Resveratrol Lozenges: A New Proof of Concept Experiment

For the most part, the vast majority of studies examining the health effects of resveratrol (a compound found in red wine) have used oral consumption of the product, such as an oral pill or capsule, as well as a powder swallowed by the participants.  As you probably know from your experiences with various health concerns or maladies, there are other mechanisms for drug delivery in addition to a pill form, including various types of injections as well as through a lozenge held in the mouth.  While many studies have shown that the lozenge is an excellent form of drug delivery for some medications in terms of its efficiency and subsequent bioavailability in the blood stream, using the lozenge as a form of resveratrol delivery has

Photo from

Photo from

been largely ignored.

In humans, large doses of resveratrol are required in order to achieve the positive health benefits that are associated with this kind of treatment.  However, these higher doses, while they have been shown to provide various positive health benefits for the recipient, they have also been shown to be associated with a few not-so-pleasant side effects, including gastrointestinal upset and diarrhea in otherwise healthy patients.

One of the downsides to administering resveratrol through an oral tablet or pill is that there is quite a lot of variability in terms of the metabolism and bioavailability of the compound in blood/plasma, stemming from the mechanism of swallowing the drug and the subsequent path of that drug through the digestion system.  Specifically, when taking resveratrol using an oral supplement, it is metabolized and undergoes a wealth of structural and chemical changes as it passes through the small intestine as well as the liver.  In the small intestine, resveratrol has been shown to be glycosolated and sulfated, in addition to possible alterations made by native gut microbes present in the digestive system.  After making it through the small intestine, resveratrol travels to the liver which metabolizes the compound further prior to its entry into the blood stream.

Utilizing a different drug delivery system, such as through a lozenge, may bypass this metabolism by being directly absorbed into the blood stream through the mucosa in the mouth.  Oral transmucosal delivery (OTM) basically avoids all the metabolism of resveratrol by the gut, and goes directly into the blood stream at theoretically higher concentrations.  In theory, the dose administered using OTM delivery could be significantly less than the doses needed for oral supplements, since much more of the drug is

Photo By Adrian Michael (Own work) [GFDL ( or CC-BY-SA-3.0-2.5-2.0-1.0 (], via Wikimedia Commons

Photo By Adrian Michael (Own work) [GFDL ( or CC-BY-SA-3.0-2.5-2.0-1.0 (], via Wikimedia Commons

absorbed in pure form right off the bat instead of metabolizing a lot of it prior to absorption.

With today’s post, I present to you the results of a new proof-of-concept study examining the effectiveness of resveratrol administration through a lozenge, which could have possible implications for clinical relevance.


Solubility of resveratrol in different solutions was measured in order to find an appropriate medium for the lozenge.  Solutions tested were: dextrose, fructose, ribose, sucrose, and xylitol.  Based on the results of this test (shown below), the ribose solution was used to create the resveratrol lozenges for the pilot experiment.

Four 2000mg resveratrol lozenges were created using established hard lozenge techniques.  Contents of the lozenges were as follows: 46% ribose, 46% fructose/sucrose mixture, and 8% resveratrol.

Final concentrations of resveratrol in the lozenges were determined using HPLC techniques.

Human participants for the pilot study were required to be at least 18 years old with no history of cardiorespiratory, neurological, or metabolic disease.  Participants were excluded from the study if they reported to regularly take medications or supplements that were derived from grapes.

Participants were required to fast the evening prior to the experimental procedures.  A fasting blood sample was taken for baseline measurements.

After baseline blood samples were taken, participants were given one of the resveratrol lozenges and were instructed to keep the lozenge between their gums and their cheek until it was completely dissolved.  Participants were discouraged from swallowing any piece of the lozenge or their saliva during the course of the experiment.

Blood samples were taken every 15 minutes over the course of 1 hour throughout the experiment.  This time frame was selected based on previous research that indicates within 1 hour is the expected time frame for OTM absorption.

Blood plasma concentrations were analyzed using HPLC with UV detection.

When referring to resveratrol in this paper, I am referring to the trans-resveratrol configuration.


  • The solubility of resveratrol was significantly improved using the ribose solution medium, whereas solubility was not enhanced using any of the other solutions.
  • Four resveratrol lozenges were created, with a mean resveratrol concentration of 146.2mg (+/-5.5) per 2000mg lozenge.
  • 2 healthy male participants were recruited for this pilot study (NOTE:  we won’t have statistical significance anywhere in a sample size this small.  Remember: this is a proof of concept test).
  • Participants noted the resveratrol lozenges had a pepper-like taste to them, and that they were able to follow all instructions as required.
  • Neither participant reported any side effects or unusual events during the experiment.
  • Blood plasma concentrations of resveratrol at baseline were below the level of detection, and were assumed to be zero.
  • Blood plasma concentrations of resveratrol peaked at 15 minutes after lozenge administration.
  • At 30, 45, and 60 minutes post lozenge administration, blood plasma concentrations of resveratrol were below detectable limits.
  • The dosage of resveratrol in the lozenges (0.14g) resulted in blood plasma concentrations much higher than similar doses reported using resveratrol supplements.  For example, peak blood plasma levels of resveratrol were over 300ng/mL for lozenge delivery (0.14g dose of resveratrol), while other studies have reported peak blood plasma levels of resveratrol were below 50ng/mL for oral supplements at a similar dose of resveratrol (0.15g).
  • Time to peak blood plasma concentrations of resveratrol was faster for the lozenge delivery method compared with oral supplement reported in the literature.  For example, for a 0.14g dose of resveratrol as seen in the resveratrol lozenges, time to peak blood plasma concentrations was less than 20 minutes.  On the other hand, for a 0.15g dose of resveratrol in an oral supplement (as reported by other studies), time to peak blood plasma concentrations was closer to 80 minutes.


According to the results of this proof of concept study, administering resveratrol through an OTM delivery system, such as a ribose-based lozenge, may enhance the absorption of resveratrol directly into the blood stream.  The authors noted that the concentrations of resveratrol found in the blood plasma of participants after 15 minutes were much higher than what has been reported for gut delivery systems (such as supplements or other pills), though this should be taken with a grain of salt due to the very low sample size.

Also of note: while ribose was the solution that provided the greatest enhancement of resveratrol solubility, it may not be the only option.  Future studies should focus on varying concentrations of ribose in addition to other solutions and mixtures, in order to find the most optimal solution base for resveratrol

"The Great Lozenge Maker" (1858; John Leech).  Photo courtesy of Flickr user electrons_fishgils (

“The Great Lozenge Maker” (1858; John Leech). Photo courtesy of Flickr user electrons_fishgils (

lozenges to maximize solubility and ultimately absorption of resveratrol into the blood stream.

In terms of peak blood plasma levels of resveratrol, this proof of concept study noted that after 15 minutes, resveratrol levels in plasma had peaked, and then dropped off to undetectable levels after 30 minutes and later.  While 15 minutes was the peak time noted in this study, it may not be the exact timing of this peak, since 15 minutes was the first time point measured in the experiment.  It is possible that peak blood plasma concentrations rose even higher either before or after the 15 minute mark, but according to this study is not likely to occur after 30 minutes.  Future studies should further refine this time of peak blood plasma concentrations of resveratrol.

Since this was a proof of concept study, there are many more questions that have been raised in additions to the few that I mentioned above.  How much resveratrol is metabolized using this OTM delivery method via lozenge?  What metabolites are present in the blood after OTM delivery of resveratrol? How do the concentrations resveratrol in blood plasma vary from person to person after OTM/lozenge delivery?

In general, this proof of concept study has provided results that I believe are worthy of more large-scale studies.  If these results are repeatable, the resveratrol lozenge may be a treatment method that will allow for increased absorption into the blood stream using much lower doses, and may allow for acute treatment of various health problems due to the rapid absorption time.

I am intrigued by the results of this proof of concept study and am looking forward to seeing if these results are repeatable on a larger scale.

Source: Blanchard, O.L., Friesenhahn, G., Javors, M.A., and Smoliga, J.A. 2014. Development of a lozenge for oral transmucosal delivery of trans-resveratrol in humans: Proof of Concept. PLOS ONE 9(2): e90131.

1 comment for “Resveratrol Lozenges: A New Proof of Concept Experiment

  1. March 28, 2014 at 1:01 am

    I have read lots of good reviews about Resveratrol. As what I have read it is good for the heart and also it can help you to lose weight.

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