- Selenium (Se) is a trace mineral with a role in multiple biologic functions through the activation of glutathione peroxidase, which plays a crucial role in antioxidant defense.
- Exerts its anti-inflammatory effect through its protection against endoplasmic reticulum stress and down regulation of pro-inflammatory cytokine release.
- Selenium has also been shown to demonstrate the ability to protect cartilage tissue in patients with KBD (Kashin-Beck disease) degenerative osteoarthritis.
- Seafood, kidney, liver, yeast and nuts (especially Brazil nuts) are good sources of selenium.
- Selenium deficiency is associated with skeletal muscle dysfunction, cardiomyopathy, mood disorders and impaired immune function.
- Impaired cell-mediated immunity has been demonstrated when tissue stores of selenium are depleted.
- Natural killer cell activity is enhanced when selenium is supplemented in the diet of selenium depleted individuals.
- Selenium supplementation may decrease inflammatory activity in patients with autoimmune thyroiditis.
- More studies need to be done on the link of selenium and reduction in pain and joint inflammation in people with rheumatoid arthritis.
- The RDA (recommended dietary allowance) of selenium is 55 micrograms/day with tolerable upper intake limit of 400 micrograms/day.
- In a double-blind study, bioavailability of selenium was evaluated alone and in combination with BioPerine®.
- The serum selenium levels were approximately 30% higher in the group receiving selenium with BioPerine® after 2 weeks of treatment with a plateau in the subsequent time-points tested, working synergerically with Joint Edge Rx’s BioPerine.
- The serum selenium levels were within normal limits in both groups at all time-points tested.
- Rayman MP. Selenium and human health. Lancet 2012; 379:1256.
- Holben DH, Smith AM. The diverse role of selenium within selenoproteins: a review. J Am Diet Assoc 1999; 99:836.
- Massoure PL, Camus O, Fourcade L, Simon F. Bilateral leg oedema after bariatric surgery: A selenium-deficient cardiomyopathy. Obes Res Clin Pract 2017; 11:622.
- Finley JW, Penland JG. Adequacy or deprivation of dietary selenium in healthy men: Clinical and psychologica findings. J Trace Elem Exp Med 1998; 11:11.
- Spallholz JE, Boylan LM, Larsen HS. Advances in understanding selenium's role in the immune system. Ann N Y Acad Sci 1990; 587:123.
- Look MP, Rockstroh JK, Rao GS, et al. Serum selenium versus lymphocyte subsets and markers of disease progression and inflammatory response in human immunodeficiency virus-1 infection. Biol Trace Elem Res 1997; 56:31.
- Kiremidjian-Schumacher L, Roy M, Wishe HI, et al. Supplementation with selenium and human immune cell functions. II. Effect on cytotoxic lymphocytes and natural killer cells. Biol Trace Elem Res 1994; 41:115.
- Mazokopakis EE, Papadakis JA, Papadomanolaki MG, et al. Effects of 12 months treatment with L-selenomethionine on serum anti-TPO Levels in Patients with Hashimoto's thyroiditis. Thyroid 2007; 17:609.
- Nève J. Selenium as a risk factor for cardiovascular diseases. J Cardiovasc Risk 1996; 3:42.
- Wang X, Wu H, Long Z, et al. Differential effect of Se on insulin resistance: regulation of adipogenesis and lipolysis. Mol Cell Biochem 2016; 415:89.
- Yao Y, Pei F, Kang P. Selenium, iodine, and the relation with Kashin-Beck disease. Nutrition. (2011).
- Kre-Celazine® is a “non-drug” patented ingredient that has been clinically shown to help reduce pain and promote joint flexibility and mobility along with reducing inflammation.
- Kre-Celazine® is a complex material consisting of bonding Kre-Alkalyn® (US Patent 6,399,661) with esterified fatty acid carbons.
- The esterifying process makes the fatty acid stable so it does not react with oxygen. (This is not esterified creatine, the fatty acids have been esterified).
- Kre-Celazine® was granted Orphan Drug status in the treatment of Juvenile Idiopathic Arthritis by the FDA in 2013.
- Juvenile Idiopathic Arthritis (JIA) is a complex, chronic childhood autoimmune inflammatory disease.
- Like rheumatoid arthritis in adults, joint and soft tissue destruction is relentless, except that this inflammation can begin when the patient is as young as a one-year old infant.
- In the clinical study published by LIEBERT, participants (ranging 7 to 17 years , who had been suffering from longstanding JIA, despite their use of chronic anti-inflammatory prescription medication) received two 750 mg capsules (total, 1,500 mg) of Kre-Celazine® to be taken daily for a period of 30 consecutive days. These patients experienced:
(a) significant reduction or elimination of palpable inflammation
(b) renormalization of range of motion
(c) reduction/absence of perceived pain
(d) renormalization of blood values for C-reactive protein and Erythrocyte Sedimentation rate.
- Based on the study results reported above, as well as those of a previous study published by JANA (Journal of the American Nutraceutical Association) using arthritic adults (Golini J, et al. 2009), Kre-Celazine® is a moderately effective non-prescription drug for the reduction of pain and stiffness of the extremities, neck, knee and shoulder regions in humans.
- Kre-Celazine® delivers a quad core of critical mechanism factors.
- Core Factor 1: Supports Cellular Integrity.
- Kre-Celazine® supports the integrity of cellular membranes to enhance their function with a precision blend of specialized lipids.This enables cell membranes to better repel stressors and offer greater cellular protection.
- Core Factor 2: Reduces Inflammation
- Plays a role in suppressing inflammation by reducing COX-2 enzyme, by inhibiting pro-inflammatory arachidonic acid and by helping to reduce the production of the inflammatory signaling Interleukin 6 molecule.
- Core Factor 3: Restore and Support Optimal pH
- The alkalizing power of Kre-Celazine® helps get your body working in a state that may be likened to a “greenhouse effect.”
- This is a pH where your body’s cells and biological systems work in perfect harmony to function, grow, and recover optimally.
- Core Factor 4: Support Muscle Energy and Strength
- Kre-Celazine® features Kre-Alkalyn® (US Patent 6,399,661), a premium form of alkalinized pH-stable and soluble creatine.
- Supplemental creatine, like Kre-Alkalyn®, may boost the muscles’ stores of creatine. In turn, this may allow for greater exercise potential and muscle stimulation that can strengthen muscles, like those around joints.
- Ameye LG, Chee WS. Osteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence. Arthritis Res Ther. 2006; 8(4):R127.And at www.arthritis-research.com/content/8/4/R127Pages 1-22. [Accessed on 10-1-2008]
- Buford TW, Kreider RB, Stout JR, Greenwood M, Campbell B, Spano M, Ziegenfuss T, Lopez H, Landis J, Antonio J. International Society of Sports Nutrition position stand: creatine supplementation and exercise. Journal of the International Society of Sports Nutrition 2007, 4:6 doi:10.1186/15502783-4-6.
- Cassidy JT, Petty RE: Introduction to the Study of Rheumatic Diseases in Children. In Textbook of Pediatric Rheumatology – 5th Ed. Philadelphia: WB Saunders Company 2005:2–8. 5. Johnson K: Imaging of juvenile idiopathic arthritis. Pediatr Radiol 2006;36:743–758.
- Curtis JL, Wolber FM, Sonstein J, Craig RA, Polak T, Knibbs RN, et al.: Lymphocyte-endothelial cell adhesive interactions in lung immunity: lessons from the murine response to particulate antigen. Immunopharmacology 2000;48:223–229.
- Golini J, Beeson M, ND, Angersbach D, ND, Moore J, ND, Holl P, DC, Amicone C, ND, Jones W. A Single-Center, Double-Blind Placebo Controlled Study to Evaluate the Efficacy of Kre-Celazine®, an Oral Buffered Creatine-Cetylated Fatty Acid Compound, in its Ability to Reduce Site-specific Inflammation and Pain. JANA. Vol. 12, No. 1, 2009: 20-25. ISSN-1521-4524. [www.ana-jana.org]
- Hesslink R Jr, Armstrong D 3rd, Nagendran MV, Sreevatsan S, Barathur R: Cetylated fatty acids improve knee function in patients with osteoarthritis. J Rheumatol 2002;29:1708–1712.
- Kraemer WJ, Ratamess NA, Anderson JM, et al. Effect of a cetylated fatty acid topical cream on functional mobility and quality of life of patients with osteoarthritis. J Rheumatol. 2004; 31(4):767-774.
- Kremer JM: n-3 fatty acid supplements in rheumatoid arthritis. Am J Clin Nutr 2000;71:349S–351S.
- Lawrence RC, Felson DT, Helmick CG, et al. National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008; 58(1):26-35.
- Morelli V, Naquin C, Weaver V. Alternative therapies for traditional disease states: osteoarthritis. Am Fam Physician. 2003; 15:67(2):339-344.
- Nomura A, Zhang M, Sakamoto T, Ishii Y, Morishima Y, Mochizuki M, et al.: Anti-inﬂammatory activity of creatine supplementation in endothelial cells in vitro. Br J Pharmacol 2003;139:715–720.
- O’Connor RS, Steeds CM, Wiseman RW, Pavlath GK. Phosphocreatine as an energy source for actin cytoskeletal rearrangements during myoblast fusion. J Physiol. 2008; 15;586(Pt 12):2841-2853.
- Silver FH, Bradica G, Tria A. Relationship among biomechanical, biochemical, and cellular changes associated with osteoarthritis. Rev Biomed Eng. 2001; 29(4):373-379.
- Wang D, DuBois RN: An inﬂammatory mediator, prostaglandin E2, in colorectal cancer. Cancer J 2013;19:502–510.
- Curcumin is the natural active extract found in the turmeric plant and the yellow pigment found in curry spice.
- It has been used therapeutically in Chinese medicine for thousands of years.
- Research has shown that curcumin has powerful anti-oxidant and anti-inflammatory proprieties.
- Curcumin has anti-inflammatory properties by inhibiting the major inflammatory pathway (Tnf-α and nF-kB) and the ability to mimic aspirin as a COX2 inhibitor.
- Supplements containing curcumin reduce the severity of joint pain in individuals with osteoarthritis and even in those with rheumatoid arthritis.
- Studies have shown that curcumin inhibits protein degradation after injury and in cases of cachexia (general wasting usually associated with chronic illnesses).
- Curcumin supplementation following eccentric exercise led to reduced post-exercise inflammation and markers of muscle damage while also improving exercise recovery.
- Over 200 studies have appeared demonstrating curcumin's cancer-preventive effects.
- Curcumin activates PPAR (peroxisome proliferator-activator receptor), which is a group of key nuclear proteins that regulate gene expression and modulate sugar uptake and utilization in the bloodstream, modulating blood sugar and increasing insulin sensitivity, working synergistically with LionEdge’s Insulin Activation Matrix.
- Bioavailability of Curcumin when co-administered with 20mg BioPerine was enhanced by 20-fold or 2000% compared to bioavailability of Curcumin alone.
- Bharat B. Aggarwal, Chitra Sundaram, Nikita Malani, and Haruyo Ichikawa. Curcumin: The Indian Solid Gold. Advances in Experimental Medicine and Biology 595 (2007): 1–75.
- Deng YT, Chang TW, Lee MS, Lin JK. Suppression of free fatty acid-induced insulin resistance by phytopolyphenols in C2C12 mouse skeletal muscle cells. J Agric Food Chem. 2012 Feb 1;60(4):1059-66.
- Sita Aggarwal, Haruyo Ichikawa, Yasunari Takada, Santosh K. Sandur, Shishir Shishodia, and Bharat B. Aggarwal. Curcumin (Diferuloylmethane) Down-Regulates Expression of Cell Proliferation and Antiapoptotic and Metastatic Gene Products through Suppression of IκBα Kinase and Akt Activation. Molecular Pharmacology 69, no. 1 (2006): 195–206. doi: 10.1124/mol.105.017400.
- Li YP, Chen Y, John J, Moylan J, Jin B, Mann DL, Reid MB. TNF-alpha acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle. FASEB J. 2005 Mar;19(3):362-70.
- Deepa Thaloor, Kristy J. Miller , Jonathan Gephart , Patrick O. Mitchell , Grace K. Pavlath. Systemic administration of the NF-κB inhibitor curcumin stimulates muscle regeneration after traumatic injury. American Journal of Physiology - Cell PhysiologPublished 1 August 1999, Vol. 277no. C320-C32.
- Preetha Anand, Ajaikumar B. Kunnumakkara, Robert A. Newman, and Bharat B. Aggarwal, Bioavailability of Curcumin: Problems and Promises. Molecular Pharmaceutics 4, no. 6 (2007): 807–18. doI: 10.1021/mp700113r.
- Guido Shoba, David Joy, Thangam Joseph, Muhammed Majeed, Rajesh Rajendran, and Priya S. S. R. Srinivas. Influence of Piperine on the Pharmacokinetics of Curcumin in Animals and Human Volunteers.Pharmacology 64, no. 4 (1998): 353–56. doi: 10.1055/s-2006-957450.
- Chainani-Wu N. Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa). J Altern Complement Med. 2003 Feb;9(1):161-8.
- R.R. Kulkarnia, P.S. Patkia, V.P. Joga, S.G. Gandagea, Bhushan Patwardhan Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol. 1991 May-Jun;33(1-2):91-5.
- Chandran B, Goel A. A Randomized, Pilot Study to Assess the Efficacy and Safety of Curcumin in Patients with Active Rheumatoid Arthritis. Phytother Res. 2012 Nov;26(11):1719-25.
- G.K. Jayaprakasha, L. Jaganmohan Rao, K.K. Sakariah. Antioxidant activities of curcumin, demethoxycurcumin and bisdemethoxycurcumin. Food Chemistry. Volume 98, Issue 4, 2006, 720-724.
- The spice ginger is the natural underground rhizome of the ginger plant, known botanically as Zingiber officinale, used in many countries as a spice and condiment to add flavor to food.
- Ginger has a very potent anti-inflammatory effect which has been shown to reduce muscle pain after intense physical activity.
- During the past 40 years, many studies have provided scientific support for the long-held belief that ginger contains potent anti-inflammatory properties; the original discovery of ginger's inhibitory effects on prostaglandin biosynthesis in the early 1970s has been repeatedly confirmed.
- Ginger suppresses prostaglandin synthesis through inhibition of cyclooxygenase-1, cyclooxygenase-2 and 5-lipoxygenase.
- A University of Miami study compared the effects of ginger extract to placebo in 247 patients with osteoarthritis (OA) of the knee. The ginger reduced pain and stiffness in knee joints by 40 percent over the placebo.
- Researchers at the University of Georgia in Athens and Georgia State College & University in Milledgeville reported in the Journal of Pain that a few tablespoons of grated ginger can help ease muscle pain caused by exercise.
- If the anti-inflammatory properties of ginger mentioned above aren’t enough, ginger also has insulinoptropic properties through the 5-HT3 receptor channel, increasing plasma insulin secretion up to 10%, working synergistically with LionEdge’s Insulin Activation Anabolic Matrix.
- Ginger has staring potential for treating a number of ailments including degenerative disorders (arthritis and rheumatism), digestive health (indigestion, constipation and ulcer), cardiovascular disorders (atherosclerosis and hypertension), vomiting, diabetes mellitus, and cancer.
- It also has anti-inflammatory and anti-oxidative properties for controlling the process of aging.
- Phan PV, Sohrabi A, Polotsky A, Hungerford DS, Lindmark L, Frondoza CG. Ginger extract components suppress induction of chemokine expression in human synoviocytes. J Altern Complement Med. 2005 Feb;11(1):149-54. 2005.
- Jagetia GC, Baliga MS, Venkatesh P, Ulloor JN. Influence of ginger rhizome (Zingiber officinale Rosc) on survival, glutathione and lipid peroxidation in mice after whole-body exposure to gamma radiation. Radiat Res. 2003 Nov;160(5):584-92. 2003.
- Kiuchi F, et al. Inhibition of prostaglandin and leukotriene biosynthesis by gingerols and diarylheptanoids. Chem Pharm Bull 40 (1992):387-91. 1992.
- Srivastava KC, Mustafa T. Ginger (Zingiber officinale) in rheumatism and musculoskeletal disorders. Med Hypothesis 39(1992):342-8. 1992.
- Wigler I, Grotto I, Caspi D, Yaron M. The effects of Zintona EC (a ginger extract) on symptomatic gonarthritis. Osteoarthritis Cartilage. 2003 Nov;11(11):783-9. 2003.
- Terry R, Posadzki P, Watson LK, Ernst E. The use of ginger for the treatment of pain: a systematic review of clinical trials. Pain Med. 2011 Dec;12(12):1808-18.
- 7. Nammi S, Sreemantula S, Roufogalis BD. Protective effects of ethanolic extract of Zingiber officinale rhizome on the development of metabolic syndrome in high-fat diet-fed rats. Basic Clin Pharmacol Toxicol. 2009;104:366–73.
- Heimes K, Feistel B, Verspohl EJ. Impact of the 5-HT receptor channel system for insulin secretion and interaction of ginger extracts. Eur J Pharmacol. 2009;624:58–65.
- Dugasani S, Pichika MR, Nadarajah VD, Balijepalli MK, Tandra S, Korlakunta JN. Comparative antioxidant and anti-inflammatory effects of -gingerol, -gingerol, -gingerol and -shogaol. J Ethnopharmacol. 2010;127:515–20.
- Ohshima H, Tatemicho M, Sawa T. Chemical basis of inflammation-induced carcinogenesis. Arch Biochem Biophys. 2003;417:3–11.
- Ramaa CS, Shirode AR, Mundada AS, Kadam VJ. Nutraceuticals an emerging era in the treatment and prevention of cardiovascular diseases. Curr Pharm Biotechnol. 2006;7:15–23.
- Bromelain belongs to a group of natural protein digesting enzymes obtained from the fruit or stem of pineapple.
- Research has shown that bromelain has anti-inflammatory and analgesic properties
- Bromelain's action as an anti-inflammatory is mediated via the following factors: reducing plasma fibrinogen levels, decreasing bradykinin levels (which results in reduced vascular permeability and hence reducing edema and pain), decreasing levels of PGE2 and thromboxane.
- Bromelain was first reported to be of value as an analgesic and anti-inflammatory for use in both rheumatoid arthritis and osteoarthritic patients in 1964.
- Ten studies have been identified that have assessed bromelain in osteoarthritis of the knee, most of which indicated that the use of bromelain had positive clinical effects (as measured by assessment of reduction in soft tissue swelling, pain and/or joint stiffness) and no adverse events associated with the medication were reported in any of these case reports.
- In a blinded study from Germany, researchers divided 90 patients with painful osteoarthritis of the hip into two groups: one half receiving bromelain for six weeks, while the other half received the anti-inflammatory drug diclofenac. They found that the bromelain preparation was as effective as diclofenac in standard scales of pain, stiffness and physical function, and better tolerated than the drug comparator.
- Bromelain helps break down and digest protein, working alongside LionEdge’s Absorption Enhancing Matrix.
- Bromelain accounts for many therapeutic benefits including the treatment of angina pectoris, inflammatory bowel disease, sinusitis, surgical trauma, debridement of wounds, and enhanced absorption of drugs, particularly antibiotics.
- Maurer HR. Bromelain: biochemistry, pharmacology and medical use. Cell Mol Life Sci. 2003 Aug;58(9):1234-45.
- Brien S, Lewith G, Walker A, Hicks SM, Middleton D. Bromelain as a treatment for osteoarthritis: a review of clinical studies. Evid Based Complement Alternat Med. 2004 Dec;1(3):251-7.
- Klein G, Kullich W, Schnitker J, Schwann H. Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs. Clin Exp Rheumatol. 2006 Jan-Feb;24(1):25-30.
- Akhtar NM, Naseer R, Farooqi AZ, Aziz W, Nazir M. Oral enzyme combination versus diclofenac in the treatment of osteoarthritis of the knee—a double-blind prospective randomized study. Clin Rheumatol. 2004 Oct;23(5):410-5.
- Cohen A, Goldman J. Bromelain therapy in rheumatoid arthritis. Penn Med J. 1964;67:27–30.
- Leipner J, Iten F, Saller R. Therapy with proteolytic enzymes in rheumatic disorders. Biodrugs. 2001;15:779–789.
- Singer F, Oberleitner H. Drug therapy of activated arthrosis. On the effectiveness of an enzyme mixture versus diclofenac. Wien Med Wochenschr. 1996;146:55–58.
- Klein G, Kullich W. Short-term treatment of painful osteoarthritis of the knee with oral enzymes: a randomised, double-blind study versus Diclofenac. Clin Drug Invest. 2000;19:15–23.
- Singer F, Singer C, Oberleitner H. Phlyoenzym versus diclofenac in the treatment of activated osteoarthritis of the knee. Int J Immunother. 2001;17:135–141.
- Tilwe GH, Beria S, Turakhia NH, Daftary GV, Schiess W. Efficacy and tolerability of oral enzyme therapy as compared to diclofenac in active osteoarthritis of the knee joint: an open randomized controlled clinical trial. Journal of the Association of Physicians of India. JAPI. 2001;49:621.
- Walker AF, Bundy R, Hicks SM, Middleton RW. Bromelain reduces mild acute knee pain and improves well being in a dose dependant fashion in an open study of otherwise healthy adults. Phytomedicine. 2002;9:681–686.
- BioPerine® is the only patented piperine which is extracted from black pepper.
- The only source from piperine to have undergone several clinical studies in the U.S. to substantiate its safety and efficacy for nutritional use.
- Gastrointestinal absorption of all the studied nutrients, as measured by amounts present in the blood, increased dramatically when administered with BioPerine® as compared to the control group receiving the nutrient alone.
- Research suggests it enhances nutrient digestion and absorption by increasing blood flow to the digestive tract through thermogenesis , thus significantly increasing bioavailiblity of the nutrients.
- Bioperine® enhances amino acids, water-soluble and fat-soluble vitamins, anti-oxidants and minerals – all of which are included in Post-Edge™.
- Bioavailability of Curcumin when co-administered with 20mg BioPerine was enhanced by 20-fold or 2000% compared to bioavailability of Curcumin alone.
- Srinivasan, K. Black pepper and its pungent principle-piperine: a review of diverse physiological effects. Critical reviews in food science and nutrition. 2007; 47.8:735-748.
- Brewer, M. S. Natural antioxidants: sources, compounds, mechanisms of action, and potential applications. Comprehensive Reviews in Food Science and Food Safety. 2011; 10.4:221-247.
- Reanmongkol, Wantana, et al. Effects of piperine on bioenergetic functions of isolated rat liver mitochondria. Biochemical pharmacology. 1988; 37.4:753-757
- Shoba, G, et al. Influence Of Piperine On The Pharmacokinetics Of Curcumin In Animals And Human Volunteers. Planta Med. 1998; 64(4):353-356.
- Badmaev, V, et al. Piperine, An Alkaloid Derived From Black Pepper, Increases Serum Response Of Beta-Carotene During 14-Days Of Oral Beta-Carotene Supplementation. Nutrition Research. 1999; 19(3) 381-388.
- Epstein, William W.; Netz, David F.; Seidel, Jimmy L. (1993). "Isolation of piperine from black pepper". J. Chem. Ed. 70 (7): 598.
- Badmaev, V, et al. Piperine Derived From Black Pepper Increases The Plasma Levels Of Coenzyme Q10 Following Oral Supplementation. J. Nutr. Biochem. 2000; 11: 109-113