Dietary Protein and Bone Health Across the Life-Course : an updated systematic review and meta-analysis over 40 years

Abstract Purpose: This systematic review and meta-analysis analysed the relationship between dietary protein and bone health across the life-course. Methods: The PubMed database was searched for all relevant human studies from the 1st 4 January 1976 to 22nd January 2016, including all bone outcomes except calcium metabolism. Results: The searches identified 127 papers for inclusion, including 74 correlational studies, 23 fracture or osteoporosis risk studies and 30 supplementation trials. Protein intake accounted for 0 - 4% of areal BMC and areal BMD variance in adults and 0-14% of areal BMC variance in children and adolescents. However, when confounder adjusted (5 studies) adult lumbar spine and femoral neck BMD associations were not statistically significant. There was no association between protein intake and relative risk (RR) of osteoporotic fractures for total (RR(random) = 0.94; 0.72 to 1.23, I2=32%), animal (RR (random) = 0.98; 0.76 to 1.27, I2 = 46%) or vegetable protein (RR (fixed)= 0.97 (0.89 to 1.09, I2 = 15%). In total protein supplementation studies, pooled effect sizes were not statistically significant for LSBMD (total n=255, MD(fixed)=0.04 g/cm2 (0.00 to 0.08, P=0.07), I2=0%) or FNBMD (total n=435, MD(random)=0.01 g/cm2 (-0.03 to 0.05, P=0.59), I2=68%). Conclusions: There appears to be little benefit of increasing protein intake for bone health in healthy adults but there is also clearly no indication of any detrimental effect, at least within the protein intakes of the populations studied (around 0.8-1.3 g/Kg/day). More studies are urgently required on the association between protein intake and bone health in children and adolescents. Key Words: Aging, Epidemiology, IGF-1, Nutrition, Osteoporosis, Die

Development of a computer-based algorithm for supporting community pharmacists in providing personalised lifestyle interventions for men with prostate cancer

Background: The number of people living with and beyond a cancer diagnosis has increased, however survivors may experience long-term side-effects from treatment that can impact on physical fitness and cardiovascular health. Lifestyle interventions enhance outcomes after cancer treatment but innovations and technology are needed to provide consistency and scalability. Interventions to support exercise and dietary modification in secondary care settings have been limited by the lack of personalisation, clinician time and resources. Community pharmacies are well positioned to provide lifestyle advice for people with cancer and long-term conditions. This study is the first to develop a tailored lifestyle intervention using a computer algorithm to enable community pharmacists to provide personalised advice for cancer patients. Objective: To create a computer-based algorithm to support community pharmacists to deliver a tailored lifestyle intervention for men during and after treatment for prostate cancer. Method: An observational study was conducted at two UK centres involving 83 men with prostate cancer who were 3-36 months’ post-diagnosis. Physical fitness, strength and cardiovascular health were assessed. Qualitative interviews were undertaken with 20 participants to understand their interpretation of the assessment and analysed using a framework analysis. These data were used to inform our computer-based algorithm and lifestyle prescriptions. Results: Physical fitness varied across participants. Limb strength was categorised with upper body strength low for 40% of men compared to their age (40 out of 83) and lower limb strength (44 of 83) 53% of men were low in comparison to age normative values. The Siconolfi step test provided classification of cardiopulmonary fitness with 26.5% (22 of 83) men unable to complete level 1 with very low physical fitness and 41% (34 of 83) of men moderate completing stage 2 of the test. Cardiovascular risk was categorised as high (>20% QRISK2) in 41% of men contributed to by the number of men who had a high hip to waist ratio 72 of 83 men (86.7%) indicating abdominal fat.Three emergent themes from the qualitative analysis highlighted different perceptions of the physical assessment experience. The algorithm provided a clear pathway for decision making, that it was safe and effective to enable community pharmacists to prescribe tailored lifestyle advice for men with prostate cancer. Conclusion: We have developed a computer algorithm that uses simple, safe and validated assessments to provide tailored lifestyle advice which addresses specific areas of cardiovascular risk, strength and physical fitness in men with prostate cancer. It generates a real-time lifestyle prescription at the point of care and has been integrated into the software platform used by pharmacies in the UK. The algorithm was integrated into the software platform used by pharmacies within the UK

Insulinotropic and Muscle Protein Synthetic Effects of Branched-Chain Amino Acids: Potential Therapy for Type 2 Diabetes and Sarcopenia

The loss of muscle mass and strength with aging (i.e., sarcopenia) has a negative effect on functional independence and overall quality of life. One main contributing factor to sarcopenia is the reduced ability to increase skeletal muscle protein synthesis in response to habitual feeding, possibly due to a reduction in postprandial insulin release and an increase in insulin resistance. Branched-chain amino acids (BCAA), primarily leucine, increases the activation of pathways involved in muscle protein synthesis through insulin-dependent and independent mechanisms, which may help counteract the “anabolic resistance” to feeding in older adults. Leucine exhibits strong insulinotropic characteristics, which may increase amino acid availability for muscle protein synthesis, reduce muscle protein breakdown, and enhance glucose disposal to help maintain blood glucose homeostasis.Health and Social Development, Faculty of (Okanagan)Non UBCHealth and Exercise Sciences, School of (Okanagan)ReviewedFacult

Increased endoplasmic reticulum stress in mouse osteocytes with aging alters Cox-2 response to mechanical stimuli

Aging reduces bone mass as well as the anabolic response of bone to mechanical stimuli, resulting in osteopenia. Endoplasmic reticulum (ER) stress impairs the response of myogenic cells to anabolic stimuli, and is involved in sarcopenia, but whether ER stress also contributes to osteopenia is unknown. Therefore, we tested whether ER stress exists in bones of aged mice, and whether this impairs the osteocyte response to mechanical stimulation. Primary osteocytes were obtained from long bones of adult (8 months) and old (24-26 months) mice, treated with or without the pharmacological ER stress inducer tunicamycin, and either or not subjected to mechanical loading by pulsating fluid flow (PFF). The osteocyte response to PFF was assessed by measuring cyclooxygenase-2 (Cox-2) mRNA levels and nitric oxide (NO) production. mRNA levels of ER stress markers were higher in old versus adult osteocytes (+40% for activating transcription factor-4, +120% for C/EBP homologous protein, and +120% for spliced X-box binding protein-1, p < 0.05). The Cox-2 response to PFF was fourfold decreased in cells from old bones (p < 0.001), while tunicamycin decreased PFF-induced Cox-2 expression by threefold in cells from adult bones (p < 0.01). PFF increased NO production by 50% at 60 min in osteocytes from old versus adult bones (p < 0.01). In conclusion, our data indicate that the expression of several ER stress markers was higher in osteocytes from bones of old compared to adult mice. Since ER stress altered the response of osteocytes to mechanical loading, it could be a novel factor contributing to osteopenia

Postprandial hyperglycemia is highly prevalent throughout the day in type 2 diabetes patients

Aim: Although postprandial hyperglycemia is recognized as an important target in type 2 diabetes treatment, information on the prevalence of postprandial hyperglycemia throughout the day is limited. Therefore, we assessed the prevalence of hyperglycemia throughout the day in type 2 diabetes patients and healthy controls under standardized dietary, but otherwise free-living conditions. Methods: 60 male type 2 diabetes patients (HbA1c 7.5 ± 0.1% [58 ± 1 mmol/mol]) and 24 age- and BMI-matched normal glucose tolerant controls were recruited to participate in a comparative study of daily glycemic control. During a 3-day experimental period, blood glucose concentrations throughout the day were assessed by continuous glucose monitoring. Results: Type 2 diabetes patients experienced hyperglycemia (glucose concentrations > 10 mmol/L) 38 ± 4% of the day. Even diabetes patients with an HbA1c level below 7.0% (53 mmol/mol) experienced hyperglycemia for as much as 24 ± 5% throughout the day. Hyperglycemia was negligible in the control group (3 ± 1%). Conclusion: Hyperglycemia is highly prevalent throughout the day in type 2 diabetes patients, even in those patients with a HbA1c level well below 7.0% (53 mmol/mol). Standard medical care with prescription of oral blood glucose lowering medication does not provide ample protection against postprandial hyperglycemia

Kracht- en duurinspanning verbeteren 24-uurs bloedglucosehomeostase bij personen met een verminderde glucosetolerantie bij patiënten met type 2 diabetes

De mate van hyperglycemie, en met name postprandiale hyperglycemie, wordt geassocieerd met het risico op diabetesgerelateerde complicaties. Daarom staat glycemische controle centraal bij de behandeling van type 2 diabetes. Fysieke inspanning is bewezen effectief om de glycemische controle te verbeteren bij patiënten met type 2 diabetes

Aging related ER stress is not responsible for anabolic resistance in mouse skeletal muscle.

Anabolic resistance reflects the inability of skeletal muscle to maintain protein mass by appropriate stimulation of protein synthesis. We hypothesized that endoplasmic reticulum (ER) stress contributes to anabolic resistance in skeletal muscle with aging. Muscles were isolated from adult (8 mo) and old (26 mo) mice and weighed. ER stress markers in each muscle were quantified, and the anabolic response to leucine was assessed by measuring the phosphorylation state of S6K1 in soleus and EDL using an ex vivo muscle model. Aging reduced the muscle-to-body weight ratio in soleus, gastrocnemius, and plantaris, but not in EDL and tibialis anterior. Compared to adult mice, the expression of ER stress markers BiP and IRE1α was higher in EDL, and phospho-eIF2α was higher in soleus and EDL of old mice. S6K1 response to leucine was impaired in soleus, but not in EDL, suggesting that anabolic resistance contributes to soleus weight loss in old mice. Pre-incubation with ER stress inducer tunicamycin before leucine stimulation increased S6K1 phosphorylation beyond the level reached by leucine alone. Since tunicamycin did not impair leucine-induced S6K1 response, and based on the different ER stress marker regulation patterns, ER stress is probably not involved in anabolic resistance in skeletal muscle with aging

The relationship between vitamin D status, intake and exercise performance in UK university-level athletes and healthy inactive controls

The potential ergogenic effects of vitamin D (vitD) in high performing athletes has received considerable attention in the literature and media. However, little is known about non-supplemented university athletes and students residing at a higher latitude. This study aimed to investigate the effects of vitD (biochemical status and dietary intake) on exercise performance in UK university athletes and sedentary students. A total of 34 athletes and 16 sedentary controls were studied during the spring and summer months. Serum vitD status and sunlight exposure were assessed using LC-MS/MS and dosimetry, respectively. Muscular strength of the upper and lower body was assessed using handgrip and knee extensor dynamometry (KE). Countermovement jump (CMJ) and aerobic fitness were measured using an Optojump and VO2max test, respectively. Statistical analysis was performed using paired/ independent t-tests, ANCOVA and Pearson/ Spearman correlations, depending on normality. VitD status increased significantly over the seasons, with athletes measuring higher status both in spring (51.7±20.5 vs. 37.2±18.9 nmol/L, p = 0.03) and summer (66.7 ±15.8 vs 55.6±18.8 nmol/L, p = 0.04) when compared to controls, respectively. Notably, 22% of the subjects recruited were vitD deficient during the spring term only (&lt;25nmol/L, n 9). Subjects with ‘insufficient’ vitD status (&lt;50nmol/L) elicited significantly lower CMJ when contrasted to the vitD ‘sufficient’ (&gt;50nmol/l) group (p = 0.055) and a lower VO2 max (p = 0.05) in the spring and summer term (p = 0.05 and p = 0.01, respectively). However, an ANCOVA test showed no significant difference detected for either CMJ or VO2max following adjustments for co-variates. In conclusion, we provide novel information on the vitD status, dietary intake, physical fitness and sunlight exposure of UK young adults across two separate seasons, for which there is limited data at present.</p