Purpose This study aimed to investigate the effects of different work and recovery characteristics on the W′ reconstitution and to test the predictive capabilities of the W′BAL model. Methods Eleven male participants (22 ± 3 yr, 55 ± 4 mL·kg−1⋅min−1) completed three to five constant work rate tests to determine CP and W′. Subsequently, subjects performed 12 experimental trials, each comprising two exhaustive constant work rate bouts (i.e., WB1 and WB2), interspersed by an active recovery interval. In each trial, work bout characteristics (P4 or P8, i.e., the work rate predicted to result in exhaustion in 4 and 8 min, respectively), recovery work rate (33% CP or 66% CP), and recovery duration (2, 4, or 6 min) were varied. Actual (W′ACT) and model-predicted (W′PRED) reconstitution values of W′ were calculated. Results After 2, 4, and 6 min recovery, W′ACT averaged 46% ± 2.7%, 51.2% ± 3.3%, and 59.4% ± 4.1%, respectively (P = 0.003). W′ACT was 9.4% higher after recovery at 33% CP than at 66% CP (56.9% ± 3.9% vs 47.5% ± 3.2%) (P = 0.019). P4 exercise yielded a 11.3% higher W′ACT than P8 exercise (57.8% ± 3.9% vs 46.5% ± 2.7%) (P = 0.001). W′ACT was higher than W′PRED in the conditions P4-2 min (+29.7%), P4-4 min (+18.4%), and P8-2 min (+18%) (P < 0.01). A strong correlation (R = 0.68) between the rate of W′ depletion and W′ recovery was found (P = 0.001). Conclusion This study demonstrated that both the work and recovery characteristics of a prior exhaustive exercise bout can affect the W′ reconstitution. Results revealed a slower W′ reconstitution when the rate of W′ depletion was slower as well. Furthermore, it was shown that the current W′BAL model underestimates actual W′ reconstitution, especially after shorter recovery.

Exercise training is a powerful strategy to prevent and combat cardiovascular and metabolic diseases, although the integrative nature of the training-induced adaptations is not completely understood. We show that chronic blockade of histamine H1/H2 receptors led to marked impairments of microvascular and mitochondrial adaptations to interval training in humans. Consequently, functional adaptations in exercise capacity, whole-body glycemic control, and vascular function were blunted. Furthermore, the sustained elevation of muscle perfusion after acute interval exercise was severely reduced when H1/H2 receptors were pharmaceutically blocked. Our work suggests that histamine H1/H2 receptors are important transducers of the integrative exercise training response in humans, potentially related to regulation of optimal post-exercise muscle perfusion. These findings add to our understanding of how skeletal muscle and the cardiovascular system adapt to exercise training, knowledge that will help us further unravel and develop the exercise-is-medicine concept.

Background Recent studies suggest that acute-combined carnosine and anserine supplementation has the potential to improve the performance of certain cycling protocols. Yet, data on optimal dose, timing of ingestion, effective exercise range, and mode of action are lacking. Three studies were conducted to establish dosing and timing guidelines concerning carnosine and anserine intake and to unravel the mechanism underlying the ergogenic effects. Methods First, a dose response study A was conducted in which 11 men randomly received placebo, 10, 20, or 30 mg.kg −1 of both carnosine and anserine. They performed 3x maximal voluntary isometric contractions (MVC), followed by a 5 x 6 s repeated cycling sprint ability test (RSA), once before the supplement and 30 and 60 minutes after. In a second study, 15 men performed 3x MVCs with femoral nerve electrical stimulation, followed by an RSA test, once before 30 mg.kg −1 carnosine and anserine and 60 minutes after. Finally, in study C, eight men performed a high intensity cycling training after randomly ingesting 30 mg.kg −1 of carnosine and anserine, a placebo or antihistamines (reduce post-exercise blood flow) to investigate effects on muscle perfusion. Results Study A showed a 3% peak power (p = 0.0005; 95% CI = 0.07 to 0.27; ES = 0.91) and 4.5% peak torque (p = 0.0006; 95% CI = 0.12 to 0.50; ES = 0.87) improvement on RSA and MVC, with 30 mg.kg −1 carnosine + anserine ingestion 60 minutes before the performance yielding the best results. Study B found no performance improvement on group level; however, a negative correlation (r = −0.54; p = 0.0053; 95% CI = −0.77 to −0.19) was found between carnosinase enzyme activity (responsible for carnosine and anserine breakdown) and performance improvement. No effect of the supplement on neuromuscular function nor on muscle perfusion was found. Conclusions These studies reveal that acute ingestion of 30 mg.kg −1 of both carnosine and anserine, 60 minutes before a high intensity exercise, can potentially improve performance, such as short cycling sprints or maximal muscle contractions. Subjects with lower carnosinase activity, and thus a slower breakdown of circulating dipeptides, appear to benefit more from this ergogenic effect. Finally, neither the involvement of a direct effect on neuromuscular function, nor an indirect effect on recovery through increased muscle perfusion could be confirmed as potential mechanism of action. The ergogenic mechanism therefore remains elusive.

Manipulation of circulating histidine-containing dipeptides (HCD) has been shown to affect the development of diabetes and early-stage diabetic nephropathy (DN). The aim of the present study was to investigate whether such interventions, which potentially alter levels of circulating HCD, also affect the development of advanced-stage DN. Two interventions, aerobic exercise training and overexpression of the human carnosinase-1 (hCN1) enzyme, were tested. BTBR ob/ob mice were either subjected to aerobic exercise training (20 wk) or genetically manipulated to overexpress hCN1, and different diabetes- and DN-related markers were compared with control ob/ob and healthy (wild-type) mice. An acute exercise study was performed to elucidate the effect of obesity, acute running, and hCN1 overexpression on plasma HCD levels. Chronic aerobic exercise training did not affect the development of diabetes or DN, but hCN1 overexpression accelerated hyperlipidemia and aggravated the development of albuminuria, mesangial matrix expansion, and glomerular hypertrophy of ob/ob mice. In line, plasma, kidney, and muscle HCD were markedly lower in ob/ob versus wild-type mice, and plasma and kidney HCD in particular were lower in ob/ob hCN1 versus ob/ob mice but were unaffected by aerobic exercise. In conclusion, advanced glomerular damage is accelerated in mice overexpressing the hCN1 enzyme but not protected by chronic exercise training. Interestingly, we showed, for the first time, that the development of DN is closely linked to renal HCD availability. Further research will have to elucidate whether the stimulation of renal HCD levels can be a therapeutic strategy to reduce the risk for developing DN.