solubility of curcumin could be increased from 0.6 μg/ml to 7.4 μg/ml (12-fold increase) by the use of heat. A 12-fold increase in water solubility? That’s nothing to sneeze at. These researchers also found [ ] no significant heat-mediated disintegration of curcumin. Well we certainly do NOT want curcumin to disintegrate, do we? Now, I already knew that curcumin dissolves in fats (I have seen that happen with my own eyes) and I have read that it dissolves in alcohol (bring on the vodka, hic!), but heat? And then, boom!, it hit me. When I first started taking curcumin, I mixed the powder with very warm, but not boiling, coconut milk. At that time I hadn’t even heard of bioperine nor was I taking any oil capsules. I had simply read that it was best to take curcumin powder mixed with a fat. I drank this concoction for months. And by the way, after the first eight weeks my IgG count went down almost 20 %.

Consideration. As I have said before, curcumin is not water-soluble. However, recently another blog reader commented that she mixes her curcumin with heated organic whole milk. She wrote that one day she ran out of milk but managed, eventually, to dissolve her curcumin in hot water. Well, so this heating curcumin business may make sense after all. Another consideration: back in May I wrote a post on a study (http://tinyurl.com/2fh26z) that examined the degradation of curcumin when heated up. I reread it yesterday and found that curcumin was affected after being boiled in water for ten and twenty minutes. Well, no worries, then. I don’t plan to BOIL my curcumin as I do pasta, not even for a few seconds, but just heat it up enough to make it more bioavailable. And that leads to the obvious question: how much is enough ? Ok, NOW I’m in trouble!

While looking for material on this topic, I came across an interesting Dutch website called Food Info Net, which is (and I quote): an independent joint project, initiated and run by Wageningen University (the Netherlands) in co-operation with several other partner universities in Europe. The site is non-commercial and all responsibility on content and lay-out is with the university partners. Hmmm, interesting. I will go back at some point and have a look at the various sections on food allergies etc. At any rate, Food Info has info on curcumin (http://tinyurl.com/ywf75z), as follows: Curcumin is light sensitive but stable at temperatures used in food processing. So, that is reassuring. It would appear that heating it up for a few seconds wouldn’t alter its properties. Or would it? My final question is: should we try taking curcumin mixed in, or simply accompanied by, a cup of hot milk? I knew I should have been a Science major. Drat. Well, the search continues.

September 29 2007 post. A blog reader recently wrote me a fascinating (private) message. With his permission, I am posting parts of it (it’s a long message, so I had to edit it a bit). This is a brilliant presentation of the bioavailability of curcumin with a few interesting suggestions on how to increase it: Biocurcumax is giving us curcumin that is predissolved in 10–15% oil by weight. Isn’t that what I am doing by mixing curcumin with full fat yogurt: predissolving it before ingesting it? Could it be that those of us who predissolve in oil are already getting the benefit of the improved bioavailability that Biocurcumax wants to offer us? And why does the dissolution of curcumin in oil help the bioavailability? I believe it is becausethe way the body digests fat is that it the chunks go through the stomach and then it becomes emulsified when bile is added to the initial end of the small intestine. Then those small droplets of oil, containing molecules of dissolved curcumin, are small enough to pass through the vilii of the small intestine into the network of lymph ducts that parallel all the network of blood veins, into which other molecules enter through the vein pores in the walls of the vessels (but the fat droplets don’t).Fats are not digested much in the stomach or the small intestine, but enter the lymph system, along with the enzyme lipase, which breaks down the fat globules and converts the fats into glycerol and fatty acids, both of which are soluble in water. So when the lymph is dumped back into the blood vein system up near the thorax, the fat has been changed into water soluble components. Presumably, the curcumin that was dissolved in the fat globules (dissolved means that it then existed in molecular form, not crystalline form), now remains attached to the fatty acids molecules or exists as free curcumin molecules in the blood to be carried throughout the body to find their home on some ugly little cancer cell in the bone marrow, where it frightens that cancer cell into committing hara-kiri, or your favorite word APOPTOSIS. So my theory is the Biocurcumax improves bioavailability by dissolving part of the curcumin in the oil, making easier for part of it to get into the blood stream through the lymph system. But I want to dissolve ALL of the curcumin in oil so that All of it gets into the blood stream through the lymph system. Maybe we already are there and don’t know it because no one ever measured.Finally, I have two more brainstorm ideas to push on you. First, you must realize that curcumin will dissolve in alkaline aqueous solutions, but not acid solutions. The stomach is very acidic but the small intestine is very alkaline. First idea is to ferry the curcumin through the stomach, where a lot of it gets turned into curcumin glucorinide and curcumin sulfate, neither of which are bioactive, and into the small intestine by encapsulating the fine curcumin powder in an enteric coated capsule that can resist the stomach acids, but will dissolve in the alkaline environment of the small intestine, releasing its contents, which promptly dissolve in that environment and enter the vein system in molecular form. Some may still get lost through conjugation into glucorinide and sulfate, but more will at least get dissolved and able to enter the blood stream because it wasn’t conjugated while in the stomach.Second idea is to dissolve the curcumin into some kind of fat (how about cocoa butter?) that is hard at room temperature, like chocolate, and form it into a capsule form, which gets swallowed whole. As it makes it way through the stomach it slowly melts and the fat breaks into droplets with the curcumin still dissolved in them. These droplets are then emulsified in the small intestine and go on their way into the lymph system to be digested by the lipase, as in the above description.The main advantage of this approach is convenience.Just pop a few delicious chocolate-flavored lozenges into your mouth and swallow them WHOLE, and your curcumin is on its way to lymph heaven.

I particularly liked his second idea: chocolate, my favourite thing in the world, AND curcumin? I must do some experimenting. And why not mix curcumin with a ganache, i.e., warm cream with unsweetened dark chocolate? Ahhh, the possibilities are endless.

September 30 2007 post. Two interesting comments to yesterday’s post. First, I would like to address Don’s comment. With my almost non-existent scientific background, I think the idea of swallowing the chocolate lozenge just as you would swallow a pill is in order for it to melt slowly not in the mouth but in the stomach. If it melts in the mouth, wouldn’t that defeat the purpose? How would curcumin bypass the stomach if it were not still encapsulated in fat? I could be totally wrong, of course.Second, Marcelo’s comment. I agree, I would love to have a chemist comment on all of this, too! At any rate, his wife now dissolves curcumin in olive oil. A possible suggestion to improve taste would be to add herbs and spices to this concoction. In the past, I tried flaxseed oil, but the taste was so dreadful that after a couple of weeks I became nauseous just at the sight of this mixture, no matter how much I tried to think of it as a Harry Potter potion. However, I still think an oil mixture is a good way to take curcumin (and Biocurcumax would be proof of that, although where to get our hands on essential oil of turmeric is beyond me), perhaps THE best way, but you have to have a strong stomach for it. By the way, if you would like to read the Biocurcumax patent application, go to: http://tinyurl.com/2nqcjf I will go through this application more carefully soon.As for milk cream (would that just be cream, Marcelo, as in whipping cream or double cream?), I would suggest heating it. It seems strange that your curcumin didn’t dissolve in cream. In the past, I tried the warm cream/curcumin (another yuck!) mixture, and the former dissolved rather easily. There may not be enough fat content in your milk cream. (?)A good question would be: how to make all these great concoctions more palatable? I am very open to suggestions.Here are a couple of things that I would like to try in the future. One is the chocolate lozenge idea; the other is the oil idea, with, as I mentioned previously, the addition of other spices (spices have anti-inflammatory effects, generally speaking, so I very much doubt that they would interact negatively with curcumin) in order to make the concoction more palatable. Speaking of palatable, I remember that last year, after preparing a huge Indian feast, I took my curcumin mixed in the oily part of the food, and it tasted absolutely fantastic. I couldn’t taste the curcumin at all when mixed with all those wonderful spices. Well, in my September 12th post ( Signaling Protein for Multiple Myeloma Identified ), I wrote about an Indian dish called Vindaloo. Given my previously-described successful (in terms of taste, anyway!) experiment with curcumin and spicy oil, this reinforced my idea of mixing curcumin with the warmed up oily part of this dish. That might well be the best way to take curcumin. Ahhh, with spices there really are so many different possibilities. I wish I could do one experiment for two weeks, have blood tests done, then do another experiment for two weeks, and so on. But patience is a virtue, no? And in fact, according to an Italian proverb, la pazienza è la virtù dei forti, which roughly means patience is the virtue of strong people. So I will be patient, I will be strong, and try one thing at a time, for two months at a time.

October 1 2007 post. Last week I stopped taking the Doctor’s Best curcumin capsules, fearing a possible interference between the bioperine and my massive daily dose of antibiotics (I am not sure that that would be the case, but better safe than sorry!). Since I don’t want to stop taking curcumin for obvious reasons, though, I figured that now would be a good time to try one of the new increased bioavailability ideas.Since I am not up to making chocolate candies yet, I decided to try my chocolate ganache idea. All I have in my kitchen right now is some 70% dark chocolate, which yesterday afternoon I melted over low heat, adding a small amount of organic butter, then some whole organic milk. I mixed about two grams of curcumin powder into this thick dark liquid and drank it. Now, keeping in mind that right at the moment I have quite a head cold and my taste buds are, consequently, a bit altered, this mixture tasted just fine to me. Quite an interesting color, too.

This morning I upped the dose of curcumin to four grams. The taste was definitely worse but not horrendous. Once I get my hands on some double cream and some cocoa butter (which has a 50–57% fat content), I won’t need to use butter to increase the fat content of my fake ganache. Still, even without the cocoa butter etc., I can confirm that curcumin will dissolve easily in what is essentially warm (almost hot) chocolate milk, without sugar. Whether it works on my myeloma markers well, I won’t know that until I have my next set of tests. My experiment continues.

October 2 2007 post. Today I thought I would gather together a few more of my blog reader suggestions (if I have forgotten anyone, please let me know!), and also show a few photos documenting how I am currently taking curcumin (see explanation below). The curcumin powder here depicted (see photo on the left) is the C3 Complex curcumin, without bioperine, that I order from the Italian distributor for the Sabinsa Corporation. I keep it in a hermetically sealed ceramic jar so no air and light will make it deteriorate. A blog reader with a plasmacytoma (diagnosed three years ago) is currently stable. He takes curcumin together with a product called Barley Green, which, from what I gathered on Internet, is composed mainly of organic barley grass containing active enzymes, minerals, B-vitamins, amino acids, essential fatty acids, carotenoids, bioflavonoids, and chlorophyll. This mix allegedly gives a boost to the immune system and reduces inflammation. I have never tried it, but I HAVE been curious to try wheatgrass, which is not readily available here in Italy, though. I love what this blog reader says about myeloma cells, i.e., that they don’t like green. When I visualize, I focus sometimes on things that my myeloma cells don’t like, and it makes sense that they don’t care for healthful diets full of green veggies. So this is interesting. Does anybody else here take a similar green product?Another blog reader suggests letting curcumin rest in the flaxseed or liquid preparation for about a half hour before drinking it in order to give it time to go through and finish its chemical processes. This is analogous, I suppose, to letting fresh homemade pasta dough rest before rolling it out. An interesting idea. The only thing that would concern me is that curcumin is not happy when exposed to air and light. But perhaps mixed in a liquid would lessen its chances of losing any of its healthful properties. Any thoughts on this?

Blog reader number three dissolves curcumin powder in very warm milk and then adds the omega 3 oil from a capsule (Omega 3–6–9 lemon flavor from Nordic Natural). She says this makes it very palatable. When she mixed it with coconut milk (as yours truly used to do), she did not like it (neither did I).It was the smell from the milk what make her sick (no kidding! Me, too!).Sometimes she adds coconut oil to her concoction, which tastes very good, too, she reports.

A fourth blog reader does the following: I mix the caps of curcumin in a teaspoon or two of organic flax seed oil — it dissolves easily. Then I add about 1/3 cup of organic fruit yoghurt and stir it up. Next I add a 1/4 to 1/2 cup of frozen raspberries (or other small frozen fruit). Stirring this turns it into a kind of frozen yoghurt ice cream which doesn’t taste wonderful but is palatable due to the fruit flavour and the cold (which reduces the flavour). This is also an interesting method. I tried mixing curcumin powder in organic fruit yoghurt in the winter of 2006, between November and January 2007, and my IgG numbers didn’t decline at all. I just checked, though, and my monoclonal component did indeed decrease, which is important. So, that method might work after all, even though there is no heat involved (remember the abstract on increasing the bioavailability of curcumin by heating it up?). At any rate, in January 2007 I switched to curcumin capsules with bioperine, and my subsequent tests showed a decline in my IgG count, the first decline since November 2006, but also a slight increase in the monoclonal component. Sigh, this is SO hard to figure out.

Here are three not-so-great photos documenting my now daily chocolate curcumin preparation (two preparations/day). The photo at the top shows a full teaspoonful of curcumin, about four grams; the second photo shows four grams of curcumin powder sprinkled over the warm, almost hot, chocolate, butter and milk mixture, and the third shows what I actually drink, which is lighter in colour compared to the mixture in photo 2, obviously. The taste is not bad at all. And this is also not a bad way to get my chocolate hit for the day!

Update. October 28 post: 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?

November 29 update, please read November 25 and 26 2007 posts on a new bioavailability study and the following: about a month after I wrote my most recent update (October 28, that is), I have changed my mind about dosage timing. It all began when a friend told me that she decided to take her dose of curcumin all at once, yes, all eight grams, in the late afternoon because that is when she felt most relaxed. Soon thereafter I found out about and wrote a post on circadian rhythms. An eye-opener. As a result, I now take my curcumin powder (mixed with melted cocoa mass and a bit of honey) all at once just before going to bed, when my enzymes, I hope!, are not as active as they are during the day. My idea is that if my body is not so active perhaps curcumin has a better chance of being absorbed. Not sure how scientific this is, but as soon as I can ask someone with the proper scientific know-how, I will report the answer. Taking curcumin in one big evening dose is a big change for me, but it makes my life easier especially on the days when I teach. Of course, matters would be different if I took curcumin capsules with bioperine. In that case, I would divide the doses into two, mainly because I really hate to take so many capsules. For now, I am sticking to the cocoa mass concoction.