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Osteoarthritis and Cartilage (2008) 16, 1275e1276

ª 2008 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.joca.2008.02.017

International
Cartilage
Repair
Society

Letter to the Editor

Avocado/soybean unsaponifiables, ASU EXPANSCIENCE, are strictly

different from the nutraceutical products claiming ASU appellation

Laboratoires EXPANSCIENCE have discovered, devel- pharmaceutical company and the related research teams
oped and produced a pharmaceutical product, PIASCLE- on ASU EXPANSCIENCE for nearly 20 years2e10.
DINE 300, which is effective for the ‘‘symptomatic, To give the scientific community appropriate clarification
delayed-effect treatment of arthrosis of the hip and knee’’ on these structural differences, we can say that ‘‘the
(wording from the MA indication). The active principle of originality of PIASCLEDINE 300 is based on the A/S ratio
this pharmaceutical product is called ASU EXPAN- (1:2) and specific composition of both unsaponifiables. The
SCIENCE and is composed of a mixture of soybean main components of these unsaponifiables are tocopherols,
unsaponifiables and specific avocado unsaponifiables. sterols and specific molecules from avocado obtained by
The specificities of the product and elements of the process proprietary and particular patented process’’11e13. Such
are protected by patents. avocado unsaponifiable (AU) is quite different from com-
Recently, Au RY et al. have demonstrated that a so called mon, natural AU. The active substance, ASU EXPAN-
ASU extract, named ASU-NMX 1000TM (Nutramax Labora- SCIENCE, is obtained in the pharmaceutical quality
tories Inc, Edgewood, MD, USA), suppressed tumour ne- context by controlling all in-process steps and the traceabil-
crosis factor (TNF)-a, IL-1b, cyclooxygenase (COX)-2 and ity of the entire production chain.
iNOS gene expression, and PGE2 and nitric oxide produc- We have also studied three NUTRAMAX commercial
tion in articular chondrocytes and monocyte/macrophages1. products containing ASU-NMX 100:
In the introduction, following a brief point on arthrosis, the
mediators involved and the usual treatments (NSAIDs)  DASUQUIN with MSM;
prescribed for treating this pathology, the authors propose  DASUQUIN; and
the use of avocado and soybean unsaponifiables (ASU)  AVOCA ASU,
as an alternative or additional therapeutic approach. To
make their case, the authors list and describe several in comparison with our ASU EXPANSCIENCE. The
clinical, animal and in vitro studies demonstrating the phar- results of the study were presented at the poster session
macological and clinical efficacy of ASU. of the last OARSI World Congress on Osteoarthritis 2007
We must draw your attention to the fact that the ASU in Fort Lauderdale14.
used and tested in all of the studies referred to in the text In order to characterise each product chemically, we have
are strictly original and unique ASU EXPANSCIENCE e used different analytical methods that have been validated
active ingredient of the patented pharmaceutical product according to ICH Q2R1 guidelines:
PIASCLEDINE 300 from Laboratoires EXPANSCIENCE
and there is no existing alternative on the market. For
many years, mainly in Europe but also in other parts of gas chromatography;
the world, the action of ASU EXPANSCIENCE in the UV spectrometry;
symptomatic treatment of arthrosis has been recognised unsaponifiable content determined by ‘‘the American Oil
through the pioneering, original investment of Laboratoires Chemistry Society N Ca 6a-40’’ method; and
EXPANSCIENCE. a mathematical approach to the analytical data has
In the following sections of the text, the authors describe been performed by Normalised Principal Component
and discuss in vitro studies aiming to demonstrate the Analysis (nPCA)14.
biological activity of ASU-NMX1000 (NUTRAMAX Labora-
tories), which have nothing in common structurally with The analysis of data significantly demonstrated that the
ASU EXPANSCIENCE, except for the general label commercial nutraceutical products from NUTRAMAX claim-
ASU. ing the ASU label are totally different from the common and
As such, scientifically speaking, these results cannot natural sterol based avocado and soybean unsaponifiables
under any circumstances be put into perspective or and also from ASU EXPANSCIENCE (PIASCLEDINE
combined with the data that have been published by our 300) (Tables I and II):

1. Absence of or no detectable specific molecules from

*Address correspondence and reprint requests to: C. Baudouin, common natural avocado unsaponifiables like the
Ph.D., Laboratoires EXPANSCIENCE, Rue des quatre filles, BP key molecule, citrostadienol;
25034, 28231 Epernon Cedex, France. Tel: 33-2-37-20-36-02; 2. Absence of patented molecules from Laboratoires
Fax: 33-2-37-20-33-91; E-mail: [email protected] EXPANSCIENCE;

1275
1276 P. Msika et al.: Avocado/soybean unsaponifiables

Table I
Content of each fraction evaluated by chromatographic analyses
Content in %w/w EXPANSCIENCE Tocopherols Sterols Proportion of Proportion of
patented molecules (alpha-tocopherol, (brassicasterol, brassicasterol* citrostadienoly
delta-tocopherol, campesterol, in the phytosterols in the phytosterols
gamma- stigmasterol, pool pool
tocopherol) beta-sitosterol,
citrostadienol)
ASU EXPANSCIENCE >10 >10 >15 Not detected Presence
DASUQUIN with MSM e Not detected 0.1 28.2 1.4% Not detected
NUTRAMAX
(DASU MSM NUTR)
DASUQUIN e NUTRAMAX Not detected 0.5 30.0 1.3% Not detected
(DASU NUTR)
AVOCA ASU e NUTRAMAX Not detected 1.0 49.9 1.4% Not detected
(AVOCA ASU NUTR)

*Rapeseed oil or related unsaponifiables imprint.

yAvocado unsaponifiable imprint.

P. Msika, Ph.D., C. Baudouin, Ph.D.*,

A. Saunois, Ph.D., T. Bauer, Ph.D.
Laboratoires EXPANSCIENCE, R&D Center,
Table II Rue des quatre filles BP 25034,
Analysis of the differences in composition
28231 Epernon Cedex, France
ASU NUTRAMAX
EXPANSCIENCE commercial
(PIASCLEDINE 300) nutraceutical products References
Patented Yes No 1. Au RY, Al-Talib TK, Au AY, Phan PV, Rondoza CG. Avocado soybean
molecules unsaponifiables (ASU) suppress TNF-alpha, IL-1beta, COX-2, iNOS
Tocopherols Yes Yes but divided by 25e50 gene expression, and prostaglandin E(2) and nitric oxide production
in articular chondrocytes and monocyte/macrophages. Osteoarthritis
Sterols Cartilage 2007;15(11):1249e55.
From Yes Yes 2. Maheu E, Mazières B, Valat JP, Loyau G, Le Loët X, Bourgeois P, et al.
soybean Symptomatic efficacy of avocado/soybean unsaponifiables in the treat-
From Yes No (citrostadienol ment of osteoarthritis of the knee and hip. Arthritis Rheum 1998;41:81e91.
avocado absent or non detectable) 3. Appelboom T, Schuermans J, Verbruggen G, Henrotin Y, Reginster JY.
From No Yes ( presence of Symptoms modifying effect of avocado/soybean unsaponifiables
(ASU) in knee osteoarthritis. A double blind, prospective, placebo-
rapeseed brassicasterol)
controlled study. Scand J Rheumatol 2001;30:242e7.
ASU as Yes 100% No (NUTRAMAX 4. Blotman F, Maheu E, Wulwik A, Caspard H, Lopez A. Efficacy and safety
conclusion commercial nutraceutical of avocado/soybean unsaponifiables in the treatment of symptomatic
products presented as osteoarthritis of the knee and hip. Rev Rhum Engl 1997;64:825e34.
5. Lequesne M, Maheu E, Cadet C, Dreiser RL. Structural effect of
unsaponifiables are mainly avocado/soybean unsaponifiables on joint space loss in osteoarthritis
composed of soybean and of the hip. Arthritis Rheum 2002;47:50e8.
rapeseed sterols) 6. Cake MA, Read RA, Guillou B, Ghosh P. Modification of articular
cartilage and subchondral bone pathology in an ovine meniscectomy
model of osteoarthritis by avocado and soya unsaponifiables (ASU).
Osteoarthritis Cartilage 2000;8:404e11.
7. Khayyal MT, el-Ghazaly MA. The possible ‘‘chondroprotective’’ effect of
the unsaponifiable constituents of avocado and soya in vitro. Drugs
3. Presence of brassicasterol, which is highly specific for Exp Clin Res 1998;24:41e50.
8. Boumediene K, Felisaz N, Bogdanowicz P, Galera P, Guillou GB,
rapeseed oil and related unsaponifiables; Pujol JP. Avocado/soya unsaponifiables enhance the expression of
4. Very low tocopherols content: it demonstrates that the transforming growth factor beta1 and beta2 in cultured articular
compositions of NUTRAMAX commercial nutraceuti- chondrocytes. Arthritis Rheum 1999;42:148e56.
cal products do not correspond to real soybean oil 9. Henrotin YE, Sanchez C, Deberg MA, Piccardi N, Guillou GB, Msika P,
et al. Avocado/soybean unsaponifiables increase aggrecan synthesis
unsaponifiables; and and reduce catabolic and proinflammatory mediator production by
5. The specific proportion of ASU EXPANSCIENCE human osteoarthritis chondrocytes. J Rheumatol 2003;30:1825e34.
(1:2) is not maintained. 10. Henrotin YE, Deberg MA, Crielaard JP, Piccardi N, Msika P, Sanchez C.
Avocado/soybean unsaponifiables prevent the inhibitory effect of
osteoarthritis subchondral osteoblasts on aggrecan and type II colla-
In conclusion, we would like to remind scientists and gen synthesis by chondrocytes. J Rheumatol 2006;33:1668e78.
rheumatologists of the risk of confusion arising from the 11. Patent US 314 118, 1994.
commercial or scientific use of the acronym ASU with no 12. Patent PCT FR00/02601, 2000.
chemical basis, the unauthorised use of scientific property, 13. Patent PCT FR02/02715, 2002.
14. Bauer T, Baudouin C, Saunois A, Legrand J, Msika P. Comparison of
and the abused backing of ASU EXPANSCIENCE original and authentic pharmaceutical avocado and soybean unsapo-
(PIASCLEDINE 300). The specific composition of ASU nifiables versus some alleged nutraceutical imitations determined by
EXPANSCIENCE (PIASCLEDINE 300) is associated gas chromatoraphy and spectrophotometry analyses (Abstract). Os-
with the widely demonstrated in vitro and in vivo clinical teoarthitis Cartilage 2007;15(Suppl C):C79,128.
15. Christensen R, Bartels EM, Astrup A, Bliddal H. Symptomatic efficacy of
activities allowing the recommendation of the original, avocado-soybean unsaponifiables (ASU) in osteoarthritis (OA)
authentic and pharmaceutical ASU EXPANSCIENCE in patients: a meta-analysis of randomized controlled trials. Osteoarthri-
the management of osteoarthritis2e10,15. tis Cartilage 2007.