Joint Max-Flex
Supplement Facts

Supplement Facts
Serving Size: 1 capsule
Serving per Container: 60

Amount per Serving                                              % Daily Value

Glucosamine Sulfate                   1500mg                            *
SAMe Butanedisulfonate              120mg                            *

Proprietary Blend 716mg
Collagen Type II, Chondroitin Sulfate, Glucosamine Sulfate, SAMe Butanedisulfonate, Devil’s Claw Extract, Indian Frankincense Extract, Curcumin Extract

*Daily Value not established

Other Ingredients: Maltodextrin, Magnesium Stearate, Gelatin, Glycerin & Purified Water

GLUCOSAMINE SULFATE**

Glucosamine sulfate is a naturally occurring chemical found in the human body. It is used by the body to produce a variety of other chemicals that are involved in building tendons, ligaments, cartilage, and the thick fluid that surrounds joints.

Joints are cushioned by the fluid and cartilage that surround them. In some people with osteoarthritis, the cartilage breaks down and becomes thin. This results in more joint friction, pain, and stiffness. Researchers think that taking glucosamine supplements may either increase the cartilage and fluid surrounding joints or help prevent breakdown of these substances, or maybe both.

Some researchers think the “sulfate” part of glucosamine sulfate is also important. Sulfate is needed by the body to produce cartilage. This is one reason why researchers believe that glucosamine sulfate might work better than other forms of glucosamine such as glucosamine hydrochloride or N-acetyl glucosamine.

Help maintain healthy joints: Clinical trials show that taking glucosamine sulfate orally significantly improves symptoms of pain and functionality compared to placebo in patients with osteoarthritis of the knee in studies lasting up to 3 years (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12). *

Glucosamine sulfate seems to decrease pain scores by about 28% to 41% and improve functionality scores by 21% to 46% (12, 13).*

Clinical research shows that glucosamine sulfate is comparable to the nonsteroidal anti-inflammatory drugs (NSAIDs) ibuprofen and piroxicam (Feldene) for symptom relief (3, 5, 6).*

Other clinical research shows that glucosamine sulfate 1500 mg once daily for 6 months might be more effective than acetaminophen 1 gram 3 times daily for reducing symptoms in patients with moderate osteoarthritis of the knee (11). *

Patients taking glucosamine for up to 3 years seem to have significantly less knee joint degeneration, less joint space narrowing, and significant symptom improvement when compared with placebo (7, 8,14). *

A meta-analysis suggests that glucosamine sulfate might reduce the risk of osteoarthritis progression by up to 54% (13).*

A retrospective analysis of patients who took glucosamine sulfate for 1-3 years also shows that glucosamine sulfate is associated with a 57% decreased risk of total knee replacement (15, 16).*

SAMe Butanedisulfonate**

S-adenosylmethionine (SAMe) is a naturally occurring molecule that is distributed throughout virtually all body tissues and fluids. Concentrations are highest in childhood and decrease with age (1, 2). *

The body uses SAMe to make certain chemicals in the body that play a role in pain, depression, liver disease, and other conditions. People who don’t make enough SAMe naturally may be helped by taking SAMe as a supplement.  * 

Helpful for osteoarthritis: Multiple clinical trials show that taking SAMe orally is superior to placebo and comparable to NSAIDs, including the COX-2 inhibitor celecoxib (Celebrex), for decreasing symptoms associated with osteoarthritis. SAMe is associated with fewer adverse effects than NSAIDs and is comparable in reducing pain and improving functional limitation (3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13) .*

After take for seven days, SAMe levels in synovial fluid increase by 3 to 4 fold (14).*

Preliminary evidence suggests SAMe might stimulate articular cartilage growth and repair, specifically chondrocyte proteoglycan synthesis and proliferation rate (11, 14). *

SAMe might also protect against cytokine-induced cell damage (14).*

Significant symptom relief with SAMe may require up to 30 days of treatment compared to only 15 days with NSAIDs. *

Currently, several oral salt forms of SAMe are available: sulfate, sulfate-p-toluenesulfonate (also labeled as tosylate), and butanedisulfonate (15). *

The oral bioavailability of the tosylate salt is 1%, and the oral bioavailability of the butanedisulfonate salt is 5%, presumably due to a large first pass effect (16, 17, 18).*

Chondroitin sulfate**

Chondroitin sulfate is normally found in cartilage around joints in the body. Chondroitin sulfate belongs to a class of very large molecules called glycosaminoglycans (GAGs), which are made up of glucuronic acid and galactosamine. People use chondroitin for osteoarthritis because it is endogenously found in cartilaginous tissues and serves as a substrate for the formation of the joint matrix structure (1, 2, 3).*

Helpful for osteoarthritis: Most early research from the 1980s until 2001 shows that taking chondroitin sulfate along with conventional analgesics or nonsteroidal anti-inflammatory drugs (NSAIDs) significantly reduces pain and improves functionality in patients with osteoarthritis of the hip and knee after several weeks of treatment (4, 5, 6, 7, 8, 9,1, 10,11,12) .*

Some evidence also shows that a specific combination product, which contains chondroitin sulfate plus glucosamine and manganese can improve both objective and subjective measures of pain in patients with osteoarthritis of the knee (13, 14).*

There is evidence that chondroitin sulfate protects cartilage against degradation by inhibiting the action of the enzyme leukocyte elastase, by decreasing the migration of polymorphonuclear leukocytes, and by increasing the synthesis of proteoglycans and hyaluronic acid (3, 15).*

Devil's claw**

Devil’s claw is an herb. This plant, which is native to Africa, gets its name from the appearance of its fruit, which is covered with hooks meant to attach onto animals in order to spread the seeds.

Helpful for osteoarthritis: Taking devil's claw orally alone or in conjunction with nonsteroidal anti-inflammatory drugs (NSAIDs) seems to help decrease osteoarthritis-related pain (1, 2, 3, 4).*

Some evidence suggests that devil's claw is comparable to diacerhein (a slow-acting drug for osteoarthritis; not available in the US) for improving osteoarthritis pain in the hip and knee after 16 weeks of treatment. Patients taking devil's claw also seem to be able to decrease use of NSAIDs for pain relief (1). *

Devil's claw contains iridoid glycoside constituents primarily harpagoside, but also including harpagide, and procumbide; it appears that other compounds besides harpagoside contribute to its effect (5, 6). *

Research suggests that harpagoside inhibits both the cyclooxygenase (COX) and lipoxygenase inflammatory pathways (7).*

 Devil's claw seems to inhibit COX-2 (but not COX-1) and nitric oxide synthetase, a modulator of inflammation (8，9).*

Indian frankincense**

Indian frankincense is a plant. It is used for osteoarthritis, rheumatoid arthritis, joint pain (rheumatism), bursitis, and tendonitis.

The principle constituents of Indian frankincense are boswellic acid and alpha- and beta-boswellic acid, which have anti-inflammatory properties (1).*

In preliminary research, Indian frankincense extracts show anti-inflammatory and antiarthritis effects, but not all Indian frankincense-containing products have antiarthritis, anti-inflammatory, or antipyretic effects (2).*

There is some preliminary evidence that taking Indian frankincense extract orally might reduce osteoarthritis symptoms such as knee pain and swelling (2).*

Curcumin**

Curcumin is a plant. You probably know turmeric as the main spice in curry. It has a warm, bitter taste and is frequently used to flavor or color curry powders, mustards, butters, and cheeses.*

Curcumin seems to have anti-inflammatory activity, possibly by inhibiting cyclooxygenase-2 (COX-2), prostaglandins, and leukotrienes (1, 2, 3, 4).*

Preliminary clinical research suggests that the turmeric constituent, curcumin, might reduce some symptoms of rheumatoid arthritis (RA) (5，6).*

* These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure or prevent any disease.

GLUCOSAMINE SULFATE**

1. McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA 2000;283:1469-75.
2. Drovanti A, Bignamini AA, Rovati AA. Therapeutic activity of oral glucosamine sulfate in osteoarthrosis: a placebo-controlled, double-blind investigation. Clin Ther 1980;3:260-72.
3. Lopes Vaz AL. Double-blind, clinical evaluation of the relative efficacy of ibuprofen and glucosamine sulphate in the management of osteoarthrosis of the knee in out-patients. Curr Med Res Opin 1982;8:145-9.
4. Pujalte JM, Llavore EP, Ylescupidez FR. Double-blind clinical evaluation of oral glucosamine sulphate in the basic treatment of osteoarthrosis. Curr Med Res Opin 1980;7:110-4.
5. Qiu GX, Gao SN, Giacovelli G, et al. Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with knee osteoarthritis. Arzneimittelforschung 1998;48:469-74.
6. Forster K, Schmid K, Rovati L, et al. Longer-term treatment of mild-to-moderate osteoarthritis of the knee with glucosamine sulfate- a randomized controlled, double-blind clinical study. Eur J Clin Pharmacol 1996;50:542.
7. Reginster JY, Deroisy R, Rovati LC, et al. Long-term effects of glucosamine sulfate on osteoarthritis progression: a randomised, placebo-controlled trial. Lancet 2001;357:251-6.
8. Pavelka K, Gatterova J, Olejarova M, et al. Glucosamine sulfate use and delay of progression of knee osteoarthritis: A 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med 2002;162:2113-23.
9. Richy F, Bruyere O, Ethgen O, et al. Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis. Arch Intern Med 2003;163:1514-22.
10. Braham R, Dawson B, Goodman C. The effect of glucosamine supplementation on people experiencing regular knee pain. Br J Sports Med 2003;37:45-9.
11. Bruyere O, Pavelka K, Rovati LC, et al. Glucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: evidence from two 3-year studies. Menopause 2004;11:138-43.
12. Poolsup N, Suthisisang C, Channark P, Kittikulsuth W. Glucosamine long-term treatment and the progression of knee osteoarthritis: systematic review of randomized controlled trials. Ann Pharmacother 2005;39:1080-7.
13. Towheed TE, Maxwell L, Anastassiades TP, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev 2005;(2):CD002946.
14. Zhang W, Doherty M, Arden N, et al. EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2005;64:669-81.
15.**Jellin JM, Gregory PJ, et al. Pharmacist’s letter/Prescriber’s Letter Natural Medicines Comprehensive Database. 12th ed. Stockton, CA: Therapeutic Research Faculty; 2009: P797-801.
16. Bruyere O, Pavelka K, Rovati LC, et al. Total joint replacement after glucosamine sulphate treatment in knee osteoarthritis: results of a mean 8-year observation of patients from two previous 3-year, randomised, placebo-controlled trials. Osteoarthritis Cartilage 2008;16:254-60.

SAMe Butanedisulfonate**

1.**Jellin JM, Gregory PJ, et al. Pharmacist’s letter/Prescriber’s Letter Natural Medicines Comprehensive Database. 12th ed. Stockton, CA: Therapeutic Research Faculty; 2009: P1488-1492.
2. Saletu B, Anderer P, Di Padova C. Electrophysiological neuroimaging of the central effects of S-adenosyl-L-methionine by mapping of electroencephalograms and event-related potentials and low-resolution brain electromagnetic tomography. Am J Clin Nutr 2002;76:1162S-71S.
3. Bradley JD, Flusser D, Katz BP, et al. A randomized, double blind, placebo controlled trial of intravenous loading with S-adenosylmethionine (SAM) followed by oral SAM therapy in patients with knee osteoarthritis. J Rheumatol 1994;21:905-11.
4. Domljan Z, Vrhovac B, Durrigl T, Pucar I. A double-blind trial of ademetionine vs naproxen in activated gonarthrosis. Int J Clin Pharmacol Ther Toxicol 1989;27:329-33.
5. Konig B. A long-term (two years) clinical trial with S-adenosylmethionine for the treatment of osteoarthritis. Am J Med 1987;83:78-80.
6. Berger R, Nowak H. A new medical approach to the treatment of osteoarthritis. Report of an open phase IV study with ademetionine (Gumbaral). Am J Med 1987;83:84-8.
7. Muller-Fassbender H. Double-blind clinical trial of S-adenosylmethionine versus ibuprofen in the treatment of osteoarthritis. Am J Med 1987;83:81-3.
8. Vetter G. Double-blind comparative clinical trial with S-adenosylmethionine and indomethacin in the treatment of osteoarthritis. Am J Med 1987;83:78-80.
9. Maccagno A, Di Giorgio EE, Caston OL, Sagasta CL. Double-blind controlled clinical trial of oral S-adenosylmethionine versus piroxicam in knee osteoarthritis. Am J Med 1987;83:72-7.
10.  Caruso I, Pietrogrande V. Italian double-blind, multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint disease. Am J Med 1987;83:66-71.
11. di Padova C. S-adenosylmethionine in the treatment of osteoarthritis. Review of the clinical studies. Am J Med 1987;83:60-5.
12. Glorioso S, Todesco S, Mazzi A, et al. Double-blind, multicentre study of the activity of S-adenosylmethionine in hip and knee osteoarthritis. Int J Clin Pharmacol Res 1985;5:39-49.
13. Hardy M, Coulter I, Morton SC, et al. S-Adenosyl-L-Methionine for Treatment of Depression, Osteoarthritis, and Liver Disease. Evidence Report/Technology Assessment Number 64. Agency for Healthcare Research and Quality, US Dept of Health and Human Services; 2002. AHRQ publication 02-E033. Rockville, Md. Available at: http://www.ahrq.gov/clinic/tp/sametp.htm.
14. Bottiglieri T. S-Adenosyl-L-methionine (SAMe): from the bench to the bedside--molecular basis of a pleiotrophic molecule. Am J Clin Nutr 2002;76:1151S-7S.
15. Friedel HA, Goa KL, Benfield P. S-adenosyl-L-methionine. A review of its pharmacological properties and therapeutic potential in liver dysfunction and affective disorders in relation to its physiological role in cell metabolism. Drugs 1989;38:389-416.
16. Investigator's Brochure: Ademetionine 1,4-butanedisulfonate. Knoll Pharmaceuticals.
17. Stramentinoli G, Gualano M, Galli-Kienle M. Intestinal absorption of S-adenosyl-L-methionine. J Pharmacol Exp Ther 1979;209:323-6.

Chondroitin sulfate**

1.Bucsi L, Poor G. Efficacy and tolerability of oral chondroitin sulfate as a symptomatic slow-acting drug for osteoarthritis (SYSADOA) in the treatment of knee osteoarthritis. Osteoarthritis Cartilage 1998;6 Suppl A:31-6.
2.Kelly GS. The role of glucosamine sulfate and chondroitin sulfates in the treatment of degenerative joint disease. Altern Med Rev 1998;3:27-39.
3.Pipitone VR. Chondroprotection with chondroitin sulfate. Drugs Exp Clin Res 1991;17:3-7 .
4.Morreale P, Manopulo R, Galati M, et al. Comparison of the anti-inflammatory efficacy of chondroitin sulfate and diclofenac sodium in patients with knee osteoarthritis. J Rheumatol 1996;23:1385-91.
5.Conrozier T. [Anti-arthrosis treatments: efficacy and tolerance of chondroitin sulfates]. Presse Med 1998;27:1862-5.
6.Mazieres B, Loyau G, Menkes CJ, et al. [Chondroitin sulfate in the treatment of gonarthrosis and coxarthrosis. 5-months result of a multicenter double-blind controlled prospective study using placebo]. Rev Rhum Mal Osteoartic 1992;59:466-72.
7.Leeb BF, Schweitzer H, Montag K, Smolen JS. A meta-analysis of chondroitin sulfate in the treatment of osteoarthritis. J Rheumatol 2000;27:205-11.
8.Uebelhart D, Thonar EJ, Delmas PD, et al. Effects of oral chondroitin sulfate on the progression of knee osteoarthritis: a pilot study. Osteoarthritis Cartilage 1998;6:39-46.
9.Bourgeois P, Chales G, Dehais J, et al. Efficacy and tolerability of chondroitin sulfate 1200 mg/day vs chondroitin sulfate 3 x 400 mg/day vs placebo. Osteoarthritis Cartilage 1998;6:25-30.
10.*Jellin JM, Gregory PJ, et al. Pharmacist’s letter/Prescriber’s Letter Natural Medicines Comprehensive Database. 12th ed. Stockton, CA: Therapeutic Research Faculty; 2009: P426-429.
11.McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA 2000;283:1469-75.
13.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.
14.Das A Jr, 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;8:343-50.
15.12.Mazieres B, Combe B, Phan Van A, et al. Chondroitin sulfate in osteoarthritis of the knee: a prospective, double blind, placebo controlled multicenter clinical study. J Rheumatol 2001;28:173-81.

Devil's claw**

1.Chantre P, Cappelaere A, Leblan D, et al. Efficacy and tolerance or Harpagophytum procumbens versus diacerhein in treatment of osteoarthritis. Phytomedicine 2000;7:177-84.
2.Chrubasik S, Thanner J, Kunzel O, et al. Comparison of outcome measures during treatment with the proprietary Harpagophytum extract doloteffin in patients with pain in the lower back, knee or hip. Phytomedicine 2002;9:181-94.
3.Gagnier JJ, Chrubasik S, Manheimer E. Harpgophytum procumbens for osteoarthritis and low back pain: a systematic review. BMC Complement Altern Med 2004;4:13.
4.Wegener T, Lupke NP. Treatment of patients with arthrosis of hip or knee with an aqueous extract of devil's claw (Harpagophytum procumbens DC). Phytother Res 2003;17:1165-72.
5.Lanhers MC, Fleurentin J, Mortier F, et al. Anti-inflammatory and analgesic effects of an aqueous extract of Harpagophytum procumbens. Planta Med 1992;58:117-23 .
6.Fiebich BL, Heinrich M, Hiller KO, Kammerer N. Inhibition of TNF-alpha synthesis in LPS-stimulated primary human monocytes by Harpagophytum extract SteiHap 69. Phytomedicine 2001;8:28-30..
7.Chrubasik S, Sporer F, Dillmann-Marschner R, et al. Physicochemical properties of harpagoside and its in vitro release from Harpagophytum procumbens extract tablets. Phytomedicine 2000;6:469-73.
8.**Jellin JM, Gregory PJ, et al. Pharmacist’s letter/Prescriber’s Letter Natural Medicines Comprehensive Database. 12th ed. Stockton, CA: Therapeutic Research Faculty; 2009: P562-565.
9.Jang MH, Lim S, Han SM, et al. Harpagophytum procumbens suppresses lipopolysaccharide-stimulated expressions of cyclooxygenase-2 and inducible nitric oxide synthase in fibroblast cell line L929. J Pharmacol Sci 2003;93:367-71.

Indian frankincense**

1.Ammon HP, Safayhi H, Mack T, Sabieraj J. Mechanism of antiinflammatory actions of curcumine and boswellic acids. J Ethnopharmacol 1993;38:1139.
2.Kimmatkar N, Thawani V, Hingorani L, et al. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee--a randomized double blind placebo controlled trial. Phytomedicine 2003;10:3-7.

Curcumin**

1.Zhang F, Altorki NK, Mestre JR, et al. Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells. Carcinogenesis 1999;20:445-51.
2.Surh YJ. Anti-tumor promoting potential of selected spice ingredients with antioxidative and anti-inflammatory activities: a short review. Food Chem Toxicol 2002;40:1091-7.
3.Araujo CC, Leon LL. Biological activities of Curcuma longa L. Mem Inst Oswaldo Cruz 2001;96:723-8.
4.Takada Y, Bhardwaj A, Potdar P, Aggarwal BB. Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-kappaB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation. Oncogene 2004;23:9247-58.
5.*Jellin JM, Gregory PJ, et al. Pharmacist’s letter/Prescriber’s Letter Natural Medicines Comprehensive Database. 12th ed. Stockton, CA: Therapeutic Research Faculty; 2009: P1684-1686.
6.Deodhar SD, Sethi R, Srimal RC. Preliminary study on antirheumatic activity of curcumin (diferuloyl methane). Indian J Med Res 1980;71:632-4.

1.     What are the health benefits of taking Joint Max-Flex?

The powerful, fast-acting natural ingredients in the Joint Max-Flex are key structural support for your joints and cartilage. It helps to nourish, lubricate, cushion, and rebuild joints. It also supports mobility, flexibility, and comfortable movement.*

2.     Is it best to take the Joint Max-Flex with meal?

Yes, it is always best to take your nutritional supplements with a meal. This allows your body to absorb the nutrients more efficiently and with a greater degree of tolerance.*

3.     How many Joint Max-Flex capsules should I take a day?

For adult, take 2 capsules with meal, 2 times a day at day time.

4.     Can I take at night time?

Take Joint Max-Flex at day time with meal; do not take it at night time.

* These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure or prevent any disease.