Hype and Potential Behind the Therapeutic Promises of Curcumin: From Alzheimer’s to Cystic Fibrosis

turmeric

Turmeric root contains biologically active curcumin.

Turmeric is a root belonging to the ginger family, and like ginger, is used prominently in oriental cuisines.  Owing its yellow color to a compound called curcumin, the root is probably best known as the spice used in curries.  Like its ginger cousin, turmeric has been used for medicinal purposes for thousands of years.  I’m not entirely sure how we know the timeline or how much truth is in that statement.  Nonetheless, I will parrot that as truth since we as humans often have this immutable faith in the supposed medicinal value of things we pull out of the ground.  As it turns out, there does appear to be some real potential medical applications, not with turmeric itself, but with curcumin.  Some of the claims are hype, some of them show a lot of promise with a little more research, and there may actually be some benefit in taking curcumin now.

Curcumin was identified as a compound in turmeric in the 1800’s, but the biological importance of curcumin was not touched on until 1949 when a paper published in Nature described the antibacterial properties of curcumin, specifically, the ability to inhibit the growth of Staphylococcus aureus.  Scientists gave little attention to curcumin over the next 25 years when it was discovered that curcumin exhibited anti-inflammatory and anti-oxidant activity, and then anti-cancer activity by the mid-1980’s.  Since that period of time, curcumin has been heralded in scientific circles as a potential safe, effective, treatment or preventative measure to many difficult to treat diseases.

I will touch on only a few areas that are being investigated, of which effect me personally in some way.  Curcumin-related therapy is a topic surprisingly deep in scope and I could not possibly cover every aspect.  Moreover, I am attempting to draw from evidence in peer-reviewed science provided by experts on the subject and I am by no means an expert myself.

Cystic Fibrosis

Cystic fibrosis or CF is an inherited genetic disorder and something that I am personally afflicted with.   CF results in the mutation of a gene that codes for a protein called CFTR.  This mutation causes the CFTR protein to be absent or malfunctioning in people who have CF and leads to the inability to properly transport water and salt across cells lining important organs such as the lungs, pancreas and small intestines.  Ultimately, this causes thick mucous build up in the affected organs and significantly damages the lungs over time, facilitated by recurring bacteria infection, eventually leading to mortality with a current average life expectancy of 38 years old.

Its thought that curcumin can restore some function to the CFTR protein, and this is what drew my attention to curcumin.  The hype began when a study published in 2004 purported that curcumin was able to correct the defect in CF mice with the most common mutation, referred to as delta F508, improving their survival rate, and in cell culture.  However, another group independently attempted to recreate these results and were unable to achieve even a modest affect as a result of curcumin given to CF mice or in cell culture, citing potential flaws in the original study design and perhaps misinterpreting the apparent reasons behind the increased survival rate in mice.  These negative results were again confirmed in epithelial cells, Baby Hamster Kidney cells and other cell lines exposed to curcumin.  Its worth noting, however, that one lab did find that curcumin restored function in CFTR in a delta F508 cell line, although with methods differing from those previous studies.  More recently, a study found that a combination of curcumin and genistein improved CFTR function in cell lines containing the less common G551D mutation.

Overwhelmingly, however, the evidence does not suggest that curcumin will improve the health of people with CF.  It is interesting that curcumin persists in the scientific literature as a CFTR inducer.  Maybe there will be good reason to include as part of a  therapeutic regiment in the future with an improved curcumin formulation.  There’s no harm in taking curcumin though and it may actually provide other positive health benefits.  The real harm comes from naturalists touting curcumin and other natural substances as a cure, which may be enough to convince some people to stop their currently suggested therapeutic routines and pharmaceuticals that are backed by real clinical science, robbing them of any hope of a long life.  This seems to be an unfortunate reality based on the little reading I’ve done online.

Alzheimer’s Disease

Alzheimer’s Disease (AD) is a form of dementia characterized by a progressive deterioration of cognitive function, loss of memory, behavioral and personality changes.  AD patients form amyloid-β-protein aggregates in the brain over time, which are essentially abnormal deposits of protein, or plaques, that aren’t supposed to be there.  As a result neurons die off and the plaques interfere with the ability of existing neurons in the brain to communicate with each other.

Brain disorders are extremely difficult to treat because the obvious difficulty in studying the brain itself but also because any drugs have to cross the blood brain barrier, which is our bodies natural defense that keeps harmful agents from reaching our most vital organ.  Any substance we use to treat a brain disorder needs to have the ability to cross the blood brain barrier naturally, or we need to find ways to “trick” our bodies into allowing it pass to the brain.

It appears that curcumin is one of those molecules that are allowed to pass the blood brain barrier, at least when given to mice at high doses.  A link between AD and curcumin was originally drawn from epidemiological data that shows India has a much lower incidence of AD than the US.  In fact, current data from The World Health Organization shows that American’s are 8 times more likely to die of Alzheimer’s than Indians.  It must be something in the diet….or it could be that Americans are expected to live 10 years longer than Indians, or that Alzheimer’s Disease is severely under reported in a country faced with extreme poverty.

There actually has been a study using survey data reporting the amount of curry consumption in the Asian elderly population and found a positive association between curry consumption and improved cognitive function, again this kind of data should be taken with a grain of salt since this is not a controlled study and the observed effect could be due to any number of factors.  There has also been a wealth of evidence shown in the lab using rodents and cell culture to demonstrate that curcumin inhibits formation of amyloid-β-protein aggregates, restores synaptic plasticity, and protects neurons.  Unfortunately, there has been no improvement shown in humans with AD who take curcumin in clinical trials.  This may suggest that curcumin can only help prevent AD, or that not enough of it is reaching the brain to cause a clinically significant effect due to poor bio-availability (explained in the last section of the article).

Cancer

Cancer is the second leading cause of the death in the US, right below heart disease and there’s no real indication of that changing soon.  In addition to environmental and genetic factors, cancer is largely an unfortunate side effect of aging.  As we live longer, cancer is bound to become more prevalent.

Cancer is such a difficult disease to treat because there is nearly an infinite number of ways that cancer can manifest itself beginning at the cellular level and involves multiple cumulative steps that take place over several years.  To further compound the problem, different tissue types present unique challenges. We need to find ways to target the cancer cells specifically while leaving the normal cells alone.  Not an easy task when those cancer cells are your cells.  Most effective therapies that we use to treat diseases today target something that is foreign to the body, like bacteria.  We can target these with minimal effect to the person being treated because the bacterial cells are different on a molecular level than cells that originate from us.

Despite all the promising research that is coming forward, the best we can do to treat cancer comes in the form of approaches that “poison” the cancer, but also damages normal cells in hopes that we can kill the cancer without taking out the person too.  It sounds archaic because it is.  It’s like using a wrecking ball to remove one window in a building.

So the future in cancer therapy is targeted and individual treatment.  Something that will target the cancer cells specifically and therapy that can be catered to an individual based on specific properties of their cancer.  Cancer prevention is the next best thing we can currently offer, and we now know that diet plays an important role in prevention.  As we’ll see, curcumin may potentially have a role in both prevention and treatment.

In 1987, the first clinical trial using an ointment containing curcumin on patients with cancerous lesions on the skin found a reduction (90%) in symptoms and a small (10%) reduction in the size and pain of the lesions.  Since then, multiple studies involving mice and cell culture have found curcumin to be effective in treating multiple types of cancers by multiple mechanisms: stopping cancer cell proliferation, blocking various transcription factors, inhibiting inflammation, providing antioxidant activity and causing apoptosis (cell death) specifically in cancer cells.

However, these dramatic and almost miraculous effects observed in the lab have not been duplicated in human clinical trials, most likely due to poor bio-availability of curcumin (again, I cover this in the final section of this article since this is a limiting factor in all curcumin-related therapies). One study did find that an oral dose of  no less than 4 g of curcumin a day may improve the prevention of colorectal cancer.  Another study found a reduction in size and number of polyps in patients genetically predisposed to colorectal cancer with treatment combination of 480 mg of curcumin and quercetin 20 mg orally 3 times a day over the course of 6 months.  Curcumin was also found to be effective in slowing the progression of pancreatic cancer in a limited number of patients given 8 g of oral curcumin a day.

So, given what we know, curcumin may be helpful in the prevention and slowing of cancers that most directly involve the colon and pancreas.

Arthritis

One of the first clinical properties discovered in curcumin was its ability to act as an anti-inflammatory agent by inhibiting pro-inflammatory cytokines.  It should follow that curcumin would be an effective treatment for arthritis, there is plenty of evidence from studies performed in the lab, but a surprising lack of clinical data specifically assessing arthritis treated with curcumin.

The most solid study I could find was a pilot study comparing the effectiveness of daily 500 mg curcumin, 50 mg of diclofenac sodium (a traditional nonsteroidal anti-inflammatory drug (NSAID) used to treat arthritis), or a combination of both in patients with rheumatoid arthritis over 8 weeks.  The curcumin used in this study was a patented formulation with supposed improved bio-availability called BCM-95.  Overall, they found BCM-95 curcumin and curcumin+diclofenac to be just as effective, if not more effective at relieving pain and symptoms than diclofenac alone.  Providing some evidence that curcumin could be used to supplement treatment of arthritis.

Failure of Curcumin to Deliver

So why does curcumin appear to succeed so often in the lab in a way that can’t be repeated in humans?  The most likely answer is due to poor bio-availability of curcumin.  Meaning, the amount of active curcumin that reaches the blood stream is well below the amount needed to cause a clinically significant change.  Consuming turmeric root alone, which has very little curcumin to begin with, provides the absolute least amount of bio-available curcumin.  High doses of isolated curcumin, even though there may be detectable levels in the blood stream, is still metabolized too quickly to be meaningful.  However, a daily dose of at least 3.6 g of curcumin a day does appear to result in a quantity necessary to exert an effect in colorectal tissue, since this is one of the first places curcumin will pass after consumption.  This is probably the reason curcumin appears to be effective in preventing colorectal cancers.

The major reasons for bio-availability are due to curcumin being water insoluble and fast metabolism upon reaching the gut.  Little of the compound reaches the liver or systemic circulation, and 40% is excreted in the feces unchanged.  To circumvent this problem, multiple strategies are being developed to modify the structure or encapsulating curcumin for improved uptake by the body and survival in the blood stream.

One such formulation with improved bio-availability that I have already mentioned was BCM-95 which is backed by at least one clinical trial that I have cited involving arthritis.  Other brands currently available for purchase include Longvida and Meriva.  I can not speak of the effectiveness for any of these.  However, I have to imagine that any of those brands must be more effective, or just as effective at the very least, than curcumin alone based on the wealth of evidence we have on curcumin studies.  So far there has been no dose related toxicity reported with curcumin that I am aware of.

I’ll end with a word of caution that whatever you use should never replace, but rather compliment traditional treatments prescribed by your doctor.  Curcumin could potentially offer some relief for arthritis and help prevent cancer and alzheimer’s disease.

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  1. #1 by Cftr Potentiators (@potentiater) on July 17, 2014 - 5:01 AM

    You are dangerously wrong about curcumin for cystic fibrosis. Your “balanced” evaluation of curcumin for Cystic fibrosis is balanced towards old studies. New information – that you even reference! – shows that in combination with genistein, they are an efficious potentiator for CFTR. Testimonials from patients at http://www.potentiate.info are evidence of the curcumin/genistein combo working in-vivo. Recent studies have shown that curcumin has the same (but weaker) potentiating mechanism as ivacaftor (kalydeco) – http://www.potentiate.info/?q=kalydeco-genistein, and genistein has a different (but, complementary/additive) mechanism.
    I really hope Vertex didn’t pay for this advice 😦

    • #2 by Jesse Thornton on July 17, 2014 - 10:10 AM

      You’re not bringing any new information to the discussion. My evaluation was based on all the available peer-reviewed evidence that I could find. Anecdotal evidence is not good enough and THAT can be dangerous to perpetuate. As you mentioned, I do cite the study that found the genistein and curcumin combination to be effective in rescuing CFTR function in cell culture BUT with the rare G551D mutation only. I can’t comment on the in-vivo study as I don’t have access to that article and have no way to evaluate the methods used. You seem to elude to clinical studies with curcumin combination therapies in your article, however, I have not seen any clinical evidence to support these claims, in fact, the 2014 Jonge paper that you cite acknowledges the need for clinical studies. Furthermore, how are they purposing to overcome the poor bio-availability of curcumin? Is there something about genistein that allows the molecule to survive longer in the bloodstream? It’s easy to deliver clinically relevant doses to cells and even in mice but that simply does not translate to humans.

      Why were these studies performed exclusively in a rare CFTR mutation, where is the evidence for Delta F508? If it works for G551D only, that’s great, I just find it curious that was the mutation chosen…I certainly would be cautious if I were you when you make blanket statements about the effectiveness of certain CFTR potentiators in regards to all CFTR mutations, especially based on the scant evidence available. You may have good intentions but you don’t know how your audience will act on the information you present.

      All I’m seeing are red flags. What I offer is a realistic and cautious approach to the information I present. If you read my article, you would find that I DO NOT advocate AGAINST taking curcumin, stressing that there’s no harm in trying it in conjunction WITH your normally prescribed medication. In fact, I actually point out curcumin formulations that can be purchased over the counter that would likely offer the highest bio-availability, therefore, offering the greatest chance of being clinically beneficial. I wish I was paid for this! Unfortunately no one pays me to write anything 😦

  2. #3 by Cftr Potentiators (@potentiater) on July 29, 2014 - 4:10 PM

    The in-vitro studies which have been published on the curcumin-genistein combo are only shown to work on G551D. That is correct. There is no evidence either in-vivo or otherwise that it would work on F508del – which requires a corrector (or two) to help the misfolded mutant protein reach the cell surface. The curcumin-genistein combo is a potentiator, not a corrector, – of course it won’t fix F508del. Ivacaftor studies have shown that it is efficious on about 12.5% of the CF population – not just the 5% of G551D patients. What the new evidence shows (Jih and Hwang, 2013 from DeJonge paper) is a model for the mechanism of potentiation of Ivacaftor. DeJonge describes how curcumin has the same mechanism of action, and genistein has a different, but complementary mechanism of actions (based on the O1 and O2 states, see blog post link above). This is in-vitro evidence – also evidence (maybe not in your in-vivo only world). It shows that genistein helps in-vitro. We now also have many testimonies of patients that it is working in vivo. Real results – significant sweat test drops of 62 mmol/L and 35 mmol/L using bioavailable formulations of curcumin (curcumin with bioperine and bcm95, respectively).
    You will not see pharmaceutical companies conduct trials for curcumin/genistein as a potentiator, as you cannot patent them. You will not see PIII study results for CF – the only evidence you seem to value. However, there are plenty of in-vivo safety studies and toxicity studies for curcumin and genistein, so we know they are largely safe, even at high doses. We also know that they work in-vivo, just like Ivacaftor did in-vivo. We now know that they work in many patients who have tried them (I know the people reporting the testimonies through facebook). In my world, that’s evidence enough to encourage people who have mutations who can benefit from a potentiator to try and see if they help their CF. If you’re a doctor, however, you’ll only worry about covering your ass….

  3. #4 by Jesse Thornton on July 29, 2014 - 6:28 PM

    I weigh the entirety of evidence that is presented to me and I certainly give more weight to certain types of evidence than others, that’s generally how science is supposed to work. I don’t only value in-vivo studies as you seem think, but as a scientist, I know how often cell culture results simply do not translate to humans, or even mice, because you can never mimic the body’s complex microenvironment and interplay between different cell types in a glass dish. That doesn’t stop the lay person or even the scientist from reciting the results of those studies as gospel. Its disingenuous and it can be a dangerous practice bordering on the realm of unethical pseudoscience. How many people die of cancer due to stopping their treatments because they hear about cell culture studies involving phytonutrients that fight cancer, or because of a general distrust in science and pharmaceuticals? How many people with Cystic Fibrosis shorten their lifespan unnecessarily because they stop their traditional treatments in favor of a naturalistic approach? How we communicate findings through research is very important for those reasons.

    Just to hit on a couple other things. Ivacaftor does not = curcumin/genistein. There certainly could be clinical trials involving curcumin and CF provided researchers can make a convincing enough case to draw funding, they’ve done it in other studies like the arthritis study I mentioned in the original post. Curcumin itself cannot be patented, and yet you named a couple curcumin formulations that are indeed patented…curcumin still needs a delivery system to make it more bioavailable so there is a potential to make money. I believe that BCM95 has actually been used in a couple phase III clinical trials.

    However, my stance is and remains the same as yours, so I’m not entirely sure why you have a problem with me. I’ll say it again: There’s no harm in trying curcumin, as long as you stay on the current medical regiment given by your doctor. However, unlike yourself, I’m very careful about how I word my statements and try to put everything into the correct context rather than making statements based on emotion. I myself have CF, and I want to be able say “this works” but the best I can say based on the science is “this might work, just know that it might not work.”

  4. #5 by Cftr Potentiators (@potentiater) on August 9, 2014 - 4:25 PM

    We’re going to get a chance to see if the curcumin/genistein combo works, as a clinical trial on it has just begun in the Nethrland: http://www.potentiate.info/?q=tictac-clinical-trial
    They will be testing for a gating mutation whether if curcumin/genistein is comparable as Ivacaftor as a potentiator.

  5. #6 by Jesse Thornton on August 9, 2014 - 6:00 PM

    Great news, seems like it was only a matter of time, hopefully they will have success!

  6. #7 by John Wilkinson IV on December 10, 2014 - 10:30 AM

    To stimulate further discussion, perhaps another section to this excellent review: has any research been done to see which Phase I and Phase II detoxication enzymes metabolize curcumin? Are these perhaps stimulated by curcumin? This could be important as these enzyme systems are also responsible for breaking down most pharmaceuticals. Curcumin engagement of particular phase I enzymes could lead to changes in blood levels of other treatments, either increasing the levels or halflife in the blood of them (if curcumin acts to block their breakdown) or decreasing their levels or halflife in the blood (if curcumin leads to upregulation of the enzymes). This could lead to either potentiation of or a reduction in the impact of treatments that are concurrent with curcumin consumption.

    • #8 by Jesse Thornton on January 23, 2015 - 3:22 PM

      I meant to answer this question sooner, but it slipped my mind. It seems that curcumin does inhibit Phase I enzymes, which would lead to less activation of harmful compounds, while stimulating Phase II enzymes which would lead to enhanced detoxification of already active carcinogens. So, potentially it could lead to a longer lasting duration for a drug that has to pass through Phase I and II before it is eliminated by the body. In fact, one study found exactly that: concurrent use of curcumin with tamoxifen increased the bioavailability of tamoxifen (http://www.ncbi.nlm.nih.gov/pubmed/22512082) by inhibiting a Phase I enzyme.

  7. #9 by Siri on January 3, 2015 - 11:51 AM

    In Ayurvedic medicine it would be suggested to heat the turmeric before intake
    by cooking in a little water or frying in dry pan, and then ingesting in fatty medium like milk or butter – all this probably to increase uptake in body.

  8. #10 by Sally Robertson on January 6, 2015 - 7:13 PM

    Thank you for this informative and interesting review of the effects of curcumin. My son is engaged to a woman who has a child with CF. I do not know which mutation, but I know it is an uncommon one. Your article is helping me to understand more about the disease and the possibility of curcumin as a help. John, it is nice to hear from someone who has CF.

    • #11 by Jesse Thornton on January 23, 2015 - 3:26 PM

      I’m glad you found it informative Sally! Treatment for CF has improved drastically over the years and we’re getting closer to a cure every year. I imagine a child born with CF today has a bright future. Eating well, plenty of exercise and compliance with a prescribed medical regiment is very important and will help ensure that as well.

  9. #12 by Kirsty on September 30, 2015 - 7:18 PM

    Simply fantastic review Jesse.

    I’ve been doing a lot of research recently on Turmeric (and more specifically Curcumin) and it’s numerous health benefits. This article is by far the most informative I’ve come across to date.

    Take a bow 🙂 x

  10. #14 by Kirsty on October 2, 2015 - 10:21 AM

    Hey Jesse!

    Its just come to my attention that one of the guys in the office put out an article on Turmeic I think might interest you.

    He’s like you in the sense he backs up everything with solid research so take a peek if you have the chance – http://www.oxfordvitality.co.uk/turmeric-as-good-as-gold.

    Funnily enough it was because of the peripherpal ‘Turmeric chatter’ in the office that I then came across your site initially. Now it’s come full circle, hahaha. Great shout on the Poppy the herbalist recommendation by the way, really nice site. Many thanks x

    • #15 by Jesse Thornton on October 2, 2015 - 1:31 PM

      I’ll look into that!

      Good to know there is turmeric chatter in offices around the world driving traffic to my site, haha 😉

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