Jason G.E. Zelt

Resveratrol supplementation does not augment performance adaptations or fibre-type-specific responses to high-intensity interval training in humans

The present study examined the effect of concurrent exercise training and daily resveratrol (RSV) supplementation (150 mg) on training-induced adaptations following low-dose high-intensity interval training (HIIT). Sixteen recreationally active (∼22 years, ∼51 mL·kg(-1)·min(-1)) men were randomly assigned in a double-blind fashion to either the RSV or placebo group with both groups performing 4 weeks of HIIT 3 days per week. Before and after training, participants had a resting muscle biopsy taken, completed a peak oxygen uptake test, a Wingate test, and a submaximal exercise test. A main effect of training (p < 0.05) and interaction effect (p < 0.05) on peak aerobic power was observed; post hoc pairwise comparisons revealed that a significant (p < 0.05) increase occurred in the placebo group only. Main effects of training (p < 0.05) were observed for both peak oxygen uptake (placebo - pretraining: 51.3 ± 1.8, post-training: 54.5 ± 1.5 mL·kg(-1)·min(-1), effect size (ES) = 0.93; RSV - pretraining: 49.6 ± 2.2, post-training: 52.3 ± 2.5 mL·kg(-1)·min(-1), ES = 0.50) and Wingate peak power (placebo: pretraining: 747 ± 39, post-training: 809 ± 31 W, ES = 0.84; RSV - pretraining: 679 ± 39, post-training: 691 ± 43 W, ES = 0.12). Fibre-type distribution was unchanged, while a main effect of training (p < 0.05) was observed for succinate dehydrogenase activity and glycogen content, but not α-glycerophosphate dehydrogenase activity or intramuscular lipids in type I and IIA fibres. The fold change in PGC-1α, SIRT1, and SOD2 gene expression following training was significantly (p < 0.05) lower in the RSV group than placebo. These results suggest that concurrent exercise training and RSV supplementation may alter the normal training response induced by low-volume HIIT.

Changes in mechanisms proposed to mediate fat loss following an acute bout of high-intensity interval and endurance exercise.

The purpose of this study was to investigate the acute effects of endurance exercise (END; 65% V̇O2peak for 60 min) and high-intensity interval exercise (HIE; four 30 s Wingates separated by 4.5 min of active rest) on cardiorespiratory, hormonal, and subjective appetite measures that may account for the previously reported superior fat loss with low volume HIE compared with END. Recreationally active males (n = 18) completed END, HIE, and control (CON) protocols. On each test day, cardiorespiratory measures including oxygen uptake (V̇O2), respiratory exchange ratio (RER), and heart rate were recorded and blood samples were obtained at baseline (BSL), 60 min after exercise, and 180 min after exercise (equivalent times for CON). Subjective measures of appetite (hunger, fullness, nausea, and prospective consumption) were assessed using visual analogue scales, administered at BSL, 0, 60, 120, and 180 min after exercise. No significant differences in excess postexercise oxygen consumption (EPOC) were observed between conditions. RER was significantly (P < 0.05) depressed in HIE compared with CON at 60 min after exercise, yet estimates of total fat oxidation over CON were not different between HIE and END. No differences in plasma adiponectin concentrations between protocols or time points were present. Epinephrine and norepinephrine were significantly (P < 0.05) elevated immediately after exercise in HIE compared with CON. Several subjective measures of appetite were significantly (P < 0.05) depressed immediately following HIE. Our data indicate that increases in EPOC or fat oxidation following HIE appear unlikely to contribute to the reported superior fat loss compared with END.

Incidence of nonresponse and individual patterns of response following sprint interval training

The current study sought to explore the incidence of nonresponders for maximal or submaximal performance following a variety of sprint interval training (SIT) protocols. Data from 63 young adults from 5 previously published studies were utilized in the current analysis. Nonresponders were identified using 2 times the typical error (TE) of measurement for peak oxygen uptake (2 × TE = 1.74 mL/(kg·min)), lactate threshold (2 × TE = 15.7 W), or 500 kcal time-to-completion (TTC; 2 × TE = 306 s) trial. TE was determined on separate groups of participants by calculating the test-retest variance for each outcome. The overall rate of nonresponders for peak oxygen uptake across all participants studied was 22% (14/63) with 4 adverse responders observed. No nonresponders for peak oxygen uptake were observed in studies where participants trained 4 times per week (n = 18), while higher rates were observed in most studies requiring training 3 times per week (30%-50%; n = 45). A nonresponse rate of 44% (8/18) and 50% (11/22) was observed for the TTC test and lactate threshold, respectively. No significant correlations were observed between the changes in peak oxygen uptake and TTC (r = 0.014; p = 0.96) or lactate threshold (r = 0.17; p = 0.44). The current analysis demonstrates a significant incidence of nonresponders for peak oxygen uptake and heterogeneity in the individual patterns of response following SIT. Additionally, these data support the importance of training dose and suggest that the incidence of nonresponse may be mitigated by utilizing the optimal dose of SIT.

Magnesium Modifies the impact of Calcitriol Treatment on Vascular Calcification in Experimental Chronic Kidney Disease

Chronic kidney disease (CKD) patients are commonly treated with vitamin D analogs, such as calcitriol. Recent epidemiologic evidence revealed a significant interaction between vitamin D and magnesium, since an inverse relationship between vitamin D levels and mortality mainly occurs in patients with a high magnesium intake. The aim of the study was to assess the mechanisms involved by determining whether magnesium alone or combined with calcitriol treatments differentially impacts vascular calcification (VC) in male Sprague-Dawley rats with adenine-induced CKD. Treatment with moderate doses of calcitriol (80 μg/kg) suppressed parathyroid hormone to near or slightly below control levels. Given alone, this dose of calcitriol increased the prevalence of VC; however, when magnesium was given in combination, the severity of calcification was attenuated in the abdominal aorta (51% reduction), iliac (44%), and carotid arteries (46%) compared with CKD controls. The decreases in vascular calcium content were associated with a 20–50% increase in vascular magnesium. Calcitriol treatment alone significantly decreased TRPM7 protein (↓ to ∼11%), whereas the combination treatment increased both mRNA (1.7×) and protein (6.8×) expression compared with calcitriol alone. In summary, calcitriol increased VC in certain conditions, but magnesium prevented the reduction in TRPM7 and reduced the severity of VC, thereby increasing the bioavailable magnesium in the vascular microenvironment. These findings suggest that modifying the adverse effect profile of calcitriol with magnesium may be a plausible approach to benefiting the increasing number of CKD patients being prescribed calcitriol.

Calcitriol Accelerates Vascular Calcification Irrespective of Vitamin K Status in a Rat Model of Chronic Kidney Disease with Hyperphosphatemia and Secondary Hyperparathyroidism

Patients with chronic kidney disease (CKD) have a markedly increased risk for developing cardiovascular disease. Nontraditional risk factors, such as increased phosphate retention, increased serum fibroblast growth factor 23 (FGF-23), and deficiencies in vitamins D and K metabolism, likely play key roles in the development of vascular calcification during CKD progression. Calcitriol [1,25-(OH)2-D3] is a key transcriptional regulator of matrix Gla protein, a vitamin K–dependent protein that inhibits vascular calcification. We hypothesized that calcitriol treatment would inhibit the development of vascular calcification and this inhibition would be dependent on vitamin K status in a rat model of CKD. Rats were treated with dietary adenine (0.25%) to induce CKD, with either 0, 20, or 80 ng/kg of calcitriol with low or high dietary vitamin K1 (0.2 or 100 mg/kg) for 7 weeks. Calcitriol at both lower (20 ng/kg) and moderate (80 ng/kg) doses increased the severity of vascular calcification, and contrary to our hypothesis this was not significantly improved by high dietary vitamin K1. Calcitriol had a dose-dependent effect on: 1) lowering serum parathyroid hormone, 2) increasing serum calcium, and 3) increasing serum FGF-23. Calcitriol treatment significantly increased aortic expression of the calcification genes Runx2 and Pit-1. These data also implicate impaired vitamin D catabolism in CKD, which may contribute to the development of calcitriol toxicity and increased vascular calcification. The present findings demonstrate that in an adenine-induced rat model of CKD calcitriol treatment at doses as low as 20 ng/kg can increase the severity of vascular calcification regardless of vitamin K status.

Acute Tissue Mineral Deposition in Response to a Phosphate Pulse in Experimental CKD: VASCULAR MINERAL ACCRUAL IN CKD

Pathogenic accumulation of calcium (Ca) and phosphate (PO4) in vasculature is a sentinel of advancing cardiovascular disease in chronic kidney disease (CKD). This study sought to characterize acute distribution patterns of radiolabeled 33PO4 and 45Ca in cardiovascular tissues of rats with CKD (0.25% dietary adenine). The disposition of 33PO4 and 45Ca was assessed in blood and 36 tissues after a 10‐minute intravenous infusion of one of the following: (i) PO4 pulse + tracer 33PO4; (ii) PO4 pulse + tracer 45Ca; or (iii) saline + tracer 45Ca in CKD and non‐CKD animals. After the infusion, 33PO4 in blood was elevated (2.3× at 10 minutes, 3.5× at 30 minutes, p < 0.05) in CKD compared with non‐CKD. In contrast, there was no difference in clearance of 45Ca from the blood. Compared with controls, CKD rats had a markedly increased 33PO4 incorporation in several tissues (skeletal muscle, 7.8×; heart, 5.5×), but accrual was most pronounced in the vasculature (24.8×). There was a significant, but smaller, increase in 45Ca accrual in the vasculature of CKD rats (1.25×), particularly in the calcified rat, in response to the acute phosphate load. Based on the pattern of tissue uptake of 33PO4 and 45Ca, this study revealed that an increase in circulating PO4 is an important stimulus for the accumulation of these minerals in vascular tissue in CKD. This response is further enhanced when vascular calcification is also present. The finding of enhanced vascular mineral deposition in response to an acute PO4 pulse provides evidence of significant tissue‐specific susceptibility to calcification.