Exercise Training and Natural Killer Cells in Cancer Survivors: Current Evidence and Research Gaps Based on a Systematic Review and Meta-analysis.

BACKGROUND: Exercise training can positively impact the immune system and particularly natural killer (NK) cells, at least in healthy people. This effect would be of relevance in the context of cancer given the prominent role of these cells in antitumor immunity. In this systematic review and meta-analysis, we aimed to summarize current evidence on the effects of exercise training on the levels and function of NK cells in cancer survivors (i.e., from the time of diagnosis until the end of life). METHODS: Relevant articles were searched in PubMed, Scopus, Web of Science and Cochrane Central Register of Controlled Trials (until January 11, 2022). Randomized controlled trials (RCT) of exercise training (i.e., non-acute) interventions vs usual care conducted in cancer survivors and assessing NK number and/or cytotoxic activity (NKCA) before and upon completion of the intervention were included. Methodological quality of the studies was assessed with the PEDro scale, and results were meta-analyzed using a random effects (Dersimoian and Laird) model. RESULTS: Thirteen RCT including 459 participants (mean age ranging 11-63 years) met the inclusion criteria. Methodological quality of the studies was overall fair (median PEDro score = 5 out of 10). There was heterogeneity across studies regarding cancer types (breast cancer, non-small cell lung cancer and other solid tumors), treatment (e.g., receiving vs having received chemotherapy), exercise modes (aerobic or resistance exercise, Tai Chi, Yoga) and duration (2-24 weeks). No consistent effects were observed for NK number in blood (mean difference [MD]: 1.47, 95% confidence interval [CI] - 0.35 to 3.29, p = 0.113) or NKCA as assessed in vitro (MD: - 0.02, 95%CI - 0.17 to 0.14, p = 0.834). However, mixed results existed across studies, and some could not be meta-analyzed due to lack of information or methodological heterogeneity. CONCLUSIONS: Current evidence does not support a significant effect of exercise training intervention on NK cells in blood or on their 'static response' (as assessed in vitro) in cancer survivors. Several methodological issues and research gaps are highlighted in this review, which should be considered in future studies to draw definite conclusions on this topic.

Perspective: Ketone Supplementation in Sports-Does It Work?

Oral ketone supplements have gained popularity in recent years. There is biological rationale for a potential ergogenic effect of this type of supplement, as they might not only alter muscle fuel preference during exercise (and promote glycogen sparing, with potential benefits for endurance performance) but also favor cognition performance during exertion or muscle glycogen synthesis after exercise. However, as discussed in this Perspective, evidence to date does not support a benefit of acute ketone supplementation on sports performance, cognition, or muscle recovery [although further research with long-duration exercise (i.e., >60 min), is needed], and the evidence for chronic supplementation is sparse. In addition, acute intake of ketone supplements might be associated with gastrointestinal symptoms, and further research is warranted on the long-term safety of repeated use of ketone supplements. In summary, there is currently insufficient evidence to support the overall effectiveness of ketone supplements in sports.

Intradialytic neuromuscular electrical stimulation improves functional capacity and muscle strength in people receiving haemodialysis: a systematic review.

QUESTIONS: Does neuromuscular electrical stimulation (NMES) applied during haemodialysis sessions improve functional capacity in people with end-stage renal disease? Does NMES used in this way also improve muscle strength, muscle mass/architecture, psychological outcomes, cardiovascular outcomes and biochemical variables? Does it have any adverse effects? DESIGN: Systematic review of randomised controlled trials with meta-analysis. PubMed, Web of Science, Scopus and SPORTDiscus were searched from inception to 15 October 2019. PARTICIPANTS: Patients receiving haemodialysis for end-stage renal disease. INTERVENTION: NMES administered during haemodialysis sessions versus control. OUTCOMES MEASURES: Functional capacity, muscle strength, muscle mass, psychological outcomes, cardiovascular outcomes, biochemical variables and adverse events. DATA ANALYSIS: Data were meta-analysed where possible and results were expressed as the pooled mean difference between groups with a 95% confidence interval. RESULTS: Eight studies (221 patients) were included in the analysis. Overall, the methodological quality of the studies was fair to good. NMES improved functional capacity as assessed by the 6-minute walk distance test (MD 31 m, 95% CI 13 to 49) and peak workload attained in incremental exercise (MD 12.5 W, 95% CI 3.2 to 21.9). NMES increased knee extensor muscle strength (MD 3.5 kg, 95% CI 2.3 to 4.7) and handgrip strength (MD 2.4 kg, 95% CI 0.4 to 4.4). Muscle mass/architecture was not substantially affected. NMES was estimated to be beneficial for several domains of quality of life in several studies, although most of these estimates were imprecise. No benefits were found for cardiovascular outcomes. The available data did not establish any clear effects on cardiovascular outcomes or biochemical variables (dialysis efficiency, urea and creatinine). No major NMES-related adverse events were observed. CONCLUSIONS: NMES is safe, practical and effective for improving functional capacity and muscle strength in haemodialysis patients. Further research is needed to confirm the clinical relevance of these findings. REGISTRATION: PROSPERO CRD42018107323.

Does Beef Protein Supplementation Improve Body Composition and Exercise Performance? A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Protein supplementation might improve body composition and exercise performance. Supplements containing whey protein (WP) have received the most attention, but other protein sources such as beef protein (BP) are gaining popularity. We conducted a systematic review and meta-analysis of randomized controlled trials that compared the effects of exercise training combined with BP, WP or no protein supplementation (NP), on body composition or exercise performance. Secondary endpoints included intervention effects on total protein intake and hematological parameters. Seven studies (n = 270 participants) were included. No differences were found between BP and WP for total protein intake (standardized mean difference (SMD) = 0.04, p = 0.892), lean body mass (LBM) (SMD = -0.01, p = 0.970) or fat mass (SMD = 0.07, p = 0.760). BP significantly increased total daily protein intake (SMD = 0.68, p < 0.001), LBM (SMD = 0.34, p = 0.049) and lower-limb muscle strength (SMD = 0.40, p = 0.014) compared to NP, but no significant differences were found between both conditions for fat mass (SMD = 0.15, p = 0.256), upper-limb muscle strength (SMD = 0.16, p = 0.536) or total iron intake (SMD = 0.29, p = 0.089). In summary, BP provides similar effects to WP on protein intake and body composition and, compared to NP, might be an effective intervention to increase total daily protein intake, LBM and lower-limb muscle strength.

Supplements with purported effects on muscle mass and strength.

PURPOSE: Several supplements are purported to promote muscle hypertrophy and strength gains in healthy subjects, or to prevent muscle wasting in atrophying situations (e.g., ageing or disuse periods). However, their effectiveness remains unclear. METHODS: This review summarizes the available evidence on the beneficial impacts of several popular supplements on muscle mass or strength. RESULTS: Among the supplements tested, nitrate and caffeine returned sufficient evidence supporting their acute beneficial effects on muscle strength, whereas the long-term consumption of creatine, protein and polyunsaturated fatty acids seems to consistently increase or preserve muscle mass and strength (evidence level A). On the other hand, mixed or unclear evidence was found for several popular supplements including branched-chain amino acids, adenosine triphosphate, citrulline, ß-Hydroxy-ß-methylbutyrate, minerals, most vitamins, phosphatidic acid or arginine (evidence level B), weak or scarce evidence was found for conjugated linoleic acid, glutamine, resveratrol, tribulus terrestris or ursolic acid (evidence level C), and no evidence was found for other supplements such as ornithine or α-ketoglutarate (evidence D). Of note, although most supplements appear to be safe when consumed at typical doses, some adverse events have been reported for some of them (e.g., caffeine, vitamins, α-ketoglutarate, tribulus terrestris, arginine) after large intakes, and there is insufficient evidence to determine the safety of many frequently used supplements (e.g., ornithine, conjugated linoleic acid, ursolic acid). CONCLUSION:  In summary, despite their popularity, there is little evidence supporting the use of most supplements, and some of them have been even proven ineffective or potentially associated with adverse effects.