Impact of Plant and Animal Protein-Based Meals on Serum Fibroblast Growth Factor-23 Levels in Healthy Young Men: A Randomized Crossover Trial.

Fibroblast growth factor-23 (FGF23) is a phosphaturic hormone secreted by osteocytes in response to dietary phosphate intake. An increase in FGF23 level is an indicator of excess phosphate intake relative to the residual nephron number. Therefore, avoiding excessive phosphate intake and inhibiting the elevation of serum FGF23 levels are important to preserve the number of functional nephrons. This randomized crossover trial aimed to determine the potential differences in the impacts on serum FGF23 levels between plant protein and animal protein-based meals in individuals with normal renal function. Nine young men were administered plant (no animal protein) or animal protein-based meals (70% of their protein was from animal sources) with the same phosphate content. The test meals consisted of breakfast, lunch, and dinner. Blood samples were collected in the morning, after overnight fasting, and before and after eating the test meals (for two consecutive days at the same hour each day). Furthermore, a 24-h urine sample was obtained on the day the test meal was consumed. No significant interactions were found among serum phosphate, calcium, and 1,25-dihydroxyvitamin D levels. However, after eating plant protein-based meals, serum FGF23 levels decreased and serum intact parathyroid hormone levels increased (interaction, p<0.05). Additionally, urine 24-h phosphate excretion tended to be lower in individuals consuming plant protein-based meals than in those consuming animal protein-based meals (p=0.06). In individuals with normal renal function, plant protein-based meals may prevent an increase in serum FGF23 levels and kidney damage caused by phosphate loading.

Effects of plant- and animal-based-protein meals for a day on serum nitric oxide and peroxynitrite levels in healthy young men.

Plant-based diets that replace animal-based proteins with plant-based proteins have received increased attention for cardiovascular protection. Nitric oxide (NO) plays an essential role in the maintenance of endothelial function. However, under higher oxidative stress, NO generation produces peroxynitrite, a powerful oxidant and vasoconstrictor. Diet-replaced protein sources has been reported to decrease oxidative stress. However, the effects of plant-based protein on NO and peroxynitrite have not yet been clarified. Therefore, this study aimed to compare the effects of plant- and animal-based-protein meals for a day on NO, peroxynitrite, and NO/peroxynitrite balance. A crossover trial of two meal conditions involving nine healthy men was performed. Participants ate standard meals during day 1. On day 2, baseline measurements were performed and the participants were provided with plant-based-protein meals or animal-based-protein meals. The standard and test meals consisted of breakfast, lunch, and dinner and were designed to be isocaloric. Plant-based-protein meals contained no animal protein. Blood samples were collected in the morning after overnight fasting before and after the test meals consumption. In the plant-based-protein meal condition, serum NOx levels (the sum of serum nitrite and nitrate) significantly increased, while serum peroxynitrite levels did not change significantly. Animal-based-protein meals significantly increased serum peroxynitrite levels but showed a trend of reduction in the serum NOx levels. Furthermore, serum NO/peroxynitrite balance significantly increased after plant-based-protein meals consumption, but significantly decreased after animal-based-protein meals consumption. These results suggest that, compared with animal-based-protein meals, plant-based-protein meals increase NO levels and NO/peroxynitrite balance, which reflects increased endothelial function.

Association of Lower Extremity Muscle Strength and Function with Renal Resistive Index in Individuals with and without Chronic Kidney Disease.

Age-related loss of lower extremity muscle strength is pronounced in individuals with chronic kidney disease (CKD). In contrast, an increase in intrarenal flow pulsatility results in initial age-related changes in renal hemodynamics, leading to the development of CKD. To date, it remains unclear whether lower extremity muscle strength determines elevated renal flow pulsatility. This study aimed to determine the association of lower extremity muscle strength and function with intrarenal hemodynamics in individuals with and without CKD. One hundred seventy-six individuals without CKD (aged 63 ± 9 years) and 101 individuals with CKD (aged 66 ± 8 years) were included in this study. Using Doppler ultrasound, the renal resistive index (RI) was measured as a parameter of renal hemodynamics. Knee extensor muscle strength (KES), gait speed (GS), and the 30 s chair stand test (30s-CST) were used to measure lower extremity muscle strength and function. Multivariate analyses showed that GS and 30s-CST scores were independent determinants of renal RI, whereas the KES score was not associated with renal RI in individuals with and without CKD. In the two-way analysis of covariance, renal RI was the highest in individuals with CKD who had lower KES, GS, and 30s-CST scores. Reduced lower extremity muscle strength and function are independent determinants of elevated renal flow pulsatility in individuals with and without CKD.

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.

Association between the intake of plant and animal proteins and the serum fibroblast growth factor-23 level in patients with chronic kidney disease analyzed by the isocaloric substitution model.

Fibroblast growth factor-23 (FGF23) is a phosphaturic hormone secreted by the bone in response to dietary phosphate intake. Since the phosphate content in the diet correlates with the protein content, both plant- and animal-based protein intake can increase the serum FGF23 level. However, a higher percentage of energy from plant protein than from animal protein is associated with a lower serum FGF23 level in patients with chronic kidney disease (CKD) in the United States. Since dietary habits differ between Asian and Western populations, we performed a cross-sectional study to determine the association between the percentages of energy from plant and animal proteins and the serum FGF23 level in Japanese CKD patients. In 107 non-dialysis CKD patients (age: 66 ± 9 years; estimated glomerular filtration rate: 56 ± 21 mL/min/1.73 m2), the percentages of energy from plant and animal proteins were assessed using a food frequency questionnaire based on food groups. Venous blood samples were used to measure the serum FGF23, phosphate, 1,25-dihydroxyvitamin D, and intact parathyroid hormone levels. The percentages of energy from plant and animal proteins showed a negative and positive association, respectively, with the serum FGF23 level. Furthermore, isocaloric substitution modeling showed that replacing animal protein with plant protein was associated with a low serum FGF23 level. Our findings suggest that encouraging diets with high plant protein level may prevent an increase in the serum FGF23 level in Japanese CKD patients.

Acute influences of tennis services on cardiac output and brachial hemodynamics in young male tennis players.

OBJECTIVES: This study aimed to examine the influences of tennis service exercise on cardiac output (CO) and bilateral brachial hemodynamics in young tennis players. DESIGN: Experimental study. METHODS: Ten young male tennis players (21 ±â€¯2 years of age) participated. Each performed 100 tennis services without a return shot for experimental tennis exercise. Cardiovascular hemodynamic variables, including bilateral brachial blood flow (BF), shear rate (SR), blood pressure, and CO, were collected under three conditions: 1) baseline, 2) immediately after the tennis services (post), and 3) 1 h after the tennis services (1-hour). The positive incremental area under the curve (iAUC) for brachial hemodynamic variables was calculated. RESULTS: Immediately after the 100 tennis services, CO, brachial BF, SR, and brachial vascular conductance (VC) in the dominant and non-dominant arms increased (p < 0.05). At the 1-hour condition, CO returned to baseline; the brachial BF, SR, and VC in the non-dominant arm returned to baseline levels, whereas the same variables in the dominant arm remained increased. The iAUC for brachial BF and VC in the dominant arm was higher than that in the non-dominant arm. Furthermore, the brachial BF/CO ratio index in the dominant arm increased at the post and 1-hour conditions, whereas that in the non-dominant arm was unchanged. CONCLUSIONS: Tennis service exercise specifically increases brachial BF, SR, and VC in the dominant arm, independent of increased CO. Our findings contribute to unveiling the underlying mechanisms of brachial artery adaptations in tennis players.

Cerebral and renal hemodynamics: similarities, differences, and associations with chronic kidney disease and aortic hemodynamics.

Elevated arterial pulsatility is a common risk factor for cerebrovascular disease and chronic kidney disease (CKD), which suggests that the brain and kidneys may have similar hemodynamic profiles. The objectives of this study were twofold: 1) to compare and contrast the cerebral and renal blood flow parameters in adults without CKD (hereafter, non-CKD adults) and CKD patients and 2) to determine the common predictor(s) of cerebral and renal hemodynamics among pressure pulsatility and several cardiovascular risk factors. In 110 non-CKD adults and 66 CKD patients, cerebral and renal blood flow velocity (BFV) were measured by transcranial Doppler and Duplex ultrasonography, respectively. Pulsatile hemodynamics were assessed by the pulsatility (PI) and resistive (RI) indices. Aortic pulse pressure was measured by tonometry. Compared with non-CKD adults, CKD patients showed greater pulsatility of the BFV (i.e., systolic minus diastolic BFV), PI, and RI in the kidneys but not the brain. However, the cerebral and renal PI and RI values were strongly correlated in both non-CKD adults (both PI and RI values: rs = 0.695) and CKD patients (both PI and RI values: rs = 0.640) (all P < 0.001). Multiple linear regression analysis further demonstrated that the cerebral and renal PI and RI associations remained significant after adjustment for potential covariates (e.g., age, sex, the presence of CKD). The aortic pulse pressure was a significant predictor for both cerebral and renal PI and RI values. Collectively, our findings suggest that CKD patients have higher renal flow pulsatility, which is strongly and independently associated with cerebral flow pulsatility and aortic hemodynamics.

Sedentary behavior is associated with reduced cardiovagal baroreflex sensitivity in healthy adults.

Sedentary behavior is an established risk factor for cardiovascular disease; however, it remains unclear whether sedentary behavior is associated with the deterioration of arterial blood pressure regulation. The purpose of this study was to determine the association between the time spent in sedentary behavior and cardiovagal baroreflex sensitivity (cBRS) in healthy adults. We investigated the cross-sectional relationship between sedentary time and cBRS in 179 adults aged 22-81 years. Sedentary time was objectively measured using a triaxial accelerometer. cBRS was evaluated by the transfer function gain of beat-by-beat changes in systolic blood pressure and the R-R interval during 5 min of spontaneous resting. Glycemic, lipidemic, and vascular risk factors were measured as potential covariates of cBRS and sedentary behavior. Men had a longer sedentary time and lower cBRS than women (p = 0.001). In a simple correlation analysis, older age was negatively associated with cBRS and positively associated with sedentary time, but sedentary time was not correlated with cBRS. However, after adjustment for age and sex, a longer sedentary time was associated with a lower cBRS. Multiple linear regression analysis showed that sedentary time was independently associated with lower cBRS with adjustment for covariates (ß = -0.325, p = 0.002). A significant association was also confirmed when the analysis was performed separately in the younger and older groups. This finding suggests that high sedentary behavior may have an adverse effect on arterial blood pressure regulation.

Effects of the number of sit-stand maneuver repetitions on baroreflex sensitivity and cardiovascular risk assessments.

Sit-stand maneuvers (SSMs) have increasingly been used for baroreflex sensitivity (BRS) measurement in physiological research, but it remains unknown as to how many SSMs need to be performed to measure BRS and assess its relationship with cardiovascular disease (CVD) risk. Therefore, this study aimed to determine 1) the effect of the number of SSM repetitions on BRS, and 2) the association between BRS and CVD risk factors. Data were collected from 174 individuals during 5 min of spontaneous rest and 5 min of repeated SSMs at 0.05 Hz (i.e., 15 cycles of 10-s sit and 10-s stand). During SSMs, BRS was calculated from the incremental cycles of 3, 6, 9, 12, and 15 SSMs using transfer function analysis of heart rate (HR) and systolic blood pressure (SBP). General CVD risk factors, carotid arterial stiffness, and cardiorespiratory fitness were measured. In result, HR and SBP increased during SSMs (P < 0.05). The BRS remained at a similar level during the resting and SSM conditions, whereas the coherence function reached its peak after 3 cycles of SSMs. BRS with ≥6 cycles of SSMs was strongly correlated with age (r = -0.721 to -0.740), carotid distensibility (r = 0.625-0.629), and cardiorespiratory fitness (r = 0.333-0.351) (all P < 0.001). Multiple regression analysis demonstrated that BRS with ≥6 cycles of SSMs explained >60% of the variance in CVD risk factors. Therefore, our findings suggest that repeated SSMs significantly strengthens the association between BRS and CVD risk factors. Particularly, BRS with ≥6 cycles of SSMs is strongly associated with CVD risk.

Sedentary behavior and estimated nephron number in middle-aged and older adults with or without chronic kidney disease.

BACKGROUND: Excessive sedentary behavior may contribute to the pathogenesis of chronic kidney disease (CKD). The nephron index is a novel methodology for non-invasively estimating the number of functional nephrons, under the assumption that serum fibroblast growth factor 23 (FGF23) concentrations should correlate with phosphate excretion per nephron. The purpose of this study was to investigate the cross-sectional associations between daily sedentary time and the nephron index in middle-aged and older adults with or without CKD. METHODS: The daily time spent in sedentary behavior was assessed using a tri-axial accelerometer in 294 participants (182 non-CKD adults and 112 CKD patients). The nephron index value was calculated by measuring blood and spot urine phosphate and creatinine, together with serum FGF23 concentrations and estimated glomerular filtration rate. RESULTS: We observed that advancing age and CKD were associated with a progressive decrease in the nephron index value. Additionally, CKD patients with more sedentary time also had a greater nephron index decrease compared to those with less sedentary time (P < 0.05). Multiple linear regression analysis confirmed the independent association between sedentary time and the nephron index after adjusting for age, sex, presence of CKD, overweight/obesity, medication use, and total wear time (ß = -0.13, P = 0.035). CONCLUSIONS: These cross-sectional findings suggest that age- or CKD-related decreases in the estimated nephron number (that is, the nephron index) may be accelerated by increased sedentary behavior.

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.