Endothelial dysfunction correlates with exaggerated exercise pressor response during whole body maximal exercise in chronic kidney disease.

Chronic kidney disease (CKD) patients have exercise intolerance associated with increased cardiovascular mortality. Previous studies demonstrate that blood pressure (BP) and sympathetic nerve responses to handgrip exercise are exaggerated in CKD. These patients also have decreased nitric oxide (NO) bioavailability and endothelial dysfunction, which could potentially lead to an impaired ability to vasodilate during exercise. We hypothesized that CKD patients have exaggerated BP responses during maximal whole body exercise and that endothelial dysfunction correlates with greater exercise pressor responses in these patients. Brachial artery flow-mediated dilation (FMD) was assessed before maximal treadmill exercise in 56 participants: 38 CKD (56.7 ± 1.2 yr old, 38 men) and 21 controls (52.8 ± 1.8 yr old, 20 men). During maximal treadmill exercise, the slope-of-rise in systolic BP (+10.32 vs. +7.75 mmHg/stage, P < 0.001), mean arterial pressure (+3.50 vs. +2.63 mmHg/stage, P = 0.004), and heart rate (+11.87 vs. +10.69 beats·min-1·stage-1, P = 0.031) was significantly greater in CKD compared with controls. Baseline FMD was significantly lower in CKD (2.76 ± 0.42% vs. 5.84 ± 0.97%, P = 0.008). Lower FMD values were significantly associated with a higher slope-of-rise in systolic BP (+11.05 vs. 8.71 mmHg/stage, P = 0.003) during exercise in CKD, as well as poorer exercise capacity measured as peak oxygen uptake (V̇o2peak; 19.47 ± 1.47 vs. 24.57 ± 1.51 ml·min-1·kg-1, P < 0.001). These findings demonstrate that low FMD in CKD correlates with augmented BP responses during exercise and lower V̇o2peak, suggesting that endothelial dysfunction may contribute to exaggerated exercise pressor responses and poor exercise capacity in CKD patients.

Tetrahydrobiopterin ameliorates the exaggerated exercise pressor response in patients with chronic kidney disease: a randomized controlled trial.

Chronic kidney disease (CKD) patients have an exaggerated increase in blood pressure (BP) during rhythmic handgrip exercise (RHG 20%) and static handgrip exercise (SHG 30%). Nitric oxide levels increase during exercise and help prevent excessive hypertension by both increasing vasodilation and reducing sympathetic nerve activity (SNA). Therefore, we hypothesized that tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthase, would ameliorate the exaggerated exercise pressor response in CKD patients. In a randomized, double-blinded, placebo-controlled trial, we tested the effects of 12 wk of sapropterin dihydrochloride (6R-BH4; n = 18) versus placebo (n = 14) treatement on BP and muscle SNA (MSNA) responses during RHG 20% and SHG 30% in CKD patients. The 6R-BH4-treated group had a significantly lower systolic BP (+6 ± 1 vs. +13 ± 2 mmHg, P = 0.002) and mean arterial pressure response (+5 ± 1 vs. +10 ± 2 mmHg, P = 0.020) during RHG 20% and a significantly lower systolic BP response (+19 ± 3 vs. +28 ± 3 mmHg, P = 0.043) during SHG 30%. Under baseline conditions, there was no significant difference in MSNA responses between the groups; however, when the BP response during exercise was equalized between the groups using nitroprusside, the 6R-BH4-treated group had a significantly lower MSNA response during RHG 20% (6R-BH4 vs. placebo, +12 ± 1 vs. +21 ± 2 bursts/min, P = 0.004) but not during SHG 30%. These findings suggest that 6R-BH4 ameliorates the augmented BP response during RHG 20% and SHG 30% in CKD patients. A reduction in reflex activation of SNA may contribute to the decreased exercise pressor response during RHG 20% but not during SHG 30% in CKD patients.

The Role of Diet on the Gut Microbiome, Mood and Happiness.

The gut microbiome may be both helpful and harmful, and not only is it affected by diet, it has also been shown to affect mental health including personality, mood, anxiety and depression. In this clinical study we assessed dietary nutrient composition, mood, happiness, and the gut microbiome in order to understand the role of diet in the gut microbiome and how that affects mood and happiness. For this pilot study, we enrolled 20 adults to follow this protocol: recording a 2-day food log, sampling their gut microbiome, and completing five validated surveys of mental health, mood, happiness and well-being, followed by a minimum 1 week diet change and repeating the food log, microbiome sampling and the 5 surveys. The change from a predominantly Western diet to vegetarian, Mediterranean and ketogenic diets led to changes in calorie and fiber intake. After the diet change, we observed significant changes in measures of anxiety, well-being and happiness, and without changes in gut microbiome diversity. We found strong correlations between greater consumption of fat and protein to lower anxiety and depression, while consuming higher percentages of carbohydrates was associated with increased stress, anxiety, and depression. We also found strong negative correlations between total calories and total fiber intake with gut microbiome diversity without correlations to measures of mental health, mood or happiness. We have shown that changing diet affects mood and happiness, that greater fat and carbohydrate intake is directly associated with anxiety and depression and inversely correlated with gut microbiome diversity. This study is an important step towards understanding how our diet affects the gut microbiome and in turn our mood, happiness and mental health.

Body composition and lung function in cystic fibrosis and their association with adiposity and normal-weight obesity.

OBJECTIVES: This study aimed to evaluate the relationship between lung function and body composition in cystic fibrosis (CF) and examine the presence of normal-weight obesity (NWO), a high body fat percentage with a normal body mass index (BMI), in this population. METHODS: In a pilot, cross-sectional study, 32 subjects with CF and a reference group of 20 adults without CF underwent body composition analysis with air displacement plethysmography. NWO was defined as a BMI <25 kg/m(2) and body fat >30% (for women) or >23% (for men). Lung function in subjects with CF was determined by the percentage of predicted forced expiratory volume in 1 s (FEV1% predicted). RESULTS: Despite lower BMI and fat-free mass index (P < 0.01), fat mass index and percent body fat did not differ between subjects with CF and the reference group. Among subjects with CF, FEV1% predicted was positively associated with fat-free mass index (ß = 6.31 ± 2.93, P = 0.04) and inversely associated with fat mass index (ß = -6.44 ± 2.93, P = 0.04), after adjusting for age, sex, and BMI. Ten subjects with CF (31%) had NWO, which corresponded with lower fat-free mass index and FEV1% predicted compared with overweight subjects (P = 0.006 and 0.004, respectively). CONCLUSIONS: Excess adiposity, particularly in the form of NWO, was inversely associated with lung function in CF. Larger prospective studies should be undertaken to confirm these findings and determine the long-term metabolic and clinical consequences of excess adiposity in CF. As the lifespan of individuals with CF increases, nutrition screening protocols, which primarily rely on BMI, may require reassessment.

Habitual nutrient intake in HIV-infected youth and associations with HIV-related factors.

Few studies have evaluated habitual nutrient intake among HIV-infected youth in the United States, even though diet may influence disease progression and risk of comorbidities. This study determined habitual micronutrient and macronutrient intake in HIV-infected youth. HIV-infected subjects and healthy controls 1-25 years old were prospectively enrolled. Nutrient intake was assessed via 24-h dietary recalls performed every 3 months for 1 year and compared to recommended intake from the U.S. Dietary Reference Intakes (DRIs) and Acceptable Macronutrient Distribution Ranges (AMDRs). Subjects with two or more food recalls were analyzed (175 HIV(+) and 43 healthy controls). Groups were similar in age, race, sex, body mass index, and kilocalorie intake. In both groups, intake of several micronutrients was below the DRI. In addition, HIV(+) subjects had a lower percentage DRI than controls for vitamins A, D, E, pantothenic acid, magnesium, calcium, folate, and potassium. HIV(+) subjects' percentage caloric intake from fat was above the AMDR and was higher than controls. Caloric intake was negatively correlated with current and nadir CD4 count. Zinc, riboflavin, and magnesium percentage DRI were positively associated with current CD4 count. In HIV(+) subjects not on antiretroviral therapy, HIV-1 RNA levels were negatively correlated with protein intake. HIV(+) youth have an inadequate dietary intake of several essential nutrients and poorer dietary intake compared to controls. Intake of some nutrients was associated with important HIV-related factors. Further investigation is warranted to determine the impact of dietary intake of specific nutrients on HIV progression and chronic complication risk in this population.