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Effect of gummy candy containing ubiquinol on secretion of saliva: A randomized, double-blind, placebo-controlled parallel-group comparative study and an in vitro study.
Ushikoshi-Nakayama, R, Ryo, K, Yamazaki, T, Kaneko, M, Sugano, T, Ito, Y, Matsumoto, N, Saito, I
PloS one. 2019;(4):e0214495
Abstract
A randomized, double-blind, placebo-controlled, parallel-group comparative clinical study was conducted to examine the effects of ubiquinol (the reduced form of Coenzyme Q10) on secretion of saliva. This interventional study enrolled 40 subjects aged 65 years or younger who were healthy, but noted slight dryness of the mouth. Subjects were randomized with stratification according to gender and age to ingestion of gummy candy containing 50 mg of ubiquinol or placebo twice daily for 8 weeks. At the end of study, along with a significant increase of the CoQ10 level in saliva (p = 0.025*, d = 0.65), there was a significant increase of the saliva flow rate (p = 0.048*, d = 0.66) in the ubiquinol candy group (n = 18; 47.4±6.2 years; 6 men and 12 women) compared to the placebo group (n = 20; 52.2±7.7 years; 4 men and 16 women). The strength of the stomatognathic muscles was not significantly enhanced by ingestion of ubiquinol candy. Compared with baseline, significant improvement of the following four questionnaire items was observed in the ubiquinol group at the end of the study: feeling tired (p = 0.00506, d = -0.726), dryness of the mouth (p = 0.04799, d = -0.648), prone to catching a cold (p = 0.00577, d = -0.963), and diarrhea (p = 0.0166, d = -0.855). There were no serious adverse events. An in vitro study revealed that ubiquinol stimulated a significant and concentration-dependent increase of ATP production by a cell line derived from human salivary gland epithelial cells (p<0.05), while 1 nM ubiquinol significantly suppressed (p = 0.028) generation of malondialdehyde by cells exposed to FeSO4-induced oxidative stress. These findings suggest that ubiquinol increases secretion of saliva by suppressing oxidative stress in the salivary glands and by promoting ATP production. Trial Registration: UMIN-CTR UMIN000024406.
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A Single Dose of Oral ATP Supplementation Improves Performance and Physiological Response During Lower Body Resistance Exercise in Recreational Resistance-Trained Males.
Freitas, MC, Cholewa, JM, Gerosa-Neto, J, Gonçalves, DC, Caperuto, EC, Lira, FS, Rossi, FE
Journal of strength and conditioning research. 2019;(12):3345-3352
Abstract
Freitas, MC, Cholewa, JM, Gerosa-Neto, J, Gonçalves, DC, Caperuto, EC, Lira, FS, and Rossi, FE. A single dose of oral ATP supplementation improves performance and physiological response during lower body resistance exercise in recreational resistance-trained males. J Strength Cond Res 33(12): 3345-3352, 2019-The aim of this study was to investigate the acute effect of adenosine-5'-triphosphate (ATP) supplementation on performance and physiological responses during resistance exercise in recreationally resistance-trained males. Eleven men (age = 27.5 ± 5.5 years, mass = 83.4 ± 9.8 kg, height = 182 ± 0.04 cm) completed 2 randomized, double-blind trials: ATP supplement condition (ATP = 400 mg) or a placebo condition. Thirty minutes after supplement consumption, subjects performed 4 sets of half-squats until momentary muscular failure at 80% of the 1 repetition maximum with 2 minutes of recovery between sets. The total number of repetitions, blood pressure, heart rate, blood lactate, and oxygen consumption were evaluated. The total weight lifted were higher for the ATP condition compared with placebo (Placebo = 3,995.7 ± 1,137.8, ATP = 4,967.4 ± 1,497.9 kg; p = 0.005). Heart rate was higher at set-4 for ATP compared with placebo (p < 0.001) and oxygen consumption during exercise was greater for ATP (p = 0.021). There were no differences between conditions for lactate and blood pressure. In summary, a single oral dose of ATP supplementation improved lower-body resistance training performance and energy expenditure in recreational resistance-trained males.
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Constant hepatic ATP concentrations during prolonged fasting and absence of effects of Cerbomed Nemos® on parasympathetic tone and hepatic energy metabolism.
Gancheva, S, Bierwagen, A, Markgraf, DF, Bönhof, GJ, Murphy, KG, Hatziagelaki, E, Lundbom, J, Ziegler, D, Roden, M
Molecular metabolism. 2018;:71-79
Abstract
OBJECTIVE Brain insulin-induced improvement in glucose homeostasis has been proposed to be mediated by the parasympathetic nervous system. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) activating afferent branches of the vagus nerve may prevent hyperglycemia in diabetes models. We examined the effects of 14-min taVNS vs sham stimulation by Cerbomed Nemos® on glucose metabolism, lipids, and hepatic energy homeostasis in fasted healthy humans (n = 10, age 51 ± 6 yrs, BMI 25.5 ± 2.7 kg/m2). METHODS Heart rate variability (HRV), reflecting sympathetic and parasympathetic nerve activity, was measured before, during and after taVNS or sham stimulation. Endogenous glucose production was determined using [6,6-2H2]glucose, and hepatic concentrations of triglycerides (HCL), adenosine triphosphate (ATP), and inorganic phosphate (Pi) were quantified from 1H/31P magnetic resonance spectroscopy at baseline and for 180 min following stimulation. RESULTS taVNS did not affect circulating glucose, free fatty acids, insulin, glucagon, or pancreatic polypeptide. Rates of endogenous glucose production (P = 0.79), hepatic HCL, ATP, and Pi were also not different (P = 0.91, P = 0.48 and P = 0.24) between taVNS or sham stimulation. Hepatic HCL, ATP, and Pi remained constant during prolonged fasting for 3 h. No changes in heart rate or shift in cardiac autonomic function from HRV towards sympathetic or parasympathetic predominance were detected. CONCLUSION Non-invasive vagus stimulation by Cerbomed Nemos® does not acutely modulate the autonomic tone to the visceral organs and thereby does not affect hepatic glucose and energy metabolism. This technique is therefore unable to mimic brain insulin-mediated effects on peripheral homeostasis in humans.
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Differences in Mitochondrial Coupling Reveal a Novel Signature of Mitohormesis in Muscle of Healthy Individuals.
Sparks, LM, Redman, LM, Conley, KE, Harper, ME, Hodges, A, Eroshkin, A, Costford, SR, Gabriel, ME, Yi, F, Shook, C, et al
The Journal of clinical endocrinology and metabolism. 2016;(12):4994-5003
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Abstract
CONTEXT Reduced mitochondrial coupling (ATP/O2 [P/O]) is associated with sedentariness and insulin resistance. Interpreting the physiological relevance of P/O measured in vitro is challenging. OBJECTIVE To evaluate muscle mitochondrial function and associated transcriptional profiles in nonobese healthy individuals distinguished by their in vivo P/O. DESIGN Individuals from an ancillary study of Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy phase 2 were assessed at baseline. SETTING The study was performed at Pennington Biomedical Research Center. PARTICIPANTS Forty-seven (18 males, 26-50 y of age) sedentary, healthy nonobese individuals were divided into 2 groups based on their in vivo P/O. INTERVENTION None. Main Outcome(s): Body composition by dual-energy x-ray absorptiometry, in vivo mitochondrial function (P/O and maximal ATP synthetic capacity) by 31P-magnetic resonance spectroscopy and optical spectroscopy were measured. A muscle biopsy was performed to measure fiber type, transcriptional profiling (microarray), and protein expressions. RESULTS No differences in body composition, peak aerobic capacity, type I fiber content, or mitochondrial DNA copy number were observed between the 2 groups. Compared with the uncoupled group (lower P/O), the coupled group (higher P/O) had higher rates of maximal ATP synthetic capacity (maximal ATP synthetic capacity, P < .01). Transcriptomics analyses revealed higher expressions of genes involved in mitochondrial remodeling and the oxidative stress response in the coupled group. A trend for higher mitonuclear protein imbalance (P = .06) and an elevated mitochondrial unfolded protein response (heat shock protein 60 protein; P = .004) were also identified in the coupled group. CONCLUSIONS Higher muscle mitochondrial coupling is accompanied by an overall elevation in mitochondrial function, a novel transcriptional signature of oxidative stress and mitochondrial remodeling and indications of an mitochondrial unfolded protein response.
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Twelve weeks supplementation with an extended-release caffeine and ATP-enhancing supplement may improve body composition without affecting hematology in resistance-trained men.
Joy, JM, Vogel, RM, Moon, JR, Falcone, PH, Mosman, MM, Kim, MP
Journal of the International Society of Sports Nutrition. 2016;:25
Abstract
BACKGROUND Increased ATP levels may enhance training-induced muscle accretion and fat loss, and caffeine is a known ergogenic aid. A novel supplement containing ancient peat and apple extracts has reported enhanced mitochondrial ATP production and it has been coupled with an extended-release caffeine. Therefore, the purpose of this investigation was to determine the effects of this supplement on body composition when used in conjunction with 12 weeks of resistance training. METHODS Twenty-one resistance-trained subjects (27.2 ± 5.6y; 173.5 ± 5.7 cm; 82.8 ± 12.0 kg) completed this study. Subjects supplemented daily with either 1 serving of the supplement (TRT), which consisted of 150 mg ancient peat and apple extracts, 180 mg blend of caffeine anhydrous and pterostilbene-bound caffeine, and 38 mg B vitamins, or an equal-volume, visually-identical placebo (PLA) 45 min prior to training or at the same time of day on rest days. Supervised resistance training consisted of 8 weeks of daily undulating periodized training followed by a 2-week overreach and a 2-week taper phase. Body composition was assessed using DEXA and ultrasound at weeks 0, 4, 8, 10, and 12. Vital signs and blood markers were assessed at weeks 0, 8, and 12. RESULTS Significant group x time (p < 0.05) interactions were present for cross-sectional area of the rectus femoris, which increased in TRT (+1.07 cm(2)) versus PLA (-0.08 cm(2)), as well as muscle thickness (TRT: +0.49 cm; PLA: +0.04 cm). A significant group x time (p < 0.05) interaction existed for creatinine (TRT: +0.00 mg/dL; PLA: +0.15 mg/dL) and estimated glomerular filtration rate (TRT: -0.70 mL/min/1.73; PLA: -14.6 mL/min/1.73), which remained within clinical ranges, but no other significant observations were observed. CONCLUSIONS Supplementation with a combination of extended-release caffeine and ancient peat and apple extracts may enhance resistance training-induced skeletal muscle hypertrophy without adversely affecting blood chemistry.
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Effects of adenosine triphosphate (ATP) on early recovery after total knee arthroplasty (TKA): a randomized, double-blind, controlled study.
Long, G, Zhang, GQ
The Journal of arthroplasty. 2014;(12):2347-51
Abstract
Functional exercise after total knee arthroplasty (TKA) is necessary. However, it may be a difficult and painful process for the patient. Desirable methods of relieving the patient's pain are worth exploring. Oral supplement of adenosine triphosphate (ATP) is a potential option. In the present study, we decide to investigate whether short-term administration of ATP benefits patients undergoing TKA. A total of 244 subjects were randomized to receive 120mg ATP or placebo each day for 4weeks. Significant differences in quadriceps strength, pain scores at postoperative days 7, 14, 21, and 28 and total opioid consumption were detected. It follows that oral supplement of ATP could benefit patients recovering from TKA.
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Oral sucrose for heel lance increases adenosine triphosphate use and oxidative stress in preterm neonates.
Asmerom, Y, Slater, L, Boskovic, DS, Bahjri, K, Holden, MS, Phillips, R, Deming, D, Ashwal, S, Fayard, E, Angeles, DM
The Journal of pediatrics. 2013;(1):29-35.e1
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OBJECTIVE To examine the effects of sucrose on pain and biochemical markers of adenosine triphosphate (ATP) degradation and oxidative stress in preterm neonates experiencing a clinically required heel lance. STUDY DESIGN Preterm neonates that met study criteria (n = 131) were randomized into 3 groups: (1) control; (2) heel lance treated with placebo and non-nutritive sucking; and (3) heel lance treated with sucrose and non-nutritive sucking. Plasma markers of ATP degradation (hypoxanthine, xanthine, and uric acid) and oxidative stress (allantoin) were measured before and after the heel lance. Pain was measured with the Premature Infant Pain Profile. Data were analyzed by the use of repeated-measures ANOVA and Spearman rho. RESULTS We found significant increases in plasma hypoxanthine and uric acid over time in neonates who received sucrose. We also found a significant negative correlation between pain scores and plasma allantoin concentration in a subgroup of neonates who received sucrose. CONCLUSION A single dose of oral sucrose, given before heel lance, significantly increased ATP use and oxidative stress in premature neonates. Because neonates are given multiple doses of sucrose per day, randomized trials are needed to examine the effects of repeated sucrose administration on ATP degradation, oxidative stress, and cell injury.
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Insulin fails to enhance mTOR phosphorylation, mitochondrial protein synthesis, and ATP production in human skeletal muscle without amino acid replacement.
Barazzoni, R, Short, KR, Asmann, Y, Coenen-Schimke, JM, Robinson, MM, Nair, KS
American journal of physiology. Endocrinology and metabolism. 2012;(9):E1117-25
Abstract
Systemic insulin administration causes hypoaminoacidemia by inhibiting protein degradation, which may in turn inhibit muscle protein synthesis (PS). Insulin enhances muscle mitochondrial PS and ATP production when hypoaminoacidemia is prevented by exogenous amino acid (AA) replacement. We determined whether insulin would stimulate mitochondrial PS and ATP production in the absence of AA replacement. Using l-[1,2-¹³C]leucine as a tracer, we measured the fractional synthetic rate of mitochondrial as well as sarcoplasmic and mixed muscle proteins in 18 participants during sustained (7-h) insulin or saline infusion (n = 9 each). We also measured muscle ATP production, mitochondrial enzyme activities, mRNA levels of mitochondrial genes, and phosphorylation of signaling proteins regulating protein synthesis. The concentration of circulating essential AA decreased during insulin infusion. Mitochondrial, sarcoplasmic, and mixed muscle PS rates were also lower during insulin (2-7 h) than during saline infusions despite increased mRNA levels of selected mitochondrial genes. Under these conditions, insulin did not alter mitochondrial enzyme activities and ATP production. These effects were associated with enhanced phosphorylation of Akt but not of protein synthesis activators mTOR, p70(S6K), and 4EBP1. In conclusion, sustained physiological hyperinsulinemia without AA replacement did not stimulate PS of mixed muscle or protein subfractions and did not alter muscle mitochondrial ATP production in healthy humans. These results support that insulin and AA act in conjunction to stimulate muscle mitochondrial function and mitochondrial protein synthesis.
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Effect of adenosine 5'-triphosphate infusions on the nutritional status and survival of preterminal cancer patients.
Beijer, S, Hupperets, PS, van den Borne, BE, Eussen, SR, van Henten, AM, van den Beuken-van Everdingen, M, de Graeff, A, Ambergen, TA, van den Brandt, PA, Dagnelie, PC
Anti-cancer drugs. 2009;(7):625-33
Abstract
The aim of the study was to investigate the effect of intravenous infusions of adenosine 5'-triphosphate (ATP) on nutritional status and survival in preterminal cancer patients. Ninety-nine preterminal cancer patients (estimated life expectancy 1-6 months) with mixed tumor types were randomly allocated to receive either intravenous ATP weekly (8-10 h/week, maximum 50 microg/kg/min) for 8 weeks, or no ATP (control group). Nutritional status parameters were assessed until 8 weeks, and analyzed by repeated-measures analysis of covariance. Cox proportional hazards models were fitted to assess the effect of ATP on short-term (0-8 weeks) and long-term (0-6 months) survival. Fifty-one patients were randomized to ATP and 48 to the control group. Results showed a significant favorable effect of ATP on triceps skin fold thickness [between-group difference per 8 weeks 1.76 mm, 95% confidence interval (CI): 0.48-3.12 mm; P = 0.009] and on short-term survival [0-8 weeks hazard ratio (HR): 0.40, 95% CI: 0.17-0.95; P = 0.037]. In weight-stable patients and in lung cancer patients, long-term survival (0-6 months) was also significantly better in ATP-treated patients (weight-stable patients HR: 0.40, 95% CI: 0.19-0.83; P = 0.014; patients with lung cancer: HR: 0.35, 95% CI: 0.14-0.88; P = 0.025). In conclusion, in this population of preterminal cancer patients, ATP infusions, at the dose and schedule studied, had a favorable effect on triceps skin fold thickness and survival, especially in weight-stable patients and patients with lung cancer. Larger studies are warranted to confirm these findings and to further define the effect of ATP on tumor growth and survival.
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Pioglitazone improves cardiac function and alters myocardial substrate metabolism without affecting cardiac triglyceride accumulation and high-energy phosphate metabolism in patients with well-controlled type 2 diabetes mellitus.
van der Meer, RW, Rijzewijk, LJ, de Jong, HW, Lamb, HJ, Lubberink, M, Romijn, JA, Bax, JJ, de Roos, A, Kamp, O, Paulus, WJ, et al
Circulation. 2009;(15):2069-77
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BACKGROUND Cardiac disease is the leading cause of mortality in type 2 diabetes mellitus (T2DM). Pioglitazone has been associated with improved cardiac outcome but also with an elevated risk of heart failure. We determined the effects of pioglitazone on myocardial function in relation to cardiac high-energy phosphate, glucose, and fatty acid metabolism and triglyceride content in T2DM patients. METHODS AND RESULTS Seventy-eight T2DM men without structural heart disease or inducible ischemia as assessed by dobutamine stress echocardiography were assigned to pioglitazone (30 mg/d) or metformin (2000 mg/d) and matching placebo for 24 weeks. The primary end point was change in cardiac diastolic function from baseline relative to myocardial metabolic changes, measured by magnetic resonance imaging, proton and phosphorus magnetic resonance spectroscopy, and [(18)F]-2-fluoro-2-deoxy-D-glucose and [(11)C]palmitate positron emission tomography. No patient developed heart failure. Both therapies similarly improved glycemic control, whole-body insulin sensitivity, and blood pressure. Pioglitazone versus metformin improved the early peak flow rate (P=0.047) and left ventricular compliance. Pioglitazone versus metformin increased myocardial glucose uptake (P<0.001), but pioglitazone-related diastolic improvement was not associated with changes in myocardial substrate metabolism. Metformin did not affect myocardial function but decreased cardiac work relative to pioglitazone (P=0.006), a change that was paralleled by a reduced myocardial glucose uptake and fatty acid oxidation. Neither treatment affected cardiac high-energy phosphate metabolism or triglyceride content. Only pioglitazone reduced hepatic triglyceride content (P<0.001). CONCLUSIONS In T2DM patients, pioglitazone was associated with improvement in some measures of left ventricular diastolic function, myocardial glucose uptake, and whole-body insulin sensitivity. The functional changes, however, were not associated with myocardial substrate and high-energy phosphate metabolism.