Influence of menstrual cycle and oral contraceptive phases on bone (re)modelling markers in response to interval running

To explore how sex hormone fluctuations may affect bone metabolism, this study aimed to examine P1NP and β-CTX-1 concentrations across the menstrual and oral contraceptive (OC) cycle phases in response to running. 17β-oestradiol, progesterone, P1NP and β-CTX-1 were analysed pre- and post-exercise in eight eumenorrheic females in the early-follicular, late-follicular, and mid-luteal phases, while 8 OC users were evaluated during the withdrawal and active pill-taking phases. The running protocol consisted of 8 × 3min treadmill runs at 85% of maximal aerobic speed. 17β-oestradiol concentrations (pg·ml−1) were lower in early-follicular (47.22 ± 39.75) compared to late-follicular (304.95 ± 235.85;p = < 0.001) and mid-luteal phase (165.56 ± 80.6;p = 0.003) and higher in withdrawal (46.51 ± 44.09) compared to active pill-taking phase (10.88 ± 11.24;p < 0.001). Progesterone (ng·ml−1) was higher in mid-luteal (13.214 ± 4.926) compared to early-follicular (0.521 ± 0.365; p < 0.001) and late-follicular phase (1.677 ± 2.586;p < 0.001). In eumenorrheic females, P1NP concentrations (ng·ml−1) were higher in late-follicular (69.97 ± 17.84) compared to early-follicular (60.96 ± 16.64;p = 0.006;) and mid-luteal phase (59.122 ± 11.77;p = 0.002). β-CTX-1 concentrations (ng·ml−1) were lower in mid-luteal (0.376 ± 0.098) compared to late-follicular (0.496 ± 0.166; p = 0.001) and early-follicular phase (0.452 ± 0.148; p = 0.039). OC users showed higher post-exercise P1NP concentrations in withdrawal phase (61.75 ± 8.32) compared to post-exercise in active pill-taking phase (45.45 ± 6;p < 0.001). Comparing hormonal profiles, post-exercise P1NP concentrations were higher in early-follicular (66.91 ± 16.26;p < 0.001), late-follicular (80.66 ± 16.35;p < 0.001) and mid-luteal phases (64.57 ± 9.68;p = 0.002) to active pill-taking phase. These findings underscore the importance of studying exercising females with different ovarian hormone profiles, as changes in sex hormone concentrations affect bone metabolism in response to running, showing a higher post-exercise P1NP concentrations in all menstrual cycle phases compared with active pill-taking phase of the OC cycle

P1NP and β-CTX-1 responses to a prolonged, continuous running bout in young healthy adult males: a systematic review with individual participant data meta-analysis.

Circulating biomarkers of bone formation and resorption are widely used in exercise metabolism research, but their responses to exercise are not clear. To quantify group responses and inter-individual variability of P1NP and β-CTX-1 after prolonged, continuous running (60-120 min at 65-75% VO2max) in young healthy adult males using individual participant data (IPD) meta-analysis. The protocol was designed following PRISMA-IPD guidelines. Changes in P1NP and β-CTX-1 relative to baseline were measured during, immediately after, and in the hours and days following exercise. Typical hourly and daily variations were estimated from P1NP and β-CTX-1 changes relative to baseline in non-exercise (control) conditions. Group responses and inter-individual variability were quantified with estimates of the mean and standard deviation of the difference, and the proportion of participants exhibiting an increased response. Models were conducted within a Bayesian framework with random intercepts to account for systematic variation across studies. P1NP levels increased during and immediately after running, where the proportion of response was close to 100% (75% CrI: 99 to 100%). P1NP levels returned to baseline levels within 1 hour and over the next 4 days, showing comparable mean and standard deviation of the difference with typical hourly (0.1 ± 7.6 ng·ml-1) and daily (-0.4 ± 5.7 ng·ml-1) variation values. β-CTX-1 levels decreased during and up to 4 hours after running with distributions comparable to typical hourly variation (-0.13 ± 0.11 ng·ml-1). There was no evidence of changes in β-CTX-1 levels during the 4 days after the running bout, where distributions were also similar between the running data and typical daily variation and (-0.03 ± 0.10 ng·ml-1). Transient increases in P1NP were likely biological artefacts (e.g., connective tissue leakage) and not reflective of bone formation. Comparable small decreases in β-CTX-1 identified in both control and running data, suggested that these changes were due to the markers' circadian rhythm and not the running intervention. Hence, prolonged continuous treadmill running did not elicit bone responses, as determined by P1NP and β-CTX-1, in this population. The protocol for this review was pre-registered on the Open Science Framework prior to implementation (https://osf.io/y69nd)

Experiences of physical activity, healthy eating and quality of life during and following pregnancy in overweight and obese postpartum women

Objectives This retrospective study explored the experiences of women with overweight or obesity regarding physical activity, diet and quality of life leading up to, during, and following pregnancy. Methods A qualitative descriptive design was adopted, whereby data collected through semi-structured interviews were analysed using thematic analysis. Throughout the interviews, individuals were asked to describe their barriers to a healthy lifestyle during and following pregnancy. Results Ten women (34.5 ± 5.2 years old, BMI 30.4 ± 3.5 kg·m− 2) who were between 12 and 52 weeks postpartum participated. A range of themes were identified when discussing barriers to physical activity and healthy eating during and following pregnancy. For example, tiredness, especially in the third trimester of pregnancy, and a lack of support at home, was often cited as preventing engagement in exercise and healthy eating practices. A lack of convenience when attending exercise classes, medical complications following the birth and the cost of attending pregnancy-specific classes were identified as barriers to exercise engagement. Cravings and nausea were identified as barriers to healthy eating during pregnancy. Quality of life was positively associated with exercise and healthy eating, whilst a lack of sleep, loneliness and a loss of freedom since the baby had arrived negatively influenced quality of life. Discussion Postpartum women with overweight and obesity experience many barriers when attempting to engage in a healthy lifestyle during and following pregnancy. These findings can be used to inform the design and delivery of future lifestyle interventions in this population. Significance What is Already Known on this Subject? Pregnant and postpartum women experience a multitude of barriers when attempting to engage in a healthy lifestyle. What this Study adds? Until now, investigations into barriers to participation in a healthy lifestyle in overweight and obese pregnant and postpartum women have been lacking. Akin to normal weight women, women with a BMI > 25 kg/m2 experience many barriers to a healthy lifestyle during and following pregnancy. In this exclusive overweight and obese population, medical complications was the most cited barrier to postpartum exercise engagement. These results will be considered when designing future postpartum lifestyle interventions

Feminae: an international multi-site innovative project for female athletes.

Sufficient high-quality studies in sport science using women as participants are lacking, meaning that our knowledge and understanding of female athletes in relation to their ovarian hormone profiles is limited. Consortia can be used to pool talent, expertise, and data, thus accelerating our learning on a given topic and reducing research waste through collaboration. To this end, we have assembled an international multi-site team, described herein, to investigate the effects of the menstrual cycle and oral contraceptive pill phase on aspects of exercise physiology and sports performance in female athletes. We intend to produce an adequately powered, high-quality dataset which can be used to inform the practices of female athletes. Our approach will also employ research transparency – through the inclusion of a process evaluation - and reproducibility – through a standardised study protocol

Effect of carbohydrate feeding on the bone metabolic response to running

Bone resorption is increased after running, with no change in bone formation. Feeding during exercise might attenuate this increase, preventing associated problems for bone. This study investigated the immediate and short-term bone metabolic responses to carbohydrate (CHO) feeding during treadmill running. Ten men completed two 7-day trials, once being fed CHO (8% glucose immediately before, every 20 min during, and immediately after exercise at a rate of 0.7 g CHO·kg body mass-1·h-1) and once being fed placebo (PBO). On day 4 of each trial, participants completed a 120-min treadmill run at 70% of maximal oxygen consumption (VO2 max). Blood was taken at baseline (BASE), immediately after exercise (EE), after 60 (R1) and 120 (R2) min of recovery, and on three follow-up days (FU1-FU3). Markers of bone resorption [COOH-terminal telopeptide region of collagen type 1 (β-CTX)] and formation [NH2-terminal propeptides of procollagen type 1 (P1NP)] were measured, along with osteocalcin (OC), parathyroid hormone (PTH), albumin-adjusted calcium (ACa), phosphate, glucagon-like peptide-2 (GLP-2), interleukin-6 (IL-6), insulin, cortisol, leptin, and osteoprotogerin (OPG). Area under the curve was calculated in terms of the immediate (BASE, EE, R1, and R2) and short-term (BASE, FU1, FU2, and FU3) responses to exercise. β-CTX, P1NP, and IL-6 responses to exercise were significantly lower in the immediate postexercise period with CHO feeding compared with PBO (β-CTX: P=0.028; P1NP: P=0.021; IL-6: P=0.036), although there was no difference in the short-term response (β-CTX: P=0.856; P1NP: P=0.721; IL-6: P=0.327). No other variable was significantly affected by CHO feeding during exercise. We conclude that CHO feeding during exercise attenuated the β-CTX and P1NP responses in the hours but not days following exercise, indicating an acute effect of CHO feeding on bone turnover

Exercise-induced ‘browning’ of adipose tissues

Global rates of obesity continue to rise and are necessarily the consequence of a long-term imbalance between energy intake and energy expenditure. This is the result of an expansion of adipose tissue due to both the hypertrophy of existing adipocytes and hyperplasia of adipocyte pre-cursors. Exercise elicits numerous physiological benefits on adipose tissue, which are likely to contribute to the associated cardiometabolic benefits. More recently it has been demonstrated that exercise, through a range of mechanisms, induces a phenotypic switch in adipose tissue from energy storing white adipocytes to thermogenic beige adipocytes. This has generated the hypothesis that the process of adipocyte ‘browning’ may partially underlie the improved cardiometabolic health in physically active populations. Interestingly, ‘browning’ also occurs in response to various stressors and could represent an adaptive response. In the context of exercise, it is not clear whether the appearance of beige adipocytes is metabolically beneficial or whether they occur as a transient adaptive process to exercise-induced stresses. The present review discusses the various mechanisms (e.g. fatty acid oxidation during exercise, decreased thermal insulation, stressors and angiogenesis) by which the exercise-induced ‘browning’ process may occur

Prevalence of reducing carbohydrate intake and fasted training in elite endurance athletes and association with bone injury

There are conflicting reports both within the lay media and scientific literature regarding the use and benefit of dietary practices that aim to reduce CHO intake in endurance athletes. This study aimed to determine the prevalence of intentional reduction of CHO intake and fasted training in elite endurance-based athletes using a semi-quantitative questionnaire. Bone is a nutritionally modulated tissue; therefore, this study also aimed to explore if these dietary practices are potentially associated with bone injury incidence. The reported reduction of CHO intake was prevalent (28%) with the primary motivation being maintenance or manipulation of body composition. However, discrepancies in athletes' awareness of CHO intake were identified providing a potential avenue of intervention especially within applied practice. The use of fasted training was more prevalent (38%) with athletes using this practice for both body composition manipulation and promoting a desired adaptive response. Forty-four per cent of participants had suffered a radiographically confirmed bone injury at some point in their career. There was no association between reduction in CHO intake and bone injury incidence; however, the incidence of bone injury was 1.61 times higher in those who currently use fasted training compared to those who have never used it or who have used it in the past. Although a direct causal link between these dietary practices and the incidence of bone injury cannot be drawn, it provides robust justification for future investigations of the potential mechanisms that could explain this finding

Protein and bone health across the lifespan

Bone health is determined by the rate of accrual in early life, followed by the rate of age associated bone loss. Dietary protein intake might have a role in bone health across both of these phases via pleiotropic mechanistic pathways. Herein we summarise the pathways through which protein may exert either a positive or negative influence on bone. In Section 1, we describe the acid-ash hypothesis, which states that a high protein intake may lead to an acidic residue that must be neutralised through the leaching of calcium and other minerals from the bone, subsequently leading to demineralisation and bone weakening. Conversely, and as described in Section 2, protein intake may act to strengthen bone by stimulating the activity of various anabolic hormones and growth factors, or by optimising muscle mass and functionality, which itself has an osteogenic influence. The net effect of these contrasting pathways is described in Section 3, where a number of meta-analyses have demonstrated that higher protein intakes have a small positive impact on bone mass and fracture risk. Sometimes higher than recommended protein intakes are advised, e.g., during the earlier and later phases of the lifespan or during reduced energy availability. We conclude that protein is an essential nutrient for bone health, although further research is required to clarify the mechanistic pathways through which it exerts its influence, along with clarification of the quantities, food sources and timing to allow for the optimisation of this protective influence and ultimately a reduction in fracture risk

Carnosine increases insulin-stimulated glucose uptake and reduces methylglyoxal-modified proteins in type-2 diabetic human skeletal muscle cells

Type-2 diabetes (T2D) is characterised by a dysregulation of metabolism, including skeletal muscle insulin resistance, mitochondrial dysfunction, and oxidative stress. Reactive species, such as methylglyoxal (MGO) and 4-hydroxynonenal (4-HNE), positively associate with T2D disease severity and can directly interfere with insulin signalling and glucose uptake in skeletal muscle by modifying cellular proteins. The multifunctional dipeptide carnosine, and its rate-limiting precursor β-alanine, have recently been shown to improve glycaemic control in humans and rodents with diabetes. However, the precise mechanisms are unclear and research in human skeletal muscle is limited. Herein, we present novel findings in primary human T2D and lean healthy control (LHC) skeletal muscle cells. Cells were differentiated to myotubes, and treated with 10 mM carnosine, 10 mM β-alanine, or control for 4-days. T2D cells had reduced ATP-linked and maximal respiration compared with LHC cells (p = 0.016 and p = 0.005). Treatment with 10 mM carnosine significantly increased insulin-stimulated glucose uptake in T2D cells (p = 0.047); with no effect in LHC cells. Insulin-stimulation increased MGO-modified proteins in T2D cells by 47%; treatment with carnosine attenuated this increase to 9.7% (p = 0.011). There was no effect treatment on cell viability or expression of other proteins. These findings suggest that the beneficial effects of carnosine on glycaemic control may be explained by its scavenging actions in human skeletal muscle

Intermittent tensile strain induces an increased response in bone formation markers compared to continuous load in mouse pre-osteoblasts when loading magnitude is matched

Intermittent and continuous mechanical loads are known to influence osteogenic activity. The present study examines the effects of matched intermittent and continuous load in vitro on bone formation markers. MC3T3 (mouse pre-osteoblasts) were cultured and placed in a bioreactor to undergo continuous, intermittent, or unloading for 1, 3 and 12 days. Loading conditions were matched for magnitude, duration and frequency. Each time point was analysed for alkaline phosphatase (ALP) activity, procollagen 1 N-terminal propeptide (PINP) and alizarin red staining (ARS). Intermittent load caused an increase in ALP activity across all time points compared to continuous loading (↑30%-59%) and unloaded conditions (↑70%-90%). PINP concentrations from intermittent load were lower than continuous load (↓112%) on day 3. However, no differences were observed in PINP concentrations between loading conditions at other time points. No differences were observed for ARS between loading conditions. Intermittent load caused an increase in bone formation marker ALP, but not PINP, when compared to continuous loading and unloaded conditions. These findings further our knowledge in bone formation response and provide additional tools for the analysis of osteogenesis in vitro