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Title:
Phase I single center trial of ketogenic diet for adults with traumatic brain injury
Authors:
Arora, Niraj; Litofsky, N. Scott; Golzy, Mojgan; Aneja, Rachna; Staudenmyer, Danielle; Qualls, Kathyrn; Patil, Sachin
Abstract:
BACKGROUND: Traumatic Brain injury (TBI) is a major cause of mortality and morbidity in the United States. Ketogenic diet (KD) has been shown to have neuroprotective effects in acute brain injury, but limited data about its use in adult TBI patients is available. The objective of this study is to investigate the feasibility and safety of ketogenic diet (KD) for adult TBI patients in the Neuroscience Intensive Care Unit (NSICU). METHODS: TBI patients admitted to NSICU between June 2019 to March 2021 were enrolled in this single-center, open label, single-arm prospective intervention study. The primary feasibility outcome was achievement of ketosis (detection and maintenance of serum beta-hydroxybutyrate (BOB) levels above normal); secondary outcomes included laboratory and clinical adverse effects related to KD. RESULTS: 10 adults with TBI with Abbreviated Injury Score (AIS)-Head ≥3 and ventriculostomy catheter to monitor intracranial pressure met inclusion/exclusion criteria and were placed on KD. Mean age was 47 years, and all patients were male. Eight out of 10 patients achieved ketosis within mean 2.2 days. KD was initiated within 8-33 h (average 23 h) of hospital admission. No clinical adverse effects were noted, 2 patients developed hypertriglyceridemia and 1 patient developed hypoglycemia. Serum glucose showed a decreasing trend in most patients. CONCLUSIONS: This pilot study shows that KD is feasible in the management of TBI patients. A randomized controlled trial (RCT) is justified to further understand the optimal serum BOB levels, dose and duration of KD in TBI and its effect on the outcome. CLINICALTRIALS. GOV IDENTIFIER: NCT03982602, Registered 06/11/2019, https://clinicaltrials.gov/ct2/show/NCT03982602?term=brain+injury&cond=ketogenic+diet&draw=2&rank=3.
Published:
2022-02
Title:
Sex differences in endurance exercise capacity and skeletal muscle lipid metabolism in mice
Authors:
Holcomb, Lola E.; Rowe, Patrick; O'Neill, Caitlin C.; DeWitt, Elizabeth A.; Kolwicz, Stephen C.
Abstract:
Previous studies suggest that sex differences in lipid metabolism exist with females demonstrating a higher utilization of lipids during exercise, which is mediated partly by increased utilization of muscle triglycerides. However, whether these changes in lipid metabolism contribute directly to endurance exercise performance is unclear. Therefore, the objective of this study was to investigate the contribution of exercise substrate metabolism to sex differences in endurance exercise capacity (EEC) in mice. Male and female C57BL/6-NCrl mice were subjected to an EEC test until exhaustion on a motorized treadmill. The treadmill was set at a 10% incline, and the speed gradually increased from 10.2 m/min to 22.2 m/min at fixed intervals for up to 2.5 h. Tissues and blood were harvested in mice immediately following the EEC. A cohort of sedentary, non-exercised male and female mice were used as controls. Females outperformed males by ~25% on the EEC. Serum levels of both fatty acids and ketone bodies were ~50% higher in females at the end of the EEC. In sedentary female mice, skeletal muscle triglyceride content was significantly greater compared to sedentary males. Gene expression analysis demonstrated that genes involved in skeletal muscle fatty acid oxidation were significantly higher in females with no changes in genes associated with glucose uptake or ketone body oxidation. The findings suggest that female mice have a higher endurance exercise capacity and a greater ability to mobilize and utilize fatty acids for energy.
Published:
2022-02
Title:
AGC1 Deficiency: Pathology and Molecular and Cellular Mechanisms of the Disease
Authors:
Pardo, Beatriz; Herrada-Soler, Eduardo; Satrústegui, Jorgina; Contreras, Laura; del Arco, Araceli
Abstract:
AGC1/Aralar/Slc25a12 is the mitochondrial carrier of aspartate-glutamate, the regulatory component of the NADH malate-aspartate shuttle (MAS) that transfers cytosolic redox power to neuronal mitochondria. The deficiency in AGC1/Aralar leads to the human rare disease named “early infantile epileptic encephalopathy 39” (EIEE 39, OMIM # 612949) characterized by epilepsy, hypotonia, arrested psychomotor neurodevelopment, hypo myelination and a drastic drop in brain aspartate (Asp) and N-acetylaspartate (NAA). Current evidence suggest that neurons are the main brain cell type expressing Aralar. However, paradoxically, glial functions such as myelin and Glutamine (Gln) synthesis are markedly impaired in AGC1 deficiency. Herein, we discuss the role of the AGC1/Aralar-MAS pathway in neuronal functions such as Asp and NAA synthesis, lactate use, respiration on glucose, glutamate (Glu) oxidation and other neurometabolic aspects. The possible mechanism triggering the pathophysiological findings in AGC1 deficiency, such as epilepsy and postnatal hypomyelination observed in humans and mice, are also included. Many of these mechanisms arise from findings in the aralar-KO mice model that extensively recapitulate the human disease including the astroglial failure to synthesize Gln and the dopamine (DA) mishandling in the nigrostriatal system. Epilepsy and DA mishandling are a direct consequence of the metabolic defect in neurons due to AGC1/Aralar deficiency. However, the deficits in myelin and Gln synthesis may be a consequence of neuronal affectation or a direct effect of AGC1/Aralar deficiency in glial cells. Further research is needed to clarify this question and delineate the transcellular metabolic fluxes that control brain functions. Finally, we discuss therapeutic approaches successfully used in AGC1-deficient patients and mice.
Published:
2022-01
Title:
Analysis of Factors That May Affect the Effectiveness of Ketogenic Diet Treatment in Pediatric and Adolescent Patients
Authors:
Winczewska-Wiktor, Anna; Hirschfeld, Adam Sebastian; Badura-Stronka, Magdalena; Komasińska-Piotrowska, Paulina; Steinborn, Barbara
Abstract:
Purpose. The aim was to find predictors for ketogenic diet (KD) treatment effectiveness. In addition, recognized factors influencing the efficacy of KD were analyzed based on the ILAE (International League Against Epilepsy) proposed Classification and Definition of the Epilepsy Syndromes. Methods. A sample of 42 patients treated with KD were analyzed. The effectiveness of KD was assessed according to the type of diet, the type of seizures, and the known (KE) or undetermined genetic etiology (UNKE). The group of KE consisted of patients with CACNA1S, CHD2, DEPDC5, KIF1A, PIGN, SCN1A, SCN8A, SLC2A1, SYNGAP1 pathogenic variants. The usefulness of the new Classification and Definition of Epilepsy Syndromes proposed by the ILAE was evaluated. Results. KD therapy was effective in 69.05% of cases. No significant correlation was observed with the type of diet used. KE was related to greater effectiveness after KD treatment. KD treatment was most effective in the reduction of non-focal seizures. Considering the ILAE proposed classification, it was found that KD efficacy was higher in patients with simultaneous focal and tonic-clonic seizures compared to patients with only tonic-clonic or focal seizures. Conclusion. The occurrence of focal seizures does not determine the potential ineffectiveness of treatment with a ketogenic diet. A significant efficacy of ketogenic diet treatment was observed in the group of patients with focal and generalized seizures, as well as epileptic and developmental encephalopathies. The etiology of epileptic seizures plays a more significant role. The new classification will make it easier to select patients who can benefit from this form of treatment.
Published:
2022-01
Title:
Circulating metabolite homeostasis achieved through mass action
Authors:
Li, Xiaoxuan; Hui, Sheng; Mirek, Emily T.; Jonsson, William O.; Anthony, Tracy G.; Lee, Won Dong; Zeng, Xianfeng; Jang, Cholsoon; Rabinowitz, Joshua D.
Abstract:
Homeostasis maintains serum metabolites within physiological ranges. For glucose, this requires insulin, which suppresses glucose production while accelerating its consumption. For other circulating metabolites, a comparable master regulator has yet to be discovered. Here we show that, in mice, many circulating metabolites are cleared via the tricarboxylic acid cycle (TCA) cycle in linear proportionality to their circulating concentration. Abundant circulating metabolites (essential amino acids, serine, alanine, citrate, 3-hydroxybutyrate) were administered intravenously in perturbative amounts and their fluxes were measured using isotope labelling. The increased circulating concentrations induced by the perturbative infusions hardly altered production fluxes while linearly enhancing consumption fluxes and TCA contributions. The same mass action relationship between concentration and consumption flux largely held across feeding, fasting and high- and low-protein diets, with amino acid homeostasis during fasting further supported by enhanced endogenous protein catabolism. Thus, despite the copious regulatory machinery in mammals, circulating metabolite homeostasis is achieved substantially through mass action-driven oxidation.
Published:
2022-01
Title:
Meal Timing and Macronutrient Composition Modulate Human Metabolism and Reward-Related Drive to Eat
Authors:
Chamorro, Rodrigo; Kannenberg, Swantje; Wilms, Britta; Kleinerüschkamp, Christina; Meyhöfer, Svenja; Park, Soyoung Q.; Lehnert, Hendrik; Oster, Henrik; Meyhöfer, Sebastian M.
Abstract:
The ‘time-of-day’ modifies the metabolic response to meals, but less data exist on the diurnal variations in the hedonic drive to eat. In the present paper, we evaluate the effects of meal timing and macronutrient composition on metabolic responses and the homeostatic vs. hedonic regulation of appetite. In study 1, 84 young, healthy adults completed an online computer-based task assessing the homeostatic and hedonic drive to eat in the morning and evening. In study 2, 24 healthy, young men received 2 identical (850 kcal each) meals in the morning (8:45 h) and evening (18:00 h), of 2 experimental conditions: (i) regular carbohydrate (CH) meals (regular-CH), and (ii) high carbohydrate (high-CH) meals, containing 50 and 80% of energy from CHs, respectively. Serial blood samples were obtained, and the postprandial feelings of hunger, satiety, wanting and liking were assessed. Study 1 revealed a higher hedonic drive to eat in the evening compared to the morning. Study 2 confirmed this diurnal pattern of hedonic appetite regulation and, moreover, showed increased glucose and insulin responses to the evening meal. Postprandial ghrelin and leptin as well as feelings of hunger and satiety were not different between the mealtimes nor between the macronutrient conditions. In line with this, the homeostatic drive to eat was neither affected by the mealtime nor macronutrient composition. Increased the hedonic drive to eat in the evening may represent a vulnerability to palatable food and, thus, energy overconsumption. Together with lower evening glucose tolerance, these findings reflect an adverse metabolic constellation at the end of the day, especially after the ingestion of CH-rich foods.
Published:
2022-01
Title:
Metabolic Adaptions/Reprogramming in Islet Beta-Cells in Response to Physiological Stimulators—What Are the Consequences
Authors:
Newsholme, Philip; Rowlands, Jordan; Rose’Meyer, Roselyn; Cruzat, Vinicius
Abstract:
Irreversible pancreatic β-cell damage may be a result of chronic exposure to supraphysiological glucose or lipid concentrations or chronic exposure to therapeutic anti-diabetic drugs. The β-cells are able to respond to blood glucose in a narrow concentration range and release insulin in response, following activation of metabolic pathways such as glycolysis and the TCA cycle. The β-cell cannot protect itself from glucose toxicity by blocking glucose uptake, but indeed relies on alternative metabolic protection mechanisms to avoid dysfunction and death. Alteration of normal metabolic pathway function occurs as a counter regulatory response to high nutrient, inflammatory factor, hormone or therapeutic drug concentrations. Metabolic reprogramming is a term widely used to describe a change in regulation of various metabolic enzymes and transporters, usually associated with cell growth and proliferation and may involve reshaping epigenetic responses, in particular the acetylation and methylation of histone proteins and DNA. Other metabolic modifications such as Malonylation, Succinylation, Hydroxybutyrylation, ADP-ribosylation, and Lactylation, may impact regulatory processes, many of which need to be investigated in detail to contribute to current advances in metabolism. By describing multiple mechanisms of metabolic adaption that are available to the β-cell across its lifespan, we hope to identify sites for metabolic reprogramming mechanisms, most of which are incompletely described or understood. Many of these mechanisms are related to prominent antioxidant responses. Here, we have attempted to describe the key β-cell metabolic adaptions and changes which are required for survival and function in various physiological, pathological and pharmacological conditions.
Published:
2022-01
Title:
Metabolic Implications of Immune Checkpoint Proteins in Cancer
Authors:
Stirling, Elizabeth R.; Bronson, Steven M.; Mackert, Jessica D.; Cook, Katherine L.; Triozzi, Pierre L.; Soto-Pantoja, David R.
Abstract:
Expression of immune checkpoint proteins restrict immunosurveillance in the tumor microenvironment; thus, FDA-approved checkpoint inhibitor drugs, specifically PD-1/PD-L1 and CTLA-4 inhibitors, promote a cytotoxic antitumor immune response. Aside from inflammatory signaling, immune checkpoint proteins invoke metabolic reprogramming that affects immune cell function, autonomous cancer cell bioenergetics, and patient response. Therefore, this review will focus on the metabolic alterations in immune and cancer cells regulated by currently approved immune checkpoint target proteins and the effect of costimulatory receptor signaling on immunometabolism. Additionally, we explore how diet and the microbiome impact immune checkpoint blockade therapy response. The metabolic reprogramming caused by targeting these proteins is essential in understanding immune-related adverse events and therapeutic resistance. This can provide valuable information for potential biomarkers or combination therapy strategies targeting metabolic pathways with immune checkpoint blockade to enhance patient response.
Published:
2022-01
Title:
Metabolic Rewiring by Human Placenta-Derived Mesenchymal Stem Cell Therapy Promotes Rejuvenation in Aged Female Rats
Authors:
Kim, Kyeoung-Hwa; Lee, Kyung-Ah
Abstract:
Aging is a degenerative process involving cell function deterioration, leading to altered metabolic pathways, increased metabolite diversity, and dysregulated metabolism. Previously, we reported that human placenta-derived mesenchymal stem cells (hPD-MSCs) have therapeutic effects on ovarian aging. This study aimed to identify hPD-MSC therapy-induced responses at the metabolite and protein levels and serum biomarker(s) of aging and/or rejuvenation. We observed weight loss after hPD-MSC therapy. Importantly, insulin-like growth factor-I (IGF-I), known prolongs healthy life spans, were markedly elevated in serum. Capillary electrophoresis-time-of-flight mass spectrometry (CE-TOF/MS) analysis identified 176 metabolites, among which the levels of 3-hydroxybutyric acid, glycocholic acid, and taurine, which are associated with health and longevity, were enhanced after hPD-MSC stimulation. Furthermore, after hPD-MSC therapy, the levels of vitamin B6 and its metabolite pyridoxal 5′-phosphate were markedly increased in the serum and liver, respectively. Interestingly, hPD-MSC therapy promoted serotonin production due to increased vitamin B6 metabolism rates. Increased liver serotonin levels after multiple-injection therapy altered the expression of mRNAs and proteins associated with hepatocyte proliferation and mitochondrial biogenesis. Changes in metabolites in circulation after hPD-MSC therapy can be used to identify biomarker(s) of aging and/or rejuvenation. In addition, serotonin is a valuable therapeutic target for reversing aging-associated liver degeneration.
Published:
2022-01
Title:
Metabolic Therapy of Heart Failure: Is There a Future for B Vitamins?
Authors:
Piquereau, Jérôme; Boitard, Solène E.; Ventura-Clapier, Renée; Mericskay, Mathias
Abstract:
Heart failure (HF) is a plague of the aging population in industrialized countries that continues to cause many deaths despite intensive research into more effective treatments. Although the therapeutic arsenal to face heart failure has been expanding, the relatively short life expectancy of HF patients is pushing towards novel therapeutic strategies. Heart failure is associated with drastic metabolic disorders, including severe myocardial mitochondrial dysfunction and systemic nutrient deprivation secondary to severe cardiac dysfunction. To date, no effective therapy has been developed to restore the cardiac energy metabolism of the failing myocardium, mainly due to the metabolic complexity and intertwining of the involved processes. Recent years have witnessed a growing scientific interest in natural molecules that play a pivotal role in energy metabolism with promising therapeutic effects against heart failure. Among these molecules, B vitamins are a class of water soluble vitamins that are directly involved in energy metabolism and are of particular interest since they are intimately linked to energy metabolism and HF patients are often B vitamin deficient. This review aims at assessing the value of B vitamin supplementation in the treatment of heart failure.
Published:
2022-01
Title:
Pathophysiological Integration of Metabolic Reprogramming in Breast Cancer
Authors:
Corchado-Cobos, Roberto; García-Sancha, Natalia; Mendiburu-Eliçabe, Marina; Gómez-Vecino, Aurora; Jiménez-Navas, Alejandro; Pérez-Baena, Manuel Jesús; Holgado-Madruga, Marina; Mao, Jian-Hua; Cañueto, Javier; Castillo-Lluva, Sonia; Pérez-Losada, Jesús
Abstract:
Metabolic changes that facilitate tumor growth are one of the hallmarks of cancer. The triggers of these metabolic changes are located in the tumor parenchymal cells, where oncogenic mutations induce an imperative need to proliferate and cause tumor initiation and progression. Cancer cells undergo significant metabolic reorganization during disease progression that is tailored to their energy demands and fluctuating environmental conditions. Oxidative stress plays an essential role as a trigger under such conditions. These metabolic changes are the consequence of the interaction between tumor cells and stromal myofibroblasts. The metabolic changes in tumor cells include protein anabolism and the synthesis of cell membranes and nucleic acids, which all facilitate cell proliferation. They are linked to catabolism and autophagy in stromal myofibroblasts, causing the release of nutrients for the cells of the tumor parenchyma. Metabolic changes lead to an interstitium deficient in nutrients, such as glucose and amino acids, and acidification by lactic acid. Together with hypoxia, they produce functional changes in other cells of the tumor stroma, such as many immune subpopulations and endothelial cells, which lead to tumor growth. Thus, immune cells favor tissue growth through changes in immunosuppression. This review considers some of the metabolic changes described in breast cancer.
Published:
2022-01
Title:
Punicalagin and Ketogenic Amino Acids Loaded Organic Lipid Carriers Enhance the Bioavailability, Mitochondrial β-Oxidation, and Ketogenesis in Maturing Adipocytes
Authors:
Subash-Babu, Pandurangan; Al-Numair, Nouf; Almuzaini, Tahani; Athinarayanan, Jegan; Alshatwi, Ali Abdullah
Abstract:
The identification of lipolytic bioactive compounds via the functional stimulation of carbohydrate response element-binding protein-1 (CREBp-1) and AMP-activated protein kinase (AMPK) is most warranted. Nano lipid carriers (NLCs) are currently being considered within drug delivery development as they facilitate controlled drug release and have intracellular bioavailability after encapsulating the active principles with lipid matrix. The present study has been designed to synthesize punicalagin, and ketogenic amino acids (KAA) loaded with organic lipid carriers to optimize the liposome-assisted intracellular delivery’s bioavailability. Punicalagin (PUNI) and KAA (tryptophan, methionine, threonine, lysine, and leucine) were encapsulated with chia seed phospholipids by homogenization, emulsification, and cold ultra-sonication method to obtain nano lipid carriers (NLC). The physicochemical characterization of NLCs has been carried out using Zetasizer, FT-IR, and TEM analysis. Punicalagin and ketogenic amino acid-loaded NLCs (NLC-PUNI-KAA) were identified with an average diameter of 240 to 800 nm. The biosafety of NLC-PUNI-KAA has been evaluated in human mesenchymal stem cells. PI staining confirmed that a 0.4, 0.8 or 1.6μg/dL dose of NLC-PUNI-KAA potentially maintains nuclear integration. NLC-PUNI-KAA treated with maturing adipocytes decreased lipid accumulation and significantly increased the gene expression levels of fatty acid beta-oxidation (PPARγC1α, UCP-1 and PRDM-16) pathways when compared to free PUNI (5 μg/dL) treatment. The lipolytic potential has been confirmed by the functional activation of AMPK and CREBp-1 protein levels. In conclusion, NLC-PUNI-KAA treatment effectively increased mitochondrial efficiency more than free punicalagin or orlistat treated maturing adipocyte. Enhanced lipolysis and decreased hypertrophic adipocyte resulted in decreased adipokine secretion, which has been associated with the suppression of obesity-associated comorbidities and vascular cell inflammation. The bioefficacy and lipolytic potential of water-soluble punicalagin have been improved after functional modification into NLCs.
Published:
2022-01
Title:
Randomized Clinical Trial to Evaluate the Morphological Changes in the Adventitial Vasa Vasorum Density and Biological Markers of Endothelial Dysfunction in Subjects with Moderate Obesity Undergoing a Very Low-Calorie Ketogenic Diet
Authors:
Sánchez, Enric; Santos, Maria-Dolores; Nuñez-Garcia, Maitane; Bueno, Marta; Sajoux, Ignacio; Yeramian, Andree; Lecube, Albert
Abstract:
Weight loss after bariatric surgery decreases the earlier expansion of the adventitial vasa vasorum (VV), a biomarker of early atheromatous disease. However, no data are available regarding weight loss achieved by very low calorie ketogenic diets (VLCKD) on VV and lipid-based atherogenic indices. A randomized clinical trial was performed to examine changes in adventitial VV density in 20 patients with moderate obesity who underwent a 6-month very low calorie ketogenic diet (VLCKD, 600–800 kcal/day), and 10 participants with hypocaloric diet based on the Mediterranean Diet (MedDiet, estimated reduction of 500 kcal on the usual intake). Contrast-enhanced carotid ultrasound was used to assess the VV. Body composition analysis was also used. The atherogenic index of plasma (log (triglycerides to high-density lipoprotein cholesterol ratio)) and the triglyceride-glucose index were calculated. Serum concentrations of soluble intercellular adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured. The impact of weight on quality of life-lite (IWQOL-Lite) questionnaire was administered. Participants of intervention groups displayed a similar VV values. Significant improvements of BMI (−5.3 [−6.9 to −3.6] kg/m2, p < 0.001), total body fat (−7.0 [−10.7 to −3.3] %, p = 0.003), and IWQOL-Lite score (−41.4 [−75.2 to −7.6], p = 0.027) were observed in VLCKD group in comparison with MedDiet group. Although after a 6-months follow-up period VV density (mean, right and left sides) did not change significantly in any group, participants in the VLCKD exhibited a significantly decrease both in their atherogenic index of plasma and serum concentration of sICAM-1. A 6-month intervention with VLCKD do not impact in the density of the adventitial VV in subjects with moderate obesity, but induces significant changes in markers of endothelial dysfunction and CV risk.
Published:
2022-01
Title:
Starvation Ketosis in the Pediatric Emergency Department: A Prospective Estimate of Prevalence
Authors:
Millar, Robert; Chiappazzo, Amelia; Palmer, Bethany
Abstract:
Objectives Starvation ketosis may occur in children during intercurrent illnesses due to metabolic adaptation to fasting, resulting in significant ketonemia and sometimes ketoacidosis. Also known as accelerated starvation, common symptoms are vomiting, lethargy, and seizures. Previous studies found the prevalence of ketotic hypoglycemia to be 4 per 100,000 presentations to the emergency department (ED). We hypothesized that the prevalence had been underestimated due to the retrospective nature and restricted definitions of previous studies. Our aim was to determine if a prospective study would confirm a higher prevalence of starvation ketosis in pediatric patients presenting to the ED. Methods A prospective observational study of consecutive patients was performed in an urban pediatric ED utilizing point-of-care testing of capillary blood glucose and ketones in symptomatic children. Results This study found the prevalence of clinically significant ketosis (defined as beta-hydroxybutyrate 2.5 mmol/L or more) to be approximately 1800 per 100,000 ED presentations, with more than 170 per 100,000 also being hypoglycemic. Affected patients were 3 months to 9 years of age. Fifty-five percent of the presentations were boys, and 56% were under the 50th centile for weight. Conclusions This prospective observational study using a targeted testing regimen found the prevalence of both starvation ketosis and hypoglycemia to be much greater than previous studies which used retrospective analyses. A simple capillary test for ketones should be considered in unwell children younger than 10 years who present with vomiting or lethargy, as this may identify the need for specific therapy to resolve ketosis.
Published:
2022-01
Title:
The Effect of the Ketogenic Diet on Adiponectin, Omentin and Vaspin in Children with Drug-Resistant Epilepsy
Authors:
Chyra, Marcin; Roczniak, Wojciech; Świętochowska, Elżbieta; Dudzińska, Magdalena; Oświęcimska, Joanna
Abstract:
Background: Changes in adipokine secretion may be involved in the anti-epileptic effect of a ketogenic diet (KD) in drug-resistant epilepsy (DRE). Objectives: The assessment of the influence of KD on serum adiponectin, omentin-1, and vaspin in children with DRE. Methods: Anthropometric measurements (weight, height, BMI, and waist-to-hip circumference ratio) were performed in 72 children aged 3–9 years, divided into 3 groups: 24 children with DRE treated with KD, 26—treated with valproic acid (VPA), and a control group of 22 children. Biochemical tests included fasting glucose, insulin, beta-hydroxybutyric acid, lipid profile, aminotransferases activities, and blood gasometry. Serum levels of adiponectin, omentin-1 and vaspin were assayed using commercially available ELISA tests. Results: Serum levels of adiponectin and omentin-1 in the KD group were significantly higher and vaspin—lower in comparison to patients receiving VPA and the control group. In all examined children, serum adiponectin and omentin-1 correlated negatively with WHR and serum triglycerides, insulin, fasting glucose, and HOMA-IR. Vaspin levels correlated negatively with serum triglycerides and positively with body weight, BMI, fasting glucose, insulin, and HOMA-IR. Conclusion: One of the potential mechanisms of KD in children with drug-resistant epilepsy may be a modulation of metabolically beneficial and anti-inflammatory adipokine levels.
Published:
2022-01
Title:
The Impact of the Microbiome on Resistance to Cancer Treatment with Chemotherapeutic Agents and Immunotherapy
Authors:
Sevcikova, Aneta; Izoldova, Nikola; Stevurkova, Viola; Kasperova, Barbora; Chovanec, Michal; Ciernikova, Sona; Mego, Michal
Abstract:
Understanding the mechanisms of resistance to therapy in human cancer cells has become a multifaceted limiting factor to achieving optimal cures in cancer patients. Besides genetic and epigenetic alterations, enhanced DNA damage repair activity, deregulation of cell death, overexpression of transmembrane transporters, and complex interactions within the tumor microenvironment, other mechanisms of cancer treatment resistance have been recently proposed. In this review, we will summarize the preclinical and clinical studies highlighting the critical role of the microbiome in the efficacy of cancer treatment, concerning mainly chemotherapy and immunotherapy with immune checkpoint inhibitors. In addition to involvement in drug metabolism and immune surveillance, the production of microbiota-derived metabolites might represent the link between gut/intratumoral bacteria and response to anticancer therapies. Importantly, an emerging trend of using microbiota modulation by probiotics and fecal microbiota transplantation (FMT) to overcome cancer treatment resistance will be also discussed.
Published:
2022-01
Title:
The Implication of Physiological Ketosis on The Cognitive Brain: A Narrative Review
Authors:
Altayyar, Mansour; Nasser, Jennifer A.; Thomopoulos, Dimitra; Bruneau, Michael
Abstract:
Optimal cognitive functions are necessary for activities of daily living and self-independence. Cognitive abilities are acquired during early childhood as part of progressive neurodevelopmental milestones; unfortunately, regressive changes can occur as part of physiological aging, or more ominously, pathological diseases, such as Alzheimer’s disease (AD). Cases of AD and its milder subset, mild cognitive impairment (MCI), are rising and would impose a burdensome impact beyond the individual level. Various dietary and nutritional approaches have potential for promising results in managing cognitive deterioration. Glucose is the core source of bioenergy in the body; however, glucose brain metabolism could be affected in aging cells or due to disease development. Ketone bodies are an efficient alternate fuel source that could compensate for the deficient glycolytic metabolism upon their supra-physiologic availability in the blood (ketosis), which, in turn, could promote cognitive benefits and tackle disease progression. In this review, we describe the potential of ketogenic approaches to produce cognitive benefits in healthy individuals, as well as those with MCI and AD. Neurophysiological changes of the cognitive brain in response to ketosis through neuroimaging modalities are also described in this review to provide insight into the ketogenic effect on the brain outside the framework of purely molecular explanations.
Published:
2022-01
Title:
The Ketogenic Diet: Is It an Answer for Sarcopenic Obesity?
Authors:
Ilyas, Zahra; Perna, Simone; A. Alalwan, Tariq; Zahid, Muhammad Nauman; Spadaccini, Daniele; Gasparri, Clara; Peroni, Gabriella; Faragli, Alessandro; Alogna, Alessio; La Porta, Edoardo; Ali Redha, Ali; Negro, Massimo; Cerullo, Giuseppe; D’Antona, Giuseppe; Rondanelli, Mariangela
Abstract:
This review aims to define the effectiveness of the ketogenic diet (KD) for the management of sarcopenic obesity. As the combination of sarcopenia and obesity appears to have multiple negative metabolic effects, this narrative review discusses the effects of the ketogenic diet as a possible synergic intervention to decrease visceral adipose tissue (VAT) and fatty infiltration of the liver as well as modulate and improve the gut microbiota, inflammation and body composition. The results of this review support the evidence that the KD improves metabolic health and expands adipose tissue γδ T cells that are important for glycaemia control during obesity. The KD is also a therapeutic option for individuals with sarcopenic obesity due to its positive effect on VAT, adipose tissue, cytokines such as blood biochemistry, gut microbiota, and body composition. However, the long-term effect of a KD on these outcomes requires further investigations before general recommendations can be made.
Published:
2022-01
Title:
The Role of the Gut Microbiota on the Beneficial Effects of Ketogenic Diets
Authors:
Attaye, Ilias; van Oppenraaij, Sophie; Warmbrunn, Moritz V.; Nieuwdorp, Max
Abstract:
The ketogenic diet is a dietary regime focused on strongly reducing carbohydrate intake and increasing fat intake; leading to a state of ketosis. The ketogenic diet has gained much popularity over the years due to its effects on promoting weight loss, increasing insulin sensitivity and reducing dyslipidaemia. All these factors play a crucial role in the development of cardio-metabolic diseases; one of the greatest health challenges of the time. Moreover, the ketogenic diet has been known to reduce (epileptic) seizure activity. It is still poorly understood how following a ketogenic diet can lead to these beneficial metabolic effects. However, in recent years it has become clear that diet and the gut microbiota interact with one another and thus influence host health. The goal of this review is to summarize the current state of knowledge regarding the beneficial metabolic effects of the ketogenic diet and the role of gut microbiota in these effects.
Published:
2022-01
Title:
Editorial: Carbohydrate-Restricted Nutrition and Diabetes Mellitus
Authors:
Westman, Eric C.
Abstract:
Published:
2022
Title:
United States Dietary Trends Since 1800: Lack of Association Between Saturated Fatty Acid Consumption and Non-communicable Diseases
Authors:
Lee, Joyce H.; Duster, Miranda; Roberts, Timothy; Devinsky, Orrin
Abstract:
We reviewed data on the American diet from 1800 to 2019.Methods: We examined food availability and estimated consumption data from 1808 to 2019 using historical sources from the federal government and additional public data sources.Results: Processed and ultra-processed foods increased from 60% of foods. Large increases occurred for sugar, white and whole wheat flour, rice, poultry, eggs, vegetable oils, dairy products, and fresh vegetables. Saturated fats from animal sources declined while polyunsaturated fats from vegetable oils rose. Non-communicable diseases (NCDs) rose over the twentieth century in parallel with increased consumption of processed foods, including sugar, refined flour and rice, and vegetable oils. Saturated fats from animal sources were inversely correlated with the prevalence of NCDs.Conclusions: As observed from the food availability data, processed and ultra-processed foods dramatically increased over the past two centuries, especially sugar, white flour, white rice, vegetable oils, and ready-to-eat meals. These changes paralleled the rising incidence of NCDs, while animal fat consumption was inversely correlated.
Published:
2022
Title:
Effect of Anti-Inflammatory Diets on Pain in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis
Authors:
Schönenberger, Katja A.; Schüpfer, Anne-Catherine; Gloy, Viktoria L.; Hasler, Paul; Stanga, Zeno; Kaegi-Braun, Nina; Reber, Emilie
Abstract:
Various nutritional therapies have been proposed in rheumatoid arthritis, particularly diets rich in ω-3 fatty acids, which may lead to eicosanoid reduction. Our aim was to investigate the effect of potentially anti-inflammatory diets (Mediterranean, vegetarian, vegan, ketogenic) on pain. The primary outcome was pain on a 10 cm visual analogue scale. Secondary outcomes were C-reactive protein levels, erythrocyte sedimentation rate, health assessment questionnaire, disease activity score 28, tender/swollen joint counts, weight, and body mass index. We searched MEDLINE (OVID), Embase (Elsevier), and CINAHL for studies published from database inception to 12 November 2021. Two authors independently assessed studies for inclusion, extracted study data, and assessed the risk of bias. We performed a meta-analysis with all eligible randomized controlled trials using RevMan 5. We used mean differences or standardized mean differences and the inverse variance method of pooling using a random-effects model. The search retrieved 564 unique publications, of which we included 12 in the systematic review and 7 in the meta-analysis. All studies had a high risk of bias and the evidence was very low. The main conclusion is that anti-inflammatory diets resulted in significantly lower pain than ordinary diets (−9.22 mm; 95% CI −14.15 to −4.29; p = 0.0002; 7 RCTs, 326 participants).
Published:
2021-12
Title:
Effects of a low carbohydrate diet on sports performance
Authors:
REBIĆ, NEMANJA
Abstract:
Although high carbohydrate intake (>60%) is generally recommended for athletes, nowadays many experiments involve a low carbohydrate diet. Carbohydrate restriction leads to significant hormonal changes as well as reduced glucose utilization and increased utilization of free fatty acids and ketone bodies as energy sources. This narrative review aimed to discuss the physiological basis of low carbohydrate ketogenic diets (LCKD) and their both positive and negative effects on body composition, power, strength, aerobic capacity and anaerobic performance of athletes and physically active subjects. We searched and analyzed earlier and recently published papers on the subject. Research results showed that LCKD facilitates a reduction of body mass and fat mass while promoting maintenance of lean body mass (LBM). However, compared to a diet with a high carbohydrate content, it is challenging to increase LBM. Despite significant metabolic changes and increased fat oxidation LCKD did not show clear and convincing effects on endurance ability. While LCKD can preserve endurance performance in sports where intensity does not exceed 65-70% VO2max, it is not superior compared to a diet high in carbohydrates. Also negative effects on aerobic capacity can be manifested, especially in women, which may be related to a lower status and transport of iron and due to the difference in fat oxidation between genders. Reduced availability of glucose, decreased glycolytic enzyme activity and metabolic inefficiency (higher oxygen consumption for fat oxidation compared to glucose oxidation) might impair anaerobic performance where the intensity exceeds 70-80%. It seems that LCKD has no particular effects on maximum strength, power and anaerobic lactate abilities because they depend on the phosphagen energy system.
Published:
2021-12
Title:
Seasonal variation in added sugar or sugar sweetened beverage intake in Alaska native communities: an exploratory study
Authors:
Hill, Courtney; Nash, Sarah H.; Bersamin, Andrea; Hopkins, Scarlett E.; Boyer, Bert B.; O'Brien, Diane M.; Chi, Donald L.
Abstract:
Excess added sugar intake contributes to tooth decay risk in Alaska Native communities. The goal of this exploratory study was to determine if there is seasonal variation in total added sugar intake or in the leading sources of added sugars in a Yup'ik population. Data were collected in spring and winter from 2008-2010 using self-reported intake data measured by 24-hour recall and by hair biomarker (carbon and nitrogen stable isotope). Seventy Yup'ik participants ages 14-70 years were recruited from two communities and data were collected twice from a subset of 38 participants. Self-reported added sugar intake (g/day), biomarker-predicted added sugar intake (g/day), and leading sources of added sugar were calculated. Seasonal variation was evaluated using a paired sample t-test. Total added sugar intake was 93.6 g/day and did not significantly differ by season. Sodas and other sugar-sweetened beverages (e.g. Tang, Kool-Aid) were the leading sources and added sugar from these sources did not significantly differ by season (p=.54 and p=.89, respectively). No seasonal variation in added sugar intake was detected by either self-report or biomarker. Dietary interventions that reduce intake of added sugars have the potential to reduce tooth decay in Yup'ik communities.
Published:
2021-12
Title:
The Role of Short-Chain Fatty Acids in Mediating Very Low-Calorie Ketogenic Diet-Infant Gut Microbiota Relationships and Its Therapeutic Potential in Obesity
Authors:
Alsharairi, Naser A.
Abstract:
As the very low-calorie ketogenic diet (VLCKD) gains increased interest as a therapeutic approach for many diseases, little is known about its therapeutic use in childhood obesity. Indeed, the role of VLCKD during pregnancy and lactation in influencing short chain fatty acid (SCFA)-producing bacteria and the potential mechanisms involved in the protective effects on obesity are still unclear. Infants are characterized by a diverse gut microbiota composition with higher abundance of SCFA-producing bacteria. Maternal VLCKD during pregnancy and lactation stimulates the growth of diverse species of SCFA-producing bacteria, which may induce epigenetic changes in infant obese gene expression and modulate adipose tissue inflammation in obesity. Therefore, this review aims to determine the mechanistic role of SCFAs in mediating VLCKD-infant gut microbiota relationships and its protective effects on obesity.
Published:
2021-11
Title:
Alternative Dietary Patterns for Americans: Low-Carbohydrate Diets
Authors:
Volek, Jeff S.; Phinney, Stephen D.; Krauss, Ronald M.; Johnson, Richard J.; Saslow, Laura R.; Gower, Barbara; Yancy, William S.; King, Janet C.; Hecht, Frederick M.; Teicholz, Nina; Bistrian, Bruce R.; Hamdy, Osama
Abstract:
The decades-long dietary experiment embodied in the Dietary Guidelines for Americans (DGA) focused on limiting fat, especially saturated fat, and higher carbohydrate intake has coincided with rapidly escalating epidemics of obesity and type 2 diabetes (T2D) that are contributing to the progression of cardiovascular disease (CVD) and other diet-related chronic diseases. Moreover, the lack of flexibility in the DGA as it pertains to low carbohydrate approaches does not align with the contemporary trend toward precision nutrition. We argue that personalizing the level of dietary carbohydrate should be a high priority based on evidence that Americans have a wide spectrum of metabolic variability in their tolerance to high carbohydrate loads. Obesity, metabolic syndrome, and T2D are conditions strongly associated with insulin resistance, a condition exacerbated by increased dietary carbohydrate and improved by restricting carbohydrate. Low-carbohydrate diets are grounded across the time-span of human evolution, have well-established biochemical principles, and are now supported by multiple clinical trials in humans that demonstrate consistent improvements in multiple established risk factors associated with insulin resistance and cardiovascular disease. The American Diabetes Association (ADA) recently recognized a low carbohydrate eating pattern as an effective approach for patients with diabetes. Despite this evidence base, low-carbohydrate diets are not reflected in the DGA. As the DGA Dietary Patterns have not been demonstrated to be universally effective in addressing the needs of many Americans and recognizing the lack of widely available treatments for obesity, metabolic syndrome, and T2D that are safe, effective, and sustainable, the argument for an alternative, low-carbohydrate Dietary Pattern is all the more compelling.
Published:
2021-10
Title:
Carbohydrate-restricted diets and Type 1 diabetes mellitus: research considerations
Authors:
Dikeman, David T.; Westman, Eric C.
Abstract:
Purpose of review Type 1 diabetes mellitus (T1DM) is managed via careful control of blood glucose, exogenous insulin, diet, exercise, and other physiologic factors. Interestingly, the dietary recommendations for T1DM have had very little systematic research. Many clinical observations, as well as emerging research studies, have noted that a carbohydrate-restricted diet can lead to normalization of blood glucoses with reduction in hypoglycemic reactions among motivated individuals. Recent findings In this paper, we review observations of carbohydrate restriction and propose a series of studies to test two levels of dietary carbohydrate intake for the management of individuals affected by T1DM. We recommend that the studies start in otherwise healthy adults with hemoglobin A1c > 8%, and then progress to more complicated populations including children, those with secondary complications and/or good glycemic control. Larger, long-term studies would then address growth in children, and diabetic complications including cardiovascular outcomes. Summary Due to the clinical observations of improvements using carbohydrate-restricted nutrition for T1DM, we recommend that these types of studies addressing the level of dietary carbohydrate be urgently conducted.
Published:
2021-10
Title:
Dietary Saturated Fats and Health: Are the U.S. Guidelines Evidence-Based?
Authors:
Astrup, Arne; Teicholz, Nina; Magkos, Faidon; Bier, Dennis M.; Brenna, J. Thomas; King, Janet C.; Mente, Andrew; Ordovas, José M.; Volek, Jeff S.; Yusuf, Salim; Krauss, Ronald M.
Abstract:
The last decade has seen nearly 20 papers reviewing the totality of the data on saturated fats and cardiovascular outcomes, which, altogether, have demonstrated a lack of rigorous evidence to support continued recommendations either to limit the consumption of saturated fatty acids or to replace them with polyunsaturated fatty acids. These papers were unfortunately not considered by the process leading to the most recent U.S. Dietary Guidelines for Americans, the country’s national nutrition policy, which recently reconfirmed its recommendation to limit saturated fats to 10% or less of total energy intake, based on insufficient and inconsistent evidence. Continuation of a cap on saturated fat intake also fails to consider the important effects of the food matrix and the overall dietary pattern in which saturated fatty acids are consumed.
Published:
2021-10
Title:
Ketogenic diet as an advanced option for the management of pediatric obesity
Authors:
Favret, Jenny; Wood, Charles T.; Maradiaga Panayotti, Gabriela M.
Abstract:
Purpose of review The Duke Healthy Lifestyles Program (HL), established in 2006, has treated over 15,000 pediatric patients with obesity. A subset of patients with obesity do not respond to dietary and lifestyle changes. Development of the Staged Transitional Eating Plan (STEP) in 2012 provided a ketogenic advanced dietary option for these specific patients. Recent findings The goal of STEP is to facilitate weight loss, while assuring adequacy and the promotion of health through the abundant inclusion of vegetables, fatty fish, nuts, olive oil, and other foods consistent with the Mediterranean Diet. STEP is a three-phase eating plan, each with a defined carbohydrate limit. STEP is ideal for patients eager to try a low carbohydrate diet, those with good vegetable acceptance, and those with families who are able to participate in the same eating plan as them. Summary STEP, the HL version of low carbohydrate high fat eating, is a safe dietary intervention for a carefully selected subset of pediatric patients with obesity who are trying to lose weight.
Published:
2021-10
Title:
Processed Meat Consumption and the Risk of Cancer: A Critical Evaluation of the Constraints of Current Evidence from Epidemiological Studies
Authors:
Händel, Mina Nicole; Rohde, Jeanett Friis; Jacobsen, Ramune; Heitmann, Berit Lilienthal
Abstract:
Based on a large volume of observational scientific studies and many summary papers, a high consumption of meat and processed meat products has been suggested to have a harmful effect on human health. These results have led guideline panels worldwide to recommend to the general population a reduced consumption of processed meat and meat products, with the overarching aim of lowering disease risk, especially of cancer. We revisited and updated the evidence base, evaluating the methodological quality and the certainty of estimates in the published systematic reviews and meta-analyses that examined the association between processed meat consumption and the risk of cancer at different sites across the body, as well as the overall risk of cancer mortality. We further explored if discrepancies in study designs and risks of bias could explain the heterogeneity observed in meta-analyses. In summary, there are severe methodological limitations to the majority of the previously published systematic reviews and meta-analyses that examined the consumption of processed meat and the risk of cancer. Many lacked the proper assessment of the methodological quality of the primary studies they included, or the literature searches did not fulfill the methodological standards needed in order to be systematic and transparent. The primary studies included in the reviews had a potential risk for the misclassification of exposure, a serious risk of bias due to confounding, a moderate to serious risk of bias due to missing data, and/or a moderate to serious risk of selection of the reported results. All these factors may have potentially led to the overestimation of the risk related to processed meat intake across all cancer outcomes. Thus, with the aim of lowering the risk of cancer, the recommendation to reduce the consumption of processed meat and meat products in the general population seems to be based on evidence that is not methodologically strong.
Published:
2021-10
Title:
Retrospective cohort study of changes in estimated glomerular filtration rate for patients prescribed a low carb diet
Authors:
Mitchell, Nia S.; Batch, Bryan C.; Tyson, Crystal C.
Abstract:
Purpose of review Obesity and diabetes contribute to chronic kidney disease (CKD) and accelerate the loss of kidney function. Low carbohydrate diets (LCDs) are associated with weight loss and improved diabetes control. Compared to the typical Western diet, LCDs contain more protein, so individuals with CKD are not included in studies of LCDs. Therefore, there are no studies of LCDs for weight loss and their effects on kidney function. Recent findings Obesity, hyperglycemia, and hyperinsulinemia can be detrimental to kidney function. LCDs may improve kidney function in patients with obesity and diabetes because they are associated with weight loss, improve blood sugar control, and decrease endogenous insulin production and exogenous insulin requirements. Summary In this study, for patients with mildly reduced and moderately to severely reduced kidney function who were prescribed an LCD, their estimated glomerular filtration rate (eGFR) was either unchanged or improved. For those with normal or elevated eGFR, their kidney function was slightly decreased. For those without diabetes, greater weight loss was associated with improved eGFR. Future studies should prospectively measure low carbohydrate dietary adherence and physical activity and directly measure changes in GFR and albuminuria for participants with CKD before and during that diet.
Published:
2021-10
Title:
A common genetic variant of a mitochondrial RNA processing enzyme predisposes to insulin resistance
Authors:
Rossetti, Giulia; Ermer, Judith A.; Stentenbach, Maike; Siira, Stefan J.; Richman, Tara R.; Milenkovic, Dusanka; Perks, Kara L.; Hughes, Laetitia A.; Jamieson, Emma; Xiafukaiti, Gulibaikelamu; Ward, Natalie C.; Takahashi, Satoru; Gray, Nicola; Viola, Helena M.; Hool, Livia C.; Rackham, Oliver; Filipovska, Aleksandra
Abstract:
Mitochondrial energy metabolism plays an important role in the pathophysiology of insulin resistance. Recently, a missense N437S variant was identified in the MRPP3 gene, which encodes a mitochondrial RNA processing enzyme within the RNase P complex, ...
Published:
2021-09
Title:
Association between Carbohydrate Intake and the Prevalence of Metabolic Syndrome in Korean Women
Authors:
Cho, Young-Ae; Choi, Jeong-Hwa
Abstract:
Carbohydrates consist of a large proportion of calories in the Asian diet. Therefore, we aimed to investigate the association between carbohydrate intake and metabolic syndrome in Korean women. A cross-sectional analysis was conducted with a total of 4294 Korean women aged 40–69 years from the Korean Genomic and Epidemiology Study (KoGES). Carbohydrate intake was calculated based on a validated food frequency questionnaire. Metabolic syndrome was defined by using the National Cholesterol Education Program, Adult Treatment Panel III (NCEPIII). Logistic regression was used to estimate the association of carbohydrate intake with metabolic syndrome and its components. In this study, high carbohydrate intake seemed to be associated with low socioeconomic status and an imbalanced diet. After adjusting for confounding factors, subjects with higher carbohydrate intake showed an increased risk of metabolic syndrome (odds ratio (OR) 1.34, 95% confidence interval (CI) 1.08–1.66, p-trend = 0.004, highest vs. lowest quartile [≥75.2 vs. <67.0% of energy]), particularly elevated waist circumference. This association was stronger among those with low levels of C-reactive protein (CRP) and those with low dairy intake. In conclusion, higher carbohydrate intake is associated with a higher risk of metabolic syndrome, particularly abdominal obesity, in Korean women. This association may differ according to individuals’ CRP level and dairy intake.
Published:
2021-09
Title:
Association of Lipid Peroxidation Product 4-Hydroxynonenal with Post-Traumatic Stress Disorder
Authors:
Perković, Matea Nikolac; Milković, Lidija; Uzun, Suzana; Mimica, Ninoslav; Pivac, Nela; Waeg, Georg; Žarković, Neven
Abstract:
Repeated activation of the hypothalamic-pituitary-adrenal axis system, sleep disturbances, and other symptoms related to posttraumatic stress disorder (PTSD) elevate reactive oxygen species, increase inflammation, and accelerate cellular aging, leading to neuroprogression and cognitive decline. However, there is no information about possible involvement of 4-hydroxynonenal (4-HNE), the product of lipid peroxidation associated with stress-associated diseases, in the complex etiology of PTSD. Therefore, the aim of this study was to compare the plasma levels of 4-HNE between war veterans with PTSD (n = 62) and age-, sex- and ethnicity- matched healthy control subjects (n = 58) in order to evaluate the potential of HNE-modified proteins as blood-based biomarker of PTSD. The genuine 4-HNE-Enzyme-Linked Immunosorbent Assay (HNE-ELISA), based on monoclonal antibody specific for HNE-histidine (HNE-His) adducts, was used to determine plasma HNE-protein conjugates. Our results revealed significantly elevated levels of 4-HNE in patients with PTSD. Moreover, the accumulation of plasma 4-HNE seems to increase with aging but in a negative correlation with BMI, showing specific pattern of change for individuals diagnosed with PTSD. These findings suggest that oxidative stress and altered lipid metabolism reflected by increase of 4-HNE might be associated with PTSD. If confirmed with further studies, elevated 4-HNE plasma levels might serve as a potential biomarker of PTSD.
Published:
2021-09
Title:
Biologically Active Compounds in Mustard Seeds: A Toxicological Perspective
Authors:
Lietzow, Julika
Abstract:
Mustard plants have been widely cultivated and used as spice, medicine and as source of edible oils. Currently, the use of the seeds of the mustard species Sinapis alba (white mustard or yellow mustard), Brassica juncea (brown mustard) and Brassica nigra ...
Published:
2021-09
Title:
Can Ketogenic Diet Therapy Improve Migraine Frequency, Severity and Duration?
Authors:
Haslam, Rebecca L.; Bezzina, Aaron; Herbert, Jaimee; Spratt, Neil; Rollo, Megan E.; Collins, Clare E.
Abstract:
Migraine is the third most common condition worldwide and is responsible for a major clinical and economic burden. The current pilot trial investigated whether ketogenic diet therapy (KDT) is superior to an evidence-informed healthy “anti-headache” dietary pattern (AHD) in improving migraine frequency, severity and duration. A 12-week randomised controlled crossover trial consisting of the two dietary intervention periods was undertaken. Eligible participants were those with a history of migraines and who had regularly experienced episodes of moderate or mildly intense headache in the previous 4 weeks. Migraine frequency, duration and severity were assessed via self-report in the Migraine Buddy© app. Participants were asked to measure urinary ketones and side effects throughout the KDT. Twenty-six participants were enrolled, and 16 participants completed all sessions. Eleven participants completed a symptom checklist; all reported side-effects during KDT, with the most frequently reported side effect being fatigue (n = 11). All completers experienced migraine during AHD, with 14/16 experiencing migraine during KDT. Differences in migraine frequency, severity or duration between dietary intervention groups were not statistically significant. However, a clinically important trend toward lower migraine duration on KDT was noted. Further research in this area is warranted, with strategies to lower participant burden and promote adherence and retention.
Published:
2021-09
Title:
Can the Mitochondrial Metabolic Theory Explain Better the Origin and Management of Cancer than Can the Somatic Mutation Theory?
Authors:
Seyfried, Thomas N.; Chinopoulos, Christos
Abstract:
A theory that can best explain the facts of a phenomenon is more likely to advance knowledge than a theory that is less able to explain the facts. Cancer is generally considered a genetic disease based on the somatic mutation theory (SMT) where mutations in proto-oncogenes and tumor suppressor genes cause dysregulated cell growth. Evidence is reviewed showing that the mitochondrial metabolic theory (MMT) can better account for the hallmarks of cancer than can the SMT. Proliferating cancer cells cannot survive or grow without carbons and nitrogen for the synthesis of metabolites and ATP (Adenosine Triphosphate). Glucose carbons are essential for metabolite synthesis through the glycolysis and pentose phosphate pathways while glutamine nitrogen and carbons are essential for the synthesis of nitrogen-containing metabolites and ATP through the glutaminolysis pathway. Glutamine-dependent mitochondrial substrate level phosphorylation becomes essential for ATP synthesis in cancer cells that over-express the glycolytic pyruvate kinase M2 isoform (PKM2), that have deficient OxPhos, and that can grow in either hypoxia (0.1% oxygen) or in cyanide. The simultaneous targeting of glucose and glutamine, while elevating levels of non-fermentable ketone bodies, offers a simple and parsimonious therapeutic strategy for managing most cancers.
Published:
2021-09
Title:
Dietary behaviors and patterns of centenarians in Hainan: A cross-sectional study
Authors:
Yang, Shanshan; Wang, Shengshu; Wang, Lili; Liu, Guangdong; Tai, Penggang; Kou, Fuyin; Jia, Wangping; Han, Ke; Liu, Miao; He, Yao
Abstract:
OBJECTIVES: The aim of this study was to understand the diet-related behaviors of Hainan centenarians and to analyze dietary factors that affect their nutritional status. METHODS: Data were collected from the China Hainan Centenarian Cohort Study, a full sample survey including questionnaires, physical examinations, and physiologic indices of the centenarian population. The study included 1002 centenarians. The diet-related behaviors were assessed using the food frequency questionnaire; nutritional status was determined according to the Mini Nutritional Assessment - short form scale scores. We used logistic regression models to analyze the main dietary risk factors of malnutrition. RESULTS: Of all the centenarians, 94.6% maintained regular meals, 80.4% had three meals a day, 53.4% ate each meal until 80% full, 88.7% ate vegetables daily, and 70% drank one to two cups of water daily. Centenarians ate rice-based staple foods; eggs, dairy, legumes, nuts, and poultry were not popular. The main sources of meat were red meat and seafood. None liked fried food, and 19.3% preferred sweet flavors. People with normal nutritional status accounted for 12.3% of the population, whereas those with malnutrition comprised 20.8%. Dietary factors that affected nutritional status included three meals a day (odds ratio [OR], 0.366; 95% confidence interval [CI], 0.173-0.778), tea drinking (OR, 0.236; 95% CI, 0.087-0.641), and the frequency of poultry (OR, 0.261; 95% CI, 0.088-0.771), seafood (OR, 0.247; 95% CI, 0.110-0.554), nuts (OR, 0.381; 95% CI, 0.150-0.965), and pastry (OR, 0.219; 95% CI, 0.080-0.600) consumption. CONCLUSION: This was the first study on the dietary behaviors and nutritional status of centenarians using survey data. We highlighted the factors affecting nutritional status and provided scientific support for dietary strategies that may improve the nutritional status of the elderly population.
Published:
2021-09
Title:
Eating Behaviors and Dietary Patterns of Women during Pregnancy: Optimizing the Universal ‘Teachable Moment’
Authors:
Kebbe, Maryam; Flanagan, Emily W.; Sparks, Joshua R.; Redman, Leanne M.
Abstract:
Understanding women’s perceptions of eating behaviors and dietary patterns can inform the ‘teachable moment’ model of pregnancy. Our objectives were to describe eating behaviors and dietary patterns in pregnancy. This was a cross-sectional, ...
Published:
2021-09
Title:
Food Intolerance: The Role of Histamine
Authors:
Shulpekova, Yulia O.; Nechaev, Vladimir M.; Popova, Irina R.; Deeva, Tatiana A.; Kopylov, Arthur T.; Malsagova, Kristina A.; Kaysheva, Anna L.; Ivashkin, Vladimir T.
Abstract:
Histamine is a natural amine derived from L-histidine. Although it seems that our knowledge about this molecule is wide and diverse, the importance of histamine in many regulatory processes is still enigmatic. The interplay between different types of histamine receptors and the compound may cause ample effects, including histamine intoxication and so-called histamine intolerance or non-allergic food intolerance, leading to disturbances in immune regulation, manifestation of gastroenterological symptoms, and neurological diseases. Most cases of clinical manifestations of histamine intolerance are non-specific due to tissue-specific distribution of different histamine receptors and the lack of reproducible and reliable diagnostic markers. The diagnosis of histamine intolerance is fraught with difficulties, in addition to challenges related to the selection of a proper treatment strategy, the regular course of recovery, and reduced amelioration of chronic symptoms due to inappropriate treatment prescription. Here, we reviewed a history of histamine uptake starting from the current knowledge about its degradation and the prevalence of histamine precursors in daily food, and continuing with the receptor interactions after entering and the impacts on the immune, central nervous, and gastrointestinal systems. The purpose of this review is to build an extraordinarily specific method of histamine cycle assessment in regard to non-allergic intolerance and its possible dire consequences that can be suffered.
Published:
2021-09
Title:
Food Metabolites as Tools for Authentication, Processing, and Nutritive Value Assessment
Authors:
Pedrosa, Mariana C.; Lima, Laíres; Heleno, Sandrina; Carocho, Márcio; Ferreira, Isabel C. F. R.; Barros, Lillian
Abstract:
Secondary metabolites are molecules with unlimited applications that have been gaining importance in various industries and studied from many angles. They are mainly used for their bioactive capabilities, but due to the improvement of sensibility in analytical ...
Published:
2021-09
Title:
Human Hazard Assessment Using Drosophila Wing Spot Test as an Alternative In Vivo Model for Genotoxicity Testing—A Review
Authors:
Pitchakarn, Pornsiri; Inthachat, Woorawee; Karinchai, Jirarat; Temviriyanukul, Piya
Abstract:
Genomic instability, one of cancer’s hallmarks, is induced by genotoxins from endogenous and exogenous sources, including reactive oxygen species (ROS), diet, and environmental pollutants. A sensitive in vivo genotoxicity test is required for ...
Published:
2021-09
Title:
More Than Meets the Eye Regarding Cancer Metabolism
Authors:
Kubicka, Anna; Matczak, Karolina; Łabieniec-Watała, Magdalena
Abstract:
In spite of the continuous improvement in our knowledge of the nature of cancer, the causes of its formation and the development of new treatment methods, our knowledge is still incomplete. A key issue is the difference in metabolism between normal and ...
Published:
2021-09
Title:
Prostate Cancer—Focus on Cholesterol
Authors:
Škara, Lucija; Turković, Ana Huđek; Pezelj, Ivan; Vrtarić, Alen; Sinčić, Nino; Krušlin, Božo; Ulamec, Monika
Abstract:
Prostate cancer presents a significant global public health burden. One of its established risk factors is high fat diet. It has been proven that cholesterol levels in blood and prostate tissue are out of balance, while cholesterol metabolism in prostate ...
Published:
2021-09
Title:
Rethinking Fragility Fractures in Type 2 Diabetes: The Link between Hyperinsulinaemia and Osteofragilitas
Authors:
Cooper, Isabella D.; Brookler, Kenneth H.; Crofts, Catherine A. P.
Abstract:
Patients with type 2 diabetes mellitus (T2DM) and/or cardiovascular disease (CVD), conditions of hyperinsulinaemia, have lower levels of osteocalcin and bone remodelling, and increased rates of fragility fractures. Unlike osteoporosis with lower bone mineral density (BMD), T2DM bone fragility “hyperinsulinaemia-osteofragilitas” phenotype presents with normal to increased BMD. Hyperinsulinaemia and insulin resistance positively associate with increased BMD and fragility fractures. Hyperinsulinaemia enforces glucose fuelling, which decreases NAD+-dependent antioxidant activity. This increases reactive oxygen species and mitochondrial fission, and decreases oxidative phosphorylation high-energy production capacity, required for osteoblasto/cytogenesis. Osteocytes directly mineralise and resorb bone, and inhibit mineralisation of their lacunocanalicular space via pyrophosphate. Hyperinsulinaemia decreases vitamin D availability via adipocyte sequestration, reducing dendrite connectivity, and compromising osteocyte viability. Decreased bone remodelling and micropetrosis ensues. Trapped/entombed magnesium within micropetrosis fossilisation spaces propagates magnesium deficiency (MgD), potentiating hyperinsulinaemia and decreases vitamin D transport. Vitamin D deficiency reduces osteocalcin synthesis and favours osteocyte apoptosis. Carbohydrate restriction/fasting/ketosis increases beta-oxidation, ketolysis, NAD+-dependent antioxidant activity, osteocyte viability and osteocalcin, and decreases excess insulin exposure. Osteocalcin is required for hydroxyapatite alignment, conferring bone structural integrity, decreasing fracture risk and improving metabolic/endocrine homeodynamics. Patients presenting with fracture and normal BMD should be investigated for T2DM and hyperinsulinaemia.
Published:
2021-09
Title:
Sodium Intake and Health: What Should We Recommend Based on the Current Evidence?
Authors:
Mente, Andrew; O’Donnell, Martin; Yusuf, Salim
Abstract:
Several health organizations recommend low sodium intake (below 2.3 g/day, 5.8 g/day of salt) for entire populations, on the premise that lowering of sodium intake, irrespective of its level of intake, will lower blood pressure and, in turn, will result in a lower incidence of cardiovascular disease. These guidelines were developed without effective interventions to achieve long term sodium intakes at low levels in free-living individuals and without high-quality evidence that low sodium intake reduces cardiovascular events (compared with average levels of intake). In this review, we examine whether advice to consume low amounts of sodium is supported by robust evidence. We contend that current evidence indicates that most people around the world consume a moderate range of dietary sodium (3 to 5 g/day), that this level of intake is associated with the lowest risk of cardiovascular disease and mortality, and that the risk of adverse health outcomes increases when sodium intakes exceeds 5 g/day or is below 3 g/day. While the current evidence has limitations, it is reasonable, based upon prospective cohort studies, to suggest a mean target of below 5 g/day in populations, while awaiting the results of large randomized controlled trials of sodium reduction on cardiovascular disease and death.
Published:
2021-09
Title:
Differential Effects of Western and Mediterranean-Type Diets on Gut Microbiota: A Metagenomics and Metabolomics Approach
Authors:
Barber, Claudia; Mego, Marianela; Sabater, Carlos; Vallejo, Fernando; Bendezu, Rogger Alvaro; Masihy, Marcela; Guarner, Francisco; Espín, Juan Carlos; Margolles, Abelardo; Azpiroz, Fernando
Abstract:
Our aim was to determine the effect of diet on gut microbiota, digestive function and sensations, using an integrated clinical, metagenomics and metabolomics approach. We conducted a cross-over, randomised study on the effects of a Western-type diet versus a fibre-enriched Mediterranean diet. In 20 healthy men, each diet was administered for 2 weeks preceded by a 2-week washout diet. The following outcomes were recorded: (a) number of anal gas evacuations; (b) digestive sensations; (c) volume of gas evacuated after a probe meal; (d) colonic content by magnetic resonance imaging; (e) gut microbiota taxonomy and metabolic functions by shotgun sequencing of faecal samples; (f) urinary metabolites using untargeted metabolomics. As compared to a Western diet, the Mediterranean diet was associated with (i) higher number of anal gas evacuations, (ii) sensation of flatulence and borborygmi, (iii) larger volume of gas after the meal and (iv) larger colonic content. Despite the relatively little difference in microbiota composition between both diets, microbial metabolism differed substantially, as shown by urinary metabolite profiles and the abundance of microbial metabolic pathways. The effects of the diet were less evident in individuals with robust microbiotas (higher beta-diversity). To conclude, healthy individuals tolerate dietary changes with minor microbial modifications at the composition level but with remarkable variation in microbial metabolism.
Published:
2021-08
Title:
Five‐day water‐only fasting decreased metabolic‐syndrome risk factors and increased anti‐aging biomarkers without toxicity in a clinical trial of normal‐weight individuals
Authors:
Jiang, Yanyu; Yang, Xi; Dong, Changsheng; Lu, Yun; Yin, Hongmei; Xiao, Biying; Yang, Xuguang; Chen, Wenlian; Cheng, Wei; Tian, Hechuan; Guo, Lin; Hu, Xiaobo; Fang, Hong; Chen, Weiqin; Li, Zhen; Zhou, Wenqin; Sun, Weijun; Guo, Xiyan; Li, Shaobin; Lin, Yuli; He, Rui; Chen, Xiaoyun; Liu, Di; Zhang, Minghui; Zhang, Yanmei; Zhao, Hu; Zheng, Peiyong; Seyfried, Thomas N.; Hoffman, Robert M.; Jia, Wei; Ji, Guang; Jia, Lijun
Abstract:
Published:
2021-08
Title:
Plant‐eating carnivores: Multispecies analysis on factors influencing the frequency of plant occurrence in obligate carnivores
Authors:
Yoshimura, Hiroto; Hirata, Satoshi; Kinoshita, Kodzue
Abstract:
Plant‐eating behavior is one of the greatest mysteries in obligate carnivores. Despite unsuitable morphological and physiological traits for plant consumption, the presence of plants in scat or stomach contents has been reported in various carnivorous ...
Published:
2021-08
Title:
Relationship between traditional maternal diet pattern and breastmilk composition of rural lactating women during the first month postpartum in Shigatse, Tibet
Authors:
Zhang, Xiaomei; Zhang, Minghui; Lin, Tie; Zhao, Junying; Luo, Zhang; Hou, Juncai; Sun, Baoguo; Chen, Lijun
Abstract:
Maternal nutrition can influence the composition of human breastmilk by altering the components that are sensitive to maternal diet pattern. Traditional Tibetan maternal diet pattern among native rural lactating women possesses distinct characteristics due to its unique geographical environment and dietary habits. This study investigated maternal diet pattern and human breastmilk composition of Tibetan lactating women through different lactation stages during the first month postpartum in Shigatse. The results indicated that Tibetan maternal diet profile was apparently monotonous, mainly sufficient in Zanba, buttered tea, red meat, and fatty soup, yet insufficient in white meat, eggs, leafy vegetables, and fruits, leading to imperfect maternal nutritional intakes with high-level carbohydrates and deficient proteins. Distinctions of maternal diet profiles in various degrees can be discovered upon different lactation stages, which brings multiple influences to the composition of human milk. There was significantly weak-to-medium correlation of protein contents between maternal diet intakes and human milk, while other macronutrients correlated insignificantly. Micronutrient constituents in human milk, involving functional unsaturated fatty acids and free essential amino acids, were also impacted by maternal diet intakes through different lactation stages. These results show that more systematic and profound research is requisite for the clarification and development of Tibetan maternal diet to offer more enhanced and individualized nutritional recommendations for Tibetan lactating women and infants.
Published:
2021-08
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