Effects of lactotripeptide ingestion and physical activity intervention on the fatigue status of middle-aged and older adults: a randomized controlled trial.

This randomized controlled trial aimed to investigate the effects of eight weeks of lactotripeptide (LTP) ingestion, physical activity (PA) intervention, and combined intervention on the fatigue status of middle-aged and older adults. A total of 78 middle-aged and older adults (63 ± 8 years of age) were randomly assigned to four groups: placebo, LTP, placebo with PA intervention (placebo + PA), and LTP with PA intervention (LTP + PA). All participants ingested the placebo or LTP tablets daily (three tablets/day). The placebo + PA and LTP + PA groups participated in a weekly supervised exercise class and were instructed to increase their moderate- to vigorous-intensity PA at home. The visual analog scale, Brief Fatigue Inventory, Profile of Mood States second edition (POMS2), and Beck Depression Inventory second edition (BDI-II) were administered before and after the intervention. No significant interactions or main effects were observed between LTP ingestion and PA intervention on any of the fatigue scales. The main-effect analyses revealed that the PA intervention improved the total mood disturbance score of the POMS2 (F = 5.22, P = 0.03) and BDI-II score (F = 4.81, P = 0.03). After the post hoc paired comparisons, the total mood disturbance and BDI-II scores improved more with the combined intervention than with the PA intervention alone (percentage difference between the effect of combined intervention and PA intervention alone was 3.7% for total mood disturbance score and 13.7% for BDI-II score). The present study suggests that eight weeks of LTP ingestion and PA intervention did not have a significant effect on fatigue status. However, the PA intervention improved mood status and depressive symptoms, and these effects were enhanced by LTP ingestion.

Ratio of serum creatinine to cystatin C is related to leg strength in predialysis CKD patients.

BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) patients have lower levels of physical function. Especially, leg strength is important for daily living and preventing falls. However, physical function screenings are difficult to perform at clinical sites. To find clinically useful method to evaluate physical function in predialysis CKD patients, we tried to evaluate the relationship between the ratio of serum creatinine to serum cystatin C (Cre/CysC), and knee extensor muscle strength/body weight (KEMS) which reflects their leg strength. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We recruited 147 outpatients with CKD (87 men; mean age, 61.6 ± 9.8 years; mean eGFRcreat, 40.7 ± 12.9 mL/min/1.73m2) in this cross-sectional study. KEMS was assessed using a wire strain gauge dynamometer. Skeletal muscle mass and body fat mass were assessed by bioelectrical impedance analysis. RESULTS: The mean value of Cre/CysC was 1.01 ± 0.18. The mean value of KEMS was 1.60 ± 0.47 Nm/kg. In multivariate linear regression analysis, skeletal muscle mass (p < 0.01), body fat mass (p < 0.01), hemoglobin (p = 0.01), and Cre/CysC (p < 0.01) was independently related to KEMS. The correlation between Cre/CysC and KEMS is stronger in high quantile of Cre/CysC. CONCLUSIONS: In predialysis CKD patients, KEMS showed lower as CKD stage advanced. Cre/CysC is significantly related to KEMS independently. Cre/CysC may be an alternative marker for leg strength in CKD patients and even more valuable to utilize in cases with high Cre/CysC.

Replacing sedentary time for physical activity on bone density in patients with chronic kidney disease.

INTRODUCTION: This study aimed to examine the cross-sectional associations of sedentary time and physical activity time with bone density in patients with chronic kidney disease (CKD). The isotemporal substitution (IS) modeling was used to estimate the beneficial effects of behavioral changes (e.g., replacing sedentary time with physical activity time) on bone density in these patients. MATERIALS AND METHODS: A total of 92 patients with CKD (age: 65 ± 9 years; estimated glomerular filtration rate: 57 ± 22 mL/min/1.73 m2) were included in this cross-sectional study. The times spent in sedentary behavior (SB), light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) were assessed using a triaxial accelerometer. Through quantitative ultrasound measurements, the stiffness index, as a measure of bone density, was calculated using the speed of sound and broadband ultrasound attenuation. RESULTS: In multivariate analyses, the stiffness index was beneficially associated with the MVPA time (ß = 0.748), but was not significantly associated with the SB and LPA times. The IS models showed that replacing 10 min/day of SB with the equivalent LPA time was not significantly associated with the stiffness index; however, replacing 10 min/day of SB with the equivalent MVPA time was beneficially associated with the stiffness index (ß = 0.804). CONCLUSION: These results suggest that a small increase in MVPA time (e.g., 10 min/day) may attenuate the decline in bone density in patients with CKD. Our findings may provide insight for the development of novel strategies for improving bone health in patients with CKD.

High Salt Diet Impacts the Risk of Sarcopenia Associated with Reduction of Skeletal Muscle Performance in the Japanese Population.

The World Health Organization has recommended 5 g/day as dietary reference intakes for salt. In Japan, the averages for men and women were 11.0 g/day and 9.3 g/day, respectively. Recently, it was reported that amounts of sodium accumulation in skeletal muscles of older people were significantly higher than those in younger people. The purpose of this study was to investigate whether the risk of sarcopenia with decreased muscle mass and strength was related to the amount of salt intake. In addition, we investigated its involvement with renalase. Four groups based on age and salt intake ("younger low-salt," "younger high-salt," "older low-salt," and "older high-salt") were compared. Stratifying by age category, body fat percentage significantly increased in high-salt groups in both younger and older people. Handgrip strength/body weight and chair rise tests of the older high-salt group showed significant reduction compared to the older low-salt group. However, there was no significant difference in renalase concentrations in plasma. The results suggest that high-salt intake may lead to fat accumulation and muscle weakness associated with sarcopenia. Therefore, efforts to reduce salt intake may prevent sarcopenia.

Sedentary behaviour, physical activity, and renal function in older adults: isotemporal substitution modelling.

BACKGROUND: Physical inactivity and sedentary behaviour (too much sitting) can contribute to renal dysfunction. However, the potential benefits of behavioural change (e.g. replacing sedentary behaviour with physical activity) on renal function are not well understood. We used isotemporal substitution to model potential impacts of behaviours on renal function by replacing time spent in one behaviour to another. METHODS: In 174 older Japanese adults (age, 50-83 years; females, 76%), the time spent in sedentary behaviour, light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) were assessed using an uniaxial accelerometer. Renal function was evaluated by the estimated glomerular filtration rate (eGFR) from serum creatinine and cystatin C levels. RESULTS: In univariate analyses, eGFR was significantly, albeit weakly, correlated with time spent in sedentary behaviour (rs = - 0.229), LPA (rs = 0.265), and MVPA (rs = 0.353). In the isotemporal substitution models, replacement of 30 min/day of sedentary behaviour with an equivalent LPA time was not significantly associated with eGFR (ß = 2.26, p = 0.112); however, replacement with an equivalent time of MVPA was beneficially associated with eGFR (ß = 5.49, p < 0.05). CONCLUSIONS: These cross-sectional findings suggest that sedentary behaviour (detrimentally) and physical activity (beneficially) may affect renal function and that replacing sedentary behaviour with MVPA may benefit renal health in older adults.

Increased fibroblast growth factor-21 in chronic kidney disease is a trade-off between survival benefit and blood pressure dysregulation.

Circulating levels of fibroblast growth factor-21 (FGF21) start increasing in patients with chronic kidney disease (CKD) since early stages during the cause of disease progression. FGF21 is a liver-derived hormone that induces responses to stress through acting on hypothalamus to activate the sympathetic nervous system and the hypothalamus-pituitary-adrenal endocrine axis. However, roles that FGF21 plays in pathophysiology of CKD remains elusive. Here we show in mice that FGF21 is required to survive CKD but responsible for blood pressure dysregulation. When introduced with CKD, Fgf21-/- mice died earlier than wild-type mice. Paradoxically, these Fgf21-/- CKD mice escaped several complications observed in wild-type mice, including augmentation of blood pressure elevating response and activation of the sympathetic nervous system during physical activity and increase in serum noradrenalin and corticosterone levels. Supplementation of FGF21 by administration of an FGF21-expressing adeno-associated virus vector recapitulated these complications in wild-type mice and restored the survival period in Fgf21-/- CKD mice. In CKD patients, high serum FGF21 levels are independently associated with decreased baroreceptor sensitivity. Thus, increased FGF21 in CKD can be viewed as a survival response at the sacrifice of blood pressure homeostasis.

Lactotripeptide ingestion increases cerebral blood flow velocity in middle-aged and older adults.

The age-related decrease in cerebral blood flow velocity increases the risk of cerebrovascular disease. Milk protein-derived bioactive peptides, e.g., lactotripeptide (LTP), have been shown to inhibit angiotensin converting enzyme activities and increase vasodilator production. We hypothesized that LTP ingestion increases cerebral blood flow velocity in middle-aged and older adults. In a randomized, placebo-controlled, double-blind design, 15 healthy middle-aged and older adults were assigned to either a LTP group or a placebo group. The subjects ingested LTP or placebo orally for 8 weeks. Before and after intervention, middle cerebral blood flow velocity was measured using transcranial Doppler ultrasonography. The baseline middle cerebral blood flow velocity and most other key dependent variables did not differ between the groups. LTP ingestion significantly increased middle cerebral blood flow velocity, but there was no such improvement in the placebo groups. We concluded that 8 weeks of LTP ingestion increased middle cerebral blood flow velocity in middle-aged and older adults.