Dose-Response of Myofibrillar Protein Synthesis To Ingested Whey Protein During Energy Restriction in Overweight Postmenopausal Women: A Randomized, Controlled Trial.

BACKGROUND: Diet-induced weight loss is associated with a decline in lean body mass, as mediated by an impaired response of muscle protein synthesis (MPS). The dose-response of MPS to ingested protein, with or without resistance exercise, is well characterized during energy balance but limited data exist under conditions of energy restriction in clinical populations. OBJECTIVE: To determine the dose-response of MPS to ingested whey protein following short-term diet-induced energy restriction in overweight, postmenopausal, women at rest and postexercise. DESIGN: Forty middle-aged (58.6±0.4 y), overweight (BMI: 28.6±0.4), postmenopausal women were randomly assigned to 1 of 4 groups: Three groups underwent 5 d of energy restriction (∼800 kcal/d). On day 6, participants performed a unilateral leg resistance exercise bout before ingesting either a bolus of 15g (ERW15, n = 10), 35g (ERW35, n = 10) or 60g (ERW60, n = 10) of whey protein. The fourth group (n = 10) ingested a 35g whey protein bolus after 5 d of an energy balanced diet (EBW35, n = 10). Myofibrillar fractional synthetic rate (FSR) was calculated under basal, fed (FED) and postexercise (FED-EX) conditions by combining an L-[ring-13C6] phenylalanine tracer infusion with the collection of bilateral muscle biopsies. RESULTS: Myofibrillar FSR was greater in ERW35 (0.043±0.003%/h, P = 0.013) and ERW60 (0.042±0.003%/h, P = 0.026) than ERW15 (0.032 ± 0.003%/h), with no differences between ERW35 and ERW60 (P = 1.000). Myofibrillar FSR was greater in FED (0.044 ± 0.003%/h, P < 0.001) and FED-EX (0.048 ± 0.003%/h, P < 0.001) than BASAL (0.027 ± 0.003%/h), but no differences were detected between FED and FED-EX (P = 0.732) conditions. No differences in myofibrillar FSR were observed between EBW35 (0.042 ± 0.003%/h) and ERW35 (0.043 ± 0.003%/h, P = 0.744). CONCLUSION: A 35 g dose of whey protein, ingested with or without resistance exercise, is sufficient to stimulate a maximal acute response of MPS following short-term energy restriction in overweight, postmenopausal women, and thus may provide a per serving protein recommendation to mitigate muscle loss during a weight loss program. TRIAL REGISTRY: clinicaltrials.gov (ID: NCT03326284).

Resistance Exercise Counteracts the Impact of Androgen Deprivation Therapy on Muscle Characteristics in Cancer Patients.

CONTEXT: Androgen deprivation therapy (ADT) forms the cornerstone in prostate cancer (PCa) treatment. However, ADT also lowers skeletal muscle mass. OBJECTIVE: To identify the impact of ADT with and without resistance exercise training on muscle fiber characteristics in PCa patients. METHODS: Twenty-one PCa patients (72 ± 6 years) starting ADT were included. Tissue samples from the vastus lateralis muscle were assessed at baseline and after 20 weeks of usual care (n = 11) or resistance exercise training (n = 10). Type I and II muscle fiber distribution, fiber size, and myonuclear and capillary contents were determined by immunohistochemistry. RESULTS: Significant decreases in type I (from 7401 ± 1183 to 6489 ± 1293 µm2, P < .05) and type II (from 6225 ± 1503 to 5014 ± 714 µm2, P < .05) muscle fiber size were observed in the usual care group. In addition, type I and type II individual capillary-to-fiber ratio (C/Fi) declined (-12% ± 12% and -20% ± 21%, respectively, P < .05). In contrast, significant increases in type I (from 6700 ± 1464 to 7772 ± 1319 µm2, P < .05) and type II (from 5248 ± 892 to 6302 ± 1385 µm2, P < .05) muscle fiber size were observed in the training group, accompanied by an increase in type I and type II muscle fiber myonuclear contents (+24% ± 33% and +21% ± 23%, respectively, P < .05) and type I C/Fi (+18% ± 14%, P < .05). CONCLUSION: The onset of ADT is followed by a decline in both type I and type II muscle fiber size and capillarization in PCa patients. Resistance exercise training offsets the negative impact of ADT and increases type I and II muscle fiber size and type I muscle fiber capillarization in these patients.

Resistance Exercise Training Increases Muscle Mass and Strength in Prostate Cancer Patients on Androgen Deprivation Therapy.

PURPOSE: This study aimed to assess the effects of 20 wk resistance exercise training with or without protein supplementation on body composition, muscle mass, muscle strength, physical performance, and aerobic capacity in prostate cancer patients receiving androgen deprivation therapy (ADT). METHODS: Sixty prostate cancer patients receiving ADT were randomly assigned to perform 20 wk of resistance exercise training with supplementation of 31 g whey protein (EX + PRO, n = 30) or placebo (EX + PLA, n = 30), consumed immediately after exercise and every night before sleep. A separate control group (CON, n = 36) only received usual care. At baseline and after 20 wk, body composition (dual-energy x-ray absorptiometry), muscle mass (computed tomography scan), muscle strength (1-repetition maximum strength tests), physical performance (Timed Up and Go Test, 30-Second Chair Stand Test, and Stair Climb Test), aerobic capacity (cardiopulmonary exercise test), and habitual dietary intake (food diary) were assessed. Data were analyzed using a two-factor repeated-measures ANOVA. RESULTS: Over time, muscle mass and strength increased in EX + PRO and EX + PLA and decreased in CON. Total fat mass and fat percentage increased in EX + PRO and CON, but not in EX + PLA. Physical performance did not significantly change over time in either group. Aerobic capacity was maintained in EX + PLA, but it decreased in EX + PRO and CON. Habitual protein intake (without supplements) averaged >1.0 g·kg body weight -1 ·d -1 , with no differences over time or between groups. CONCLUSIONS: In prostate cancer patients, resistance exercise training counteracts the adverse effects of ADT on body composition, muscle mass, muscle strength, and aerobic capacity, with no additional benefits of protein supplementation.

The effect of daily protein supplementation, with or without resistance training for 1 year, on muscle size, strength, and function in healthy older adults: A randomized controlled trial.

BACKGROUND: Protein supplementation alone or combined with resistance training has been proposed to be effective in counteracting age-related losses of muscle mass and strength. OBJECTIVES: To investigate the effect of protein supplementation alone or combined with light-intensity or heavy-load resistance exercise on muscle size, strength, and function in older adults. METHODS: In a 1-y randomized controlled trial, 208 healthy older adults (>65 y) were randomly assigned to 1 of 5 interventions: 1) carbohydrate supplementation (CARB); 2) collagen protein supplementation (COLL); 3) whey protein supplementation (WHEY); 4) light-intensity resistance training 3-5 times/wk with whey protein supplementation (LITW); and 5) heavy resistance training 3 times weekly with whey protein supplementation (HRTW). Protein supplements contained 20 g protein + 10 g carbohydrate, whereas CARB contained 30 g of carbohydrates. All intervention groups received the supplement twice daily. The primary outcome was change in the quadriceps cross-sectional area (qCSA). Secondary outcomes included measures of lower extremity strength and power, functional capabilities, and body composition. RESULTS: There were 184 participants who completed the study. COLL and WHEY did not affect any measured parameter compared to CARB. Compared to WHEY, HRTW improved the qCSA size (between-group difference, +1.68 cm2; 95% CI, +0.41 to +2.95 cm2; P = 0.03), as well as dynamic (+18.4 Nm; 95% CI, +10.1 to +26.6 Nm; P < 10-4) and isometric knee extensor strength (+23.9 Nm; 95% CI, +14.2 to +33.6 Nm; P < 10-5). LITW did not improve the qCSA size, but increased dynamic knee extensor strength compared to WHEY (+13.7 Nm; 95% CI, +5.3 and +22.1 Nm; P = 0.01). CONCLUSIONS: Recommending protein supplementation as a stand-alone intervention for healthy older individuals seems ineffective in improving muscle mass and strength. Only HRTW was effective in both preserving muscle mass and increasing strength. Thus, we recommend that future studies investigate strategies to increase long-term compliance to heavy resistance exercise in healthy older adults. This trial was registered at clinicaltrials.gov as NCT02034760.

ß-Lactoglobulin Elevates Insulin and Glucagon Concentrations Compared with Whey Protein-A Randomized Double-Blinded Crossover Trial in Patients with Type Two Diabetes Mellitus.

Whey protein is an insulinotropic fraction of dairy that reduces postprandial glucose levels in patients with type 2 diabetes mellitus (T2DM). We have recently shown that ß-lactoglobulin (BLG), the largest protein fraction of whey, elevates insulin concentrations compared with iso-nitrogenous whey protein isolate (WPI) in healthy individuals. We therefore hypothesized that BLG pre-meals would lower glucose levels compared with WPI in patients with T2DM. We investigated 16 participants with T2DM using a randomized double-blinded cross-over design with two pre-meal interventions, (i) 25 g BLG and (ii) 25 g WPI prior to an oral glucose tolerance test (OGTT), followed by four days of continuous glucose monitoring (CGM) at home. BLG increased concentrations of insulin with 10%, glucagon with 20%, and glucose with 10% compared with WPI after the OGTT (all p < 0.05). Both BLG and WPI reduced the interstitial fluid (ISF) glucose concentrations (using CGM) with 2 mM and lowered glycemic variability with 10-15%, compared with tap-water (p < 0.05), and WPI lowered the ISF glucose with 0.5 mM compared with BLG from 120 min and onwards (p < 0.05). In conclusion, BLG pre-meals resulted in higher insulin, glucagon, and glucose concentrations compared with WPI in participants with T2DM. Pre-meal servings of WPI remains the most potent protein in terms of lowering postprandial glucose excursions.

Effects of Prolonged Whey Protein Supplementation and Resistance Training on Biomarkers of Vitamin B12 Status: A 1-Year Randomized Intervention in Healthy Older Adults (the CALM Study).

We investigated the effect of long-term whey supplementation on biomarkers of B12 status in healthy older adults subjected to different schemes of supplements and exercise. The total study population examined at baseline consisted of 167 healthy older adults (age ≥ 65 year) who were randomized to 1-y intervention with two daily supplements of (1) whey protein (3.1 µg B12/day) (WHEY-ALL), (2) collagen (1.3 µg B12/day) (COLL), or (3) maltodextrin (0.3 µg B12/day) (CARB). WHEY-ALL was comprised of three groups, who performed heavy resistance training (HRTW), light resistance training (LITW), or no training (WHEY). Dietary intake was assessed through 3-d dietary records. For the longitudinal part of the study, we included only the participants (n = 110), who met the criteria of ≥ 50% compliance to the nutritional intervention and ≥ 66% and ≥ 75% compliance to the heavy and light training, respectively. Fasting blood samples collected at baseline and 12 months and non-fasting samples collected at 6 and 18 months were examined for methylmalonic acid, B12 and holotranscobalamin. At baseline, the study population (n = 167) had an overall adequate dietary B12 intake of median (range) 5.3 (0.7-65) µg/day and median B12 biomarker values within reference intervals. The whey intervention (WHEY-ALL) caused an increase in B12 (P < 0.0001) and holotranscobalamin (P < 0.0001). In addition, methylmalonic acid decreased in the LITW group (P = 0.04). No change in B12 biomarkers was observed during the intervention with collagen or carbohydrate, and the training schedules induced no changes. In conclusion, longer-term daily whey intake increased plasma B12 and holotranscobalamin in older individuals. No effect of intervention with collagen or carbohydrate or different training regimes was observed. Interestingly, the biomarkers of B12 status appeared to be affected by fasting vs. non-fasting conditions during sample collection.

Effects of protein intake prior to carbohydrate-restricted endurance exercise: a randomized crossover trial.

BACKGROUND: Deliberately training with reduced carbohydrate availability, a paradigm coined training low, has shown to promote adaptations associated with improved aerobic capacity. In this context researchers have proposed that protein may be ingested prior to training as a means to enhance the protein balance during exercise without spoiling the effect of the low carbohydrate availability. Accordingly, this is being practiced by world class athletes. However, the effect of protein intake on muscle protein metabolism during training low has not been studied. This study aimed to examine if protein intake prior to exercise with reduced carbohydrate stores benefits muscle protein metabolism in exercising and non-exercising muscles. METHODS: Nine well-trained subjects completed two trials in random order both of which included a high-intensity interval ergometer bike ride (day 1), a morning (day 2) steady state ride (90 min at 65% VO2peak, 90ss), and a 4-h recovery period. An experimental beverage was consumed before 90ss and contained either 0.5 g whey protein hydrolysate [WPH]/ kg lean body mass or flavored water [PLA]. A stable isotope infusion (L-[ring-13C6]-phenylalanine) combined with arterial-venous blood sampling, and plasma flow rate measurements were used to determine forearm protein turnover. Myofibrillar protein synthesis was determined from stable isotope incorporation into the vastus lateralis. RESULTS: Forearm protein net balance was not different from zero during 90ss exercise (nmol/100 ml/min, PLA: 0.5 ± 2.6; WPH: 1.8, ± 3.3) but negative during the 4 h recovery (nmol/100 ml/min, PLA: - 9.7 ± 4.6; WPH: - 8.7 ± 6.5); no interaction (P = 0.5) or main effect of beverage (P = 0.11) was observed. Vastus lateralis myofibrillar protein synthesis rates were increased during 90ss exercise (+ 0.02 ± 0.02%/h) and recovery (+ 0.02 ± 0.02%/h); no interaction (P = 0.3) or main effect of beverage (P = 0.3) was observed. CONCLUSION: We conclude that protein ingestion prior to endurance exercise in the energy- and carbohydrate-restricted state does not increase myofibrillar protein synthesis or improve net protein balance in the exercising and non-exercising muscles, respectively, during and in the hours after exercise compared to ingestion of a non-caloric control. TRIAL REGISTRATION: clinicaltrials.gov, NCT01320449. Registered 10 May 2017 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03147001.

Presleep Protein Supplementation Does Not Improve Recovery During Consecutive Days of Intense Endurance Training: A Randomized Controlled Trial.

Recent studies demonstrate that protein ingestion immediately before sleep improves muscle recovery during the night following resistance exercise. Whether this feeding strategy benefits recovery from endurance training has yet to be established. The aim of this study was to investigate the effects of whey protein isolate ingested every night before sleep on subsequent performance and circulatory markers of muscular recovery during a week of intensified endurance training mimicking a training camp. In a parallel design, 32 trained runners underwent a 1-week intervention with a rigorously controlled diet (carbohydrate = 7.2 g·kg-1·day-1, protein = 1.8 g·kg-1·day-1, and fat = 1.0 g·kg-1·day-1) and exercise program (11 sessions) while receiving either a protein (0.5 g·kg-1·day-1) or carbohydrate (0.5 g·kg-1·day-1) beverage every night before sleep. Blood samples were obtained on the morning of Days 1, 4, 7, and 8 and analyzed for markers of muscle damage (creatine kinase, lactate dehydrogenase, and myoglobin). The postintervention 5-km time-trial performance was significantly impaired in both groups (11 ± 24 s, p < .01). Plasma creatine kinase (227% ± 221%, p < .01), lactate dehydrogenase (18% ± 22%, p < .01), and myoglobin (72% ± 62%, p < .01) increased gradually throughout the week with no difference between the groups (p > .05). In conclusion, the presleep protein ingestion did not reduce the decline in performance or ameliorate the rise of circulatory markers of muscle damage during a week of intensified training when compared with the isocaloric carbohydrate ingestion.

Even effect of milk protein and carbohydrate intake but no further effect of heavy resistance exercise on myofibrillar protein synthesis in older men.

PURPOSE: The responsiveness of older individuals' skeletal muscle to anabolic strategies may be impaired. However, direct comparisons within the same experimental setting are sparse. The aim of this study was to assess the resting and post-resistance exercise muscle protein synthesis rates in response to two types of milk protein and carbohydrate using a unilateral exercise leg model. METHODS: Twenty-seven older (69 ± 1 year, mean ± SE) men were randomly assigned one of three groups: Whey hydrolysate (WH), caseinate (CAS), or carbohydrate (CHO). By applying stable isotope tracer techniques (L-[15N]phenylalanine), the fasted-rested (basal) myofibrillar fractional synthesis rate (FSR) was measured. Hereafter, FSR was measured in the postprandial phase (0.45 g nutrient/kg LBM) in both legs, one rested (fed-rest) and one exercised (10 × 8 reps at 70% 1RM; fed-exercise). In addition, the activity of p70S6K and venous plasma insulin, phenylalanine, and leucine concentrations were measured. RESULTS: Insulin, phenylalanine, and leucine concentrations differed markedly after intake of the different study drinks. The basal FSR in WH, CAS, and CHO were 0.027 ± 0.003, 0.030 ± 0.003, and 0.030 ± 0.004%/h, the fed-rested FSR were 0.043 ± 0.004, 0.045 ± 0.003, and 0.035 ± 0.004%/h, and the fed-exercised FSR were 0.041 ± 0.004, 0.043 ± 0.004, and 0.034 ± 0.004%/h, respectively. No significant differences were observed at any state between the groups. Fed-rested- and fed-exercised FSR were higher than basal (P < 0.001). 3 h after exercise and feeding, no significant group differences were detected in the activity of p70S6K. CONCLUSIONS: Milk protein and carbohydrate supplementation stimulate myofibrillar protein synthesis in older men, with no further effect of heavy resistance exercise within 0-3 h post exercise.

Matters of fiber size and myonuclear domain: Does size matter more than age?

INTRODUCTION: The relationship between fiber size and myonuclear content is poorly understood. METHODS: Biopsy cross-sections from young and old trained and untrained healthy individuals were analyzed for fiber area and myonuclei, and 2 fiber-size-dependent cluster analyses were performed. RESULTS: When comparing fibers of similar size, no effect of training or age was found for myonuclear domain. There was a linear relationship between fiber area and myonuclei per fiber (r = 0.99; P < 0.001) and a non-linear relationship between fiber area and domain (r = 0.97-0.99; P < 0.0001), with a markedly smaller domain in fibers <3,000 µm(2). A higher proportion of type II fibers <3,000 µm(2) was observed in the old subjects. CONCLUSIONS: These findings suggest that age-related reductions in myonuclear domain size could be explained by the greater proportion of small fibers. The data also highlight the usefulness of determining fiber-size-based clusters for gaining mechanistic insight into the relationship between skeletal muscle fiber size and myonuclear content.

Bosentan improves exercise capacity in adolescents and adults after Fontan operation: the TEMPO (Treatment With Endothelin Receptor Antagonist in Fontan Patients, a Randomized, Placebo-Controlled, Double-Blind Study Measuring Peak Oxygen Consumption) study.

BACKGROUND: The Fontan procedure has improved survival in children with functionally univentricular hearts. With time, however, complications such as reduced exercise capacity are seen more frequently. Exercise intolerance is multifactorial, but pulmonary vascular resistance probably plays a crucial role. Elevated pulmonary vascular resistance has been associated with raised levels of endothelin-1, which are common both before and after Fontan operations. Treatment with endothelin-1 receptor antagonists could theoretically improve cardiopulmonary hemodynamics and exercise capacity. The aim of this study was therefore to examine the efficacy and safety of bosentan in Fontan patients. METHODS AND RESULTS: Seventy-five adolescents and adults were randomized 1:1 to 14 weeks of treatment with bosentan or placebo. Cardiopulmonary exercise test, functional class, blood samples, and quality-of-life questionnaires were evaluated at baseline and at the end of treatment. Sixty-nine patients (92%) completed the study. Peak oxygen consumption increased 2.0 mL·kg(-1)·min(-1) (from 28.7 to 30.7 mL·kg(-1)·min(-1)) in the bosentan group compared with 0.6 mL·kg(-1)·min(-1) (from 28.4 to 29.0 mL·kg(-1)·min(-1)) in the placebo group (P=0.02). Cardiopulmonary exercise test time increased by 0.48 minute (from 6.79 to 7.27 minutes) versus 0.08 minute (from 6.94 to 7.02 minutes; P=0.04). Nine bosentan-treated patients improved 1 functional class, whereas none improved in the placebo group (P=0.0085). Side effects were mild and occurred equally in both groups. No serious adverse effects were seen, and no patients had liver enzyme levels above the 3-fold upper limit. CONCLUSIONS: Bosentan improves exercise capacity, exercise time, and functional class in Fontan patients without serious adverse events or hepatotoxicity. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01292551.

Hemodynamic causes of exercise intolerance in Fontan patients.

BACKGROUND: Exercise intolerance is frequent among Fontan patients and an important determinant for quality of life. This study investigated the hemodynamic causes of impaired exercise capacity in Fontan patients with particular focus on the influence of stroke volume index (SVI) and heart rate (HR). METHODS AND RESULTS: In 38 Fontan patients, peak oxygen consumption (VO2), SVI and HR were recorded during incremental load exercise test and compared with 19 age and gender matched controls. SVI (ml/m(2)) was lower in patients than controls during warm-up (28[26-31] vs. 35[30-39], p=0.0093), at submaximal (40[37-43] vs. 55[51-59], p<0.0001) and at maximal exercise (38[35-40] vs. 54[51-58], p<0.0001). Similarly, HR (% of expected maximum) was lower in patients at warm-up (45[43-48]% vs. 64[57-64]%, p<0.0001), submaximal (71[68-75]% vs 85[82-88]%, p<0.0001) and maximal exercise (84[80-88]% vs. 97[95-99]%, p<0.0001). Furthermore, SVI dropped 14% (from 44[41-48] to 38[35-40] ml/m(2)) in Fontan patients from the peak plateau to maximal exercise vs. 5% (from 57[53-61] to 54[51-58] ml/m(2)) in controls, p<0.0001. The low SVI and HR explained 67% and 20% of the difference in peak VO2 between Fontan patients and controls respectively. CONCLUSION: SVI decreased significantly in Fontan patients near the end of maximal effort exercise. The low SVI at maximal exercise was the most important hemodynamic factor limiting exercise capacity in Fontan patients, whereas chronotropic impairment had a smaller impact. The low SVI and HR at maximal exercise accounted for the difference in peak VO2 between Fontan patients and controls in this study. CLINICAL TRIAL REGISTRATION: http://www.cvk.sum.dk/CVK/Home/English.aspx (protocol nr: H-3-2010-045).

Activated protein synthesis and suppressed protein breakdown signaling in skeletal muscle of critically ill patients.

BACKGROUND: Skeletal muscle mass is controlled by myostatin and Akt-dependent signaling on mammalian target of rapamycin (mTOR), glycogen synthase kinase 3ß (GSK3ß) and forkhead box O (FoxO) pathways, but it is unknown how these pathways are regulated in critically ill human muscle. To describe factors involved in muscle mass regulation, we investigated the phosphorylation and expression of key factors in these protein synthesis and breakdown signaling pathways in thigh skeletal muscle of critically ill intensive care unit (ICU) patients compared with healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: ICU patients were systemically inflamed, moderately hyperglycemic, received insulin therapy, and showed a tendency to lower plasma branched chain amino acids compared with controls. Using Western blotting we measured Akt, GSK3ß, mTOR, ribosomal protein S6 kinase (S6k), eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), and muscle ring finger protein 1 (MuRF1); and by RT-PCR we determined mRNA expression of, among others, insulin-like growth factor 1 (IGF-1), FoxO 1, 3 and 4, atrogin1, MuRF1, interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and myostatin. Unexpectedly, in critically ill ICU patients Akt-mTOR-S6k signaling was substantially higher compared with controls. FoxO1 mRNA was higher in patients, whereas FoxO3, atrogin1 and myostatin mRNAs and MuRF1 protein were lower compared with controls. A moderate correlation (r2=0.36, p<0.05) between insulin infusion dose and phosphorylated Akt was demonstrated. CONCLUSIONS/SIGNIFICANCE: We present for the first time muscle protein turnover signaling in critically ill ICU patients, and we show signaling pathway activity towards a stimulation of muscle protein synthesis and a somewhat inhibited proteolysis.

Exercise increases interleukin-10 levels both intraarticularly and peri-synovially in patients with knee osteoarthritis: a randomized controlled trial.

INTRODUCTION: The microdialysis method was applied to the human knee joint with osteoarthritis (OA) in order to reveal changes in biochemical markers of cartilage and inflammation, intraarticularly and in the synovium, in response to a single bout of mechanical joint loading. METHODS: Thirty-one female subjects with OA of the knee were randomized to non-exercise (NEx) or exercise (Ex) groups. Following acute resistance exercise (25 sets of 10 repetitions at 60% of 1 Repetition Maximum) or none (NEx), peripheral nerve blocks just below the inguinal ligament were applied and two microdialysis catheters were positioned in two different compartments, intraarticularly and peri-synovially. The microdialysis catheters were perfused at a slow rate (2 µl/minute) with a solution of Ringer-acetate and radioactively labelled glucose allowing for determination of relative recovery (RR) and calculation of interstitial concentrations of inflammatory and cartilage biomarkers over a three-hour period. RESULTS: A significant increase of Interleukin (IL) -10 was discovered in both positions of the knee in the Ex group over the three hours post exercise, whereas IL-10 remained stationary over time in the NEx group. IL-6 and IL-8 displayed significant increases over time regardless of group and position of the catheter. Cartilage oligomeric matrix protein (COMP) decreased intraarticularly in the post exercise period in the Ex group compared to the NEx group. CONCLUSIONS: Exercise caused an increase in both intraarticular and peri-synovial concentrations of IL-10 in a group of human females with knee OA. This suggests a positive effect of exercise on a chondroprotective anti-inflammatory cytokine response in patients with knee OA and might contribute to explaining the beneficial effect that exercise has on OA. TRIAL REGISTRATION: NCT01090375.