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ABSORPTION AND BIOAVAILABILITY OF LIQUID GLUCOSAMINE VERSUS GLUCOSAMINE PILLS AND TABLETS

Bioavailability defined.  "The commonly accepted definition of bioavailability is the proportion of the nutrient that is digested, absorbed and metabolized through normal pathways. Consequently, it is not enough to know how much of a nutrient is present in a dietary supplement; the more important issue is how much of that present is bioavailable."  [V.S. Srinivasan, Bioavailability of Nutrients:  A Practical Approach to In Vitro Demonstration of the Availability of Nutrients I Multivitamin-Mineral Combination Products, Journal of Nutrition, 2001; 131:1349S-1350S.] 

"Bioavailability is a pharmacokinetic term that describes the rate and extent to which the active drug ingredient is absorbed from a drug product and becomes available at the site of  drug action."  [M. Makoid, P. Vuchetich, and U. Banakar, Basic Pharmacokinetics, Chapter 8: 8-2 (1999) (can be viewed at http://pharmacy.creighton.edu/pha443/pdf/Default.asp])

"[D]ecreasing bioavailability is related to the number of steps involved in the absorption process following administration.  The greater the number of steps a product must undergo before the final absorption step, the slower is the availability and the greater is the potential for bioavailability differences to occur.  Thus, solutions (elixirs, syrups, or simple solutions) generally result in faster and more complete absorption of drug, since a dissolution step is not required.  Enteric-coated tablets, on the other hand, do not even begin to release the drug until the tablets empty from the stomach, resulting in poor and erratic bioavailability.  

Factors affecting bioavailability  --  Science showing reasons why glucosamine pills and capsules are not as easily absorbed and as bioavailable as liquid glucosamine. 
There are no direct studies measuring the percentages of absorbability and bioavailability of liquid glucosamine versus pill, capsule, or powder forms of glucosamine.  There are such studies measuring oral glucosamine against IV and IM glucosamine.  Nevertheless, the general science seems to support a finding that liquid glucosamine is more absorbable and more bioavailable than the solid forms of glucosamine found in pills, capsules, and powders.  The general science shows:

*          solutions
*          suspensions
*          capsules
*          tablets
*          coated tablets
*          controlled-release formulations.

There are other factors related to the dosage form that can affect the dissolution rate of a supplement, its bioavailability and, therefore, its therapeutic performance and the needed dosage: 

Physiochemical properties of the supplement
Formulation and
manufacturing variables
particle size amount of disintegrant
crystalline structure amount of disintegrant
degree of hydration of crystal amount of disintegrant
salt or ester form nature of diluent
compression force

Binders and fillers.

Absorption in mouth

Liquids are in part absorbed by the sublingual mucosa (floor of the mouth) and buccal mucosa (sides and top of the oral cavity) whereas pills, capsules, and powders are unlikely to be absorbed at all until they reach the intestine to be dissolved in digestive enzymes.  The buccal mucosa is much thicker than the sublingual mucosa but absorption through either of them allows the active ingredient to avoid mixing with digestive enzymes.

The Glucosamine Studies on Absorption and Bioavailability

Most of the studies concerning glucosamine show that they used either pills or intravenous insertion.  The best studies on the pharmacokinetics of liquid glucosamine are:

*          Setnikar I., Palumbo R, Canali S et al., Pharmacokinetics of glucosamine in man, Arzneim Forsch 1993; 44:1109-1113 (hereinafter "Setnikar on Man");
*          Setnikar I, Giachetti C, Zanolo G, , Pharmacokinetics of glucosamine in the dog and in man, Arzneim Forsch 1986; 36:729-735 (hereinafter "Setnikar on Dog").


Setnikar on Man noted that glucosamine is very soluble in water, has a small molecule, and is easily diffusible in the body compartments.  The study examined iv, im, and oral administration of GS and found that after oral administration, about 90% of glucosamine sulfate is absorbed thru the gastrointestinal tract (determined by noting that about 11.3% of the radioactivity passed thru fecal excretion; therefore, the rest was absorbed).  The bioavailability in blood plasma proteins of the orally administered GS relative to iv administration is only 26%.  The bioavailability of im administered GS was 96% of that of iv administration.  The absorption time for the orally administered GS is hours behind that of the iv (which is fastest for obvious reasons) and im administration.  The study used glucosamine HCL in a .615% solution in water diluted with unlabelled GS and water for oral administration.


Setnikar on Dog, done 7 years earlier, also looked at iv and oral administration of GS.  They used glucosamine HCL in a .615% solution in water diluted with unlabelled GS and salt and water for oral administration.  They used a gastric tube on the dogs and GS in commercial sugar-coated tablets for the humans.  They found 87% gastrointestinal absorption in the dogs of the orally administered dose and concluded the result was about the same with humans but could not show it because they could not ethically use the radioactivity on the humans.  Note that in Setnikar on Man they had 2 human subjects ingesting the radioactive substance.

On March 15, 2000, Dr. Robert C. Schenck, Jr., of the Department of the Orthopaedics, University of Texas Health Science Center, San Antonio, Texas, made a presentation on oral glucosamine and chondroitin sulfate.  I obtained a copy of the 4-page outline of that presentation.  On the first page, he mentions that in an industry funded study in 1997, McNamara and Barr found that oral glucosamine sulfates was absorbed 70-87% through the gut though I could not find on the internet the reference for McNamara and Barr arriving at those percentages. 

The Institute of Medicine and National Research Council of the National Academies created certain dietary supplement ingredient prototype monographs as examples for a report entitled "Dietary Supplement:  A Framework for Evaluating Safety."  The prototype was published by the National Academies Cress in Washington, D.C.  Both the IOM and the NRC were established by the National Academy of Sciences.  They prepared six prototype monographs.  One of the them is on "Glucosamine."  Another is on "Shark Cartilage."  On page C-2 of the Glucosamine Monograph at paragraph I.B.2., the report states that "[g]lucosamine sulfate is a salt that is easily absorbed with 90% of the compound being absorbed at most doses used."  It also notes in section I.C. on page C-3 that manufacturers typically suggest a daily dose of between 500 and 2000 milligrams per day with 500 milligrams taken three times daily as the most frequently recommended.  They note at page C-10 that glucosamine is absorbed from the "gastrointestinal tract and significantly metabolized on the first pass through the liver (or possibly within the gastrointestinal tract) and are rapidly excreted as carbon dioxide in urine and feces."  On page C-12 they note that "[o]rally-ingested glucosamine appears to be rapidly absorbed but to be largely metabolized before it reaches the blood stream."

In the review of numerous studies of various chondroprotective agents, several doctors took note of Setnikar on Man study and stated that:
Glucosamine sulfate is a small, water-soluble molecule that is readily absorbed by the gastrointestinal tract (90% absorption) by carrier-mediated transport.  It is not clear whether the glucosamine sulfate molecule is absorbed in its entirety or is degraded prior to absorption.  Bioavailability in humans after first-pass metabolism by the liver is approximately 26% for the oral preparation, 96% for the intra-muscular form, and 100% for the intravenous agent.

In another review of studies, Kasra Pournadeali, the Director of Stephens Naturopathic Medical Center wrote an article entitled "Glucosamine Sulfate:  A Review of Efficacy for the Pharmacy Professional" in the International Journal of Pharmaceutical Compounding, Nov.-Dec. 1999, pp. 1-9.  On page 2, the report states:

Absorption of oral glucosamine sulfate is highly efficient (with studies showing a 90% to 98% absorption), although parenteral use of glucosamine sulfate does achieve a five-fold higher plasma concentration.  [citing to Setnikar on Man and the 1996 Encyclopedia of Nutritional Supplements, pp,. 336-341).]

In Glucosamine Sulfate:  A Review of Efficacy for the Pharmacy Professional, in the November/December 199 issue of the International Journal of Pharmaceutical Compounding, Kasra Pournadeali, ND, of the Stevens Naturopathic Medical Center in Edmonds, Washington wrote:

Absorption of oral glucosamine sulfate is highly efficient (with studies showing a 90% to 98% absorption), although parenteral use of glucosamine sulfate does achieve a fivefold higher plasma concentration . . .  Interestingly, articular cartilage and a few other tissues display active uptake for glucosamine sulfate; while passive diffusion is typical of most tissues.   Glucosamine sulfate has been shown to cross the blood-synovial barrier; and, despite resulting in lower serum concentrations than with parenteral use, orally administered glucosamine sulfate has near-identical pharmacokinetics after the first-pass effect of the liver.      

She does not distinguish between pills and liquid glucosamine in her report. 

 

 


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