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TECHNICAL MONOGRAPHS
OUR FAMILY OF PRODUCTS
FOR JOINT HEALTH
REFERENCES
Mission Statement
To provide safe, effective,
quality products that improve
the quality of life
for our customers using:
1. Homandberg GA, Guo D, Ray LM, et al. Mixtures of glucosamine and chondroitin sulfate reverse fibronectin fragment mediated damage to cartilage more effectively than either agent alone.
Osteoarthritis Cartilage 2006;14:793-806.
2. Adebowale A, Du J, Liang Z, et al. The bioavailability and pharmacokinetics of glucosamine hydrochloride and low molecular weight chondroitin sulfate after single and multiple doses to beagle dogs.
Biopharm Drug Dispos 2002;23:217-225.
3. Chan PS, Caron JP, Orth MW. Effect of glucosamine and chondroitin sulfate on regulation of gene expression of proteolytic enzymes and their inhibitors in interleukin-1-challenged bovine articular cartilage explants.
Am J Vet Res 2005;66:1870-1876.
4. Chan PS, Caron JP, Rosa GJM, et al. Glucosamine and chondroitin sulfate regulate gene expression and synthesis of nitric oxide and prostaglandin E(2) in articular cartilage explants.
Osteoarthritis Cartilage 2005;13:387-394.
5. Dechant JE, Baxter GM, Frisbie DD, et al. Effects of glucosamine hydrochloride and chondroitin sulphate, alone and in combination, on normal and interleukin-1 conditioned equine articular cartilage explant
metabolism. Equine Vet J 2005;37:227-231.
6. Lippiello L, Woodward J, Karpman R, et al. In vivo chondroprotection and metabolic synergy of glucosamine and chondroitin sulfate. Clin Orthop Relat Res 2000;381:229-240.
7. McNamara PS, Barr SC, Erb HN, et al. Hematologic, hemostatic, and biochemical effects in cats receiving an oral chondroprotective agent for thirty days. Vet Therapeutics 2000;1:108-117.
8. McNamara PS, Barr SC, Erb HN. Hematologic, hemostatic, and biochemical effects in dogs receiving an oral chondroprotective agent for thirty days. Am J Vet Res 1996;57:1390-1394.
9. Orth MW, Peters TL, Hawkins JN. Inhibition of articular cartilage degradation by glucosamine-HCl and chondroitin sulphate. Equine Vet J Suppl 2002:224-229.
10. Sauve F, Paradis M, Refsal KR, et al. Effects of oral administration of meloxicam, carprofen, and a nutraceutical on thyroid function in dogs with osteoarthritis. Can Vet J 2003;44:474-479.
11. Chan PS, Caron JP, Orth MW. Effects of glucosamine and chondroitin sulphate on bovine cartilage explants under long-term cartilage conditions. Am J Vet Res 2007;68:709-715.
12. Chan PS, Caron JP, Orth MW. Short-term gene expression changes in cartilage explants stimulated with interleukin 1-beta plus glucosamine and chondroitin sulfate. J Rheumatol 2006;33:1329-1340.
13. Das AK, Hammad TA. Efficacy of a combination of FCHG49® glucosamine hydrochloride, TRH122® low molecular weight sodium chondroitin sulfate and manganese ascorbate in the management of knee osteoarthritis.
Osteoarthritis Cartilage 2000;8:343-350.
14. Leffler CT, Philippi AF, Leffler SG, et al. Glucosamine, chondroitin and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized, double-blind, placebo-controlled pilot study.
Mil Med 1999;164:85-91.
15. Scroggie DA, Albright A, Harris MD. The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus. Arch Intern Med 2003;163:1587-1590.
16. van Blitterswijk WJ, van de Nes JCM, Wuisman PIJM. Glucosamine and chondroitin sulfate supplementation to treat symptomatic disc degeneration: biochemical rationale and case report.
BMC Complement Altern Med 2003;3:2.
17. Schenck RC, Clare DJ, Gilley JS, et al. Role of a glucosamine/chondroitin sulfate formula in treatment of an osteochondral impaction injury in a collegiate basketball player. Ortho Tech Rev 2000;2:12-15.
18. Williams A, Gillis A, McKenzie C, et al.Glycosaminoglycan distribution in cartilage as determined by delayed gadolinium-enhanced MRI of cartilage (dGEMRIC): potential clinical applications. AJR 2004;182:167-172.
19. Lippiello L, Saiz P. Glucosamine and chondroitin sulfate: biological response modifiers of chondrocytes under simulated conditions of joint stress. Osteoarthritis Cartilage 2003;11:335-342.
20. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate and the two in combination for painful knee osteoarthritis. N Engl J Med 2006;354:795-808.
21. Leeb BF, Schweitzer H, Montag K, Smolen JS. A metaanalysis of chondroitin sulfate in the treatment of osteoarthritis. J Rheum 2000;27:205-211.
22. Richy F, Bruyere O, et al. Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis. Arch Intern Med 2003;163:1514-1522.
23. McAlindon TE, LaValley MP, Gulin JP, et al. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA 2000;283:1469-1475.
24. Kahan A, Uebelhart D, De Vathaire F, et al. Long term effects of chondroitins 4 and 6 sulfate on knee osteoarthritis: The study on osteoarthritis progression prevention, a two-year, randomized, double-blind,
placebo-controlled trial. Arthritis Rheum 2009;60(2):524-533.
25. Muniyappa R, Karne RJ, Hall G, et al. Oral glucosamine for 6 weeks at standard doses does not cause or worsen insulin resistance or endothelial dysfunction in lean or obese subjects.
Diabetes 2006;55:3142-3150.
26. Barnhill JG, Fye CL, Williams DW, et al. Chondroitin product selection for the glucosamine/chondroitin arthritis intervention trial. J Am Pharm Assoc 2006;46:14-24.
27. Data on file, Nutramax Laboratories, Inc.
28. Lippiello L, Nardo J, Harlan R, and Chiou T. Metabolic effects of avocado/soy unsaponifiables on articular chondrocytes. Evid Based Complement Alternat Med 2008;5:191-197.
29. Au R, Al-Talib TK, Au AY, et al. Avocado soybean unsaponifiables (ASU) suppress TNF- ␣, IL-1␤ ‚ COX-2, iNOS gene expression, and prostaglandin E2 and nitric oxide production in articular chondrocytes and
monocyte/macrophages. Osteoarthritis Cartilage 2007;15:1249-1255.
30. Au RY, Au AY, Frondoza CF. Suppression of TNF- ␣ , IL-1␤, iNOS, and P38 expression by the combination of avocado soy unsaponifiables, glucosamine, and chondroitin sulfate in human macrophage-like
THP-1 cells. [abstract] In Proceedings of the Osteoarthritis Research Society International. 11th World Congress on Osteoarthritis. Prague, Czech Republic.; Dec 7-10, 2006. P304.
31. Au RY, Au AY, Rashmir-Raven AM, et al. Inhibition of pro-inflammatory gene expression in chondrocytes, monocytes, and fibroblasts by the combination of avocado soybean unsaponifiables,
glucosamine, and chondroitin sulfate. Faseb J 2007;21(7):A702.7.
32. Au RY, Au AY, Cade M, et al. Down-regulation of pro-inflammatory markers in equine chondrocytes and osteoblasts by avocado soybean unsaponifiables, glucosamine, and chondroitin sulfate.
In Proceedings of the 2007 ACVS Veterinary Symposium. Chicago, IL; October 18-21, 2007.
33. Jomphe C, Gabriac M, Hale TM, et al. Chondroitin sulfate inhibits the nuclear translocation of nuclear factor-K ␤ in interleukin-1␤ -stimulated chondrocytes. Basic Clin Pharmacol Toxicol 2008;102:59-65.
34. Punke JP, Au AY, Au RY, et al. Modulation of prostaglandin E2 production in feline articular chondrocytes propagated in monolayer and dynamic microcarrier culture.
In Proceedings of the 2007 ACVS Veterinary Symposium.Chicago, IL; October 18-21, 2007.
35. Demko JL, Phan PV, Kramer EA, et al. Modulation of prostaglandin E-2 production in IL-1␤ activated chondrocytes propagated on microcarrier spinner culture. Proceedings of the 53rd Annual Meeting of
the Orthopaedic Research Society. San Diego, CA; February 11-14, 2007. A:507.
36. Ameye LG, Chee WS. Osteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence. Arthritis Res Ther 2006;8:R127.
37. Usha PR, Naidu MUR. Randomised, double-blind, parallel, placebo-controlled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis. Clin Drug Invest 2004;24:353-363.
38. Kim LS, Axelrod LJ, Howard P, et al. Efficacy of methylsulfonyl-methane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial. Osteoarthritis Cartilage 2006;14:286-294.
High quality ingredients
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practiced by the
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2208 Lakeside Boulevard • Edgewood, Maryland 21040
nutramaxlabs.com 1-800-925-5187
Patient samples and informative brochures
are available and easy to request.
Your choice:
• Call Customer Service 1-877-COSAMIN
• Visit cosaminsamples.com
These statements have not been evaluated by the Food & Drug Administration.
This product is not intended to diagnose, treat, cure, or prevent any disease.
13-1015-00
Printed on recycled paper.
Exclusive Formula
Published randomized, double-blinded, placebo-controlled clinical
trials have concluded that the combination of glucosamine
hydrochloride and pharmaceutical-grade chondroitin sulfate that
constitutes Cosamin DS is effective in improving joint function and
reducing joint pain.13,14,20 Several meta-analyses of published randomized clinical trials (RCTs) have reported the effectiveness of
pharmaceutical-grade chondroitin sulfate when compared to
placebo.21-23 A two year RCT published February 2009 in Arthritis
and Rheumatism, The Study on Osteoarthritis Progression
Prevention (STOPP), demonstrated that long-term administration
of CS (800 mg/daily) can slow knee joint structure degradation.
The minimum joint space width loss was significantly reduced in
the CS group as compared with the placebo group. In addition,
pain improved significantly faster in the CS group (P< 0.01) than
in the placebo group. The researchers concluded that CS has combined structure-modifying and symptom-modifying effects.24
Experimental in vitro and in vivo trials have demonstrated that the
combination of glucosamine and chondroitin sulfate was more
effective than either substance alone in inhibiting progression of
cartilage lesions and in maintaining cartilage health.1,5,6
▲
Source: SLACK Incorporated Market Research Survey, June 2005 and February 2006.
Surveys conducted of orthopedic surgeons and rheumatologists relating to glucosamine/chondroitin sulfate brands.
In published, controlled clinical trials, reported adverse effects
were similar in type and frequency among participants receiving a
placebo and those receiving glucosamine and/or sodium chondroitin sulfate as used in Cosamin DS. Additional clinical studies
have demonstrated that Cosamin DS, and glucosamine as a single
agent, have no effect on blood glucose concentrations, hemoglobin A1c or insulin resistance among those studied.15,25 There are no
known drug or dietary supplement interactions, or serious side
effects with Cosamin DS.
ASU is a potent compound derived from avocados and soybeans.
NMX1000® ASU is standardized to contain a minimum of 30%
avocado/soybean unsaponifiables. In vitro studies support the
effects of ASU for the promotion of joint health by:
. Stimulating production of collagen and proteoglycans, major
constituents of cartilage.
. Decreasing the expression of cyclooxygenase-2, the enzyme
that controls the production of prostaglandin E (PGE ).
. Decreasing expression of inducible nitric oxide synthase
(iNOS) which regulates the production of nitric oxide.
. Inhibiting the expression of tumor necrosis factor- (TNF- )
28
29†
2
2
10.5
10
p=0.04
9.5
ISK 9
8.5
8
7.5
7
Baseline
2
4
6
Months
Cosamin DS
Placebo
Fig. A WITH COSAMIN DS
Statistically significant functional improvement in the
Cosamin DS group versus placebo.
A double-blind, placebo-controlled study recruited 93 patients with knee pain
and mild or moderate radiographic changes of the knee from a single center.
Patients were evaluated initially and then every two months for six months.
The authors reported that patients in the Cosamin DS group showed significant improvement in knee pain scores as measured by Lequesne index of
severity of osteoarthritis of the knee (ISK) at four and six months compared
to the placebo group.13 Lower ISK values correlate with decreased knee pain.
Articular
Cartilage
NIH Study: Moderate-Severe Pain Group
100
Fig. B WITHOUT COSAMIN DS
90
79.2%
80
69%
70
p=0.002
p=0.06
60
50
Placebo
Celecoxib
Glu
CS
Glu/CS
Response rates in the subset of patients with
moderate to severe pain as measured by WOMAC.
Articular
Cartilage
Fig. A and B
Shown above are photomicrographs of representative safranin 0-stained histological sections
from femoral condyles harvested following a four-month placebo-controlled study which measured the influence of the orally administered ingredients of Cosamin DS on progression of cartilage breakdown in an animal model of joint destabilization. Proteoglycan is stained red by this
process, enabling the cartilage to be clearly visualized. Figure (A) demonstrates the protective
effect provided by the specific ingredients of Cosamin DS, which was typical of the subject cartilage in this group. Figure (B) is representative of the state of cartilage breakdown observed in
the placebo-administered group.6
For even greater control of inflammatory markers than
the combination of glucosamine and chondroitin sulfate
Cosamin®ASU is an advanced proprietary formulation that combines NMX1000® avocado/soybean unsaponifiables (ASU) with
Cosamin’s FCHG49® glucosamine and pharmaceutical-grade
TRH122® sodium chondroitin sulfate. This advanced formulation
was developed to provide an increased level of joint health support, with an even greater effect on inflammatory markers than the
combination of glucosamine and chondroitin sulfate.
Six-month follow up of patients
given Cosamin DS (Lequesne index data)
% Responders
The combined benefits of FCHG49® glucosamine and pharmaceutical grade TRH122® sodium chondroitin sulfate have been well
documented through published in vitro, in vivo, and human clinical studies.1-19 These specific trademarked ingredients have been
shown in laboratory in vitro research to inhibit expression of
degradative enzymes and mediators involved in the process of
cartilage breakdown. They also stimulate production of the cartilage matrix components which are comprised primarily of proteoglycans and type II collagen.
EFFICACY WITHOUT WORRY
Additional in vitro studies have elucidated potential mechanisms
by which the ingredients in Cosamin ASU may inhibit expression of
the mediators of cartilage breakdown. The combination of ingredients in Cosamin ASU decrease expression of transcription factor
nuclear factor KB and signal transduction gene, mitogen activated
protein kinase-14 (MAPK-14 also known as p38).30,33 The signal
transduction genes are key in the pathway of cartilage breakdown.
Inhibition of their expression may intervene in the process of cartilage breakdown.
The beneficial effects of inhibiting the expression of mediators
which contribute to the destruction of cartilage by the ingredients
in Cosamin ASU have been shown in vitro to extend across multiple cell types in the joint.30-32,34,35 The combination of ingredients
found in Cosamin ASU does not, however, completely block the
expression of inflammatory mediators. This is beneficial as low
levels of the mediators are necessary for normal cell, organ and
tissue function.
In the NIH-sponsored Glucosamine/chondroitin Arthritis Intervention Trial
(GAIT), efficacy in the reduction of knee pain was assessed on both glucosamine hydrochloride and chondroitin sulfate individually as well as in
combination. In the double-blind study conducted at 16 U.S. rheumatology
centers, 1583 patients with knee pain persisting at least 6 months and with
radiographic evidence of cartilage breakdown were each randomized to
receive one of five agents: a placebo, celecoxib, glucosamine hydrochloride,
chondroitin sulfate, or the combination of glucosamine hydrochloride and
chondroitin sulfate. The study concluded that the combination of glucosamine hydrochloride and chondroitin sulfate is effective in managing
moderate to severe knee pain.20 In the U.S. and Canada, the pharmaceutical-grade, 95% chondroitin sulfate used in this clinical trial is exclusively
found in Cosamin DS.26,27
ASU, Glucosamine, and Chondroitin Sulfate
Inhibits TNF- ␣ Expression in THP-1
Macrophage-Like Cells
120
Percent of Activated Control (%)
Cosamin®DS is the #1 orthopedic surgeon and rheumatologist
recommended brand ▲ of glucosamine/chondroitin sulfate. As a
joint health supplement, Cosamin DS helps reduce joint pain by
using ingredients that are safe, effective, easily absorbed, and
proven effective in controlled published U.S. clinical studies.
Proven effective for joint pain reduction in U.S. published clinical trials
100
80
60
p < 0.001
40
20
0
Control
Control+LPS
CS+GLU+LPS
ASU+CS+GLU+LPS
© 2008 Nutramax Laboratories, Inc.
Inhibition of TNF- ␣ gene expression in THP-1 macrophage-like cells
ASU, Glucosamine, and Chondroitin Sulfate
Inhibits IL-1␤ Expression
in THP-1 Macrophage-Like Cells
120
Percent of Activated Control (%)
THE ORTHOPEDIC SURGEON
AND RHEUMATOLOGIST
#1 RECOMMENDED BRAND
100
80
p = 0.004
60
40
20
0
Control
Control+LPS
CS+GLU+LPS
ASU+CS+GLU+LPS
28,29 †
␣
␣
© 2008 Nutramax Laboratories, Inc.
Inhibition of IL-1␤ expression in THP-1 macrophage-like cells
†Mediators involved in cartilage breakdown
and interleukin-1 ␤ (IL-1 ␤).29†
In vitro studies indicate that glucosamine and pharmaceuticalgrade sodium chondroitin sulfate when combined with
avocado/soybean unsaponifiables (ASU) are even more effective
at suppressing expression of inflammatory mediators than the
combination of glucosamine and chondroitin sulfate alone.30-32
Examples of these findings are illustrated in the graphs at right.
The cells used in these studies were stimulated with
Lipopolysaccharide (LPS). The untreated controls indicate the normal level of TNF- ␣ and IL-1␤ gene expression by the cells in these
studies.31
In vitro research has shown that the combination of
avocado/soybean unsaponifiables (ASU), glucosamine and
chondroitin sulfate decreases the levels of inflammatory markers associated with joint discomfort and cartilage breakdown
better than the combination of glucosamine and chondroitin
sulfate.
The benefits of Cosamin and MSM combined
Perfect for athletes and active people
Cosamin®MSM is an innovative once-a-day formulation that combines Cosamin’s proprietary FCHG49 glucosamine and pharmaceutical-grade TRH122 sodium chondroitin sulfate with methylsulfonylmethane (MSM) in a natural and artificial orange flavored dietary supplement–just add to water. Cosamin MSM was developed to offer a convenient, delicious way to support joint
health while providing an option for those who have difficulty swallowing capsules and tablets.
MSM is a di-methylated sulfone molecule [(CH3)2SO2]. This sulfur-containing organic compound is naturally present in low amounts in fruits,
corn, tomatoes, coffee and milk.36 Research supports the inclusion of
MSM into a Cosamin formulation as published clinical studies have
reported that study participants who were administered at least 1,500
mg of MSM demonstrated improved pain scores and quality of life.36-38
Many other products contain sub-optimal levels of MSM.
Convenient
once-a-day
serving