Osteoarthritis is a degenerative disease that is characterized by focal erosive lesions, cartilage destruction, subchondral sclerosis, cyst formation, and large osteophyte formation at joint margins that result in the structural and functional failure of synovial joints [13, 40]. It is the most prevalent musculoskeletal disorder diagnosed in the United States which affects nearly 15% of Americans and costs an estimated $80 billion dollars annually . Athletes with prior knee injuries and individuals who maintain an active lifestyle as they age are also at risk to experience knee pain or degenerative joint issues [5, 27, 28]. Although the etiology of OA involves multiple factors, obesity has been identified as a primary risk factor involved in the development of the disease . Individuals with a BMI greater than 30 kg/m2 are four times as likely to have knee OA than those with a BMI less than 25.0 kg/m2. Although the specific amount of weight loss needed to improve or prevent OA has yet to be determined, empirical research has found that for every one pound of weight loss, there is a four pound reduction in knee joint load per step . With such a drastic reduction in pressure on OA affected knees, alleviating obesity through weight loss has been suggested to be among the most beneficial methods of relieving pressure on osteoarthritic joints.
Participation in a therapeutic exercise program has been reported to aid in the management of OA symptoms [12, 43, 44]. The American College of Sports Medicine recommends that OA patients engaged in daily static stretching exercises to improve flexibility; low intensity resistance training involving major muscle groups (10-12 repetitions, 40-60% of 1RM, 2-3 d/week); and, aerobic exercise (40-60% of peak VO2, up to 30-min, 3-5 d/week) as tolerated [45, 46]. Regular exercise has also been reported to improve the balance and functionality of overweight and obese individuals with knee OA . Therefore, exercise and weight loss have been recommended as effective strategies in managing symptoms of OA [8–10, 12, 13, 42, 43, 47].
A number of studies support these recommendations. For example, Felson and colleagues  reported that weight loss reduced the risk for development of OA in women. Christensen and associates  reported that OA patients following a low-energy diet (~840 kcal/d) that included weekly dietary counseling sessions was more effective in promoting weight loss (11.1% vs. 4.3%) and improving WOMAC index scores (-35% vs. -14%) than patients educated about weight loss who maintained a moderately hypo-energetic diet (~1,200 kcal/d). Similarly, Miller and coworkers  reported that older obese adults with symptomatic knee OA who followed an intensive weight loss program for 6-months that included meal replacement bars and drinks (~1,000 kcal/d) experienced greater weight loss (0.1% vs. 8.5%), fat loss (0.08% vs. 23.2%); and, improvement in WOMAC scores (-5% vs. -33%), 6-min walking distance (2.3% vs. 16.7%), and stair climb time (7.5% vs. -16.3%) than those who maintained weight. Penninx and associates  reported that aerobic and resistance exercise may reduce and/or prevent the incidence of disability in activities of daily living in patients with knee OA. Finally, Messier and coworkers  examined the effects of long-term weight loss and exercise on self-reported physical function in older obese adults with knee OA. Participants followed a diet program, an exercise program that involved aerobic and resistance-exercise, a diet plus exercise intervention, or usual care. The researchers found that participants following the diet plus exercise program experienced significant improvements in self-reported physical function, 6-min walk distance, stair climb time, and knee pain compared to those in the usual care group. Exercise alone improved 6-min walk distance while dieting alone did not result in greater functional improvement than usual care.
Present findings support prior reports indicating that weight loss and exercise training provided therapeutic benefit for women with knee OA. In this regard, the circuit style resistance-training program and weight loss program used in this study promoted significant reductions in body mass (-2.4%), fat mass (-6%), and body fat (-3.5%) while increasing symptom-limited peak VO2 (5%), upper body 1RM strength (12%), upper body muscular endurance (20%), isokinetic knee extension and flexion peak torque (12-46%), step up and over knee function (8-15%), and forward lunge knee function (7-20%). These changes were accompanied by significant improvements in total cholesterol (-8%), low-density lipoproteins (-12%), HOMAIR (-17%), and leptin (-30%) values. Interestingly, reductions in serum leptin levels have been reported to be associated with improved physical function in patients with OA . Participants also reported less perceptions of pain (-53%), joint stiffness (-44%), and limitations in physical function (-49%) on the WOMAC index as well as a 59% reduction in VAS pain ratings. These findings provide additional evidence that patients with knee OA may experience significant improvements in markers of health, fitness, functional capacity, and perceptions of pain when following a weight loss and exercise program that includes resistance-training.
However, present findings add to our understanding of how different types of diets and concomitant dietary supplementation with a GCM affect weight loss, training adaptations, functional capacity, and/or perceptions of pain in women with knee OA. In this regard, a number of studies have indicated that replacing carbohydrate with protein while following a hypo-energetic diet promotes greater fat loss [14, 15, 19, 49]. The rationale has been that there are thermogenic advantages in metabolizing protein compared to carbohydrate and that a higher amount of protein in the diet can help maintain fat free mass during weight loss thereby helping minimize reductions in resting energy expenditure that is often associated with weight loss [14, 16]. Our previous research examining the efficacy of the exercise and diet program used in this study provides some support to this theory [20, 21, 23]. Therefore, we hypothesized that women with knee OA may experience greater weight loss and therapeutic benefits from following a higher protein diet. Present findings, however, indicate that women with knee OA benefited from both a higher carbohydrate and higher protein diet. Although there was some evidence that women following the HP diet experienced greater gains in symptom-limited peak aerobic capacity, no significant differences were observed in amount of weight loss, fat loss, or resting energy expenditure when diets were compared. Participants in both groups effectively maintained fat free mass and resting energy expenditure levels despite experiencing significant reductions in weight and fat mass. Additionally, no significant differences were observed between diet types among changes in strength, muscular endurance, functional tests, or markers of health. These findings indicate that the type of diet does not appear to influence weight loss or training adaptations in sedentary obese women with knee OA initiating a weight loss and exercise training program. The lack of statistical significance could be due to the small sample-size studied and/or that the exercise stimulus was effective enough to negate any additional metabolic benefits from adherence to a higher protein diet in this population. Nevertheless, present findings do not support our hypothesis that women with knee OA may experience greater benefits from following a higher protein hypo-energetic diet.
Several studies have also indicated that glucosamine and/or chondroitin supplementation may provide therapeutic benefits in individuals with knee OA. For example, Reginster and associates  reported that 3-years of glucosamine sulphate supplementation (1,500 mg/d) prevented progression of joint-space narrowing and improved WOMAC scores in patients with knee OA. Similarly, Pavelka and colleagues  found that dietary supplementation of glucosamine sulfate (1,500 mg/d for 3-years) retarded the clinical progression of knee OA. Braham et al  found that 2,000 mg/d of glucosamine supplementation for 12-weeks improved markers of quality of life and self-reported perceptions of knee pain in individuals with regular knee pain. Usha and coworkers  reported that dietary supplementation of 1,500 mg/d of glucosamine and/or MSM for 12-weeks produced an analgesic and anti-inflammatory effect, reduced perceptions of pain, and improved functional ability of joints in patients with mild to moderate knee OA. Moreover, Matsuno and colleagues  investigated the effects of 12-weeks of ingesting a dietary supplement containing glucosamine hydrochloride (1,200 mg/d), shark cartiliage powder (300 mg/d), chondroitin (75-111 mg/d), and quercetin (45 mg/d) on synovial fluid properties of patients with OA. The researchers reported that the OA patients experienced significant improvements in pain symptoms, ability to perform daily activities (walking and climbing up and down stairs), and changes in synovial fluid properties. Finally, Ng and coworkers  reported that dietary supplementation of glucosamine sulphate (1,500 mg/d) for 6-weeks reduced OA symptoms in individuals walking a minimum of approximately 30-min per day. These findings provide support to the theory that glucosamine and chondroitin supplementation may provide some therapeutic benefits to patients with knee OA.
In the present study, subjects ingested in a double blind and randomized manner a placebo or a dietary supplement containing 1,500 mg/d of glucosamine, 1,200 mg/d of chondroitin sulfate, and 900 mg/d of MSM. We found that symptom-limited peak aerobic capacity was increased to a greater degree in participants ingesting the GCM supplement with the greatest effects observed in the HP-GCM group. In addition, mean group upper extremity muscular endurance was greater in the GCM group compared to the P group. However, GCM supplementation did not significantly affect remaining markers of isotonic or isokinetic strength, balance, functional capacity, markers of health, self-reported perceptions of pain, or indicators of quality of life. These findings indicate that GCM supplementation provides only marginal additive benefit to a resistance-based exercise and weight loss program. The lack of additive benefits observed could be due to limitations in sample size, length of the intervention, and/or the fact that the exercise intervention resulted in marked improvement in functional capacity and perceptions of pain thereby minimizing the impact of dietary supplementation of GCM. However, additional research is needed to examine the influence of GCM supplementation during a training and weight loss program before definitive conclusions can be drawn.