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López-Cervantes SP, Toledo-Pérez R, De Lira-Sánchez JA, García-Cruz G, Esparza-Perusquía M, Luna-López A, Pardo JP, Flores-Herrera O, Konigsberg M. Sedentary Lifestyles and a Hypercaloric Diets During Middle Age, are Binomial Conducive to Fatal Progression, That is Counteracted by the Hormetic Treatment of Exercise, Metformin, and Tert-Butyl Hydroquinone: An Analysis of Female Middle-Aged Rat Liver Mitochondria. Dose Response 2024; 22:15593258241272619. [PMID: 39399210 PMCID: PMC11471012 DOI: 10.1177/15593258241272619] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 06/15/2024] [Accepted: 07/08/2024] [Indexed: 10/15/2024] Open
Abstract
The world's population continuous to shift towards older, less active and more sedentary lifestyles especially during middle age. In addition consumption of high-caloric diets, increases the risk of metabolic and cardiovascular afflictions. Developing clinical strategies to mitigate those health complications represent a difficult challenge. Our group has previously shown that combining metformin (MTF) and tert-butyl hydroquinone (tBHQ) treatments, in addition to exercise, partially prevents liver damage associated with obesity. Hence, we evaluated the role of exercise in combination with MTF and tBHQ (triple-treatment) to counteract mitochondrial damage in the liver from obese middle-aged female rats. Animals were fed a high-fat diet (HFD) starting at 21 days till 15 months of age. The treated groups performed a Fartlek-type exercise 5 days/week for 30 min/session. MTF and tBHQ were administered at a dose of 250 mg/kg/day, and 10 mg/kg/day, respectively, for 7 days/month from 10 to 15 months of age. Triple-treatment therapeutic approach promoted animal survival, and increased AMPK and PGC1α expression. Treatments increased mitochondrial ATP synthesis and OXPHOS complexes activities, recovered membrane potential, and decreased ROS production. In summary, exercise in combination with intermittent tBHQ and MTF treatments proved to be an excellent intervention to prevent mitochondrial damage caused by HFD.
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Affiliation(s)
- Stefanie Paola López-Cervantes
- Departamento Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, México
- Departamento Ciencias de la Salud, Universidad Autónoma Metropolitana, Iztapalapa, México
- Posgrado en Biología Experimental, Universidad Autónoma Metropolitana, Iztapalapa, México
| | - Rafael Toledo-Pérez
- Departamento Ciencias de la Salud, Universidad Autónoma Metropolitana, Iztapalapa, México
- Posgrado en Biología Experimental, Universidad Autónoma Metropolitana, Iztapalapa, México
| | | | - Giovanni García-Cruz
- Departamento Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, México
| | - Mercedes Esparza-Perusquía
- Departamento Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, México
| | - Armando Luna-López
- Departamento de Investigación Básica, Instituto Nacional de Geriatría, Ciudad de Mexico, México
| | - Juan Pablo Pardo
- Departamento Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, México
| | - Oscar Flores-Herrera
- Departamento Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, México
| | - Mina Konigsberg
- Departamento Ciencias de la Salud, Universidad Autónoma Metropolitana, Iztapalapa, México
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Shawahna R, Batta A, Asa'ad M, Jomaah M, Abdelhaq I. Exercise as a complementary medicine intervention in type 2 diabetes mellitus: A systematic review with narrative and qualitative synthesis of evidence. Diabetes Metab Syndr 2021; 15:273-286. [PMID: 33482523 DOI: 10.1016/j.dsx.2021.01.008] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 01/02/2021] [Accepted: 01/07/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND AND AIMS Type 2 diabetes mellitus (T2DM) is a rapidly growing public health issue. This systematic review aimed to narrate and qualitatively synthesize evidence and recommendations of physical activity/exercise for patients with T2DM. METHODS The databases Medline through Pubmed, Cochrane, and Scopus were systematically searched from inception to February 08, 2020 using MeSH terms related to "diabetes mellitus" and "physical activity/exercise". Studies were included if they reported on the roles of physical activity/exercise in managing patients with T2DM or effects of physical activity/exercise on glycemic control. Documents identified through the search were analyzed and evidence and recommendations were synthesized qualitatively. RESULTS Data were extracted from 16 original articles and 11 systematic reviews with meta-analyses. A qualitative summary of evidence included general items (n = 6) and recommendations for physical activity/exercise (n = 12). Physical activity/exercise can reduce incidence of T2DM, hyperinsulinemia, fasting plasma/blood glucose, HbA1c, body fats, cholesterol, blood pressure, heart rate, cardiovascular risk, and dosage of antidiabetic medications. Physical activity/exercise can improve sensitivity to insulin, muscle strength, oxygen consumption, aerobic capacity, and mental health of patients with T2DM. CONCLUSION Despite the increasing interest in incorporating physical activity/exercise in the management of T2DM and improving healthcare delivery, there are still limited clear instructions and guidelines for both the patient and the healthcare provider.
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Affiliation(s)
- Ramzi Shawahna
- Department of Physiology, Pharmacology and Toxicology, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine; An-Najah BioSciences Unit, Centre for Poisons Control, Chemical and Biological Analyses, An-Najah National University, Nablus, Palestine.
| | - Ahmad Batta
- Department of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Mahmoud Asa'ad
- Department of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Marwan Jomaah
- Department of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Imad Abdelhaq
- Department of Physical Education, Faculty of Educational Sciences and Teachers' Training, An-Najah National University, Nablus, Palestine
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Jevtovic F. Combination of Metformin and Exercise in Management of Metabolic Abnormalities Observed in Type 2 Diabetes Mellitus. Diabetes Metab Syndr Obes 2021; 14:4043-4057. [PMID: 34557007 PMCID: PMC8453852 DOI: 10.2147/dmso.s328694] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 09/07/2021] [Indexed: 12/19/2022] Open
Abstract
Excess nutrient intake and lack of exercise characterize the problem of obesity and are common factors in insulin resistance (IR). With an increasing number of prediabetic, and type 2 diabetic populations, metformin is still the most prescribed glucose-lowering drug and is often accompanied by recommendations for regular physical exercise. Metformin, by the inhibition of complex 1 of the electron transport chain, and exercise, by increasing energy expenditure, both elicit a low cellular energy state that leads to improvements in glucose control via activation of adenosine 5' monophosphate-activated protein kinase (AMPK). An augmented stimulation of the energy-sensing enzyme AMPK by either of the two modalities leads to an increase in glycogenolysis, glucose uptake, fat oxidation, a decrease in glycogen and protein synthesis, and gluconeogenesis in muscle and the liver, which are remarked as having positive effects on metabolic pathophysiology observed in IR and type 2 diabetes mellitus (T2DM). While both modalities exploit the energy-sensing enzyme AMPK to attain glucose homeostasis, the synergistic effect of these two treatments is not distinctly supported by the literature. Further, an antagonistic dynamic has been observed in cases where metformin and exercise were combined. Reduction of insulin-sensitizing effects of exercise and an overall hindrance of exercise performance and adaptations have been reported and could suggest the possible incongruity of these two modalities. The aim of this review is to elucidate the effect that metformin and exercise have on the management of the metabolic abnormalities observed in T2DM and to provide an insight into the interaction of these two modalities.
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Affiliation(s)
- Filip Jevtovic
- Department of Kinesiology, College of Health and Human Performance, East Carolina University, Greenville, NC, USA
- Correspondence: Filip Jevtovic East Carolina University; School of Dental Medicine, Ledyard E. Ross Hall; 1851 MacGregor Downs Road, Mail Stop 701, Greenville, NC, 27834, USATel +1 616 844 8323Fax +1 252 737 7024 Email
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Chelette BM, Thomas AM, Fadool DA. Long-term obesogenic diet and targeted deletion of potassium channel K v 1.3 have differing effects on voluntary exercise in mice. Physiol Rep 2020; 7:e14254. [PMID: 31646751 PMCID: PMC6811687 DOI: 10.14814/phy2.14254] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2019] [Accepted: 09/03/2019] [Indexed: 12/27/2022] Open
Abstract
Voluntary exercise is frequently employed as an intervention for obesity. The voltage‐gated potassium channel Kv1.3 is also receiving attention as a therapeutic target for obesity, in addition to potential therapeutic capabilities for neuroinflammatory diseases. To investigate the combinatorial effects of these two therapies, we have compared the metabolic status and voluntary exercise behavior of both wild‐type mice and a transgenic line of mice that are genetic knockouts for Kv1.3 when provided with a running wheel and maintained on diets of differing fat content and caloric density. We tracked the metabolic parameters and wheel running behavior while maintaining the mice on their assigned treatment for 6 months. Wild‐type mice maintained on the fatty diet gain a significant amount of bodyweight and adipose tissue and display significantly impaired glucose tolerance, though all these effects were partially reduced with provision of a running wheel. Similar to previous studies, the Kv1.3‐null mice were resistant to obesity, increased adiposity, and impaired glucose tolerance. Both wild‐type and Kv1.3‐null mice maintained on the fatty diet displayed increased wheel running activity compared to control‐fed mice, which was caused primarily by a significant increase in the amount of time spent running as opposed to an increase in running velocity. Interestingly, the patterns of running behavior differed between wild‐type and Kv1.3‐null mice. Kv1.3‐null mice spent significantly less time running during the light phase and displayed a decrease in running 1–2 h before the onset of the light phase, seemingly in anticipation of the dark‐to‐light phase transition. These studies indicate that voluntary exercise combats metabolic maladies and running behavior is modified by both consumption of an obesogenic diet and deletion of the Kv1.3 channel.
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Affiliation(s)
- Brandon M Chelette
- Department of Biological Science, The Florida State University, Tallahassee, Florida.,Programs in Neuroscience, The Florida State University, Tallahassee, Florida
| | - Abigail M Thomas
- Department of Biological Science, The Florida State University, Tallahassee, Florida
| | - Debra Ann Fadool
- Department of Biological Science, The Florida State University, Tallahassee, Florida.,Programs in Neuroscience, The Florida State University, Tallahassee, Florida.,Molecular Biophysics, The Florida State University, Tallahassee, Florida
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Hernández-Álvarez D, Mena-Montes B, Toledo-Pérez R, Pedraza-Vázquez G, López-Cervantes SP, Morales-Salazar A, Hernández-Cruz E, Lazzarini-Lechuga R, Vázquez-Cárdenas RR, Vilchis-DeLaRosa S, Posadas-Rodríguez P, Santín-Márquez R, Rosas-Carrasco O, Ibañez-Contreras A, Alarcón-Aguilar A, López-Díazguerrero NE, Luna-López A, Königsberg M. Long-Term Moderate Exercise Combined with Metformin Treatment Induces an Hormetic Response That Prevents Strength and Muscle Mass Loss in Old Female Wistar Rats. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:3428543. [PMID: 31814870 PMCID: PMC6877950 DOI: 10.1155/2019/3428543] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 09/18/2019] [Indexed: 12/18/2022]
Abstract
Sarcopenia is a syndrome characterized by a progressive and generalized skeletal muscle mass and strength loss, as well as a poor physical performance, which as strongly been associated with aging. Sedentary lifestyle in the elderly contributes to this condition; however, physical activity improves health, reducing morbidity and mortality. Recent studies have shown that metformin (MTF) can also prevent muscle damage promoting muscular performance. To date, there is great controversy if MTF treatment combined with exercise training improves or nullifies the benefits provided by physical activity. This study is aimed at evaluating the effect of long-term moderate exercise combined with MTF treatment on body composition, strength, redox state, and survival rate during the life of female Wistar rats. In this study, rats performed moderate exercise during 20 of their 24 months of life and were treated with MTF for one year or for 6 months, i.e., from 12 to 24 months old and 18 to 24 months old. The body composition (percentage of fat, bone, and lean mass) was determined using a dual-energy X-ray absorption scanner (DXA), and grip strength was determined using a dynamometer. Likewise, medial and tibial nerve somatosensory evoked potentials were evaluated and the redox state was measured by HPLC, calculating the GSH/GSSG ratio in the gastrocnemius muscle. Our results suggest- that the MTF administration, both in the sedentary and the exercise groups, might activate a mechanism that is directly related to the induction of the hormetic response through the redox state modulation. MTF treatment does not eliminate the beneficial effects of exercise throughout life, and although MTF does not increase muscle mass, it increases longevity.
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Affiliation(s)
- David Hernández-Álvarez
- Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
- Posgrado en Ciencias Biológicas, Universidad Autónoma Metropolitana, Ciudad de México 09340, Mexico
| | - Beatriz Mena-Montes
- Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
- Instituto Nacional de Geriatría, SSA, Ciudad de México 10200, Mexico
- Posgrado en Biología Experimental, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
| | - Rafael Toledo-Pérez
- Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
- Posgrado en Biología Experimental, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
| | - Gibrán Pedraza-Vázquez
- Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
- Posgrado en Biología Experimental, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
| | - Stefanie Paola López-Cervantes
- Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
- Posgrado en Biología Experimental, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
| | - Alfredo Morales-Salazar
- Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
| | - Edith Hernández-Cruz
- Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
| | - Roberto Lazzarini-Lechuga
- Departamento de Biología de la Reproducción, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
| | - Roman Royer Vázquez-Cárdenas
- Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
| | - Silvia Vilchis-DeLaRosa
- Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
| | - Pedro Posadas-Rodríguez
- Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
- Posgrado en Biología Experimental, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
| | - Roberto Santín-Márquez
- Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
- Posgrado en Biología Experimental, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
| | | | | | - Adriana Alarcón-Aguilar
- Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
| | | | | | - Mina Königsberg
- Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México 09340, Mexico
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6
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Nierenberg AA. Thoughts About Health Span. Psychiatr Ann 2019. [DOI: 10.3928/00485713-20190213-02] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Hamasaki H. Effects of glucose-lowering agents on cardiorespiratory fitness. World J Diabetes 2018; 9:230-238. [PMID: 30588285 PMCID: PMC6304298 DOI: 10.4239/wjd.v9.i12.230] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Revised: 10/15/2018] [Accepted: 11/26/2018] [Indexed: 02/05/2023] Open
Abstract
Exercise therapy is essential for the management of type 2 diabetes (T2D). However, patients with T2D show lower physical activity and reduced cardiorespiratory fitness than healthy individuals. It would be ideal for clinicians to co-prescribe glucose-lowering agents that improve cardiorespiratory fitness or exercise capacity in conjunction with exercise therapy. Metformin does not improve cardiorespiratory fitness and may attenuate any beneficial effect of exercise in patients with T2D. In contrast, thiazolidinediones appear to improve cardiorespiratory fitness in patients with T2D. Although evidence is limited, sodium-glucose cotransporter 2 (SGLT2) inhibitors may improve cardiorespiratory fitness in patients with heart failure, and the effect of glucagon-like peptide-1 (GLP-1) receptor agonists on cardiorespiratory fitness is controversial. Recent clinical trials have shown that both SGLT2 inhibitors and GLP-1 receptor agonists exert a favorable effect on cardiovascular disease. It becomes more important to choose drugs that have beneficial effects on the cardiovascular system beyond glucose-lowering effects. Further studies are warranted to determine an ideal glucose-lowering agent combined with exercise therapy for the treatment of T2D.
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Affiliation(s)
- Hidetaka Hamasaki
- Endocrinology and Metabolism, Internal Medicine, Hamasaki Clinic, Kagoshima 890-0046, Japan
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8
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Das S, Behera SK, Srinivasan A, Xavier AS, Selvarajan S, Kamalanathan S, Sahoo JP, Nair NS. Effect of metformin on exercise capacity: A meta-analysis. Diabetes Res Clin Pract 2018; 144:270-278. [PMID: 30217594 DOI: 10.1016/j.diabres.2018.08.022] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 08/22/2018] [Accepted: 08/30/2018] [Indexed: 12/27/2022]
Abstract
AIMS To evaluate the effect of metformin on various parameters of exercise capacity [oxygen consumption (VO2), peak oxygen consumption (VO2peak), heart rate (HR), exercise test duration, respiratory exchange ratio (RER), rating of perceived exertion (RPE), lactate and ventilatory anaerobic threshold (VAT)]. METHODS Studies reporting change in VO2 or VO2peak after metformin administration were included. Subgroup analyses were performed as applicable. Mean difference with 95% CIs were pooled using random-effects model [RevMan (v5.3)]. RESULTS There were no changes in VO2 and VO2peak in the overall population [VO2: n = 388, mean difference: -0.12 ml/kg/min, 95% CI: -0.74, 0.51, p = 0.71 (i2 = 0%, p = 0.99); VO2peak: n = 345, mean difference: 0.41 ml/kg/min, 95% CI: -0.51, 1.33, p = 0.38 (i2 = 0%, p = 0.89)], healthy volunteers and patients (type 2 diabetes mellitus, insulin resistance, impaired glucose tolerance/impaired fasting glucose and metabolic syndrome). For patients with insulin resistance, there was a decrease in VO2peak, but not VO2. In the overall population, there was a significant decrease in HR and RER, a significant increase in RPE, and no changes in exercise test duration and VAT. In addition, there was an increased VAT in the healthy volunteers. CONCLUSIONS In the overall population, metformin did not affect VO2, VO2peak, exercise test duration and VAT, although it significantly decreased HR, RER and increased RPE.
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Affiliation(s)
- Saibal Das
- Department of Clinical Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
| | - Sapan Kumar Behera
- Department of Clinical Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
| | - Akila Srinivasan
- Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
| | - Alphienes Stanley Xavier
- Department of Clinical Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
| | - Sandhiya Selvarajan
- Department of Clinical Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India.
| | - Sadishkumar Kamalanathan
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
| | - Jaya Prakash Sahoo
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
| | - N Sreekumaran Nair
- Department of Biostatistics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
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Woessner MN, McIlvenna LC, Ortiz de Zevallos J, Neil CJ, Allen JD. Dietary nitrate supplementation in cardiovascular health: an ergogenic aid or exercise therapeutic? Am J Physiol Heart Circ Physiol 2018; 314:H195-H212. [DOI: 10.1152/ajpheart.00414.2017] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Oral consumption of inorganic nitrate, which is abundant in green leafy vegetables and roots, has been shown to increase circulating plasma nitrite concentration, which can be converted to nitric oxide in low oxygen conditions. The associated beneficial physiological effects include a reduction in blood pressure, modification of platelet aggregation, and increases in limb blood flow. There have been numerous studies of nitrate supplementation in healthy recreational and competitive athletes; however, the ergogenic benefits are currently unclear due to a variety of factors including small sample sizes, different dosing regimens, variable nitrate conversion rates, the heterogeneity of participants’ initial fitness levels, and the types of exercise tests used. In clinical populations, the study results seem more promising, particularly in patients with cardiovascular diseases who typically present with disruptions in the ability to transport oxygen from the atmosphere to working tissues and reduced exercise tolerance. Many of these disease-related, physiological maladaptations, including endothelial dysfunction, increased reactive oxygen species, reduced tissue perfusion, and muscle mitochondrial dysfunction, have been previously identified as potential targets for nitric oxide restorative effects. This review is the first of its kind to outline the current evidence for inorganic nitrate supplementation as a therapeutic intervention to restore exercise tolerance and improve quality of life in patients with cardiovascular diseases. We summarize the factors that appear to limit or maximize its effectiveness and present a case for why it may be more effective in patients with cardiovascular disease than as ergogenic aid in healthy populations.
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Affiliation(s)
- Mary N. Woessner
- Clinical Exercise Science Research Program, Institute of Sport, Exercise and Active Living, Victoria University, Melbourne, Victoria, Australia
- Western Health, Melbourne, Victoria, Australia
| | - Luke C. McIlvenna
- Clinical Exercise Science Research Program, Institute of Sport, Exercise and Active Living, Victoria University, Melbourne, Victoria, Australia
| | - Joaquin Ortiz de Zevallos
- Clinical Exercise Science Research Program, Institute of Sport, Exercise and Active Living, Victoria University, Melbourne, Victoria, Australia
- Department of Kinesiology, University of Virginia, Charlottesville, Virginia
| | - Christopher J. Neil
- Clinical Exercise Science Research Program, Institute of Sport, Exercise and Active Living, Victoria University, Melbourne, Victoria, Australia
- Western Health, Melbourne, Victoria, Australia
| | - Jason D. Allen
- Clinical Exercise Science Research Program, Institute of Sport, Exercise and Active Living, Victoria University, Melbourne, Victoria, Australia
- Western Health, Melbourne, Victoria, Australia
- Department of Kinesiology, University of Virginia, Charlottesville, Virginia
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10
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Wahl MP, Scalzo RL, Regensteiner JG, Reusch JEB. Mechanisms of Aerobic Exercise Impairment in Diabetes: A Narrative Review. Front Endocrinol (Lausanne) 2018; 9:181. [PMID: 29720965 PMCID: PMC5915473 DOI: 10.3389/fendo.2018.00181] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Accepted: 04/04/2018] [Indexed: 12/21/2022] Open
Abstract
The prevalence of diabetes in the United States and globally has been rapidly increasing over the last several decades. There are now estimated to be 30.3 million people in the United States and 422 million people worldwide with diabetes. Diabetes is associated with a greatly increased risk of cardiovascular mortality, which is the leading cause of death in adults with diabetes. While exercise training is a cornerstone of diabetes treatment, people with diabetes have well-described aerobic exercise impairments that may create an additional diabetes-specific barrier to adding regular exercise to their lifestyle. Physiologic mechanisms linked to exercise impairment in diabetes include insulin resistance, cardiac abnormalities, mitochondrial function, and the ability of the body to supply oxygen. In this paper, we highlight the abnormalities of exercise in type 2 diabetes as well as potential therapeutic approaches.
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Affiliation(s)
- Matthew P. Wahl
- Division of Endocrinology, University of Colorado School of Medicine, Aurora, CO, United States
- Veterans Administration Eastern Colorado Health Care System, Denver, CO, United States
| | - Rebecca L. Scalzo
- Division of Endocrinology, University of Colorado School of Medicine, Aurora, CO, United States
- Center for Women’s Health Research, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, United States
| | - Judith G. Regensteiner
- Center for Women’s Health Research, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, United States
- Division of General Internal Medicine, University of Colorado School of Medicine, Aurora, CO, United States
| | - Jane E. B. Reusch
- Division of Endocrinology, University of Colorado School of Medicine, Aurora, CO, United States
- Veterans Administration Eastern Colorado Health Care System, Denver, CO, United States
- Center for Women’s Health Research, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, United States
- *Correspondence: Jane E. B. Reusch,
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