We first tested the hypothesis that consuming a high-fructose corn syrup (HFCS)-sweetened soft drink augments kidney vasoconstriction to sympathetic stimulation compared with water ( study 1). In a second study, we examined the mechanisms underlying these observations ( study 2). In study 1, 13 healthy adults completed a cold pressor test, a sympathoexcitatory maneuver, before (preconsumption) and 30 min after drinking 500 mL of decarbonated HFCS-sweetened soft drink or water (postconsumption). In study 2, venous blood samples were obtained in 12 healthy adults before and 30 min after consumption of 500 mL water or soft drinks matched for caffeine content and taste, which were either artificially sweetened (Diet trial), sucrose-sweetened (Sucrose trial), or sweetened with HFCS (HFCS trial). In both study 1 and study 2, vascular resistance was calculated as mean arterial pressure divided by blood velocity, which was measured via Doppler ultrasound in renal and segmental arteries. In study 1, HFCS consumption increased vascular resistance in the segmental artery at rest (by 0.5 ± 0.6 mmHg·cm−1·s−1, P = 0.01) and during the cold pressor test (average change: 0.5 ± 1.0 mmHg·cm−1·s−1, main effect: P = 0.05). In study 2, segmental artery vascular resistance increased in the HFCS trial (by 0.8 ± 0.7 mmHg·cm−1·s−1, P = 0.02) but not in the other trials. Increases in serum uric acid were greater in the HFCS trial (0.3 ± 0.4 mg/dL, P ≤ 0.04) compared with the Water and Diet trials, and serum copeptin increased in the HFCS trial (by 0.8 ± 1.0 pmol/L, P = 0.06). These findings indicate that HFCS acutely increases vascular resistance in the kidneys, independent of caffeine content and beverage osmolality, which likely occurs via simultaneous elevations in circulating uric acid and vasopressin.

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Exercise likely has numerous benefits for brain and cognition. However, those benefits and their causes remain imprecisely defined. If the brain does benefit from exercise it does so primarily through cumulative brief, “acute” exposures over a lifetime. The Dementia Risk and Dynamic Response to Exercise (DYNAMIC) clinical trial seeks to characterize the acute exercise response in cerebral perfusion, and circulating neurotrophic factors in older adults with and without the apolipoprotein e4 genotype (APOE4), the strongest genetic predictor of sporadic, late onset Alzheimer’s disease. DYNAMIC will enroll 60 older adults into a single moderate intensity bout of exercise intervention, measuring pre- and post-exercise cerebral blood flow (CBF) using arterial spin labeling, and neurotrophic factors. We expect that APOE4 carriers will have poor CBF regulation, i.e. slower return to baseline perfusion after exercise, and will demonstrate blunted neurotrophic response to exercise, with concentrations of neurotrophic factors positively correlating with CBF regulation. Preliminary findings on 7 older adults and 9 younger adults demonstrate that the experimental method can capture CBF and neurotrophic response over a time course. This methodology will provide important insight into acute exercise response and potential directions for clinical trial outcomes.ClinicalTrials.gov NCT04009629, Registered 05/07/2019.

Background Physical exercise may support brain health and cognition over the course of typical aging. The goal of this nonrandomized clinical trial was to examine the effect of an acute bout of aerobic exercise on brain blood flow and blood neurotrophic factors associated with exercise response and brain function in older adults with and without possession of the Apolipoprotein epsilon 4 (APOE4) allele, a genetic risk factor for developing Alzheimer’s. We hypothesized that older adult APOE4 carriers would have lower cerebral blood flow regulation and would demonstrate blunted neurotrophic response to exercise compared to noncarriers. Methods Sixty-two older adults (73±5 years old, 41 female [67%]) consented to this prospectively enrolling clinical trial, utilizing a single arm, single visit, experimental design, with post-hoc assessment of difference in outcomes based on APOE4 carriership. All participants completed a single 15-minute bout of moderate-intensity aerobic exercise. The primary outcome measure was change in cortical gray matter cerebral blood flow in cortical gray matter measured by magnetic resonance imaging (MRI) arterial spin labeling (ASL), defined as the total perfusion (area under the curve, AUC) following exercise. Secondary outcomes were changes in blood neurotrophin concentrations of insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and brain derived neurotrophic factor (BDNF). Results Genotyping failed in one individual (n = 23 APOE4 carriers and n = 38 APOE4 non-carriers) and two participants could not complete primary outcome testing. Cerebral blood flow AUC increased immediately following exercise, regardless of APOE4 carrier status. In an exploratory regional analyses, we found that cerebral blood flow increased in hippocampal brain regions, while showing no change in cerebellum across both groups. Among high inter-individual variability, there were no significant changes in any of the 3 neurotrophic factors for either group immediately following exercise. Conclusions Our findings show that both APOE4 carriers and non-carriers show similar effects of exercise-induced increases in cerebral blood flow and neurotrophic response to acute aerobic exercise. Our results provide further evidence that acute exercise-induced increases in cerebral blood flow may be regional specific, and that exercise-induced neurotrophin release may show a differential effect in the aging cardiovascular system. Results from this study provide an initial characterization of the acute brain blood flow and neurotrophin responses to a bout of exercise in older adults with and without this known risk allele for cardiovascular disease and Alzheimer’s disease. Trial registration Dementia Risk and Dynamic Response to Exercise (DYNAMIC); Identifier: NCT04009629.

In healthy humans, fructose-sweetened water consumption increases blood pressure variability (BPV) and decreases spontaneous cardiovagal baroreflex sensitivity (cBRS) and heart rate variability (HRV). However, if consuming commercially available soft drinks containing high levels of fructose elicits similar responses is unknown. We hypothesized that high-fructose corn syrup (HFCS) sweetened soft drink consumption increases BPV and decreases cBRS and HRV to a greater extent compared to artificially-sweetened (Diet) and sucrose-sweetened (Sucrose) soft drinks and water. Twelve subjects completed four randomized, double-blinded trials in which they drank 500 mL of water or commercially available soft drinks matched for taste and caffeine content. We continuously measured beat-to-beat blood pressure (photoplethysmography) and R-R interval (ECG) before and 30 minutes after drink consumption during supine rest for 5 minutes during spontaneous and paced breathing. BPV was evaluated using standard deviation (SD), average real variability (ARV), and successive variation (SV) methods for systolic and diastolic blood pressure. cBRS was assessed using the sequence method. HRV was evaluated using the root mean square of successive differences in R-R interval (RMSSD). There were no differences between conditions in the magnitude of change from baseline in SD, ARV, and SV (P≥0.07). There were greater reductions in cBRS during spontaneous breathing in the HFCS (-3±5 ms/mmHg) and Sucrose (-3±5 ms/mmHg) trials compared to Water (+1±5 ms/mmHg, P<0.03). During paced breathing, HFCS evoked greater reductions in RMSSD compared to Water (-26±34 vs. +2±26 ms, P<0.01). These findings suggest that sugar-sweetened soft drink consumption alters cBRS and HRV but not BPV.