K FLEX English Version Revised Version

Contents 1 What is Chondroitin Sulphate? . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2 What is MSM? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 3 Alleviates Joint Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 4 Anti-inflammatory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 5 Reduces Muscle Damage & Pain . . . . . . . . . . . . . . . . . . . . . . . . . 6 6 Alleviates Athritis Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 7 Improves Skin Health by Strengthening Keratin . . . . . . . . . . . . . . 9 8 Cancer Fighting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 9 What is Hyaluronic Acid (HA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 10 More supple skin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 11 Speeds up Wound Healing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 12 Relieves Joint Pain by Improving Lubrication . . . . . . . . . . . . . . . . 15 13 Relieves Dry Eyes & Discomfort . . . . . . . . . . . . . . . . . . . . . . . . . . 16 14 Preserves Bone Strength . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  17 15 What is Boswellia Serrata? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  18 16 Alleviates Osteoarthritis (OA) . . . . . . . . . . . . . . . . . . . . . . . . . . . .  19 17 Alleviates Rheumatoid Arthritis (RA) . . . . . . . . . . . . . . . . . . . . . .  20 18 Treats Inflammatory Bowel Diseases . . . . . . . . . . . . . . . . . . . . . .  21 19 Alleviates Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 20 Fights Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 1 What is Chondroitin Sulphate? www.nhf.comC.myhondroitin Sulphate, a viscous liquid polysac- charide found in the con- nective tissues of animals, is present in large quanti- ties in cartilage tissues. It is also found in the skin, ten- dons, and blood vessels, where it functions as an intercellular cement. www.nhf.com.my The function of chondroitin sulfate in the human body is extremely wide-ranging. Among its main roles are (1) Restoring skin to a youthful condition; (2) Preserving elasticity and smoothness of tissues such as joints and liga- ments; 1

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE (3) Acting on the eyes to preserve the transparency and elasticity of the corneas and crystalline lenses; (4) Supporting bone growth and preventing osteoporosis by aiding calci- um absorption. High quality (pharmaceutical grade) chondroitin sulfate is as good as a widely prescribed non-steroidal anti-inflammatory drug (celecoxib) for the treatment of painful knee osteoarthritis, concludes research pub- lished online in the Annals of the Rheumatic Diseases [1]. Its effectiveness and safety prompt the researchers to call for it to be used for long term treatment, particularly for older people, among whom os- teoarthritis is common. Osteoarthritis is a degenerative joint condition causing pain, loss of func- ytion, and often some degree of disability. It is the most common form of .mjoint disease, affecting at least 8 million people in the UK alone. w.nhf.comIt is usually treated with painkillers, specifically non-steroidal anti-inflamma- tory drugs (NSAIDs), and paracetamol. But the evidence shows that regularly taking high dose NSAIDs/paracetamol over the long term is associated with frequent and serious side effects, so effective and safe wwalternatives are needed. The research team therefore carried out a clinical trial in which 604 pa- tients from five European countries with symptomatic knee osteoarthritis were randomly assigned to one of three daily treatments and then moni- tored for 182 days (6 months) [1]. Pain, joint function, and overall acceptability to the patient were assessed using validated scoring systems on days 30, 91, and 182. The results showed that pain and joint function improved significantly with chondroitin sulfate treatments as early as day 30, and this effect persist- ed through day 182. 2

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 2 What is MSM? .myethylsulfonylmethane, M w.nhf.commore commonly known as MSM, is a pop- ular dietary supplement used to treat a wide array of symptoms and condi- wwtions. It’s a sulfur-containing compound found natural- www.nhf.com.my ly in plants, animals and humans. 3

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 3 Alleviates Joint Pain .myt has been shown to I w.nhf.combenefit those with joint degeneration, a com- mon cause of pain in the knees, back, hands and hips. wwStudies have shown that MSM significantly reduces inflammation in your body. It also inhibits the break- www.nhf.com.my down of cartilage, a flexi- ble tissue that protects the ends of your bones in joints [2]. A study in 100 people over the age of 50 found that treatment with MSM for 12 weeks decreased pain, stiffness and swelling in the joints, com- pared to a placebo [3]. The group receiving the supplement also reported improved overall quality of life and less difficulty walking and getting out of bed. 4

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 4 Anti-inflammatory www.nhf.comT.myhe anti-inflammatory properties of MSM are well documented by scientific research. It’s believed that MSM in- hibits NF-kB, a protein complex involved in in- flammatory responses in your body. www.nhf.com.my It also reduces the pro- duction of cytokines such as tumor necrosis factor alpha (TNF-ɑ) and interleukin 6 (IL-6), which are signaling proteins linked to systemic inflammation [4]. Another study in 40 physically active men showed that taking 3 grams of MSM before exhaustive exercise decreased the release of inflammatory cytokines and prevented the over-stress of immune cells, compared to a placebo [5]. 5

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 5 Reduces Muscle Damage & Pain .myuring exhaustive exer- D w.nhf.comcise, muscle dam- age occurs and oxidative stress increases. This causes athletes to expe- rience muscle soreness wwand pain, which can hin- der athletic performance and training. MSM can naturally speed www.nhf.com.my muscle recovery after in- tense exercise by reducing inflammation and oxidative stress. In one study, 22 healthy women received 3 grams of MSM or a placebo per day for three weeks leading up to a half marathon. The MSM group reported less muscle soreness and joint pain than the placebo group [6]. Another study found that athletic men taking 3 grams of MSM daily for two weeks had lower levels of IL-6 and less muscle pain after intense resis- tance exercise [7]. 6

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 6 Alleviates Athritis Symptoms www.nhf.comA.myrthritis is a common inflammatory con- dition that causes pain, stiffness and a reduced range of motion in your joints. Since MSM has powerful anti-inflammatory prop- erties, it’s often used as www.nhf.com.my a natural alternative to medications to improve arthritis-related symptoms. A study in 49 people with knee osteoarthritis found that taking 3.4 grams of MSM per day for 12 weeks reduced pain and stiffness and improved physical function, compared to a placebo [8]. Another study showed that a daily supplement containing 5 grams of MSM and 7 grams of boswellic acid was more effective than glucosamine at reducing pain and improving function in people with knee osteoarthritis [9]. 7

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE What’s more, the people who received the MSM and boswellic acid sup- plement were less dependent on anti-inflammatory medications than the glucosamine group. www.nhf.com.my 8

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 7 Improves Skin Health by Strengthening Keratin Keratin is a protein that acts as the main structural component in your hair, skin and nails. It contains high levels of the sulfur-containing amino acid cysteine. That’s why burnt hair gives off a char- acteristic sulfurous smell. MSM may be beneficial for www.nhf.com.my skin health by acting as a sulfur donor to keratin. This, in turn, can help strengthen this important protein. MSM also helps reduce inflammation, which can damage skin cells and cause signs of premature aging like wrinkles .[10] It may even reduce symptoms of problematic skin conditions such as ro- sacea, which can cause redness, irritation and inflammation of the skin. 9

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE One study showed that, when applied to the skin, MSM significantly im- proved redness, itching, inflammation, hydration and skin color in people with rosacea .[11] www.nhf.com.my 10

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 8 Cancer Fighting www.nhf.comO.myne of the newest ar- eas of research involving MSM is study- ing its effectiveness in fighting cancer cells. Although the research is limited, the results have been promising so far. Several test-tube studies www.nhf.com.my have shown that MSM inhibits the growth of stomach, oesophageal, liver, colon, skin and bladder cancer cells [12, 13, 14]. It seems to do this by damaging cancer cell DNA and stimulating cancer cell death .[15] MSM also appears to prevent the spread of cancer cells, also known as metastasis .[16] 11

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 9 What is Hyaluronic Acid (HA) .myyaluronic acid, also H w.nhf.comknown as hyaluronan, is a clear, gooey sub- stance that is naturally produced by your body. The largest amounts of wwit are found in your skin, connective tissue and eyes. Its main function is to re- www.nhf.com.my tain water to keep your tissues well lubricated and moist. 12

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 10 More supple skin www.nhf.comH.myyaluronic acid sup- plements can help your skin look and feel more supple. Rough- ly half of the hyaluron- ic acid in your body is present in your skin, where it binds to water to help retain moisture. www.nhf.com.my Doses of HA of 120–240 mg per day for at least one month have been shown to significantly increase skin moisture and reduce dry skin in adults .[17] Hydrated skin also reduces the appearance of wrinkles, which may explain why several studies show that supplementing with it can make skin ap- pear smoother .[18] 13

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 11 Speeds up Wound Healing .myyaluronic acid helps H w.nhf.comwounds heal faster by regulating inflammation levels and signaling the body to build more blood vessels in the damaged wwarea .[19] Hyaluronic acid also has antibacterial properties, so it can help reduce the www.nhf.com.my risk of infection when ap- plied directly to open wounds .[20] Since oral supplements boost the lev- els of hyaluronic acid found in the skin, it’s reasonable to suspect they may provide some benefit. 14

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 12 Relieves Joint Pain by Improving Lubrication www.nhf.comH.myyaluronic acid is also found in the joints, where it keeps the space between your bones well lubricated. When the joints are lubricated, the bones are less likely to grind against each other and cause uncomfort- able pain. www.nhf.com.my Hyaluronic acid supple- ments are very helpful for people suffering from osteoarthritis, a type of degenerative joint disease caused by wear and tear on the joints over time. Taking 80–200 mg daily for at least two months has been shown to signifi- cantly reduce knee pain in people with osteoarthritis, especially those between the ages of 40 and 70 years old 21,22]. 15

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 13 Relieves Dry Eyes & Discomfort .mypproximately 1 out of 7 A w.nhf.comolder adults suffer from symptoms of dry eye due to reduced tear production or tears evap- orating too quickly. Since wwhyaluronic acid is excel- lent at retaining moisture, it’s often used to treat dry eye. Eye drops containing 0.2– www.nhf.com.my 0.4% hyaluronic acid have been shown to reduce dry eye symptoms and improve eye health .[23] 16

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 14 Preserves Bone Strength www.nhf.comN.myew animal research has begun to in- vestigate the effects of hyaluronic acid supple- ments on bone health. Two studies have found that hyaluronic acid sup- plements can help slow the rate of bone loss in rats with osteopenia, the www.nhf.com.my beginning stage of bone loss that precedes osteo- porosis .[24,25] 17

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 15 What is Boswellia Serrata? .myoswellia, also known B w.nhf.comas Indian Frankin- cense, is an herbal extract taken from the Boswellia serrata tree. wResin made from boswellia wextract has been used for centuries in Asian and African folk medicine. It’s believed to treat chronic www.nhf.com.my inflammatory illnesses as well as a number of other health conditions. Some research shows that boswellic acid can prevent the formation of leu- kotrienes in the body. Leukotrienes are molecules that have been identi- fied as a cause of inflammation. Four acids in boswellia resin contribute to the herb’s anti-inflammatory properties. These acids inhibit 5-lipox- ygenase (5-LO), an enzyme that produces leukotriene. Acetyl-11-ke- to- -boswellic acid (AKBA) is thought to be the most powerful of the four boswellic acids. 18

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 16 Alleviates Osteoarthritis (OA) www.nhf.comM.myany studies of bo- swellia’s effect on OA have found that it’s effective in treating OA pain and inflammation. One 2003 study pub- lished in the journal Phy- tomedicine found that all 30 people with OA knee www.nhf.com.my pain who received bo- swellia reported a de- crease in knee pain. They also reported an increase in knee flexion and how far they could walk .[26] Newer studies support the continued use of boswellia for Osteoarthritis .[27] Another study also found that increasing the dosage of enriched boswellia extract led to an increase in physical ability. Osteoarthritis knee pain decreased after 90 days with the boswellia extract, compared to a less- er dosage and placebo .[28] It also helped reduce the levels of a carti- lage-degrading enzyme. 19

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 17 Alleviates Rheumatoid Arthritis (RA) .mystudy published in the A w.nhf.comJournal of Rheumatol- ogy found that boswellia helps to reduce RA joint swelling .[29] Some re- search suggests that bo- wwswellia may interfere with the autoimmune process, which would make it an ef- fective therapy for RA. Further research supports www.nhf.com.my the effective anti-inflammatory and immune-balancing properties .[30] 20

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 18 Treats Inflammatory Bowel Diseases www.nhf.comD.myue to the herb’s an- ti-inflammatory prop- erties, boswellia may be effective in treating inflammatory bowel dis- eases such as Crohn’s disease and Ulcerative Colitis (UC). A 2001 study compared www.nhf.com.my boswellia extract, to the anti-inflammatory pre- scription drug mesalamine (Apriso, Asacol HD). It showed that the bo- swellia extract may be effective in treating Crohn’s disease .[31] Several studies found the herb could be effective in treating UC as well .[32] We’re just beginning to understand how the anti-inflammatory and im- mune-balancing effects of boswellia can improve the health of an in- flamed bowel. 21

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 19 Alleviates Asthma .myoswellia can play a B w.nhf.comrole in reducing leu- kotrienes, which causes bronchial muscles to con- tract. A 1998 study of the herb’s effect on bronchial wwasthma found that people who took boswellia experi- enced decreased asthma symptoms and indicators. This shows the herb could www.nhf.com.my play an important role in treating bronchial asthma .[33] Research continues and has shown the positive immune-balancing prop- erties of boswellia can help the overreaction to environmental allergens that happens in asthma .[34] 22

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE CHAPTER 20 Fights Cancer www.nhf.comB.myoswellic acids act in a number of ways that may inhibit cancer growth. Boswellic ac- ids have been shown to prevent certain enzymes from negatively affecting DNA. Studies have also found www.nhf.com.my that boswellia may fight advanced breast cancer cells, and it may limit the spread of malignant leukemia and brain tumor cells .[35] 23

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE References 1. Reginster J, Dudler J, Blicharski T, et al, “Pharmaceutical-grade Chondroitin sulfate is as effective as celecoxib and superior to placebo in symptomatic knee osteoarthritis: the ChONdroitin versus CElecoxib versus Placebo Trial (CONCEPT)”, Annals of the Rheumatic Diseases 2017;76:1537-1543. 2. Ezaki J, Hashimoto M, Hosokawa Y, Ishimi Y. Assessment of safety and efficacy of methylsulfonylmethane on bone and knee joints in osteoarthritis animal model. J Bone Miner Metab. 2013 Jan;31(1):16-25. doi: 10.1007/s00774-012-0378-9. Epub 2012 Aug 10. PMID: 23011466. 3. Xu G, Zhou T, Gu Y, et al. Evaluation of the Effect of Mega MSM on Improving Joint Function in Populations Experiencing Joint .myDegeneration. Int J Biomed Sci. 2015;11(2):54-60. w.nhf.com4. Ahn H, Kim J, Lee MJ, Kim YJ, Cho YW, Lee GS. Methylsulfonylmethane inhibits NLRP3 inflammasome activation. Cytokine. 2015 Feb;71(2):223-31. doi: 10.1016/j.cyto.2014.11.001. Epub 2014 Nov 21. PMID: 25461402. 5. Van der Merwe M, Bloomer RJ. The Influence of wwMethylsulfonylmethane on Inflammation-Associated Cytokine Release before and following Strenuous Exercise. J Sports Med (Hindawi Publ Corp). 2016;2016:7498359. doi:10.1155/2016/7498359 6. Methylsulfonylmethane (MSM) on exercise-induced oxidative stress, muscle damage, and pain following a half-marathon: a double-blind, randomized, placebo-controlled trial. J Int Soc Sports Nutr. 2017 Jul 21;14:24. 7. Kalman, D., Feldman, S., Samson, A. and Krieger, D. (2013), A Randomized Double Blind Placebo Controlled Evaluation of MSM for Exercise Induced Discomfort/Pain.. The FASEB Journal, 27: 1076.7- 1076.7. 24

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K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE 22. Oe M, Tashiro T, Yoshida H, et al. Oral hyaluronan relieves knee pain: a review. Nutr J. 2016;15:11. Published 2016 Jan 27. doi:10.1186/ s12937-016-0128-2 23. Pinto-Fraga J, López-de la Rosa A, Blázquez Arauzo F, Urbano Rodríguez R, González-García MJ. Efficacy and Safety of 0.2% Hyaluronic Acid in the Management of Dry Eye Disease. Eye Contact Lens. 2017 Jan;43(1):57-63. doi: 10.1097/ICL.0000000000000236. PMID: 26783978. 24. Stancíková M, Svík K, Istok R, Rovenský J, Velebný V. The effects of hyaluronan on bone resorption and bone mineral density in a rat model of estrogen deficiency-induced osteopenia. Int J Tissue React. 2004;26(1-2):9-16. PMID: 15573687. 25. Ma J, Granton PV, Holdsworth DW, Turley EA. Oral administration of hyaluronan reduces bone turnover in ovariectomized rats. J Agric yFood Chem. 2013 Jan 16;61(2):339-45. doi: 10.1021/jf300651d. Epub .m2013 Jan 8. PMID: 23256527. w.nhf.com26. N. Kimmatkar, V. Thawani, L. Hingorani, R. Khiyani, Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee – A randomized double blind placebo controlled trial, Phytomedicine, Volume 10, Issue 1, 2003, Pages 3-7, ISSN 0944-7113. ww27. Grover, A.K., Samson, S.E. Benefits of antioxidant supplements for knee osteoarthritis: rationale and reality. Nutr J 15, 1 (2015). 28. Vishal AA, Mishra A, Raychaudhuri SP. A Double Blind, Randomized, Placebo Controlled Clinical Study Evaluates the Early Efficacy of Aflapin® in Subjects with Osteoarthritis of Knee. Int J Med Sci 2011; 8(7):615-622. doi:10.7150/ijms.8.615. 29. Chopra, Arvind & Lavin, P & Patwardhan, Bhushan & Chitre, Deepa. (2000). Randomized double blind trial of an Ayurvedic plant derived formulation for treatment of rheumatoid arthritis. The Journal of rheumatology. 27. 1365-72. 30. Sadiq Umar, Khalid Umar, Abu Hasnath Md. Golam Sarwar, Altaf Khan, Niyaz Ahmad, Sayeed Ahmad, Chandra Kant Katiyar, Syed Akhtar Husain, Haider A. Khan, Boswellia serrata extract attenuates 27

K FLEX ACTIVE JOINT FORMULATION COMBINING WESTERN AND EASTERN MEDICINE inflammatory mediators and oxidative stress in collagen induced arthritis, Phytomedicine, Volume 21, Issue 6, 2014, Pages 847-856, ISSN 0944-7113. 31. https://www.thieme-connect.de/products/ejournals/ abstract/10.1055/s-2001-10708 32. Sarkate A, Dhaneshwar SS. Investigation of mitigating effect of colon-specific prodrugs of boswellic acid on 2,4,6-trinitrobenzene sulfonic acid-induced colitis in Wistar rats: Design, kinetics and biological evaluation. World J Gastroenterol. 2017 Feb 21;23(7):1147- 1162. doi: 10.3748/wjg.v23.i7.1147. PMID: 28275295; PMCID: PMC5323440. 33. Gupta I, Gupta V, Parihar A, Gupta S, Lüdtke R, Safayhi H, Ammon HP. Effects of Boswellia serrata gum resin in patients with bronchial asthma: results of a double-blind, placebo-controlled, y6-week clinical study. Eur J Med Res. 1998 Nov 17;3(11):511-4. PMID: .m9810030. w.nhf.com34. https://www.thieme-connect.de/products/ejournals/ abstract/10.1055/s-0035-1556201 35. Suhail, M.M., Wu, W., Cao, A. et al. Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor wwaggressiveness in cultured human breast cancer cells. BMC Complement Altern Med 11, 129 (2011). https://doi.org/10.1186/1472- 6882-11-129 28