Naturally Combating Joint Conditions

Aging is a natural, inevitable process, unselective in who it chooses—everyone will eventually age—wrinkles will appear, energy will decrease and for many, joints will become sore and inflamed. Baby Boomers are already feeling the heat of aging as many are struggling with joint conditions such as osteoarthritis. And, as the obesity epidemic continues to swell up, so do the joints of many overweight Americans as aging and obesity both contribute to the onset of osteoarthritis.

Osteoarthritis (OA) causes the breakdown of cartilage resulting in bone to bone friction, which produces pain, swelling and a loss of joint mobility; according to Arthritis Today, it afflicts more than 27 million Americans, primarily older adults. The National Institute of Arthritis and Musculoskeletal and Skin Diseases estimates that by 2030, approximately 72 million Americans will have reached the age of 65 and be at high risk for OA.¹

Rheumatoid arthritis (RA) is a less common affliction, affecting 1.3 million Americans. This autoimmune inflammatory disease occurs when the body’s immune system attacks the synovium membrane, the soft tissue that lines the joints, causing painful swelling and inflammation.

Between these two forms of arthritis and many other joint conditions (i.e., gout, lupus, fibromyalgia), there are a lot of Americans in pain and looking for ways to relieve that pain. Often, consumers turn to daily pain killers and non-steroidal anti-inflammatories (NSAIDs); but, these drugs take a toll on the body while relieving the pressure. As the natural products industry is well aware, many consumers are looking for natural remedies that not only soothe the pain, but enhance the wellness of the joints themselves.

Fatty Acids

Omega-3 essential fatty acids (EFAs) are a popular ingredient with countless health benefits, including joint health. A meta-analysis was conducted on 17 randomized, controlled trials assessing the pain relieving effects of omega-3 EFAs in patients with rheumatoid arthritis or joint pain secondary to inflammatory bowel disease and dysmenorrhea.² Supplementation with omega-3 EFAs for three to four months reduced patient reported joint pain intensity (P=0.03), minutes of morning stiffness (P=0.003), number of painful and/or tender joints (P=0.003), and NSAID use (P=0.01). Significant effects were not detected for physician-assessed pain or Ritchie articular index (graded joint response after firm pressure).

A separate study conducted at the University of Pittsburgh Medical Center found ibuprofen and omega-3 EFAs demonstrated equivalent effect in reducing arthritic pain and omega-3 EFA supplements were a safer alternative to NSAIDs for treatment of nonsurgical neck or back pain.³

A study published in the Journal of the American College of Nutrition examined the effect of long-term feeding of 10 percent dietary omega-3 (fish oil (FO)) and omgea-6 (corn oil (CO)) EFA at six weeks of age in a mouse model of RA.⁴ After sacrificing the mice at 12 months of age, antioxidant enzyme activities were measured.

At six, nine and 12 months of age, bone mineral density (BMD) was significantly higher (P<0.05) in distal femur, proximal tibia and lumbar spine; and spleen catalase (CAT) and superoxide dismutase (SOD) activities were also significantly higher (P<0.01) in FO-fed mice than CO-fed mice. Histology of knee joints revealed mild synovitis in CO fed mice, which was not present in FO fed mice. RT-PCR analysis of lymph nodes revealed decreased receptor activator of NF-kappaB ligand (RANKL) mRNA (P<0.001) expression and enhanced osteoprotegerin (OPG) mRNA expression (P<0.01) in FO fed mice compared to CO fed mice.

Additionally, a Brazilian team investigated 43 patients with RA in a parallel randomized design, assigned to one of three groups: group 1 (G1) received placebo (soy oil), group 2 (G2) received 3 g/d of fish oil omega-3 EFAs, and group 3 (G3) received 3 g/d of fish oil omega-3 EFAs and 9.6 mL of olive oil.⁵

There was a statistically significant improvement (P<0.05) in G2 and G3 in relation to G1 with respect to joint pain intensity, right and left handgrip strength after 12 and 24 weeks; duration of morning stiffness, onset of fatigue and Ritchie's articular index after 24 weeks; and ability to bend down to pick up clothing from the floor and getting in and out of a car after 24 weeks. G3, but not G2, in relation to G1 showed additional improvements with respect to duration of morning stiffness after 12 weeks, patient global assessment after 12 and 24 weeks, ability to turn faucets on and off after 24 weeks, and rheumatoid factor after 24 weeks. In addition, G3 showed a significant improvement in patient global assessment in relation to G2 after 12 weeks.

Celadrin® (from Proprietary Nutritionals), a proprietary blend of esterified fatty acids, has been the subject of studies for its efficacy in supporting joint health. One unpublished double blind, placebo-controlled study reported after eight weeks of ingesting 894 mg/d of Celadrin, average walking ability increased 45 percent and participants claimed a 35-percent decrease in knee discomfort.

 Additionally, a study published in the Journal of Rheumatology administered Celadrin or a placebo to 64 patients with chronic knee OA for 68 days.⁶ Patients treated with Celadrin showed a significant increase in knee flexion (P<0.001) and a significant (P<0.001) shift toward functional improvement compared to the placebo group.

Cartilage Support

Chondroitin sulfate is a popular supplement for joint health as it is an important structural component of cartilage. A study published in the Journal of Veterinary Science noted chondroitin sulfate and hyaluronan levels might be used as biomarkers for OA in dogs with hip dysplasia, indicating low levels of chondroitin sulfate may point to OA.⁷

Additionally, a Spanish review noted, “Four meta-analyses showed significant clinical effects of chondroitin sulfate compared with a placebo for pain and function measures and one demonstrated greater reduction of analgesic co-medication in patients assigned to the active treatment.”(8) One of the meta-analyses noted showed pain relief after chondroitin sulfate treatment steadily increased between four and 12 weeks of treatment, whereas the time course of pain relief after treatment with NSAIDs decreased.

A 2008 Brazilian study examined joint pain and cartilage damage using the anterior cruciate ligament transection (ACLT) model.⁹ Wistar rats were subjected to ACLT of the right knee or sham operation. They were orally administered either 500 mg/kg of isolated glucosamine (Glu), 500 mg/kg of glucosamine and 400 mg/kg of chondroitin (Gluchon), or non-treated (NT) starting seven days prior to ACLT until sacrifice at 70 days.

Gluchon, but not Glu, significantly reduced joint pain (P<0.05) compared to NT. There was an increase in chondroitin sulfate content in the OA group compared to sham (P<0.05). The chondroitin sulfate from right knee samples had higher molar weight compared to sham (P<0.05). Gluchon administration significantly reversed both the increases in chondroitin sulfate content and molar weight as compared to NT. Isolated Glu decreased chondroitin sulfate content though not reaching statistical significance. Cartilage histology alterations were also significantly prevented by Gluchon administration.

Contrastingly, results from the second phase of the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) showed no benefit from supplementing with glucosamine and/or chondroitin sulfate or a COX-2 inhibitor on joint space width (JSW) loss as compared with a placebo.¹⁰ The 24-month, double blind, placebo-controlled study, enrolled 572 patients with knee OA. Patients who had been randomized to one of the five groups in the original GAIT trial continued to receive 500 mg of glucosamine three times daily, 400 mg of chondroitin sulfate three times daily, the combination of glucosamine and chondroitin sulfate, 200 mg/d of celecoxib, or a placebo.

Mean JSW loss at two years in knees with OA in the placebo group, adjusted for design and clinical factors, was 0.166 mm. No statistically significant difference in mean JSW loss was observed in any treatment group compared with the placebo group. Treatment effects on K/L grade 2 knees, but not on K/L grade 3 knees, showed a trend toward improvement relative to the placebo group. The power of the study was diminished by the limited sample size, variance of JSW measurement and a smaller than expected loss in JSW. Knees with K/L grade 2 radiographic OA appeared to have the greatest potential for modification by these treatments.

Andrew Shao, Ph.D., vice president, scientific and regulatory affairs, CRN, commented: “The results of the GAIT II trial are perplexing and extremely inconsistent with an existing large body of evidence that shows a benefit from glucosamine and chondroitin supplementation. The results are also inconsistent with the first arm of GAIT, as well as with a series of previously published clinical trials which examined the same outcome—the narrowing of the space between joints—and demonstrated clear benefit. ... [And] a series of major limitations with this study render its results questionable. For example, the original hypothesis that glucosamine and chondroitin or a combination of the two may slow or prevent normal JSW narrowing due to OA can’t be answered by this trial. In addition, the study, intending to enroll nearly 800 knee OA patients, ended up being grossly underpowered, with only 357 patients completing the study, due to loss to follow-up and exclusions, making it highly difficult to draw any meaningful conclusions from the results.”

Despite the adverse results of the GAIT II trial, countless studies provide support in favor of glucosamine and chondroitin’s affect on joint health. In a French review, researchers from the World Health Organization (WHO) conducted a research review on randomized, placebo-controlled clinical trials published or performed between January 1980 and March 2002 that assessed the efficacy of oral glucosamine or chondroitin.¹¹

Glucosamine had a significantly high efficacy on all outcomes, including joint space narrowing and WOMAC; and, chondroitin was found to be effective in terms of the Lequesne Index, visual analog scale pain, mobility and responding status. Long-term treatment with glucosamine has also been found to retard the progression of knee osteoarthritis.¹²

BioSerae Laboratories developed Osteol™, a natural ingredient from bio-active milk proteins; it was designed to improve the efficiency of the usual D-glucosamine and Chondroitin mix. In an unpublished monocentric, randomized, placebo-controlled study, Osteol was combined with D-glucosamine and chondroitin (OGC) to access its efficiency in reducing joint pain on 60-year-old subjects. Volunteers (n=57) suffering from mild to moderate OA of the knee consumed either 1.2 g/d of the ternary formula in the form of 400 mg capsules, or a placebo for 90 days.

The OGC-treated group saw a slight reduction of the Lequesne score (-32 percent) and the WOMAC score (-22 percent). The effects were not significantly different from those obtained in the placebo group (respectively, -26 percent and –21 percent), pointing to a placebo effect during this short treatment period. However, volunteers with a nascent OA experienced a significantly decreased WOMAC score, and more particularly, the pain WOMAC score (-50 percent, P=0.0094).

Another unpublished study combined Osteol with D-glucosamine and chondroitin sulfate in order to compare it to usual anti-inflammatory drugs (ibuprofen, aspirin and indomethacin). In three independent experiments, mice consumed 5 mg/d of OGC in water 15 days before the induction of arthritis with collagen.

The mice showed a significantly reduced incidence of arthritis (20 percent to 55 percent), compared to mice in the control group (84 percent to 100 percent). The production of TNF induced after collagen treatment was significantly lower, and the production of IFN-g, and tumor necrosis factor by spleen lymphoid cells in response to collagen II was significantly reduced in OGC-fed animals. The total IgG and type II collagen-specific IgG levels were lower in the serum of OGC-fed mice. When the OGC formula was compared to the usual anti-inflammatory drugs, the preventive anti-inflammatory effect of the OGC formulation was equivalent.

Another popular method for the natural treatment of joint conditions is collagen type II. There are 14 different kinds of collagen altogether, but the primary collagen is collagen type II. Collagen type II is often derived from chicken sternal cartilage, which contains a high number of anti-inflammatory and joint supporting proteoglycans.

BioCell Technology supplies a patented blend of hyaluronic acid (HA), chondroitin sulfate and collagen type II from hydrolyzed chicken sternal cartilage called BioCell Collagen II®. It has been proven to be well-tolerated in toxicity studies.¹³

Additionally, in a randomized, double blind, placebo-controlled clinical trial, BioCell Collagen II was found to be a safe and effective dietary supplement for the adjunctive treatment for OA.¹⁴ Sixteen subjects with OA of the knee or hand were enrolled for a two-month intervention study and randomized to 1000 mg of BioCell or a placebo. The BioCell group experienced a significant improvement in all Western Ontario and McMaster Osteoarthritis Index (WOMAC) subscales and in total WOMAC scores when compared to the placebo group (P<0.05).

In an unpublished study, collagen type II (as UC-II®, from InterHealth Nutraceuticals) was found to be twice as effective in reducing OA pain and stiffness compared to glucosamine + chondroitin. In the randomized, double blind, placebo-controlled study, 52 patients took 40 mg/d of UC-II or a combination of 1,500 mg/d of glucosamine + 1,200 mg/d of chondroitin for 90 days.

After 90 days, UC-II treatment reduced the WOMAC score by 33 percent compared to 14 percent in the glucosamine + chondroitin-treated group. The UC-II-treated group showed a 40-percent decrease in the VAS score compared to 15.4 percent in the glucosamine + chondroitin-treated group. Treatment with UC-II also reduced Lequesne's functional index score by 20.1 percent compared to 5.9 percent in the glucosamine + chondroitin treated groups.

Similarly, 20 dogs in a 120-day, placebo-controlled study were divided into four groups: group 1, placebo; group 2, 10 mg/d of UC-II (from InterHealth Nutraceuticals); group 3, 2,000 mg/d of glucosamine HCL + 1,600 mg/d of chondroitin sulfate; or group 4, 10 mg/d of UC-II + 2,000 mg/d of glucosamine HCL + 1,600 mg/d of chondroitin sulfate, followed by a 30-day withdraw period.¹⁵

Within 30 days, group 2 showed significant reductions in overall pain (33 percent) and after 60 days reductions in pain upon limb manipulation and exercise-associated lameness (66 percent and 44 percent, respectively). After 120 days, overall pain (62 percent), pain upon limb manipulation (91 percent) and exercise-associated lameness (78 percent) were all reduced. Group 4 was significantly better than group 3 with significant reductions in overall pain (57 percent), pain upon limb manipulation (53 percent) and exercise-associated lameness (53 percent). In groups 2 and 4, the dogs experienced a relapse of pain after the supplements were withdrawn.

Kolla2® (from AIDP Inc.) is manufactured from chicken sternum cartilage that contains a minimum of 16.1 percent HA, 17.4 percent glucosamine sulfate, 15.3 percent chondroitin sulfate and 71 percent total collagen type II. According to the company, results from long-term micro-research revealed a canine, diagnosed with hip dysplasia, was able to resume normal mobility and retain normal hip cartilage after six years of daily supplementation with ArthroPet™, a supplement formula with Kolla2. AIDP also reported an additional canine taking ArthroPet had a 75-percent improvement in joint comfort and mobility after six months of supplementation.

Botanicals, Minerals and Herbs

Harpagophytum procumbens, better known as devil’s claw, is a plant native to southern Africa and is commonly used in arthritic patients. One double blind, randomized, multicentre clinical study, compared 6 capsules/d of Harpadol (435 mg of cryoground powdered Harpagophytum procumbens) to 100 mg/d of diacerhein, a European slow-acting drug for osteoarthritis (SADOA) for four months in 122 patients suffering from OA of the knee and hip.¹⁶

Spontaneous pain showed a significant improvement during the course of the study and there was no difference in the efficacy of the two treatments. Similarly, there was a progressive and significant reduction in the Lequesne functional index and no statistical difference was found between Harpadol and diacerhein. At the end of the study, patients taking Harpadol were using significantly less NSAIDs and antalgic drugs and the frequency of adverse events was significantly lower in the Harpadol group. The most frequent event reported was diarrhea, occurring in 8.1 percent and 26.7 percent of Harpadol and diacerhein patients, respectively.

Burgundy Botanical Extracts, distributed by Pharmline Inc., manufactures IridoForce™, a patented Devil’s Claw extract designed to work on both inflammation and damage prevention of joints and cartilage. In unpublished studies, IridoForce significantly effected inhibition on human COX-2 of 31 percent, stimulated the synthesis of glycosaminoglycans by the normal human chondrocytes, and stimulated the synthesis of hyaluronic acid by the normal human chondrocytes.

Seaweed has proven to have positive affects on arthritis. Aquamin™, distributed by GTC Nutrition, is a natural multi-mineral ingredient derived from the red seaweed Lithothamnium calcareum found in certain cold and temperate seas. In a study published in Nutrition Journal, 70 subjects with moderate to severe OA of the knee were randomized to four double blinded treatments for 12 weeks: 1,500 mg/d of glucosamine sulfate; 2,400 mg/d of Aquamin; a combined treatment of 1,500 mg/d of glucosamine sulfate and 2,400 mg/d of Aquamin; or a placebo.¹⁷

Fifty subjects completed the study and analysis of the data showed significant differences between the groups for changes in WOMAC pain scores over time (P= 0.009 ANCOVA); however, these data must be reviewed with caution since significant differences were found between the groups at baseline for WOMAC pain and stiffness scores (P= 0.0039 and P= 0.013, respectively, ANOVA).

Only the Aquamin and glucosamine groups demonstrated significant improvements in symptoms over the course of the study. The combination and placebo groups did not show any significant improvements in OA symptoms in this trial. WOMAC scores on pain, activity, composite and stiffness and the six minute walking distances significantly improved for subjects in the Aquamin and glucosamine treatment groups. The Aquamin and glucosamine groups walked 101 feet (+7 percent) and 56 feet (+3.5 percent) extra, respectively.

Arnica montana is a perennial herb that grows in Europe, the northern United States, Canada and eastern Asian. In a randomized, double blind study published in Rheumatology International, arnica was as effective as ibuprofen in treating OA of the hands.¹⁸ The effects of 5 percent ibuprofen and 50 g tincture/100 g, DER arnica (as Arnica Rub, from Bioforce USA), as gel preparations in 204 patients with OA of interphalangeal joints of hands was evaluated for 21 days. There were no differences between the two groups in pain and hand function improvements, or in any secondary end points evaluated. Adverse events were reported by six patients (6.1 percent) on ibuprofen and by five patients (4.8 percent) on arnica.

However, a systematic review of placebo-controlled clinical trials on arnica was conducted to review the clinical efficacy of homeopathic arnica.¹⁹ From the eight trials that fulfilled the requirements, researchers concluded the claim that homeopathic arnica is efficacious beyond a placebo effect was not supported by rigorous clinical trials.

French maritime pine bark has been used for centuries to heal wounds. Research shows it also helps reduce pain associated with OA. A study published in Phytotherapy Research randomly allocated 100 patients with stage I or II OA to either 150 mg/d of Pycnogenol® (from Natural Health Sciences) or placebo for three months.²⁰ Subjects were allowed to continue taking NSAIDs or analgesics prescribed before the study but had to record every pill taken.

The overall score, summarizing pain, stiffness and daily activities, improved significantly by 20.9 percent in the Pycnogenol group. Joint improvement achieved with Pycnogenol persisted after intake was discontinued for four weeks. Joint pain decreased by 40.3 percent after completion of the three months supplementation with Pycnogenol and two weeks later the pain was still 36.1 percent lower than at baseline. Furthermore, 38 percent of patients in the Pycnogenol group required less NSAIDs or other analgesic medication for joint pain.

In a separate randomized, double blind, placebo-controlled trial, 37 OA patients received either a placebo or 50 mg of Pycnogenol three times daily three months.²¹ At 90 days, significant reductions of 43 percent, 35 percent, 52 percent and 49 percent in self-reported pain, stiffness, physical function and composite WOMAC score, respectively, were reported in the Pycnogenol group, whereas the placebo group showed no significant changes. The dosage and frequency of NSAIDs or COX-2 inhibitors usage were increased in the placebo group and were significantly less in Pycnogenol group.

Keratin and Creatine

Kre-Celazine®, manufactured by All American Pharmaceuticals, is a complex material consisting of Kre-Alkayn® (from All American Pharmaceuticals), a pH correct creatine, with esterified fatty acid carbons. In a 2007 unpublished case study, Kre-Celazine was found free of side effects in addition to decreasing pain during the day and at night; and increasing mobility, daily routines and energy. Researchers concluded Kre-Celazine worked as well or better than prescription and over the counter (OTC) drugs for arthritics.

A separate unpublished study orally administered 750 mg/d of Kre-Celazine to a male youth born with double club feet with a short Achilles tendon for three months. In the less than eight hours of administration, the subjected reported his pain had disappeared. At the end of the three-month study, the subject was still pain-free and Kre-Celazine healed his chronic inflammation.

Keratin is a fibrous structural protein known to stimulate new joint tissue and deliver antioxidant protection. Cynatine FLX™ (from Keratec Ltd.) is a functional keratin that is extracted from pure New Zealand wool. According to the company, Cynatine FLX offers a four-fold action by building joint resilience, helping to reduce inflammation, improving mobility and protecting joints.

Independent tests on rats showed orally ingested Cynatine FLX activated two important joint antioxidant defense enzymes, glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD).²² It increased GSH-PX levels and increased SOD levels, which is reduced in damaged joints. The same set of tests indicated Cynatine FLX supports the body's natural antioxidant processes, shown by reductions in malondialdehde (MDA), a biological marker of oxidative stress. In a separate trial, laboratory testing with human and bovine cells demonstrated Cynatine FLX stimulated cell growth up to 50 percent faster than control samples.

Thankfully, there are myriad options for those who suffer from arthritic pain and as more research is conducted, the field of natural supplements for joint health will continue to grow.

References on the next page...

References for "Naturally Combatting Joint Conditions"