Habitual isomaltulose intake reduces arterial stiffness associated with postprandial hyperglycemia in middle-aged and elderly people: a randomized controlled trial.

Endothelin-1 (ET-1), produced by vascular endothelial cells, plays a pivotal role in the regulation of vascular tone. Isomaltulose, a naturally occurring sweetener and structural isomer of sucrose, reduces postprandial hyperglycemia, but its effect on arteriosclerosis due to hyperglycemia is unknown. The effects of 12 weeks of isomaltulose administration on ET-1 levels, a peptide that regulates arterial stiffness, blood pressure, and vascular tone, were tested before and after an oral glucose tolerance test. Fifty-four healthy middle-aged and older adults (30 men and 24 women) were divided into two groups: (1) a 25 g isomaltulose jelly drink intake group (Group I, 27 participants, mean age 55 ± 1 years) and (2) a sucrose jelly drink intake group (Group S, 27 participants, mean age 55 ± 1 years), each consuming isomaltulose or sucrose daily for 12 weeks, and a randomized, controlled study was conducted. Participants visited the laboratory before the intervention and 4, 8, and 12 weeks after the intervention to measure carotid-femoral (cf) and brachial-ankle (ba) pulse wave velocity (PWV), systolic blood pressure (BP), plasma glucose (PG), insulin, and ET-1 levels before and 60 and 120 min after a 75-g OGTT. baPWV, and ET-1 levels before intervention were significantly increased after 75-g OGTT compared to before 75-g OGTT in both groups (p < 0.05). The post-intervention baPWV, and ET-1 levels were significantly increased after 75-g OGTT in Group S compared to before 75-g OGTT (p < 0.05), whereas no significant changes were observed in Group I. These results suggest that consumption of isomaltulose, which has a lower GI than sucrose, is more effective in preventing the increases in systemic arterial stiffness associated with postprandial hyperglycemia in healthy middle-aged and older adults.

A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.

Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously.

Once-weekly muscle endurance and strength training prevents deterioration of muscle oxidative function and attenuates the degree of strength decline during 3-week forearm immobilization.

PURPOSE: Muscle unloading causes muscle function deterioration, but the extent to which training frequency or volume can be reduced while preserving muscle function during muscle unloading is unknown. We examined the effects of low-volume muscle endurance and strength training on forearm muscle oxidative capacity, endurance, and strength during a 3-week immobilization. METHODS: Twenty-seven, healthy, male volunteers were divided into four groups: immobilization only (IMM); immobilization with endurance and strength training, once-weekly (IMM + EST1) or twice-weekly (IMM + EST2); and control, without immobilization or training (CNT). Endurance training involved dynamic handgrip exercise, at 30% of maximal voluntary contraction (MVC), until exhaustion (~60 s). Strength training involved intermittent isometric handgrip exercise at 70% MVC (40 s). Muscle oxidative capacity was evaluated after exercise using the phosphocreatine recovery time constant using (31)phosphorus magnetic resonance spectroscopy. Endurance performance was evaluated according to the total work during dynamic handgrip exercise at 30% MVC at 1 Hz until exhaustion. RESULTS: Muscle oxidative capacity and total work deterioration was restricted to the IMM (P < 0.05) group. MVC decreased in the IMM and IMM + EST1 (P < 0.05) groups. However, the MVC amplitude decrease in the IMM + EST1 group was smaller than that in the IMM (P < 0.05) group. MVC remained unchanged in the other groups. CONCLUSION: During the 3-week immobilization, twice-weekly low-volume muscle endurance and strength training prevented deterioration in muscle strength, oxidative capacity, and endurance performance. Moreover, once-weekly muscle endurance and strength training prevented the deterioration of muscle oxidative capacity and endurance performance, and attenuated the degree of muscle strength decline.

Low-volume strength and endurance training prevent the decrease in exercise hyperemia induced by non-dominant forearm immobilization.

We examined the effect of 3-week upper limb immobilization on conduit artery cross-sectional area and peak hyperemia (BF(peak)) after exhaustive dynamic handgrip exercise (Ex(dyn)), and that of low-volume strength and endurance training during immobilization. Healthy volunteers (n = 21; mean age, 22 years) were divided into 3 groups: immobilization only (IMM; n = 7), immobilization with training (STR + END; n = 7), and control (no immobilization or training, CNT; n = 7). Endurance training comprised Ex(dyn) at 30% maximum voluntary contraction (MVC) (duration of each session, ~60 s; twice weekly). Strength training involved intermittent isometric handgrip exercise at 70% MVC (duration of each session, 40 s; twice weekly), repeated 10 times. We used ultrasound methods to measure the brachial artery cross-sectional area and the BF(peak) after Ex(dyn) for 5 min pre- and post-immobilization. We found a significant group by time interaction in BF(peak) (p < 0.05). A significant decrease was found in BF(peak) in the IMM (p < 0.05) between pre- and post-immobilization and a protective effect in the STR + END. The 3-week upper limb immobilization did not influence the baseline artery cross-sectional area. In conclusion, BF(peak) decreased after 3-week upper limb immobilization and a combination of strength training and endurance training preserved the blunted BF(peak).

A study of passive weight-bearing lower limb exercise effects on local muscles and whole body oxidative metabolism: a comparison with simulated horse riding, bicycle, and walking exercise.

BACKGROUND: We have developed an exercise machine prototype for increasing exercise intensity by means of passively exercising lower limb muscles. The purpose of the present study was to compare the passive exercise intensity of our newly-developed machine with the intensities of different types of exercises. We also attempted to measure muscle activity to study how these forms of exercise affected individual parts of the body. METHODS: Subjects were 14 healthy men with the following demographics: age 30 years, height 171.5 cm, weight 68.3 kg. They performed 4 types of exercise: Passive weight-bearing lower limb exercise (PWLLE), Simulated horse riding exercise (SHRE), Bicycle exercise, and Walking exercise, as described below at an interval of one week or longer. Oxygen uptake, blood pressure, heart rate, and electromyogram (EMG) were measured or recorded during exercise. At rest prior to exercise and immediately after the end of each exercise intensity, the oxygenated hemoglobin levels of the lower limb muscles were measured by near-infrared spectroscopy to calculate the rate of decline. This rate of decline was obtained immediately after exercise as well as at rest to calculate oxygen consumption of the lower limb muscles as expressed as a ratio of a post-exercise rate of decline to a resting one. RESULTS: The heart rate and oxygen uptake observed in PWLLE during maximal intensity were comparable to that of a 20-watt bicycle exercise or 2 km/hr walking exercise. Maximal intensity PWLLE was found to provoke muscle activity comparable to an 80-watt bicycle or 6 km/hr walking exercise. As was the case with the EMG results, during maximal intensity PWLLE, the rectus femoris muscle consumed oxygen in amounts identical to that of an 80-watt bicycle or a 6 km/hr walking exercise. CONCLUSION: Passive weight-bearing lower limb exercise using our trial machine could provide approximately 3 MET of exercise and the thigh exhibited muscle activity equivalent to that of 80-watt bicycle or 6 km/hr walking exercise. Namely, given the same oxygen uptake, PWLLE exceeded bicycle or walking exercise in muscle activity, thus PWLLE is believed to strengthen muscle power while reducing the load imposed on the cardiopulmonary system.

Low-volume muscular endurance and strength training during 3-week forearm immobilization was effective in preventing functional deterioration.

PURPOSE: The purpose of this study was to determine whether endurance and strength hand grip exercises during 3-week upper limb immobilization preserve muscle oxidative capacity, endurance performance and strength. METHODS: Ten healthy adult men underwent non-dominant forearm immobilization by plaster cast for 21 days. Five healthy adult subjects were designated as the immobilization (IMM) group and five were designated as the immobilization + training (IMM+TRN) group. Grip strength, forearm circumference, dynamic handgrip endurance and muscle oxygenation response were measured before and after the 21 day immobilization period. Using near-infrared spectroscopy (NIRS), muscle oxygen consumption recovery (VO2mus) was recorded after a submaximal exercise and the recovery time constant (TcVO2mus) was calculated. Reactive hyperemic oxygenation recovery was evaluated after 5 minutes ischemia. Two training programs were performed by the IMM+TRN group twice a week. One exercise involved a handgrip exercise at 30% maximum voluntary contraction (MVC) at a rate of 1 repetition per 1 second until exhaustion (about 60 seconds). The other involved a handgrip exercise at 70% MVC for 2 seconds with a 2 second rest interval, repeated 10 times (40 seconds). RESULTS: There was a significant group-by-time interaction between the IMM and IMM+TRN groups in the TcVO2mus (p = 0.032, F = 6.711). A significant group-by-time interaction was observed between the IMM and IMM+TRN groups in the MVC (p = 0.001, F = 30.415) and in grip endurance (p = 0.014, F = 9.791). No significant group-by-time interaction was seen in forearm circumference and reactive hyperemic oxygenation response either in IMM or IMM+TRN group. CONCLUSION: The training programs during immobilization period used in this experiment were effective in preventing a decline in muscle oxidative function, endurance and strength.

Association between regional quadriceps oxygenation and blood oxygen saturation during normoxic one-legged dynamic knee extension.

It is not clear whether muscle oxygenation (O(2-NIRS)) measured by near-infrared spectroscopy (NIRS) correlates with femoral venous SO2 (S(fv)o2) during normoxic exercise. Therefore, the purpose of this study was to compare physiologically calibrated O(2-NIRS) with S(fv)o2 in subjects performing one-legged dynamic knee extension exercise (1L-KEE). Five healthy male subjects (age 25+/-2 year, height 177.8+/-4.8 cm, body weight 67.1 +/- 5.0 kg; mean +/- SD) performed 1L-KEE at 20, 40, and 60% of peak work rate (WR-peak) each for 4 min. S(fv)o2 was measured at rest and during the 3rd minute of each work rate. O(2-NIRS) was continuously monitored in a proximal region of the vastus lateralis (VL-p), a distal region of VL (VL-d), and a proximal region of the rectus femoris (RF-p). S(fv)o2 was 56.0% at rest and decreased to 36.6 at 20% WR-peak, 35.8 at 40% WR-peak, and 31.1 at 60% WR-peak. There was a significant correlation between O(2-NIRS) and S(fv)o2(VL-p: r (2) = 0.62, VL-d: r2 = 0.35, RF-p: r2 = 0.62, with a moderate variation among individuals at each site; residual values = 4.83 - 11.75). These data indicate that NIRS measurement provides a reflection of S(fv)o2 during 20-60% WR-peak of normoxic 1L-KEE.

Muscle oxidative metabolism accelerates with mild acidosis during incremental intermittent isometric plantar flexion exercise.

BACKGROUND: It has been thought that intramuscular ADP and phosphocreatine (PCr) concentrations are important regulators of mitochondorial respiration. There is a threshold work rate or metabolic rate for cellular acidosis, and the decrease in muscle PCr is accelerated with drop in pH during incremental exercise. We tested the hypothesis that increase in muscle oxygen consumption (o2mus) is accelerated with rapid decrease in PCr (concomitant increase in ADP) in muscles with drop in pH occurs during incremental plantar flexion exercise. METHODS: Five male subjects performed a repetitive intermittent isometric plantar flexion exercise (6-s contraction/4-s relaxation). Exercise intensity was raised every 1 min by 10% maximal voluntary contraction (MVC), starting at 10% MVC until exhaustion. The measurement site was at the medial head of the gastrocnemius muscle. Changes in muscle PCr, inorganic phosphate (Pi), ADP, and pH were measured by 31P-magnetic resonance spectroscopy. o2mus was determined from the rate of decrease in oxygenated hemoglobin and/or myoglobin using near-infrared continuous wave spectroscopy under transient arterial occlusion. Electromyogram (EMG) was also recorded. Pulmonary oxygen uptake (o2pul ) was measured by the breath-by-breath gas analysis. RESULTS: EMG amplitude increased as exercise intensity progressed. In contrast, muscle PCr, ADP, o2mus, and o2pul did not change appreciably below 40% MVC, whereas above 40% MVC muscle PCr decreased, and ADP, o2mus, and o2pul increased as exercise intensity progressed, and above 70% MVC, changes in muscle PCr, ADP, o2mus, and o2pul accelerated with the decrease in muscle pH (~6.78). The kinetics of muscle PCr, ADP, o2mus, and o2pul were similar, and there was a close correlation between each pair of parameters (r = 0.969~0.983, p < 0.001). CONCLUSION: With decrease in pH muscle oxidative metabolism accelerated and changes in intramuscular PCr and ADP accelerated during incremental intermittent isometric plantar flexion exercise. These results suggest that rapid changes in muscle PCr and/or ADP with mild acidosis stimulate accelerative muscle oxidative metabolism.

Muscle oxygen consumption at onset of exercise by near infrared spectroscopy in humans.

In this study, we tried to continuously measure muscle oxygen consumption (m-VO2) by near infrared spectroscopy (NIRS) without arterial occlusions. We used an intermittent isometric exercise at high intensity, which elicits a spontaneous occlusion of the blood flow to the muscle due to an increase in intramuscular pressure. Changes in muscle oxygenation and phosphocreatine (PCr) concentration were monitored in 5 subjects during an intermittent isometric exercise (5 sec. contraction/5 sec. relaxation) at 50% of maximum voluntary contraction for 3 minutes. The rate of deoxygenation was measured from the 2nd sec. to the 3rd sec. of each muscle contraction. The rate of deoxygenation at the onset of exercise followed an exponential time course with a time constant of 42.0 +/- 12.5 sec. (mean +/- SD). This value agreed with the time constant of the decrease in PCr (48.2 +/- 10.2 sec.). This result suggests that m-VO2 was successfully monitored with a time resolution of 10 sec. by NIRS during exercise without arterial occlusion.

Effect of moderate acute exercise on expression of mRNA involved in the calcineurin signaling pathway in human skeletal muscle.

Calcineurin, a calcium-regulated protein phosphatase, activates gene expression specific to slow muscle fibers by dephosphorylating a family of the nuclear factor of activated T cells (NFAT), which cooperates with myocyte enhancer factor-2 (MEF2) and AP-1. However, it remains unknown how acute exercise influences this signaling pathway and leads to the development of slow muscle fibers. In the present study, we investigated the effect of moderate acute exercise on mRNA expression of genes in the calcineurin signaling pathway in human skeletal muscle. Five healthy volunteers underwent 1 h bicycle ergometer at 50%VO2max, and vastus lateralis muscle biopsies were collected before and after exercise. Four hours after exercise, alterations in mRNA expression of NFAT 1-3 were observed with a wide variety among subjects, while c-fos mRNA was significantly induced in all subjects. By contrast, the expression of calcineurin, MEF2, and myocyte-enriched calcineurin-interacting protein 1 (MCIP1) remained unchanged. These results suggest that even moderate acute exercise may change mRNA expression of genes in the calcineurin-signaling pathway.