The effects of exercise interventions on the inflammatory profile of older adults: A systematic review of the recent literature.

INTRODUCTION: Inflammageing - characterized by age-related chronic low-grade inflammation is considered to be positively influenced by physical exercises. The aim of this systematic review is to provide an update of the most recent literature regarding exercise effects on the inflammatory profile in older adults. METHODS: This review is an update of an earlier published literature review and was performed according to the NICE guidelines. Databases PubMed and Web-of-Science were systematically searched by two independent authors screening for papers published since 2016. Effect sizes of outcome parameters related to the inflammatory profile were calculated where possible. RESULTS & DISCUSSION: Twenty-three articles were included. Resistance training (RT) was the most investigated type of exercise (13 articles: 8 in healthy, 1 in frail and 4 in older adults with a specific condition or disease). Aerobic training (AT) was investigated in 8 articles, including 5 studies in older adults with a specific disease or condition. Combined resistance & aerobic training (CT) was investigated in 7 articles: 3 were in healthy, 1 in frail and 3 in older adults with a specific condition or disease. 1 study investigated the effects of Tai Chi in older adults with mild cognitive impairment. In frail older subjects, IGF-1 - sole marker investigated - significantly increased after 8 weeks RT and CT, whereas AT showed no significant effects compared to control. Most consistent exercise effects consisted in lowering of circulating levels of CRP, IL-6 and TNF-α; which seemed more prominent in healthy older adults compared to those with a specific disease or condition. None of the studies reported an exacerbation of inflammation following exercise and all studied exercise protocols were feasible and safe for older adults. CONCLUSIONS: Overall, significant anti-inflammatory effects of exercise in older persons were reported. Literature remains extremely scarce regarding the exercise-induced effects in frail older persons. Therefore, there is an urgent need for more studies focusing on the frail elderly. There is growing literature data on exercise interventions in older adults with a specific condition or disease; however, it appears more challenging to reduce inflammageing through exercise in these specific patient groups. Importantly, the exercise interventions performed in all studies appeared to be feasible and safe for older patients, thus the presence of a specific condition or disease should not be considered as a contra-indication to perform physical exercise.

Nutritional interventions to improve muscle mass, muscle strength, and physical performance in older people: an umbrella review of systematic reviews and meta-analyses.

CONTEXT: Sarcopenia is a progressive and generalized skeletal muscle disorder associated with an increased risk of adverse outcomes such as falls, disability, and death. The Belgian Society of Gerontology and Geriatrics has developed evidence-based guidelines for the prevention and treatment of sarcopenia. This umbrella review presents the results of the Working Group on Nutritional Interventions. OBJECTIVE: The aim of this umbrella review was to provide an evidence-based overview of nutritional interventions targeting sarcopenia or at least 1 of the 3 sarcopenia criteria (ie, muscle mass, muscle strength, or physical performance) in persons aged ≥ 65 years. DATA SOURCES: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the PubMed and Web of Science databases were searched for systematic reviews and meta-analyses reporting the effect of nutritional supplementation on sarcopenia or muscle mass, strength, or physical performance. DATA EXTRACTION: Two authors extracted data on the key characteristics of the reviews, including participants, treatment, and outcomes. Methodological quality of the reviews was assessed using the product A Measurement Tool to Assess Systematic Reviews. Three authors synthesized the extracted data and generated recommendations on the basis of an overall synthesis of the effects of each intervention. Quality of evidence was rated with the Grading of Recommendations Assessment, Development and Evaluation approach. DATA ANALYSIS: A total of 15 systematic reviews were included. The following supplements were examined: proteins, essential amino acids, leucine, ß-hydroxy-ß-methylbutyrate, creatine, and multinutrient supplementation (with or without physical exercise). Because of both the low amount and the low to moderate quality of the reviews, the level of evidence supporting most recommendations was low to moderate. CONCLUSIONS: Best evidence is available to recommend leucine, because it has a significant effect on muscle mass in elderly people with sarcopenia. Protein supplementation on top of resistance training is recommended to increase muscle mass and strength, in particular for obese persons and for ≥ 24 weeks. Effects on sarcopenia as a construct were not reported in the included reviews.

Safety and tolerability of 6-month supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink in sarcopenic older adults.

AIMS: Safety and tolerability of prolonged supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink (WP-MND) was evaluated in sarcopenic older adults. METHODS: A 13-week double-blinded, randomized, isocaloric placebo-controlled trial (PROVIDE study; n = 380) was extended with a voluntary 13-week open-label extension (OLE). OLE participants were randomized to receive daily 1 or 2 servings of WP-MND (21 g protein, 3 g leucine, 10 µg vitD and 500 mg calcium per serving). Gastro-intestinal tolerability, kidney function and serum levels of calcidiol, parathyroid hormone (PTH) and calcium were evaluated at week 0, 13 and 26. RESULTS AND DISCUSSION: In response to the high daily protein intake (median1.5; IQR: 1.3, 1.7 g/kg BW/day), the estimated glomerular filtration rate (eGFR) increased in the test group during the RCT (p = 0.013). The same trend was observed for those participants with moderate chronic kidney disease. During OLE no eGFR change was observed in any of the groups. Serum calcidiol and calcium reached a plateau after 13-week WP-MND supplementation. As expected, PTH significantly changed in the opposite direction, decreasing during RCT in the test group (T vs C: p < 0.001) and during OLE in former control groups. During RCT, 20/366 participants with normal baseline calcidiol reached levels ≥ 100 nmol/L (T: n = 18; C: n = 2) and 6 developed albumin-corrected calcium levels > 2.55 mmol/L (T: n = 3; C: n = 3), without associated adverse events. CONCLUSION: A 6 months intervention with up to 2 servings of WP-MND did neither result in kidney function deterioration nor symptoms of vitamin D or calcium toxicity. The product was overall well tolerated.

A Vitamin D, Calcium and Leucine-Enriched Whey Protein Nutritional Supplement Improves Measures of Bone Health in Sarcopenic Non-Malnourished Older Adults: The PROVIDE Study.

Alterations in musculoskeletal health with advanced age contribute to sarcopenia and decline in bone mineral density (BMD) and bone strength. This decline may be modifiable via dietary supplementation. To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of bone health. Participants (n 380) were participants of the PROVIDE study, a 13-week, multicenter, randomized, controlled, double-blind, 2 parallel-group study among non-malnourished older participants (≥ 65 years) with sarcopenia [determined by Short Physical Performance Battery (SPPB; 0-12) scores between 4 and 9, and a low skeletal muscle mass index (SMI; skeletal muscle mass/BW × 100) ≤ 37% in men and ≤ 28% in women using bioelectric impedance analysis] Supplementation of a vitamin D, calcium and leucine-enriched whey protein drink that comprises a full range of micronutrients (active; 2/day) was compared with an iso-caloric control. Serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), biochemical markers of bone formation (osteocalcin; OC, procollagen type 1 amino-terminal propeptide; P1NP) and resorption (carboxy-terminal collagen crosslinks; CTX), insulin like growth factor 1 (IGF-1) and total-body BMD were analysed pre- and post-intervention. Serum 25(OH)D concentrations increased from 51.1 ± 22.9 nmol/L (mean ± SD) to 78.9 ± 21.1 nmol/L in the active group (p < 0.001 vs. control). Serum PTH showed a significant treatment difference (p < 0.001) with a decline in the active group, and increase in the control group. Serum IGF-1 increased in the active group (p < 0.001 vs. control). Serum CTX showed a greater decline in the active group (p = 0.001 vs. control). There were no significant differences in serum OC or P1NP between groups during the intervention. Total body BMD showed a small (0.02 g/cm2; ~ 2%) but significant increase in the active group after supplementation (p = 0.033 vs. control). Consuming a vitamin D, calcium and leucine-enriched whey protein supplement for 13 weeks improved 25(OH)D, suppressed PTH and had small but positive effects on BMD, indicative of improved bone health, in sarcopenic non-malnourished older adults.

Thirteen weeks of supplementation of vitamin D and leucine-enriched whey protein nutritional supplement attenuates chronic low-grade inflammation in sarcopenic older adults: the PROVIDE study.

BACKGROUND: A chronic low-grade inflammatory profile (CLIP) is associated with sarcopenia in older adults. Protein and Vitamin (Vit)D have immune-modulatory potential, but evidence for effects of nutritional supplementation on CLIP is limited. AIM: To investigate whether 13 weeks of nutritional supplementation of VitD and leucine-enriched whey protein affected CLIP in subjects enrolled in the PROVIDE-study, as a secondary analysis. METHODS: Sarcopenic adults (low skeletal muscle mass) aged ≥ 65 years with mobility limitations (Short Physical Performance Battery 4-9) and a body mass index of 20-30 kg/m2 were randomly allocated to two daily servings of active (n = 137, including 20 g of whey protein, 3 g of leucine and 800 IU VitD) or isocaloric control product (n = 151) for a double-blind period of 13 weeks. At baseline and after 13 weeks, circulating interleukin (IL)-8, IL-1 receptor antagonist (RA), soluble tumor-necrosis-factor receptor (sTNFR)1, IL-6, high-sensitivity C-reactive protein, pre-albumin and 25-hydroxyvitamin(OH)D were measured. Data-analysis included repeated measures analysis of covariance (corrected for dietary VitD intake) and linear regression. RESULTS: IL-6 and IL-1Ra serum levels showed overall increases after 13 weeks (p = 0.006 and p < 0.001, respectively). For IL-6 a significant time × treatment interaction (p = 0.046) was observed, with no significant change over time in the active group (p = 0.155) compared to control (significant increase p = 0.012). IL-8 showed an overall significant decrease (p = 0.03). The change in pre-albumin was a significant predictor for changes in IL-6 after 13 weeks. CONCLUSIONS: We conclude that 13 weeks of nutritional supplementation with VitD and leucine-enriched whey protein may attenuate the progression of CLIP in older sarcopenic persons with mobility limitations.

Pharmacological Interventions to Improve Muscle Mass, Muscle Strength and Physical Performance in Older People: An Umbrella Review of Systematic Reviews and Meta-analyses.

BACKGROUND: Sarcopenia, defined as the pathological decline in muscle mass, muscle strength and physical performance with aging, has become one of the geriatric giants because of its increasing prevalence and devastating health effects. The Belgian Society of Gerontology and Geriatrics (BSGG) is currently developing evidence-based guidelines for the prevention and therapy of sarcopenia for use in broad clinical practice. This systematic review summarizes the results of the Working Group on Pharmacology. OBJECTIVE: Our objective was to provide an evidence-based overview of the possible pharmacological interventions for sarcopenia with a focus on interventions that have already been studied in systematic reviews or meta-analyses. METHODS: We conducted a systematic umbrella review. Using the electronic databases PubMed and Web of Science, we identified systematic reviews and meta-analyses that assessed the effect of pharmacological interventions on criteria for sarcopenia in subjects aged ≥ 65 years. Study selection, quality assessment and data extraction were performed by two independent reviewers. RESULTS: We identified seven systematic reviews or meta-analyses, encompassing ten pharmacological interventions: vitamin D, combined estrogen-progesterone, dehydroepiandrosterone, growth hormone, growth hormone-releasing hormone, combined testosterone-growth hormone, insulin-like growth factor-1, pioglitazone, testosterone and angiotensin-converting enzyme inhibitors. Importantly, very few systematic reviews or meta-analyses clearly mentioned baseline sarcopenia status. Therefore, our recommendations are generalised to older people, without specifying whether the muscle effect is more effective in healthy, pre-sarcopenic or sarcopenic older people. Vitamin D had a significant effect on muscle strength and physical performance, especially in women with low baseline values (< 25 nmol/l). Adverse events were rare. Testosterone had a strong effect on muscle mass and a modest to minimal effect on muscle strength and physical performance, respectively, when supplementing men with low serum levels (< 200-300 ng/dl). The adverse events were rare and mild. Insufficient evidence was available to recommend other pharmacological interventions. CONCLUSION: Only vitamin D, especially in older women, and testosterone in older men with clinical muscle weakness and low testosterone serum levels can be justified in daily clinical practice to improve muscle mass, muscle strength and/or physical performance.

Effect of Transcutaneous Electric Nerve Stimulation on Pain after Total Knee Arthroplasty: A Blind Randomized Controlled Trial.

Transcutaneous electric nerve stimulation (TENS) has proven to be effective for postsurgical pain relief. However, there is a lack of well-constructed clinical trials investigating the effect of TENS after total knee arthroplasty (TKA). In addition, previous investigations reported that low- and high-frequency TENSs produced analgesic tolerance after 4 or 5 days of treatment. The aim of this study is to explore the effect of burst TENS on pain during hospitalization after TKA and to investigate whether burst TENS produces analgesic tolerance after 4 or 5 days of treatment. This stratified, triple blind, randomized controlled trial was approved by the University Hospital Brussels. Sixty-eight subjects were screened for eligibility before surgery; 54 were found eligible and 53 were included in the analyses. Patients were allocated to either a burst TENS or sham burst TENS group. TENS was applied daily during continuous passive mobilization. Knee pain intensity, knee range of motion, and analgesic consumption were assessed daily. Patients received burst TENS (N = 25) or sham burst TENS (N = 28). No significant differences in knee pain intensity were found between the groups (p > 0.05). Within the TENS and the sham TENS groups, the difference in knee pain before and after treatment did not evolve over time (p > 0.05). This study found no effects of burst TENS compared with sham burst TENS on pain during hospitalization after TKA.

Sufficient levels of 25-hydroxyvitamin D and protein intake required to increase muscle mass in sarcopenic older adults - The PROVIDE study.

BACKGROUND: Inadequate nutritional intake and altered response of aging muscles to anabolic stimuli from nutrients contribute to the development of sarcopenia. Nutritional interventions show inconsistent results in sarcopenic older adults, which might be influenced by their basal nutritional status. OBJECTIVE: To test if baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations and dietary protein intake influenced changes in muscle mass and function in older adults who received nutritional intervention. METHODS AND DESIGN: Post-hoc analysis was performed in the PROVIDE study that was a randomized controlled, double blind trial among 380 sarcopenic older adults. This study showed that those who received a vitamin D and leucine-enriched whey protein medical nutrition drink for 13 weeks gained more appendicular muscle mass (aMM), and improved lower-extremity function as assessed by the chair stand test compared with controls. To define low and high groups, a baseline serum concentration of 50 nmol/L 25(OH)D and baseline dietary protein intake of 1.0 g/kg/d were used as cut offs. RESULTS: At baseline, participants with lower 25(OH)D concentrations showed lower muscle mass, strength and function compared with participants with a high 25(OH)D, while the group with lower protein intake (g/kg/day) had more muscle mass at baseline compared with the participants with higher protein intake. Participants with higher baseline 25(OH)D concentrations and dietary protein intake had, independent of other determinants, greater gain in appendicular muscle mass, skeletal muscle index (aMM/h2), and relative appendicular muscle mass (aMM/body weight × 100%) in response to the nutritional intervention. There was no effect modification of baseline 25(OH)D status or protein intake on change in chair-stand test. CONCLUSIONS: Sufficient baseline levels of 25(OH)D and protein intake may be required to increase muscle mass as a result of intervention with a vitamin D and protein supplement in sarcopenic older adults. This suggests that current cut-offs in the recommendations for vitamin D and protein intake could be considered the "minimum" for adults with sarcopenia to respond adequately to nutrition strategies aimed at attenuating muscle loss.

Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE study: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Age-related losses of muscle mass, strength, and function (sarcopenia) pose significant threats to physical performance, independence, and quality of life. Nutritional supplementation could positively influence aspects of sarcopenia and thereby prevent mobility disability. OBJECTIVE: To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of sarcopenia. DESIGN: A multicenter, randomized, controlled, double-blind, 2 parallel-group trial among 380 sarcopenic primarily independent-living older adults with Short Physical Performance Battery (SPPB; 0-12) scores between 4 and 9, and a low skeletal muscle mass index. The active group (n = 184) received a vitamin D and leucine-enriched whey protein nutritional supplement to consume twice daily for 13 weeks. The control group (n = 196) received an iso-caloric control product to consume twice daily for 13 weeks. Primary outcomes of handgrip strength and SPPB score, and secondary outcomes of chair-stand test, gait speed, balance score, and appendicular muscle mass (by DXA) were measured at baseline, week 7, and week 13 of the intervention. RESULTS: Handgrip strength and SPPB improved in both groups without significant between-group differences. The active group improved more in the chair-stand test compared with the control group, between-group effect (95% confidence interval): -1.01 seconds (-1.77 to -0.19), P = .018. The active group gained more appendicular muscle mass than the control group, between-group effect: 0.17 kg (0.004-0.338), P = .045. CONCLUSIONS: This 13-week intervention of a vitamin D and leucine-enriched whey protein oral nutritional supplement resulted in improvements in muscle mass and lower-extremity function among sarcopenic older adults. This study shows proof-of-principle that specific nutritional supplementation alone might benefit geriatric patients, especially relevant for those who are unable to exercise. These results warrant further investigations into the role of a specific nutritional supplement as part of a multimodal approach to prevent adverse outcomes among older adults at risk for disability.

A systematic review investigating the relationship between efficacy and stimulation parameters when using transcutaneous electrical nerve stimulation after knee arthroplasty.

OBJECTIVE: To evaluate the clinical efficacy of transcutaneous electric nerve stimulation in the treatment of postoperative knee arthroplasty pain and to relate these results to the stimulation parameters used. DATA SOURCES: PubMed, Pedro and Web of Knowledge were systematically screened for studies investigating effects of transcutaneous electric nerve stimulation on postoperative knee arthroplasty pain. REVIEW METHODS: Studies were screened for their methodological and therapeutical quality. We appraised the influence of the stimulation settings used and indicated whether or not a neurophysiological and/or mechanistic rationale was given for these stimulation settings. RESULTS: A total of 5 articles met the inclusion criteria. In total, 347 patients were investigated. The number of patients who received some form of transcutaneous electric nerve stimulation was 117, and 54 patients received sham transcutaneous electric nerve stimulation. Pain was the primary outcome in all studies. The stimulation settings used in the studies (n = 2) that reported significant effects differed from the others as they implemented a submaximal stimulation intensity. Stimulation parameters were heterogeneous, and only one study provided a rationale for them. CONCLUSION: This review reveals that an effect of transcutaneous electric nerve stimulation might have been missed due to low methodological and therapeutical quality. Justifying the choice of transcutaneous electric nerve stimulation parameters may improve therapeutical quality.

Effect of tens on pain in relation to central sensitization in patients with osteoarthritis of the knee: study protocol of a randomized controlled trial.

BACKGROUND: Central sensitization has recently been documented in patients with knee osteoarthritis (OAk). So far, the presence of central sensitization has not been considered as a confounding factor in studies assessing the pain inhibitory effect of tens on osteoarthritis of the knee. The purpose of this study is to explore the pain inhibitory effect of burst tens in OAk patients and to explore the prognostic value of central sensitization on the pain inhibitory effect of tens in OAk patients. METHODS: Patients with knee pain due to OAk will be recruited through advertisements in local media. Temporal summation, before and after a heterotopic noxious conditioning stimulation, will be measured. In addition, pain on a numeric rating score, WOMAC subscores for pain and function and global perceived effect will be assessed. Patients will be randomly allocated to one of two treatment groups (tens, sham tens). Follow-up measurements will be scheduled after a period of 6 and 12 weeks. DISCUSSION: Tens influences pain through the electrical stimulation of low-threshold A-beta cutaneous fibers. The responsiveness of central pain-signaling neurons of centrally sensitized OAk patients may be augmented to the input of these electrical stimuli. This would encompass an adverse therapy effect of tens. To increase treatment effectiveness it might be interesting to identify a subgroup of symptomatic OAk patients, i.e., non-sensitized patients, who are likely to benefit from burst tens. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01390285.

Rehabilitation using manual mobilization for thoracic kyphosis in elderly postmenopausal patients with osteoporosis.

OBJECTIVE: To explore the feasibility and effects of rehabilitation using manual mobilization of the thoracic spine in elderly female patients with osteoporosis. METHODS: Forty-eight postmenopausal patients with osteoporosis (age 76 -/+ 7 years) were randomly assigned to 3 months rehabilitation (18 sessions including manual mobilization, taping and exercises, n = 29) or control (wait-list, n = 19). The primary outcome was thoracic kyphosis degree (Spinal-Mouse). Secondary outcomes were back pain (visual analogue scale) and quality of life (Qualeffo-41). Explanatory outcomes were compliance with rehabilitation, complications, and patients' and therapists' perceptions regarding the rehabilitation programme. RESULTS: Thoracic kyphosis improved significantly following rehabilitation compared with controls (intention-to-treat analysis, p = 0.017); and in patients who were compliant with rehabilitation (n = 15) compared with those who were non-compliant (p = 0.002) and controls (p = 0.001). Mental health worsened slightly in the rehabilitation group (p = 0.029), but not significantly compared with controls. Neither patients nor physical therapists reported serious adverse effects. CONCLUSION: Three months of rehabilitation with manual mobilization can attenuate thoracic kyphosis in elderly patients with osteoporosis. Its impact on back pain and quality of life remains unclear and needs further investigation.