Joint pain and inflammation cause much distress, especially to aging
populations. Diseases such as arthritis are not really "curable," but the right
remedies can help manage the pain and underlying causes, sometimes even
improving function of the affected joints. Natural products have drawn attention
from consumers looking for alternatives to conventional joint pain and
inflammation medications that often come with unhealthy side effects.
Arthritis strikes in two distinct ways. Osteoarthritis (OA) causes a
breakdown in the cartilage that coats the ends of bones at the joint. Because
this cartilage protected the ends of the bones, any damage to this connective
tissue affects the ability of the joints to operate smoothly, and can promote
bone-on-bone contact during joint motion, resulting in pain, swelling and
further damage to the cartilage. This form of arthritis is the most common and
affects about 27 million people in the United States, according to the National
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), which
estimated 20 percent of Americans—about 72 million people—will be past their
65th birthday and at high risk of OA by 2030. NIAMS reported the most common
areas of the body affected by OA are the hands, spine, knees and hips.
On the other hand, rheumatoid arthritis (RA) attacks the synovial membrane,
the soft tissue covering the non-cartilaginous surfaces, forming a cavity in the
joint in which synovial fluid helps reduce joint friction. RA, which affects 1.3
million Americans, is an autoimmune condition that causes inflammation and
thickening of the membrane, resulting in pain and reduced joint function. The
inflamed synovium can damage cartilage and bone within the joint, and lead to
weakened muscles, tendons and ligaments. RA is symmetrical, so if the left hand
is afflicted, so is the right hand.
Both forms of arthritis tend to primarily affect older adults, due to aging,
but are also more prevalent in women. In fact, the Natural Marketing Institute (NMI)
has reported Boomers are significantly more likely to be managing arthritis and
joint problems, compared to younger generations. The Arthritis Foundation
supports this data, reporting half of people older than 65 have some form of
arthritis. And, Heather Whitson, Ph.D., Duke University Medical Center, Durham,
NC, presented data from the Cardiovascular Health Study showing women suffered
up to two and a half times more disabilities, including arthritis, than men of
the same age.
Thanks in part to the downfall of conventional joint pain remedies such as
non-steroidal anti-inflammatory drugs (NSAIDs), which has dangerous side effects
including heart problems, natural products have caught the attention of
consumers and their physicians.
The Council for Responsible Nutrition (CRN) conducted a survey of physicians,
finding bone, joint and heart health are among the primary health conditions for
which U.S. health professionals recommend dietary supplements to patients.
Specifically, 33 percent reported recommending supplements for bone health
issues, the top condition, and 29 percent for joint problems, the third most
common.
According to the National Health Interview Survey (NHIS), overseen by the
National Center for Health Statistics/Centers for Disease Control and Prevention
(CDC), Glucosamine and fish oil/omega-3 essential fatty acids (EFAs) are among
the most popular complementary and alternative medicine (CAM) products sought by
adults and children for back and neck pain, joint pain, arthritis and other
musculoskeletal conditions.
Krista Faron, senior analyst at Mintel, reported glucosamine, chondroitin,
MSM and omega-3 fatty acids are the most common natural remedies; 25 percent of
arthritis sufferers turn to glucosamine, chrondroitin and/or herbal remedies to
treat their arthritis, while 60 percent turn to over-the-counter (OTC) drugs and
40 percent choose prescription drugs.
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The Joint Chiefs
Glucosamine leads the joint health category, backed by a body of research
showing supplementation with this amino sugar can help fight OA, possibly by
protecting cartilage from damage, contributing to compounds that rebuild
cartilage and helping to manage inflammation in the joint.1,2,3
Despite many years of positive study results on joint pain, mobility and
inflammation, researchers from the second arm of the Glucosamine/Chondroitin
Arthritis Intervention Trial (GAIT)4 concluded glucosamine had no
effect on joint space narrowing—the smaller the joint space, the greater the
chances of friction and pain.
However, nutrition industry experts, including Andrew Shao, Ph.D., CRN, noted
the GAIT II trial was unable to draw any real conclusion on joint-space
narrowing, as it was underpowered (ended up with fewer than half of its intended
800 subjects); and the placebo group experienced nowhere near the joint-space
narrowing expected, making comparison difficult or impossible.
Still, a 2009 Brazilian study found the combination of glucosamine and
chondroitin, but not glucosamine alone, showed a positive analgesic effect on
joint pain and protected against cartilage damage in an animal OA model.5
This combination of natural ingredients is often also paired in dietary
supplements and other products with MSM (methylsulfonylmethane), which provides
sulfur for cartilage formation and can help joint health via anti-inflammatory
and antioxidant actions.6 Combined with glucosamine, MSM may decrease
joint swelling and pain intensity among patients with mild to moderate OA,
compared to either ingredient on its own.7
A couple of branded MSM ingredients are popular in joint products based on
researched evidence of efficacy. In an animal study, OptiMSM®, from Bergstrom
Nutrition, modified immune response to arthritis, reducing swelling and
arthritic deformation of the joint.8 Bergstrom also makes ActivMSM®,
which is marketed by TandemRain Innovations. In mid-2009, Miami Research
Associates reported ActivMSM was rapidly absorbed and retained in the body for
an extended time period. MSM expert Stanley Jacobs, Ph.D., Oregon Health
Sciences University, noted while MSM has been thought to work by donating
sulfur, data from the ActivMSM trial suggest, "MSM functions as a sulfur
metabolism modifier, promoting the apparent retention of sulfur and rapidly
altering sulfur metabolism—as evidenced in changes seen with homocysteine."
Omega-3 EFAs round out the leading joint ingredients list, offering consumers
a tool to affect the inflammatory cascades in the body. Omega-3s docosahexaenoic
acid (DHA) and eicosapentaenoic acid (EPA), found commonly in fish oil, are
central to the inflammatory cascade and produce anti-inflammatory mediators,
compared to bad fats that produce inflammatory mediators. While omega-3s promote
anti-inflammatory compounds, NSAIDs block the enzyme (LOX and COX) pathways that
produce both pro- and anti-inflammatory eicosanoids.
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Supplementation with omega-3s for three to four months has been credited with
relieving joint pain, tenderness, morning stiffness and NSAID use.9
It appears fish oil is more beneficial to joint health than other forms of
omega-3s. In RA patients, 3 g/d of fish oil with or without 9.6 mL of olive oil
has been shown to improve joint pain intensity, and right and left handgrip
strength after 12 and 24 weeks.10
Membranes, Tissues and Proteins
A number of specialty supplements are helping to address joint health and
arthritis pain by nourishing the various joint structures and providing natural
anti-inflammatory compounds.
Hyaluronic acid (HA) is a major component of synovial fluid, which provides
lubrication for joints. Many studies have found positive results with HA
injections directly into the joint, improving joint pain and mobility via
modulation of several inflammatory markers.11 However, oral HA has
begun to positively affect such inflammatory markers,12 and many
joint health supplements offer HA as an ingredient in combination formulas or as
a component within a broader joint health compound.
For example, synovial fluid is often thought of as egg-like; one of the
latest ingredients to hit the joint health market is made from egg shell
membrane (ESM), which contains glycosaminoglycans such as chondroitin and
hyaluronic acid, as well as collagen and other proteins that contribute to
healthy cartilage and synovium. In 2009, researchers reported ESM (as NEM®, from
ESM Technologies) is an effective and safe option for the treatment of pain and
stiffness associated with knee OA.13 The dose used in their study was
500 mg/d of NEM for eight weeks, and no side effects were reported.
Collagen type II is most commonly derived from chicken sternal cartilage,
which contains a high number of anti-inflammatory and joint-supporting
proteoglycans. UC-II® from InterHealth has performed well in published and
unpublished OA research, addressing joint pain and stiffness, and even
outperforming glucosamine-chondroitin combinations.14 BioCell
Collagen II® from BioCell technologies contains HA, chondroitin sulfate and
collagen type II from hydrolyzed chicken sternal cartilage. In published
research, two months of supplementation with 1,000 mg/d BioCell Collagen II
helped OA knee and hand patients significantly improve their key OA scores.15
Lubrication a is key factor in a smooth, healthy joint. A proprietary blend
of cetylated fatty acids (Celadrin® from Proprietary Nutritionals) is designed
to lubricate cell membranes, especially those in the joints. Topical Celadrin
cream has demonstrated an ability to help improve mobility, function, range of
motion and pain in studies on patients with OA in the knee, wrist or elbow.16,17
Oral Celadrin has tested well on chronic knee OA, increasing flexion and
function after about two months of supplementation.18
All American Pharmaceuticals combined esterified fatty acid carbons with its
Kre-Celazine® pH correct creatine to make a joint-health ingredient called
Kre-Celazine®. A 2007 case study conducted by BioCeutical R&D Labs in Montana
showed Kre-Celazine can decrease pain and increase mobility, as well as or
better than prescription and OTC arthritis medications. This followed a 2002
case study at the same lab, which found pro football players with initial joint
pain were pain-free after six weeks of supplementation with Kre-Alkalyn. Joe
Archer, All American Pharmaceuticals, noted results depend on the person and the
extent of their joint problem, but relief could be achieved in as little 30
minutes or as much as one week; but, most people get results within two or three
days. He recommended a dose of 1,400 mg/d, which amounts to two capsules.
On the protein side, a specialty ingredient made from milk protein
concentrate (Microlactin™ from Humanetics) has shown benefit to people suffering
OA, possible via anti-inflammatory actions. Six weeks of supplementation with
2,000 mg twice daily of Microlactin resulted in reduced pain and stiffness, in
addition to improving the daily activity index.19
Anti-Inflammatory Botanicals
When joints are damaged due to OA and RA progression, the resulting
inflammation is the root of pain and decreased function. Numerous herbs have
scientifically supported anti-inflammatory properties that have proven useful to
consumers managing joint pain.
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Boswellia serrata affects a couple of the inflammatory cascades tied to
enzymes such as COX and LOX. In one study, boswellia extract (WOKVEL® from
Verdure Sciences Corp.) decreased arthritis pain and inflammation scores
compared to the NSAID valdecoxib during a seven-month period. Ohio State
University scientists studying another specialty boswellia compound (5-LOXIN
from Laila Nutraceuticals and P.L. Thomas) discovered the herb affected 113 of
522 induced genes related to inflammation, cell adhesion and proteolysis
(protein breakdown).20 They noted 5-LOXIN also acted on several
inflammatory mediators, including matrix metalloproteinases (MMPs) that
contribute to cartilage breakdown.
Turmeric and its anti-inflammatory active constituent curcumin also inhibit
MMPs and other inflammatory mediators.21 Further, curcumin was found
to affect the COX-2 enzyme, which affects inflammation, but not the COX-1 enzyme
that affects gastrointestinal (GI) tract health.22 This is important,
because non-selective drugs can affect both forms of COX enzymes, and cause GI
problems. This is behind the finding that curcumin works synergistically with
COX-2 inhibitor celecoxib, possibly decreasing the drug dosage required for
arthritis patients.23
Devil's claw is another herb that works against MMPs and assorted
inflammatory mediators.24 It can provide an analgesic action in acute
and subacute inflammation, and has been shown to reduce pain and improve
mobility in OA patients.25,26 In a U.K. trial, 259 patients with
arthritis and other rheumatoid problems were able to improve global pain,
stiffness and function, as well as various quality of life measurements, after
taking devil's claw.27 In patients with knee or hip OA, cryoground
devil's claw powder (Harpadol from Arkopharma) supplementation was as effective
as the arthritis drug diacerhein, suggesting the herb could decrease the amount
of drugs required by OA patients.28
French maritime pine bark might also help OA patients need less
pharmaceutical medication. One study on pine bark extract (Pycnogenol® from
Natural Health Sciences) found 100 patients with stage I or II OA had
significant improvement in joint pain, stiffness and function after taking 150
mg/d of Pycnogenol for three months.29 The benefits persisted as much
as two weeks after the supplementation ended. These results on pain, stiffness
and function were equaled in another study that featured OA patients taking
Pycnogenol with smaller NSAID dosages and a placebo group that took increasing
amounts of NSAIDs.30
While maritime pine trees are found commonly near the sea, a supplement made
from a plant found in the sea, red seaweed (Aquamin™ distributed by GTC
Nutrition), has generated recent buzz for also improving pain and mobility while
relieving OA patients of the need for NSAID use.31 Another study
produced some mixed results, as Aquamin compared favorably to glucosamine on
pain and mobility in patients with moderate to severe knee OA, but the two
supplements in combination did not produce the same benefit, compared to
placebo.32
Mixed results also mark the use of Arnica montana on OA. One study
found topical arnica (Arnica Rub from Bioforce USA) was as effective as
ibuprofen in improving pain and function parameters in 204 patients with OA of
interphalangeal joints of hands.33 However, a systematic review of
placebo-controlled clinical trials on homeopathic arnica found no evidence of
efficacy beyond a placebo effect.34
Still, some experts such as Ellen Kamhi, Ph.D., R.N., who is known as the
Natural Nurse, recommend various homeopathic remedies for joint pain, soreness
and various arthritis symptoms. Specifically, Kamhi advocated Arnica, Rhus
toxicodendron (Rhus Tox), Dulcamara, Colocynthis and Bryonia.
Lou Paradise, chief of research at Topical BioMedics Inc., agreed homeopathic
products can help manage pain in inflammatory health problems such as arthritis.
Topricin has a synergy of homeopathic medicines—Arnica, Rhus Tox, Belladonna,
Lachesis Muta and Crotalus—and is designed to help balance the body’s molecular
chemistry for optimum healing. "The body’s challenge when there is an
inflammatory response is to drain the toxins from the cells, and provide a
restoration of oxygen-rich blood to all cells for repair," Paradise said. "Topricin’s
medicines stimulate the lymphatic system to drain allowing a relaxing of
constriction of the capillaries returning blood flow back to normal." He noted
Topricin has succeeded in pain relief performance, from pediatric to geriatric
care, where the vast majority of other pain management products and/or OTC
medicines have failed.
Cherry on Top
A 2007 pilot study conducted by Baylor Research Institute, Dallas, found half
of all OA patients enrolled experienced significant improvement in pain and
function after taking tart cherry pills (As CherryFlex®, from Brownwood Acres
Foods) for eight weeks. The Arthritis Care & Research Institute has joined in
for a follow-up study, initiated in early 2009. John J. Crush, M.D.,
rheumatologist and principal investigator of the study, said, “This specific
type of tart cherry is one of the best studied natural products and anecdotally
has been claimed to have a salutary effect on osteoarthritis and other types of
arthritis as well."
Gobbling Up Inflammation
Enzymes like COX and LOX contribute to the metabolism of fatty acids and the
resultant production of prostaglandins that can be either pro- or
anti-inflammatory. Many arthritis and joint pain treatments, whether natural or
conventional, target the production of these prostaglandins. How selective these
remedies are can determine their effectiveness and/or side effects. However
systemic enzyme supplements can actually digest, or break down, certain
prostaglandins responsible for inflammation, avoiding the question of side
effects due to lack of proper selectivity.
For example, protease enzymes can help remove excess fibrin that causes
inflammation and joint pain. "Inflammation is especially tender in moving joints
where more dense tissues rub against each other and fibrin increases blood
viscosity and blood pressure," said Daniel Curtin, Arthur Andrew Medical. He
explained enzymes in his company's Neprinol supplement digest fibrin and
pro-inflammatory prostaglandins leaving the blood purified, quelling the immune
response and retuning inflammatory levels to normal.
In published research, a combination of the enzymes rutosid, bromelain and
trypsin in patients with knee OA improved functionality and decreased pain at
rest and on motion.35 In other studies, this combination of protease
enzymes (Phlogenzym® from Mucos Pharma) decreased pain and stiffness measures in
patients with a high level of pain from hip OA, and reduced pain and joint
tenderness and swelling in knee OA patients after three weeks of
supplementation.36,37
Poor Joint Nutrition Gets a D
Vitamin D levels have been linked to many inflammatory diseases, including
arthritis. It appears vitamin D deficiency contributed to increased
inflammation, according to new research from the University of Missouri (J
Inflamm. 2008 Jul 24;5:10). Vitamin D deficiency in female subjects
correlated to increased concentrations of serum TNF-α, an inflammatory marker.
This is the first time researchers have found this particular link in a healthy,
non-diseased population.
Market Outlook
Many of the natural ingredients that help improve joint pain and mobility in
people with arthritis have generated positive research results on their own,
consumers seem to prefer the combination products that are increasingly hitting
the market.
Ken Halvorsrude, Doctor's Best, confirmed the trend in the market is for
combination formulas. "Doctor's Best had been selling, as individual products,
MSM, glucosamine sulfate and chondroitin sulfate for several years prior to
combining them," he said. "Once we launched the combo product, the sales of the
combo took off, while the sales of the individual ingredient products dwindled."
However, the sales data is less clear on how consumers are trending on single
verses multiple ingredient products in the joint category. Euromonitor
International has reported U.S. sales of glucosamine supplements were $872
million in 2007, up 16 percent compared to 2003 figures. However, according to
Krista Faron, Mintel, U.S. sales of glucosamine and chondroitin in the natural
channel declined nearly 3 percent from 2007 to 2008, settling at $26.6 million.
Despite this trend, Faron said the cause is not likely declining interest in
these products, but rather other economic factors. The continuing decline in the
overall unit cost of these products has affected sales data; and the flat growth
reflects the continued migration of the sales of specialty supplements into
food, drug and mass outlets.
The good news for the entire joint health category domestically is U.S. sales
of joint health supplements have increased 3 percent per year since 2003,
according to Euromonitor. This lags behind growth rates in the rest of the world
and is expected to slow to about 2 percent growth per year, and it seems recent
breakthroughs including vegetarian glucosamine and the emergence of functional
food and beverage joint products have not energized the U.S. growth rate as much
as the global rate, which was about 62-percent total growth from 2003 to 2008.
Perhaps it is just a sign of the times, but the once hot category of
functional food and beverage joint health products seems to be cooling off, at
least temporarily. Mintel recently reported global food and beverage
bone-and-joint new product introductions, as a percentage of total product
introductions, slowed between 2004 and 2008. In fact, Faron noted vitamins and
dietary supplements still dominate the joint category, with 85 percent of all
new products introductions; within the joint health segment, pain relief is the
biggest subcategory.
The growth outlook for glucosamine, chondroitin and the other natural joint
health ingredients backed by scientific evidence may be relatively flat and
amidst a tough economic climate. However, market research data indicates a
growing number of consumers are managing joint health issues such as arthritis,
and many are turning to natural alternatives for help in managing pain,
stiffness, mobility and quality-of-life issues associated with joint woes. It is
up to knowledgeable retailers to use the resources available from manufacturers
and research reports to educate their customers on all the ways various
nutrients, herbs and specialty supplements can address joint structural
integrity and inflammation.
1. Wang SX et al. “The effects of glucosamine hydrochloride on subchondral
bone changes in an animal model of osteoarthritis.” Arthritis Rheum. 2007
May;56(5):1537-48.
2. Rafi MM, Yadav PN, Rossi AO. “Glucosamine inhibits LPS-induced COX-2 and
iNOS expression in mouse macrophage cells (RAW 264.7) by inhibition of p38-MAP
kinase and transcription factor NF-kappaB.” Mol Nutr Food Res. 2007
May;51(5):587-93.
3. Tiku ML et al. “Glucosamine prevents in vitro collagen degradation in
chondrocytes by inhibiting advanced lipoxidation reactions and protein
oxidation.” Arthritis Res Ther. 2007 Aug 8;9(4):R76.
4. Allen D. Sawitzke et al. “The effect of glucosamine and/or chondroitin
sulfate on the progression of knee osteoarthritis: A report from the glucosamine/chondroitin
arthritis intervention trial” Arthritis Rheumatis. 2008;58(10):3183-91
5. Silva FS et al. "Combined glucosamine and chondroitin sulfate provides
functional and structural benefit in the anterior cruciate ligament transection
model." Clin Rheumatol. 2009 Feb;28(2):109-17.
6. “Methylsulfonylmethane monograph” Alt Med Rev. 2003;8(4):438-11.
7. Usha PR, Naidu MU. “Randomised, Double-Blind, Parallel, Placebo-Controlled
Study of Oral Glucosamine, Methylsulfonylmethane and their Combination in
Osteoarthritis.” Clin Drug Investig. 2004;24(6):353-63.
8. Hasegawa T et al. “Suppressive effect of methylsulfonylmethane (MSM) on
type II collagen-induced arthritis in DBA/1J mice.” Jpn Pharmacol Ther.
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9. 2.Goldberg RJ, Katz J “A meta-analysis of the analgesic effects of omega-3
polyunsaturated fatty acid supplementation for inflammatory joint pain” Pain.
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10. 5.Berbert AA et al. “Supplementation of fish oil and olive oil in
patients with rheumatoid arthritis” Nutrition. 2005 Feb;21(2):131-6.
11. Waddell DD. “Viscosupplementation with hyaluronans for osteoarthritis of
the knee: clinical efficacy and economic implications.” Drugs Aging.
2007;24(8):629-42.
12. Kalman DS et al. "Effect of a natural extract of chicken combs with a
high content of hyaluronic acid (Hyal-Joint) on pain relief and quality of life
in subjects with knee osteoarthritis: a pilot randomized double-blind
placebo-controlled trial." Nutr J. 2008 Jan 21;7:3.
13. Ruff KJ et al. "Eggshell membrane in the treatment of pain and stiffness
from osteoarthritis of the knee: a randomized, multicenter, double-blind,
placebo-controlled clinical study." Clin Rheumatol. 2009 April, Epub ahead of
print.
14. 15.M D’Altilio et al. “Therapeutic Efficacy and Safety of Undenatured
Type II Collagen Singly or in Combination with Glucosamine and Chondroitin in
Arthritic Dogs” Toxicol Mechani Meth. 2007;17:189-96.
15. Kalman DS et al. “A randomized double blind clinical pilot trial
evaluating the safety and efficacy of hydrolyzed collagen type II in adults with
osteoarthritis” FASEB Experimental Biology 2004 Abstracts, Washington DC, April
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16. Kraemer WJ et al. "A cetylated fatty acid topical cream with menthol
reduces pain and improves functional performance in individuals with arthritis."
J Strength Cond Res. 2005 May;19(2):475-80.
17. Kraemer WJ et al. "Effects of treatment with a cetylated fatty acid
topical cream on static postural stability and plantar pressure distribution in
patients with knee osteoarthritis." J Strength Cond Res. 2005 Feb;19(1):115-21.
18. R Hesslink et al. “Cetylated Fatty Acids Improve Knee Function in
Patients with Osteoarthritis” J Rheumatol. 2002;29(8):1708-12
19. Zenk JL, Helmer TR, Kuskowski MA. “The effects of milk protein
concentrate on the symptoms of osteoarthritis in adults: An exploratory,
randomized, double-blind, placebo-controlled trial.” Curr Ther Res.
2002;63(7):430-42.
20. Roy S et al. “Human Genome Screen to Identify the Genetic Basis of the
Anti-inflammatory Effects of Boswellia in Microvascular Endothelial Cells.” DNA
Cell Biol. 24, 4:244-55, 2005.
21. Shakibaei M et al. “Suppression of NF-kappaB activation by curcumin leads
to inhibition of expression of cyclo-oxygenase-2 and matrix metalloproteinase-9
in human articular chondrocytes: Implications for the treatment of
osteoarthritis.” Biochem Pharmacol. 2007 May 1;73(9):1434-45.
22. Park C et al. “Curcumin induces apoptosis and inhibits prostaglandin E(2)
production in synovial fibroblasts of patients with rheumatoid arthritis.” Int J
Mol Med. 2007 Sep;20(3):365-72.
23. Lev-Ari S et al. “Curcumin synergistically potentiates the
growth-inhibitory and pro-apoptotic effects of celecoxib in osteoarthritis
synovial adherent cells.” Rheumatology (Oxford). 2006 Feb;45(2):171-7.
24. Schulze-Tanzil G, Hansen C, Shakibaei M. “[Effect of a Harpagophytum
procumbens DC extract on matrix metalloproteinases in human chondrocytes in
vitro][Article in German].” Arzneimittelforschung. 2004;54(4):213-20.
25. Grant L et al. “A review of the biological and potential therapeutic
actions of Harpagophytum procumbens.” Phytother Res. 2007
Mar;21(3):199-209.
26. Wegener T, Lüpke NP. “Treatment of patients with arthrosis of hip or knee
with an aqueous extract of devil's claw (Harpagophytum procumbens DC.).”
Phytother Res. 2003 Dec;17(10):1165-72.
27. Warnock M et al. "Effectiveness and safety of Devil's Claw tablets in
patients with general rheumatic disorders." Phytother Res. 2007
Dec;21(12):1228-33.
28. Chantre P et al. “Efficacy and tolerance of Harpagophytum procumbens
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2000;7(3):177-83
29. 20.Peter Cisár et al. “Effect of pine bark extract (Pycnogenol®) on
symptoms of knee osteoarthritis” Phytother Res. 2008;22(8):1087-92.
30. Reza Farid et al. “Pycnogenol supplementation reduces pain and stiffness
and improves physical function in adults with knee osteoarthritis” Nutr. Res.
2007;27(11):692-97.
31. Frestedt JL et al. "A natural seaweed derived mineral supplement (Aquamin
F) for knee osteoarthritis: A randomised, placebo controlled pilot study."
Nutrition. 2009, 8:7.
32. 17.Joy L Frestedt et al. “A natural mineral supplement provides relief
from knee osteoarthritis symptoms: a randomized controlled pilot trial” Nutr J
2008;7:9 DOI:10.1186/1475-2891-7-9
33. 18.Reto Widrig et al. “Choosing between NSAID and arnica for topical
treatment of hand osteoarthritis in a randomized, double-blind study” Rheumatol
Int. 2007;27:585-91
34.Ernst E, Pittler MH. “Efficacy of homeopathic arnica: a systematic review
of placebo-controlled clinical trials” Arch Surg. 1998;133(11):1187-1190.
35. Akhtar NM et al. “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.
36. Klein G et al. “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.
37. Tilwe GH et al. “Efficacy and tolerability of oral enzyme therapy as
compared to diclofenac in active osteoarthrosis of knee joint: an open
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