Curcumin and the H1N1 flu virus: the full study

This is a continuation of my November 7 2009 post on *the first report demonstrating that curcumin exerts anti-influenza activity*. Before jumping into the full study, let’s have a quick look at a couple of items mentioned in the abstract (see: http://tinyurl.com/ybug9sl). The first is one that I had never seen (or paid attention to) before: haema-something-or-other, uhm…let’s see…ah yes, haemagglutination, or hemagglutination with the U.S. spelling. The linguist in me tried to figure out the etymology of this term, but that led me nowhere: the gluing of blood? Blood glue? I finally had to look it up. It means: the clumping of red blood cells (voilà!) caused by viruses, antibodies or other substances. And, according to this study, curcumin inhibits the hemawhatever process. My first question was: is that a good thing? Let me see…yes indeedie, it is. See, e.g.: http://tinyurl.com/q2zys9 and http://tinyurl.com/yfdab7j

The second item is amantadine, which is an antiviral drug administered in cases of oseltamivir-resistant H1N1 flu (oseltamivir is better known as Tamiflu). Amantadine was used in this study as a control for the drug resistance test. Two important findings: 1. in contrast to amantadine, viruses did not develop resistance to curcumin; 2. like amantadine, curcumin inhibited influenza virus plaque formation. Okay, now for the full study.

After giving us the usual overview of curcumin’s multifaceted effects, the authors tell us that Recently, several reports demonstrated that NF-kB inhibitors efficiently blocked propagation of influenza, suggesting that modulation of NF-kB signalling may be a target for anti-influenza intervention. Aha! Inhibition of our old archenemy, NF-kappaB…well, that happens to be right up curcumin’s alley. In fact, that is why curcumin was tested in this study in the first place. And, come to think of it, wouldn’t it follow that any old NF-kappa B inhibitor would block the H1N1 virus? If so, then we would be able to choose from a wide array of natural extracts…not just curcumin but also resveratrol and green tea, just to mention a couple…

At any rate, the researchers administered various doses of curcumin (dissolved in DMSO) at three different times: 1. before infection, 2. together with the virus, and 3. after the virus had been added to the cells. They found that the production of virus was significantly reduced upon treatment with curcumin in a dose-dependent manner; in the presence of 30 micromoles of curcumin, the titre of virus was less than 5% of that in mock-treated cells at all time points of infection analysed.

Based on their tests (I will spare you all the details!), the authors postulate that curcumin may directly interfere with a very early stage (possibly directly with the virus particle), to prevent infection. Curcumin was also found to be effective against avian flu (=H6N1).

Let’s go back to the abstract for a second. It ends with a rather puzzling sentence: the methoxyl groups of curcumin do not play a significant role in the haemagglutinin interaction. The full study sheds some light on this issue (skip this paragraph unless you are fascinated by methoxyl groups…): Commercially available curcumin consists of three major components: curcumin, demethoxycurcumin, and bisdemethoxycurcumin. The structure of curcuminoids differs only by the number of methoxyl groups. So one of the study aims was to determine what part these methoxyl groups played in the Flu Virus Battle. Apparently none whatsoever, since all three curcuminoids were effective against the virus, regardless of methoxyl group content. (Yep, I am yawning, too!)

An issue of huge importance is viral resistance. Flu variants resistant to oseltamivir/zanamivir as well as to amantadine and rimantadine have already popped up all over the world. The researchers compared amantadine and curcumin and found that resistant strains developed to amantadine but not to curcumin, indicating treatment of curcumin is not prone to emerging of resistant viruses. Good to know.

Many blog readers have asked me about dosage. Ah, this is where things get a bit muddled (for me, at any rate). Since the abstract is available online, let’s look at this excerpt: treatment with 30 micromoles of curcumin reduced the yield of virus by 180px-Close-up_of_mole[1]over 90% in cell culture. Okay, let’s take a deep breath…micromoles. No, these are not teeny tiny moles (right photo) digging teeny tiny holes in our gardens and no, they are not even itsy bitsy marilyn monroe[1]beauty marks (left photo). Okay then, if you really must know, in scientific measurements, a micromole is a concentration of one one-millionth of a mole per liter. Ah yes, this is soooo helpful (not!!!).

Well, I have never hidden the fact that math has never been my forte. I looked at conversion charts and molecular weights and filled page after page with divisions and multiplications until I became quite giddy. I gave up.

My blog reader Rebecca has already tried to answer the question for me: her naturopath told her that it would be impossible for us to reach the concentrations used in this cell study. Well, that is certainly, uhm, encouraging…

But hey, all is not lost, in my opinion. As I have mentioned in previous posts (and this is confirmed by private exchanges I have had with Prof. Aggarwal), curcumin works at different levels inside the body. Not just in the bloodstream. And in fact, ever since I began taking curcumin I have been much healthier, as strange as that may sound. It could be a mere question of mind over matter, but I doubt it. Something is definitely happening…

In conclusion, I figure that curcumin, in association with a healthy diet, exercise and a huge dose of caution–avoiding crowded places, washing our hands frequently, etc.–will lend a hand, if only a micromole-sized hand!, in protecting us during this flu-ridden period (I just heard that 1.5 million Italians have contracted the influenza A, or H1N1…yikes!). I have to believe that…otherwise, reading, doing research for, writing and posting about this study has been a complete waste of my/our time…sigh!

12 Comments

  1. I found a very helpful table:
    Reference ranges for blood tests by molarity (mole/l)

    http://upload.wikimedia.org/wikipedia/commons/b/b8/Reference_ranges_for_blood_tests_-_by_molarity.png

    By the way:
    m = M x n
    Curcumin has a mole mass (M) of 368,39 g/mole
    (n)= 30 micromoles of Curcumin are equivalent
    to (m)= 11,052 mg Curcumin.
    (If i am wrong please don´t hesitate to correct me)
    We need approx. 11 milligrams of curcumin in one liter of blood in our body.
    How many grams of Curcumin we have to take to get this concentration of 11 milligram in 1 liter of our blood????
    It´s a question of the curcumin solubility or bio availability of curcumin in our blood.

    (sorry for my poor english – but i am German)

  2. The serum concentration of curcumin usually peaked at 1–2 h after oral
    intake of curcumin and gradually declined within 12 h. The average
    peak serum concentrations after taking 4000, 6000 and 8000mg of
    curcumin were 0.51±0.11, 0.63±0.06 and 1.77±1.87 microMole, respectively.

    That means we have to take approx. 136000mg (136 g) curcumin (oral intake) to reach the level of 30 microMole serum concentration !!!!
    That´s a lot of curcumin !!!! Uffa !!!

  3. Just thought I’d chime in on the hemagglutinin bit: hemagglutinin is a protein on the surface of the virus, involved in the binding of virus to our cells. It’s the “H” in the H1N1 (or H5N1 or H6N1) when virus names come out because it’s one of the important virulence factors that can be determined and used to differentiate major strains of virus.

    For this study, it would seem that curcumin can disrupt the ability of the virus to even get into cells. That’s great, because if virus can’t get in, it can’t replicate. And I don’t know the specifics on viral molecular biology, but I’d bet that mutations in hemagglutinin that can get around curcumin and still be effective are pretty rare. That would account for the low incidence of resistance. It’s much easier for the virus population to become resistant if the inhibition happens later, inside the cells (lots more proteins involved = more chances for a mutation to get luck out and get around the inhibition).

    This isn’t my specific field, so I could be wrong on some of this. But it makes sense to me. Just as a little side note, molecular biologists use hemagglutinin all the time in research – we can insert the DNA that encodes part of hemagglutinin in front of genes of interest, creating a fusion protein (we called them HA-tagged proteins). We can then purify or visualize those fusion proteins with antibodies to HA. It’s extremely useful. So that’s one thing the flu has been good for!

  4. I will have to study the information in that link, Rudi. The only information about curcumin levels that I knew about was from a paper on curcumin and pancreatic cancer. The authors (including Dr. Aggarwal) stated that they measured about 30 ng/ml as a steady state value in blood plasma (after eating a few grams of curcumin per day).

    Well, given the molecular weight of 368 grams/mole, I calculated that this results in a concentration of about 0.1 micromolar. So yes, this is small compared to the 30 micromolar used in the H1N1 study. But I agree with Margaret that concentration in the blood is not necessarily indicative of curcumin levels in other bodily organs.

  5. Rudi, thanks for the above link. While interesting, I find it frustrating that there appear to be no references listed for the absorption graphs. Do you know who did the work, or am I just not finding the references?

  6. Interesting link, Rudi. In October my MM seemed to be more active. I felt less and have slightly increased the dossis curcuma. Curcuma of another brand, with pepperine in it. Now I feel a lot better. I thought that the other brand also had pepperine in it, and it was not!

  7. I know this thread is old, but…

    My thought is that even though we can’t consume enough curcumin to reduce the viral load by 90%, the curcumin slows the viral replication down enough to let the white blood cells catch up. Thanks for all of your research!!

Leave a Reply

Your email address will not be published. Required fields are marked *