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1.
Testosterone Administration During Energy Deficit Suppresses Hepcidin and Increases Iron Availability for Erythropoiesis.
Hennigar, SR, Berryman, CE, Harris, MN, Karl, JP, Lieberman, HR, McClung, JP, Rood, JC, Pasiakos, SM
The Journal of clinical endocrinology and metabolism. 2020;(4)
Abstract
CONTEXT Severe energy deprivation markedly inhibits erythropoiesis by restricting iron availability for hemoglobin synthesis. OBJECTIVE The objective of this study was to determine whether testosterone supplementation during energy deficit increased indicators of iron turnover and attenuated the decline in erythropoiesis compared to placebo. DESIGN This was a 3-phase, randomized, double-blind, placebo-controlled trial. SETTING The study was conducted at the Pennington Biomedical Research Center. PATIENTS OR OTHER PARTICIPANTS Fifty healthy young males. INTERVENTION(S): Phase 1 was a 14-day free-living eucaloric controlled-feeding phase; phase 2 was a 28-day inpatient phase where participants were randomized to 200 mg testosterone enanthate/week or an isovolumetric placebo/week during an energy deficit of 55% of total daily energy expenditure; phase 3 was a 14-day free-living, ad libitum recovery period. MAIN OUTCOME MEASURE(S): Indices of erythropoiesis, iron status, and hepcidin and erythroferrone were determined. RESULTS Hepcidin declined by 41%, indicators of iron turnover increased, and functional iron stores were reduced with testosterone administration during energy deficit compared to placebo. Testosterone administration during energy deficit increased circulating concentrations of erythropoietin and maintained erythropoiesis, as indicated by an attenuation in the decline in hemoglobin and hematocrit with placebo. Erythroferrone did not differ between groups, suggesting that the reduction in hepcidin with testosterone occurs through an erythroferrone-independent mechanism. CONCLUSION These findings indicate that testosterone suppresses hepcidin, through either direct or indirect mechanisms, to increase iron turnover and maintain erythropoiesis during severe energy deficit. This trial was registered at www.clinicaltrials.gov as #NCT02734238.
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Effects of oral administration of common antioxidant supplements on the energy metabolism of red blood cells. Attenuation of oxidative stress-induced changes in Rett syndrome erythrocytes by CoQ10.
Di Pierro, D, Ciaccio, C, Sbardella, D, Tundo, GR, Bernardini, R, Curatolo, P, Galasso, C, Pironi, V, Coletta, M, Marini, S
Molecular and cellular biochemistry. 2020;(1-2):101-113
Abstract
Nutritional supplements are traditionally employed for overall health and for managing some health conditions, although controversies are found concerning the role of antioxidants-mediated benefits in vivo. Consistently with its critical role in systemic redox buffering, red blood cell (RBC) is recognized as a biologically relevant target to investigate the effects of oxidative stress. In RBC, reduction of the ATP levels and adenylate energy charge brings to disturbance in intracellular redox status. In the present work, several popular antioxidant supplements were orally administrated to healthy adults and examined for their ability to induce changes on the energy metabolism and oxidative status in RBC. Fifteen volunteers (3 per group) were treated for 30 days per os with epigallocatechin gallate (EGCG) (1 g green tea extract containing 50% EGCG), resveratrol (325 mg), coenzyme Q10 (CoQ10) (300 mg), vitamin C (1 g), and vitamin E (400 U.I.). Changes in the cellular levels of high-energy compounds (i.e., ATP and its catabolites, NAD and GTP), GSH, GSSG, and malondialdehyde (MDA) were simultaneously analyzed by ion-pairing HPLC. Response to oxidative stress was further investigated through the oxygen radical absorptive capacity (ORAC) assay. According to our experimental approach, (i) CoQ10 appeared to be the most effective antioxidant inducing a high increase in ATP/ADP, ATP/AMP, GSH/GSSG ratio and ORAC value and, in turn, a reduction of NAD concentration, (ii) EGCG modestly modulated the intracellular energy charge potential, while (iii) Vitamin E, vitamin C, and resveratrol exhibited very weak effects. Given that, the antioxidant potential of CoQ10 was additionally assessed in a pilot study which considered individuals suffering from Rett syndrome (RTT), a severe X-linked neuro-developmental disorder in which RBC oxidative damages provide biological markers for redox imbalance and chronic hypoxemia. RTT patients (n = 11), with the typical clinical form, were supplemented for 12 months with CoQ10 (300 mg, once daily). Level of lipid peroxidation (MDA production) and energy state of RBCs were analyzed at 2 and 12 months. Our data suggest that CoQ10 may significantly attenuate the oxidative stress-induced damage in RTT erythrocytes.
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Canagliflozin Increases Calorie Intake in Type 2 Diabetes Without Changing the Energy Ratio of the Three Macronutrients: CANA-K Study.
Matsuba, I, Kanamori, A, Takihata, M, Takai, M, Maeda, H, Kubota, A, Iemitsu, K, Umezawa, S, Obana, M, Kaneshiro, M, et al
Diabetes technology & therapeutics. 2020;(3):228-234
Abstract
Background: Sodium/glucose cotransporter-2 (SGLT2) inhibitors improve glycemic control and reduce body weight by increasing glycosuria. Although a compensatory increase of food intake has been reported, the long-term effect of SGLT2 inhibitors on food intake remains unclear. This study investigated the influence of canagliflozin on calorie and nutrient intake over 1 year. Materials and Methods: Patients with type 2 diabetes (n = 107) were enrolled and followed prospectively while receiving canagliflozin at 100 mg/day for 12 months. Intake of nutrients was investigated by using the food frequency questionnaire. Hemoglobin A1c, body weight, and satisfaction with diabetes treatment (assessed by the Diabetes Treatment Satisfaction Questionnaire: DTSQ) were also investigated. Results: The baseline total energy intake was 1723 ± 525 kcal/day and it showed a persistent increase during treatment with canagliflozin, being 132 kcal higher at 6 months (P = 0.0058) and 113 kcal higher at 12 months (P = 0.0516). Intake of all three macronutrients (carbohydrate, protein, and fat) was significantly increased after 6 months of canagliflozin treatment (P = 0.0129, P = 0.0160, and P = 0.0314, respectively), but their ratio was unchanged. The DTSQ score improved significantly and both hemoglobin A1c and body weight showed a significant decrease throughout treatment (all P < 0.0001). Conclusions: After patients with type 2 diabetes commenced canagliflozin, their calorie intake increased without changing the ratio of the three macronutrients. Despite elevation of the calorie intake, glycemic control improved and weight loss was achieved. Satisfaction with treatment of diabetes also increased.
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MECCIAS trial: Metabolic consequences of continuous veno-venous hemofiltration on indirect calorimetry.
Jonckheer, J, Demol, J, Lanckmans, K, Malbrain, MLNG, Spapen, H, De Waele, E
Clinical nutrition (Edinburgh, Scotland). 2020;(12):3797-3803
Abstract
BACKGROUND and aims: Caloric prescription based on resting energy expenditure (REE) measured with indirect calorimetry (IC) improves outcome and is the gold standard in nutritional therapy of critically ill patients. Until now continuous renal replacement therapy (CRRT) precluded the use of IC due to several mechanisms. We investigated the impact of CRRT on V̇CO2, V̇O2 and REE to facilitate indirect calorimetry during CRRT. METHODS In 10 critically ill ventilated patient in need of continuous veno-venous hemofiltration (CVVH) using citrate predilution we performed IC in 4 different states: baseline, high dose, baseline with NaCl predilution and without CVVH. CO2 content of effluent fluid was measured by a point of care blood gas analyzer. Carbon dioxide production (V̇CO2) measured with IC was adapted by adding the CO2 flow of effluent and deducing CO2 flow in postdilution fluid to calculate a true V̇CO2. True REE was calculated with the Weir equation using the true V̇CO2. RESULTS CO2 removal in effluent during baseline, high dose and NaCl predilution was respectively 24 mL/min, 38 mL/min and 23 mL/min. Together with the CO2 delivery by the postdilution fluid this led to an adaptation of REE respectively by 34 kcal/d or 2% (p = 0,002), 44 kcal/d or 3% (p = 0,002) and 33 kcal/d or 2% (p = 0,002). Compared to the true REE during baseline of 1935 ± 921 kcal/d, true REE during high dose was 1723 ± 752 kcal/d (p = 0.65), during NaCl predilution it was 1604 ± 633 kcal/d (p = 0.014) and without CRRT it was 1713 ± 704 kcal/d (p = 0.193). CONCLUSIONS CO2 alterations due to CVVH are clinically of no importance so no correction factor of REE is needed with or without CVVH. IC must be performed during CVVH as CVVH seems to alter metabolism. These changes may be mainly explained by the use of citrate predilution.
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Validation of energy intake recorded by a 7-day pre-coded food diary against measured energy expenditure in a group of Norwegian adults.
Johansen, AMW, Myhre, JB, Hjartåker, A, Andersen, LF
PloS one. 2019;(4):e0215638
Abstract
The aim of this study was to validate energy intake (EI) reported by a pre-coded food diary (PFD) against energy expenditure (EE) measured by the ActiReg system consisting of an activity and position monitor and a calculation program (ActiCalc). Dietary intake was recorded by the PFD and EE was measured by the ActiReg system over a 7-day period. One hundred and twenty adult participants completed the study, 42 men and 78 women. The average group EI was 17% lower compared to measured EE. The 95% limits of agreement were 6.7 and -2.9 MJ/day. Of all participants, 68% were classified as acceptable reporters, 29% as underreporters and only 3% as overreporters. Fifty percent of the men and 30% of the women were classified into the same quartile for EI and EE, whereas 5% of both men and women were ranked in the opposite quartile by the two methods (weighted kappa coefficient = 0.29). Pearson correlation coefficient between reported EI and measured EE was 0.49 (p<0.001). High BMI was related to larger underreporting when EE was low. Furthermore, this study found that PFD underestimates EI on the group level with an average of 17% and showed large variation in the validity of the PFD on the individual level.
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Energy expenditure associated with posture transitions in preschool children.
Downing, KL, Janssen, X, Cliff, DP, Okely, AD, Reilly, JJ
PloS one. 2019;(4):e0215169
Abstract
BACKGROUND Despite growing scientific interest in the benefits of breaking up sedentary time with intermittent standing or walking, few studies have investigated the energy cost of posture transitions. This study aimed to determine whether posture transitions are associated with increased energy expenditure in preschool children. METHODS Forty children (mean age 5.3 ± 1.0y) completed a ~150-min room calorimeter protocol involving sedentary, light, and moderate- to vigorous-intensity activities. This study utilised data from ~65-min of the protocol, during which children were undertaking sedentary behaviours (TV viewing, drawing/colouring in, and playing with toys on the floor). Posture was coded as sit/lie, stand, walk, or other using direct observation; posture transitions were classified as sit/lie to stand/walk, sit/lie to other, stand/walk to other, or vice versa. Energy expenditure was calculated using the Weir equation and used to calculate individualised MET and activity energy expenditure (AEE) values. Spearman's rank correlations were used to compare the number of posture transitions, in the individual activities separately and combined, with corresponding MET and AEE values. Participants were divided into tertiles based on the number of posture transitions; MET and AEE values of children in the lowest and highest tertiles of posture transitions were compared using unpaired t-tests. Effect sizes (Cohen's d) were calculated. RESULTS There was a positive correlation between the total number of posture transitions and average METs (rs = 0.42, p = 0.02) and AEE (rs = 0.43, p = 0.02). MET differences between the lowest and highest tertiles of posture transitions resulted in a small effect size for playing with toys (d = 0.27), and moderate effect sizes for TV viewing, drawing and all three activities combined (d = 0.61, 0.50 and 0.64 respectively). Similar results were found for AEE. CONCLUSIONS Results from this study showed that variation in posture transitions may be associated with variation in energy expenditure in preschool children. The findings suggest that the concept that variation in posture transitions may have meaningful biological or health effects in early childhood is worth investigating further.
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Metabolic rate and substrate utilisation resilience in men undertaking polar expeditionary travel.
Hattersley, J, Wilson, AJ, Thake, CD, Facer-Childs, J, Stoten, O, Imray, C
PloS one. 2019;(8):e0221176
Abstract
The energy expenditure and substrate utilisation were measured in 5 men pre- and post- a 67 day, 1750km unassisted Antarctic traverse from the Hercules Inlet to the Ross Sea Ice via the South pole pulling sledges weighing 120kg whilst experiencing temperatures as low as -57°C. A 36-hours protocol in a whole body calorimeter was employed to measure periods of rest, sleep and three periods of standardised stepping exercises at 80, 100 and 120 steps min-1; participants were fed isocalorically. Unlike previous expeditions where large weight loss was reported, only a modest loss of body weight (7%, P = 0.03) was found; fat tissue was reduced by 53% (P = 0.03) together with a small, but not statistically significant, increase in lean tissue weight (P = 0.18). This loss occurred despite a high-energy intake (6500 kcal/day) designed to match energy expenditure. An energy balance analysis suggested the loss in body weight could be due to the energy requirements of thermoregulation. Differences in energy expenditure [4.9 (0.1) vs 4.5 (0.1) kcal/min. P = 0.03], carbohydrate utilisation [450 (180) vs 569 (195) g/day; P = 0.03] and lipid utilisation [450 (61) vs 388 (127) g/day, P = 0.03] at low levels of exertion were different from pre-expedition values. Only carbohydrate utilisation remained statistically significant when normalised to body weight. The differences in energy expenditure and substrate utilisation between the pre- and post-expedition for other physiological states (sleeping, resting, higher levels of exercise, etc) were small and not statistically significant. Whilst inter-subject variability was large, there was a tendency for increased carbohydrate utilisation, post-expedition, when fasted that decreased upon feeding.
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Effect of skipping breakfast for 6 days on energy metabolism and diurnal rhythm of blood glucose in young healthy Japanese males.
Ogata, H, Kayaba, M, Tanaka, Y, Yajima, K, Iwayama, K, Ando, A, Park, I, Kiyono, K, Omi, N, Satoh, M, et al
The American journal of clinical nutrition. 2019;(1):41-52
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Abstract
BACKGROUND Skipping breakfast has become a common trend that may lead to obesity and type 2 diabetes. Previous studies, which imposed a single incidence of breakfast skipping, did not observe any decrease in 24-h energy expenditure. Furthermore, the effects of breakfast skipping on diurnal blood glucose profiles over 24 h are contradictory. OBJECTIVE The aim of this study was to clarify the influence of 6 consecutive days of breakfast skipping and sedentary behavior on energy metabolism and glycemic control. METHODS Ten young men participated in 2 trials (with or without breakfast) that lasted for 6 consecutive days, and the 2 trials were conducted 1 wk apart with a repeated-measures design. During the meal intervention, each subject's blood glucose was measured using the continuous glucose monitoring system. If breakfast was skipped, subjects ate large meals at lunch and dinner such that the 24-h energy intake was identical to that of the 3-meal condition. At 2200 on the fifth day, the subjects entered a room-sized respiratory chamber, where they remained for 33 h, and were instructed to carry out sedentary behavior. RESULTS The glucose levels were similar between the 2 meal conditions during the first 5 d of meal intervention, but the blood glucose at 2300 was higher in the breakfast-skipping condition than in the 3-meal condition. Breakfast skipping elevated postprandial glycemic response after lunch on the first day of meal intervention. On the sixth day, there were no significant differences in 24-h energy expenditure and substrate oxidation. When subjects remained in a metabolic chamber, the level of physical activity significantly decreased, glycemic stability slightly deteriorated, and mean blood glucose over 24 h was higher in the breakfast-skipping trial than in the 3-meal trial. CONCLUSIONS Sedentary lifestyle and repeated breakfast skipping caused abnormal glucose fluctuations, whereas 24-h energy metabolism remained unaffected. Clinical Trial Registry: This trial was registered at http://www.umin.ac.jp/english/ as UMIN000032346.
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Severe negative energy balance during 21 d at high altitude decreases fat-free mass regardless of dietary protein intake: a randomized controlled trial.
Berryman, CE, Young, AJ, Karl, JP, Kenefick, RW, Margolis, LM, Cole, RE, Carbone, JW, Lieberman, HR, Kim, IY, Ferrando, AA, et al
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2018;(2):894-905
Abstract
In this 2-phase randomized controlled study, we examined whether consuming a higher-protein (HP) diet would attenuate fat-free mass (FFM) loss during energy deficit (ED) at high altitude (HA) in 17 healthy males (mean ± sd: 23 ± 6 yr; 82 ± 14 kg). During phase 1 at sea level (SL, 55 m), participants consumed a eucaloric diet providing standard protein (SP; 1.0 g protein/kg,) for 21 d. During phase 2, participants resided at HA (4300 m) for 22 d and were randomly assigned to either an SP or HP (2.0 g protein/kg) diet designed to elicit a 40% ED. Body composition, substrate oxidation, and postabsorptive whole-body protein kinetics were measured. Participants were weight stable during SL and lost 7.9 ± 1.9 kg ( P < 0.01) during HA, regardless of dietary protein intake. Decrements in whole-body FFM (3.6 ± 2.4 kg) and fat mass (3.6 ± 1.3 kg) were not different between SP and HP. HP oxidized 0.95 ± 0.32 g protein/kg per day more than SP and whole-body net protein balance was more negative for HP than for SP ( P < 0.01). Based on changes in body energy stores, the overall ED was 70% (-1849 ± 511 kcal/d, no group differences). Consuming an HP diet did not protect FFM during severe ED at HA.-Berryman, C. E., Young, A. J., Karl, J. P., Kenefick, R. W., Margolis, L. M., Cole, R. E., Carbone, J. W., Lieberman, H. R., Kim, I.-Y., Ferrando, A. A., Pasiakos, S. M. Severe negative energy balance during 21 d at high altitude decreases fat-free mass regardless of dietary protein intake: a randomized controlled trial.
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Interventional left atrial appendage closure may affect metabolism of essential amino acids and bioenergetic efficacy.
Rusnak, J, Behnes, M, Saleh, A, Fastner, C, Sattler, K, Barth, C, Wenke, A, Sartorius, B, Mashayekhi, K, Hoffmann, U, et al
International journal of cardiology. 2018;:125-131
Abstract
BACKGROUND Interventional closure of left atrial appendage (LAAC) represents an alternative for stroke prevention in patients with non-valvular atrial fibrillation. Whether LAAC may affect metabolomic pathways has not been investigated yet. This study evaluates the impact of LAAC on the metabolism of essential amino acids, kynurenine and creatinine. METHODS Peripheral blood samples of prospectively enrolled patients undergoing successful LAAC were taken before (T0) and 6 months after (T1, mid-term follow-up). Targeted metabolomic profiling was performed using electrospray ionization liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and MS/MS measurements focusing on metabolism of essential amino acids. RESULTS 44 patients with non-valvular AF (mean CHA2DS2-VASc score 4, mean HAS-BLED score 4) were enrolled. Changes in metabolites of essential amino acids, myocardial contraction and bioenergetic efficacy, such as phenylalanine (percentage change 8.2%, p = 0.006), tryptophan (percentage change 20.3%, p = 0.0006), tyrosine (percentage change 20.2%, p = 0.0001), creatinine (percentage change 7.2%, p > 0.05) and kynurenine (percentage change 8.3%, p = 0.0239) were found at mid-term follow-up. CONCLUSIONS LAAC may affect the metabolism of essential amino acids and bioenergetic efficacy. ClinicalTrials.gov Identifier: NCT02985463.