FLEXAGILITY™* MAX

(Product No. 01686)

 

DESCRIPTION:

FlexAgility MAX is a unique, proprietary formula designed to reduce pain and relieve stiffness associated with occasional overuse.*  Its clinically studied ingredients have been shown to help balance the body's natural anti-inflammatory response through three separate mechanisms.* Patented IsoOxygene^1M safely and significantly inhibits cyclooxygenase enzyme-2 , an important biochemical regulator of inflammation.*'  FlexAgility MAX also includes powerful free radical scavengers, and the enzyme bromelain, which have unique activity in blocking compounds that cause inflammation.*²"³

FlexAgility MAX:

•    A unique, proprietary formula

•     Includes clinically studied ingredients

•    Features patented IsoOxygene

•    Contains supercritical extracts of hops and ginger

•    Provides triple-action activity against occasional pain and inflammation*

STRUCTURE/FUNCTION:

FlexAgility MAX reduces pain and relieves stiffness due to occasional overuse.* FlexAgility MAX supports the body's natural anti-inflammatory function during times of occasional

FORMULA:

Each tablet contains:

Vitamin C (ascorbic acid)                                                                60 mg
Proprietary Flex Blend                                                                     545 mg

hops (Humulus lupulus) (Isooxygene

brand) flower extract, ginger (Zingiber officinale)

rhizome extract, and Boswellia serrata gum extract
Bromelain (2,400 G.D.U./g)                                                           100 mg
Japanese Sophora (Sophora japonica) Flower Bud                            75 mg

standardized to contain 95% rutin

European Elder (Sambucus nigra) Berry Extract 4:1                             25 mg
Green Tea (Camellia sinensis) Leaf Extract (decaffeinated)                  25 mg
standardized to contain a minimum of 70% polyphenols
N-Acetylcysteine (NAC)                                                                     25 mg

Other ingredients: See label for most current information.

Contains no: sugar, salt, yeast, wheat, gluten, corn, dairy products, artificial flavoring, preservatives, or ingredients of animal origin.   This product contains natural ingredients; color variations are normal.

HOW IT WORKS:

IsoOxygene™ and Cyclooxygenase-2 (COX-2)

The cyclooxygenase enzyme plays an important role in the production and regulation of prostaglandins, the hormone-like compounds that regulate many biochemical processes in the body. The enzyme exists in two primary forms, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Although the enzymes possess similar structures and kinetics, they differ in terms of genetics, biochemistry, and function.⁴

COX-1, which is present in most cells throughout the body, is necessary for the formation and regulation of prostaglandins. Through its influence on prostaglandin synthesis, COX-1 helps maintain the integrity of the stomach lining, proper circulation, and kidney function.⁴

COX-2, on the other hand, is generally only found in areas of the central nervous system. The synthesis of COX-2 is triggered by the exposure of inflammatory cells to the stress-induced immune compounds, cytokines and interleukins. COX-2 is responsible for the generation of the pro-inflammatory prostaglandins. An increase in these prostaglandins leads to increased inflammatory responses.'⁴

Because of its important role in the inflammatory cascade, much research has focused on COX-2 inhibition. COX-2 inhibitors decrease prostaglandin production, thereby halting the inflammatory cascade. Certain botanicals possess the ability to affect COX-2. For example, studies have shown that the alpha acids, humulone, isohumulone, and cohumulone, present in hops inhibit this enzyme.*

IsoOxygene^IM is a patented hops extract specifically designed to inhibit the COX-2 enzyme without affecting COX-1 .* The herb undergoes special processing known as supercritical extraction. This type of extraction method utilizes carbon dioxide rather than traditional solvents, thereby eliminating the presence of alcohol residue in the final product. The low temperature processing associated with supercritical extraction also ensures the key compounds retain full biological strength and activity without the potential chemical alterations caused by other extraction methods. Studies have shown IsoOxygene COX-2 inhibition is 20 times more potent than that of other tested popular products, including curcumin and grape seed.  IsoOxygene is also far more selective than botanicals and drugs designed to reduce pain due to occasional overuse.* IsoOxygene can therefore be used safely without adversely affecting the homeostatic functions regulated by COX-1.*¹

Antioxidants and Free Radicals and Reactive Oxygen Species (ROS)

*This statement has not been evaluated by the Food and Drug Administration.  This product is not intended to diagnose, treat, cure or prevent any disease.

 

 Antioxidants play an important role in the prevention and elimination of free radicals and reactive oxygen species (ROS).* Free radicals and ROS are unstable molecules that attack other cells in order to regain the appropriate number of electrons and re-establish stability. However, in the process, the attacked cells themselves become free radicals, thereby initiating a chain reaction. Free radicals are naturally formed during cell metabolism and are also created by the body's immune system. The chain reaction can be controlled by antioxidants, which have the ability to share electrons while still maintaining molecular stability. Unfortunately, external factors, like pollution, cigarette smoke, and poor diet, can lead to significant free radical and ROS formation. If production of these unstable compounds becomes excessive and limited antioxidants are available in the body to neutralize them, cellular damage can occur.*²

When free radicals and ROS react with our cells, the inflammatory cascade is initiated.* Clinical studies have shown that antioxidant supplementation can reduce the pain and stiffness associated with occasional overuse.*⁸ Through the neutralization of free radicals and ROS, antioxidants play an important role in maintaining optimum health.*"

Vitamin C is a well-known antioxidant and powerful free radical scavenger. Research has shown that supplemental vitamin C prevents oxidative damage.⁹ In addition, studies confirm that treatment with vitamin C supports the production of healthy collagen.*¹⁰'¹'

Many phytochemicals have also been studied for their antioxidant activities. Green tea, for example, is a potent ROS scavenger that has been used in traditional Chinese medicine for over 4,000 years. When compared to common vitamin antioxidants, the polyphenols in green tea were shown to exhibit significantly greater protection against free radical damage. " '   Although its most common applications are immune support and energy enhancement, recent scientific research has focused on other beneficial effects of the herb. In particular, the ROS-scavenger activity of green tea has been associated with reducing inflammation due to occasional overuse.*¹²"¹⁴ In fact, one clinical study found a 50% improvement in symptoms following green tea supplementation.¹⁴

Ginger is another phytochemical that has been used for centuries.* Recent studies have shown that ginger and its polyphenolic constituents, gingerol and shogoal, play a role in reducing inflammation due to occasional overuse.* The herb is also protective against peroxynitrite-mediated oxidation.*'³'¹⁶

Traditionally used for bladder health and immune system support, elder berry is also known for its significant antioxidant properties.*¹⁷ Like green tea, the key components present in elder berry have shown superior free radical scavenging activity when compared to vitamin E and selenium, two well known antioxidants.'⁸ Elder berry continues to gain recognition for its ability to support the body's natural anti-inflammatory response.*¹⁷ Studies have shown that supplementation with elder berry increases the production of certain inflammatory mediators, called cytokines, by 2-45 fold compared to placebo.¹⁹

Research has shown that plant-derived bioflavonoids also possess strong antioxidant properties. They modulate key enzyme reactions involved in the inflammatory pathway.   Bioflavonoids play a major role in reducing free radical damage through synthesis and cross-linking of collagen.*" Rutin is a well-known, potent bioflavonoid. A comparative study of flavonoids found that rutin effectively reduces pain and stiffness due to occasional overuse.

 

 

  

Ancient Ayruvedic medicine utilized boswellia for a variety of conditions. Boswellic acids, the key component of Boswellia serrata, have been shown to reduce pain associated with occasional overuse.* The herb blocks synthesis of inflammatory mediators, such as leukotrienes, which are known to promote free radical damage.*²² As with green tea, ginger, and elder berry, long term use of boswellia has been shown to be safe and effective.*²³"²⁶

In addition to vitamins, minerals, and herbs, certain amino acids are gaining recognition as powerful antioxidants. N-acetylcysteine, also known as NAC, is a form of cysteine, which enhances free radical and ROS scavenging activity.²⁷ Through its ability to influence the production of the enzyme glutathione, another effective reducing agent, NAC has been shown to protect synovial fluid cells from the damaging effects of oxidation.²⁸'²⁹

Enzymatic Activity

Bromelain is a proteolytic enzyme sourced from pineapple. Bromelain supports optimum health by reducing prostaglandin and increasing blood flow.*''³⁰ A randomized, controlled, clinical trial found that bromelain reduces pain and stiffness due to occasional overuse.*³¹

The following chart summarizes the benefits of the ingredients in FlexAgility™* MAX:

Ingredient	Benefit
Vitamin C (ascorbic acid)	Provides powerful free-radical scavenging activity.* Clinically studied to support collagen health.*10'"
Hops (Humulus lupulus) (IsoOxygene'M brand) Flower Extract	Significantly inhibits COX-2 with minimal affect on COX- 1 levels*  Does not adversely affect gastrointestinal, renal, or platelet function.'
Ginger (Zingiber officinale) Rhizome Extract	Inhibits the inflammatory mediator, nitric oxide and protects against peroxynitrite-mediated oxidation*15'16
Boswellia Serrata Gum Extract	Reduces free radical damage by blocking leukotriene synthesis*"2
Bromelain (2,400 G.D.U./g)	Reduces prostaglandin and increases blood flow, supporting the body's natural anti-inflammatory function.*30
Japanese Sophora (Sophora japonica) Flower Bud standardized to contain 95% rutin	Possesses free radical scavenging activity and supports healthy collagen.*2'20
European Elder (Sambucus nigra) Berry Extract 4:1	Like green tea, the free radical scavenging activity of elder is superior to vitamin E and selenium. '    Significantly influences inflammatory mediators, thereby supporting the body's natural anti-inflammatory response.* l9
Green Tea (Camellia sinensis) Leaf Extract (decaffeinated) standardized to contain a minimum of 70% polyphenols	Possesses greater free radical scavenging activity than common vitamin and mineral antioxidants. i2'13 Shown to support collagen and connective tissue health.* l4
N-Acetylcysteine (NAC)	A powerful free radical and ROS scavenger, NAC has been shown to support the health of collagen. * 2S'2<;
*This statement has not been evaluated by the Food and Drug Administration.  This product is not intended to diagnose, treat, cure or prevent any disease.

 

Conclusion

The ingredients in FlexAgility MAX work together to provide triple action activity to reduce the pain and stiffness associated with occasional overuse or overexertion. By providing three separate mechanisms of inflammatory mediation, the formula effectively supports optimum health.

RECOMMENDATIONS:

One tablet twice daily with meals.

LABEL PRECAUTIONS:

If pregnant, nursing, or taking prescription drugs, consult your healthcare practitioner prior to use.

HOW IS IT SUPPLIED:

Product No. 01686 60 tablets

STORAGE RECOMMENDATIONS:

Store at controlled room temperature, 59° to 86°F (15° - 30°C). REFERENCES:

1.    IsoOxygeneTM, a new botanical anti-inflammatory COX-2 inhibitor. Lipoprotein Technologies.  Unpublished data.

2.   Cooper, C. Relieving lingering musculoskeletal pain may be as straightforward as A, C, and E. Nutrition Science News.  1999 Jan.

3.   Gaspani L, et al.  In vivo and in vitro effects of bromelain on PGE(2) and SP concentrations in the inflammatory exudates in rates. Pharmacology. 2002 May;65(2):83-6.

4.    Lehne RA. Nonsteroidal anti-inflammatory drugs In: Pharmacology for Nursing Care. 3rd ed. Philadelphia, Pa: W.B. Saunders; 1998: 695-700.

5.   Yamamoto K, et al. Suppression of cyclooxygenase-2 gene transcription by humulon. Adv ExpMedBiol. 2002;507:73-7.

6.    Yamamoto K, et al. Suppression of cyclooxygenase-2 gene transcription by humulon beer hop extract studied with reference to glucocorticoid. FEES Lett. 2000 Jan 14;465(2-3):103-6.

7.    Lemay M, et al. In vitro and ex vivo cyclooxygenase inhibition by a hops extract. Asia Pac J din Nutr. 2004; 13(Suppl):S 110.

8.    De las Heras CG, et al. Use of antioxidants to treat pain in chronic pancreatitis. Rev Esp Enferm Dig. 2000;92:375-385.

9.   Ghosh MK, Chattopadhyay DJ, Chatterjee IB. Vitamin C Prevents Oxidative Damage. Free Rad Res.   1996;25(2): 173-9.

10. Houglum KP, Brenner DA, Chojkier M. Ascorbic acid stimulation of collagen biosynthesis independent of hydroxylation. Am JClin Nutr.  1991 ;54:1141S-3S.

1 1. Ono M, Aratani Y, Kitagawa K, Kitagawa Y. Ascorbic acid phosphate stimulates type IV collagen synthesis and accelerates adipose conversion of 3T3-L1 cells. Experimental Cell Research. 1990; 187:309-14.

12. Zhao B, Li X, He R, Cheng S, Wenjuan X. Scavenging effect of extracts of green tea and natural antioxidants on active oxygen radicals. Cell Biophysics. \ 989; 14:175-85.

13. Wiseman SA, Balentine DA, Frei B. Antioxidants in tea. Critical Reviews in Food Sci and Nutr.   1997;37(8):705-18.

14. Haqqi TM, Anthony DD, Gupta S, Ahmad N, Lee MS, Kumar GD, Mukhtar H. Prevention of collagen-induced arthritis in mice by a polyphenolic fraction from green tea. Proc Natl AcadSci.   1999 Apr;96:4524-9.

15. Ippoushi K, et al. [6]-Gingerol inhibits nitric oxide synthesis in activated J774.1 mouse macrophages and prevents peroxynitrite-induces oxidation and nitration reactions. Life Sci. 2003 Nov 14;73(26):3427-37.

16. Shen CL, et al. Effects of ginger (Zingiber officinale Rose.) on decreasing the production of inflammatory mediators in sow osteoarthrotic cartilage explants. JMedFood. 2003 Winter; 6(4):323-8.

17. "Elder" Whole Health MD web site. Available at:

http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10024,00.html. Accessed November 15,2004.

18. Milbury PE, Cao G, Prior RL, Blumberg J. Bioavailablity of elderberry anthocyanins. Mech Ageing Dev. 2002 Apr 30; 123(8):997-1006.

19. Barak V, Halperin T, Kalickman I. The effect of Sambucol, a black elderberry-based, natural product, on the production of human cytokines: I. Inflammatory cytokines. Eur Cytokine Netw. 2001 Apr-Jim; 12(2):290-6.

20. Rao CM, et al. Influence of bioflavonoids on the metabolism and crosslinking of collagen. ItalJBiochem. 1981 JuI-Aug;30(4):259-70.

21. Rotelli AE, etal. Comparative study of flavonoids in experimental models of inflammation. Pharmacol Res. 2003 Dec;48(6):601-6.

22. Safayhi H, et al. Inhibition by boswellic acids of human leukocyte elastase. J Pharmacol ExpTher. 1997 Apr;281(l):460-3.

23. Lininger S, et al. Green Tea (Camellia sinensis). In: The Natural Pharmacy. U.S.A.: Prima Publishing; 1998:272-

4. Lininger S, et al. Boswellia (Boswellia serrata). In: The Natural Pharmacy. U.S.A.: Prima Publishing; 1998:238-9.

25. Lininger S, et al. Elderberry (Sambucus nigra). \\v. The Natural Pharmacy. U.S.A.: Prima Publishing; 1998:256-7.

26. Lininger S, et al. Ginger (Zingiber officinale).  In: The Natural Pharmacy.  U.S.A.: Prima Publishing;1998:267-8.

27. "NAC (N-acetylcysteine)" Whole Health MD web site. Available at:

http://www.wholehealthmd.com/refshelf/substances_view/l, 1525,809,00.html. Accessed November 15, 2004.

28. Maurice MM, van der Voort EA, Leow A, Levarht N, Breedveld FC, Verweij CL. CD28 co-stimulation is intact and contributes to prolonged ex vivo survival of hyporesponsive synovial fluid T cells in rheumatoid arthritis. Eur JImmunol. 1998 May;28(5): 1554-62.

29. Grootveld M, Silwood CJ, Lynch EJ, Patel IY, Blake DR. The role of N-acetylcysteine in protecting synovial fluid biomolecules against radiolytically-meditated oxidative damage: a high field proton NMR study. Free Radic Res.   \999 May;30(5):35 1 -69.

30. Lininger S, et al. Enzymes, Proteolytic. In: The Natural Pharmacy. U.S.A.: Prima Publishing; 1998:156-7.

31. Walker AF, et al. Bromelain reduces mild acute knee pain and improves well-being in dose-dependent fashion in an open study of otherwise healthy adults. Phylomedicine. 2002 Dec;9(8):681-6.