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Title:
Ketosis versus carbotoxicity – metabolism determines the outcome of cancer immunotherapy
Authors:
Buqué, Aitziber; Galluzzi, Lorenzo; Kroemer, Guido
Abstract:
Carbohydrate-rich diets have been consistently associated with detrimental effects for human health, including diabetes and obesity. Moreover, high glucose levels appear to mediate immunosuppressive effects in preclinical tumor models. Recent data from Ferrere and colleagues point to the intriguing possibility that carbotoxicity may originate from the abolition of ketosis.
Published:
January 2, 2021
Title:
A new ketogenic formulation improves functional outcome and reduces tissue loss following traumatic brain injury in adult mice
Authors:
Thau-Zuchman, Orli; Svendsen, Linda; Dyall, Simon C.; Paredes-Esquivel, Ursula; Rhodes, Molly; Priestley, John V.; Feichtinger, René G.; Kofler, Barbara; Lotstra, Susanne; Verkuyl, J. Martin; Hageman, Robert J.; Broersen, Laus M.; van Wijk, Nick; Silva, Jose P.; Tremoleda, Jordi L.; Michael-Titus, Adina T.
Abstract:
Rationale: Traumatic brain injury (TBI) leads to neurological impairment, with no satisfactory treatments available. Classical ketogenic diets (KD), which reduce reliance on carbohydrates and provide ketones as fuel, have neuroprotective potential, but their high fat content reduces compliance, and experimental evidence suggests they protect juvenile brain against TBI, but not adult brain, which would strongly limit their applicability in TBI., Methods: We designed a new-KD with a fat to carbohydrate plus protein ratio of 2:1, containing medium chain triglycerides (MCT), docosahexaenoic acid (DHA), low glycaemic index carbohydrates, fibres and the ketogenic amino acid leucine, and evaluated its neuroprotective potential in adult TBI. Adult male C57BL6 mice were injured by controlled cortical impact (CCI) and assessed for 70 days, during which they received a control diet or the new-KD., Results: The new-KD, that markedly increased plasma Beta-hydroxybutyrate (β-HB), significantly attenuated sensorimotor deficits and corrected spatial memory deficit. The lesion size, perilesional inflammation and oxidation were markedly reduced. Oligodendrocyte loss appeared to be significantly reduced. TBI activated the mTOR pathway and the new-KD enhanced this increase and increased histone acetylation and methylation., Conclusion: The behavioural improvement and tissue protection provide proof of principle that this new formulation has therapeutic potential in adult TBI.
Published:
January 1, 2021
Title:
Association between Dietary Patterns and Non-alcoholic Fatty Liver Disease: Results from a Case-Control Study
Authors:
Tutunchi, Helda; Saghafi-Asl, Maryam; Asghari-Jafarabadi, Mohammad; Ostadrahimi, Alireza
Abstract:
BACKGROUND: This study aimed to investigate the association between dietary patterns and non-alcoholic fatty liver disease (NAFLD) among Iranian adults. METHODS: This case-control study was conducted on 210 subjects. NAFLD diagnosis was made by ultrasound examination. Anthropometric measures, physical activity, fasting serum levels of glucose, alanine aminotransferase (ALT), aspartate aminotransferase, and lipid profile were assessed. A three-day food diary was used to assess dietary intakes of the subjects. Dietary patterns were determined using factor analysis. To determine the relationship between dietary patterns and NAFLD, multivariable-adjusted odds ratio (OR) obtained from the logistic regression analysis was used. RESULTS: Two dietary patterns were extracted as follows: vegetables, legumes, fruits, and low-fat dairy products (VLFD) ; and sweet, hydrogenated fat, red and processed meat, and soft drink (SHMS) dietary patterns. By taking all possible confounders into account, the VLFD dietary pattern was found to be significantly related to lower odds of NAFLD, while the SHMS dietary pattern was independently related to higher odds of NAFLD (P < 0.05). Among major food groups, high consumption of processed meat, hydrogenated fats, sweets and desserts, and soft drinks was positively related to NAFLD (P
Published:
January 1, 2021
Title:
Chapter Four - The physiological activity of bioactive peptides obtained from meat and meat by-products
Authors:
Xing, Lujuan; Li, Guanhao; Toldrá, Fidel; Zhang, Wangang
Abstract:
Meat and meat products constitute an important source of nutrients and play vital roles for growth, maintenance and repair of the body. In addition to the high quality of proteins, meat is also regarded as a major resource to produce bioactive peptides. Meat processing industry also produces by-products such as bones, blood and viscera, which could be further used for the production of bioactive compounds. In the physiological analysis, meat bioactive peptides have been reported to exert antioxidant, anti-hypertensive, anti-inflammatory, anti-microbial and antitumoral activities, which endow nutritional and functional value of meat. With the objective to exert the functional effect, the bioavailability should also be considered due to the degradation by digestion enzymes and the absorption process in intestinal mucosa. In this chapter, the general source, the enzymatic hydrolysis, the physiological effects as well as the bioavailability of bioactive peptides in meat are discussed.
Published:
January 1, 2021
Title:
MIND Diet, Common Brain Pathologies, and Cognition in Community-Dwelling Older Adults
Authors:
Dhana, Klodian; James, Bryan D.; Agarwal, Puja; Aggarwal, Neelum T.; Cherian, Laurel J.; Leurgans, Sue E.; Barnes, Lisa L.; Bennett, David A.; Schneider, Julie A.
Abstract:
Background: MIND diet, a hybrid of the Mediterranean diet and the Dietary Approaches to Stop Hypertension diet, is associated with a slower cognitive decline and lower risk of Alzheimer’s disease (AD) dementia in older adults. Objective: We aim to ex
Published:
January 1, 2021
Title:
Nutritional ketosis to treat pulmonary hypertension associated with obesity and metabolic syndrome: a case report
Authors:
Kim, Darlene; Roberts, Caroline; McKenzie, Amy; George, M. Patricia
Abstract:
Metabolic syndrome is characterized by insulin resistance/hyperinsulinemia, atherogenic dyslipidemia (elevated triglycerides, low HDL), and hyperglycemia. The high prevalence of metabolic syndrome in pulmonary hypertension leads to the hypothesis that metabolic syndrome may play a contributing role in pulmonary hypertension and heart failure with preserved ejection fraction pathogenesis. We present a 62-year-old woman with morbid obesity, mild pre-capillary pulmonary hypertension, and metabolic syndrome. Her metabolic syndrome was treated with a medically-supervised ketogenic diet delivered by a telehealth healthcare team via a continuous remote care platform. Following one year of treatment, metabolic syndrome was reversed, leading to successful weight loss concurrent with hemodynamic improvement. This case highlights the feasibility of using a nutritional strategy to treat pulmonary hypertension associated with obesity and metabolic syndrome, common contributors to group 2 and 3 pulmonary hypertension. We bring this case and technique to the pulmonary hypertension community to share a tool in our therapeutic toolkit and highlight the importance of nutritional advice extending beyond telling a patient they should lose weight to invoking a rational strategy. We argue that strategic nutritional intervention through reversal of her metabolic syndrome using a medically-supervised ketogenic diet is a safe and effective treatment strategy in metabolic syndrome-associated pulmonary hypertension.
Published:
January 1, 2021
Title:
Small Amounts of Dietary Medium-Chain Fatty Acids Protect Against Insulin Resistance During Caloric Excess in Humans
Authors:
Lundsgaard, Anne-Marie; Fritzen, Andreas M.; Sjøberg, Kim A.; Kleinert, Maximilian; Richter, Erik A.; Kiens, Bente
Abstract:
Medium-chain fatty acids (MCFAs) have in rodents been shown to have protective effects on glucose homeostasis during high-fat overfeeding. In this study, we investigated whether dietary MCFAs protect against insulin resistance induced by a hypercaloric high-fat diet in humans. Healthy, lean men ingested a eucaloric control diet and a 3-day hypercaloric high-fat diet (increase of 75% in energy, 81–83% energy [E%] from fat) in randomized order. For one group (n = 8), the high-fat diet was enriched with saturated long-chain FAs (LCSFA-HFD), while the other group (n = 9) ingested a matched diet, but with ∼30 g (5E%) saturated MCFAs (MCSFA-HFD) in substitution for a corresponding fraction of the saturated long-chain fatty acids (LCFAs). A hyperinsulinemic-euglycemic clamp with femoral arteriovenous balance and glucose tracer was applied after the control and hypercaloric diets. In LCSFA-HFD, whole-body insulin sensitivity and peripheral insulin-stimulated glucose disposal were reduced. These impairments were prevented in MCSFA-HFD, accompanied by increased basal fatty acid oxidation, maintained glucose metabolic flexibility, increased nonoxidative glucose disposal related to lower starting glycogen content, and increased glycogen synthase activity, together with increased muscle lactate production. In conclusion, substitution of a small amount of dietary LCFAs with MCFAs rescues insulin action in conditions of lipid-induced energy excess.
Published:
January 1, 2021
Title:
Effects of fructose restriction on liver steatosis (FRUITLESS); a double-blind randomized controlled trial
Authors:
Simons, Nynke; Veeraiah, Pandichelvam; Simons, Pomme I H G; Schaper, Nicolaas C; Kooi, M Eline; Schrauwen-Hinderling, Vera B; Feskens, Edith J M; van der Ploeg, E M C (Liesbeth); Van den Eynde, Mathias D G; Schalkwijk, Casper G; Stehouwer, Coen D A; Brouwers, Martijn C G J
Abstract:
There is an ongoing debate on whether fructose plays a role in the development of nonalcoholic fatty liver disease.The aim of this study was to investigate the effects of fructose restriction on intrahepatic lipid (IHL) content in a double-blind randomized controlled trial using an isocaloric comparator.Between March 2017 and October 2019, 44 adult overweight individuals with a fatty liver index ≥ 60 consumed a 6-wk fructose-restricted diet (<7.5 g/meal and <10 g/d) and were randomly assigned to supplementation with sachets of glucose (= intervention group) or fructose (= control group) 3 times daily. Participants and assessors were blinded to the allocation. IHL content, assessed by proton magnetic resonance spectroscopy, was the primary outcome and glucose tolerance and serum lipids were the secondary outcomes. All measurements were conducted in Maastricht University Medical Center.Thirty-seven participants completed the study protocol. After 6 wk of fructose restriction, dietary fructose intake and urinary fructose excretion were significantly lower in the intervention group (difference: −57.0 g/d; 95% CI: −77.9, −39.5 g/d; and −38.8 μmol/d; 95% CI: −91.2, −10.7 μmol/d, respectively). Although IHL content decreased in both the intervention and control groups (P < 0.001 and P = 0.003, respectively), the change in IHL content was more pronounced in the intervention group (difference: −0.7% point, 95% CI: −2.0, −0.03% point). The changes in glucose tolerance and serum lipids were not significantly different between groups.Six weeks of fructose restriction per se led to a small, but statistically significant, decrease in IHL content in comparison with an isocaloric control group.This trial was registered at clinicaltrials.gov as NCT03067428.
Published:
December 31, 2020
Title:
The effect of oral glucose tolerance testing on changes in arterial stiffness and blood pressure in elderly women with hypertension and relationships between the stage of diabetes and physical fitness levels
Authors:
Lee, Jaesong; Park, Wonil; Sung, Eunsook; Kim, Bokbeom; Kim, Nahyun; Park, Saejong; Shin, Chulho; Park, Jonghoon
Abstract:
Published:
December 31, 2020
Title:
Retired generals say young Americans are too fat and it’s a national security issue
Authors:
Morgan, Ryan
Abstract:
A group of retired U.S. military admirals and generals is warning that too many Americans are overweight, poorly educated, or otherwise ineligible for service and it represents a 'significant threat' to America's ability to recruit new troops. Mission: Readiness, a non-partisan group consisting of nearly 800 retired U.S. admirals and generals, recently sent a letter to acting Defense Secretary Chris Miller, calling on the Department of Defense to address the major issues preventing 71 percent of Americans between the ages of 17 and 24 from being eligible to serve. 'As you know, 71 percent of young Americans between the ages
Published:
December 29, 2020
Title:
Niacin and Butyrate: Nutraceuticals Targeting Dysbiosis and Intestinal Permeability in Parkinson's Disease
Authors:
Karunaratne, Tennekoon B.; Okereke, Chijioke; Seamon, Marissa; Purohit, Sharad; Wakade, Chandramohan; Sharma, Amol
Abstract:
Dysbiosis is implicated by many studies in the pathogenesis of Parkinson's disease (PD). Advances in sequencing technology and computing have resulted in confounding data regarding pathogenic bacterial profiles in conditions such as PD. Changes in the microbiome with reductions in short-chain fatty acid (SCFA)-producing bacteria and increases in endotoxin-producing bacteria likely contribute to the pathogenesis of PD. GPR109A, a G-protein coupled receptor found on the surface of the intestinal epithelium and immune cells, plays a key role in controlling intestinal permeability and the inflammatory cascade. The absence of GPR109A receptors is associated with decreased concentration of tight junction proteins, leading to increased intestinal permeability and susceptibility to inflammation. In inflammatory states, butyrate acts via GPR109A to increase concentrations of tight junction proteins and improve intestinal permeability. Niacin deficiency is exacerbated in PD by dopaminergic medications. Niacin supplementation has been shown to shift macrophage polarization from pro-inflammatory to an anti-inflammatory profile. Niacin and butyrate, promising nutrients and unique ligands for the G protein-coupled receptor GPR109A, are reviewed in this paper in detail.
Published:
December 23, 2020
Title:
Niacin and Butyrate: Nutraceuticals Targeting Dysbiosis and Intestinal Permeability in Parkinson's Disease
Authors:
Karunaratne, Tennekoon B.; Okereke, Chijioke; Seamon, Marissa; Purohit, Sharad; Wakade, Chandramohan; Sharma, Amol
Abstract:
Dysbiosis is implicated by many studies in the pathogenesis of Parkinson's disease (PD). Advances in sequencing technology and computing have resulted in confounding data regarding pathogenic bacterial profiles in conditions such as PD. Changes in the microbiome with reductions in short-chain fatty acid (SCFA)-producing bacteria and increases in endotoxin-producing bacteria likely contribute to the pathogenesis of PD. GPR109A, a G-protein coupled receptor found on the surface of the intestinal epithelium and immune cells, plays a key role in controlling intestinal permeability and the inflammatory cascade. The absence of GPR109A receptors is associated with decreased concentration of tight junction proteins, leading to increased intestinal permeability and susceptibility to inflammation. In inflammatory states, butyrate acts via GPR109A to increase concentrations of tight junction proteins and improve intestinal permeability. Niacin deficiency is exacerbated in PD by dopaminergic medications. Niacin supplementation has been shown to shift macrophage polarization from pro-inflammatory to an anti-inflammatory profile. Niacin and butyrate, promising nutrients and unique ligands for the G protein-coupled receptor GPR109A, are reviewed in this paper in detail.
Published:
December 23, 2020
Title:
Leaky Gut and Autoimmunity: An Intricate Balance in Individuals Health and the Diseased State
Authors:
Paray, Bilal Ahmad; Albeshr, Mohammed Fahad; Jan, Arif Tasleem; Rather, Irfan A.
Abstract:
Damage to the tissue and the ruining of functions characterize autoimmune syndromes. This review centers around leaky gut syndromes and how they stimulate autoimmune pathogenesis. Lymphoid tissue commonly associated with the gut, together with the neuroendocrine network, collaborates with the intestinal epithelial wall, with its paracellular tight junctions, to maintain the balance, tolerance, and resistance to foreign/neo-antigens. The physiological regulator of paracellular tight junctions plays a vital role in transferring macromolecules across the intestinal barrier and thereby maintains immune response equilibrium. A new paradigm has explained the intricacies of disease development and proposed that the processes can be prevented if the interaction between the genetic factor and environmental causes is barred by re-instituting the intestinal wall function. The latest clinical evidence and animal models reinforce this current thought and offer the basis for innovative methodologies to thwart and treat autoimmune syndromes.
Published:
December 21, 2020
Title:
Adiponectin/leptin ratio increases after a 12-week very low-carbohydrate, high-fat diet, and exercise training in healthy individuals: A non-randomized, parallel design study
Authors:
Cipryan, Lukas; Dostal, Tomas; Plews, Daniel J.; Hofmann, Peter; Laursen, Paul B.
Abstract:
This study aimed to investigate the effect of a 12-week very low-carbohydrate, high-fat (VLCHF) diet and exercise on biomarkers of inflammation in healthy individuals. Since the anti-inflammatory effects of a ketogenic diet have been established, we hypothesized that the VLCHF diet, along with exercise, would have an additional favorable effect on biomarkers of inflammation. Twenty-four healthy individuals were allocated to the VLCHF diet (VLCHF: N = 12, age 25.3 ± 2.0 years, body mass 66.7 ± 9.8 kg, fat mass 21.5% ± 4.9%), or habitual diet (HD: N = 12, age 23.9 ± 3.8 years, body mass 72.7 ± 15.0 kg, fat mass 23.4 ± 8.4 %) group. Biomarkers of inflammation (adiponectin, leptin, and high-sensitive interleukin-6 [hs-IL-6]) and substrate metabolism (glycated hemoglobin, fasting glucose, triacylglycerides, and cholesterol) were analyzed from blood at baseline and after 12 weeks. The adiponectin-leptin ratio significantly increased in the VLCHF group after the intervention period (ES [95% CL]: -0.90 [-0.96, -0.77], P ≤ .001, BF10 = 22.15). The adiponectin-leptin ratio changes were associated with both a significant increase in adiponectin (-0.79 [-0.91, -0.54], P ≤ .001, BF10 = 9.43) and a significant decrease in leptin (0.58 [0.19, 0.81], P = .014, BF10 = 2.70). There was moderate evidence of changes in total cholesterol (-1.15 [-2.01, -0.27], P = .010, BF10 = 5.20), and LDL cholesterol (-1.12 [-2.01, -0.21], P = .016, BF10 = 4.56) in the VLCHF group. Body weight (kg) and fat mass (%) decreased in the VLCHF group by 5.4% and 14.9%, respectively. We found that in healthy young individuals, consuming a VLCHF diet while performing regular exercise over a 12-week period produced favorable changes in body weight and fat mass along with beneficial changes in serum adiponectin and leptin concentrations. These data support the use of a VLCHF diet strategy for the primary prevention of chronic diseases associated with systemic low-grade inflammation.
Published:
December 10, 2020
Title:
Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial
Authors:
Nicholls, Stephen J.; Lincoff, A. Michael; Garcia, Michelle; Bash, Dianna; Ballantyne, Christie M.; Barter, Philip J.; Davidson, Michael H.; Kastelein, John J. P.; Koenig, Wolfgang; McGuire, Darren K.; Mozaffarian, Dariush; Ridker, Paul M; Ray, Kausik K.; Katona, Brian G.; Himmelmann, Anders; Loss, Larrye E.; Rensfeldt, Martin; Lundström, Torbjörn; Agrawal, Rahul; Menon, Venu; Wolski, Kathy; Nissen, Steven E.
Abstract:
It remains uncertain whether the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce cardiovascular risk.To determine the effects on cardiovascular outcomes of a carboxylic acid formulation of EPA and DHA (omega-3 CA) with documented favorable effects on lipid and inflammatory markers in patients with atherogenic dyslipidemia and high cardiovascular risk.A double-blind, randomized, multicenter trial (enrollment October 30, 2014, to June 14, 2017; study termination January 8, 2020; last patient visit May 14, 2020) comparing omega-3 CA with corn oil in statin-treated participants with high cardiovascular risk, hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol (HDL-C). A total of 13 078 patients were randomized at 675 academic and community hospitals in 22 countries in North America, Europe, South America, Asia, Australia, New Zealand, and South Africa.Participants were randomized to receive 4 g/d of omega-3 CA (n = 6539) or corn oil, which was intended to serve as an inert comparator (n = 6539), in addition to usual background therapies, including statins.The primary efficacy measure was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization.When 1384 patients had experienced a primary end point event (of a planned 1600 events), the trial was prematurely halted based on an interim analysis that indicated a low probability of clinical benefit of omega-3 CA vs the corn oil comparator. Among the 13 078 treated patients (mean [SD] age, 62.5 [9.0] years; 35% women; 70% with diabetes; median low-density lipoprotein [LDL] cholesterol level, 75.0 mg/dL; median triglycerides level, 240 mg/dL; median HDL-C level, 36 mg/dL; and median high-sensitivity C-reactive protein level, 2.1 mg/L), 12 633 (96.6%) completed the trial with ascertainment of primary end point status. The primary end point occurred in 785 patients (12.0%) treated with omega-3 CA vs 795 (12.2%) treated with corn oil (hazard ratio, 0.99 [95% CI, 0.90-1.09]; P = .84). A greater rate of gastrointestinal adverse events was observed in the omega-3 CA group (24.7%) compared with corn oil–treated patients (14.7%).Among statin-treated patients at high cardiovascular risk, the addition of omega-3 CA, compared with corn oil, to usual background therapies resulted in no significant difference in a composite outcome of major adverse cardiovascular events. These findings do not support use of this omega-3 fatty acid formulation to reduce major adverse cardiovascular events in high-risk patients.ClinicalTrials.gov Identifier: NCT02104817
Published:
December 8, 2020
Title:
Impact of a 2-year trial of nutritional ketosis on indices of cardiovascular disease risk in patients with type 2 diabetes
Authors:
Athinarayanan, Shaminie J.; Hallberg, Sarah J.; McKenzie, Amy L.; Lechner, Katharina; King, Sarah; McCarter, James P.; Volek, Jeff S.; Phinney, Stephen D.; Krauss, Ronald M.
Abstract:
BACKGROUND: We have previously reported that in patients with type 2 diabetes (T2D) consumption of a very low carbohydrate diet capable of inducing nutritional ketosis over 2 years (continuous care intervention, CCI) resulted in improved body weight, glycemic control, and multiple risk factors for cardiovascular disease (CVD) with the exception of an increase in low density lipoprotein cholesterol (LDL-C). In the present study, we report the impact of this intervention on markers of risk for atherosclerotic cardiovascular disease (CVD), with a focus on lipoprotein subfraction particle concentrations as well as carotid-artery intima-media thickness (CIMT). METHODS: Analyses were performed in patients with T2D who completed 2 years of this study (CCI; n = 194; usual care (UC): n = 68). Lipoprotein subfraction particle concentrations were measured by ion mobility at baseline, 1, and 2 years and CIMT was measured at baseline and 2 years. Principal component analysis (PCA) was used to assess changes in independent clusters of lipoprotein particles. RESULTS: At 2 years, CCI resulted in a 23% decrease of small LDL IIIb and a 29% increase of large LDL I with no change in total LDL particle concentration or ApoB. The change in proportion of smaller and larger LDL was reflected by reversal of the small LDL subclass phenotype B in a high proportion of CCI participants (48.1%) and a shift in the principal component (PC) representing the atherogenic lipoprotein phenotype characteristic of T2D from a major to a secondary component of the total variance. The increase in LDL-C in the CCI group was mainly attributed to larger cholesterol-enriched LDL particles. CIMT showed no change in either the CCI or UC group. CONCLUSION: Consumption of a very low carbohydrate diet with nutritional ketosis for 2 years in patients with type 2 diabetes lowered levels of small LDL particles that are commonly increased in diabetic dyslipidemia and are a marker for heightened CVD risk. A corresponding increase in concentrations of larger LDL particles was responsible for higher levels of plasma LDL-C. The lack of increase in total LDL particles, ApoB, and in progression of CIMT, provide supporting evidence that this dietary intervention did not adversely affect risk of CVD.
Published:
December 8, 2020
Title:
Insulin directly stimulates mitochondrial glucose oxidation in the heart
Authors:
Karwi, Qutuba G.; Wagg, Cory S.; Altamimi, Tariq R.; Uddin, Golam M.; Ho, Kim L.; Darwesh, Ahmed M.; Seubert, John M.; Lopaschuk, Gary D.
Abstract:
BACKGROUND: Glucose oxidation is a major contributor to myocardial energy production and its contribution is orchestrated by insulin. While insulin can increase glucose oxidation indirectly by enhancing glucose uptake and glycolysis, it also directly stimulates mitochondrial glucose oxidation, independent of increasing glucose uptake or glycolysis, through activating mitochondrial pyruvate dehydrogenase (PDH), the rate-limiting enzyme of glucose oxidation. However, how insulin directly stimulates PDH is not known. To determine this, we characterized the impacts of modifying mitochondrial insulin signaling kinases, namely protein kinase B (Akt), protein kinase C-delta (PKC-δ) and glycogen synthase kinase-3 beta (GSK-3β), on the direct insulin stimulation of glucose oxidation. METHODS: We employed an isolated working mouse heart model to measure the effect of insulin on cardiac glycolysis, glucose oxidation and fatty acid oxidation and how that could be affected when mitochondrial Akt, PKC-δ or GSK-3β is disturbed using pharmacological modulators. We also used differential centrifugation to isolate mitochondrial and cytosol fraction to examine the activity of Akt, PKC-δ and GSK-3β between these fractions. Data were analyzed using unpaired t-test and two-way ANOVA. RESULTS: Here we show that insulin-stimulated phosphorylation of mitochondrial Akt is a prerequisite for transducing insulin's direct stimulation of glucose oxidation. Inhibition of mitochondrial Akt completely abolishes insulin-stimulated glucose oxidation, independent of glucose uptake or glycolysis. We also show a novel role of mitochondrial PKC-δ in modulating mitochondrial glucose oxidation. Inhibition of mitochondrial PKC-δ mimics insulin stimulation of glucose oxidation and mitochondrial Akt. We also demonstrate that inhibition of mitochondrial GSK3β phosphorylation does not influence insulin-stimulated glucose oxidation. CONCLUSION: We identify, for the first time, insulin-stimulated mitochondrial Akt as a prerequisite transmitter of the insulin signal that directly stimulates cardiac glucose oxidation. These novel findings suggest that targeting mitochondrial Akt is a potential therapeutic approach to enhance cardiac insulin sensitivity in condition such as heart failure, diabetes and obesity.
Published:
December 7, 2020
Title:
Maintenance of contractile force and increased fatigue resistance in slow-twitch skeletal muscle of mice fed a high-fat diet
Authors:
Eshima, Hiroaki; Tamura, Yoshifumi; Kakehi, Saori; Kakigi, Ryo; Kawamori, Ryuzo; Watada, Hirotaka
Abstract:
Consumption of a high-fat diet (HFD) significantly increases exercise endurance performance during treadmill running. However, whether HFD consumption increases endurance capacity via enhanced muscle fatigue resistance has not been clarified. In this study, we investigated the effects of HFDs on contractile force and fatigue resistance of slow-twitch dominant muscles. The soleus (SOL) muscle of male C57BL/6J mice fed an HFD (60% kcal from fat) or a low-fat diet (LFD) for 12 weeks was analyzed. Muscle contractile force was measured under resting conditions and during fatigue induced by repeated tetanic contractions (100 Hz, 50 contractions, 2-second intervals). Differences in muscle twitch or tetanic force were not evident between HFD and LFD groups whereas fatigue resistance was higher for the entire end-stage period in the HFD groups. The SOL muscle of HFD-fed mice showed increased levels of markers related to oxidative capacity such as succinate dehydrogenase and citrate synthase activity. In addition, electron microscopy analyses indicated that the total number of mitochondria and mitochondrial volume density increased in the SOL muscle of the HFD groups. These findings suggest that HFD consumption induces increased muscle fatigue resistance in slow-twitch dominant muscle fibers. This effect of HFD may be related to elevated oxidative enzyme activity, high mitochondrial content, or both.
Published:
December 3, 2020
Title:
A Cross-cultural Survey of On-site Fire Use by Recent Hunter-gatherers: Implications for Research on Palaeolithic Pyrotechnology
Authors:
McCauley, Brea; Collard, Mark; Sandgathe, Dennis
Abstract:
The ability to control fire clearly had a significant impact on human evolution, but when and how hominins developed this ability remains poorly understood. Improving our understanding of the history of hominin fire use will require not only additional fieldwork but also comparative analyses of fire use by ethnographically-documented hunter-gatherer groups. Here, we report a study that focused on the second of these tasks. In the study, we consulted ethnographic texts for a sample of 93 hunter-gatherer groups and collected data pertaining to fire use in settlements. We focused on the groups’ methods of making fire, the ways in which they used fire, and when and where they created fires. While many of the observations were in line with expectations, some were surprising. Perhaps most notably, we found that several groups did not know how to make fire and that even within some of the groups who were able to make fire, the relevant knowledge was restricted to a very small number of individuals. Another surprising finding was that many groups preferred to preserve fire rather than creating it anew, to the point that they would carry it between camps. In the final section of the paper, we discuss the implications of the survey’s findings for understanding the early archaeological record of fire use.
Published:
December 1, 2020
Title:
Meat eating by nonhuman primates: A review and synthesis
Authors:
Watts, David P.
Abstract:
Most nonhuman primates prey on vertebrates. Meat-eating, defined as ingestion of vertebrate tissue, occurs in 12 families, ≥39 genera, and ≥89 species. It is most common in capuchins (Cebus and Sapajus spp.), baboons (Papio spp.), bonobos (Pan paniscus), and chimpanzees (Pan troglodytes) and modestly common in blue monkeys (Cercopithecus mitis), callitrichids (Callithrix spp. and Saguinus spp.), and squirrel monkeys (Saimiri spp.). It is uncommon in other cercopithecines, rare in other haplorhines and in lemurs, and virtually absent in colobines. Birds are the prey class eaten by the most species (≥53), followed by reptiles (≥48), amphibians (≥38), mammals (≥35), and fish (≥7). Major hypotheses for the importance of meat eating are that it is (1) mainly an energy source, especially (1a) when plant-source foods (PSFs) with high energy return rates are scarce (energy shortfall hypothesis); (2) mainly a protein source; and (3) mainly a source of micronutrients scarce in PSFs. Meat eating bouts sometimes provide substantial energy and protein, and some chimpanzees gain substantial protein from meat monthly or annually. However, meat typically accounts for only small proportions of feeding time and of total energy and protein intake, and quantitative data are inconsistent with the energy shortfall hypothesis. PSFs and/or invertebrates are presumably the main protein sources, even for chimpanzees. Support is strongest for the micronutrient hypothesis. Most chimpanzees eat far less meat than recorded for hunter-gatherers, but the highest chimpanzee estimates approach the lowest for African hunter-gatherers. In fundamental contrast to the human predatory pattern, other primates only eat vertebrates much smaller than they are, tool-assisted predation is rare except in some capuchins and chimpanzees, and tool use in carcass processing is virtually absent. However, harvesting of small prey deserves more attention with reference to the archaeological and ethnographic record.
Published:
December 1, 2020
Title:
Transomics analysis reveals allosteric and gene regulation axes for altered hepatic glucose-responsive metabolism in obesity
Authors:
Kokaji, Toshiya; Hatano, Atsushi; Ito, Yuki; Yugi, Katsuyuki; Eto, Miki; Morita, Keigo; Ohno, Satoshi; Fujii, Masashi; Hironaka, Ken-ichi; Egami, Riku; Terakawa, Akira; Tsuchiya, Takaho; Ozaki, Haruka; Inoue, Hiroshi; Uda, Shinsuke; Kubota, Hiroyuki; Suzuki, Yutaka; Ikeda, Kazutaka; Arita, Makoto; Matsumoto, Masaki; Nakayama, Keiichi I.; Hirayama, Akiyoshi; Soga, Tomoyoshi; Kuroda, Shinya
Abstract:
A regulatory switch in obesity The liver not only produces glucose, it also consumes a large amount of glucose, making this organ critical for glucose homeostasis. To understand how obesity alters glucose-responsive metabolism in the liver, Kokaji et al. performed multiomics analyses on the livers and blood of normal or ob/ob mice, a genetic model for obesity. The authors next reconstructed the glucose-sensitive biochemical network that encompassed metabolites, metabolic reactions, metabolic enzymes, transcription factors, and proteins in the insulin signaling pathway in both normal and ob/ob mice. Their analysis suggested that whereas normal hepatic metabolic responses to glucose were rapid and relied on regulation by metabolites, those in ob/ob mice were slow and depended on changes in gene expression. The authors note that their data imply that obesity not only slows hepatic metabolic responses to glucose, but also makes these responses more energy-consuming (through phosphorylation of enzymes and transcription factors and through gene expression changes) and less precise (due to the slowness and nature of the responses). Impaired glucose tolerance associated with obesity causes postprandial hyperglycemia and can lead to type 2 diabetes. To study the differences in liver metabolism in healthy and obese states, we constructed and analyzed transomics glucose-responsive metabolic networks with layers for metabolites, expression data for metabolic enzyme genes, transcription factors, and insulin signaling proteins from the livers of healthy and obese mice. We integrated multiomics time course data from wild-type and leptin-deficient obese (ob/ob) mice after orally administered glucose. In wild-type mice, metabolic reactions were rapidly regulated within 10 min of oral glucose administration by glucose-responsive metabolites, which functioned as allosteric regulators and substrates of metabolic enzymes, and by Akt-induced changes in the expression of glucose-responsive genes encoding metabolic enzymes. In ob/ob mice, the majority of rapid regulation by glucose-responsive metabolites was absent. Instead, glucose administration produced slow changes in the expression of carbohydrate, lipid, and amino acid metabolic enzyme–encoding genes to alter metabolic reactions on a time scale of hours. Few regulatory events occurred in both healthy and obese mice. Thus, our transomics network analysis revealed that regulation of glucose-responsive liver metabolism is mediated through different mechanisms in healthy and obese states. Rapid changes in allosteric regulators and substrates and in gene expression dominate the healthy state, whereas slow changes in gene expression dominate the obese state. Obesity shifts glucose-responsive hepatic metabolism from rapid regulation by metabolites to slower changes in gene expression. Obesity shifts glucose-responsive hepatic metabolism from rapid regulation by metabolites to slower changes in gene expression.
Published:
December 1, 2020
Title:
Could the keto diet help prevent or mitigate severe COVID-19?
Authors:
Abstract:
A new study published in the journal of Translational Medicine reports that the ketogenic diet (KD) may be useful in this area, with its track history of effectual reduction of fat mass, anti-inflammatory and immunomodulatory effects, and consequent improvement of cardiovascular health.
Published:
November 30, 2020
Title:
Effect of the ketogenic diet on glycemic control, insulin resistance, and lipid metabolism in patients with T2DM: a systematic review and meta-analysis
Authors:
Yuan, Xiaojie; Wang, Jiping; Yang, Shuo; Gao, Mei; Cao, Lingxia; Li, Xumei; Hong, Dongxu; Tian, Suyan; Sun, Chenglin
Abstract:
BACKGROUND: At present, the beneficial effect of the ketogenic diet (KD) on weight loss in obese patients is generally recognized. However, a systematic research on the role of KD in the improvement of glycemic and lipid metabolism of patients with diabetes is still found scarce. METHODS: This meta-study employed the meta-analysis model of random effects or of fixed effects to analyze the average difference before and after KD and the corresponding 95% CI, thereby evaluating the effect of KD on T2DM. RESULTS: After KD intervention, in terms of glycemic control, the level of fasting blood glucose decreased by 1.29 mmol/L (95% CI: -1.78 to -0.79) on average, and glycated hemoglobin A1c by 1.07 (95% CI: -1.37 to -0.78). As for lipid metabolism, triglyceride was decreased by 0.72 (95% CI: -1.01 to -0.43) on average, total cholesterol by 0.33 (95% CI: -0.66 to -0.01), and low-density lipoprotein by 0.05 (95% CI: -0.25 to -0.15); yet, high-density lipoprotein increased by 0.14 (95% CI: 0.03-0.25). In addition, patients' weight decreased by 8.66 (95% CI: -11.40 to -5.92), waist circumference by 9.17 (95% CI: -10.67 to -7.66), and BMI by 3.13 (95% CI: -3.31 to -2.95). CONCLUSION: KD not only has a therapeutic effect on glycemic and lipid control among patients with T2DM but also significantly contributes to their weight loss.
Published:
November 30, 2020
Title:
Effect of the ketogenic diet on glycemic control, insulin resistance, and lipid metabolism in patients with T2DM: a systematic review and meta-analysis
Authors:
Yuan, Xiaojie; Wang, Jiping; Yang, Shuo; Gao, Mei; Cao, Lingxia; Li, Xumei; Hong, Dongxu; Tian, Suyan; Sun, Chenglin
Abstract:
BACKGROUND: At present, the beneficial effect of the ketogenic diet (KD) on weight loss in obese patients is generally recognized. However, a systematic research on the role of KD in the improvement of glycemic and lipid metabolism of patients with diabetes is still found scarce. METHODS: This meta-study employed the meta-analysis model of random effects or of fixed effects to analyze the average difference before and after KD and the corresponding 95% CI, thereby evaluating the effect of KD on T2DM. RESULTS: After KD intervention, in terms of glycemic control, the level of fasting blood glucose decreased by 1.29 mmol/L (95% CI: -1.78 to -0.79) on average, and glycated hemoglobin A1c by 1.07 (95% CI: -1.37 to -0.78). As for lipid metabolism, triglyceride was decreased by 0.72 (95% CI: -1.01 to -0.43) on average, total cholesterol by 0.33 (95% CI: -0.66 to -0.01), and low-density lipoprotein by 0.05 (95% CI: -0.25 to -0.15); yet, high-density lipoprotein increased by 0.14 (95% CI: 0.03-0.25). In addition, patients' weight decreased by 8.66 (95% CI: -11.40 to -5.92), waist circumference by 9.17 (95% CI: -10.67 to -7.66), and BMI by 3.13 (95% CI: -3.31 to -2.95). CONCLUSION: KD not only has a therapeutic effect on glycemic and lipid control among patients with T2DM but also significantly contributes to their weight loss.
Published:
November 30, 2020
Title:
Effect of the ketogenic diet on glycemic control, insulin resistance, and lipid metabolism in patients with T2DM: a systematic review and meta-analysis
Authors:
Yuan, Xiaojie; Wang, Jiping; Yang, Shuo; Gao, Mei; Cao, Lingxia; Li, Xumei; Hong, Dongxu; Tian, Suyan; Sun, Chenglin
Abstract:
Background At present, the beneficial effect of the ketogenic diet (KD) on weight loss in obese patients is generally recognized. However, a systematic research on the role of KD in the improvement of glycemic and lipid metabolism of patients with diabetes is still found scarce. Methods This meta-study employed the meta-analysis model of random effects or of fixed effects to analyze the average difference before and after KD and the corresponding 95% CI, thereby evaluating the effect of KD on T2DM. Results After KD intervention, in terms of glycemic control, the level of fasting blood glucose decreased by 1.29 mmol/L (95% CI: −1.78 to −0.79) on average, and glycated hemoglobin A1c by 1.07 (95% CI: −1.37 to −0.78). As for lipid metabolism, triglyceride was decreased by 0.72 (95% CI: −1.01 to −0.43) on average, total cholesterol by 0.33 (95% CI: −0.66 to −0.01), and low-density lipoprotein by 0.05 (95% CI: −0.25 to −0.15); yet, high-density lipoprotein increased by 0.14 (95% CI: 0.03−0.25). In addition, patients’ weight decreased by 8.66 (95% CI: −11.40 to −5.92), waist circumference by 9.17 (95% CI: −10.67 to −7.66), and BMI by 3.13 (95% CI: −3.31 to −2.95). Conclusion KD not only has a therapeutic effect on glycemic and lipid control among patients with T2DM but also significantly contributes to their weight loss.
Published:
November 30, 2020
Title:
Effect of the ketogenic diet on glycemic control, insulin resistance, and lipid metabolism in patients with T2DM: a systematic review and meta-analysis
Authors:
Yuan, Xiaojie; Wang, Jiping; Yang, Shuo; Gao, Mei; Cao, Lingxia; Li, Xumei; Hong, Dongxu; Tian, Suyan; Sun, Chenglin
Abstract:
BACKGROUND: At present, the beneficial effect of the ketogenic diet (KD) on weight loss in obese patients is generally recognized. However, a systematic research on the role of KD in the improvement of glycemic and lipid metabolism of patients with diabetes is still found scarce. METHODS: This meta-study employed the meta-analysis model of random effects or of fixed effects to analyze the average difference before and after KD and the corresponding 95% CI, thereby evaluating the effect of KD on T2DM. RESULTS: After KD intervention, in terms of glycemic control, the level of fasting blood glucose decreased by 1.29 mmol/L (95% CI: -1.78 to -0.79) on average, and glycated hemoglobin A1c by 1.07 (95% CI: -1.37 to -0.78). As for lipid metabolism, triglyceride was decreased by 0.72 (95% CI: -1.01 to -0.43) on average, total cholesterol by 0.33 (95% CI: -0.66 to -0.01), and low-density lipoprotein by 0.05 (95% CI: -0.25 to -0.15); yet, high-density lipoprotein increased by 0.14 (95% CI: 0.03-0.25). In addition, patients' weight decreased by 8.66 (95% CI: -11.40 to -5.92), waist circumference by 9.17 (95% CI: -10.67 to -7.66), and BMI by 3.13 (95% CI: -3.31 to -2.95). CONCLUSION: KD not only has a therapeutic effect on glycemic and lipid control among patients with T2DM but also significantly contributes to their weight loss.
Published:
November 30, 2020
Title:
Effect of the ketogenic diet on glycemic control, insulin resistance, and lipid metabolism in patients with T2DM: a systematic review and meta-analysis
Authors:
Yuan, Xiaojie; Wang, Jiping; Yang, Shuo; Gao, Mei; Cao, Lingxia; Li, Xumei; Hong, Dongxu; Tian, Suyan; Sun, Chenglin
Abstract:
BACKGROUND: At present, the beneficial effect of the ketogenic diet (KD) on weight loss in obese patients is generally recognized. However, a systematic research on the role of KD in the improvement of glycemic and lipid metabolism of patients with diabetes is still found scarce. METHODS: This meta-study employed the meta-analysis model of random effects or of fixed effects to analyze the average difference before and after KD and the corresponding 95% CI, thereby evaluating the effect of KD on T2DM. RESULTS: After KD intervention, in terms of glycemic control, the level of fasting blood glucose decreased by 1.29 mmol/L (95% CI: -1.78 to -0.79) on average, and glycated hemoglobin A1c by 1.07 (95% CI: -1.37 to -0.78). As for lipid metabolism, triglyceride was decreased by 0.72 (95% CI: -1.01 to -0.43) on average, total cholesterol by 0.33 (95% CI: -0.66 to -0.01), and low-density lipoprotein by 0.05 (95% CI: -0.25 to -0.15); yet, high-density lipoprotein increased by 0.14 (95% CI: 0.03-0.25). In addition, patients' weight decreased by 8.66 (95% CI: -11.40 to -5.92), waist circumference by 9.17 (95% CI: -10.67 to -7.66), and BMI by 3.13 (95% CI: -3.31 to -2.95). CONCLUSION: KD not only has a therapeutic effect on glycemic and lipid control among patients with T2DM but also significantly contributes to their weight loss.
Published:
November 30, 2020
Title:
Metabolic and appetite effects of fructose and glucose in subjects with type 1 diabetes: a randomized crossover clinical trial
Authors:
Dos Santos Lima, Érika; Souto, Débora Lopes; Rodacki, Melanie; Pereira, Joana Rodrigues Dantas; Zajdenverg, Lenita; Rosado, Eliane Lopes
Abstract:
BACKGROUND: Fructose has been widely used for producing lower post-infusion glucose increase than other carbohydrates, but seems that it promotes an increase in post-infusion triglycerides. OBJECTIVE: The present study investigated the effects of fructose and glucose in metabolic variables and appetite sensations in patients with type 1 diabetes mellitus (T1DM). METHODS: This is a single-blind, randomized and crossover study (washout of 1-5 weeks), which has evaluated 16 adult T1DM patients, accompanied at University Hospital. After eight hours overnight fasting, were assessment of capillary blood glucose, anthropometric variables, appetite sensations and laboratory tests (glycemia, lipemia, leptin and glucagon). Subsequently, they received 200mL of solutions with water and 75g of crystal fructose or glucose. Appetite sensations and capillary blood glucose were evaluated in different post-infusion times. Blood was drawn after 180 minutes for the laboratory tests. RESULTS: Blood glucose increased after the intake of both solutions, but the glucose induced a higher elevation. None of them increased triglycerides or glucagon. Glucagon maintenance was similar among the solutions. Furthermore, both solutions reduced leptin and increased fullness, but only fructose increased lack of interest in eating sweets. CONCLUSIONS: Fructose induced smaller increase in postprandial blood glucose than glucose, without changes in triglycerides and glucagon. In addition, leptin levels and appetite sensations were similar to glucose. Other studies are needed in order to confirm these findings, especially in the long term, so that their use becomes really reliable.
Published:
November 30, 2020
Title:
The world's largest producer of insulin, Novo Nordisk, is also the founder and funder of the World Diabetes Foundation, which has no information on using low carb diets to reverse diabetes. NN's chief medical officer recently left for Virta Health because he wanted sustainable drugless solutions.
Authors:
dem0n0cracy
Abstract:
Published:
November 30, 2020
Title:
Hepatic metabolic adaptation and adipose tissue expansion are altered in mice with steatohepatitis induced by high-fat high sucrose diet
Authors:
Baiges-Gaya, Gerard; Fernández-Arroyo, Salvador; Luciano-Mateo, Fedra; Cabré, Noemí; Rodríguez-Tomàs, Elisabet; Hernández-Aguilera, Anna; Castañé, Helena; Romeu, Marta; Nogués, Maria-Rosa; Camps, Jordi; Joven, Jorge
Abstract:
BACKGROUND: Obesity is a chronic progressive disease with several metabolic alterations. Non-alcoholic fatty liver disease (NAFLD) is an important co-morbidity of obesity that can progress to non-alcoholic steatohepatitis (NASH), cirrhosis or hepatocarcinoma. This study aimed at clarifying the molecular mechanisms underlying the metabolic alterations in hepatic and adipose tissue during high-fat high-sucrose diet-induced NAFLD development in mice. METHODS: Twenty-four male mice (C57BL/6J) were randomly allocated into 3 groups (n=8 mice per group) to receive a chow diet, a high-fat diet (HFD), or a high-fat high-sucrose diet (HF-HSD) for 20 weeks. At sacrifice, liver and adipose tissue were obtained for histopathological, metabolomic, and protein expression analyses. RESULTS: HF-HSD (but not HFD) was associated with NASH and increased oxidative stress. These animals presented an inhibition of hepatic autophagy and alterations in AMP-activated protein kinase/mammalian target of rapamycin activity. We also observed that the ability of metabolic adaptation was adversely affected by the increase of damaged mitochondria. NASH development was associated with changes in adipose tissue dynamics and increased amounts of saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids in visceral adipose tissue. CONCLUSION: HF-HSD led to a metabolic blockage and impaired hepatic mitochondria turnover. In addition, the continuous accumulation of fatty acids produced adipose tissue dysfunction and hepatic fat accumulation that favored the progression to NASH.
Published:
November 29, 2020
Title:
Info from the Sodfather part three: PDCAAS and DIAAS
Authors:
EvaOgg
Abstract:
Published:
November 29, 2020
Title:
Info from the Sodfather part two: Crude v True Protein.
Authors:
EvaOgg
Abstract:
Published:
November 29, 2020
Title:
Info on Amino Acids from the Sodfather.
Authors:
EvaOgg
Abstract:
Published:
November 29, 2020
Title:
Autophagy is not involved in lipid accumulation and the development of insulin resistance in skeletal muscle
Authors:
Morales-Scholz, María G.; Swinton, Courtney; Murphy, Robyn M.; Kowalski, Greg M.; Bruce, Clinton R.; Howlett, Kirsten F.; Shaw, Christopher S.
Abstract:
OBJECTIVE: To investigate the effect of high fat diet-induced insulin resistance on autophagy markers in the liver and skeletal muscle of mice in the fasted state and following an oral glucose bolus. METHODS: Forty C57BL/6J male mice were fed either a high fat, high sucrose (HFSD, n = 20) or standard chow control (CON, n = 20) diet for 16 weeks. Upon trial completion, mice were gavaged with water or glucose and skeletal muscle and liver were collected 15 min post gavage. Protein abundance and gene expression of autophagy markers and activation of related signalling pathways were assessed. RESULTS: Compared to CON, the HFSD intervention increased LC3B-II and p62/SQSTM1 protein abundance in the liver which is indicative of elevated autophagosome content via reduced clearance. These changes coincided with inhibitory autophagy signalling through elevated p-mTOR S2448 and p-ULK1S758. HFSD did not alter autophagy markers in skeletal muscle. Administration of an oral glucose bolus had no effect on autophagy markers or upstream signalling responses in either tissue regardless of diet. CONCLUSION: HFSD induces tissue-specific autophagy impairments, with autophagosome accumulation indicating reduced lysosomal clearance in the liver. In contrast, autophagy markers were unchanged in skeletal muscle, indicating that autophagy is not involved in the development of skeletal muscle insulin resistance.
Published:
November 28, 2020
Title:
Corrigendum to “A Review of the Science of Colorful, Plant-Based Food and Practical Strategies for “Eating the Rainbow””
Authors:
Minich, Deanna M.
Abstract:
In the article titled “A Review of the Science of Colorful, Plant-Based Food and Practical Strategies for “Eating the Rainbow”” [1], conflicts of interest should have been declared because the review is directly linked to principles covered by the author’s courses and books operated via Food & Spirit, LLC. Copyright © 2020 Deanna M. Minich. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Published:
November 28, 2020
Title:
Short-term effects of a Paleolithic lifestyle intervention in breast cancer patients undergoing radiotherapy: a pilot and feasibility study
Authors:
Klement, Rainer J.; Koebrunner, Petra S.; Krage, Kelley; Weigel, Michael M.; Sweeney, Reinhart A.
Abstract:
Evolutionary principles are rarely considered in clinical oncology. We here aimed to test the feasibility and effects of a dietary and physical activity intervention based on evolutionary considerations in an oncological setting. A total of 13 breast cancer patients referred to our clinic for curative radiotherapy were recruited for this pilot study. The women were supposed to undertake a "Paleolithic lifestyle" (PL) intervention consisting of a Paleolithic diet and daily outdoor activity of at least 30 min duration while undergoing radiotherapy. Body composition was measured weekly by bioimpedance analysis. Blood parameters were assessed before, during, and at the end of radiotherapy. A control group on an unspecified standard diet (SD) was assigned by propensity score matching. A total of eleven patients completed the study. The majority of patients (64%) reported feeling good or very good during the intervention. The intervention group experienced an average decrease of 0.4 kg body weight (p < 0.001) and 0.34 kg (p < 0.001) fat mass per week, but fat-free and skeletal muscle mass were not significantly affected. Vitamin D levels increased slightly from 23.8 (11-37.3) ng/ml to 25.1 (22.6-41.6) ng/ml (p = 0.053). β-hydroxybutyrate levels were significantly increased and triglycerides and free T3 hormone levels significantly reduced by the PL intervention. This pilot study shows that adoption of a PL intervention during curative radiotherapy of breast cancer patients is feasible and able to reduce fat mass. Daily outdoor activity could eliminate vitamin D deficiency (vitamin D
Published:
November 28, 2020
Title:
Maintenance of Energy Homeostasis during Calorically Restricted Ketogenic Diet and Fasting-MR-Spectroscopic Insights from the ERGO2 Trial
Authors:
Wenger, Katharina J.; Wagner, Marlies; Harter, Patrick N.; Franz, Kea; Bojunga, Jörg; Fokas, Emmanouil; Imhoff, Detlef; Rödel, Claus; Rieger, Johannes; Hattingen, Elke; Steinbach, Joachim P.; Pilatus, Ulrich; Voss, Martin
Abstract:
Background: The ERGO2 (Ernaehrungsumstellung bei Patienten mit Rezidiv eines Glioblastoms) MR-spectroscopic imaging (MRSI) subtrial investigated metabolism in patients randomized to calorically restricted ketogenic diet/intermittent fasting (crKD-IF) versus standard diet (SD) in addition to re-irradiation (RT) for recurrent malignant glioma. Intracerebral concentrations of ketone bodies (KB), intracellular pH (pHi), and adenosine triphosphate (ATP) were non-invasively determined. Methods: 50 patients were randomized (1:1): Group A keeping a crKD-IF for nine days, and Group B a SD. RT was performed on day 4-8. Twenty-three patients received an extended MRSI-protocol (1H decoupled 31P MRSI with 3D chemical shift imaging (CSI) and 2D 1H point-resolved spectroscopy (PRESS)) at a 3T scanner at baseline and on day 6. Voxels were selected from the area of recurrent tumor and contralateral hemisphere. Spectra were analyzed with LCModel, adding simulated signals of 3-hydroxybutyrate (βOHB), acetone (Acn) and acetoacetate (AcAc) to the standard basis set. Results: Acn was the only reliably MRSI-detectable KB within tumor tissue and/or normal appearing white matter (NAWM). It was detected in 4/11 patients in Group A and in 0/8 patients in Group B. MRSI results showed no significant depletion of ATP in tumor tissue of patients at day 6 during crKD-IF, even though there were a significant difference in ketone serum levels between Group A and B at day 6 and a decline in fasting glucose in Group A from baseline to day 6. The tumor specific alkaline pHi was maintained. Conclusions: Our metabolic findings suggest that tumor cells maintain energy homeostasis even with reduced serum glucose levels and may generate additional ATP through other sources.
Published:
November 27, 2020
Title:
Ketone body metabolism in failing heart
Authors:
Monzo, Luca; Sedlacek, Kamil; Hromanikova, Katarina; Tomanova, Lucie; Borlaug, Barry A.; Jabor, Antonin; Kautzner, Josef; Melenovsky, Vojtech
Abstract:
AIMS: Upregulation of ketone body (β-hydroxybutyrate, βHB) utilization has been documented in human end-stage heart failure (HF), but is unclear if this is due to intrinsic cardiac metabolic remodeling or a HF-related catabolic state. This study sought to evaluate the maximal ketone body utilization capacity and its determinants in controls and in patients with moderate HF and reduced ejection fraction (HFrEF). METHODS AND RESULTS:
Published:
November 25, 2020
Title:
Genetic Factors of Alzheimer’s Disease Modulate How Diet is Associated with Long-Term Cognitive Trajectories: A UK Biobank Study
Authors:
Klinedinst, Brandon S.; Le, Scott T.; Larsen, Brittany; Pappas, Colleen; Hoth, Nathan J.; Pollpeter, Amy; Wang, Qian; Wang, Yueying; Yu, Shan; Wang, Li; Allenspach, Karin; Mochel, Jonathan P.; Bennett, David A.; Willette, Auriel A.
Abstract:
Background: Fluid intelligence (FI) involves abstract problem-solving without prior knowledge. Greater age-related FI decline increases Alzheimer’s disease (AD) risk, and recent studies suggest that certain dietary regimens may influence rates of decline. However, it is uncertain how long-term food consumption affects FI among adults with or without familial history of AD (FH) or APOE4 (ɛ4). Objective: Observe how the total diet is associated with long-term cognition among mid- to late-life populations at-risk and not-at-risk for AD. Methods: Among 1,787 mid-to-late-aged adult UK Biobank participants, 10-year FI trajectories were modeled and regressed onto the total diet based on self-reported intake of 49 whole foods from a Food Frequency Questionnaire (FFQ). Results: Daily cheese intake strongly predicted better FIT scores over time (FH-: β= 0.207, p
Published:
November 24, 2020
Title:
Should Americans Get Half Their Calories From Carbs? Two Camps Battle It Out
Authors:
Reddy, Sumathi
Abstract:
As the U.S. government revises its dietary recommendations, opposing groups are fighting over the healthiness of carbohydrates.
Published:
November 23, 2020
Title:
Sodium-Glucose Cotransporter Type 2 (SGLT-2) Inhibitors and Ketogenesis: the Good and the Bad
Authors:
Ekanayake, Preethika; Hupfeld, Christopher; Mudaliar, Sunder
Abstract:
PURPOSE OF REVIEW: The micro/macrovascular complications of diabetes cause considerable morbidity and premature mortality. The SGLT2 inhibitors are the first diabetes medications with significant benefits on microvascular disease (nephropathy) and macrovascular cardiovascular disease. In this review, we evaluate one of the potential mechanisms for these cardiorenal benefits-the production of ketones, their benefits, and risks. RECENT FINDINGS: In recent cardiovascular outcome trials (CVOTs), the SGLT2 inhibitors demonstrated significant cardiorenal benefits and they are now approved to reduce CV events/death, heart failure hospitalization, and progression to end-stage renal disease. Glucosuria induced by the SGLT2 inhibitors leads to increased ketone production. Ketones are an efficient fuel source and can improve myocardial and renal function. Further, the ketone body beta-hydroxybutyrate exhibits anti-inflammatory/anti-oxidative actions, which favorably impact myocardial and renal remodeling/fibrosis. Uncontrolled ketogenesis leads to ketoacidosis, especially during conditions of acute illness and excessive insulin dose reductions. The SGLT2 inhibitors have demonstrated significant cardiorenal benefits in large CVOTs. Studies are in progress to elucidate whether SGLT2 inhibitor-induced low-grade hyperketonemia contributes to these benefits.
Published:
November 23, 2020
Title:
Vegetarian and vegan diets and risks of total and site-specific fractures: results from the prospective EPIC-Oxford study
Authors:
Tong, Tammy Y. N.; Appleby, Paul N.; Armstrong, Miranda E. G.; Fensom, Georgina K.; Knuppel, Anika; Papier, Keren; Perez-Cornago, Aurora; Travis, Ruth C.; Key, Timothy J.
Abstract:
There is limited prospective evidence on possible differences in fracture risks between vegetarians, vegans, and non-vegetarians. We aimed to study this in a prospective cohort with a large proportion of non-meat eaters.
Published:
November 23, 2020
Title:
Increased advanced glycation end product and meat consumption is associated with childhood wheeze: analysis of the National Health and Nutrition Examination Survey
Authors:
Wang, Jing Gennie; Liu, Bian; Kroll, Francesca; Hanson, Corrine; Vicencio, Alfin; Coca, Steven; Uribarri, Jaime; Bose, Sonali
Abstract:
We examined 4388 children from the 2003 to 2006 National Health and Nutrition Examination Survey and used survey-design-adjusted multivariable logistic regression to evaluate associations between dietary advanced glycation end product (AGE) and meat consumption frequencies and respiratory symptoms. Higher AGE intake was significantly associated with increased odds of wheezing (adjusted OR 1.18; 95% CI 1.02 to 1.36), wheeze-disrupted sleep (1.26; 95% CI 1.05 to 1.51) and exercise (1.34; 95% CI 1.08 to 1.67) and wheezing requiring prescription medication (1.35; 95% CI 1.13 to 1.63). Higher intake of non-seafood meats was associated with wheeze-disrupted sleep (2.32; 95% CI 1.11 to 4.82) and wheezing requiring prescription medication (2.23; 95% CI 1.10 to 4.54).
Published:
November 22, 2020
Title:
Gastric acid level of humans must decrease in the future
Authors:
Fujimori, Shunji
Abstract:
Proton pump inhibitors strongly inhibit gastric acid production, but digestion problems do not generally arise. We can intake almost ordinary food even after total gastrectomy. Small intestine itself can digest and absorb food using various digestive ...
Published:
November 21, 2020
Title:
Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases
Authors:
Jensen, Nicole Jacqueline; Wodschow, Helena Zander; Nilsson, Malin; Rungby, Jørgen
Abstract:
Under normal physiological conditions the brain primarily utilizes glucose for ATP generation. However, in situations where glucose is sparse, e.g., during prolonged fasting, ketone bodies become an important energy source for the brain. The brain's utilization of ketones seems to depend mainly on the concentration in the blood, thus many dietary approaches such as ketogenic diets, ingestion of ketogenic medium-chain fatty acids or exogenous ketones, facilitate significant changes in the brain's metabolism. Therefore, these approaches may ameliorate the energy crisis in neurodegenerative diseases, which are characterized by a deterioration of the brain's glucose metabolism, providing a therapeutic advantage in these diseases. Most clinical studies examining the neuroprotective role of ketone bodies have been conducted in patients with Alzheimer's disease, where brain imaging studies support the notion of enhancing brain energy metabolism with ketones. Likewise, a few studies show modest functional improvements in patients with Parkinson's disease and cognitive benefits in patients with-or at risk of-Alzheimer's disease after ketogenic interventions. Here, we summarize current knowledge on how ketogenic interventions support brain metabolism and discuss the therapeutic role of ketones in neurodegenerative disease, emphasizing clinical data.
Published:
November 20, 2020
Title:
The dark side of the spoon - glucose, ketones and COVID-19: a possible role for ketogenic diet?
Authors:
Paoli, Antonio; Gorini, Stefania; Caprio, Massimiliano
Abstract:
The novel coronavirus disease (COVID-19) is posing a serious challenge to the health-care systems worldwide, with an enormous impact on health conditions and loss of lives. Notably, obesity and its related comorbidities are strictly related with worse clinical outcomes of COVID-19 disease. Recently, there is a growing interest in the clinical use of ketogenic diets (KDs), particularly in the context of severe obesity with related metabolic complications. KDs have been proven effective for a rapid reduction of fat mass, preserving lean mass and providing an adequate nutritional status. In particular, the physiological increase in plasma levels of ketone bodies exerts important anti-inflammatory and immunomodulating effects, which may reveal as precious tools to prevent infection and potential adverse outcomes of COVID-19 disease. We discuss here the importance of KDs for a rapid reduction of several critical risk factors for COVID-19, such as obesity, type 2 diabetes and hypertension, based on the known effects of ketone bodies on inflammation, immunity, metabolic profile and cardiovascular function. We do believe that a rapid reduction of all modifiable risk factors, especially obesity with its metabolic complications, should be a pillar of public health policies and interventions, in view of future waves of SARS-CoV-2 infection.
Published:
November 20, 2020
Title:
The dark side of the spoon - glucose, ketones and COVID-19: a possible role for ketogenic diet?
Authors:
Paoli, Antonio; Gorini, Stefania; Caprio, Massimiliano
Abstract:
The novel coronavirus disease (COVID-19) is posing a serious challenge to the health-care systems worldwide, with an enormous impact on health conditions and loss of lives. Notably, obesity and its related comorbidities are strictly related with worse clinical outcomes of COVID-19 disease. Recently, there is a growing interest in the clinical use of ketogenic diets (KDs), particularly in the context of severe obesity with related metabolic complications. KDs have been proven effective for a rapid reduction of fat mass, preserving lean mass and providing an adequate nutritional status. In particular, the physiological increase in plasma levels of ketone bodies exerts important anti-inflammatory and immunomodulating effects, which may reveal as precious tools to prevent infection and potential adverse outcomes of COVID-19 disease. We discuss here the importance of KDs for a rapid reduction of several critical risk factors for COVID-19, such as obesity, type 2 diabetes and hypertension, based on the known effects of ketone bodies on inflammation, immunity, metabolic profile and cardiovascular function. We do believe that a rapid reduction of all modifiable risk factors, especially obesity with its metabolic complications, should be a pillar of public health policies and interventions, in view of future waves of SARS-CoV-2 infection.
Published:
November 20, 2020
Title:
The Lancet Commission on diabetes: using data to transform diabetes care and patient lives
Authors:
Chan, Juliana C N; Lim, Lee-Ling; Wareham, Nicholas J; Shaw, Jonathan E; Orchard, Trevor J; Zhang, Ping; Lau, Eric S H; Eliasson, Björn; Kong, Alice P S; Ezzati, Majid; Aguilar-Salinas, Carlos A; McGill, Margaret; Levitt, Naomi S; Ning, Guang; So, Wing-Yee; Adams, Jean; Bracco, Paula; Forouhi, Nita G; Gregory, Gabriel A; Guo, Jingchuan; Hua, Xinyang; Klatman, Emma L; Magliano, Dianna J; Ng, Boon-Peng; Ogilvie, David; Panter, Jenna; Pavkov, Meda; Shao, Hui; Unwin, Nigel; White, Martin; Wou, Constance; Ma, Ronald C W; Schmidt, Maria I; Ramachandran, Ambady; Seino, Yutaka; Bennett, Peter H; Oldenburg, Brian; Gagliardino, Juan José; Luk, Andrea O Y; Clarke, Philip M; Ogle, Graham D; Davies, Melanie J; Holman, Rury R; Gregg, Edward W
Abstract:
Published:
November 12, 2020
Title:
Association of Obesity with Depressive Symptomatology, Eating Habits, Interleukin-8 and Cortisol in a Young Population
Authors:
López-Pulido, Edgar Iván; Ramírez-De Los Santos, Saúl; González-Sánchez, Grecia Denisse; Becerra-Ruiz, Julieta Saraí; Rivas-Delgado, Mariana Elizabeth; Becerra-Hurtado, Jessica; Ramírez-De Los Santos, María Luisa; Alonso-Sánchez, Carmen Celina; González-Silva, Napoleón; Guzmán-Flores, Juan Manuel
Abstract:
Obesity is the result of a complex combination of psychological, biological, and environmental factors. In this work, we evaluate whether obesity is related to eating habits, depressive symptomatology, as well as interleukin-8 and cortisol. A descriptive cross-sectional study was carried out in 232 university students. All youths were surveyed to determine their eating habits and depressive symptomatology. Anthropometric measures and a blood sample were taken to determine its biochemical profile and its concentration of interleukin-8 and cortisol. The results show that interleukin-8 increase in the overfat group. The altered eating behaviors were frequent in the studied group; they were associated with the presence of obesity and the variation of interleukin-8 and cortisol. Besides, we found correlations of interleukin-8 with age, glucose, and lipid profile in the overfat group. In conclusion, these results indicate that high adiposity is related to changes in the concentrations of interleukin-8 and eating habits, confirming that obesity is the consequence of a complex network of various factors.
Published:
November 11, 2020
Title:
Effect of Very-Low-Calorie Ketogenic Diet on Psoriasis Patients: A Nuclear Magnetic Resonance-Based Metabolomic Study
Authors:
Castaldo, Giuseppe; Pagano, Imma; Grimaldi, Manuela; Marino, Carmen; Molettieri, Paola; Santoro, Angelo; Stillitano, Ilaria; Romano, Rocco; Montoro, Paola; D'Ursi, Anna Maria; Rastrelli, Luca
Abstract:
Psoriasis is an inflammatory disease of the epidermis based on an immunological mechanism involving Langerhans cells and T lymphocytes that produce pro-inflammatory cytokines. Genetic factors, environmental factors, and improper nutrition are considered triggers of the disease. Numerous studies have reported that in a high number of patients, psoriasis is associated with obesity. Excess adipose tissue, typical of obesity, causes a systemic inflammatory status coming from the inflammatory active adipose tissue; therefore, weight reduction is a strategy to fight this pro-inflammatory state. This study aimed to evaluate how a nutritional regimen based on a ketogenic diet influenced the clinical parameters, metabolic profile, and inflammatory state of psoriasis patients. To this end, 30 psoriasis patients were subjected to a ketogenic nutritional regimen and monitored for 4 weeks by evaluating the clinical data, biochemical and clinical parameters, NMR metabolomic profile, and IL-2, IL-1β, TNF-α, IFN-γ, and IL-4 concentrations before and after the nutritional regimen. Our data show that a low-calorie ketogenic diet can be considered a successful strategy and therapeutic option to gain an improvement in psoriasis-related dysmetabolism, with significant correction of the full metabolic and inflammatory status.
Published:
November 9, 2020
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