The Search for the Elixir of Life: On the Therapeutic Potential of Alkaline Reduced Water in Metabolic Syndromes

Our body composition is enormously influenced by our lifestyle choices, which affect our health and longevity. Nutrition and physical activities both impact overall metabolic condition, thus, a positive energy balance causes oxidative stress and inflammation, hastening the development of metabolic syndrome. With this knowledge, boosting endogenous and exogenous antioxidants has emerged as a therapeutic strategy for combating metabolic disorders. One of the promising therapeutic inventions is the use of alkaline reduced water (ARW). Aside from its hydrating and non-caloric properties, ARW has demonstrated strong antioxidant and anti-inflammatory properties that can help stabilize physiologic turmoil caused by oxidative stress and inflammation. This review article is a synthesis of studies where we elaborate on the intra- and extracellular effects of drinking ARW, and relate these to the pathophysiology of common metabolic disorders, such as obesity, diabetes mellitus, non-alcoholic fatty liver disease, and some cancers. Highlighting the health-promoting benefits of ARW, we also emphasize the importance of maintaining a healthy lifestyle by incorporating exercise and practicing a balanced diet as forms of habit.

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Abstract 268: Vascular Dysfunction in High BMI Black College Football Players

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.268 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Edward M Powers ◽

Murat Fudim ◽

Heidi J Silver ◽

Robert W Fitch ◽

Kevin D Niswender

Keyword(s):

Oxidative Stress ◽

Vascular Dysfunction ◽

Caloric Intake ◽

Positive Energy ◽

Football Players ◽

Arterial Elasticity ◽

Black Athletes ◽

Positive Energy Balance ◽

And Oxidative Stress ◽

High Bmi

Background: Former football players (FP) who competed with BMI > 30 have high rates of atherosclerosis and early mortality (28% by age 50). FP are disproportionately black, a group predisposed to hypertension and atherosclerosis. Hypothesis: Positive energy balance and oxidative stress lead to vascular dysfunction in black FP. Methods: High BMI college FP (n=33) underwent metabolic and vascular testing at the Vanderbilt Medical Center during the offseason training program. Endothelial function was tested using flow-mediated dilation (FMD) of the brachial artery. Arterial elasticity and vascular resistance were tested using a calibrated tonometer. Regression was performed using least squares on Stat, version 12. Results: Elevated blood pressure (EBP) (SBP > 130) was common in both black (n = 14) and white (n = 19) athletes (78% vs 63%, p = .34). Black players had significantly higher systemic vascular resistance and lower arterial elasticity. However, they had significantly better lipid profiles and body composition, and comparable insulin resistance assessed by HOMA. In black FP, EBP was associated with positive energy balance (4.3 kg gained during six weeks from enrollment to clinic visit vs. 0.7 kg, p = .05). Daily caloric intake predicted endothelial function as measured by flow mediated vasodilation (FMD) (r=.76, p=.001). Caloric intake and oxidative stress (F2-isoprostanes) trended to inversely correlate with larger artery elasticity (r=.40, p=.09 and r=.41, p=.09, respectively). HOMA did not predict FMD (r < .01, p = .56). Respiratory quotient (RQ) correlated with f2-isoprostanes (r=.53, p=.02), suggesting a link between mitochondrial dysfunction and oxidative stress. Conclusion: High BMI black FP suffer from vascular dysfunction, possibly due to oxidative stress from overfeeding. This correlates with studies of non-athlete adult population, but differs notably in being independent of insulin resistance. A larger, longitudinal study is needed to establish a link between overfeeding, vascular dysfunction and early cardiovascular morbidity and mortality in high BMI black athletes. The role of oxidative stress and selective use of nitric oxide donor drugs in black athletes should be explored.

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N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature

Antioxidants ◽

10.3390/antiox9121283 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1283

Author(s):

Phiwayinkosi V. Dludla ◽

Bongani B. Nkambule ◽

Sithandiwe E. Mazibuko-Mbeje ◽

Tawanda M. Nyambuya ◽

Fabio Marcheggiani ◽

...

Keyword(s):

Oxidative Stress ◽

Lipid Accumulation ◽

Randomized Clinical Trials ◽

Therapeutic Potential ◽

Therapeutic Effects ◽

Metabolic Complications ◽

Alcoholic Fatty Liver ◽

Hepatic Lipid ◽

Hepatic Lipid Accumulation ◽

Acetyl Cysteine

Impaired adipose tissue function and insulin resistance remain instrumental in promoting hepatic lipid accumulation in conditions of metabolic syndrome. In fact, enhanced lipid accumulation together with oxidative stress and an abnormal inflammatory response underpin the development and severity of non-alcoholic fatty liver disease (NAFLD). There are currently no specific protective drugs against NAFLD, and effective interventions involving regular exercise and healthy diets have proved difficult to achieve and maintain. Alternatively, due to its antioxidant and anti-inflammatory properties, there has been growing interest in understanding the therapeutic effects of N-acetyl cysteine (NAC) against metabolic complications, including NAFLD. Here, reviewed evidence suggests that NAC blocks hepatic lipid accumulation in preclinical models of NAFLD. This is in part through the effective regulation of a fatty acid scavenger molecule (CD36) and transcriptional factors such as sterol regulatory element-binding protein (SREBP)-1c/-2 and peroxisome proliferator-activated receptor gamma (PPARγ). Importantly, NAC appears effective in improving liver function by reducing pro-inflammatory markers such as interleukin (IL)-6 IL-1β, tumour necrosis factor alpha (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). This was primarily through the attenuation of lipid peroxidation and enhancements in intracellular response antioxidants, particularly glutathione. Very few clinical studies support the beneficial effects of NAC against NAFLD-related complications, thus well-organized randomized clinical trials are still necessary to confirm its therapeutic potential.

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Oxidative Stress during Development of Alcoholic Fatty Liver: Therapeutic Potential of Cacao Polyphenol

Bioscience Biotechnology and Biochemistry ◽

10.1271/bbb.130380 ◽

2013 ◽

Vol 77 (8) ◽

pp. 1792-1794 ◽

Cited By ~ 8

Author(s):

Koichiro SUZUKI ◽

Kiyotaka NAKAGAWA ◽

Taiki MIYAZAWA ◽

Shunji KATO ◽

Fumiko KIMURA ◽

...

Keyword(s):

Oxidative Stress ◽

Fatty Liver ◽

Therapeutic Potential ◽

Alcoholic Fatty Liver

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Paraoxonase-1 as a Regulator of Glucose and Lipid Homeostasis: Impact on the Onset and Progression of Metabolic Disorders

International Journal of Molecular Sciences ◽

10.3390/ijms20164049 ◽

2019 ◽

Vol 20 (16) ◽

pp. 4049 ◽

Cited By ~ 10

Author(s):

Meneses ◽

Silvestre ◽

Sousa-Lima ◽

Macedo

Keyword(s):

Oxidative Stress ◽

Metabolic Disorders ◽

Physiological Role ◽

Normal Activity ◽

Protective Role ◽

Paraoxonase 1 ◽

Alcoholic Fatty Liver ◽

Glucose And Lipid Homeostasis ◽

The Impact ◽

And Oxidative Stress

Metabolic disorders are characterized by an overall state of inflammation and oxidative stress, which highlight the importance of a functional antioxidant system and normal activity of some endogenous enzymes, namely paraoxonase-1 (PON1). PON1 is an antioxidant and anti-inflammatory glycoprotein from the paraoxonases family. It is mainly expressed in the liver and secreted to the bloodstream, where it binds to HDL. Although it was first discovered due to its ability to hydrolyze paraoxon, it is now known to have an antiatherogenic role. Recent studies have shown that PON1 plays a protective role in other diseases that are associated with inflammation and oxidative stress, such as Type 1 and Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease. The aim of this review is to elucidate the physiological role of PON1, as well as the impact of altered PON1 levels in metabolic disorders.

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Abstract 17720: Unique Features of Metabolic Syndrome in High BMI College Football Players

Circulation ◽

10.1161/circ.132.suppl_3.17720 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Edward M Powers ◽

Heidi J Silver ◽

Lynn A Seabolt ◽

Abbie L Warren ◽

Hakmook Kang ◽

...

Keyword(s):

Oxidative Stress ◽

Metabolic Syndrome ◽

Energy Balance ◽

Medical Center ◽

College Football ◽

Positive Energy ◽

Football Players ◽

The Metabolic Syndrome ◽

Positive Energy Balance ◽

High Bmi

Background: Metabolic syndrome in football players is a common, yet poorly understood phenomenon. With 88,000 college football players and one million high school football players, there is a large, at-risk population. Hypothesis: We hypothesized that metabolic syndrome in football players is driven by oxidative stress and positive energy balance. Methods: A single site, cross-sectional study was performed at Vanderbilt University Medical Center of high BMI college football players (n=33). Prevalence of metabolic syndrome was determined. Data related to diet composition, oxidative stress, inflammation, body composition, glucose disposition, lipoprotein metabolism, and endothelial function were assessed to identify drivers of the metabolic syndrome in this cohort. Results: Prevalence of clinical metabolic syndrome was 33% (11/33) despite high cardiorespiratory fitness in all players (Table 1). Elevated waist circumference, HDL, and elevated blood pressure were present together in 73% of cases. Cases had increased oxidative stress (F2-isoprostanes) and inflammation (CRP). Insulin resistance was not worse by HOMA. Visceral fat predicted HDL and CRP. Respiratory quotient was identical between groups but metabolomics revealed decreased TCA cycle intermediates in cases. There were no differences in caloric intake but cases had gained more weight (4.2 vs 2.0 kg, p=.06). Conclusion: High BMI collegiate football players have metabolic syndrome at unexpectedly high rates with a unique set of risk factors and unusual pathophysiology. They have low HDL despite normal triglyceride levels and no defects in glucose metabolism. These data suggest deleterious effects of positive energy balance and oxidative stress irrespective of exercise quantity. These results provide strong rationale to conduct larger, longitudinal studies.

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Leaf powder supplementation of Senna alexandrina ameliorates oxidative stress, inflammation, and hepatic steatosis in high-fat diet-fed obese rats

PLoS ONE ◽

10.1371/journal.pone.0250261 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0250261

Author(s):

Shariful Islam Nayan ◽

Faizul Islam Chowdhury ◽

Noushin Akter ◽

Md Mizanur Rahman ◽

Saima Selim ◽

...

Keyword(s):

Oxidative Stress ◽

Fatty Liver ◽

High Fat Diet ◽

Therapeutic Potential ◽

High Fat ◽

Gene Expressions ◽

Alcoholic Fatty Liver ◽

Leaf Powder ◽

Natural Leaf ◽

Senna Alexandrina

Obesity is an enduring medical issue that has raised concerns around the world. Natural plant extracts have shown therapeutic potential in preventing oxidative stress and inflammation related to obesity complications. In this study, Senna alexandrina Mill. leaves were utilized to treat high-fat diet-related metabolic disorders and non-alcoholic fatty liver diseases. Plasma biochemical assays were conducted to determine the lipid profiles and oxidative stress parameters, and the gene expression of antioxidant enzymes and inflammatory mediators was measured. Histological stained livers of high-fat diet-fed rats were observed. S. alexandrina leaf powder supplementation prevented the increase in cholesterol and triglyceride levels in high-fat diet-fed rats. Moreover, S. alexandrina leaves also reduced lipid peroxidation and nitric oxide production in these rats. Prevention of oxidative stress by S. alexandrina leaf supplementation in high-fat diet-fed rats is regulated by enhancing the antioxidant enzyme activity, followed by the restoration of corresponding gene expressions, such as NRF-2, HO-1, SOD, and CAT. Histological staining provides further evidence that S. alexandrina leaf supplementation prevents inflammatory cell infiltration, lipid droplet deposition, and fibrosis in the liver of high-fat diet-fed rats. Furthermore, this investigation revealed that S. alexandrina leaf supplementation controlled non-alcoholic fatty liver disease by modulating the expression of fat metabolizing enzymes in high-fat diet-fed rats. Therefore, S. alexandrina leaf supplementation inhibits fatty liver inflammation and fibrosis, suggesting its usefulness in treating non-alcoholic steatohepatitis. Thus, this natural leaf extract has potential in treatment of obesity related liver dysfunction.

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Oxidative Stress and Non-Alcoholic Fatty Liver Disease: Effects of Omega-3 Fatty Acid Supplementation

Nutrients ◽

10.3390/nu11040872 ◽

2019 ◽

Vol 11 (4) ◽

pp. 872 ◽

Cited By ~ 42

Author(s):

Jinchunzi Yang ◽

Marta Fernández-Galilea ◽

Leyre Martínez-Fernández ◽

Pedro González-Muniesa ◽

Adriana Pérez-Chávez ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Metabolic Diseases ◽

Therapeutic Potential ◽

Omega 3 ◽

Alcoholic Fatty Liver ◽

Pufa Supplementation ◽

Alcoholic Fatty Liver Disease

Aging is a complex phenomenon characterized by the progressive loss of tissue and organ function. The oxidative-stress theory of aging postulates that age-associated functional losses are due to the accumulation of ROS-induced damage. Liver function impairment and non-alcoholic fatty liver disease (NAFLD) are common among the elderly. NAFLD can progress to non-alcoholic steatohepatitis (NASH) and evolve to hepatic cirrhosis or hepatic carcinoma. Oxidative stress, lipotoxicity, and inflammation play a key role in the progression of NAFLD. A growing body of evidence supports the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFA), mainly docosahaexenoic (DHA) and eicosapentaenoic acid (EPA), on metabolic diseases based on their antioxidant and anti-inflammatory properties. Here, we performed a systematic review of clinical trials analyzing the efficacy of n-3 PUFA on both systemic oxidative stress and on NAFLD/NASH features in adults. As a matter of fact, it remains controversial whether n-3 PUFA are effective to counteract oxidative stress. On the other hand, data suggest that n-3 PUFA supplementation may be effective in the early stages of NAFLD, but not in patients with more severe NAFLD or NASH. Future perspectives and relevant aspects that should be considered when planning new randomized controlled trials are also discussed.

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EVALUATION OF ANTI DIABETIC DRUG ALOGLIPTIN FOR THE TREATMENT OF OBESITY IN RATS

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v8i5.1857 ◽

2018 ◽

Vol 8 (5) ◽

pp. 209-216

Author(s):

Mohd. Fasih Ahmad ◽

D. J. Mani Babu ◽

Anup Pradhan

Keyword(s):

Metabolic Disorders ◽

Complex Disease ◽

The Body ◽

Health Concern ◽

Positive Energy ◽

Cholesterol Levels ◽

Vldl Cholesterol ◽

Positive Energy Balance ◽

High Doses ◽

Treatment Of Obesity

Obesity is a complex disease caused by the interaction of a myriad of genetic, dietary, lifestyle, and environmental factors, which favors a chronic positive energy balance, and leads to increased body fat mass. The incidence of obesity is rising at an alarming rate and is becoming a major public health concern with incalculable social costs. Indeed, obesity facilitates the development of metabolic disorders such as diabetes, hypertension, and cardiovascular diseases in addition to chronic diseases such as stroke, osteoarthritis, sleep apnea, some cancers, and inflammation based pathologies. Standard reference Sibutramine produced a significant anti obesity activity in HFD induced obesity in rats. Alogliptin with medium and high doses exhibited a significant anti obesity activity by reducing the body weight, food intake, organ and fat pads weight and serum GLU, CHO, TRG, LDL and VLDL cholesterol levels with an increased HDL levels in HFD induced obesity models in rats. Keywords: Alogliptin, Anti-obesity, Anti-diabetics, DPP-4

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Therapeutic potential of policosanol in the concurrent management of dyslipidemia and non-alcoholic fatty liver disease

Future Journal of Pharmaceutical Sciences ◽

10.1186/s43094-022-00399-4 ◽

2022 ◽

Vol 8 (1) ◽

Author(s):

Mandeep K. Arora ◽

Sudhanshu Pandey ◽

Ritu Tomar ◽

Jagannath Sahoo ◽

Dinesh Kumar ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Wistar Rats ◽

Therapeutic Potential ◽

Serum Glutamic Oxaloacetic Transaminase ◽

Alcoholic Fatty Liver ◽

Hepatic Oxidative Stress ◽

Alcoholic Fatty Liver Disease

Abstract Background High-fat diet (HFD) possesses a major cause of cardiovascular disease, and hepatosteatosis. Unfortunately, long-term use of statins has a theoretical possibility of worsening of hepatic histology in the patients with non-alcoholic fatty liver disease (NAFLD). The objective of the study was to explore hepatoprotective potential of policosanol as an alternative to statins in experimental NAFLD. For the same, young male Wistar rats were fed with HFD for 8 weeks to induce NAFLD. 48 adult Wistar rats were distributed into six investigational groups: normal control, HFD control, and four treatment groups, receiving policosanol (50 and 100 mg/kg/day), atorvastatin (30 mg/kg/day), and silymarin (100 mg/kg/day) for 8 weeks along with HFD. Result HFD consumption caused profound hepatotoxicity evident by hepatic oxidative stress, increased Serum glutamic oxaloacetic transaminase (SGOT), Serum glutamic pyruvic transaminase (SGPT), Alkaline phosphatase (ALP), and bilirubin content. Treatment with policosanol (100 mg/kg) markedly reduced the elevated SGOT, SGPT, and ALP levels in HFD-fed rats. Moreover, policosanol significantly reduced hepatic oxidative stress manifest by reduced malondialdehyde (MDA) and increased glutathione (GSH) level. The treatment with policosanol (100 mg/kg) was found to be more active in attenuating the HFD-induced hepatotoxicity as compared to policosanol (50 mg/kg) and atorvastatin (30 mg/kg). Moreover, we observed that the hepatoprotective potential of policosanol was comparable to the silymarin. Conclusions The results of the study clearly indicated that the policosanol could be considered an intriguing approach for the treatment of NAFLD.

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Phytochemicals: Targeting Mitophagy to Treat Metabolic Disorders

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.686820 ◽

2021 ◽

Vol 9 ◽

Author(s):

Zuqing Su ◽

Yanru Guo ◽

Xiufang Huang ◽

Bing Feng ◽

Lipeng Tang ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

Metabolic Disorders ◽

Molecular Mechanisms ◽

Therapeutic Effects ◽

Alcoholic Fatty Liver ◽

Calorie Diet ◽

Underlying Mechanisms ◽

High Calorie

Metabolic disorders include metabolic syndrome, obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease and cardiovascular diseases. Due to unhealthy lifestyles such as high-calorie diet, sedentary and physical inactivity, the prevalence of metabolic disorders poses a huge challenge to global human health, which is the leading cause of global human death. Mitochondrion is the major site of adenosine triphosphate synthesis, fatty acid β−oxidation and ROS production. Accumulating evidence suggests that mitochondrial dysfunction-related oxidative stress and inflammation is involved in the development of metabolic disorders. Mitophagy, a catabolic process, selectively degrades damaged or superfluous mitochondria to reverse mitochondrial dysfunction and preserve mitochondrial function. It is considered to be one of the major mechanisms responsible for mitochondrial quality control. Growing evidence shows that mitophagy can prevent and treat metabolic disorders through suppressing mitochondrial dysfunction-induced oxidative stress and inflammation. In the past decade, in order to expand the range of pharmaceutical options, more and more phytochemicals have been proven to have therapeutic effects on metabolic disorders. Many of these phytochemicals have been proved to activate mitophagy to ameliorate metabolic disorders. Given the ongoing epidemic of metabolic disorders, it is of great significance to explore the contribution and underlying mechanisms of mitophagy in metabolic disorders, and to understand the effects and molecular mechanisms of phytochemicals on the treatment of metabolic disorders. Here, we investigate the mechanism of mitochondrial dysfunction in metabolic disorders and discuss the potential of targeting mitophagy with phytochemicals for the treatment of metabolic disorders, with a view to providing a direction for finding phytochemicals that target mitophagy to prevent or treat metabolic disorders.

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