What Happens To Curcumin Once It Is Ingested?

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?


  1. Hi Margaret-
    In addition to ingesting high dose curcumin, we are also experimenting with dissolving curcumin in DMSO and applying it to areas of the skin – inside the elbow, under the arms, top of groin area (gets around the issue of bioavailability – in the latter two areas, the hair folicles provide an excellent mechanism of drug delivery. The scalp and face of a male also excellent for drug delivery – but who wants a yellow head/face). http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16260102&itool=pubmed_docsum It sounds wacky I know, but a lot of sound science behind it. Would be happy to provide additional if interested.

    Also, recent MD Anderson research (the first ever that discusses efficacious doses in-vivo) used 500mg/kg

    That is a lot of curcumin! But given the bioavailability issue, we’re trying it.

  2. Hi Margaret,
    I was wondering if curcumin could be administered through implants (retention enemas). Many holistic protocols advocate wheatgrass implants and coffee enemas. According to them these substances go directly to the liver. This may sound crazy. It is just a thought.
    Take good care.

  3. Hi Margaret,

    Many traditional recipes include burning turmeric and inhaling the fumes.
    And another thing – nasal sprays are equivalent to injections. I found some traditional recipes for preparing nasal drops with turmeric but I am not sure how safe are they.



  4. To put numbers on Eileen’s comments, as a 68 kg (150 lb) person, I would need to take 0.5×68= 34 grams of curcumin. Reading the abstract, it’s hard to say whether that is a once-daily dose, but in any case it is a lot.

    However I’m almost halfway there, IF YOU BELIEVE that the new LEF “Super Bio-Curcumin” really is seven times more bioavailable than standard 95% extract. IF SO, then I’m taking the equivalent of about 14 grams/day. To get to the equivalent of 34 grams/day, a person could take twelve 400-mg capsules of the LEF stuff or, as I do, take a combination of both kinds just to be seated squarely on the center of the fence.

    I do take it in four equal doses each day, at approximately 6-hour intervals, adjusted somewhat to avoid mealtimes. One dose is in the middle of the night, when I get up briefly for another reason anyway. If I happen to miss a dose, I just double up on the next one – no worries.

    Fingers crossed as always.

    What an intriguing comment by Snezhi. Talk about bioavailability! But for now,…

  5. Hi Minnestodan-

    Your calculations correct! We take this amount (500mg/kg) in two divided doses (i.e. 250mg/kg twice a day). This is taken EVERY OTHER DAY (since curcumin bioavailable for 48 hours). Of course, this is a direct translation from rats to humans. Small animals metabolize and excrete quicker than humans, so for translating animal studies to humans, the dose would be smaller. However, until definitive studies on humans are published, we’re not taking any chances since there is no toxicity at this high dose (this latter statement based solely on the 6 foot and 5.5 foot lab rats in our house!)

  6. The above description of what happens to curcumin once it is ingested only treats one approach to getting it into the system, i.e. to swallow powdered curcumin crystals and enough of it so that some of it survives the passage through the stomach and gets to the small intestine where it is capable of going into solution, because the pH there is alkaline. Curcumin will dissolve in alkaline solutions but not in acid, as exists in the stomach. But even if some of it makes it through, dissolves in the alkaline aqueous solution in the small intestine and some of those molecules pass through the vilii into the hepatic vein, then a good part of them get metabolized at once because the hepatic vein takes them directly to the liver. Those that are left after going through the liver then enter the general cirulation and some can likely find their way into the bone marrow, where they can attack the cancerous MM cells.
    However, there is a second and I think better way. That is to first dissolve the curcumin in a fat before ingesting it. In the fat a good part of the curcumin is now in solution and exists as free molecules in the liquid fat. Fat is very little dissolved in the stomach because fat simply does not dissolve in water, even if quite acidic. Lipase enzymes in the stomach attempt to begin to digest the fat and release the curcumin, but lipase can only attack the fat at the surface of the fairly large globules that exist there. However, once the stomach contents enter the small intestine the chemistry changes, because bile and other fluids are injected by the body, which causes the pH to go into the alkaline range, but more importantly, bile is a strong surfactant and breaks up the fat globules and forms an emulsion of very fine fat droplets, having very much larger surface area than when the fat was in the stomach. Fat is simply digested differently than protein and carbohydrates and most of its digestion by lipase takes place in the small intestine after the fat is emulsified. Digestion by lipase converts the fat into fatty acids and monoglycerides, which are absorbed through the wall of the intestine, then are reassembled into triglycerides and carried into the body through the lymph system on chylomicrons. A discussion of this digestion process can be found at:
    The key point here is that the digested fat products and curcumin end up in the lymph, rather than the blood serum. Once in the lymph system the curcumin molecules that are released by conversion of the fat into fatty acids can stay in solution in the lymph fluid, because it is slightly alkaline, with a pH of about 7.4, same as the blood serum. The lymph trunk vessel dumps into the vein system up in the region of the thorax, and then to the hearat,which enables the blood circulation to then disperse the curcumin throughout the body. So by dissolving the curcumin in fat it is protected in its passage through the stomach against conjugation into curcumin sulfate and curcumin glucoronide, and then enters a favorable environment in the lymph system before finally reaching the blood circulation system, and without having to make that first pass metabolism in the liver. That means that the concentration of curcumin molecules in the serum that reachs MM cells will be considerably higher. Thus, first dissolving curcumin in fat before ingesting it will improve its bioavailability and not require such massive doses of curcumin powder directly taken orally, like 500 mg/kg.
    But what we curcumin users desperately need is more real test data on humans to verify that the curcumin concentration in the blood serum is indeed higher when first dissolved in fat. But what we need even more desperately is real test data that shows what serum concentration level, on a continuous basis, is needed to produce the favorable changes in the markers for the disease that we are treating, i.e. Phase II clinical trial type data.
    How about some brainstorming ideas on how we can get that real data, so we don’t have to keep running blind experiments on ourselves and our loved ones?

  7. Hi everybody. I’ve just started taking curcumin, so I do not have any experience to share, yet. But the more I think about it the more I’m convinced that I’ll try to take curcumin in just one big daily dose and not two ore more. Whatever the dose you take – I’ll get 8 gr. a day – the important thing is to cause as much apoptosis as you can. Now, if you take 4 gr twice a day, those 4 gr. taken twice might not cause as much apoptosis as 8 gr. all toghether. This because of the bioavailability problems we all know. In the labs mice are given the big dose all in once.

    A question for Eileen: what about your blood test? Can you give us some data on your before-post curcumin intake?

    Have a nice day,

  8. Hi Ana-
    We’re dealing with a brain tumor, so there are no blood markers. The only way to read is through bi-monthly MRIs. In addition to being a solid tumor, we need to cross the blood brain barrier. At the risk of sounding completely crazy, one way to get around this is to dissolve a small amount of the curcumin in a fat like flax oil and use a Q-Tip to apply inside the nose. There are no side effects (for us)doing it this way either. While I haven’t researched if this could be efficacious for other cancers, I guess it’s the equivalent of nasal drops mentioned in the posting above??? The key though is dissolving in fat.

  9. Can anyone comment on JHope’s suggestion of rectal administration of curcumin via enemas? Would it pass through the sigmoid colon wall via hepatic vein straight into the liver? I can’t find any studies demonstrating this mode of administration.

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