Curcumin is one of the most heavily researched herbs due to its potential to impact the inflammatory process in several models. One key concern, in some studies, is bioavailability or absorption, which has likewise raised concerns as to its true efficacy in regards to health conditions.  Are these concerns truly founded or is it all hype? Experience tells us that it is a little of both.

This bright orange, very expensive herb in pure form is something that I personally work with daily.  It is used not only in clinical research, but also a staple in the middle Eastern diet, most often in the form of Turmeric.  Curcumin is also used in the dye and cosmetic industry, taking advantage of its bright orange color and staining ability. It’s power is strong, both medicinally and in its staining capabilities…trust me on this.  I have come to know curcumin on a personal and intimate level.

Curcumin is one of the most heavily researched herbs, impacting the inflammatory process on a more complete level compared to any medication on the open market.  The mode of action is through inhibition or actually a downregulation of a transcription factor called NF-kB, which when stimulated or turned on, is responsible for the production of numerous pro-inflammatory proteins which impact pain, swelling, circulation, cell turnover, altered cellular function and cellular death or degeneration. 

In 2005, I began my investigations with curcumin, being intrigued by research and seeing potential as a therapy option in my equine patients afflicted with joint disease, who were dependent on medications and injections to get them through the month. Looking over past human data, curcumin was noted to impact the inflammatory process on a much higher level than traditional medications, providing potentially higher benefits to the patient, not only in reduction of pain but also improving cellular function. This last benefit is huge, as dysfunction at a cellular level is tied in with most health conditions, pain is often just a byproduct and a symptom.  The concern, as noted in human studies was that serum levels of curcumin were low, thus raising the question of bioavailability.  In-vitro testing on cells proved encouraging, but this is different than using it in a real, living, breathing body. Would it work?

In our first equine model, in 2006, we evaluated a 95% extract of Curcumin along with Boswellia, flax seed and trace antioxidants, delivered with a meal to the patients once daily for 30 days.  The majority of these patients were in their teens, suffered chronic joint ailments and had a dependence on pain medications.  During the study, we monitored joint fluid, evaluating inflammatory cytokines or proteins before and after therapy. The patients were removed from their current medications in order to assess improvement.  At the end of this study, the patients were improved significantly on lameness scores.  They did not require continued use of their pain medications and the owners noted that a few freely ran about in the pasture, something they had not done in a long while.  Upon repeat evaluation of the joint fluid, there was a moderate decrease in inflammatory cytokines, PGE-2 and MMP-9, both involved not only in pain perception but also joint deterioration. This was all good news and opened up the door for a new tool for us to use in our practice, but what about serum levels? We noted at the end of the study that the average curcumin serum level was 1.5 µM, 2 hours post ingestion, which is consistent with human models.1

The ultimate question here is what levels should we expect and do higher blood levels equate to higher levels of efficacy for the patient? Clearly, based on our study, despite perceived low serum levels, something took place in that patient.  There was obvious down regulation of inflammatory proteins and the patients also improved clinically in regards to overall lameness.

Human studies seem to either focus on absorption and bioavailability or efficacy, but rarely both at the same time.  There are many models out there that clearly demonstrate efficacy in human models of osteoarthritis, noting improvement in trial recruits with reduction of pain, but don’t focus on bioavailability. Then on the other side of the coin, we have models that strictly set out to determine bioavailability parameters, but not necessarily also evaluating efficacy at the same time.  To me, this creates confusion for on one hand we have several studies that demonstrate clinical improvement, but on the other side, we have studies claiming that bioavailability is a concern.  This low bioavailability then raises the question of efficacy.  How can it possibly work clinically if the blood levels are too low?  I think, personally, this is the misconception.

In human models, using a 95% curcumin extract at variable dosing of 1000 – 12,000 mg per day, they averaged serum levels ranged from 0.51 – 1.77 µM.In some rat models, curcumin was noted to have the highest tissue levels in the intestine and liver, while maintaining trace to non-existent levels elsewhere in the body. It was determined that curcumin undergoes extensive reduction via alcohol dehydrogenase, followed by conjugation, which mainly takes place in the liver.  In rats, the major biliary metabolites of curcumin are glucuronides of tetrahydrocurcumin (THC) and hexahydrocurcumin (HHC). The ultimate question comes as to whether if these metabolites are as active as curcumin itself? 3

Again, the issue of bioavailability is constantly raised, despite having clinical evidence in other studies of efficacy, despite potentially low serum levels. Is this concern real?  In my opinion, based on clinical and research experience, I do not believe that the two are as dependent as we’d like to think.  Despite this, research continues to enhance bioavailabilty, seeking the holy grail, if you will, to further improve patient outcome. But, is the right way to go?

There are a few things to keep in mind when discussing curcumin. First, in traditional cultures, the mother herb Turmeric was most often consumed not only as part of the diet but also medicinally.  Curcumin is one of many active components of Turmeric, being discovered many years later and soon formed into concentrated extracts up to 95%. Curcumin is fat soluble, meaning it does not dissolve in water but fat instead.  Interestingly enough, Turmeric is a root or herb that contains high levels of naturally occuring fats or volatile oils.  When we look at nature, as a whole, we see that these naturally present oils in the root, actually help to enhance the absorption of its active ingredients, including Curcumin. If we were to look at curcuminoid levels in the blood, post ingestion of Turmeric, potentially we would see higher levels.  However, the ultimate issue is that Turmeric only contains about 2-4% curcumin by volume, so the levels of this vital active ingredient are low, in respect to the volume of herb consumed.  If a human study was utlizing 8000 mg of a 95% Curcumin extract to get results, then potentially if using Turmeric, one would have to consume upwards of 40 grams.  That volume would likely create difficulties for the average person.  Considering this, researchers move onward, fixated on making that curcumin more bioavailable.

In recent years, it has been noted that concurrent administration of piperine along with a curcumin extract improved bioavailability and serum levels.  This is true, but most of these studies only noted an increase in serum levels for the first few hours post ingestion with a usual peak at 3 hours, then a steady decline.  Piperine was utilized as it interferes with normal curcumin metabolism in the liver, thus contributing to higher serum levels.  However, there have been some concerns with piperine toxicity in experimental animals. In other models, researchers are binding curcumin analogues to liposomes or fat molecules with the goal to enhance absorption.  This route has proven encouraging, but in most of these products, the actual level of curcumin present per dose is much lower than desired, in my opinion, thus there is potential to have to increase the dose based on my experience when compared side by side with other formulations in my research patients.4

A newer, interesting and logical approach is being demonstrated in the BCM-95® Curcumin formulation.  In this product, the volatile oils present naturally in the Turmeric root are combined back with the curcumin extract to enhance absorption naturally.  In a side by side study, BCM-95® was compared to standard curcumin and also to a piperine based curcumin formulation.   The BCM-95® demonstrated not only higher serum levels, but also a longer duration of those serum levels, lasting upwards of 7 hours post ingestion.

As a comparison, standard curcumin demonstrated a peak plasma level of 150 ng/g at 2 hours.  The piperine-curcumin formulation demonstrated a peak of 300 ng/g at 3 hours, while the BCM-95® formulation indicated a level of 400 ng/g at 3 hours which continued to rise with a peak of 600 ng/g at 6 hours post ingestion.  In all models, a dose of 2000 mg was used.4  This is why we choose to utilize BCM-95® on a daily basis in our Cur-OST® formulas.

So, what does all of this tell us?  To be honest, no one is really sure.  On one hand, we have studies raising concern over bioavailability, then other studies clearly demonstrating efficacy in patients.  Do the two conflict?  Yes, but on what level?  Is a high serum level truly needed or even desirable? Is it possible that curcumin is acting in a different manner, potentially outside of high serum levels that we’d like to see with pharmaceutical medications? History tells us that something is astray here, as in ancient medicinal cultures they simply used Turmeric with good results, no fancy science, no serum levels. Could they have done better, maybe through concentrated curcumin extracts?  Quite possibly.

The one thing that I note, based on reading through research, clinical experience and doing our own research, is that in most human studies or even rat models, there is no mention of the herb being consumed with food.  This is important from my perspective as curcumin or actually Turmeric was a staple of the diet, taken as food.  Also, the herb is fat soluble, so thus potentially if taken with a meal, naturally present fats may enhance absorption.  To the best of my knowledge, this factor has not been explored.  Could this explain why patients in our trials did so well?  Maybe, but even with them consuming the herb along with food, they still had perceived low serum levels.  And despite low serum levels, there was clinical improvement

One thing that I noted in our equine research patients was that while on curcumin, it was not uncommon for me to wipe their hooves with an alcohol swab and have it come back orange in color.  Alcohol actually dries out fats, pulls them from tissues, thus by seeing curcumin color on the swab, it indicates to me that the curcuminoids had actually accumulated in the fats or oils within the hoof capsule.  These are just observations on my part.

In more recent research that we have conducted, focusing on the equine gastrointestinal tract, it becomes obvious that this organ system is directly involved with the generalized inflammatory response.  This has been demonstrated by the existence of bacterial overgrowths that when resolved or improved, equates to a lower generalized inflammatory response in that patient with clinical improvement.  If we step back, look at this data and also take into consideration the volume of human data, we begin to see connections and possibilities.  Inflammation is really about cellular signaling, passing back and forth proteins and chemicals, which then trigger cellular reactions.  It is almost like telling a secret in one location and watching it spread to another by word of mouth.  Is it possible, considering that curcumin maintains the highest levels in the intestinal tract and liver, that potentially it is acting locally, more than systemically?  Meaning, is it impacting cellular signaling and function at a local level, which then transfers upstream to the rest of the body, like a secret?  This is only a theory on my end, again based on experience, but it is a theory that is agreed upon as a potential by other curcumin researchers as well.

There is some newer research coming out in regards to an enzyme, IAKLP, or intestinal alkaline phosphatase.  This enzyme (ALKP) is produced by the liver, intestine and bone.  It is therefore something we monitor in routine blood work for indications of liver problems, specifically the gallbladder.  The intestinal form, IAKLP, is known to be very important in regards to controlling inflammation, maintaining tight cell junctions (preventing leaky gut) and also modifying bacterial populations within the gut.  In many diseases or conditions, there is a noted decrease in IAKLP, which may result or contribute to further health problems and even leaky gut with all of its subsequent concerns.  Stress, in general, and also diet can negatively impact IAKLP, contributing to digestive issues.  Curcumin has been noted to impact IAKLP, by increasing its expression and production, thereby exhibiting gastrointestinal protective benefits, not only on inflammation, but also by potentially helping to stablize bacterial populations.  Going back to complete body cellular signaling, we now question if curcumin’s power actually is being exhibited in the gut, with impact on IAKLP, which then further signals and anti-inflammatory trend throughout the body.5  If this is the case, then low serum or plasma levels may not actually be a player in curcumin’s mode of action on the body and overall health.

Curcumin is a very valuable herb, not only in dollars but also medicinally.  Tremendous potential exists for this herb and it deserves special attention and respect when it comes to human, equine and companion pet health.  It is one of the most potent down regulators of inflammation, often rivaling the abilities of prescription medications when it comes to restoring comfort.  Considering the lack of side effects, even at high doses, it is one that deserves real attention for therapy options, despite perceived low serum or plasma levels.

Thank you.

Tom Schell, D.V.M.

Nouvelle Research, Inc.

www.nouvellresearch.com

 

 

References:

1. Schell, T. A promising natural therapy for equine osteoarthritis. JAHVMA, 2009, vol 28, 1, 11-15.

2. Goel, A et al. Curcumin as ‘Curecumin’; From Kitchen to Clinic. Biochem Pharmacol, 2007

3. Anand, P et al. Bioavailability of Curcumin; Problems and Promises. Mol Pharma, 2007

4. Antony, B et al. A Pilot Cross Over Study to Evaluate Human Oral Bioavailability of BCM-95; A Novel Bioenhanced Preparation of Curcumin. Ind Jour             Pharma Sci, 2008, 70(4), 445-450

5. Ghosh, S et al. Curcumin and Chronic Kidney Disease; Major mode of action by stimulating endogenous intestinal alkaline phosphatase. Molecules,             2014, 19, 20139-20156.

 

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