Biological Clock and Bioavailability: Possible Connection?

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: 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:, 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:, 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!!!).


  1. I guess I have known about Circadian rhythms for a while. As you know, my son Jamie has been diabetic since he was two years old. When he was a baby, it was difficult to get the balance between his injected insulin and food consumption right and he would regularly have hypos (diabetic fits) in the night. It was almost always at 4am when the body apparently reaches it’s low point.

    On another matter: as you know I followed up the lead you posted a couple of days ago concerning the people on the cancer compass website who are connecting coeliac disease and MM. I am very excited about this and very grateful to you for pointing me in that direction. There are several case histories on the site that are so similar to mine that I am going to write a post which will add to the evidence. I think that coeliac’s could be an important factor for some of us, although it is not certain which comes first, or whether MM/MGUS can be cured in the long term by following a gluten free diet. However, given an increasing amount of evidence, it is certainly worth pursuing. Thanks so much for pointing it out. Paul

  2. Dear Margaret
    There is a saying, “Timing is everything!” I don’t know the context in which it might first have been recorded, but I truly believe that in… everything… timing is everything.
    (Even in.. always eat breakfast, etc.)
    Surely in when we take supplements and medications. Keeping giving us your research!
    Really, am off to run/walk now….

  3. I guess I’ll find out if “cut and paste” from a web browser actually works when commenting…

    Of particular interest to MMer’s and bone resorption is the circadian
    rhythms of calcium metabolism.[1]
    For all of us who live in more northern climates the seasonal rhythms
    and Vitamin D (the hormone of sunlight) should be noted. MMer’s need to
    be aware that excess Vitamin D can cause hypercalcemia a problem some
    of us face already. On the other hand vitamin D has been recognized for
    more than a century as essential for
    the normal development and mineralization of a healthy skeleton and
    proper immune system function.[2]
    Our fragile kidneys play an import role in vitamin D bioavailability.[3]
    Vitamin D and cancer risk have a long well documented history.[4]
    My GP runs a 1,25 dihydroxy-vitamin D test a few times a year.[5]

    My ND recommended the general rule
    of vitamins in the morning and minerals at night.The second general rule is “you are what you
    eat.” 70-80% of your immune system is located in and around your
    gastrointestinal (GI) system, so its ability to function optimally
    greatly influences your overall health. The specific recommendations
    are talored to my present status, but could be generalized to, “Start
    building a healthy GI system before moving on to the deeper issues.”

  4. Question for LP Cells:

    I was particularly interested in your last paragraph – particularly the phrase, “70-80% of your immune system is located in and around your gastrointestinal (GI) system, so its ability to function optimally
    greatly influences your overall health”.

    Could you go in to more detail please and are you aware of the connections some of us are making between celiac’s disease and MGUS/MM?


  5. As I am sure we all know if you want to catch a nasty bug act like a toddler and put every you can in your mouth… Or just hang out at a day care center. Our ability to remain healthy depends mostly on our GI system’s ability to combat pathogens. Our respiratory system is probably the next most vulnerable line of defense. Our skin being the least vulnerable. If any of these defenses is compromised the potential for disaster is heightened. The folks at Pettygrove
    Classical Chinese Medicine Clinic
    recommended “L- Glutumine Powder – 1 tbsp (up to 24gm) 2x day This is food for the gastric mucosa. It will help strengthen the cells integrity which is very important during chemo and surgery. These events particularly damage your fast dividing cells such as the intestines. The importance of gastric health is more than just digestion/nutrient absorption. 70-80% of your immune system is located in and around your gastrointestinal (GI) system, so its ability to function optimally greatly influences your overall health.”

    Here are just a couple of the recent publications I have read. There is an enormous amount of info related to colon cancer, irritable bowel, celiac and the likes that might have implications, but I can’t connect the dots. (yet)

    UID: 17679289
    …The main functions of intestinal microflora include (1) metabolic activities translating into energy and nutrients uptake, and (2) host protection against invasion by foreign microorganisms. Intestinal bacteria play an essential role in the development and homeostasis of the immune system. Lymphoid follicles within the intestinal mucosa are the main areas for immune system induction and regulation. On the other hand, there is evidence implicating intestinal microbiota in certain pathological processes including multi-organ failure, colon cancer, and inflammatory bowel disease.

    UID: 16498248
    …It is important to underscore that the specialised lymphoid
    follicles of the gut mucosa are the major sites for induction and regulation of the immune system. On the other hand, there is evidence implicating the gut flora in certain pathological conditions, including multisystem organ failure, colon cancer and inflammatory bowel diseases.

  6. Hello,

    There is a clever example of using “chrono-biology” or cyrcadian biological rhythms for therapeutic purposes for the treatment of a number of diseases, including cancer, using low-dose naltrexone. The general idea is to influence opioid receptors in the human body at night-time, when they are particularly receptive for therapeutic purposes.

    You can find information on the “chrono-biological” use of low-dose naltrexone at:

    The theory behind the use of low-dose naltrexone is somewhat complex, and I will not try to summarize here… please check the low-dose naltrexone website.

    regards, Marcelo

  7. Thanks for your post L.P.
    I’m still not sure I understand what is meant by “induction and regulation of the immune system” or how it works. I thought that the MM problem with our immune sytems started in the bones but perhaps we do need to go back a stage.
    Maybe my assumption that chronic digestive problems were over-exciting the immune system is wrong. However, the source of the problem might remain the same. It’s just a different mechanism that causes MM.

  8. Paul et al, Be very careful to not confuse correlation with causality. MM has a long reach. Each and every one of us has a unique manifestation of the malignancy with a correspondingly unique reaction to it. It would be my first guess that MM is the cause of countless ills many of which are auto-immune in nature. Digestive disorders being high on the list because of our suppressed immunoglobulins. Of course even if there is a causal link the real question at this point is, will fixing it have any effect on the MM? Fixing anything so you feel better is probably a good thing. 🙂

  9. I know what you are saying L.P. I have described MM as a diseased tree. The symptoms can show up in various branches but pruning the branches is no good if the disease is in the roots. You can assume the blood and bones are the tree trunk equivalent if you wish. It’s the root cause that I am looking for and I suspect that it will be different for each one of us. However, quite a few people seem to be associating MM with celiacs so there might be something there.

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